Libre Pathology - User contributions [en]

Endometrioid endometrial carcinoma

2017-06-24T18:15:42Z

Mitchell: /* Micro */ added MELF as something to look for

{{ Infobox diagnosis
| Name = {{PAGENAME}}
| Image = Endometrioid endometrial adenocarcinoma high mag.jpg
| Width =
| Caption = Endometrioid endometrial adenocarcinoma. [[H&E stain]].
| Synonyms = endometrioid endometrial adenocarcinoma
| Micro =
| Subtypes =
| LMDDx = [[complex endometrial hyperplasia]], [[microglandular hyperplasia]] of the cervix, [[endocervical adenocarcinoma]], [[serous carcinoma of the endometrium]] - esp. for high-grade tumours, [[clear cell carcinoma of the endometrium]], [[simple endometrial hyperplasia]], [[endometrium with squamous morules]]
| Stains =
| IHC = ER +ve, PR +ve, vimentin +ve, p16 -ve, CEA -ve
| EM =
| Molecular =
| IF =
| Gross = endometrial thickening
| Grossing = [[hysterectomy for endometrial cancer grossing]]
| Site = [[endometrium]] - see ''[[endometrial carcinoma]]''
| Assdx = [[obesity]]
| Syndromes = [[Lynch syndrome]], [[Cowden syndrome]]
| Clinicalhx =
| Signs = [[abnormal uterine bleeding]] (AUB)
| Symptoms =
| Prevalence = common
| Bloodwork =
| Rads =
| Endoscopy =
| Prognosis = good - esp. low-grade
| Other =
| ClinDDx =
| Tx = usu. total hysterectomy
}}
'''Endometrioid endometrial carcinoma''', abbreviated '''EEC''', is the most common type of [[endometrial carcinoma]]. It is strongly associated with [[obesity]].

It is also known as '''endometrioid endometrial adenocarcinoma'''.

==General==
*Good prognosis - usually.
*Women in 40s & 50s.
*Associated with estrogen excess.
**Typical patient is [[obese]].

Associated syndromes:
*[[Lynch syndrome]].<ref name=pmid11873308>{{Cite journal | last1 = Lax | first1 = SF. | title = [Dualistic model of molecular pathogenesis in endometrial carcinoma]. | journal = Zentralbl Gynakol | volume = 124 | issue = 1 | pages = 10-6 | month = Jan | year = 2002 | doi = 10.1055/s-2002-20303 | PMID = 11873308 }}</ref><ref name=pmid23426126>{{Cite journal | last1 = Karamurzin | first1 = Y. | last2 = Soslow | first2 = RA. | last3 = Garg | first3 = K. | title = Histologic evaluation of prophylactic hysterectomy and oophorectomy in Lynch syndrome. | journal = Am J Surg Pathol | volume = 37 | issue = 4 | pages = 579-85 | month = Apr | year = 2013 | doi = 10.1097/PAS.0b013e3182796e27 | PMID = 23426126 }}</ref>
*[[Cowden syndrome]].

==Gross==
*Thickened endometrium.

==Microscopic==
Features:
*Atypical (ovoid) glands with - one of the following four:<ref name=Ref_GP239>{{Ref GP|239}}</ref><ref name=pmid7074572>{{Cite journal | last1 = Kurman | first1 = RJ. | last2 = Norris | first2 = HJ. | title = Evaluation of criteria for distinguishing atypical endometrial hyperplasia from well-differentiated carcinoma. | journal = Cancer | volume = 49 | issue = 12 | pages = 2547-59 | month = Jun | year = 1982 | doi = | PMID = 7074572 }}</ref><ref>URL: [http://www.cap.org/apps/docs/committees/cancer/cancer_protocols/2011/Endometrium_11protocol.pdf http://www.cap.org/apps/docs/committees/cancer/cancer_protocols/2011/Endometrium_11protocol.pdf]. Accessed on: 12 January 2012.</ref>
*#[[Desmoplastic stromal response]].
*#Confluent cribriform growth. †
*#Extensive papillary growth. †
*#Severe cytologic atypia. †
*Endometrioid features:
**+/-Low-grade nuclear features.
**Squamous metaplasia - very common.
***Look for ''squamous morules'':
****Ball of cells with an intensely eosinophilic cytoplasm - '''key feature'''.
****Central nucleus.
****Intercellular bridges - may be hard to find.
****+/-Dyskeratotic cells.

Notes:
* † There is a size cut-off for criteria 2, 3 and 4: > 2.1 mm.<ref name=pmid7074572/>
*Dyskeratosis = abnormal keratinization;<ref>URL: [http://dictionary.reference.com/browse/dyskeratosis http://dictionary.reference.com/browse/dyskeratosis]. Accessed on: 5 September 2011.</ref> classically have intensely eosinophilic cytoplasm +/- nuclear fragmentation ([http://dictionary.reference.com/browse/karyolysis?db=medical&q=karyolysis karyorrhexis]) - see: [http://www.drmihm.com/pictures/Figure%203.jpg several dyskeratotic cells].
*[[Squamous metaplasia]] != neoplastic -- it may occur due to hormones.<ref name=pmid7748076>{{Cite journal | last1 = Miranda | first1 = MC. | last2 = Mazur | first2 = MT. | title = Endometrial squamous metaplasia. An unusual response to progestin therapy of hyperplasia. | journal = Arch Pathol Lab Med | volume = 119 | issue = 5 | pages = 458-60 | month = May | year = 1995 | doi = | PMID = 7748076 }}</ref>
*Squamous morules in endometrioid endometrial carcinoma - not associated with [[HPV]] infection.<ref name=pmid15333650>{{Cite journal | last1 = Chinen | first1 = K. | last2 = Kamiyama | first2 = K. | last3 = Kinjo | first3 = T. | last4 = Arasaki | first4 = A. | last5 = Ihama | first5 = Y. | last6 = Hamada | first6 = T. | last7 = Iwamasa | first7 = T. | title = Morules in endometrial carcinoma and benign endometrial lesions differ from squamous differentiation tissue and are not infected with human papillomavirus. | journal = J Clin Pathol | volume = 57 | issue = 9 | pages = 918-26 | month = Sep | year = 2004 | doi = 10.1136/jcp.2004.017996 | PMID = 15333650 }}</ref>

DDx:
*[[Complex endometrial hyperplasia with atypia]].
*[[Complex endometrial hyperplasia]].
*[[Microglandular hyperplasia]] of the cervix.
*[[Endocervical adenocarcinoma]].
*[[Serous carcinoma of the endometrium]] - esp. if high-grade nuclear features are present diffusely.
*[[Clear cell carcinoma of the endometrium]] - esp. when clear cells present.

===Grading===
*FIGO system most commonly used.
*Based on gland formation & adjusted by nuclear pleomorphism.

Preliminary grade based on gland formation:<ref>{{Ref PBoD|1087-8}}</ref><ref>URL: [http://www.pathologyoutlines.com/uterus.html#endometrialcarc http://www.pathologyoutlines.com/uterus.html#endometrialcarc].</ref><ref>URL: [http://www.emedicine.com/med/topic2832.htm http://www.emedicine.com/med/topic2832.htm].</ref><ref name=pmid12496701>{{cite journal |author=Ayhan A, Taskiran C, Yuce K, Kucukali T |title=The prognostic value of nuclear grading and the revised FIGO grading of endometrial adenocarcinoma |journal=Int. J. Gynecol. Pathol. |volume=22 |issue=1 |pages=71–4 |year=2003 |month=January |pmid=12496701 |doi= |url=}}</ref>
*Grade 1: <5% solid component.
*Grade 2: 5-50% solid component.
*Grade 3: >50% solid component.

Modifiers/adjustment:
*High grade nuclei upgrades cancer by one.
**Tadrous says: high grade nuclei = increased size, irregular large nucleoli, irregular chromatin pattern (clumped, coarse).<ref>{{Ref DCHH|240}}</ref>
**Winham ''et al''. describe it as: [[nuclear pleomorphism]] identifiable with the 10× objective or enlarged nuclei (1.5-2× normal) with [[prominent nucleoli]], irregular nuclear contours, and dispersed chromatin.<ref name=pmid24487465>{{Cite journal | last1 = Winham | first1 = WM. | last2 = Lin | first2 = D. | last3 = Stone | first3 = PJ. | last4 = Nucci | first4 = MR. | last5 = Quick | first5 = CM. | title = Architectural versus nuclear atypia-defined FIGO grade 2 endometrial endometrioid adenocarcinoma (EEC): a clinicopathologic comparison of 154 cases with clinical follow-up. | journal = Int J Gynecol Pathol | volume = 33 | issue = 2 | pages = 120-6 | month = Mar | year = 2014 | doi = 10.1097/PGP.0b013e31828bb4ed | PMID = 24487465 }}</ref>

===Images===
<gallery>
Image:Endometrioid endometrial adenocarcinoma low mag.jpg | EEA - low mag. (WC)
Image:Endometrioid endometrial adenocarcinoma intermed mag.jpg | EEA - intermed. mag. (WC)
Image:Endometrioid endometrial adenocarcinoma high mag.jpg | EEA - high mag. (WC)
Image: Endometrioid endometrial adenocarcinoma very high mag.jpg | EEA - very high mag. (WC)
</gallery>
www:
*[http://www.diagnosticpathology.org/content/2/1/40/figure/F1?highres=y Squamous morule with dyskeratotic cell (diagnosticpathology.org)].

==IHC==
*Vimentin +ve.
*ER +ve.
*PR +ve.

Others:
*p16 -ve -- positive in [[serous endometrial carcinoma]]<ref name=pmid17581420>{{Cite journal | last1 = Chiesa-Vottero | first1 = AG. | last2 = Malpica | first2 = A. | last3 = Deavers | first3 = MT. | last4 = Broaddus | first4 = R. | last5 = Nuovo | first5 = GJ. | last6 = Silva | first6 = EG. | title = Immunohistochemical overexpression of p16 and p53 in uterine serous carcinoma and ovarian high-grade serous carcinoma. | journal = Int J Gynecol Pathol | volume = 26 | issue = 3 | pages = 328-33 | month = Jul | year = 2007 | doi = 10.1097/01.pgp.0000235065.31301.3e | PMID = 17581420 }}</ref> and [[endocervical adenocarcinoma]].
*CEA -ve.

==Sign out==
===Biopsy===
<pre>
Endometrium, Curettage:
- ENDOMETRIOID ENDOMETRIAL ADENOCARCINOMA, preliminary FIGO grade I.
</pre>

<pre>
Endometrium, Curettage:
- ENDOMETRIOID ENDOMETRIAL ADENOCARCINOMA, preliminary FIGO grade II.

Comment:
The architecture is in keeping with FIGO I; however, nuclear atypia is
present and therefore it is FIGO II.
</pre>

====Block letters====
<pre>
ENDOMETRIUM, BIOPSY:
- ENDOMETRIOID ENDOMETRIAL ADENOCARCINOMA, FIGO GRADE I/III.
</pre>

===Hysterectomy===
<pre>
UTERUS WITH CERVIX AND FALLOPIAN TUBES, TOTAL HYSTERECTOMY AND BILATERAL SALPINGECTOMY:
- ENDOMETRIOID ENDOMETRIAL ADENOCARCINOMA, FIGO GRADE I/III, pT2, pNx.
-- SURGICAL MARGINS NEGATIVE.
-- PLEASE SEE TUMOUR SUMMARY.
- LEIOMYOMAS WITH HYALINIZATION.
- FALLOPIAN TUBES WITHOUT SIGNIFICANT PATHOLOGY.
</pre>

===Micro===
The sections show endometrium with complex, fused and cribriform glands with scant intervening stroma over a region measuring greater than 2.1 millimetres. Focally, a desmoplastic stroma is also identified. No nuclear atypia is appreciated.

A subtle pattern of myoinvasion in low grade endometrial endometrioid carcinomas, microcystic, elongated and fragmented (MELF) should be searched for in the absence of frank invasion. At low power, microcystic tumor glands lie separated by muscle from non-invasive carcinoma in edematous stroma. At higher power lie microcystic glands with neutrophils, as well as elongated glands lined by flattened tumor cells. Eosinophilic tumor cells or squamous cells can often be seen within the lumens. <ref name=pmid14501811>{{cite journal |author= Murray SK, Young RH, Scully RE |title= Unusual epithelial and stromal changes in myoinvasive endometrioid adenocarcinoma: a study of their frequency, associated diagnostic problems, and prognostic significance |journal= Int J Gynecol Pathol |volume=22 |issue= |pages=324-333 |year=2003 | pmid=14501811 |doi=10.1097/01.pgp.0000092161.33490.a9 }}</ref>

====Endocervical versus endometrial - biopsy====
The foamy histiocytes in the stroma and lack of desmoplasia slightly favour an endometrial origin; however, the lesion would be best classified with an excisional specimen and in conjunction with the clinical impression.

==See also==
*[[Endometrial carcinoma]].
*[[Endometrial hyperplasia]].
*[[Ductal adenocarcinoma of the prostate gland]].

==References==
{{Reflist|2}}

[[Category:Diagnosis]]
[[Category:Endometrial carcinoma]]

Invasive breast cancer

2017-06-24T17:50:32Z

Mitchell: /* Invasive versus non-invasive */ added information from recent study on microinvasion

[[Image:Breast_cancer.JPG|thumb|300px|Breast cancer at [[cut-up]]. (WC/John Hayman)]]
The article deals with '''invasive [[breast]] cancer''' and the evaluation of hormone receptor & HER2 status. Non-invasive breast cancer is dealt with in ''[[non-invasive breast cancer]]''.

=Introduction=
==Overview of invasive breast cancer subtypes==
====Common epithelial subtypes====
Type and percentage of breast carcinomas:<ref name=Ref_PBoD1143>{{Ref PBoD|1143}}</ref>
*[[Invasive ductal carcinoma of the breast|Ductal]] - [[AKA]] no special type (NST) - 79%.
*[[invasive lobular carcinoma|Lobular]] - 10%.
*[[Tubular carcinoma of the breast|Cribriform / tubular]] - 6%.
*[[mucinous breast carcinoma|Mucinous]] (colloid) - 2%.
*[[medullary breast carcinoma|Medullary]] - 2%.
*Papillary - 1%.
*[[Metaplastic breast carcinoma|Metaplastic]] - <1%.

===Common stromal types===
*Malignant [[phyllodes tumour]].
*[[Angiosarcoma]] - post-radiation ~ 10 years.<ref>URL: [http://www.breastpathology.info/Case_of_the_month/2007/COTM_1007%20discussion.html http://www.breastpathology.info/Case_of_the_month/2007/COTM_1007%20discussion.html]. Accessed on: 28 November 2010.</ref>

===Good prognosis subtypes===
Three good prognosis subtypes:<ref>URL: [http://emedicine.medscape.com/article/1947145-overview http://emedicine.medscape.com/article/1947145-overview]. Accessed on: 24 August 2012.</ref>
*Tubular carcinoma.
*Mucinous carcinoma.
*Papillary carcinoma.

==Comprehensive list of invasive breast cancer subtypes==
====Epithelial====
Counterparts of in situ lesions:
*[[Invasive ductal carcinoma of the breast|Invasive ductal carinoma]], not otherwise specified.
*[[Invasive lobular carcinoma]].
*[[Invasive cribriform carcinoma of the breast|Invasive cribriform carcinoma]].
*[[Invasive papillary carcinoma of the breast|Invasive papillary carcinoma]].
*[[Invasive micropapillary carcinoma of the breast|Invasive micropapillary carcinoma]].

Other epithelial tumours:
*[[Tubular carcinoma of the breast|Tubular carcinoma]].
*[[Medullary breast carcinoma|Medullary carcinoma]].
*[[Mucinous breast carcinoma|Mucinous carinoma]].
*[[Metaplastic breast carcinoma|Metaplastic carcinoma]].
*[[Neuroendocrine tumour]].
*[[Apocrine carcinoma of the breast|Apocrine carcinoma]].
*Lipid-rich carcinoma.
*[[Secretory breast carcinoma|Secretory carcinoma]].
*Oncocytic carcinoma.
*[[Glycogen-rich clear cell carcinoma of the breast|Glycogen-rich clear cell carcinoma]].

Epithelial tumours seen in the [[salivary gland]]:
*[[Adenoid cystic carcinoma of the breast]].
*[[Acinic cell carcinoma]].
*[[Carcinoma ex pleomorphic adenoma]].

Seen in the skin:
*[[Sebaceous carcinoma]].

Clinically diagnosed:
*Inflammatory carcinoma.

In situ lesions:
*[[Ductal carcinoma in situ]].
*[[Lobular carcinoma in situ]].

Proliferative lesions:
*[[Usual ductal hyperplasia]].
*[[Flat epithelial atypia]].
*[[Atypical ductal hyperplasia]].

Non-specific:
*Microinvasive carcinoma.

Papillary:
*[[Intraductal papilloma of the breast|Papilloma]].
*Atypical papilloma.
*Intraductal papillary carcinoma.

Adenomas:
*Ductal adenoma.
*[[Tubular adenoma of the breast|Tubular adenoma]].
*[[Lactating adenoma]].
*Apocrine adenoma.
*[[Pleomorphic adenoma]].

====Myoepithelial====
*Myoepitheliosis.
*Adenomyoepithelial adenosis.
*[[Adenomyoepithelioma]].
*Malignant adenomyoepithelioma.

====Mesenchymal tumours====
:See: ''[[Soft tissue lesions]]''.

====Fibroepithelial tumours====
*[[Fibroadenoma]].
*[[Phyllodes tumour]].
*Periductal stromal sarcoma, low grade.
*[[Mammary hamartoma]].

====Nipple lesions====
*[[Nipple adenoma]].
*Syringomatous adenoma.
*[[Paget disease of the breast]].

====Other====
*[[Lymphoma]].
*[[Metastasis]].

==Familial breast cancer==
{{Main|Hereditary breast cancer}}

=Breast IHC=
==Molecular classification of ''invasive carcinoma''==
A molecular classification:<ref name=Ref_PCPBoD8_547>{{Ref PCPBoD8|547}}</ref>
{| class="wikitable sortable" style="margin-left:auto;margin-right:auto"
! Type
! Percentage
! IHC
! Histology
! Prognosis/clinical
|-
| Luminal A
| ~45%
| ER+ PR+ HER2-
| well-differentiated
| good, chemo resistant
|-
| Luminal B
| 17%
| ER+ PR+ HER2+
| high grade
| poor, +/- chemo responsive
|-
| Normal breast-like
| ~8%
| ER+ PR+ (?) HER2-
| well-differentiated
| good
|-
| Basal-like
| ~20%
| ER- PR- HER2-
| poorly differentiated
| aggressive, may have good chemo response, classic for [[BRCA1]] mutation
|-
| HER2 positive
| ~10%
| ER- PR- (?) HER2+
| poorly differentiated
| poor
|}

The above is not applied clinically. A panel of [[immunostains]] ([[ER]], PR, HER2, EGFR, [[CK5/6]]) can reproduce the molecular groupings; however, these groupings originate from gene expression profiling studies<ref name=pmid19704256>{{Cite journal | last1 = Tang | first1 = P. | last2 = Skinner | first2 = KA. | last3 = Hicks | first3 = DG. | title = Molecular classification of breast carcinomas by immunohistochemical analysis: are we ready? | journal = Diagn Mol Pathol | volume = 18 | issue = 3 | pages = 125-32 | month = Sep | year = 2009 | doi = 10.1097/PDM.0b013e31818d107b | PMID = 19704256 }}</ref>

A newer classification outlines 10 subtypes based on molecular drivers identified by analysis of genomic and transcriptomic data from 2,000 breast tumors.<ref>{{Cite journal | last1 = Curtis | first1 = C. | last2 = Shah | first2 = SP. | last3 = Chin | first3 = SF. | last4 = Turashvili | first4 = G. | last5 = Rueda | first5 = OM. | last6 = Dunning | first6 = MJ. | last7 = Speed | first7 = D. | last8 = Lynch | first8 = AG. | last9 = Samarajiwa | first9 = S. | title = The genomic and transcriptomic architecture of 2,000 breast tumours reveals novel subgroups. | journal = Nature | volume = 486 | issue = 7403 | pages = 346-52 | month = Jun | year = 2012 | doi = 10.1038/nature10983 | PMID = 22522925 }}</ref>

== Basal-like breast carcinoma==

*Overview:<ref>{{Cite journal | last1 = Badve | first1 = S. | last2 = Dabbs | first2 = DJ. | last3 = Schnitt | first3 = SJ. | last4 = Baehner | first4 = FL. | last5 = Decker | first5 = T. | last6 = Eusebi | first6 = V. | last7 = Fox | first7 = SB. | last8 = Ichihara | first8 = S. | last9 = Jacquemier | first9 = J. | title = Basal-like and triple-negative breast cancers: a critical review with an emphasis on the implications for pathologists and oncologists. | journal = Mod Pathol | volume = 24 | issue = 2 | pages = 157-67 | month = Feb | year = 2011 | doi = 10.1038/modpathol.2010.200 | PMID = 21076464 }}
</ref>
**A category of breast carcinomas defined by gene expression profiling.
**''Not used'' in clinical practice.
**Somewhere between 15-30% of breast carcinomas.
**Can be roughly be identified by immunohistochemistry - basal markers (CK14, p63, calponin, SMA).
**Not derived from myoepithelial cells, merely express a phenotype more in keeping with basal cells than ductal cells.
**Most triple negative (ER, PgR, Her-2); therefore cannot be treated with the usual therapeutic agents.
**There is an association in young women between basal-like breast cancer and BRCA1 mutation.
**Discussions of BRCA1 associated tumors, TNBC and BLBC are typically muddied by the overlap.
**Increased incidence in some populations - African-Americans, young women
**Sporadic basal-like cancers do not have a BRCA1 mutation but may have a dysfunctional BRCA1 pathway.
**p53 mutations are frequent.

*This molecular group includes a variety of morphologic phenotypes including:
**High grade [[invasive ductal carcinoma]] of no special type.
**Medullary-like carcinoma (a carcinoma with some but not all the features of medullary carcinoma).
**[[Medullary breast carcinoma|Medullary carcinoma]]
**[[Metaplastic breast carcinoma|Metaplastic carcinoma]].
**[[Adenoid cystic carcinoma of the breast|Adenoid cystic carcinoma]].
**[[Secretory carcinoma]].

*Classic morphological clues of a basal type cancer usually refer to medullary carcinoma features:
**Relatively circumscribed.
**Geographic necrosis.
**Abundant mitoses.
**Pushing margins.
**Central fibrosis or necrosis.
**High histological grade.
**Exceptionally high mitotic rate.
**Pushing borders.
**Conspicuous lymphocytic infiltrate.

*Behaviour:
**Basal-like breast cancer is a heterogeneous group.
**The behaviour of basal-like breast cancer appears to fall into two groups:
***The tumours that are by nature low grade (ie adenoid cystic carcinoma) and/or do not metastasise have a better prognosis than other types of breast carcinoma.
***The tumours with early metastasis that may behave more aggressively
****Hematogenous spread -greater tendency to metastasise to visceral sites (notably lung and brain) instead of to nodes and bone.
**Many have a complete response to chemotherapy and survival rates similar to typical breast cancer
**Non-complete response to chemotherapy is associated with low survival at 5 years.

Other sources
Minireview: Basal-Like Breast Cancer: From Molecular Profiles to Targeted Therapies <http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3035993/>

== Triple Negative Breast Carcinoma ==
Features:<ref name=pmid21076464>{{Cite journal | last1 = Badve | first1 = S. | last2 = Dabbs | first2 = DJ. | last3 = Schnitt | first3 = SJ. | last4 = Baehner | first4 = FL. | last5 = Decker | first5 = T. | last6 = Eusebi | first6 = V. | last7 = Fox | first7 = SB. | last8 = Ichihara | first8 = S. | last9 = Jacquemier | first9 = J. | title = Basal-like and triple-negative breast cancers: a critical review with an emphasis on the implications for pathologists and oncologists. | journal = Mod Pathol | volume = 24 | issue = 2 | pages = 157-67 | month = Feb | year = 2011 | doi = 10.1038/modpathol.2010.200 | PMID = 21076464 }}</ref>

**A category of breast carcinomas defined by immunohistochemical/FISH expression of ER, PR and HER2.
**''Important to identify'' in clinical practice.
**About 15% of breast carcinomas.
**Important group due to a lack of tailored therapies for this group
***Some triple negatives also express androgen receptor and have and [apocrine carcinoma] morphology.<ref>{{Cite journal | last1 = Niemeier | first1 = LA. | last2 = Dabbs | first2 = DJ. | last3 = Beriwal | first3 = S. | last4 = Striebel | first4 = JM. | last5 = Bhargava | first5 = R. | title = Androgen receptor in breast cancer: expression in estrogen receptor-positive tumors and in estrogen receptor-negative tumors with apocrine differentiation. | journal = Mod Pathol | volume = 23 | issue = 2 | pages = 205-12 | month = Feb | year = 2010 | doi = 10.1038/modpathol.2009.159 | PMID = 19898421 }}</ref>
****May respond to therapies targeting the androgen receptor.
***BCL11A overexpression recently identified as an oncogenic driver for some triple negatives <ref>{{Cite journal | last1 = Khaled | first1 = WT. | last2 = Choon Lee | first2 = S. | last3 = Stingl | first3 = J. | last4 = Chen | first4 = X. | last5 = Raza Ali | first5 = H. | last6 = Rueda | first6 = OM. | last7 = Hadi | first7 = F. | last8 = Wang | first8 = J. | last9 = Yu | first9 = Y. | title = BCL11A is a triple-negative breast cancer gene with critical functions in stem and progenitor cells. | journal = Nat Commun | volume = 6 | issue = | pages = 5987 | month = | year = 2015 | doi = 10.1038/ncomms6987 | PMID = 25574598 }}</ref>
****Targeted therapies may include inhibitors of BCL11A.
**Triple-negative and basal-like phenotypes are not synonymous but overlap
***About 70% of triple-negative tumours are basal-like.
***About 70% of basal-like tumors are triple-negative tumours.
**Discussions of BRCA1 associated tumors, TNBC and BLBC are typically muddied by the overlap.
**Classic 'morphological clues' to a triple negative cancer usually refer to medullary carcinoma features.

==Immunostains for typing and diagnosis==
===DCIS versus LCIS===
Tabular comparison for DCIS versus LCIS:<ref name=Ref_BP275>{{Ref BP|275}}</ref><ref name=pmid18318578>{{cite journal |author=Yeh IT, Mies C |title=Application of immunohistochemistry to breast lesions |journal=Arch. Pathol. Lab. Med. |volume=132 |issue=3 |pages=349-58 |year=2008 |month=March |pmid=18318578 |doi= |url=http://journals.allenpress.com/jrnlserv/?request=get-abstract&issn=0003-9985&volume=132&page=349}}</ref>
{| class="wikitable sortable"
!Disease
!E-cadherin
!Beta-catenin
!34betaE12
!CAM5.2 (CK8)
|-
|DCIS
| +ve
| +ve
| -ve
| +ve peripheral cytoplasm
|-
|LCIS
| -ve
| -ve
| +ve perinuclear
| +ve perinuclear
|}

===Invasive versus non-invasive===
Myoepithelial markers - typically lost in invasive carcinoma:<ref>{{Ref Lester3|88}}</ref>
{| class="wikitable sortable"
!Stain
!Location
!Notes
|-
| p63
| nuclear
| up to 10% of invasive tumours +ve<ref name=Ref_BP276>{{Ref BP|276}}</ref>
|-
| Smooth muscle actin (SMA)
| cytoplasmic
| stains myofibroblasts & blood vessels
|-
| Calponin
| cytoplasmic
| stains myofibroblasts & blood vessels
|-
| Smooth muscle myosin heavy chain (SMM-HC)
| cytoplasmic
| stains myofibroblasts & blood vessels
|}

Respecting findings that might indicate a more extensive search for microinvasion be undertaken in cases of pure ductal carcinoma in situ (DCIS), a recent study found 1) intermediate or high DCIS grade, 2) tumor thickness, and 3) diffuse peritumoral retraction clefts, but not such things as lymph node metastases, or HER2 score, independently increased the likelihood of finding a microinvasive component. <ref name=pmid28434924>{{cite journal |author=Mori K, Takeda M, Kodama Y, Kiyokawa H, Yasojima H, Mizutani M, Otani Y, Morikawa N, Masuda N, Mano M|title= Tumor thickness and histological features as predictors of invasive foci within preoperatively diagnosed ductal carcinoma in situ |journal=Human Pathology |volume=64 |issue= |pages=145-155 |year=2017 | pmid=28434924 |doi=10.1016/j.humpath.2017.04.004 }}</ref>

===Usual ductal hyperplasia versus ductal carcinoma in situ===
Markers for UDH versus DCIS:<ref name=Ref_BP276>{{Ref BP|276}}</ref>
{| class="wikitable sortable"
!Disease
![[CK5/6]]
![[ER]]
|-
|UDH
| diffuse +ve
| patchy +ve
|-
|DCIS
| -ve
| diffuse +ve
|}

===Lymphovascular invasion===
{{Main|Lymphovascular invasion}}
*D2-40 - marks the lymphatic spaces.<ref>{{cite journal |author=Ordóñez NG |title=Podoplanin: a novel diagnostic immunohistochemical marker |journal=Adv Anat Pathol |volume=13 |issue=2 |pages=83-8 |year=2006 |month=March |pmid=16670463 |doi=10.1097/01.pap.0000213007.48479.94 |url=}}</ref><ref>{{cite journal |author=Kahn HJ, Marks A |title=A new monoclonal antibody, D2-40, for detection of lymphatic invasion in primary tumors |journal=Lab. Invest. |volume=82 |issue=9 |pages=1255-7 |year=2002 |month=September |pmid=12218087 |doi= |url=}}</ref>
*CD31 - marks lymphovascular spaces.
*CD34 - marks lymphovascular spaces, less specific than CD31.

===Lymph node metastases===
Immunostaining of sentinel lymph nodes to look for [[isolated tumour cells]] and small [[lymph node metastases]] may be done.
*CAM5.2 may be used.
*'''Not''' done routinely.

==Treatment-related markers - overview==
*ER (estrogen receptor).
**Positive in most breast cancers; +ve in ~75-80%.<ref name=Ref_Lester241-2>{{Ref Lester|241-2}}</ref>
*PR (progesterone receptor).
**Positive in most breast cancers; +ve in ~65-70%.<ref name=Ref_Lester241-2>{{Ref Lester|241-2}}</ref>
*HER2/neu (HER2).
**Usually negative; -ve in 70-80%.<ref name=Ref_Lester241-2>{{Ref Lester|241-2}}</ref>
**Positivity associated with a worse prognosis.
**In the context of HER2 positivity, PTEN/PI3K/Akt/mTOR pathway dysregulation is a poor prognosticator.<ref name=pmid22454081>{{Cite journal | last1 = Gallardo | first1 = A. | last2 = Lerma | first2 = E. | last3 = Escuin | first3 = D. | last4 = Tibau | first4 = A. | last5 = Muñoz | first5 = J. | last6 = Ojeda | first6 = B. | last7 = Barnadas | first7 = A. | last8 = Adrover | first8 = E. | last9 = Sánchez-Tejada | first9 = L. | title = Increased signalling of EGFR and IGF1R, and deregulation of PTEN/PI3K/Akt pathway are related with trastuzumab resistance in HER2 breast carcinomas. | journal = Br J Cancer | volume = 106 | issue = 8 | pages = 1367-73 | month = Apr | year = 2012 | doi = 10.1038/bjc.2012.85 | PMID = 22454081 }}</ref><ref name=pmid22172323>{{Cite journal | last1 = Jensen | first1 = JD. | last2 = Knoop | first2 = A. | last3 = Laenkholm | first3 = AV. | last4 = Grauslund | first4 = M. | last5 = Jensen | first5 = MB. | last6 = Santoni-Rugiu | first6 = E. | last7 = Andersson | first7 = M. | last8 = Ewertz | first8 = M. | title = PIK3CA mutations, PTEN, and pHER2 expression and impact on outcome in HER2-positive early-stage breast cancer patients treated with adjuvant chemotherapy and trastuzumab. | journal = Ann Oncol | volume = | issue = | pages = | month = Dec | year = 2011 | doi = 10.1093/annonc/mdr546 | PMID = 22172323 }}</ref>

Notes:
*Male breast cancer is usually hormone receptor positive (~97%), and HER2 positivity is quite rare (~6%).<ref name=pmid24080492>{{Cite journal | last1 = Schildhaus | first1 = HU. | last2 = Schroeder | first2 = L. | last3 = Merkelbach-Bruse | first3 = S. | last4 = Binot | first4 = E. | last5 = Büttner | first5 = R. | last6 = Kuhn | first6 = W. | last7 = Rudlowski | first7 = C. | title = Therapeutic strategies in male breast cancer: Clinical implications of chromosome 17 gene alterations and molecular subtypes. | journal = Breast | volume = | issue = | pages = | month = Sep | year = 2013 | doi = 10.1016/j.breast.2013.08.008 | PMID = 24080492 }}</ref>
*ASCO/CAP guidelines recommend that cold ischemia time be <1 hour.<ref name=pmid22460807 >{{Cite journal | last1 = Yildiz-Aktas | first1 = IZ. | last2 = Dabbs | first2 = DJ. | last3 = Bhargava | first3 = R. | title = The effect of cold ischemic time on the immunohistochemical evaluation of estrogen receptor, progesterone receptor, and HER2 expression in invasive breast carcinoma. | journal = Mod Pathol | volume = 25 | issue = 8 | pages = 1098-105 | month = Aug | year = 2012 | doi = 10.1038/modpathol.2012.59 | PMID = 22460807 }}</ref>

===ER & PR scoring===
Nuclear staining:<ref name=Ref_Lester241-2>{{Ref Lester|241-2}}</ref>
*Give a percentage, i.e. 0-100%.
**Important cut points: 1% and 10%.
***0% = negative - not treated.
***<10% = low positivity - treated.

Notes:
*Normal breast epithelial cells have a patchy staining for ER and PR.
*Evaluated on the invasive component.
===HER2 scoring===
Immunohistochemical based testing:<ref name=pmid24382093>{{Cite journal | last1 = Rakha | first1 = EA. | last2 = Starczynski | first2 = J. | last3 = Lee | first3 = AH. | last4 = Ellis | first4 = IO. | title = The updated ASCO/CAP guideline recommendations for HER2 testing in the management of invasive breast cancer: a critical review of their implications for routine practice. | journal = Histopathology | volume = 64 | issue = 5 | pages = 609-15 | month = Apr | year = 2014 | doi = 10.1111/his.12357 | PMID = 24382093 }}</ref><ref>URL: [http://www.cap.org/apps/docs/committees/cancer/cancer_protocols/breast_biomarker_template.pdf http://www.cap.org/apps/docs/committees/cancer/cancer_protocols/breast_biomarker_template.pdf]. Accessed on: October 7, 2014.</ref>
{| class="wikitable sortable"
! Score
! Staining intensity
! Cells stained (%)
! Membrane staining
! Management
! Percentage of cases
|-
| '''0'''
| no staining/barely visible
| '''≤10%'''
| '''incomplete'''
| No HER2 blocker
| ~60%
|-
| '''1+'''
| minimal/barely visible
| '''>10%'''
| '''incomplete'''
| No HER2 blocker
| ~10%
|-
| '''2+'''
| weak-to-moderate
| '''>10%'''
| '''incomplete''' (circumferential)
| Needs [[SISH]] or [[FISH]]
| ~10% †
|-
| '''2+'''
| intense
| '''≤10%'''
| '''complete'''
| Needs [[SISH]] or [[FISH]]
| ~10% †
|-
| '''3+'''
| intense staining
| '''>10%''' ‡
| '''complete'''
| HER2 blocker
| ~20%
|}

Note for IHC:
*Normal breast epithelial cells do not stain with HER2.
*Evaluated on the invasive component.
*SISH = silver [[in situ hybridization]].
*FISH = fluorescence in situ hybridization.
*† Together approximately 10%.
*‡ The cut point was 10%, changed to 30% and then changed back to 10%.<ref name=pmid24382093/>

ISH based testing:<ref>URL: [http://www.cap.org/apps/docs/committees/cancer/cancer_protocols/breast_biomarker_template.pdf http://www.cap.org/apps/docs/committees/cancer/cancer_protocols/breast_biomarker_template.pdf]. Accessed on: October 7, 2014.</ref>
{| class="wikitable sortable"
! Result
! Ratio criteria
! Gene copy number criteria
|-
| Positive
| ≥2.0 HER2/CEP17
| ≥6.0 copies of HER2/cell
|-
| Equivocal
| <2.0 HER2/CEP17 (required)
| 4.0-6.0 copies of HER2/cell
|-
| Negative
| <2.0 HER2/CEP17
| <4.0 copies of HER2/cell
|}
Note for ISH:
*Can be called ''positive'' based on either ''ratio criteria'' or ''gene copy number criteria''.

===Clinical===
*ER & PR status determine whether a patient will get tamoxifen or other estrogen receptor modulators, such as raloxifene (Evista).
*HER2 status determines whether patient will get traztuzumab (Herceptin) or other HER2/neu modulators.

=Characteristics of the subtypes=
==Invasive ductal carcinoma of the breast==
*[[AKA]] "NST" = No Specific Type.
*[[AKA]] ''invasive mammary carcinoma''.
{{Main|Invasive ductal carcinoma of the breast}}

==Invasive lobular carcinoma==
*Abbreviated ''ILC''.
*[[AKA]] ''lobular carcinoma''.
{{Main|Invasive lobular carcinoma}}

==Medullary breast carcinoma==
*[[AKA]] ''medullary carcinoma of the breast''.
{{Main|Medullary breast carcinoma}}

==Tubular carcinoma of the breast==
*[[AKA]] ''tubular carcinoma''.
{{Main|Tubular carcinoma of the breast}}

==Metaplastic breast carcinoma==
*[[AKA]] ''metaplastic carcinoma''.
{{Main|Metaplastic breast carcinoma}}

==Invasive micropapillary carcinoma of the breast==
*[[AKA]] ''micropapillary carcinoma''.
{{Main|Invasive micropapillary carcinoma of the breast}}

==Apocrine carcinoma of the breast==
{{Main|Apocrine carcinoma of the breast}}

==Mucinous breast carcinoma==
*[[AKA]] ''mucinous carcinoma of the breast'', [[AKA]] ''colloid carcinoma of the breast''.
{{Main|Mucinous breast carcinoma}}

==Adenoid cystic carcinoma of the breast==
*[[AKA]] ''breast adenoid cystic carcinoma''.
{{Main|Adenoid cystic carcinoma of the breast}}

==Intracystic papillary breast carcinoma==
*[[AKA]] ''encapsulated or encysted papillary carcinoma of the breast'', abbreviated ''EPC''.
{{Main|Intracystic papillary breast carcinoma}}

==Glycogen-rich clear cell carcinoma of the breast==
*Abbreviated ''GRCC''.
{{Main|Glycogen-rich clear cell carcinoma of the breast}}

==Secretory carcinoma of the breast==
*[[AKA]] ''secretory breast carcinoma'', abbreviated ''SBC''.
{{Main|Secretory carcinoma of the breast}}

==Invasive cribriform carcinoma of the breast==
{{Main|Invasive cribriform carcinoma of the breast}}

==Invasive papillary carcinoma of the breast==
{{Main|Invasive papillary carcinoma of the breast}}
*Should '''not''' be confused with the indolent behaving [[intracystic papillary carcinoma of the breast]], also known as ''encapsulated papillary carcinoma of the breast''.

=Grading breast cancer=
{{Main|Breast cancer grading}}

=Staging breast cancer=
{{Main|Breast cancer staging}}

=Lymphovascular invasion=
{{Main|Lymphovascular invasion}}
In the context of breast pathology, the Rosen criteria for LVI are widely excepted, and are as follows:<ref name=pmid6674861>{{Cite journal | last1 = Rosen | first1 = PP. | title = Tumor emboli in intramammary lymphatics in breast carcinoma: pathologic criteria for diagnosis and clinical significance. | journal = Pathol Annu | volume = 18 Pt 2 | issue = | pages = 215-32 | month = | year = 1983 | doi = | PMID = 6674861 }}</ref><ref>URL: [http://www.cap.org/apps/docs/committees/cancer/cancer_protocols/2009/InvasiveBreast_09protocol.pdf http://www.cap.org/apps/docs/committees/cancer/cancer_protocols/2009/InvasiveBreast_09protocol.pdf]. Accessed on: 5 August 2011.</ref>
#Must be outside of the tumour proper.
#*LVI is usually very close -- typically within 0.1 cm.
#Contour of cells should differ from possible vessel wall.
#*DCIS with retraction artifact mimicing LVI has a contour that matches its surrounding fibrous tissue.
#Endothelium (usu. flat) should be visible.
#Lymphatics are found adjacent to [[blood vessels]] - vessels should be present in the vicinity.

Memory device ''LUBE-O'':
*'''L'''VI has a '''U'''nique contour, '''B'''lood vessels and '''E'''ndothelium in the vicinity, and is '''O'''utside of the tumour.

Note:
*LVI does not affect the stage.

=Other=
==Paget's disease==
{{Main|Paget disease of the breast}}
===General===
*Associated with underlying breast carcinoma.<ref name=emed_pagets>URL: [http://emedicine.medscape.com/article/1101235-diagnosis http://emedicine.medscape.com/article/1101235-diagnosis]</ref>

Notes:
*Unrelated to [[Paget disease of the bone]].

===Microscopic===
Features:<ref name=emed_pagets/>
*Cells in the epidermis:
**Epitheliod morphology (round/ovoid).
**Cells nested or single.
**Clear/pale cytoplasm '''key feature''' - may also be eosinophilic.
**Large nucleoli.

Images:
*[http://commons.wikimedia.org/wiki/File:Extramammary_Pagets_disease_low.jpg Paget's disease - low mag. (WC)].
*[http://commons.wikimedia.org/wiki/File:Extramammary_Pagets_disease_high.jpg Paget's disease - high mag. (WC)].

IHC & DDx:
*See ''[[Paget disease]]''.

==Trivia==
===Tumour size and lymph node metastases===
There is a paper<ref name=pmid18483831>{{Cite journal | last1 = Porembka | first1 = MR. | last2 = Abraham | first2 = RL. | last3 = Sefko | first3 = JA. | last4 = Deshpande | first4 = AD. | last5 = Jeffe | first5 = DB. | last6 = Margenthaler | first6 = JA. | title = Factors associated with lymph node assessment in ductal carcinoma in situ: analysis of 1988-2002 seer data. | journal = Ann Surg Oncol | volume = 15 | issue = 10 | pages = 2709-19 | month = Oct | year = 2008 | doi = 10.1245/s10434-008-9947-5 | PMID = 18483831 | url=http://onlinelibrary.wiley.com/doi/10.1002/cncr.24592/pdf}}</ref> that calculates the probability of [[lymph node]] mets based on tumour size. The developed formula is:

:<math>L_{To-Nodes}=1-exp(-Q_n D^Z)</math>

Where:
*<math>L_{To-Nodes}</math> = the probability of the lymph nodes being positive.
*D = the largest dimension of the tumour in millimetres.
*Z = 1.0041.
*<math>Q_n</math> = 0.019.

====Selected values====
{| class="wikitable"
| Tumour size (mm) || Probability
|-
| 5 || 9 %
|-
| 10 || 17 %
|-
| 15 || 25 %
|-
| 20 || 32 %
|-
| 25 || 38 %
|-
| 30 || 44 %
|-
| 35 || 49 %
|-
| 40 || 54 %
|-
| 45 || 58 %
|-
| 50 || 62 %
|}

===Natural history===
There is a theory that up to 22% of small (radiographically detected) breast tumours regress, based on an analysis in a large population.<ref name=pmid19029493>{{Cite journal | last1 = Zahl | first1 = PH. | last2 = Maehlen | first2 = J. | last3 = Welch | first3 = HG. | title = The natural history of invasive breast cancers detected by screening mammography. | journal = Arch Intern Med | volume = 168 | issue = 21 | pages = 2311-6 | month = Nov | year = 2008 | doi = 10.1001/archinte.168.21.2311 | PMID = 19029493 }}</ref> The study is supported by NCI's SEER data.<ref name=pmid19468099>{{Cite journal | last1 = Jatoi | first1 = I. | last2 = Anderson | first2 = WF. | title = Breast cancer overdiagnosis with screening mammography. | journal = Arch Intern Med | volume = 169 | issue = 10 | pages = 999-1000, author reply 1000-1 | month = May | year = 2009 | doi = 10.1001/archinternmed.2009.95 | PMID = 19468099 }}</ref> Also, it generated many comments.<ref name=pmid19029493/>

===Missed macrometastases===
The effect of missed macrometastases is small; this implies using [[IHC]] to look for isolated tumour cells is money that isn't well spent.<ref name=pmid21247310>{{Cite journal | last1 = Weaver | first1 = DL. | last2 = Ashikaga | first2 = T. | last3 = Krag | first3 = DN. | last4 = Skelly | first4 = JM. | last5 = Anderson | first5 = SJ. | last6 = Harlow | first6 = SP. | last7 = Julian | first7 = TB. | last8 = Mamounas | first8 = EP. | last9 = Wolmark | first9 = N. | title = Effect of occult metastases on survival in node-negative breast cancer. | journal = N Engl J Med | volume = 364 | issue = 5 | pages = 412-21 | month = Feb | year = 2011 | doi = 10.1056/NEJMoa1008108 | PMID = 21247310 }}</ref>

=See also=
*[[Breast]].
*[[Non-invasive breast cancer]].

=References=
{{reflist|2}}

=External links=
*[http://ww5.komen.org/BreastCancer/SubtypesofBreastCancer.html About breast cancer - molecular subtypes (komen.org)].

[[Category:Breast pathology]]
[[Category:Invasive breast cancer]]

Ampulla of Vater

2017-06-08T15:40:31Z

Mitchell: /* Ampullary adenoma */ Added obstruction as a potential mimic of tumor

The '''ampulla of Vater''', also '''hepatopancreatic ampulla''', is found in the [[duodenum]]. It has a unique histology and is a relatively common site of disease, when duodenal pathology is considered.

=Benign=
==Normal histology==
Periampullary:<ref name=pmid23026934/>
*Intestinal epithelium with goblet cells.

Papilla of Vater (the projection into the duodenal lumen):<ref name=pmid23026934/>
*Goblet cells in foveolar-like epithelium.

Note about heterotopias:<ref>{{Ref Sternberg5|1639}}</ref>
*+/-Pancreatic heterotopia - common.
*+/-Gastric heterotopia - not common.

===Sign out===
<pre>
DUODENAL BULB, BIOPSY:
- GASTRIC HETEROTOPIA.
- NEGATIVE FOR MALIGNANCY.
</pre>

==Acute inflammation==
===Sign out===
<pre>
Ampulla of Vater, Biopsy:
- Small bowel mucosa with foveolar-like glands (in keeping with
ampulla), reactive epithelial changes and mild acute inflammation.
- NEGATIVE for dysplasia.
</pre>

=Ampullary tumours=
*[[AKA]] ''tumours of the ampulla of Vater''.
*[[AKA]] ''tumours of the hepatopancreatic ampulla''.

==Ampullary Obstruction ==
[[File:5 890331478 sl 1.png|Villous appearing duodenal mass of ampulla, secondary to ampullary duct obstruction]]
[[File:5 890331478 sl 2.png|Villous appearing duodenal mass of ampulla, secondary to ampullary duct obstruction]]
[[File:5 890331478 sl 3.png|Villous appearing duodenal mass of ampulla, secondary to ampullary duct obstruction]]
[[File:5 890331478 sl 4.png|Villous appearing duodenal mass of ampulla, secondary to ampullary duct obstruction]]
[[File:5 890331478 sl 5.png|Villous appearing duodenal mass of ampulla, secondary to ampullary duct obstruction]] 
Villous appearing duodenal mass of ampulla, secondary to ampullary duct obstruction. 43 yo White man. A. Plicae show expansion of stroma by edema with inflammation including neutrophils (neutrophils not shown), by foci of lamina propria hemorrhage (red arrows), and by dilated lymphatics (black arrows). B. A fragment shows dilated ducts on left and center, with connected “proliferating” ducts at right. C. PAS AB stain shows these ducts, by virtue of the thin red line, are ampullary, not Brunner’s glands. D. Nuclei in the proliferated area show striking anisokaryosis and anisonucleosis, as well as hyperchromasia. Note the mitosis (arrow). This notwithstainging, there is an appearance of connection between the ducts. No net appears. Neither are there half glands or aberrant isolated cells. E. On PAS AB stain lay a focus of fibrinopurulent exudate near the proliferating area.
==Ampullary adenoma==
===General===
*Uncommon.
*May be associated with [[familial adenomatous polyposis]] (FAP).

===Microscopic===
Features:
*+/-Paneth cells - may be prominent.<ref name=Ref_Sternberg5_1640>{{Ref Sternberg5|1640}}</ref>
*Similar to adenoma of colon - with:
**Less pseudostratification.
**Finer chromatin pattern.

DDx:
*[[Ampullary carcinoma]].
*[[Duodenal carcinoma]] secondarily involving the ampulla.
*[[Pancreatic adenocarcinoma]] secondarily involving the ampulla.

====Images====
www:
*[http://ajcp.ascpjournals.org/content/132/4/506/F1.expansion.html Ampullary adenoma (ajcpjournals.org)].<ref name=pmid19762527/>
*[http://ajcp.ascpjournals.org/content/132/4/506/F2.expansion.html Ampullary adenoma - pitfalls (ajcpjournals.org)].<ref name=pmid19762527>{{Cite journal | last1 = Bellizzi | first1 = AM. | last2 = Kahaleh | first2 = M. | last3 = Stelow | first3 = EB. | title = The assessment of specimens procured by endoscopic ampullectomy. | journal = Am J Clin Pathol | volume = 132 | issue = 4 | pages = 506-13 | month = Oct | year = 2009 | doi = 10.1309/AJCPUZWJ8WA2IHBG | PMID = 19762527 }}</ref>

===Sign out===
:''See [[tubular adenoma of the gastrointestinal tract|tubular adenoma]]''.

==Ampullary carcinoma==
*[[AKA]] ''ampullary adenocarcinoma''.
===General===
*Uncommon.
*Textbook association: [[familial adenomatous polyposis]].<ref name=pmid15756395>{{Cite journal | last1 = Tran | first1 = TC. | last2 = Vitale | first2 = GC. | title = Ampullary tumors: endoscopic versus operative management. | journal = Surg Innov | volume = 11 | issue = 4 | pages = 255-63 | month = Dec | year = 2004 | doi = | PMID = 15756395 }}</ref><ref name=pmid9834381>{{Cite journal | last1 = Soravia | first1 = C. | last2 = Berk | first2 = T. | last3 = Haber | first3 = G. | last4 = Cohen | first4 = Z. | last5 = Gallinger | first5 = S. | title = Management of advanced duodenal polyposis in familial adenomatous polyposis. | journal = J Gastrointest Surg | volume = 1 | issue = 5 | pages = 474-8 | month = | year = | doi = | PMID = 9834381 }}</ref>
*Prognosis guarded but significantly better than [[pancreatic ductal adenocarcinoma]] - 5 year survival ~40% for ampullary carcinomas vs. 10% for pancreatic adenocarcinoma.<ref name=pmid23026934/>

===Gross===
*Ampullary carcinomas are classified by site.
*Modest differences exist in survival between the sites.

====Classification====
Adsay ''et al.'' proposed a four subtype classification system:<ref name=pmid23026934>{{Cite journal | last1 = Adsay | first1 = V. | last2 = Ohike | first2 = N. | last3 = Tajiri | first3 = T. | last4 = Kim | first4 = GE. | last5 = Krasinskas | first5 = A. | last6 = Balci | first6 = S. | last7 = Bagci | first7 = P. | last8 = Basturk | first8 = O. | last9 = Bandyopadhyay | first9 = S. | title = Ampullary Region Carcinomas: Definition and Site Specific Classification with Delineation of Four Clinicopathologically and Prognostically Distinct Subsets in an Analysis of 249 Cases. | journal = Am J Surg Pathol | volume = | issue = | pages = | month = Sep | year = 2012 | doi = 10.1097/PAS.0b013e31826399d8 | PMID = 23026934 }}</ref>
{| class="wikitable sortable"
! Subtype
! Prevalence
! Origin/definition
! Notes
|-
| Intra-ampullary papillary-tubular carcinoma
| ~25% of cases
| arises from intra-ampullary epithelium and/or distal end of CBD or pancreatic duct
| generalized category ''intra-ampullary papillary-tubular neoplasm'' -- the ampullary counterpart of the [[IPMN]] of the pancreas
|-
| Ampullary-ductal carcinoma
| ~15% of cases
| arises from intra-ampullary ducts
|
|-
| Peri-ampullary duodenal carcinoma
| ~5% of cases
| primarily in the duodenum; ampullary orfice must be clearly within lesion
|
|-
| Ampullary carcinoma not otherwise specified
| ~55% of cases
| arise from papillary projection into duodenum - from foveolar-like epithelium with goblet cells
|
|}

===Microscopic===
Dependent on histologic subtype:<ref name=pmid23026934/><ref name=pmid15549428/>
#Intestinal ampullary carcinoma.
#Pancreaticobiliary ampullary carcinoma.
#Other.

[[File:1 amp ca 1 680x512px.tif|Invasive carcinoma of duodenal ampulla.]]
[[File:2 amp ca 1 680x512px.tif|Invasive carcinoma of duodenal ampulla.]]
 
[[File:3 amp ca 1 680x512px.tif|Invasive carcinoma of duodenal ampulla.]]
[[File:4 amp ca 1 680x512px.tif|Invasive carcinoma of duodenal ampulla.]]
 
[[File:5 amp ca 1 680x512px.tif|Invasive carcinoma of duodenal ampulla.]]
[[File:6 amp ca 1 680x512px.tif|Invasive carcinoma of duodenal ampulla.]]

Invasive carcinoma of duodenal ampulla, intestinal type. A. Ulceration tops Brunner’s glands [green arrow]; at the edge lie glands [blue arrow] with changes suggesting adenoma (100X). B. Ki67 stain establishes adenoma by surface extension of brown nuclei (100X). C. The lesion was a mass, prompting rebiopsy. The cauterized fragment shows disorderly spread of glands, with dilated glands at base [arrows] not readily explained by obstruction (40X) D.Two cancerous prongs, one on left [black arrow], one on right [blue arrow] each show spread about muscle fibers (200X). E. The Whipple resection showed the same dilated spreading glands [arrows] at base, redolent of the spread of some well-differentiated colonic adenocarcinomas through muscle (40X). F. Cribriformed cancerous nests [arrows] cannot be Brunner’s glands, because the nuclei are too variable and lack polarity and because they abut crypts extending to the surface; cautery would have made this an impossible distinction (200X).

[[File:5 08466787961551 sl 1.png| 60 year old woman with poorly differentiated ampullary adenocarcinoma and obstructive cholestasis in liver]]
[[File:5 08466787961551 sl 2.png| 60 year old woman with poorly differentiated ampullary adenocarcinoma and obstructive cholestasis in liver]]
[[File:5 08466787961551 sl 3.png| 60 year old woman with poorly differentiated ampullary adenocarcinoma and obstructive cholestasis in liver]]
[[File:5 08466787961551 sl 4.png| 60 year old woman with poorly differentiated ampullary adenocarcinoma and obstructive cholestasis in liver]]
[[File:5 08466787961551 sl 5.png| 60 year old woman with poorly differentiated ampullary adenocarcinoma and obstructive cholestasis in liver]]
[[File:5 08466787961551 sl 6.png| 60 year old woman with poorly differentiated ampullary adenocarcinoma and obstructive cholestasis in liver]]
[[File:5 08466787961551 sl 7.png| 60 year old woman with poorly differentiated ampullary adenocarcinoma and obstructive cholestasis in liver]]

60 year old woman with poorly differentiated ampullary adenocarcinoma and obstructive cholestasis in liver. A. An isolated tumor fragment (black arrow) and two fragments with tumor undermining small intesatinal mucosa (green arrows) are seen. B. Large, ovoid cancer nuclei with abundant grey cytoplasm form sheets with only rare acini (arrow). C. Tumor cells are CK7 positive. D. Tumor cells are CK20 negative. E. Portal triads (black arrows) are expanded, lacking intense inflammation. A septal duct (green arrow) lacks definite onion skinning. F. Proliferated peripheral bile ductules (black arrows) sometimes have neutrophils (white arrow), which should not be interpreted as ascending cholangitis. Next to the artery (red arrow) lies the bile duct (yellow arrow), which has disturbed nuclei, but no neutrophils. Note occasional eosinophils (cyan arrows). G. Hepatocytes with feathery degeneration. Arrows point to dilated cholangioles, one filled with a bile plug.

Notes:
*May lack desmoplastic stroma.<ref name=Ref_Sternberg5_1640>{{Ref Sternberg5|1640}}</ref>

DDx:
*[[Invasive ductal carcinoma of the pancreas]] - has a much worse prognosis.
*Ectopic pancreas.<ref name=pmid18304504>{{Cite journal | last1 = Hsu | first1 = SD. | last2 = Chan | first2 = DC. | last3 = Hsieh | first3 = HF. | last4 = Chen | first4 = TW. | last5 = Yu | first5 = JC. | last6 = Chou | first6 = SJ. | title = Ectopic pancreas presenting as ampulla of Vater tumor. | journal = Am J Surg | volume = 195 | issue = 4 | pages = 498-500 | month = Apr | year = 2008 | doi = 10.1016/j.amjsurg.2007.01.043 | PMID = 18304504 }}
</ref>
*[[Duodenal adenocarcinoma]] with secondary involvement of the ampulla.

====Intestinal ampullary carcinoma====
Features:<ref name=pmid23026934/>
*Pseudostratified columnar epithelium with hyperchromatic, ellipsoid nuclei.
**Glands usually tightly packed, i.e. high gland-to-stroma ratio; often >2:1.

Note:
*Similar to [[colorectal adenocarcinoma]].

====Pancreatobiliary ampullary carcinoma====
Features:<ref name=pmid23026934/>
*Tubular arrangements consisting of cuboidal cells in one or two layers.
**Tubules usually spaced; ~1:3 gland-to-stroma ratio.

=====Images=====
<gallery>
Image: Periampullary adenocarcinoma -- low mag.jpg | PA - low mag. (WC)
Image: Periampullary adenocarcinoma -- intermed mag.jpg | PA - intermed. mag. (WC)
Image: Periampullary adenocarcinoma -- high mag.jpg | PA - high mag. (WC)
Image: Periampullary adenocarcinoma - alt -- high mag.jpg | PA - high mag. (WC)
</gallery>

====Other====
Features - any of the following characteristics:<ref name=pmid23026934/>
*Non-tubular morphology/poorly-differentiated.
*Micropapillary architecture.
*Medullary.
*Signet ring cells.
*Mucin:
*#Colloid.
*#Mixed-mucinous.
*#Mucinous-signet-ring.
<gallery>
Image:Ampulla AmpullaryACA-2 PA.JPG|Ampulla Ampullary Adeno Carcinoma -(SKB)
Image:Ampulla AmpullaryACA-3 PA.JPG|Ampulla Ampullary Adeno Carcinoma - (SKB)
Image:Ampulla AmpullaryACA PA.JPG|Ampulla Ampullary Adeno Carcinoma - (SKB)
</gallery>

===IHC===
Features:<ref name=pmid15549428>{{Cite journal | last1 = Fischer | first1 = HP. | last2 = Zhou | first2 = H. | title = Pathogenesis of carcinoma of the papilla of Vater. | journal = J Hepatobiliary Pancreat Surg | volume = 11 | issue = 5 | pages = 301-9 | month = | year = 2004 | doi = 10.1007/s00534-004-0898-3 | PMID = 15549428 }}</ref>
*CK7 +ve.
*CK20 +ve.
*MUC2 +ve.

Others:
*SMAD4 +ve/-ve.
**Lost in pancreatic neoplasia ~90% of cases vs. ~35% of ampullary tumours.<ref name=pmid12640108>{{Cite journal | last1 = McCarthy | first1 = DM. | last2 = Hruban | first2 = RH. | last3 = Argani | first3 = P. | last4 = Howe | first4 = JR. | last5 = Conlon | first5 = KC. | last6 = Brennan | first6 = MF. | last7 = Zahurak | first7 = M. | last8 = Wilentz | first8 = RE. | last9 = Cameron | first9 = JL. | title = Role of the DPC4 tumor suppressor gene in adenocarcinoma of the ampulla of Vater: analysis of 140 cases. | journal = Mod Pathol | volume = 16 | issue = 3 | pages = 272-8 | month = Mar | year = 2003 | doi = 10.1097/01.MP.0000057246.03448.26 | PMID = 12640108 }}</ref>
*p53 +ve ~55% of cases.<ref name=pmid11144926>{{Cite journal | last1 = Takashima | first1 = M. | last2 = Ueki | first2 = T. | last3 = Nagai | first3 = E. | last4 = Yao | first4 = T. | last5 = Yamaguchi | first5 = K. | last6 = Tanaka | first6 = M. | last7 = Tsuneyoshi | first7 = M. | title = Carcinoma of the ampulla of Vater associated with or without adenoma: a clinicopathologic analysis of 198 cases with reference to p53 and Ki-67 immunohistochemical expressions. | journal = Mod Pathol | volume = 13 | issue = 12 | pages = 1300-7 | month = Dec | year = 2000 | doi = 10.1038/modpathol.3880238 | PMID = 11144926 }}</ref><ref>{{Cite journal | last1 = Park | first1 = SH. | last2 = Kim | first2 = YI. | last3 = Park | first3 = YH. | last4 = Kim | first4 = SW. | last5 = Kim | first5 = KW. | last6 = Kim | first6 = YT. | last7 = Kim | first7 = WH. | title = Clinicopathologic correlation of p53 protein overexpression in adenoma and carcinoma of the ampulla of Vater. | journal = World J Surg | volume = 24 | issue = 1 | pages = 54-9 | month = Jan | year = 2000 | doi = | PMID = 10594204 }}</ref>
*E-cadherin +ve ~40% of cases.<ref name=pmid16506371/>
*Beta-catenin +ve ~65% of cases.<ref name=pmid16506371>{{Cite journal | last1 = Park | first1 = S. | last2 = Kim | first2 = SW. | last3 = Lee | first3 = BL. | last4 = Jung | first4 = EJ. | last5 = Kim | first5 = WH. | title = Expression of E-cadherin and beta-catenin in the adenoma-carcinoma sequence of ampulla of Vater cancer. | journal = Hepatogastroenterology | volume = 53 | issue = 67 | pages = 28-32 | month = | year = | doi = | PMID = 16506371 }}
</ref>

===Sign out===
*Separate CAP protocol.<ref>URL: [http://www.cap.org/apps/docs/committees/cancer/cancer_protocols/2012/Ampulla_12protocol_3101.pdf http://www.cap.org/apps/docs/committees/cancer/cancer_protocols/2012/Ampulla_12protocol_3101.pdf]. Accessed on: 12 September 2012.</ref>

==See also==
*[[Duodenum]].
*[[Small bowel]].
*[[Gastrointestinal pathology]].

==References==
{{Reflist|2}}

[[Category:Gastrointestinal pathology]]

Medical liver disease

2017-05-17T15:34:46Z

Mitchell: /* Vanishing bile duct syndrome */ added gvhd

[[Image:Ground glass hepatocytes high mag cropped 2.jpg|thumb|right|[[Micrograph]] showing ground glass hepatocytes, as seen in chronic [[hepatitis B]]. [[H&E stain]].]]
This article deals with '''medical [[liver]] disease'''. An introduction to the liver and approach is found in the ''[[liver]]'' article.

Every differential in liver pathology has "drugs"<ref>{{Ref PCPBoD8|448}}</ref> -- if it isn't clearly malignancy.

Liver neoplasms are dealt with in the ''[[liver neoplasms]]'' article.

Medical liver biopsies are often non-specific, as the liver has the same appearance for many mechanisms of injury, especially when the injury is marked. The clinical history, serology and imaging are essential for proper interpretations in this domain of pathology.

=Review of liver blood work=
===Inflammation activity===
*ALT.
*AST.

===Cholestatic markers===
*ALP.
*GGT - used to assess whether the ALP is an "honest" value, elevated in cirrhosis.

===Cirrhosis/decompensation===
*PLT - low is suggestive of dysfunction.
*INR - high is bad, unless anticoagulated.

===Other===
*Bilirubin.
**Direct (AKA conjugated).
**Indirect (AKA unconjugated).

A short DDx of elevated:<ref>{{Ref PCPBoD8|441}}</ref>
*Indirect:
**[[Gilbert syndrome]].
**Crigler-Najjar syndrome type 1.
**Crigler-Najjar syndrome type 2.
*Direct:
**Rotor syndrome.
**Dubin-Johnson syndomre.

===Viral hepatitis===
*HBV DNA.
*HCV RNA.
*HBs Ag, HBs Ab, HBe Ag, HBe Ab.
*HCV Ab.

Others:
*[[Epstein-Barr virus]] (EBV).
*[[Cytomegalovirus]] (CMV) - especially in the immune incompetent.

====Hepatitis B====
Meaning & utility of the various [[Hepatitis B]] tests:<ref>URL: [http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/hepatology/hepatitis-B/ http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/hepatology/hepatitis-B/]. Accessed on: 16 May 2011.</ref><ref name=lto_hepb>URL: [http://www.labtestsonline.org/understanding/analytes/hepatitis_b/test.html http://www.labtestsonline.org/understanding/analytes/hepatitis_b/test.html]. Accessed on: 16 May 2011.</ref>
{| class="wikitable sortable" border="1"
! Test name
! Location
! Positive test
! Negative test
! Usual question
|-
| HBs Ag||Surface||Virus active||No active infection||Active infection?
|-
| HBs Ab||Surface||Exposed OR vaccinated||No exposure OR no vaccine OR loss of Ab||Immunization status?
|-
| HBe Ag||Virus core||Infect. w/ viral replication||No active infection||Active infect. w/ viral replication?
|-
| HBe Ab||Virus core||Exposed to virus||Infect. w/o antibody response OR not exposed||Immune response to infection?
|-
| HBV DNA||-||Active||Not active/no exposure||Viral load/how active?
|-
| HBc Ab||Virus core||Virus active/previous exposure||No exposure||Early active infection?
|}
Notes:
*''HBc Ab'' may test for acute (IgM) or chronic infection - dependent on specific antibody test; it is often used to look for early infection.<ref name=lto_hepb>URL: [http://www.labtestsonline.org/understanding/analytes/hepatitis_b/test.html http://www.labtestsonline.org/understanding/analytes/hepatitis_b/test.html]. Accessed on: 16 May 2011.</ref>
*''Carriers of hepatitis B'': HBs Ag +ve, HBs Ab -ve, HBc Ag -ve, HBc Ab +ve, HBe Ag -ve, HBe Ab +ve.<ref>URL: [http://labtestsonline.org/understanding/analytes/hepatitis-b/tab/test http://labtestsonline.org/understanding/analytes/hepatitis-b/tab/test]. Accessed on: 3 May 2012.</ref>

===Markers for rare liver diseases===
*Ceruloplasm - low think ''[[Wilson's disease]]''; typical value for Wilson's ~ 0.12 g/L.
**<0.20 g/L is a criteria for Wilson's disease.<ref name=pmid18556333>Diagnostic accuracy of serum ceruloplasmin in Wilson disease: determination of sensitivity and specificity by ROC curve analysis among ATP7B-genotyped subjects. Mak CM, Lam CW, Tam S. Clin Chem. 2008 Aug;54(8):1356-62. Epub 2008 Jun 12. PMID 18556333. URL: [http://www.clinchem.org/cgi/reprint/54/8/1356.pdf http://www.clinchem.org/cgi/reprint/54/8/1356.pdf]. Accessed on: 28 September 2009.</ref>
*Alpha-1 antitrypsin - if low think ''deficiency''.

===Hemosiderosis===
*Ferritin - high.
*Iron saturation - high.

Causes:
*Hemochromatosis.
*Hemolysis, chronic.
*Cirrhosis.

=Medical imaging=
Blood flow:<ref>URL: [http://insidesurgery.com/2010/12/hepatopedal-hepatofugal-flow/ http://insidesurgery.com/2010/12/hepatopedal-hepatofugal-flow/]. Accessed on: 2 December 2011.</ref>
*Hepatopedal flow = normal portal vein flow.
*Hepatofugal flow = reversed portal vein flow.

==Interventional measurements==
Wedged to free hepatic venous pressure:<ref name=pmid1864548>{{Cite journal | last1 = Bion | first1 = E. | last2 = Brenard | first2 = R. | last3 = Pariente | first3 = EA. | last4 = Lebrec | first4 = D. | last5 = Degott | first5 = C. | last6 = Maitre | first6 = F. | last7 = Benhamou | first7 = JP. | title = Sinusoidal portal hypertension in hepatic amyloidosis. | journal = Gut | volume = 32 | issue = 2 | pages = 227-30 | month = Feb | year = 1991 | doi = | PMID = 1864548 | PMC = 1378815 | URL = http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1378815/?tool=pubmed }}</ref>
*Normal = 1-4 mmHg.
**Elevated in [[portal hypertension]].

=Liver biopsy=
==Medical liver biopsy adequacy==
Liver biopsy specimens should be:<ref>{{Ref MacSween|418}}</ref>
*2.0 cm in length and contain 11-15 portal tracts,
*The core should be deeper than 1.0 cm from the liver capsule; specimens close to the capsule may lead to over grading of fibrosis.

==Reporting==
{{Main|Pathology reports}}
<pre>
Specimen, procedure:
- Diagnosis.
</pre>
The diagnosis usually contains grading and staging information, e.g. ''activity 2 /4, Laennec fibrosis stage 1 /4''.

In the context of medical liver disease:
*Grade = inflammation/activity.
*Stage = severity of fibrosis/architectural changes.

Notes:
*The term "acute" is infrequently used in liver pathology.
*In the liver: neutrophils ''is not'' acute -- unlike most elsewhere in the body.<ref>OA. September 2009.</ref>

===A microscopic checklist===
<pre>
Size of biopsy: Adequate
Fragmentation: Absent
Fibrosis: Stage 2-3/4, mostly stage 2
Fibrous septa: Present
Septa with curved contours: Present – focally only
Large droplet steatosis (% of hepatocytes): Present, moderate 60%
Ballooning of hepatocytes: Present, rare
Mallory-Denk bodies: Present, rare
Portal inflammation: Present
Interface activity: Minimal (0-1/4)
Lobular necroinflammation: Minimal
Ducts: Present in normal numbers
Duct injury: Absent
Ductular reaction: Absent
Cholestasis: Absent
Terminal hepatic venules: Present
Iron stain: Absent
Ground glass cells with routine stains: Absent
PASD for alpha-1 antitrypsin droplets: Negative
</pre>

=Viral hepatitis=
These are common. The diagnoses are based on serology. The serology is covered in the ''[[Liver_pathology#Viral_hepatitis|viral hepatitis]]'' section in the ''[[liver pathology]]'' article.

Typically classified as:<ref name=pmid8048409>{{Cite journal | title = Terminology of chronic hepatitis, hepatic allograft rejection, and nodular lesions of the liver: summary of recommendations developed by an international working party, supported by the World Congresses of Gastroenterology, Los Angeles, 1994. | journal = Am J Gastroenterol | volume = 89 | issue = 8 Suppl | pages = S177-81 | month = Aug | year = 1994 | doi = | PMID = 8048409 }}</ref><ref>URL: [http://familydoctor.org/familydoctor/en/diseases-conditions/hepatitis-b.html http://familydoctor.org/familydoctor/en/diseases-conditions/hepatitis-b.html]. Accessed on: 2 May 2012.</ref>
#Acute < 6 months duration.
#Chronic > 6 months duration.

==Hepatitis A==
*Infection is self-limited, i.e. not persistent.
**May present as ''[[fulminant hepatic necrosis]]''.
*Usually asymptomatic in children.<ref name=pmid20068336>{{cite journal |author=Jeong SH, Lee HS |title=Hepatitis A: clinical manifestations and management |journal=Intervirology |volume=53 |issue=1 |pages=15–9 |year=2010 |pmid=20068336 |doi=10.1159/000252779 |url=}}</ref>
*Serology is diagnostic.

==Hepatitis B==
:''Hepatitis B virus'', abbreviated ''HBV'', redirects here.
{{Main|Hepatitis B}}

==Hepatitis C==
{{Main|Hepatitis C}}

=Other infections=
*Hydatid disease (Hydatid cyst).
*Ascaris.
*Fasciola

==Hydatid disease==
*[[AKA]] ''hydatid cyst''.
===General===
*Etiology: ''[[Echinococcus]]''.

===Microscopic===
Features:
*Laminated wall +/- calcification.<ref name=Ref_PBPoD8_448>{{Ref PCPBoD8|448}}</ref>
*Organisms -- see ''[[Echinococcus]]''.

====Images====
<gallery>
Image:Liver_cyst_wall_-_intermed_mag.jpg | Liver cyst wall - intermed. mag. (WC)
Image:Liver_cyst_wall_-_high_mag.jpg | Liver cyst wall - high mag. (WC)
Image: Laminated liver cyst wall - intermed mag.jpg | Characteristic laminated portion - intermed. mag. (WC)
Image: Laminated liver cyst wall - high mag.jpg | Characteristic laminated portion - high mag. (WC)
</gallery>
[[www]]:
*[http://pathmicro.med.sc.edu/parasitology/hydatid-hist1.jpg Hydatid cyst (med.sc.edu)].
*[http://www.atlas.or.kr/atlas/include/viewImg.html?uid=645 Hydatid cyst (atlas.or.kr)].
*[http://casereports.bmj.com/content/2009/bcr.04.2009.1798.full Hydatid cyst (casereports.bmj.com)].

==Abscess==
A. [[File:1 ABS 1 680x512px.tif|A process replaces most of the liver parenchyma (20X).]]
 
B. [[File:2 ABS 1 680x512px.tif|Fibrinopurulent exudate apposes granulation tissue (200X).]]
 
C. [[File:3 ABS 1 680x512px.tif|Neutrophils lie in widened sinusoids (200X)..]]
 
D. [[File:4 ABS 1 680x512px.tif|Trichrome shows collagenization of spaces of Disse. Scarring about an abscess or other mass lesion should not be interpreted as reflective of the liver in general (200X).]]
 
Abscess. A. A process replaces most of the liver parenchyma. B. Fibrinopurulent exudate apposes granulation tissue. C. Neutrophils lie in widened sinusoids. D. Trichrome shows collagenization of spaces of Disse. Scarring about an abscess or other mass lesion should not be interpreted as reflective of the liver in general (LR 200X).

==Coccidiomycosis==
A. [[File:Coccidiomycosis - 1 - 40X 680x512px shot.tif|500x500px Granulomas at low power]]
 
B. [[File:Coccidiomycosis - 1 - 200X 680x513px shot.tif|500x500px Granulomas with centrally crowded cells & lady slipper macrophage nuclei]]
 
C. [[File:Coccidiomycosis - 1 - 400X 1369x1024px shot.tif|500x500px Center of previous granuloma showing pyknotic macrophage nuclei]]
 
D. [[File:Coccidiomycosis - 1 - GMS 400X 1369x1024px shot.tif|500x500px Four Coccidiomycotic spherules]]
 
Coccidiomycosis. A. Note the granulomas in otherwise undisturbed liver (UL). B. Granuloma with centrally crowded cells & lady slipper macrophage nuclei. C. Center of granuloma with pyknotic macrophage nuclei, "necrotizing". D. Organisms on GMS stain.

=Metabolic and toxic=
==Alcoholic liver disease==
===General===
*Acute and/or chronic liver changes due to excessive [[alcohol]] use - includes:
**''[[Alcoholic steatohepatitis]]'' (ASH), [[AKA]] ''alcoholic hepatitis''.<ref>URL: [http://emedicine.medscape.com/article/170539-overview http://emedicine.medscape.com/article/170539-overview]. Accessed on: 3 May 2012.</ref>
***Alcoholic hepatitis can be with minimal steatosis.<ref>STC. 6 December 2010.</ref>
**[[Steatosis]] - classically macrovescicular and centrilobular.
**Alcoholic [[cirrhosis]].

====Classic lab findings in EtOH abusers====
*AST & ALT elevated with AST:ALT=2:1.
*GGT elevated.
*MCV increased.

===Gross pathology/radiologic findings===
*Classically micronodular pattern.
**May be macronodular.

===Microscopic===
See:
*''[[Steatohepatitis]]'' section and ''[[ballooning degeneration]]'' section.

Features:
*Often zone III damage.
*Cholestatsis common, i.e. yellow staining.
**NASH (non-alcoholic steatohepatitis) usu. does not have cholestasis.<ref>STC. 6 December 2010.</ref>
*Fibrosis starts at central veins.
*Neutrophils (often helpful) -- few other things have PMNs. (???)
**Neutrophils cluster around cells with Mallory hyaline.

====Images====

A. [[File:1 etoh 3 680x512px.tif| Alcoholic hepatitis with Metavir stage IV fibrosis (advanced fibrosis/cirrhosis).]]
 
B. [[File:2 etoh 3 680x512px.tif| Alcoholic hepatitis with Metavir stage IV fibrosis (advanced fibrosis/cirrhosis).]]
 
C. [[File:3 etoh 3 680x512px.tif| Alcoholic hepatitis with Metavir stage IV fibrosis (advanced fibrosis/cirrhosis).]]
 
D. [[File:4 etoh 3 680x512px.tif| Alcoholic hepatitis with Metavir stage IV fibrosis (advanced fibrosis/cirrhosis).]]
 
E. [[File:5 etoh 3 680x512px.tif| Alcoholic hepatitis with Metavir stage IV fibrosis (advanced fibrosis/cirrhosis).]]
 
F. [[File:6 etoh 3 680x512px.tif| Alcoholic hepatitis with Metavir stage IV fibrosis (advanced fibrosis/cirrhosis).]]
 

Alcoholic hepatitis with Metavir stage IV fibrosis (advanced fibrosis/cirrhosis).
A. Trichrome shows relatively non-inflamed fibrous bands, as well as [between green dots] nodules. The lack of regeneration throughout might have precluded a diagnosis of cirrhosis, but stage IV fibrosis under the Metavir system is justified. B. Reticulin shows regenerative nodules [left] with mostly two or more nuclei between black lines juxtaposed to non-regenerative hepatocytes on the right, without piecemeal necrosis. C. Regenerative nodules show occasional neutrophils [red arrow] and cytoplasmic tufts of ballooned cells, sometimes possibly Mallory hyalin [green arrows]. D. Triads (note vein [green arrow], artery [yellow arrow], and interlobular bile duct [blue arrow]) generally showed little or no interface hepatitis, even when expanded by fibrosis and inflamed. E. Occasional foci of spotty necrosis were seen. F. This edge of an inflamed triads shows neutrophils about proliferated bile ducts [red arrows], as well as Mallory-Denk bodies [blue arrows].
 
A. [[File:1 etoh 4 680x512px.tif| Cirrhosis in an alcoholic.]]
 
B. [[File:2 etoh 4 680x512px.tif| Cirrhosis in an alcoholic.]]
 
C. [[File:3 etoh 4 680x512px.tif| Cirrhosis in an alcoholic.]]
 
D. [[File:4 etoh 4 680x512px.tif| Cirrhosis in an alcoholic.]]
 
E. [[File:5 etoh 4 680x512px.tif| Cirrhosis in an alcoholic.]]
 
F. [[File:6 etoh 4 680x512px.tif| Cirrhosis in an alcoholic.]]
 
Definite cirrhosis in an alcoholic. A. Hepatocyte free bands parse tissue, with occasional definite islands [arrows]. B. Trichrome establishes blue fibrosis about isles [arrows]. C. Reticulin stain shows nodules with regeneration, wherein a large proportion of them are at least two nuclei thick [arrows]. D. Bile duct proliferation can be difficult, sometimes mimicking cholangiocarcinoma. Follow the double headed arrows to see how the ductules can be seen to proliferate from a single sources, with all ducts being complete, without necrotic epithelial cells. E. PAS with distase can help, as cholangiocarcinoma generally lacks the red rim of proliferating bile ductules [arrows]; again note the connections that can be made between the ductule openings by the blue double headed arrows. The cyan double headed arrows show general parallelism, consistent with uniform directionality induced by extrinsic force, not a neoplastic spread. F. Trichrome shows the most difficult focus. Double headed arrows display the connectivity seen before of the proliferated bile ductules. Note that numerous pairs of adjacent perpendicular glands without a head to foot appearance are not seen that would indicate the disorderly spread of cholangiocarcinoma.
 
A. [[File:1 ALC 2 680x512px.tif|Expanded, inflamed triads with increased bile duct/vascular openings. Mild steatosis (40X).]]
 
B. [[File:2 ALC 2 680x512px.tif|Trichrome stain shows periportal fibrosis [red arrowheads] (200X).]]
 
C. [[File:3 ALC 2 680x512px.tif|PAS with diastase stain shows proliferated bile ductules [blue arrowheads] in stroma with mixed inflammatory infiltrate (400X)]]
 
D. [[File:4 ALC 2 680x512px.tif|Neutrophils about ballooned hepatocyte (satellitosis) [yellow arrowheads]. Councilman bodies [green arrowheads] (400X).]]
 
Alcoholic hepatitis without cirrhosis. No history of viral disease. AMA negative. A. Expanded, inflamed triads with increased bile duct/vascular openings. Mild steatosis. B. Trichrome stain shows periportal fibrosis [red arrowheads]. C. PAS with diastase stain shows proliferated bile ductules [blue arrowheads] in stroma with mixed inflammatory infiltrate. D. Neutrophils about ballooned hepatocyte (satellitosis) [yellow arrowheads]. Councilman bodies [green arrowheads].

Notes:
*If portal inflammatory infiltrates more than mild, r/o other causes i.e. [[viral hepatitis]].
*Mallory bodies once thought to be characteristic; now considered non-specific and generally poorly understood.<ref>{{cite journal |author=Jensen K, Gluud C |title=The Mallory body: theories on development and pathological significance (Part 2 of a literature survey) |journal=Hepatology |volume=20 |issue=5 |pages=1330-42 |year=1994 |month=November |pmid=7927269 |doi= |url=}}</ref>
*Some consider ''alcoholic liver disease'' a clinical diagnosis, i.e. as a pathologist one does not diagnose it.<ref>MG. September 2009.</ref>

==Non-alcoholic fatty liver disease==
*Abbreviated ''NAFLD''.
*Fatty liver that is not due to alcohol; includes obesity-related fatty liver, metabolic disease/diabetes-related fatty liver.

===NASH===
*Non-alcoholic steatohepatitis - see ''steatohepatitis'' section.
*Histologically indistinguishable from ASH.
*NASH is a ''clinical diagnosis'' based on exclusion of alcohol.

==Steatohepatitis==
{{Main|Steatohepatitis}}

=Autoimmune=
==Autoimmune hepatitis==
*Abbreviated ''AIH''.
{{Main|Autoimmune hepatitis}}

==Primary biliary cirrhosis==
*Abbreviated PBC.
{{Main|Primary biliary cirrhosis}}

==Autoimmune hepatitis with obstruction - combined changes==
A. [[File:1 AIH OBS 1.tif|Low power shows inflammation; portal triads, lobules, central veins cannot be distinguished (40X).]]
 
B. [[File:2 AIH OBS 1.tif|Trichrome shows central venous sclerosis (red arrowhead), periportal fibrosis (green arrowhead), & space of Disse collagenization (yellow arrowhead); juxtaposition of central vein & portal tract indicates collapse, no definite bridging was seen (100X)]]
 
C. [[File:3 AIH OBS 1.tif|Central vein is inflamed with a rare plasma cell (cyan arrowhead) (400X).]]
 
D. [[File:4 AIH OBS 1.tif|Interface hepatitis with plasma cells (yellow arrows) and ballooned hepatocytes (red arrows). Lobule is disorganized (400X).]]
 
E. [[File:5 AIH OBS 1.tif|Proliferating bile ductules (blue arrows) with occasional neutrophils (fucsia arrows), indicative of obstruction, but not acute cholangitis, which requires inflamed bile duct itself, best diagnosed with associated blood vessel (400X).]]
 
F. [[File:6 AIH OBS 1.tif|Rare distorted rosettes with greenish brown strands of bile (left arrow) or bile plugs (right arrow) (400X).]]
 
Patient with SLE and obstructive jaundice that resolved with apparent passage of stone. A. Low power shows inflammation; portal triads, lobules, central veins cannot be distinguished. B. Trichrome shows central venous sclerosis (red arrowhead), periportal fibrosis (green arrowhead), & space of Disse collagenization (yellow arrowhead); juxtaposition of central vein & portal tract indicates collapse, no definite bridging was seen. C. Central vein is inflamed with a rare plasma cell (cyan arrowhead). D. Interface hepatitis with plasma cells (yellow arrows) and ballooned hepatocytes (red arrows). Lobule is disorganized. E. Proliferating bile ductules (blue arrows) with occasional neutrophils (fucsia arrows), indicative of obstruction, but not acute cholangitis, which requires inflamed bile duct itself, best diagnosed with associated blood vessel. F. Rare distorted rosettes with greenish brown strands of bile (left arrow) or bile plugs (right arrow).

==Autoimmune hepatitis-primary biliary cirrhosis overlap syndrome==
*Abbreviation ''AIH-PBC OS''.
===General===
Epidemiology:
*Rare.

Serology:<ref name=pmid19491855>{{Cite journal | last1 = Muratori | first1 = P. | last2 = Granito | first2 = A. | last3 = Pappas | first3 = G. | last4 = Pendino | first4 = GM. | last5 = Quarneti | first5 = C. | last6 = Cicola | first6 = R. | last7 = Menichella | first7 = R. | last8 = Ferri | first8 = S. | last9 = Cassani | first9 = F. | title = The serological profile of the autoimmune hepatitis/primary biliary cirrhosis overlap syndrome. | journal = Am J Gastroenterol | volume = 104 | issue = 6 | pages = 1420-5 | month = Jun | year = 2009 | doi = 10.1038/ajg.2009.126 | PMID = 19491855 }}</ref>
*AMA +ve.
*Anti-dsDNA +ve.

===Microscopic===
:See: ''[[autoimmune hepatitis]]'' and ''[[primary biliary cirrhosis]]''.
A. [[File:1 AIH PBC 1 680x512px.tif|Expanded portal tracts with fuzzy edges (40X).]]
 
B. [[File:2 AIH PBC 1 680x512px.tif|Interface hepatitis with plasma cells (400X).]]
 
C. [[File:3 AIH PBC 1 680x512px.tif|Loose granuloma (400X).]]
 
D. [[File:4 AIH PBC 1 680x512px.tif|Damaged bile duct (400X).]]
 
AIH/PBC overlap. AMA & ANA positive with Alkaline phosphatase > 2 upper limit of normal & one ALT > 5 times upper limit of normal. A. Expanded portal tracts with fuzzy edges. B. Interface hepatitis with plasma cells. C. Loose granuloma. D. Damaged bile duct.

==Primary sclerosing cholangitis==
*Abbreviated ''PSC''.
{{Main|Primary sclerosing cholangitis}}

=Hereditary=
==Caroli disease==
===General===
*Genetic disease.
**Frequently associated with [[autosomal recessive polycystic kidney disease]] (ARPKD).<ref name=omim263200>{{OMIM|263200}}</ref>
**May be seen in isolation.<ref name=omim600643>{{OMIM|600643}}</ref>

Clinical:<ref name=pmid17461493>{{Cite journal | last1 = Yonem | first1 = O. | last2 = Bayraktar | first2 = Y. | title = Clinical characteristics of Caroli's syndrome. | journal = World J Gastroenterol | volume = 13 | issue = 13 | pages = 1934-7 | month = Apr | year = 2007 | doi = | PMID = 17461493 }}</ref>
*Recurrent [[cholangitis]].
*Recurrent [[cholelithiasis]].
*[[Cholangiocarcinoma]]<ref name=pmid17461492>{{Cite journal | last1 = Yonem | first1 = O. | last2 = Bayraktar | first2 = Y. | title = Clinical characteristics of Caroli's disease. | journal = World J Gastroenterol | volume = 13 | issue = 13 | pages = 1930-3 | month = Apr | year = 2007 | doi = | PMID = 17461492 }}</ref> - seen in ~7% of cases.<ref name=pmid15347876>{{Cite journal | last1 = Karim | first1 = AS. | title = Caroli's disease. | journal = Indian Pediatr | volume = 41 | issue = 8 | pages = 848-50 | month = Aug | year = 2004 | doi = | PMID = 15347876 }}</ref>

Note:
*''Caroli syndrome'' = Caroli disease + congenital hepatic fibrosis.<ref name=pmid15888616>{{Cite journal | last1 = Brancatelli | first1 = G. | last2 = Federle | first2 = MP. | last3 = Vilgrain | first3 = V. | last4 = Vullierme | first4 = MP. | last5 = Marin | first5 = D. | last6 = Lagalla | first6 = R. | title = Fibropolycystic liver disease: CT and MR imaging findings. | journal = Radiographics | volume = 25 | issue = 3 | pages = 659-70 | month = | year = | doi = 10.1148/rg.253045114 | PMID = 15888616 | URL = http://radiographics.rsna.org/content/25/3/659.long }}</ref>

===Gross===
*Dilated bile ducts.<ref name=omim263200/>

===Microscopic===
Features:<ref name=pmid17461493/>
*Dilated bile ducts.
*Periductal fibrosis. (???)
*+/-Fibrosis.

Image:
*[http://www.meddean.luc.edu/lumen/MedEd/orfpath/11-3-10.jpg Caroli disease (meddean.luc.edu)].<ref>URL: [http://www.meddean.luc.edu/lumen/MedEd/orfpath/develop.htm http://www.meddean.luc.edu/lumen/MedEd/orfpath/develop.htm]. Accessed on: 1 December 2011.</ref>

==Hereditary hemochromatosis==
:''For secondary causes see [[secondary hemochromatosis]]''.
{{Main|Hereditary hemochromatosis}}

==Wilson disease==
{{Main|Wilson's disease}}

==Alpha-1 antitrypsin deficiency==
*[[AKA]] ''alpha1-antiprotease inhibitor deficiency''.
{{Main|Alpha-1 antitrypsin deficiency }}

=Other=
==Primary Systemic Sclerosis==
[[File:5 05168051 sl 1.png |Primary systemic sclerosis in the liver]]
[[File:5 05168051 sl 2.png |Primary systemic sclerosis in the liver]]
[[File:5 05168051 sl 3.png |Primary systemic sclerosis in the liver]]
[[File:5 05168051 sl 4.png |Primary systemic sclerosis in the liver]]
[[File:5 05168051 sl 5.png |Primary systemic sclerosis in the liver]]
[[File:5 05168051 sl 6.png |Primary systemic sclerosis in the liver]]
 
Primary systemic sclerosis in a 67 year old White, non-Hispanic man who had undergone renal transplantation for idiopathic nodular glomerusclerosis, which had recurred in 2013. He had been scheduled to receive a second transplantation, but had not yet received one. The patient had a positive anti-nuclear antigen study, with a positive scleroderma antibody (SCL-70), a high SCL-70 antibody index of 3.9, and negative DNA, Chromatin, Anti-Riboscomal P, SS-A, SS-B, anti Smith, RNP, JO-1, anticentromere antibody and rheumatoid factor serologic studies. Hepatitis A, B, and C serologic studies were negative. Liver function tests showed normal albumin and total bilirubin levels with alkaline phosphatase of 712 IU/L (35-129 normal range), alanine aminotransferase 59 IU/L (5-41 normal range), and aspartate aminotransferase 68 IU/L (5-37 normal range). This case provisions many of the features known to be present in primary systemic sclerosis as seen in the skin. A. At low power, triads appear almost as white ghosts against a relatively normal set of hepatocyte lobules. B. Closer examination reveals some triads to be expanded, with peripheral bile ductular proliferation and modest associated chronic inflammation without interface hepatitis. C. Portal arterioles had thick walls; inflammation included lymphocytes and occasional plasma cells. D. Trichrome failed to stain the material in the triads blue, but did show space of Disse collagenization. E. PAS with diastase showed positive staining of the material with emphasis on the arteriole walls. F. Hemosiderosis was seen on iron stain.

==Budd-Chiari syndrome==
*[[AKA]] ''hepatic vein obstruction''.
===General===
*Hepatic outflow obstruction.

Clinical triad:<ref name=pmid21573256>{{Cite journal | last1 = Fox | first1 = MA. | last2 = Fox | first2 = JA. | last3 = Davies | first3 = MH. | title = Budd-Chiari syndrome--a review of the diagnosis and management. | journal = Acute Med | volume = 10 | issue = 1 | pages = 5-9 | month = | year = 2011 | doi = | PMID = 21573256 }}</ref>
*Ascites.
*Abdominal pain.
*Hepatomegaly.

Etiology:
*~50% have a [[myeloproliferative disease]].<ref name=pmid18814079>{{Cite journal | last1 = Plessier | first1 = A. | last2 = Valla | first2 = DC. | title = Budd-Chiari syndrome. | journal = Semin Liver Dis | volume = 28 | issue = 3 | pages = 259-69 | month = Aug | year = 2008 | doi = 10.1055/s-0028-1085094 | PMID = 18814079 }}</ref>
*May be due to mass effect from a tumour.

Clinical DDx:
*[[Hepatic veno-occlusive disease]].

===Microscopic===
Features:<ref name=pmid17569137>{{Cite journal | last1 = Aydinli | first1 = M. | last2 = Bayraktar | first2 = Y. | title = Budd-Chiari syndrome: etiology, pathogenesis and diagnosis. | journal = World J Gastroenterol | volume = 13 | issue = 19 | pages = 2693-6 | month = May | year = 2007 | doi = | PMID = 17569137 | url=http://www.wjgnet.com/1007-9327/full/v13/i19/2693.htm }}</ref>
*Sinusoidal dilation in zone III (congestion).
*+/-Hepatocyte drop-out.
*+/-Centrilobular fibrosis.

DDx congestion:
*Congestive heart failure ([[congestive hepatopathy]]).
*Constrictive pericarditis.

==Vanishing bile duct syndrome==
*[[AKA]] ''bile duct loss'', [[AKA]] ''ductopenia''.<ref name=pmid11521176/>
===General===
*Fatal.

DDx:<ref name=pmid18242505/>
*[[Primary biliary cirrhosis]].
*[[Primary sclerosing cholangitis]].
*[[GVHD]].<ref name=pmid7994249>{{Cite journal | last1 = Yeh | first1 = KH. | last2 = Hsieh | first2 = HC. | last3 = Tang | first3 = JL. | last4 = Lin | first4 = MT. | last5 = Yang | first5 = CH. | last6 = Chen | first6 = YC. | title = Severe isolated acute hepatic graft-versus-host disease with vanishing bile duct syndrome. | journal = Bone Marrow Transplant | volume = 14 | issue = 2 | pages = 319-21 | month = Aug | year = 1994 | doi = | PMID = 7994249 }}</ref>
*[[Drug-induced liver disease|Drugs]].<ref name=pmid11352118>{{Cite journal | last1 = Chitturi | first1 = S. | last2 = Farrell | first2 = GC. | title = Drug-induced cholestasis. | journal = Semin Gastrointest Dis | volume = 12 | issue = 2 | pages = 113-24 | month = Apr | year = 2001 | doi = | PMID = 11352118 }}</ref>
*Chronic rejection.<ref name=pmid11521176>{{Cite journal | last1 = Inomata | first1 = Y. | last2 = Tanaka | first2 = K. | title = Pathogenesis and treatment of bile duct loss after liver transplantation. | journal = J Hepatobiliary Pancreat Surg | volume = 8 | issue = 4 | pages = 316-22 | month = | year = 2001 | doi = 10.1007/s0053410080316 | PMID = 11521176 }}</ref>

===Microscopic===
Features:<ref name=pmid18242505>{{Cite journal | last1 = Reau | first1 = NS. | last2 = Jensen | first2 = DM. | title = Vanishing bile duct syndrome. | journal = Clin Liver Dis | volume = 12 | issue = 1 | pages = 203-17, x | month = Feb | year = 2008 | doi = 10.1016/j.cld.2007.11.007 | PMID = 18242505 }}</ref>
*Loss of intrahepatitic bile ducts - '''key feature'''.
*Cholestasis.

Note:
*May occur without fibrosis and inflammation; thus, can be easy to miss.

===IHC===
*[[CK7]] -ve.
**Marks bile ducts.
==Hepatic Graft versus Host Disease (L-GVHD)==
[[File:3 579232643 sl 1.png| Hepatic graft versus host disease (L-GVHD)]]
[[File:3 579232643 sl 2.png| Hepatic graft versus host disease (L-GVHD)]]
[[File:3 579232643 sl 3.png| Hepatic graft versus host disease (L-GVHD)]]
[[File:3 579232643 sl 4.png| Hepatic graft versus host disease (L-GVHD)]]
[[File:3 579232643 sl 5.png| Hepatic graft versus host disease (L-GVHD)]]
[[File:3 579232643 sl 6.png| Hepatic graft versus host disease (L-GVHD)]]
[[File:3 579232643 sl 7.png| Hepatic graft versus host disease (L-GVHD)]]
 
Hepatic graft versus host disease (L-GVHD) in a 22 yo man who underwent bone marrow transplantation after developing ALL. A. Low power view shows brownish discoloration in triad, but is otherwise of little interest. B. Arterioles in triads were accompanied by bile ducts in only 30% of cases; this image shows an arteriole without a bile duct. Note the pigment and the accompanying macrophage/lymphocyte inflammation, not extreme. The added chronic inflammation is a feature of chronic L-GVHD. C. Bile ducts, when shown, showed extensive damage, here seen as loss of cytoplasm, and nuclear pleomorphism and hyperchromasia (other degenerative changes, not seen here, include nuclear dropout or necrosis, cytoplasmic eosinophilia, loss of duct lumen). Lymphocytosis into the ducts was not seen. D. Ballooned hepatocytes and dilated canaliculi were seen. E. Pigment was present, but mostly in Kupffer cells, not hepatocytes or as bile plugs. F. Up to two foci of spotty necrosis were seen in a 100X field (field shown is 200X); not shown are rare apoptotic hepatocytes. G. An iron stain showed the pigment represented extemsive iron deposition, with emphasis on Kupffer cells and portal triad macrophages, frustrating definite assessment of bile plugs in canaliculi. The hemosiderosis resulted from the many blood transfusions the patient had received.

==Extrahepatic biliary obstruction==
A. [[File:1 OBS 3 680x512px.tif|Sinusoidal dilatation, circular spaces of hepatocytes, small portal triads(40X).]]
 
B. [[File:2 OBS 3 680x512px.tif|Bile in hepatocytes about central vein & in plugs in canaliculi [yellow arrowhead] (400X).]]
 
C. [[File:3 OBS 3 680x512px.tif|Trichrome shows fibrosis about central vein (400X).]]
 
D. [[File:4 OBS 3 680x512px.tif|PAS with diastase shows portal triads with mild edema and chronic inflammation, without tortuous bile duct (400X).]]
 
Early extrahepatic biliary obstruction, demonstrated radiographically, transient, with rise in bilirubin, alkaline phosphatase, and transaminases. Pure canalicular cholestasis near terminal hepatic venules also seen in acute hepatitis, drug reactions, benign recurrent cholestasis, pregnancy, sepsis, & lymphomas. A. Sinusoidal dilatation, circular spaces of hepatocytes, small portal triads. B. Bile in hepatocytes about central vein & in plugs in canaliculi [yellow arrowhead]. C. Trichrome shows fibrosis about central vein. D. PAS with diastase shows portal triads with mild edema and chronic inflammation, without tortuous bile duct.
 
A. [[File:1 OBS 2 680x512px.tif|Expanded inflamed portal triads, swollen hepatocytes (40X)]]
 
B. [[File:2 OBS 2 680x512px.tif|Edematous stroma, proliferating ductules [yellow arrowheads], PAS-D macrophages [red arrowhead] (PAS with diastasse, 200X)]]
 
C. [[File:3 OBS 2 680x512px.tif|Disordered, often swollen hepatocytes,some with feathery degeneration (net like spaces in cytoplasm [blue arrowhead], rare Councilman body [green arrowhead] (400X)]]
 
D. [[File:4 OBS 2 1360x1024px.tif|Bile in hepatocytes [cyan arrrowhead] & in canaliculi [purple arrowheads]. Empty acinar spaces bounded by hepatocytes [orange arrowhead] (400X, higher pixel),]]
 
Changes of extrahepatic biliary obstruction, months duration. A. Expanded inflamed portal triads, swollen hepatocytes. B. Edematous stroma, proliferating ductules [yellow arrowheads], PAS-D macrophages [red arrowhead]. C. Disordered, often swollen hepatocytes,some with feathery degeneration (net like spaces in cytoplasm) [blue arrowhead], rare Councilman body [green arrowhead]. D. Bile in hepatocytes [cyan arrrowhead] & in canaliculi [purple arrowheads]. Empty acinar spaces bounded by hepatocytes [orange arrowhead].
 
A. [[File:1 Bd obs 4 680x512px.tif|Expanded, light colored portal triads (arrows)(20X).]]
 
B. [[File:2 Bd obs 4 680x512px.tif|Proliferating bile ductules (cyan arrows) with neutrophils (yellow arrows), not specific for acute cholangitis, of assistance with large bile duct obstruction (400X)..]]
 
C. [[File:3 Bd obs 4 680x512px.tif|Uninflamed interlobular duct (yellow arrow) with, accompanying blood vessel (red arrow) (400X)]]
 
D. [[File:4 Bd obs 4 680x512px.tif|Bile infarct with pyknotic nuclei (arrows)(400X).]]
 
E. [[File:5 Bd obs 4 680x512px.tif|Bile (arrow) in interlobular bile duct with disordered nuclei (400X).]]
 
F. [[File:6 Bd obs 4 680x512px.tif|Bile plugs in cannaliculi (red arrows), feathery degeneration producing foamy macrophage like hepatocytes (yellow arrows)(400X).]]
 
Large bile duct obstruction. A. Expanded, light colored portal triads (arrows). B. Proliferating bile ductules (cyan arrows) with neutrophils (yellow arrows), not specific for acute cholangitis, of assistance with large bile duct obstruction. C. Uninflamed interlobular duct (yellow arrow) with, accompanying blood vessel (red arrow). D. Bile infarct with pyknotic nuclei (arrows). E. Bile (arrow) in interlobular bile duct with disordered nuclei. F. Bile plugs in cannaliculi (red arrows), feathery degeneration producing foamy macrophage-like hepatocytes (yellow arrows).

==Congestive hepatopathy==
===General===
*Liver failure due to (right) heart failure.
*AKA ''cardiac cirrhosis'' - a term used by clinicians.
**Generally, it does not satisfy pathologic criteria for cirrhosis.<ref>URL: [http://emedicine.medscape.com/article/151792-overview http://emedicine.medscape.com/article/151792-overview]. Accessed on: 17 June 2010.</ref>

===Gross===
*"Nutmeg" liver - yellow spotted appearance.

===Microscopic===
Features:<ref>URL: [http://emedicine.medscape.com/article/151792-diagnosis http://emedicine.medscape.com/article/151792-diagnosis]. Accessed on: 17 June 2010.</ref>
*Zone III atrophy.
*Portal venule (central vein) distension.
*Perisinusoidal fibrosis - progresses to centrilobular fibrosis and then diffuse fibrosis.
*Dilation of sinusoids in ''all'' zone III areas - '''key feature'''.<ref>Suggested by OA. September 2009.</ref>

DDx:
*[[Hemangioma of the liver]] - should be focal lesion.
Cardiac (congestive) hepatopathy, wherein outflow obstruction occurs secondary to backflow from a failing heart, and Budd Chiari syndrome, wherein obstruction of outflow occurs secondary to obstruction, usually thrombotic, have overlapping features, including sinusoidal dilation with emphasis upon the central vein, space of Disse erythrocytes, centrilobular inflammation, hemorrhage, bile ductules, and hemosiderin, and portal inflammation, fibrosis and bile ductular reaction. Centrilobular dropout/necrosis is more common in Budd Chiari syndrome, while peri-central venous and sinusoidal fibrosis are more common in cardiac hepatopathy. In end stage liver, fibrosis for cardiac hepatopathy comprises stellate centrizonal fibrous with haphazard spread, as opposed to the more frequent nodular cirrhosis in Budd-Chiari. Clinical findings are important to take into account, as cardiac failure is usually well known at the time of diagnosis as are the clinical predictors of Budd Chiari syndrome, prothrombotic states, myeloproliferative diseases, and oral contraceptive use. <ref name=pmid27681331 >{{cite journal |author=Gonzalez RS, Gilger MA, Huh WJ, Washington MK |title=The spectrum of histologic findings in hepatic outflow obstruction |journal= Arch Pathol Lab Med |volume=141 |issue= |pages=98 |year=2017 |pmid= 27681331 ||doi= 10.5858/arpa.2015-0388-OA |url=http http://www.archivesofpathology.org/doi/10.5858/arpa.2015-0388-OA?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%3dpubmed&code=coap-site }}</ref>
====Images====
<gallery>
Image:Congestive_hepatopathy_high_mag.jpg | Mild congestive hepatopathy. (WC) 
A.[[File:1 CEN NEC 1 680x512px.tif|PAS without diastase shows ovoids of necrosis {40X).]] 
B. [[File:2 CEN NEC 1 680x512px.tif|Necrosis with central vein [yellow arrowhead], inflammatory cells, residual Councilman body [green arrowhead], and hepatocyte with mitotic figure [red arrowhead] (400X).]]
 
C. [[File:3 CEN NEC 1 680x512px.tif|Trichrome highlights fibrosis about central vein [yellow arrowhead] & shows beginning scar formation [green arrowheads]. Note residual atrophic hepatocytes [blue arrowheads] (400X).]]
 
D. [[File:4 CEN NEC 1 680x512px.tif|Portal triads are largely unaffected (400X).]]
|} 
Centrilobular necrosis (seen in circulatory failure and with toxins/drugs). A. PAS without diastase shows ovoids of necrosis. B. Necrosis with central vein [yellow arrowhead], inflammatory cells, residual Councilman body [green arrowhead], and hepatocyte with mitotic figure [red arrowhead]. C. Trichrome highlights fibrosis about central vein [yellow arrowhead] & shows beginning scar formation [green arrowheads]. Note residual atrophic hepatocytes [blue arrowheads]. D. Portal triads are largely unaffected (LR 400X)
 
A. [[File:1 CHF 1 680x512px.tif|Dilated and undilated sinusoidal regions (40X).]]
 
B. [[File:2 CHF 1 680x512px.tif|Thrombi in sinusoids; glycogenated nuclei likely reflect patient’s diabetes mellitus (400X).]]
 
C. [[File:3 CHF 1 680x512px.tif|Dilated portal vein (400X).]]
 
D. [[File:4 CHF 1 680x512px.tif|Reticulin shows collapse (thick black lines) as well as a dilated portal vein (200X).]]
 
E. [[File:5 CHF 1 680x512px.tif|Trichrome shows space of Disse collagenization (pericellular fibrosis) (200X).]]
 
F. [[File:6 CHF 1 680x512px.tif|Trichrome shows periportal fibrosis; no bridging was seen (200X).]]

Patient with congestive heart failure and stage I fibrosis. A. Dilated and undilated sinusoidal regions. B. Thrombi in sinusoids; glycogenated nuclei likely reflect patient’s diabetes mellitus. C. Dilated portal vein. D. Reticulin shows black lines of bridging, too thick for collapse. E. Trichrome shows space of Disse collagenization (pericellular fibrosis). F. Trichrome shows bridge beginning off to right; when it is more than a mere spike, it is a bridge.

==Drug-induced liver disease==
*[[AKA]] ''drug-induced liver toxicity''.
{{Main|Drug-induced liver disease}}

==Focal nodular hyperplasia==
*Abbreviated ''FNH''.
{{Main|Focal nodular hyperplasia}}

==Nodular regenerative hyperplasia==
===General===
*Associated with renal transplants, [[bone marrow transplant]]s and [[vasculitides]].<ref name=Ref_PBoD922>{{Ref PBoD|922}}</ref>
*Can lead to [[portal hypertension]] and many of the associated complications.<ref name=pmid22554152>{{Cite journal | last1 = Bissonnette | first1 = J. | last2 = Généreux | first2 = A. | last3 = Côté | first3 = J. | last4 = Nguyen | first4 = B. | last5 = Perreault | first5 = P. | last6 = Bouchard | first6 = L. | last7 = Pomier-Layrargues | first7 = G. | title = Hepatic hemodynamics in 24 patients with nodular regenerative hyperplasia and symptomatic portal hypertension. | journal = J Gastroenterol Hepatol | volume = 27 | issue = 8 | pages = 1336-40 | month = Aug | year = 2012 | doi = 10.1111/j.1440-1746.2012.07168.x | PMID = 22554152 }}
</ref>

====Etiology====
*Arterial hypervascularity secondary to loss of hepatic vein radicles (loss of central venule in hepatic lobule).<ref name=Ref_PBoD922>{{Ref PBoD|922}}</ref>

ASIDE: radicle = ramulus - smallest branch or vessel or nerve.<ref name=Dorlands2>Dorland's Medical Dictionary. 30th Ed.</ref>

===Gross===
*Diffuse nodularity - whole liver.

===Microscopic===
Features:<ref name=Ref_PBoD922>{{Ref PBoD|922}}</ref>
*"Plump" hepatocytes surrounded by atrophic ones.
*No fibrosis.

==Sinuosoidal obstruction syndrome==
*May be referred to as ''Hepatic veno-occlusive disease''.<ref name=pmid11928077>{{Cite journal | last1 = DeLeve | first1 = LD. | last2 = Shulman | first2 = HM. | last3 = McDonald | first3 = GB. | title = Toxic injury to hepatic sinusoids: sinusoidal obstruction syndrome (veno-occlusive disease). | journal = Semin Liver Dis | volume = 22 | issue = 1 | pages = 27-42 | month = Feb | year = 2002 | doi = 10.1055/s-2002-23204 | PMID = 11928077 }}.</ref>
===General===
*Term for obstruction due to toxicity from a chemotherapeutic agent.<ref name=pmid16393276>{{Cite journal | last1 = Helmy | first1 = A. | title = Review article: updates in the pathogenesis and therapy of hepatic sinusoidal obstruction syndrome. | journal = Aliment Pharmacol Ther | volume = 23 | issue = 1 | pages = 11-25 | month = Jan | year = 2006 | doi = 10.1111/j.1365-2036.2006.02742.x | PMID = 16393276 }}</ref><ref name=pmid17569137>{{Cite journal | last1 = Aydinli | first1 = M. | last2 = Bayraktar | first2 = Y. | title = Budd-Chiari syndrome: etiology, pathogenesis and diagnosis. | journal = World J Gastroenterol | volume = 13 | issue = 19 | pages = 2693-6 | month = May | year = 2007 | doi = | PMID = 17569137 | url=http://www.wjgnet.com/1007-9327/full/v13/i19/2693.htm }}</ref>

Clinical DDx:
*[[Budd-Chiari syndrome]].

===Microscopic===
Features:<ref name=pmid17569137>{{Cite journal | last1 = Aydinli | first1 = M. | last2 = Bayraktar | first2 = Y. | title = Budd-Chiari syndrome: etiology, pathogenesis and diagnosis. | journal = World J Gastroenterol | volume = 13 | issue = 19 | pages = 2693-6 | month = May | year = 2007 | doi = | PMID = 17569137 | url=http://www.wjgnet.com/1007-9327/full/v13/i19/2693.htm }}</ref>
*Subendothelial swelling in hepatic venules.

Negatives:
*No thrombosis.

==Ascending Cholangitis (Acute Cholangitis)==
===General===
*Term for infection of bile ducts, usually due to obstruction

Clinical DDx:

===Microscopic===
====Images====

A. [[File:1 asc chol 1 680x512px.tif|Rounded, clear (edematous) portal tracts (arrows) separated by hepatocytes with dilated sinusoids (Row 1 Left 40X).]]
 
B. [[File:2 asc chol 1 680x512px.tif|Neutrophils about hepatocytes (arrows) have spilled into the lobule from a portal tract (Row 1 Right 200X).]]
 
C. [[File:3 asc chol 1 680x512px.tif|Proliferated bile ductules (arrows) bearing neutrophils within epithelium and lumens are features of obstruction that should prompt a search for interlobular ducts with acute inflammation (Row 2 Left 400X).]]
 
D. [[File:4 asc chol 1 680x512px.tif|The epithelium of the ducts can be severely degenerated. Neutrophils (cyan arrows) invade epithelium of an interlobular duct that are recognizable mainly as a circle of rounded nuclei; the associated arteriole (red arrow) should be identified to ensure an interlobular duct is being evaluated. Note the proliferated bile ductules (blue arrows) (Row 2 Right 400X).]]
 
E. [[File:5 asc chol 1 680x512px.tif|A PAS without diastase stain colors the arteriole (blue arrow), as well as the rim of the interlobular duct within which lies a neutrophil (cyan arrow) (Row 2 Right 400X). .]]
 
F. [[File:6 asc chol 1 680x512px.tif|A PAS with diastase stain colors the arteriole (red arrow), as well as the rim of the interlobular duct within which lies a neutrophil (cyan arrow) (Row 1 Right 400X)]]
 
Acute cholangitis in a patient with multiple bile duct procedures. After the biopsy, removal of bile duct stones released pus. A. Rounded, clear (edematous) portal tracts (arrows) separated by hepatocytes with dilated sinusoids. B. Neutrophils about hepatocytes (arrows) have spilled into the lobule from a portal tract. C, Proliferated bile ductules (arrows) bearing neutrophils within epithelium and lumens are features of obstruction that should prompt a search for interlobular ducts with acute inflammation. D. The epithelium of the ducts can be severely degenerated. Neutrophils (cyan arrows) invade epithelium of an interlobular duct that are recognizable mainly as a circle of rounded nuclei; the associated arteriole (red arrow) should be identified to ensure an interlobular duct is being evaluated. Note the proliferated bile ductules (blue arrows). E. A PAS without diastase stain colors the arteriole (blue arrow), as well as the rim of the interlobular duct within which lies a neutrophil (cyan arrow). F. A PAS with diastase stain colors the arteriole (red arrow), as well as the rim of the interlobular duct within which lies a neutrophil (cyan arrow).

A.[[File:1 Sep Acu Cho 1 680x512px.tif|Low power shows variably sized inflamed portal tracts (40X)]]
 
B. [[File:2 Sep Acu Cho 1 680x512px.tif|Trichrome shows dilated sinusoids and space of Disse collagenization (200X)]]
 
C. [[File:3 Sep Acu Cho 1 680x512px.tif|Inflammatory focus with macrophages and neutrophils (400X).]]
 
D. [[File:4 Sep Acu Cho 1 680x512px.tif|PAS with diastase shows proliferated bile ductules at edge of triad with neutrophils, which should not be used to make a definite diagnosis of acute cholangitis (400X).]]
 
E. [[File:5 Sep Acu Cho 1 680x512px.tif|PAS without diastase showing acutely inflamed bile duct, with accompanying blood vessel of similar size, diagnostic of acute cholangitis (400X).]]
 
F. [[File:6 Sep Acu Cho 1 680x512px.tif|PAS with diastase showing neutrophil in bille duct lumen, diagnostic of acute cholangitis (400X).]]
 
Patient with sepsis and acute cholangitis. A. Low power shows variably sized inflamed portal tracts. B. Trichrome shows dilated sinusoids and space of Disse collagenization. C. Inflammatory focus with macrophages and neutrophils. D. PAS with diastase shows proliferated bile ductules at edge of triad with neutrophils, which should not be used to make a definite diagnosis of acute cholangitis. E. PAS without diastase showing acutely inflamed bile duct, with accompanying blood vessel of similar size, diagnostic of acute cholangitis. F. PAS with diastase showing neutrophil in bille duct lumen, diagnostic of acute cholangitis.

==Polycystic kidney disease and the liver==
{{Main|Cystic kidney disease}}
===General===
Complications of PKD in the liver:<ref>{{Ref MacSween|174-5}}</ref>
#Infected cyst.
#Cholangiocarcinoma.
#Cholestasis/obstruction due to duct compression.<ref>URL: [http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=9184868 http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=9184868]. Accessed on: 23 September 2009.</ref>

Cysts:
*Cysts in the liver, like the kidney, are thought to enlarge with age.

===Microscopic===
Features:<ref>{{Ref MacSween|176}}</ref>
*''Von Meyenburg complexes'' ([[bile duct hamartoma]]):
**Cluster of dilated ducts with "altered" bile.
**Surrounded by collagenous stroma.
**Separate from the portal areas.<ref>Meyenburg complex. Stedman's Medical Dictionary. 27th Ed.</reF>

Images:
*[http://commons.wikimedia.org/wiki/File:Von_Meyenburg_complex_low_mag.jpg Von Meyenburg complex - bile duct hamartoma (WC)].
*[http://commons.wikimedia.org/wiki/File:Bile_duct_hamartoma_intermed_mag.jpg Bile duct hamartoma (WC)].

Notes:
*Appearance on ultrasound<ref name=pmid17287178>Bile duct hamartomas--the von Meyenburg complex. Salles VJ, Marotta A, Netto JM, Speranzini MB, Martins MR. Hepatobiliary Pancreat Dis Int. 2007 Feb;6(1):108-9. PMID 17287178.</ref> and CT (hypodense)<ref name=pmid19294869>[The von Meyenburg complex] Schwab SA, Bautz W, Uder M, Kuefner MA. Rontgenpraxis. 2008;56(6):241-4. German. PMID 19294869.</ref> - similar to metastases.

==Peliosis hepatis==
===General===
*Associated with:
**Infections.
**Malignancy.
**Other stuff.
*Rarely biopsied.

===Microscopic===
Features:
*Cyst lined by endothelium.
**Usu. incomplete.
*Blood.
A. [[File:1 PEL 1 680x512px.tif|Hemorrhage at left end, dilated sinusoids elsewhere (20X).]]
 
B. [[File:2 PEL 1 680x512px.tif|Ramifying dilated sinusoidal spaces (100X).]]
 
C. [[File:3 PEL 1 680x512px.tif|PAS with diastase shows flat lining (400X).]]
 
D. [[File:4 PEL 1 680x512px.tif|Necrotic hepatocytes in cords, presumably due to pressure (400X).]]
 
Peliosis hepatis. A. Hemorrhage at left end, dilated sinusoids elsewhere. B. Ramifying dilated sinusoidal spaces. C. PAS with diastase shows flat lining. D. Necrotic hepatocytes in cords, presumably due to pressure.

==Total parenteral nutrition==
*Abbreviated ''TPN''.

===General===
*Indication: short gut syndrome, others.

===Microscopic===
Variable - may range from: steatosis, steatohepatitis, cholestasis, fibrosis and cirrhosis.<ref name=pmid16766237>{{cite journal |author=Guglielmi FW, Boggio-Bertinet D, Federico A, ''et al.'' |title=Total parenteral nutrition-related gastroenterological complications |journal=Dig Liver Dis |volume=38 |issue=9 |pages=623–42 |year=2006 |month=September |pmid=16766237 |doi=10.1016/j.dld.2006.04.002 |url=}}</ref>

Features (classic):<ref>{{Cite journal | last1 = Li | first1 = SJ. | last2 = Nussbaum | first2 = MS. | last3 = McFadden | first3 = DW. | last4 = Gapen | first4 = CL. | last5 = Dayal | first5 = R. | last6 = Fischer | first6 = JE. | title = Addition of glucagon to total parenteral nutrition (TPN) prevents hepatic steatosis in rats. | journal = Surgery | volume = 104 | issue = 2 | pages = 350-7 | month = Aug | year = 1988 | doi = | PMID = 3135627 }}</ref><ref>{{Cite journal | last1 = Stanko | first1 = RT. | last2 = Nathan | first2 = G. | last3 = Mendelow | first3 = H. | last4 = Adibi | first4 = SA. | title = Development of hepatic cholestasis and fibrosis in patients with massive loss of intestine supported by prolonged parenteral nutrition. | journal = Gastroenterology | volume = 92 | issue = 1 | pages = 197-202 | month = Jan | year = 1987 | doi = | PMID = 3096806 }}
</ref>
*[[Steatosis]] (periportal) - early.
*Cholestasis - late.

==Giant cell hepatitis==
*[[AKA]] ''neonatal giant cell hepatitis''.

:See: ''[[Giant cell hepatitis]]''.

==Hepatic amyloidosis==
{{Main|Amyloidosis}}
*[[AKA]] ''liver amyloidosis''.
*[[AKA]] ''amyloidosis of the liver''.
===General===
*Diffuse abundant amyloid within the space of Disse is associated with [[portal hypertension]].<ref name=pmid1864548>{{Cite journal | last1 = Bion | first1 = E. | last2 = Brenard | first2 = R. | last3 = Pariente | first3 = EA. | last4 = Lebrec | first4 = D. | last5 = Degott | first5 = C. | last6 = Maitre | first6 = F. | last7 = Benhamou | first7 = JP. | title = Sinusoidal portal hypertension in hepatic amyloidosis. | journal = Gut | volume = 32 | issue = 2 | pages = 227-30 | month = Feb | year = 1991 | doi = | PMID = 1864548 | PMC = 1378815 | URL = http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1378815/?tool=pubmed }}</ref>

===Microscopic===
Features:
*Amorphous extracellular pink stuff on H&E - see ''[[amyloid]]'' article.

DDx:
*[[Fibrolamellar hepatocellular carcinoma]].

====Images====
<gallery>
Image:Hepatic_amyloidosis_-_low_mag.jpg | Amyloidosis of the liver - low mag. (WC)
Image:Hepatic_amyloidosis_-_intermed_mag.jpg | Amyloidosis of the liver - intermed. mag. (WC)
Image:Hepatic_amyloidosis_-_high_mag.jpg | Amyloidosis of the liver - high mag. (WC)
Image:Hepatic_amyloidosis_-_very_high_mag.jpg | Amyloidosis of the liver - very high mag. (WC)
</gallery>
A. [[File:1 AMY 1 680x512px.tif|Amorphous material replaces hepatic parenchyma [4X]]]
 
B. [[File:2 AMY 1 680x512px.tif|Material barely stains blue on trichrome [10X]]]
 
C. [[File:3 AMY 1 680x512px.tif|Material stains red on unpolarized Congo Red [40X]]]
 
D. [[File:4 AMY 1 680x512px.tif|Material stains apple green on polarized Congo Red [40X]]]
 
Amyloidosis. A. Amorphous material replaces hepatic parenchyma. B. Material barely stains blue on trichrome. C. Material stains red on unpolarized Congo Red. D. Material stains apple green on polarized Congo Red.

===Stains===
*[[Congo red]] +ve.

==Fulminant hepatic necrosis==
===General===
Etiology:
*Viral, i.e. [[Hepatitis A]], [[Hepatitis B]]; [[Hepatitis C]] - extremely rare.
*Trauma.
*Shock.

===Microscopic===

A. [[File:1 Necrosis 2 680x512px.tif| Submassive hepatic necrosis.]]
 
B. [[File:2 Necrosis 2 680x512px.tif| Submassive hepatic necrosis.]]
 
C. [[File:3 Necrosis 2 680x512px.tif| Submassive hepatic necrosis.]]
 
D. [[File:4 Necrosis 2 680x512px.tif| Submassive hepatic necrosis.]]
 
E. [[File:5 Necrosis 2 680x512px.tif| Submassive hepatic necrosis.]]
 
F. [[File:6 Necrosis 2 680x512px.tif| Submassive hepatic necrosis.]]
 
Submassive hepatic necrosis. Patient had transaminases in the thousands that rapidly dropped to normal. A/ Pink preserved parenchyma strews empty necrotic spaces. B. Focus of necrosis with no apparent hepatocytes macrophages abuts apparently normal liver. C. Iron stain shows the macrophages bear hemosiderin. D. Reticulin stain highlights the recently dead liver cells. E. Reticulin stain shows a necrotic bridge forming; the multiple small black circles preclude diagnosis of a fibrous bridge. F. Trichrome shows the necrotic bridge (“collapse”) lacks much collagen deposition, as would be expected for bridging fibrosis.

Features:
*Hepatocyte [[necrosis]].
*Bile duct proliferation.

DDx:
*[[Cholangiocarcinoma]].
*[[Angiosarcoma]].

==Secondary hemochromatosis==
:''For the hereditary one see [[hereditary hemochromatosis]]''.
===General===
*Iron overload secondary to blood transfusions for hereditary or acquired anemia.<ref name=pmid19727383/>
**Primary hemochromatosis due to a defect in iron processing - called ''[[hereditary hemochromatosis]]''.
*Imaging considered the best test, as iron deposition is patchy.<ref name=pmid19727383/>

Selected hereditary causes:<ref name=pmid19727383>{{Cite journal | last1 = Gattermann | first1 = N. | title = The treatment of secondary hemochromatosis. | journal = Dtsch Arztebl Int | volume = 106 | issue = 30 | pages = 499-504, I | month = Jul | year = 2009 | doi = 10.3238/arztebl.2009.0499 | PMID = 19727383 | PMC = 2735704 | URL = http://www.ncbi.nlm.nih.gov.myaccess.library.utoronto.ca/pmc/articles/PMC2735704/?tool=pubmed}}</ref>
*Thalassemia.
*[[Sickle cell anemia]].
*Hereditary sideroblastic anemia.

Selected acquired causes:<ref name=pmid19727383/>
*[[Myelodysplastic syndromes]]
*Myelofibrosis
*Aplastic anemia, intractable.

===Microscopic===
:See ''[[hereditary hemochromatosis]]''.

==Hepatic sarcoidosis==
{{Main|Hepatic sarcoidosis}}
==Overlapping Disorders==

[[File:1 Mixed Disorder 1 680x512px.tif|Changes of steatohepatitis and interface hepatitis, with granuloma. Patient with diabetes was ANA, AMA, HCV, HBV negative, without drugs known to produce granulomas or interface hepatitis. This may be a case of AMA negative primary biliary cirrhosis, but studies to determine that with certainty were not performed.]]
[[File:2 Mixed Disorder 1 680x512px.tif|Changes of steatohepatitis and interface hepatitis, with granuloma. Patient with diabetes was ANA, AMA, HCV, HBV negative, without drugs known to produce granulomas or interface hepatitis. This may be a case of AMA negative primary biliary cirrhosis, but studies to determine that with certainty were not performed.]]
[[File:3 Mixed Disorder 1 680x512px.tif|Changes of steatohepatitis and interface hepatitis, with granuloma. Patient with diabetes was ANA, AMA, HCV, HBV negative, without drugs known to produce granulomas or interface hepatitis. This may be a case of AMA negative primary biliary cirrhosis, but studies to determine that with certainty were not performed.]]
[[File:4 Mixed Disorder 1 680x512px.tif|Changes of steatohepatitis and interface hepatitis, with granuloma. Patient with diabetes was ANA, AMA, HCV, HBV negative, without drugs known to produce granulomas or interface hepatitis. This may be a case of AMA negative primary biliary cirrhosis, but studies to determine that with certainty were not performed.]]
[[File:5 Mixed Disorder 1 680x512px.tif|Changes of steatohepatitis and interface hepatitis, with granuloma. Patient with diabetes was ANA, AMA, HCV, HBV negative, without drugs known to produce granulomas or interface hepatitis. This may be a case of AMA negative primary biliary cirrhosis, but studies to determine that with certainty were not performed.]]
[[File:6 Mixed Disorder 1 680x512px.tif|Changes of steatohepatitis and interface hepatitis, with granuloma. Patient with diabetes was ANA, AMA, HCV, HBV negative, without drugs known to produce granulomas or interface hepatitis. This may be a case of AMA negative primary biliary cirrhosis, but studies to determine that with certainty were not performed.]] 
Changes of steatohepatitis and interface hepatitis, with granuloma. Patient with diabetes was ANA, AMA, HCV, HBV negative, without drugs known to produce granulomas or interface hepatitis. This may be a case of AMA negative primary biliary cirrhosis, but studies to determine that with certainty were not performed. A. Low power shows hepatocytes afflicted by steatosis and an inflamed portal tract. B. In a region of fatty change lie cytoplasmic tufts of ballooning degeneration (green arrows) and a lipogranuloma (black arrow). C. At the portal-hepatocyte junction lies interface hepatitis (black arrows), as well as extension of inflammation into the lobule (green arrows). D. Red hepatocytes bounded by inflammation denote piecemeal necrosis [PAS without diastase]. E. Giant cells intermixed with lymphocytes prove a portal granuloma [PAS without diastase]. F. A blue fibrous bridge extends from a triad [Trichrome].

[[File:4 95599552608917 sl 1.png|Acute obstructive changes and changes of recurrent acute injury]]
[[File:4 95599552608917 sl 2.png|Acute obstructive changes and changes of recurrent acute injury]]
[[File:4 95599552608917 sl 3.png|Acute obstructive changes and changes of recurrent acute injury]]
[[File:4 95599552608917 sl 4.png|Acute obstructive changes and changes of recurrent acute injury]]
[[File:4 95599552608917 sl 5.png|Acute obstructive changes and changes of recurrent acute injury]]
[[File:4 95599552608917 sl 6.png|Acute obstructive changes and changes of recurrent acute injury]]
[[File:4 95599552608917 sl 7.png|Acute obstructive changes and changes of recurrent acute injury]] 
Acute obstructive changes and changes of recurrent injury in 46 yo man with Clostridium perfringens positive blood culture, an ERCP that showed duodenal compression by the pancreas with resultant bile duct dilatation. The patient had had and continued to have multiple bouts of acute pancreatitis. At the time of biopsy, decreased platelet count/hemoglobin/albumin, elevated lipase/amylase/PT/PTT, normal alkaline phosphatase, bilirubin, AST/ALT, AMA, hepatitis virus serology, ANA. A. Fragment biopsy shows inflamed triads and bridges. B. Trichrome shows bridges without nodules, evidence of prior injury; the patient subsequently developed multiple episodes of pancreatitis. C. Reticulin shows piecemeal necrosis, with black lines bounding individual hepatocytes at interface (arrows). D. Collapse is shown by closly approximated thick black lines; one cannot call portal-central collapse without seeing a central vein. Note on this and the other reticulin image that regeneration, two cell thick cords, is not prominent. E. PAS D of two portal triads, far nearer than normal, both expanded. Note increased number of ducts/ductules (red arrows), neutrophils, and PAS-D macrophages. F. PAS D shows collapse extending from a triad to a portion of a lobule with steatosis. No feathery degeneration or bile duct plugs were seen. Neither were foci of spotty necrosis or abscess seen. G. Other triads, again edematous, showed more of a chronic inflammatory response, with occasional plasma cells (black arrows). Also present are neutrophils (red arrows). The bile duct (grey arrow) near the artery (brown arrow) shows mildly disturbed nuclei. Note early proliferated bile ductules (cyan arrows).

[[File:6 17281676469188 sl 1.png| Hepatitis B virus with steatohepatitis]]
[[File:6 17281676469188 sl 2.png| Hepatitis B virus with steatohepatitis]]
[[File:6 17281676469188 sl 3.png| Hepatitis B virus with steatohepatitis]]
[[File:6 17281676469188 sl 4.png| Hepatitis B virus with steatohepatitis]]
[[File:6 17281676469188 sl 5.png| Hepatitis B virus with steatohepatitis]]
[[File:6 17281676469188 sl 6.png| Hepatitis B virus with steatohepatitis]] 
Hepatitis B virus with steatohepatitis in a 36 year old man with hepatitis B surface antigen and hepatitis Be antigen positivity, Hepatitis be QTPC of 1750 cop/mL, an occasionally mildly elevated (42) ALT, and normal glucose, alkaline phosphatase, bilirubin, and other transaminases. He had a history of alcohol abuse, which became controlled. A. Triads show scant inflammation without definite interface hepatitis. About one-fourth of the lobule, not pan-acinar, is afflicted by steatosis. B. Occasional tufts are seen (arrow), indicating focal ballooning sufficient for a diagnosis of steatohepatitis. C. Glycogenated nuclei (black arrows) and hepatocytes with feathery degeneration (red arrows) are seen. D. Very rare foci of spotty necrosis were seen. E. Apart from this triad and the one in the trichrome stain in F, which had moderate inflammation comprising lymphocytes and macrophages, all triads were small, most without any inflammation at all. Neither collapse nor piecemeal necrosis were seen on reticulin stain. F. Trichrome stain showed only portal fibrosis. The interhepatocyte fibrosis required for brunt fibrosis stage I was not seen. Hence, one would grade this as follows: A) Chronic hepatitis (history of hepatitis B), Metavir activity index 1, Piecemeal necrosis 0, Lobular necrosis 1, Metavir fibrosis stage 1, B) Steatohepaitits, Brunt necroinflammatory grade 1, Brunt fibrosis stage 0.

=See also=
*[[Pancreas]].
*[[Gastrointestinal pathology]].
*[[Liver neoplasms]].
*[[Liver]].

=References=
{{reflist|2}}

[[Category:Gastrointestinal pathology]]
[[Category:Liver pathology]]
[[Category:Medical liver disease]]

Dermatopathology

2017-05-09T20:41:50Z

Mitchell: /* Others */ Added a case

'''Dermatopathology''' is the pathology of skin.

Pathology is a significant part of dermatology and dermatologists spend five years in residency. So, it is a huge area.

=Specimens=
*Shave biopsy = done for what is presumed to be benign disease - classically exophytic lesions, e.g. [[seborrheic keratosis]].
*Saucerization = scooped shave biopsy.<ref>{{Cite journal | last1 = Elston | first1 = D. | title = Practical advice regarding problematic pigmented lesions. | journal = J Am Acad Dermatol | volume = 67 | issue = 1 | pages = 148-55 | month = Jul | year = 2012 | doi = 10.1016/j.jaad.2012.04.006 | PMID = 22703907 }}
</ref>
*Punch biopsy = cylindrical piece of skin, usu. epidermis and dermis - suspicious lesions/malignant lesions, e.g. [[basal cell carcinoma]].
*Incisional biopsy = a piece of the lesion for pathologic assessment; lesion not completely removed.
*Excision = lesion cut-out with intent for complete removal - usual has a generous margin, e.g. [[malignant melanoma]] excision.
*Re-excision = done to get a wider margin ''or'' remove part of a lesion that was incompletely removed in a prior excision.
**Conservative re-excision = cut-out more with a minimal rim of normal tissue.<ref>URL: [http://www.nedermatology.com/skin-cancer-treatments.php http://www.nedermatology.com/skin-cancer-treatments.php]. Accessed on: 26 February 2013.</ref>
*[[Sentinel lymph node]] removal = a special type of lymphadenectomy usu. done for [[cancer staging|staging]], esp. [[malignant melanoma]].

=Histology=
==Layers of the skin==
[[Image:Skin.png|thumb|Schematic showing the layers and structures of skin. (WC/cancer.gov)]]
*Epidermis - outer most layer, avascular, separated from dermis by a basement membrane, epithelial tissue.
*Dermis - below the epidermis, vascular, separated from the epidermis by a basement membrane, connective tissue.

Note:
*The layer below the skin is the ''subdermis'' ([[AKA]] hypodermis, [[AKA]] subcutaneous tissue).
**It is below the dermis and consists of adipose tissue.<ref>URL: [http://histologyolm.stevegallik.org/node/119 http://histologyolm.stevegallik.org/node/119]. Accessed on: 5 November 2013.</ref>

Image:
*[http://histologyolm.stevegallik.org/node/119 Dermis and hypodermis (stevegallik.org)].

===Epidermis===
====Layers of the epidermis====
[[Image:Epidermal layers.png|thumb|right|Layers of the epidermis. (WC/Wbensmith)]]
Epidermis layers - from the surface to epidermal-dermal junction:
*Stratum corneum.
*Stratum lucidum.
**Present only in "thick" skin.<ref name=Ref_Derm1>{{Ref Derm|1}}</ref>
*Stratum granulosum.
*Stratum spinosum (aka prickle layer).
*Stratum basale (germinativum).
Mnemonic: ''Corn Lovers Grow Several Bales''.

====Cells of the epidermis====
*Keratinocytes.
**Usually eosinophilic cytoplasm - '''important feature'''.
**May have clear perinuclear halo (glycogenated keratinocytes).
**Intercellular bridges (high power) - '''key feature'''.
*Melanocytes.
**Usuallly basal location.
**Epithelioid or dentritic morphology.
**Pericellular clearing - '''key feature'''.
**Clear cytoplasm.
**+/-Pigmentation.
*Other:
**Toker cell.
**Neutrophils.
***Trilobated nuclei - 2-3 little dots - '''key feature'''.
**Lymphocytes.
***Small (round) nucleus.
***Scant/indistinct cytoplasm.
**Other foreign cells:
***[[Paget disease]]: large cells with clear cytoplasm, may cluster, above basal layer.

====Normal histology====
Features:
*Keratinocytes:
**Basal ~ 2x [[RBC]].
***May palisade focally ~ 1:2 = width: height.
*Melanocytes < 25 melanocytes / 0.5 mm of basal layer.<ref name=pmid21549242>{{Cite journal | last1 = Trotter | first1 = MJ. | title = Melanoma margin assessment. | journal = Clin Lab Med | volume = 31 | issue = 2 | pages = 289-300 | month = Jun | year = 2011 | doi = 10.1016/j.cll.2011.03.006 | PMID = 21549242 }}</ref>
*Basket weave stratum corneum (non-acral skin).

===Dermis===
Subdivided into layers:
#Papillary dermis.
#*Location: superficial - opposed to the deep aspect of the epidermis.
#*Appearance: dense, thick collagen bundles.
#Reticular dermis.
#*Location: deep - between papillary dermis and subdermis.
#*Appearance: loose connective tissue.

Images:
*[http://www.biology-online.org/user_files/Image/Anatomy/AN-fibroblastF02.gif Layers of the dermis - labelled (biology-online.org)].<ref>URL: [http://www.biology-online.org/articles/fibroblast_heterogeneity_skin_deep/figures.html http://www.biology-online.org/articles/fibroblast_heterogeneity_skin_deep/figures.html]. Accessed on: 29 March 2012.</ref>
*[http://melanoma.blogsome.com/wp-admin/images/skinstr.jpg Layers of the skin (melanoma.blogsome.com)].<ref>URL: [http://melanoma.blogsome.com/category/skin-structure/ http://melanoma.blogsome.com/category/skin-structure/]. Accessed on: 29 March 2012.</ref>

===Adnexal structures===
The top five structures of the skin:<ref>{{Ref Derm|4-8}}</ref>
{| class="wikitable sortable"
! Structure / Attribute
! Histomorphology
! Function
! [[IHC]]
! Other
! Image
|-
| '''Eccrine gland'''
| clusters of tubular structures, pale cytoplasm
| thermoregulation (cooling) - produce sweat
| [[CK7]]+, [[CEA]]+, CAM5.2+, [[EMA]]+
| ?
| ?
|-
| '''Apocrine gland'''
| apical snouts, tubular structures
| ear wax, body odor
| ?
| ?
| ?
|-
| '''Sebaceous gland'''
| clusters of cells side-by-side, pale fluffy cytoplasm
| grease hair, sexual lubrication
| ?
| assoc. with hair follicle
| ?
|-
| '''Hair follicle'''
| linear structure
| keep individual warm
| ?
| assoc. with sebaceous glands
| ?
|-
| '''Nail'''
| epidermal structure
| weapon (claw-like), look pretty?
| ?
| ?
| [http://histology.osumc.edu/histology/HumanHisto/Integumentary/Img/17B-23_001.html (osumc.edu)], [http://ctrgenpath.net/static/atlas/mousehistology/Windows/integumentary/nail20.html (ctrgenpath.net)]
|-
|}

Ducts vs. glands:<ref>HJ. 27 Feb 2009.</ref>
*Eccrine glands - spindle-shaped myoepithelial cells surround luminal cells.
*Eccrine ducts - cuboidal type subepithelial cells.

=Common terms=
==Clinical descriptors==
There are multitude of clinical descriptors - common ones are:<ref>URL: [http://www.pediatrics.wisc.edu/education/derm/text.html http://www.pediatrics.wisc.edu/education/derm/text.html]. Accessed on: 18 September 2012.</ref>
{| class="wikitable sortable"
! '''Name'''
! '''Size †'''
! '''Description'''
! '''Other'''
! '''Image'''
|-
| Macule
| <= 10 mm
| flat + change of colour
| if > 10 mm --> patch
| [[Image:Macule_and_Patch.svg|thumb|center|150px| Macule (WC)]]
|-
| Patch
| > 10 mm
| flat + change of colour
| if <= 10 mm --> macule
| [[Image:Macule_and_Patch.svg|thumb|center|150px| Patch (WC)]]
|-
| Papule
| <= 10 mm
| raised
| if > 10 mm --> nodule
| [[Image:Papule_and_Plaque.svg|thumb|center|150px| Papule (WC)]]
|-
| Nodule
| > 10 mm
| raised
| if <= 10 mm --> papule
| [[Image:Nodules.svg|thumb|center|150px| Nodule (WC)]]
|-
| Plaque
| > 10 mm
| raised, flat-top
| plateau-like
| [[Image:Papule_and_Plaque.svg|thumb|center|150px| Plaque (WC)]]
|-
| Vesicle
| <= 10 mm
| raised, fluid filled
| if > 10 mm --> bulla
| [[Image:Vesicles_and_Bulla.svg |thumb|center|150px| Vesicle (WC)]]
|-
| Bulla
| > 10 mm
| raised, fluid filled
| if <= 10 mm --> vesicle
| [[Image:Vesicles_and_Bulla.svg |thumb|center|150px| Bulla (WC)]]
|}
Note:
* † Definitions vary -- some authors use a 5 mm cut-off.

==Histologic descriptors==
Dermatopathology doesn't have intuitive terms, e.g. thickening of the stratum spinosum isn't ''spinosum hyperplasia''. The terms have to committed to memory.

===Common terms in a table===
{| class="wikitable sortable"
! Term
! Meaning
! Reference
|-
|Acanthosis
| thickening of the prickle layer (stratum spinosum) of epidermis
| <ref>[http://dictionary.reference.com/browse/acanthosis http://dictionary.reference.com/browse/acanthosis]</ref>
|-
|Acantholysis
| loss of intercellular connections in the epidermis
|
|-
|Dyskeratosis
| abnormal keratinization, often refers to keratinization below the stratum granulosum; keratinization above may be abnormal (dependent on body site)
|
|-
|Parakeratosis
| retention of nuclei in the stratum corneum, normal in mucous membranes
|
|-
|Spongiosis
| epidermal intercellular edema; cells appear to have a clear halo around 'em
| <ref>{{Ref PBoD|1230}}</ref>
|-
|Basketweave stratum corneum
| appearance of the normal stratum corneum; presence in the context of pathology suggests an acute process
|
|-
|Compact hyperkeratosis
| stratum corneum layer is dense and thickened; this suggests a chronic process
| <ref>URL: [http://dermnetnz.org/pathology/pathology-glossary.html http://dermnetnz.org/pathology/pathology-glossary.html]. Accessed on: 8 August 2012.</ref>
|-
| Hyperkeratosis
| thickened stratum corneum - also see ''compact hyperkeratosis'' and ''basketweave stratum corneum''
|
|-
|Epidermotropism †
| intraepithelial lymphocytes in [[CTCL]]; how to remember: epidermotropis''m'' = ''m''alignant
| <ref name=pmid20132423>{{Cite journal | last1 = Fung | first1 = MA. | title = 'Epidermotropism' vs. 'exocytosis' of lymphocytes 101: definition of terms. | journal = J Cutan Pathol | volume = 37 | issue = 5 | pages = 525-9 | month = May | year = 2010 | doi = 10.1111/j.1600-0560.2010.01515.x | PMID = 20132423 }}</ref>
|-
|Exocytosis †
| intraepithelial lymphocytes in benign conditions
| <ref name=pmid20132423>{{Cite journal | last1 = Fung | first1 = MA. | title = 'Epidermotropism' vs. 'exocytosis' of lymphocytes 101: definition of terms. | journal = J Cutan Pathol | volume = 37 | issue = 5 | pages = 525-9 | month = May | year = 2010 | doi = 10.1111/j.1600-0560.2010.01515.x | PMID = 20132423 }}</ref>
|-
|Orthokeratosis
| anuclear keratin layer is present (stratum corneum) - seen in normal skin; ''ortho-'' means ''correct''
| <ref>URL: [http://www.medilexicon.com/medicaldictionary.php?t=63448 http://www.medilexicon.com/medicaldictionary.php?t=63448]. Accessed on: 13 March 2013.</ref><ref>URL: [http://dictionary.reference.com/browse/ortho- http://dictionary.reference.com/browse/ortho-]. Accessed on: 13 March 2013.</ref>
|}
Note:
* † These definitions are not universally accepted. ''Epidermotropism'' is sometimes used in the context of benign disease.<ref name=pmid9537476>{{Cite journal | last1 = Fung | first1 = MA. | last2 = LeBoit | first2 = PE. | title = Light microscopic criteria for the diagnosis of early vulvar lichen sclerosus: a comparison with lichen planus. | journal = Am J Surg Pathol | volume = 22 | issue = 4 | pages = 473-8 | month = Apr | year = 1998 | doi = | PMID = 9537476 }}</ref>

Image:
*[http://commons.wikimedia.org/wiki/File:Spongiotic_dermatitis_%282%29_Dyshidrotic_.JPG Spongiosis (WC)].

===Others terms===
*Crust = epithelial elements, blood.

Image:
*[http://www.eplasty.com/article_images/eplasty10e60_fig3.gif Crust (eplasty.com)].<ref>URL: [http://www.eplasty.com/index.php?option=com_content&view=article&id=492&catid=171:volume-10-eplasty-2010&Itemid=121 http://www.eplasty.com/index.php?option=com_content&view=article&id=492&catid=171:volume-10-eplasty-2010&Itemid=121]. Accessed on: 16 October 2012.</ref>

=Skin diseases=
==Neoplasms==
{{main|Dermatologic neoplasms}}

===Malignant===
Skin cancer is very common. The basic DDx of a malignant skin lesion is:
*[[Squamous cell carcinoma]] (SCC).
*[[Basal cell carcinoma]] (BCC).
*[[Malignant melanoma]].
*Metstases.

==Non-malignant disease==
{{main|Non-malignant skin disease}}
Non-malignant skin disease is common. It is the domain of dermatologists. It can be scary for general anatomical pathologists because the differential diagnosis is often broad, and, it's generally not something the general anatomical pathologist sees a lot of.

===Subarticles===
*[[Dermal cysts]], e.g. [[epidermal cyst]], [[pilar cyst]].
*[[Epidermal necrosis]], e.g. [[erythema multiforme]], [[toxic epidermal necrolysis]].
*[[Inflammatory skin diseases]].
**[[Bullous diseases]], e.g. [[pemphigus vulgaris]].
**[[Panniculitis]].

=Common entities in tables=
==Non-malignant non-cystic - very common==
{| class="wikitable sortable" style="margin-left:auto;margin-right:auto"
! Entity
! Key histologic feature
! Other features
! Clinical
! Stains/IHC
! DDx
! Other
! Image
|-
| [[Seborrheic keratosis]] (SK)
| horn cysts (intraepidermal collections of keratin)
| hyperkeratosis, brown granular material at the DE junction, sharply demarcated
| stuck on appearance
| none
| [[fibroepithelial polyp]]
| Leser–Trélat sign = many SKs in malignancy
| [[Image:Seborrheic_keratosis_(1).jpg |thumb|center|150px| SK (WC)]]
|-
| [[Dermatofibroma]]
| fibrous bundles esp. at edge of lesion
| "dirty fingers" = acanthosis + basal keratinocyte hyperpigmentation
| +/-trauma Hx
| CD34-, Factor XIIIa+
| [[DFSP]]
| very common
| [[Image:SkinTumors-P9280848.jpg|thumb|center|150px|DF (WC)]]
|-
| [[Fibroepithelial polyp]] (skin tag)
| on a stalk (epithelium on 3+ sides)
| no horn nests, no hyperkeratosis
| raised lesion
| none
| [[seborrheic keratosis]]
| very common
| [[Image:SkinTumors-P9250819.jpg|thumb|center|150px|Skin tag (WC)]]
|-
| [[Lipoma]]
| mature adipocytes - uniform size
| var. of size may be seen, should prompt search for lipoblasts
| mobile subcutaneous mass
| S100 (???)
| [[liposarcoma]]
| variants: angiolipoma (blood vessels), myolipoma (muscle)
| [[Image: Lipoma -- high mag.jpg|thumb|center|150px|Lipoma (WC)]]
|-
| [[Cicatrix]] (dermal scar)
| dense collagen bundles running parallel to DE junction, loss of dermal papillae
| loss of adnexal structures, +/-[[giant cells]], +/-foreign material, +/-inflammatory cells
| site of previous trauma/surgery
| usu. none; S-100 (to exclude melanoma)
| residual disease, [[hypertrophic scar]], (desmoplastic) [[melanoma]]
|
| [[Image:ScarHistology.JPG |thumb|center|150px| Scar (WC)]]
|- 
|}

==Non-malignant non-cystic - common==
{| class="wikitable sortable" style="margin-left:auto;margin-right:auto"
! Entity
! Key histologic feature
! Other features
! Clinical
! Stains/IHC
! DDx
! Other
! Image
|-
| [[Neurofibroma]]
| bland spindle cells
| mast cells, mixed with collagen, assoc. with a nerve
| may be associated with [[neurofibromatosis]], esp. plexiform type
| S100+, GFAP+
| neurotized [[melanocytic nevus]]
| may develop into [[MPNST]]
| [[Image:Neurofibroma_%281%29.jpg |thumb|center|150px| Neurofibroma (WC)]]
|-
| [[Keratoacanthoma]]
| keratin plug, glassy pink cytoplasm, pushing downward growth
| minimal/no nuclear atypia
| grow rapidly then involute
| none
| [[squamous cell carcinoma]]
| some don't believe in the entity
| [[Image:Skin_keratoacanthoma_whole_slide.jpg |thumb|center|150px| Keratoacathoma (WC)]]
|-
| [[Molluscum contagiosum]]
| suprabasilar cells with abundant granular eosinophilic cytoplasm
| small peripheral nucleus
| polypoid lesion; mushroom-like (?)
| none (?)
| DDx (?)
| favourite exam case
| [[Image:Molluscum_contagiosum_high_mag.jpg |thumb|center|150px|Molluscum contagiosum (WC)]]
|-
| [[Verruca vulgaris]]
| hypergranulosis (thick granular layer) + keratohyaline granules
| hyperkeratosis (thick s. corneum), acanthosis (thick s. spinosum), rete ridges lengthened (~7-10x normal), large vessels at DE junction, koilocytic change (???)
| raised lesions, classically on hand
| none (p16+?)
| [[squamous cell carcinoma of the skin|squamous cell carcinoma]]
| caused by [[HPV]]
| [[Image:Verruca_vulgaris_-_very_low_mag.jpg |thumb|center|150px| Verruca vulgaris (WC)]]
|-
| [[Condyloma acuminatum]]
| koilocytes
| parakeratosis, long folded rete ridges (papillomatosis) - pseudopapillary look
| genital lesion
| none (p16+)
| [[fibroepithelial polyp]]
| caused by [[HPV]]
| [[Image:Anal_condyloma_%282%29.jpg |thumb|center|150px| Condyloma acuminatum (WC)]]
|-
| [[Granuloma annulare]]
| dermal palisading [[granuloma]] around necrotic collagen
| mucin in centre of lesion, (peripheral) lymphocytes, usu. more superficial than necrobiosis lipoidica
| benign, self-limited
| none (CD68?)
| [[necrobiosis lipoidica]], [[rheumatoid nodule]], [[epithelioid sarcoma]]
| Other ?
| [[Image:Granuloma_annulare_-_add_-_high_mag.jpg |thumb|center|150px| GA (WC)]]
|-
| [[Necrobiosis lipoidica]]
| dermal palisading [[granuloma]] around necrotic collagen, plasma cells
| mucin in centre of lesion, (peripheral) chronic inflammatory cells
| may be assoc. [[diabetes mellitus]]
| none (CD68?)
| [[granuloma annulare]], [[rheumatoid nodule]]
| histology identical to ''necrobiosis lipoidica diabeticorum''
| [http://www.drmihm.com/cases/casefigure.cfm?figID=942&CaseID=53 (drmihm.com)]
|-
| [[Angiofibroma]]
| fibrotic dermis, dilated capillaries
| enlarged (stellate fibroblasts)
| dome-shaped - face, boys & nosebleeds ([[nasopharyngeal angiofibroma]])
| Stains/IHC
| DDx
| may be associated with [[tuberous sclerosis]]
| [[Image:Nasopharyngeal angiofibroma - 2 - high mag.jpg|thumb|150px|Angiofibroma (WC)]]
|-
| [[Keloid]]
| thick collagen bundles - surrounded by paler staining fibroblasts
| replaces adnexal structures
| site of previous trauma, esp. in blacks
| none
| [[dermatofibroma]] (???)
| [[hypertrophic scar]]
| [[Image:Keloid_-_high_mag.jpg|thumb|center|150px|Keloid (WC)]]
|-
| [[Eccrine poroma]]
| abundant basaloid cells with (small) ductal structures
| incloses islands of sclerotic stroma with edema
| erythematous lesions
| Stains/IHC ?
| DDx ?
| Other ?
| [[Image:SkinTumors-P7150495.JPG|thumb|center|150px|EP (WC)]]
|-
| [[Syringoma]]
| bilayered ducts, occasionally tadpole like shape
|
| usu. close to [[eyelid]]
| Stains/IHC ?
| DDx ?
| Other ?
| [http://dermatology.cdlib.org/144/tumors/axillary_syringoma/2.jpg (cdlib.org)]
|-
| [[Chondroid syringoma]] (mixed tumour of skin)
| [[chondromyxoid stroma]], epithelial component
| epithelial component in nests with eosinophilic cytoplasm, round/ovoid nuclei with nucleoli
| Clinical ?
| Stains/IHC ?
| DDx ?
| related to [[pleomorphic adenoma]] (???)
| Image ?
|-
| [[Angiokeratoma]]
| ectatic superficial dermal vessels + overlying hyperkeratosis
| -
| may be seen in [[Fabry disease]]
| Stains/IHC ?
| [[venous lake]]
| Other ?
| [[Image:Angiokeratoma_-_low_mag.jpg |thumb|center|150px| Angiokeratoma (WC)]]
|- 
|}

==Non-malignant non-cystic - children==
{| class="wikitable sortable" style="margin-left:auto;margin-right:auto"
! Entity
! Key histologic feature
! Other features
! Clinical
! Stains/IHC
! DDx
! Other
! Image
|-
| [[Pilomatricoma]]
| anucleate squamous cells (ghost cells), giant cells
| bland basaloid cells
| common in children
| none
| [[squamous cell carcinoma of the skin|squamous cell carcinoma]]
| mutations of CTNNB1 gene
| [[Image:Pilomatrixoma_-_intermed_mag.jpg |thumb|center|150px| Pilomatrixcoma (WC)]]
|-
| [[Juvenile xanthogranuloma]] (JXG)
| Touton giant cells - multi-nucleated cells where nuclei are distributed around the cell periphery forming a ring
| abundant cytoplasm
| children
| CD68+, CD1a-, CD207-
| [[Langerhans cell histiocytosis]]
| may be seen in adults, known as '''adult xanthogranuloma'''
| [[Image:Juvenile_xanthogranuloma_-_high_mag.jpg |thumb|center|150px| JXG (WC)]]
|}

==Non-malignant cystic==
{| class="wikitable sortable" style="margin-left:auto;margin-right:auto"
! Entity
! Key histologic feature
! Other features
! Clinical
! Stains/IHC
! DDx
! Other
! Image
|-
| [[Epidermal cyst]]
| cyst lined by squamous epithelium '''with''' a granular layer
| keratinous debris, no skin adnexal structures
| cyst
| none
| [[pilar cyst]], [[dermoid cyst]]
| Other?
| [[Image:Epidermal inclusion cyst -- high mag.jpg |thumb|center|150px| Epidermal inclusion cyst (WC)]]
|-
| [[Pilar cyst]] (trichilemmal cyst)
| cyst lined by squamous epithelium '''without''' a granular layer
| keratinous debris
| cyst
| none
| [[epidermal cyst]]
| Other?
| [[Image:Trichilemmal_cyst_-_very_high_mag.jpg |thumb|center|100px| Pilar cyst (WC)]]
|-
| [[Steatocystoma]]
| cyst lined by squamous epithelium with a corrugated eosinophilic lining
| epidermis has '''no''' granular layer
| cyst
| none
| [[dermoid cyst]], follicular cyst
| Other?
| [[Image:Steatocystoma_-_high_mag.jpg |thumb|center|150px| Steatocystoma (WC)]]
|-
| [[Dermoid cyst]]
| cyst lined by keratinizing squamous epithelium with adnexal structures
| adnexal structure = hair, sebaceous gland, sweat glands
| cyst
| none
| [[epidermal cyst]]
| may be seen in the [[ovary]]
| [http://webeye.ophth.uiowa.edu/eyeforum/cases-i/case115/larger/Figure4.jpg (uiowa.edu)]
|}

==Pre-malignant==
{| class="wikitable sortable" style="margin-left:auto;margin-right:auto"
! Entity
! Key histologic feature
! Other features
! Clinical
! Stains/IHC
! DDx
! Other
! Image
|-
| [[Actinic keratosis]]
| epidermal atypia, esp. (basal) nuclear enlargement
| var. of nuclear size, shape and staining, parakeratosis (important in early lesions); does ''not'' involves adnexal epithelium and follicular epithelium
| yellow-brown scaly
| none
| [[squamous carcinoma]], [[Bowen disease]]
| seen with [[solar elastosis]]
| [[Image:Actinic_Keratosis,_H%26E.jpg |thumb|center|150px| AK (WC)]]
|-
| [[Bowen disease]] (squamous cell carcinoma in situ)
| epidermal atypia, esp. suprabasal nuclear enlargement
| var. of nuclear size, shape and staining; usually full thickness involvement; involve adnexal epithelium and follicular epithelium
|
| none
| [[squamous carcinoma]], [[actinic keratosis]]
| typically seen with solar elastosis
| [[Image:Bowen_disease_%281%29.jpg |thumb|center|100px| Bowen's disease (WC)]]
|}

==Common malignant==
{| class="wikitable sortable" style="margin-left:auto;margin-right:auto"
! Entity
! Key histologic feature
! Other features
! Clinical
! Stains/IHC
! DDx
! Other
! Image
|-
| [[Basal cell carcinoma]] (BCC)
| basaloid cells with peripheral palisading, artificial cleft
| [[myxoid]] stroma
| raised, pearly, telangiectasia
| usu. none req., [[CK5/6]]+
| [[trichoepithelioma]], [[basaloid squamous cell carcinoma]]
| assoc. [[nevoid basal cell carcinoma syndrome]], [[Bazex syndrome]]
| [[Image:Basal cell carcinoma - high mag.jpg| thumb| center|150px|BCC (WC)]]
|-
| [[Squamous cell carcinoma]] (SCC)
| nuclear enlargement, eosinophilic cytoplasm, central nucleus
| small nucleolus, intercellular bridges
| flaky appearance
| usu. none req., p63+, HMWK+
| [[keratoacanthoma]], [[Paget disease]] ([[EMPD]] & [[PDB]]), [[malignant melanoma]], Toker cell hyperplasia
| Other
| [[Image:Oral_cancer_%281%29_squamous_cell_carcinoma_histopathology.jpg|thumb|center|150px|SCC (WC)]]
|-
| [[Malignant melanoma]]
| spindle and/or epithelioid morphology +/-nuclear atypia (esp. nucleoli)
| mitoses (esp. deep), +/-pigment, +/-nested arch., asymmetry, upward spread (into epidermis), epithelioid m. deep, +/-single cells, +/-sheets of cells
| ABCD = Asymmetry, Borders poor demarc., Colour dark, Diameter large
| S100+, Melan A+, HMB-45+, microphthalmia+, tyrosinase+
| [[melanocytic lesions]] esp. [[Spitz nevus]], [[Bowen's disease]]
| may be familial, [[dysplastic nevus]]
| [[Image:Malignant_melanoma_%281%29_at_thigh_Case_01.jpg |thumb|center|150px|Melanoma (WC)]]
|- 
|}

==Less common malignant==
{| class="wikitable sortable" style="margin-left:auto;margin-right:auto"
! Entity
! Key histologic feature
! Other features
! Clinical
! Stains/IHC
! DDx
! Other
! Image
|-
| [[Kaposi sarcoma]]
| vascular spindle cell lesion
| [[hyaline globules]] (intracytoplasmic)
| often HIV/AIDS
| [[HHV-8]]
| [[Masson's hemangioma]], [[angiosarcoma]], [[Kaposiform hemangioendothelioma]]
| stages: patch stage, plaque stage, nodular stage, exophytic, infiltrative, lymphadenopathic
| [[Image:Kaposi_sarcoma_low_intermed_mag.jpg |thumb|center|150px| Kaposi sarcoma (WC)]]
|-
| [[Cutaneous T-cell lymphoma]] (includes ''mycosis fungoides'')
| single lymphocytes in epidermis ("lymphocyte exocytosis")
| lymphocyte nests in the epidermis ("Pautrier microabscesses"), short arrays of lymphocytes along the basal layer of the epidermis ("epidermotropism")
| Clinical
| CD45, CD4
| B cell lymphoma (?)
| Other
| [[Image:Cutaneous_T-cell_lymphoma_-_intermed_mag.jpg |thumb|center|150px| CTCL (WC)]]
|-
| [[Atypical fibroxanthoma]]
| dermal lesion with marked nuclear atypia
| multinucleated cells, mitoses, vacuolated cytoplasm
| old men, head and neck
| p63-, 34betaE12-, S100-, desmin-
| sarcomatoid squamous carcinoma, [[melanoma]], [[leiomyosarcoma]]
| some classify this as '''benign'''; thought to be related to [[undifferentiated pleomorphic sarcoma]]
| [[Image:SkinTumors-P9280874.jpg|thumb|center|150px| AFX (WC)]]
|-
| [[Merkel cell carcinoma]]
| neuroendocrine nuclear features (stippled chromatin, no nucleolus), scant cytoplasm
| +/-nuclear moulding, usu. intermediate cell size
| Merkel cell polyomavirus associated, usu. head & neck or extremities
| CK20+, EMA+
| cutaneous [[Ewing sarcoma]], [[basal cell carcinoma]], (dermal) [[lymphoma]], metastatic small cell carcinoma (e.g. [[Lung tumours#Small cell carcinoma|lung]])
| rare, aggressive
| [[Image:Merkel_cell_carcinoma_-_very_high_mag.jpg |thumb|center|100px| MCC (WC)]]
|-
| [[Dermatofibrosarcoma protuberans]] (DFSP)
| spindle cell tumour with storiform pattern, tumour often contains adipocytes
| dermal tumour with preserved adnexal structures
| locally aggressive
| CD34+, factor XIIIa-
| [[dermatofibroma]], [[solitary fibrous tumour]] (usu. deeper)
| rarely metastases, characteristic [[translocation]]: t(17;22)(q22;q15) COLA1/PDGFB; may transform to [[fibrosarcoma]]
| [[Image:Storiform_pattern_-_intermed_mag.jpg |thumb|center|150px| DFSP (WC)]]
|- 
|}

=Presentations=
==Leukoplakia==
{{Main|Leukoplakia}}

DDx:<ref>{{Ref PBoD|1065}}</ref>
*Vitiligo (loss of pigment).
*Inflammation.
**Chronic dermatitis.
**[[Psoriasis]].
*Neoplasia.
**[[Vulvar intraepithelial neoplasia]].
**[[Invasive_breast_cancer#Paget.27s_disease|Paget disease]].
**Invasive carcinoma.
*Other.
**[[Lichen sclerosus]].
**[[Lichen simplex chronicus]].

=Skin disease and systemic conditions=
==Tabular list==
{| class="wikitable sortable" style="margin-left:auto;margin-right:auto"
! Entity
! Disease/syndrome
! Key histologic feature
! Image
|-
| [[Acanthosis nigricans]]
| [[diabetes mellitus]], malignancy
| basal cell hyperpigmentation, hyperkeratosis, prominent rete ridges
| [http://dermatology.cdlib.org/149/reviews/acanthosisnigricans/higgins.html (cdlib.org)]
|-
| [[Trichilemmoma]]
| [[Cowden disease]]
| "hyperkeratosis"
| [http://ccr.cancer.gov/staff/images/9033_12822_Lee_1520.jpg (cancer.gov)]<ref>URL: [http://ccr.cancer.gov/staff/gallery.asp?profileid=12822 http://ccr.cancer.gov/staff/gallery.asp?profileid=12822]. Accessed on: 14 December 2011.</ref>
|-
| [[Angiokeratoma]]
| [[Fabry disease]]
| hyperkeratosis + vessels in superficial dermis
| [http://commons.wikimedia.org/wiki/File:Angiokeratoma_-_low_mag.jpg (WC)]
|-
| [[Dermatitis herpetiformis]]
| [[Celiac disease]]
| subepidermal [[bullous disease]], papillary abscesses
| [http://www.lampyris101.com/L101/gallery1/12_JPG.html (lampyris101.com)]
|-
| [[Angiofibroma]]
| [[tuberous sclerosis]]
| fibrotic dermis + dilated blood vessels
| [http://www.drdittmar.lu/images/sce/angiofibroma-s.jpg (drdittmar.lu)]
|-
| [[Sebaceous adenoma]]
| [[Muir-Torre syndrome]]
| abundant sebaceous glands with abn. arch.
| [http://commons.wikimedia.org/wiki/File:Sebaceous_adenoma_-_low_mag.jpg (WC)]
|-
| [[Seborrheic keratosis]], multiple with explosive onset
| Leser–Trélat sign (malignancy)
| horn cysts, hyperkeratosis
| [http://commons.wikimedia.org/wiki/File:IMG_1724.JPG gross (WC)], [http://commons.wikimedia.org/wiki/File:Seborrheic_keratosis_%281%29.jpg micro. (WC)]
|- 
|}

==Acanthosis nigricans==
===General===
Associated with:
*[[Diabetes mellitus]].<ref>URL: [http://www.emedicine.com/derm/topic1.htm http://www.emedicine.com/derm/topic1.htm], URL: [http://dermatlas.med.jhmi.edu/derm/indexDisplay.cfm?ImageID=1943559504].</ref>
*Malignancy.<ref name=Ref_PCPBoD8|596>{{Ref PCPBoD8|596}}</ref>

===Microscopic===
Features (memory device ''BPH''):<ref name=Ref_PCPBoD8|596>{{Ref PCPBoD8|596}}</ref>
*Basal cell hyperpigmentation.
*Prominent rete ridges.
*Hyperkeratosis.

DDx:
*[[Seborrheic keratosis]] - typically has more hyperkeratosis, pseudohorn cysts.

Images:
*[http://dermatology.cdlib.org/149/reviews/acanthosisnigricans/higgins.html AN (cdlib.org)].

==Others==
*[[Dermatitis herpetiformis]]: gluten enteropathy ([[celiac disease]]), [[thyroid]] disease, intestinal [[lymphoma]].<ref name=Ref_TN2007_D23>{{Ref TN2007|D23}}</ref>
*[[Pemphigus vulgaris]]: [[thymoma]], myasthenia gravis, malignancy.<ref name=Ref_TN2007_D23>{{Ref TN2007|D23}}</ref>

===Lipoid proteinosis===
<gallery>
File:3767 dp sl 1.png |Lipoid proteinosis (A)
File:3767 dp sl 2.png |Lipoid proteinosis (B)
</gallery>
A. Inner labial biopsy shows subepithelial hyalinized pink/red material, about blood vessels and in general. B. The particularly glassy appearance of the material in areas is evident at high power.

===Xanthogranuloma in scrotal skin.===
<gallery>
File:DP16MR17 sl 1.png| Xanthogranuloma in scrotal skin. (A)
File:DP16MR17 sl 2.png| Xanthogranuloma in scrotal skin. (B)
File:DP16MR17 sl 3.png| Xanthogranuloma in scrotal skin. (C)
File:DP16MR17 sl 4.png| Xanthogranuloma in scrotal skin. (D)
</gallery>
A. Pseudoepitheliomatous hyperplasia seemingly forms a dermal mass. B. Parakeratosis tops epidermis. C. Neutrophils lie in the center of the apparent mass. D. Diagnostic xanthoma cells lie in dermal papillae.

===Silicone granuloma===
<gallery>
File:DP13AP17 sl1.png| Silicone granuloma (A)
File:DP13AP17 sl2.png| Silicone granuloma (B)
File:DP13AP17 sl3.png| Silicone granuloma (C)
File:DP13AP17 sl4.png| Silicone granuloma (D)
</gallery>
A. The dermis resembles Swiss cheese. B. Macrophages, some with more than one nucleus, accompany empty ovoid spaces. C. Some macrophages resemble Teuton body giant cells. D. An admixture of lymphocytes is not at all unusual.

====Histoplasmosis in skin====
<gallery>
File:DP20AP17 sl 1.png| Dermal histoplasmosis (A)
File:DP20AP17 sl 2.png| Dermal histoplasmosis (B)
File:DP20AP17 sl 3.png| Dermal histoplasmosis (C)
File:DP20AP17 sl 4.png| Dermal histoplasmosis (D)
</gallery>
A. Extending from papillary dermis into dermis is a chronic, blue inflammatory infiltrate. B. The infiltrate comprises lymphocytes, plasma cells, and macrophages. C. At the edge of the biopsy pink strews inflammatory cells; this pink invasion of inflammation, so to speak, is a good place to look for organisms. D. High power reveals sometimes budding yeast forms in clear spaces.

===Herpes Zoster===
<gallery>
File:5.049889044 sl 1.png| Changes of herpes zoster (A)
File:5.049889044 sl 2.png| Changes of herpes zoster (B)
File:5.049889044 sl 3.png| Changes of herpes zoster (C)
File:5.049889044 sl 4.png| Changes of herpes zoster (D)
</gallery>
Changes of herpes zoster in lower right abdominal skin of a 48 yo Hispanic man. A. Note the edema at the dermoepidermal junction along with a focal separation at the left as well as the inflamed superficial and deep blood vessels. B,C. Careful examination along the junction uncovers smudged chromatin diagnostic of viral infection. D. Vasculitis associated changes include extravasated neutrophils with nuclear dust, as well as pervascular macrophages, lymphocytes and occasional eosinophils.

=References=
{{reflist|2}}

[[Category:Dermatopathology]]

Atypical fibroxanthoma

2017-04-27T14:42:29Z

Mitchell: /* Images */ added a case of an important, albeit rare, diagnosis that can mimic AFX

{{ Infobox diagnosis
| Name = {{PAGENAME}}
| Image = SkinTumors-P9280874.jpg
| Width =
| Caption = Atypical fibroxanthoma. [[H&E stain]].
| Synonyms =
| Micro = dermal lesion with marked nuclear atypia, mitoses, mulitnucleated cells, cell have foamy cytoplasm
| Subtypes =
| LMDDx = [[malignant melanoma]], [[pleomorphic undifferentiated sarcoma]], [[leiomyosarcoma]], sarcomatoid [[squamous carcinoma]]
| Stains =
| IHC = S-100 -ve, CK34betaE12 -ve, p63 -ve, desmin -ve
| EM =
| Molecular =
| IF =
| Gross =
| Grossing =
| Site = [[skin]] - see [[skin tumours]], usu. head & neck
| Assdx =
| Syndromes =
| Clinicalhx = rapid growth, elderly
| Signs =
| Symptoms =
| Prevalence = uncommon
| Bloodwork =
| Rads =
| Endoscopy =
| Prognosis = good
| Other =
| ClinDDx = malignant [[skin tumours]]
| Tx = complete excision
}}
'''Atypical fibroxanthoma''', abbreviated '''AFX''', is poorly differentiated [[skin tumour]] with likeness to [[undifferentiated pleomorphic sarcoma]].

==General==
*Typically head & neck region.<ref>URL: [http://emedicine.medscape.com/article/1056204-overview http://emedicine.medscape.com/article/1056204-overview]. Accessed on 2 September 2011.</ref>
*Thought to be related to [[pleomorphic undifferentiated sarcoma]];<ref name=pmid21664889>{{Cite journal | last1 = Withers | first1 = AH. | last2 = Brougham | first2 = ND. | last3 = Barber | first3 = RM. | last4 = Tan | first4 = ST. | title = Atypical fibroxanthoma and malignant fibrous histiocytoma. | journal = J Plast Reconstr Aesthet Surg | volume = | issue = | pages = | month = Jun | year = 2011 | doi = 10.1016/j.bjps.2011.05.004 | PMID = 21664889 }}</ref><ref name=pmid23319144>{{Cite journal | last1 = Tchernev | first1 = G. | last2 = Tronnier | first2 = M. | last3 = Ananiev | first3 = J. | last4 = Taneva | first4 = T. | last5 = Patterson | first5 = JW. | last6 = Gulubova | first6 = M. | last7 = Trafeli | first7 = JP. | last8 = Gegova | first8 = A. | last9 = Harrell | first9 = M. | title = Atypical fibroxanthoma-a diagnosis of exclusion! | journal = Wien Med Wochenschr | volume = 163 | issue = 15-16 | pages = 380-386 | month = Aug | year = 2013 | doi = 10.1007/s10354-012-0173-1 | PMID = 23319144 }}</ref> some say it is the same thing.<ref name=danny>Ghazarian, Danny; 16 September 2011.</ref>
*Usually benign.
**May metastasize - case report-type of occurrence.<ref>{{Cite journal | last1 = New | first1 = D. | last2 = Bahrami | first2 = S. | last3 = Malone | first3 = J. | last4 = Callen | first4 = JP. | title = Atypical fibroxanthoma with regional lymph node metastasis: report of a case and review of the literature. | journal = Arch Dermatol | volume = 146 | issue = 12 | pages = 1399-404 | month = Dec | year = 2010 | doi = 10.1001/archdermatol.2010.206 | PMID = 20713774 | URL = http://archderm.jamanetwork.com/article.aspx?articleid=422416 }}</ref>

Clinical:
*Rapid growth.
*Elderly.
*Good prognosis.<ref name=pmid20526171>{{Cite journal | last1 = Beer | first1 = TW. | last2 = Drury | first2 = P. | last3 = Heenan | first3 = PJ. | title = Atypical fibroxanthoma: a histological and immunohistochemical review of 171 cases. | journal = Am J Dermatopathol | volume = 32 | issue = 6 | pages = 533-40 | month = Aug | year = 2010 | doi = 10.1097/DAD.0b013e3181c80b97 | PMID = 20526171 }}</ref>

==Microscopic==
Features:<ref name=Ref_Derm521>{{Ref Derm|521}}</ref>
*Dermal lesion - '''key point'''.
*Marked nuclear atypia.
*Mitoses.
*Mulitnucleated cells.
*Foamy cytoplasm - '''key feature'''.

DDx:
*[[Malignant melanoma]].
*[[Pleomorphic undifferentiated sarcoma]] (MFH) - deeper than the dermis.
*[[Leiomyosarcoma]].
*Sarcomatoid [[squamous carcinoma]].

Notes:
*No Grenz zone. (???)

===Images===
<gallery>
Image: SkinTumors-P9280873.jpg | AFX. (WC)
Image: SkinTumors-P9280874.jpg | AFX. (WC)
Image: SkinTumors-P9280875.jpg | AFX. (WC)
</gallery>
www:
*[http://dermatology.cdlib.org/141/case_reports/afx/1.jpg AFX (cdlib.org)].<ref name=pmid18319023>{{Cite journal | last1 = Vandergriff | first1 = TW. | last2 = Reed | first2 = JA. | last3 = Orengo | first3 = IF. | title = An unusual presentation of atypical fibroxanthoma. | journal = Dermatol Online J | volume = 14 | issue = 1 | pages = 6 | month = | year = 2008 | doi = | PMID = 18319023 }}</ref>

A markedly atypical lesion of far less worrisome significance is the pleomorphic hyalinizing angioectatic tumor of soft parts (subcutis).
[[File:DP27AP17 sl1.png| Pleomorphic hyalinizing angioectatic tumor of soft parts (subcutis).]]
[[File:DP27AP17 sl2.png| Pleomorphic hyalinizing angioectatic tumor of soft parts (subcutis).]]
[[File:DP27AP17 sl3.png| Pleomorphic hyalinizing angioectatic tumor of soft parts (subcutis).]]
[[File:DP27AP17 sl4.png| Pleomorphic hyalinizing angioectatic tumor of soft parts (subcutis).]]
[[File:DP27AP17 sl5.png| Pleomorphic hyalinizing angioectatic tumor of soft parts (subcutis).]]
[[File:DP27AP17 sl6.png| Pleomorphic hyalinizing angioectatic tumor of soft parts (subcutis).]]
 
Pleomorphic hyalinizing angioectatic tumor of soft parts (subcutis). A. The key distinction is at low power, wherein cluters of thin-walled, indented (ectatic) blood vessels are seen. B. The ectatic vessels have a thin endothelial lining and a thick subjacent rim of amorphous eosinophilia. Note the multinucleated cells in the stroma. C. Hyaline material extends beyond vessels to entrap stromal cells. D. Cellularity in part raises the possibility of a sarcoma. E. High power further raises the suspicion of malignancy, given the aberrant nuclei with prominent nucleoli. F. Reassurance occurs because 1) there are virtually no mitoses, 2) there is no necrosis, and 3) there are readily identifiable nuclear inclusions as seen in these tumor cells.

==IHC==
Features:<ref name=Ref_Derm521>{{Ref Derm|521}}</ref>
*S100 -ve (done to r/o melanoma).
*CK34betaE12 -ve.
*p63 -ve (done to exclude [[squamous cell carcinoma of the skin|SCC]]).
**Scant staining not considered +ve.
*Desmin -ve (done to r/o leiomyosarcoma).
*[[CD99]] +ve.<ref name=pmid11789717>{{Cite journal | last1 = Monteagudo | first1 = C. | last2 = Calduch | first2 = L. | last3 = Navarro | first3 = S. | last4 = Joan-Figueroa | first4 = A. | last5 = Llombart-Bosch | first5 = A. | title = CD99 immunoreactivity in atypical fibroxanthoma: a common feature of diagnostic value. | journal = Am J Clin Pathol | volume = 117 | issue = 1 | pages = 126-31 | month = Jan | year = 2002 | doi = 10.1309/2EXB-70CW-3U6P-VQ6H | PMID = 11789717 }}</ref>
**Usually +ve in [[melanoma]]... but negative in [[squamous carcinoma]].

Others:
*Vimentin +ve.
*SMA +ve.{{fact}}

New ''et al.'' suggests:<ref name=pmid20713774>{{Cite journal | last1 = New | first1 = D. | last2 = Bahrami | first2 = S. | last3 = Malone | first3 = J. | last4 = Callen | first4 = JP. | title = Atypical fibroxanthoma with regional lymph node metastasis: report of a case and review of the literature. | journal = Arch Dermatol | volume = 146 | issue = 12 | pages = 1399-404 | month = Dec | year = 2010 | doi = 10.1001/archdermatol.2010.206 | PMID = 20713774 }}</ref>
*Vimentin, SMA, CD68, cytokeratins, p63, desmin, CD99, CD10, S100, CD117, LN-2, procollagen I.

A panel:
*Vimentin, SMA, CD68, CK18, [[EMA]], [[CAM5.2]], CK34betaE12, [[CK5/6]], [[p63]], desmin, CD99, CD10, S100, CD34.

==Sign out==
===Incompletely excised===
<pre>
SKIN LESION, MID BACK, SHAVE BIOPSY:
- ATYPICAL SPINDLE CELL NEOPLASM, SEE MICRO AND COMMENT.

COMMENT:
The diagnosis of atypical fibroxanthoma (AFX) is favoured. The main differential
diagnosis is pleomorphic undifferentiated sarcoma.

The extent of the lesion cannot be determined, as it is present at the deep margin.

This lesion should be re-excised, as it could represent an aggressive malignancy.
</pre>

==See also==
*[[Dermatologic neoplasms]].
*[[Undifferentiated pleomorphic sarcoma]].

==References==
{{Reflist|2}}

[[Category:Diagnosis]]
[[Category:Dermatologic neoplasms]]

Dermatopathology

2017-04-20T14:38:07Z

Mitchell: /* Others */ added histoplasmosis

'''Dermatopathology''' is the pathology of skin.

Pathology is a significant part of dermatology and dermatologists spend five years in residency. So, it is a huge area.

=Specimens=
*Shave biopsy = done for what is presumed to be benign disease - classically exophytic lesions, e.g. [[seborrheic keratosis]].
*Saucerization = scooped shave biopsy.<ref>{{Cite journal | last1 = Elston | first1 = D. | title = Practical advice regarding problematic pigmented lesions. | journal = J Am Acad Dermatol | volume = 67 | issue = 1 | pages = 148-55 | month = Jul | year = 2012 | doi = 10.1016/j.jaad.2012.04.006 | PMID = 22703907 }}
</ref>
*Punch biopsy = cylindrical piece of skin, usu. epidermis and dermis - suspicious lesions/malignant lesions, e.g. [[basal cell carcinoma]].
*Incisional biopsy = a piece of the lesion for pathologic assessment; lesion not completely removed.
*Excision = lesion cut-out with intent for complete removal - usual has a generous margin, e.g. [[malignant melanoma]] excision.
*Re-excision = done to get a wider margin ''or'' remove part of a lesion that was incompletely removed in a prior excision.
**Conservative re-excision = cut-out more with a minimal rim of normal tissue.<ref>URL: [http://www.nedermatology.com/skin-cancer-treatments.php http://www.nedermatology.com/skin-cancer-treatments.php]. Accessed on: 26 February 2013.</ref>
*[[Sentinel lymph node]] removal = a special type of lymphadenectomy usu. done for [[cancer staging|staging]], esp. [[malignant melanoma]].

=Histology=
==Layers of the skin==
[[Image:Skin.png|thumb|Schematic showing the layers and structures of skin. (WC/cancer.gov)]]
*Epidermis - outer most layer, avascular, separated from dermis by a basement membrane, epithelial tissue.
*Dermis - below the epidermis, vascular, separated from the epidermis by a basement membrane, connective tissue.

Note:
*The layer below the skin is the ''subdermis'' ([[AKA]] hypodermis, [[AKA]] subcutaneous tissue).
**It is below the dermis and consists of adipose tissue.<ref>URL: [http://histologyolm.stevegallik.org/node/119 http://histologyolm.stevegallik.org/node/119]. Accessed on: 5 November 2013.</ref>

Image:
*[http://histologyolm.stevegallik.org/node/119 Dermis and hypodermis (stevegallik.org)].

===Epidermis===
====Layers of the epidermis====
[[Image:Epidermal layers.png|thumb|right|Layers of the epidermis. (WC/Wbensmith)]]
Epidermis layers - from the surface to epidermal-dermal junction:
*Stratum corneum.
*Stratum lucidum.
**Present only in "thick" skin.<ref name=Ref_Derm1>{{Ref Derm|1}}</ref>
*Stratum granulosum.
*Stratum spinosum (aka prickle layer).
*Stratum basale (germinativum).
Mnemonic: ''Corn Lovers Grow Several Bales''.

====Cells of the epidermis====
*Keratinocytes.
**Usually eosinophilic cytoplasm - '''important feature'''.
**May have clear perinuclear halo (glycogenated keratinocytes).
**Intercellular bridges (high power) - '''key feature'''.
*Melanocytes.
**Usuallly basal location.
**Epithelioid or dentritic morphology.
**Pericellular clearing - '''key feature'''.
**Clear cytoplasm.
**+/-Pigmentation.
*Other:
**Toker cell.
**Neutrophils.
***Trilobated nuclei - 2-3 little dots - '''key feature'''.
**Lymphocytes.
***Small (round) nucleus.
***Scant/indistinct cytoplasm.
**Other foreign cells:
***[[Paget disease]]: large cells with clear cytoplasm, may cluster, above basal layer.

====Normal histology====
Features:
*Keratinocytes:
**Basal ~ 2x [[RBC]].
***May palisade focally ~ 1:2 = width: height.
*Melanocytes < 25 melanocytes / 0.5 mm of basal layer.<ref name=pmid21549242>{{Cite journal | last1 = Trotter | first1 = MJ. | title = Melanoma margin assessment. | journal = Clin Lab Med | volume = 31 | issue = 2 | pages = 289-300 | month = Jun | year = 2011 | doi = 10.1016/j.cll.2011.03.006 | PMID = 21549242 }}</ref>
*Basket weave stratum corneum (non-acral skin).

===Dermis===
Subdivided into layers:
#Papillary dermis.
#*Location: superficial - opposed to the deep aspect of the epidermis.
#*Appearance: dense, thick collagen bundles.
#Reticular dermis.
#*Location: deep - between papillary dermis and subdermis.
#*Appearance: loose connective tissue.

Images:
*[http://www.biology-online.org/user_files/Image/Anatomy/AN-fibroblastF02.gif Layers of the dermis - labelled (biology-online.org)].<ref>URL: [http://www.biology-online.org/articles/fibroblast_heterogeneity_skin_deep/figures.html http://www.biology-online.org/articles/fibroblast_heterogeneity_skin_deep/figures.html]. Accessed on: 29 March 2012.</ref>
*[http://melanoma.blogsome.com/wp-admin/images/skinstr.jpg Layers of the skin (melanoma.blogsome.com)].<ref>URL: [http://melanoma.blogsome.com/category/skin-structure/ http://melanoma.blogsome.com/category/skin-structure/]. Accessed on: 29 March 2012.</ref>

===Adnexal structures===
The top five structures of the skin:<ref>{{Ref Derm|4-8}}</ref>
{| class="wikitable sortable"
! Structure / Attribute
! Histomorphology
! Function
! [[IHC]]
! Other
! Image
|-
| '''Eccrine gland'''
| clusters of tubular structures, pale cytoplasm
| thermoregulation (cooling) - produce sweat
| [[CK7]]+, [[CEA]]+, CAM5.2+, [[EMA]]+
| ?
| ?
|-
| '''Apocrine gland'''
| apical snouts, tubular structures
| ear wax, body odor
| ?
| ?
| ?
|-
| '''Sebaceous gland'''
| clusters of cells side-by-side, pale fluffy cytoplasm
| grease hair, sexual lubrication
| ?
| assoc. with hair follicle
| ?
|-
| '''Hair follicle'''
| linear structure
| keep individual warm
| ?
| assoc. with sebaceous glands
| ?
|-
| '''Nail'''
| epidermal structure
| weapon (claw-like), look pretty?
| ?
| ?
| [http://histology.osumc.edu/histology/HumanHisto/Integumentary/Img/17B-23_001.html (osumc.edu)], [http://ctrgenpath.net/static/atlas/mousehistology/Windows/integumentary/nail20.html (ctrgenpath.net)]
|-
|}

Ducts vs. glands:<ref>HJ. 27 Feb 2009.</ref>
*Eccrine glands - spindle-shaped myoepithelial cells surround luminal cells.
*Eccrine ducts - cuboidal type subepithelial cells.

=Common terms=
==Clinical descriptors==
There are multitude of clinical descriptors - common ones are:<ref>URL: [http://www.pediatrics.wisc.edu/education/derm/text.html http://www.pediatrics.wisc.edu/education/derm/text.html]. Accessed on: 18 September 2012.</ref>
{| class="wikitable sortable"
! '''Name'''
! '''Size †'''
! '''Description'''
! '''Other'''
! '''Image'''
|-
| Macule
| <= 10 mm
| flat + change of colour
| if > 10 mm --> patch
| [[Image:Macule_and_Patch.svg|thumb|center|150px| Macule (WC)]]
|-
| Patch
| > 10 mm
| flat + change of colour
| if <= 10 mm --> macule
| [[Image:Macule_and_Patch.svg|thumb|center|150px| Patch (WC)]]
|-
| Papule
| <= 10 mm
| raised
| if > 10 mm --> nodule
| [[Image:Papule_and_Plaque.svg|thumb|center|150px| Papule (WC)]]
|-
| Nodule
| > 10 mm
| raised
| if <= 10 mm --> papule
| [[Image:Nodules.svg|thumb|center|150px| Nodule (WC)]]
|-
| Plaque
| > 10 mm
| raised, flat-top
| plateau-like
| [[Image:Papule_and_Plaque.svg|thumb|center|150px| Plaque (WC)]]
|-
| Vesicle
| <= 10 mm
| raised, fluid filled
| if > 10 mm --> bulla
| [[Image:Vesicles_and_Bulla.svg |thumb|center|150px| Vesicle (WC)]]
|-
| Bulla
| > 10 mm
| raised, fluid filled
| if <= 10 mm --> vesicle
| [[Image:Vesicles_and_Bulla.svg |thumb|center|150px| Bulla (WC)]]
|}
Note:
* † Definitions vary -- some authors use a 5 mm cut-off.

==Histologic descriptors==
Dermatopathology doesn't have intuitive terms, e.g. thickening of the stratum spinosum isn't ''spinosum hyperplasia''. The terms have to committed to memory.

===Common terms in a table===
{| class="wikitable sortable"
! Term
! Meaning
! Reference
|-
|Acanthosis
| thickening of the prickle layer (stratum spinosum) of epidermis
| <ref>[http://dictionary.reference.com/browse/acanthosis http://dictionary.reference.com/browse/acanthosis]</ref>
|-
|Acantholysis
| loss of intercellular connections in the epidermis
|
|-
|Dyskeratosis
| abnormal keratinization, often refers to keratinization below the stratum granulosum; keratinization above may be abnormal (dependent on body site)
|
|-
|Parakeratosis
| retention of nuclei in the stratum corneum, normal in mucous membranes
|
|-
|Spongiosis
| epidermal intercellular edema; cells appear to have a clear halo around 'em
| <ref>{{Ref PBoD|1230}}</ref>
|-
|Basketweave stratum corneum
| appearance of the normal stratum corneum; presence in the context of pathology suggests an acute process
|
|-
|Compact hyperkeratosis
| stratum corneum layer is dense and thickened; this suggests a chronic process
| <ref>URL: [http://dermnetnz.org/pathology/pathology-glossary.html http://dermnetnz.org/pathology/pathology-glossary.html]. Accessed on: 8 August 2012.</ref>
|-
| Hyperkeratosis
| thickened stratum corneum - also see ''compact hyperkeratosis'' and ''basketweave stratum corneum''
|
|-
|Epidermotropism †
| intraepithelial lymphocytes in [[CTCL]]; how to remember: epidermotropis''m'' = ''m''alignant
| <ref name=pmid20132423>{{Cite journal | last1 = Fung | first1 = MA. | title = 'Epidermotropism' vs. 'exocytosis' of lymphocytes 101: definition of terms. | journal = J Cutan Pathol | volume = 37 | issue = 5 | pages = 525-9 | month = May | year = 2010 | doi = 10.1111/j.1600-0560.2010.01515.x | PMID = 20132423 }}</ref>
|-
|Exocytosis †
| intraepithelial lymphocytes in benign conditions
| <ref name=pmid20132423>{{Cite journal | last1 = Fung | first1 = MA. | title = 'Epidermotropism' vs. 'exocytosis' of lymphocytes 101: definition of terms. | journal = J Cutan Pathol | volume = 37 | issue = 5 | pages = 525-9 | month = May | year = 2010 | doi = 10.1111/j.1600-0560.2010.01515.x | PMID = 20132423 }}</ref>
|-
|Orthokeratosis
| anuclear keratin layer is present (stratum corneum) - seen in normal skin; ''ortho-'' means ''correct''
| <ref>URL: [http://www.medilexicon.com/medicaldictionary.php?t=63448 http://www.medilexicon.com/medicaldictionary.php?t=63448]. Accessed on: 13 March 2013.</ref><ref>URL: [http://dictionary.reference.com/browse/ortho- http://dictionary.reference.com/browse/ortho-]. Accessed on: 13 March 2013.</ref>
|}
Note:
* † These definitions are not universally accepted. ''Epidermotropism'' is sometimes used in the context of benign disease.<ref name=pmid9537476>{{Cite journal | last1 = Fung | first1 = MA. | last2 = LeBoit | first2 = PE. | title = Light microscopic criteria for the diagnosis of early vulvar lichen sclerosus: a comparison with lichen planus. | journal = Am J Surg Pathol | volume = 22 | issue = 4 | pages = 473-8 | month = Apr | year = 1998 | doi = | PMID = 9537476 }}</ref>

Image:
*[http://commons.wikimedia.org/wiki/File:Spongiotic_dermatitis_%282%29_Dyshidrotic_.JPG Spongiosis (WC)].

===Others terms===
*Crust = epithelial elements, blood.

Image:
*[http://www.eplasty.com/article_images/eplasty10e60_fig3.gif Crust (eplasty.com)].<ref>URL: [http://www.eplasty.com/index.php?option=com_content&view=article&id=492&catid=171:volume-10-eplasty-2010&Itemid=121 http://www.eplasty.com/index.php?option=com_content&view=article&id=492&catid=171:volume-10-eplasty-2010&Itemid=121]. Accessed on: 16 October 2012.</ref>

=Skin diseases=
==Neoplasms==
{{main|Dermatologic neoplasms}}

===Malignant===
Skin cancer is very common. The basic DDx of a malignant skin lesion is:
*[[Squamous cell carcinoma]] (SCC).
*[[Basal cell carcinoma]] (BCC).
*[[Malignant melanoma]].
*Metstases.

==Non-malignant disease==
{{main|Non-malignant skin disease}}
Non-malignant skin disease is common. It is the domain of dermatologists. It can be scary for general anatomical pathologists because the differential diagnosis is often broad, and, it's generally not something the general anatomical pathologist sees a lot of.

===Subarticles===
*[[Dermal cysts]], e.g. [[epidermal cyst]], [[pilar cyst]].
*[[Epidermal necrosis]], e.g. [[erythema multiforme]], [[toxic epidermal necrolysis]].
*[[Inflammatory skin diseases]].
**[[Bullous diseases]], e.g. [[pemphigus vulgaris]].
**[[Panniculitis]].

=Common entities in tables=
==Non-malignant non-cystic - very common==
{| class="wikitable sortable" style="margin-left:auto;margin-right:auto"
! Entity
! Key histologic feature
! Other features
! Clinical
! Stains/IHC
! DDx
! Other
! Image
|-
| [[Seborrheic keratosis]] (SK)
| horn cysts (intraepidermal collections of keratin)
| hyperkeratosis, brown granular material at the DE junction, sharply demarcated
| stuck on appearance
| none
| [[fibroepithelial polyp]]
| Leser–Trélat sign = many SKs in malignancy
| [[Image:Seborrheic_keratosis_(1).jpg |thumb|center|150px| SK (WC)]]
|-
| [[Dermatofibroma]]
| fibrous bundles esp. at edge of lesion
| "dirty fingers" = acanthosis + basal keratinocyte hyperpigmentation
| +/-trauma Hx
| CD34-, Factor XIIIa+
| [[DFSP]]
| very common
| [[Image:SkinTumors-P9280848.jpg|thumb|center|150px|DF (WC)]]
|-
| [[Fibroepithelial polyp]] (skin tag)
| on a stalk (epithelium on 3+ sides)
| no horn nests, no hyperkeratosis
| raised lesion
| none
| [[seborrheic keratosis]]
| very common
| [[Image:SkinTumors-P9250819.jpg|thumb|center|150px|Skin tag (WC)]]
|-
| [[Lipoma]]
| mature adipocytes - uniform size
| var. of size may be seen, should prompt search for lipoblasts
| mobile subcutaneous mass
| S100 (???)
| [[liposarcoma]]
| variants: angiolipoma (blood vessels), myolipoma (muscle)
| [[Image: Lipoma -- high mag.jpg|thumb|center|150px|Lipoma (WC)]]
|-
| [[Cicatrix]] (dermal scar)
| dense collagen bundles running parallel to DE junction, loss of dermal papillae
| loss of adnexal structures, +/-[[giant cells]], +/-foreign material, +/-inflammatory cells
| site of previous trauma/surgery
| usu. none; S-100 (to exclude melanoma)
| residual disease, [[hypertrophic scar]], (desmoplastic) [[melanoma]]
|
| [[Image:ScarHistology.JPG |thumb|center|150px| Scar (WC)]]
|- 
|}

==Non-malignant non-cystic - common==
{| class="wikitable sortable" style="margin-left:auto;margin-right:auto"
! Entity
! Key histologic feature
! Other features
! Clinical
! Stains/IHC
! DDx
! Other
! Image
|-
| [[Neurofibroma]]
| bland spindle cells
| mast cells, mixed with collagen, assoc. with a nerve
| may be associated with [[neurofibromatosis]], esp. plexiform type
| S100+, GFAP+
| neurotized [[melanocytic nevus]]
| may develop into [[MPNST]]
| [[Image:Neurofibroma_%281%29.jpg |thumb|center|150px| Neurofibroma (WC)]]
|-
| [[Keratoacanthoma]]
| keratin plug, glassy pink cytoplasm, pushing downward growth
| minimal/no nuclear atypia
| grow rapidly then involute
| none
| [[squamous cell carcinoma]]
| some don't believe in the entity
| [[Image:Skin_keratoacanthoma_whole_slide.jpg |thumb|center|150px| Keratoacathoma (WC)]]
|-
| [[Molluscum contagiosum]]
| suprabasilar cells with abundant granular eosinophilic cytoplasm
| small peripheral nucleus
| polypoid lesion; mushroom-like (?)
| none (?)
| DDx (?)
| favourite exam case
| [[Image:Molluscum_contagiosum_high_mag.jpg |thumb|center|150px|Molluscum contagiosum (WC)]]
|-
| [[Verruca vulgaris]]
| hypergranulosis (thick granular layer) + keratohyaline granules
| hyperkeratosis (thick s. corneum), acanthosis (thick s. spinosum), rete ridges lengthened (~7-10x normal), large vessels at DE junction, koilocytic change (???)
| raised lesions, classically on hand
| none (p16+?)
| [[squamous cell carcinoma of the skin|squamous cell carcinoma]]
| caused by [[HPV]]
| [[Image:Verruca_vulgaris_-_very_low_mag.jpg |thumb|center|150px| Verruca vulgaris (WC)]]
|-
| [[Condyloma acuminatum]]
| koilocytes
| parakeratosis, long folded rete ridges (papillomatosis) - pseudopapillary look
| genital lesion
| none (p16+)
| [[fibroepithelial polyp]]
| caused by [[HPV]]
| [[Image:Anal_condyloma_%282%29.jpg |thumb|center|150px| Condyloma acuminatum (WC)]]
|-
| [[Granuloma annulare]]
| dermal palisading [[granuloma]] around necrotic collagen
| mucin in centre of lesion, (peripheral) lymphocytes, usu. more superficial than necrobiosis lipoidica
| benign, self-limited
| none (CD68?)
| [[necrobiosis lipoidica]], [[rheumatoid nodule]], [[epithelioid sarcoma]]
| Other ?
| [[Image:Granuloma_annulare_-_add_-_high_mag.jpg |thumb|center|150px| GA (WC)]]
|-
| [[Necrobiosis lipoidica]]
| dermal palisading [[granuloma]] around necrotic collagen, plasma cells
| mucin in centre of lesion, (peripheral) chronic inflammatory cells
| may be assoc. [[diabetes mellitus]]
| none (CD68?)
| [[granuloma annulare]], [[rheumatoid nodule]]
| histology identical to ''necrobiosis lipoidica diabeticorum''
| [http://www.drmihm.com/cases/casefigure.cfm?figID=942&CaseID=53 (drmihm.com)]
|-
| [[Angiofibroma]]
| fibrotic dermis, dilated capillaries
| enlarged (stellate fibroblasts)
| dome-shaped - face, boys & nosebleeds ([[nasopharyngeal angiofibroma]])
| Stains/IHC
| DDx
| may be associated with [[tuberous sclerosis]]
| [[Image:Nasopharyngeal angiofibroma - 2 - high mag.jpg|thumb|150px|Angiofibroma (WC)]]
|-
| [[Keloid]]
| thick collagen bundles - surrounded by paler staining fibroblasts
| replaces adnexal structures
| site of previous trauma, esp. in blacks
| none
| [[dermatofibroma]] (???)
| [[hypertrophic scar]]
| [[Image:Keloid_-_high_mag.jpg|thumb|center|150px|Keloid (WC)]]
|-
| [[Eccrine poroma]]
| abundant basaloid cells with (small) ductal structures
| incloses islands of sclerotic stroma with edema
| erythematous lesions
| Stains/IHC ?
| DDx ?
| Other ?
| [[Image:SkinTumors-P7150495.JPG|thumb|center|150px|EP (WC)]]
|-
| [[Syringoma]]
| bilayered ducts, occasionally tadpole like shape
|
| usu. close to [[eyelid]]
| Stains/IHC ?
| DDx ?
| Other ?
| [http://dermatology.cdlib.org/144/tumors/axillary_syringoma/2.jpg (cdlib.org)]
|-
| [[Chondroid syringoma]] (mixed tumour of skin)
| [[chondromyxoid stroma]], epithelial component
| epithelial component in nests with eosinophilic cytoplasm, round/ovoid nuclei with nucleoli
| Clinical ?
| Stains/IHC ?
| DDx ?
| related to [[pleomorphic adenoma]] (???)
| Image ?
|-
| [[Angiokeratoma]]
| ectatic superficial dermal vessels + overlying hyperkeratosis
| -
| may be seen in [[Fabry disease]]
| Stains/IHC ?
| [[venous lake]]
| Other ?
| [[Image:Angiokeratoma_-_low_mag.jpg |thumb|center|150px| Angiokeratoma (WC)]]
|- 
|}

==Non-malignant non-cystic - children==
{| class="wikitable sortable" style="margin-left:auto;margin-right:auto"
! Entity
! Key histologic feature
! Other features
! Clinical
! Stains/IHC
! DDx
! Other
! Image
|-
| [[Pilomatricoma]]
| anucleate squamous cells (ghost cells), giant cells
| bland basaloid cells
| common in children
| none
| [[squamous cell carcinoma of the skin|squamous cell carcinoma]]
| mutations of CTNNB1 gene
| [[Image:Pilomatrixoma_-_intermed_mag.jpg |thumb|center|150px| Pilomatrixcoma (WC)]]
|-
| [[Juvenile xanthogranuloma]] (JXG)
| Touton giant cells - multi-nucleated cells where nuclei are distributed around the cell periphery forming a ring
| abundant cytoplasm
| children
| CD68+, CD1a-, CD207-
| [[Langerhans cell histiocytosis]]
| may be seen in adults, known as '''adult xanthogranuloma'''
| [[Image:Juvenile_xanthogranuloma_-_high_mag.jpg |thumb|center|150px| JXG (WC)]]
|}

==Non-malignant cystic==
{| class="wikitable sortable" style="margin-left:auto;margin-right:auto"
! Entity
! Key histologic feature
! Other features
! Clinical
! Stains/IHC
! DDx
! Other
! Image
|-
| [[Epidermal cyst]]
| cyst lined by squamous epithelium '''with''' a granular layer
| keratinous debris, no skin adnexal structures
| cyst
| none
| [[pilar cyst]], [[dermoid cyst]]
| Other?
| [[Image:Epidermal inclusion cyst -- high mag.jpg |thumb|center|150px| Epidermal inclusion cyst (WC)]]
|-
| [[Pilar cyst]] (trichilemmal cyst)
| cyst lined by squamous epithelium '''without''' a granular layer
| keratinous debris
| cyst
| none
| [[epidermal cyst]]
| Other?
| [[Image:Trichilemmal_cyst_-_very_high_mag.jpg |thumb|center|100px| Pilar cyst (WC)]]
|-
| [[Steatocystoma]]
| cyst lined by squamous epithelium with a corrugated eosinophilic lining
| epidermis has '''no''' granular layer
| cyst
| none
| [[dermoid cyst]], follicular cyst
| Other?
| [[Image:Steatocystoma_-_high_mag.jpg |thumb|center|150px| Steatocystoma (WC)]]
|-
| [[Dermoid cyst]]
| cyst lined by keratinizing squamous epithelium with adnexal structures
| adnexal structure = hair, sebaceous gland, sweat glands
| cyst
| none
| [[epidermal cyst]]
| may be seen in the [[ovary]]
| [http://webeye.ophth.uiowa.edu/eyeforum/cases-i/case115/larger/Figure4.jpg (uiowa.edu)]
|}

==Pre-malignant==
{| class="wikitable sortable" style="margin-left:auto;margin-right:auto"
! Entity
! Key histologic feature
! Other features
! Clinical
! Stains/IHC
! DDx
! Other
! Image
|-
| [[Actinic keratosis]]
| epidermal atypia, esp. (basal) nuclear enlargement
| var. of nuclear size, shape and staining, parakeratosis (important in early lesions); does ''not'' involves adnexal epithelium and follicular epithelium
| yellow-brown scaly
| none
| [[squamous carcinoma]], [[Bowen disease]]
| seen with [[solar elastosis]]
| [[Image:Actinic_Keratosis,_H%26E.jpg |thumb|center|150px| AK (WC)]]
|-
| [[Bowen disease]] (squamous cell carcinoma in situ)
| epidermal atypia, esp. suprabasal nuclear enlargement
| var. of nuclear size, shape and staining; usually full thickness involvement; involve adnexal epithelium and follicular epithelium
|
| none
| [[squamous carcinoma]], [[actinic keratosis]]
| typically seen with solar elastosis
| [[Image:Bowen_disease_%281%29.jpg |thumb|center|100px| Bowen's disease (WC)]]
|}

==Common malignant==
{| class="wikitable sortable" style="margin-left:auto;margin-right:auto"
! Entity
! Key histologic feature
! Other features
! Clinical
! Stains/IHC
! DDx
! Other
! Image
|-
| [[Basal cell carcinoma]] (BCC)
| basaloid cells with peripheral palisading, artificial cleft
| [[myxoid]] stroma
| raised, pearly, telangiectasia
| usu. none req., [[CK5/6]]+
| [[trichoepithelioma]], [[basaloid squamous cell carcinoma]]
| assoc. [[nevoid basal cell carcinoma syndrome]], [[Bazex syndrome]]
| [[Image:Basal cell carcinoma - high mag.jpg| thumb| center|150px|BCC (WC)]]
|-
| [[Squamous cell carcinoma]] (SCC)
| nuclear enlargement, eosinophilic cytoplasm, central nucleus
| small nucleolus, intercellular bridges
| flaky appearance
| usu. none req., p63+, HMWK+
| [[keratoacanthoma]], [[Paget disease]] ([[EMPD]] & [[PDB]]), [[malignant melanoma]], Toker cell hyperplasia
| Other
| [[Image:Oral_cancer_%281%29_squamous_cell_carcinoma_histopathology.jpg|thumb|center|150px|SCC (WC)]]
|-
| [[Malignant melanoma]]
| spindle and/or epithelioid morphology +/-nuclear atypia (esp. nucleoli)
| mitoses (esp. deep), +/-pigment, +/-nested arch., asymmetry, upward spread (into epidermis), epithelioid m. deep, +/-single cells, +/-sheets of cells
| ABCD = Asymmetry, Borders poor demarc., Colour dark, Diameter large
| S100+, Melan A+, HMB-45+, microphthalmia+, tyrosinase+
| [[melanocytic lesions]] esp. [[Spitz nevus]], [[Bowen's disease]]
| may be familial, [[dysplastic nevus]]
| [[Image:Malignant_melanoma_%281%29_at_thigh_Case_01.jpg |thumb|center|150px|Melanoma (WC)]]
|- 
|}

==Less common malignant==
{| class="wikitable sortable" style="margin-left:auto;margin-right:auto"
! Entity
! Key histologic feature
! Other features
! Clinical
! Stains/IHC
! DDx
! Other
! Image
|-
| [[Kaposi sarcoma]]
| vascular spindle cell lesion
| [[hyaline globules]] (intracytoplasmic)
| often HIV/AIDS
| [[HHV-8]]
| [[Masson's hemangioma]], [[angiosarcoma]], [[Kaposiform hemangioendothelioma]]
| stages: patch stage, plaque stage, nodular stage, exophytic, infiltrative, lymphadenopathic
| [[Image:Kaposi_sarcoma_low_intermed_mag.jpg |thumb|center|150px| Kaposi sarcoma (WC)]]
|-
| [[Cutaneous T-cell lymphoma]] (includes ''mycosis fungoides'')
| single lymphocytes in epidermis ("lymphocyte exocytosis")
| lymphocyte nests in the epidermis ("Pautrier microabscesses"), short arrays of lymphocytes along the basal layer of the epidermis ("epidermotropism")
| Clinical
| CD45, CD4
| B cell lymphoma (?)
| Other
| [[Image:Cutaneous_T-cell_lymphoma_-_intermed_mag.jpg |thumb|center|150px| CTCL (WC)]]
|-
| [[Atypical fibroxanthoma]]
| dermal lesion with marked nuclear atypia
| multinucleated cells, mitoses, vacuolated cytoplasm
| old men, head and neck
| p63-, 34betaE12-, S100-, desmin-
| sarcomatoid squamous carcinoma, [[melanoma]], [[leiomyosarcoma]]
| some classify this as '''benign'''; thought to be related to [[undifferentiated pleomorphic sarcoma]]
| [[Image:SkinTumors-P9280874.jpg|thumb|center|150px| AFX (WC)]]
|-
| [[Merkel cell carcinoma]]
| neuroendocrine nuclear features (stippled chromatin, no nucleolus), scant cytoplasm
| +/-nuclear moulding, usu. intermediate cell size
| Merkel cell polyomavirus associated, usu. head & neck or extremities
| CK20+, EMA+
| cutaneous [[Ewing sarcoma]], [[basal cell carcinoma]], (dermal) [[lymphoma]], metastatic small cell carcinoma (e.g. [[Lung tumours#Small cell carcinoma|lung]])
| rare, aggressive
| [[Image:Merkel_cell_carcinoma_-_very_high_mag.jpg |thumb|center|100px| MCC (WC)]]
|-
| [[Dermatofibrosarcoma protuberans]] (DFSP)
| spindle cell tumour with storiform pattern, tumour often contains adipocytes
| dermal tumour with preserved adnexal structures
| locally aggressive
| CD34+, factor XIIIa-
| [[dermatofibroma]], [[solitary fibrous tumour]] (usu. deeper)
| rarely metastases, characteristic [[translocation]]: t(17;22)(q22;q15) COLA1/PDGFB; may transform to [[fibrosarcoma]]
| [[Image:Storiform_pattern_-_intermed_mag.jpg |thumb|center|150px| DFSP (WC)]]
|- 
|}

=Presentations=
==Leukoplakia==
{{Main|Leukoplakia}}

DDx:<ref>{{Ref PBoD|1065}}</ref>
*Vitiligo (loss of pigment).
*Inflammation.
**Chronic dermatitis.
**[[Psoriasis]].
*Neoplasia.
**[[Vulvar intraepithelial neoplasia]].
**[[Invasive_breast_cancer#Paget.27s_disease|Paget disease]].
**Invasive carcinoma.
*Other.
**[[Lichen sclerosus]].
**[[Lichen simplex chronicus]].

=Skin disease and systemic conditions=
==Tabular list==
{| class="wikitable sortable" style="margin-left:auto;margin-right:auto"
! Entity
! Disease/syndrome
! Key histologic feature
! Image
|-
| [[Acanthosis nigricans]]
| [[diabetes mellitus]], malignancy
| basal cell hyperpigmentation, hyperkeratosis, prominent rete ridges
| [http://dermatology.cdlib.org/149/reviews/acanthosisnigricans/higgins.html (cdlib.org)]
|-
| [[Trichilemmoma]]
| [[Cowden disease]]
| "hyperkeratosis"
| [http://ccr.cancer.gov/staff/images/9033_12822_Lee_1520.jpg (cancer.gov)]<ref>URL: [http://ccr.cancer.gov/staff/gallery.asp?profileid=12822 http://ccr.cancer.gov/staff/gallery.asp?profileid=12822]. Accessed on: 14 December 2011.</ref>
|-
| [[Angiokeratoma]]
| [[Fabry disease]]
| hyperkeratosis + vessels in superficial dermis
| [http://commons.wikimedia.org/wiki/File:Angiokeratoma_-_low_mag.jpg (WC)]
|-
| [[Dermatitis herpetiformis]]
| [[Celiac disease]]
| subepidermal [[bullous disease]], papillary abscesses
| [http://www.lampyris101.com/L101/gallery1/12_JPG.html (lampyris101.com)]
|-
| [[Angiofibroma]]
| [[tuberous sclerosis]]
| fibrotic dermis + dilated blood vessels
| [http://www.drdittmar.lu/images/sce/angiofibroma-s.jpg (drdittmar.lu)]
|-
| [[Sebaceous adenoma]]
| [[Muir-Torre syndrome]]
| abundant sebaceous glands with abn. arch.
| [http://commons.wikimedia.org/wiki/File:Sebaceous_adenoma_-_low_mag.jpg (WC)]
|-
| [[Seborrheic keratosis]], multiple with explosive onset
| Leser–Trélat sign (malignancy)
| horn cysts, hyperkeratosis
| [http://commons.wikimedia.org/wiki/File:IMG_1724.JPG gross (WC)], [http://commons.wikimedia.org/wiki/File:Seborrheic_keratosis_%281%29.jpg micro. (WC)]
|- 
|}

==Acanthosis nigricans==
===General===
Associated with:
*[[Diabetes mellitus]].<ref>URL: [http://www.emedicine.com/derm/topic1.htm http://www.emedicine.com/derm/topic1.htm], URL: [http://dermatlas.med.jhmi.edu/derm/indexDisplay.cfm?ImageID=1943559504].</ref>
*Malignancy.<ref name=Ref_PCPBoD8|596>{{Ref PCPBoD8|596}}</ref>

===Microscopic===
Features (memory device ''BPH''):<ref name=Ref_PCPBoD8|596>{{Ref PCPBoD8|596}}</ref>
*Basal cell hyperpigmentation.
*Prominent rete ridges.
*Hyperkeratosis.

DDx:
*[[Seborrheic keratosis]] - typically has more hyperkeratosis, pseudohorn cysts.

Images:
*[http://dermatology.cdlib.org/149/reviews/acanthosisnigricans/higgins.html AN (cdlib.org)].

==Others==
*[[Dermatitis herpetiformis]]: gluten enteropathy ([[celiac disease]]), [[thyroid]] disease, intestinal [[lymphoma]].<ref name=Ref_TN2007_D23>{{Ref TN2007|D23}}</ref>
*[[Pemphigus vulgaris]]: [[thymoma]], myasthenia gravis, malignancy.<ref name=Ref_TN2007_D23>{{Ref TN2007|D23}}</ref>
 
[[File:3767 dp sl 1.png |Lipoid proteinosis]]
[[File:3767 dp sl 2.png |Lipoid proteinosis]] 
Lipoid proteinosis. A. Inner labial biopsy shows subepithelial hyalinized pink/red material, about blood vessels and in general. B. The particularly glassy appearance of the material in areas is evident at high power.
 
[[File:DP16MR17 sl 1.png| Xanthogranuloma in scrotal skin.]]
[[File:DP16MR17 sl 2.png| Xanthogranuloma in scrotal skin.]]
[[File:DP16MR17 sl 3.png| Xanthogranuloma in scrotal skin.]]
[[File:DP16MR17 sl 4.png| Xanthogranuloma in scrotal skin.]]
 
Xanthogranuloma in scrotal skin. A. Pseudoepitheliomatous hyperplasia seemingly forms a dermal mass. B. Parakeratosis tops epidermis. C. Neutrophils lie in the center of the apparent mass. D. Diagnostic xanthoma cells lie in dermal papillae.
 
[[File:DP13AP17 sl1.png| Silicone granuloma]]
[[File:DP13AP17 sl2.png| Silicone granuloma]]
[[File:DP13AP17 sl3.png| Silicone granuloma]]
[[File:DP13AP17 sl4.png| Silicone granuloma]]
 
Silicone granuloma. A. The dermis resembles Swiss cheese. B. Macrophages, some with more than one nucleus, accompany empty ovoid spaces. C. Some macrophages resemble Teuton body giant cells. D. An admixture of lymphocytes is not at all unusual.
[[File:DP20AP17 sl 1.png| Dermal histoplasmosis]]
[[File:DP20AP17 sl 2.png| Dermal histoplasmosis]]
[[File:DP20AP17 sl 3.png| Dermal histoplasmosis]]
[[File:DP20AP17 sl 4.png| Dermal histoplasmosis]] 
Histoplasmosis in skin. A. Extending from papillary dermis into dermis is a chronic, blue inflammatory infiltrate. B. The infiltrate comprises lymphocytes, plasma cells, and macrophages. C. At the edge of the biopsy pink strews inflammatory cells; this pink invasion of inflammation, so to speak, is a good place to look for organisms. D. High power reveals sometimes budding yeast forms in clear spaces.

=References=
{{reflist|2}}

[[Category:Dermatopathology]]

Dermatopathology

2017-04-13T14:23:38Z

Mitchell: /* Others */

'''Dermatopathology''' is the pathology of skin.

Pathology is a significant part of dermatology and dermatologists spend five years in residency. So, it is a huge area.

=Specimens=
*Shave biopsy = done for what is presumed to be benign disease - classically exophytic lesions, e.g. [[seborrheic keratosis]].
*Saucerization = scooped shave biopsy.<ref>{{Cite journal | last1 = Elston | first1 = D. | title = Practical advice regarding problematic pigmented lesions. | journal = J Am Acad Dermatol | volume = 67 | issue = 1 | pages = 148-55 | month = Jul | year = 2012 | doi = 10.1016/j.jaad.2012.04.006 | PMID = 22703907 }}
</ref>
*Punch biopsy = cylindrical piece of skin, usu. epidermis and dermis - suspicious lesions/malignant lesions, e.g. [[basal cell carcinoma]].
*Incisional biopsy = a piece of the lesion for pathologic assessment; lesion not completely removed.
*Excision = lesion cut-out with intent for complete removal - usual has a generous margin, e.g. [[malignant melanoma]] excision.
*Re-excision = done to get a wider margin ''or'' remove part of a lesion that was incompletely removed in a prior excision.
**Conservative re-excision = cut-out more with a minimal rim of normal tissue.<ref>URL: [http://www.nedermatology.com/skin-cancer-treatments.php http://www.nedermatology.com/skin-cancer-treatments.php]. Accessed on: 26 February 2013.</ref>
*[[Sentinel lymph node]] removal = a special type of lymphadenectomy usu. done for [[cancer staging|staging]], esp. [[malignant melanoma]].

=Histology=
==Layers of the skin==
[[Image:Skin.png|thumb|Schematic showing the layers and structures of skin. (WC/cancer.gov)]]
*Epidermis - outer most layer, avascular, separated from dermis by a basement membrane, epithelial tissue.
*Dermis - below the epidermis, vascular, separated from the epidermis by a basement membrane, connective tissue.

Note:
*The layer below the skin is the ''subdermis'' ([[AKA]] hypodermis, [[AKA]] subcutaneous tissue).
**It is below the dermis and consists of adipose tissue.<ref>URL: [http://histologyolm.stevegallik.org/node/119 http://histologyolm.stevegallik.org/node/119]. Accessed on: 5 November 2013.</ref>

Image:
*[http://histologyolm.stevegallik.org/node/119 Dermis and hypodermis (stevegallik.org)].

===Epidermis===
====Layers of the epidermis====
[[Image:Epidermal layers.png|thumb|right|Layers of the epidermis. (WC/Wbensmith)]]
Epidermis layers - from the surface to epidermal-dermal junction:
*Stratum corneum.
*Stratum lucidum.
**Present only in "thick" skin.<ref name=Ref_Derm1>{{Ref Derm|1}}</ref>
*Stratum granulosum.
*Stratum spinosum (aka prickle layer).
*Stratum basale (germinativum).
Mnemonic: ''Corn Lovers Grow Several Bales''.

====Cells of the epidermis====
*Keratinocytes.
**Usually eosinophilic cytoplasm - '''important feature'''.
**May have clear perinuclear halo (glycogenated keratinocytes).
**Intercellular bridges (high power) - '''key feature'''.
*Melanocytes.
**Usuallly basal location.
**Epithelioid or dentritic morphology.
**Pericellular clearing - '''key feature'''.
**Clear cytoplasm.
**+/-Pigmentation.
*Other:
**Toker cell.
**Neutrophils.
***Trilobated nuclei - 2-3 little dots - '''key feature'''.
**Lymphocytes.
***Small (round) nucleus.
***Scant/indistinct cytoplasm.
**Other foreign cells:
***[[Paget disease]]: large cells with clear cytoplasm, may cluster, above basal layer.

====Normal histology====
Features:
*Keratinocytes:
**Basal ~ 2x [[RBC]].
***May palisade focally ~ 1:2 = width: height.
*Melanocytes < 25 melanocytes / 0.5 mm of basal layer.<ref name=pmid21549242>{{Cite journal | last1 = Trotter | first1 = MJ. | title = Melanoma margin assessment. | journal = Clin Lab Med | volume = 31 | issue = 2 | pages = 289-300 | month = Jun | year = 2011 | doi = 10.1016/j.cll.2011.03.006 | PMID = 21549242 }}</ref>
*Basket weave stratum corneum (non-acral skin).

===Dermis===
Subdivided into layers:
#Papillary dermis.
#*Location: superficial - opposed to the deep aspect of the epidermis.
#*Appearance: dense, thick collagen bundles.
#Reticular dermis.
#*Location: deep - between papillary dermis and subdermis.
#*Appearance: loose connective tissue.

Images:
*[http://www.biology-online.org/user_files/Image/Anatomy/AN-fibroblastF02.gif Layers of the dermis - labelled (biology-online.org)].<ref>URL: [http://www.biology-online.org/articles/fibroblast_heterogeneity_skin_deep/figures.html http://www.biology-online.org/articles/fibroblast_heterogeneity_skin_deep/figures.html]. Accessed on: 29 March 2012.</ref>
*[http://melanoma.blogsome.com/wp-admin/images/skinstr.jpg Layers of the skin (melanoma.blogsome.com)].<ref>URL: [http://melanoma.blogsome.com/category/skin-structure/ http://melanoma.blogsome.com/category/skin-structure/]. Accessed on: 29 March 2012.</ref>

===Adnexal structures===
The top five structures of the skin:<ref>{{Ref Derm|4-8}}</ref>
{| class="wikitable sortable"
! Structure / Attribute
! Histomorphology
! Function
! [[IHC]]
! Other
! Image
|-
| '''Eccrine gland'''
| clusters of tubular structures, pale cytoplasm
| thermoregulation (cooling) - produce sweat
| [[CK7]]+, [[CEA]]+, CAM5.2+, [[EMA]]+
| ?
| ?
|-
| '''Apocrine gland'''
| apical snouts, tubular structures
| ear wax, body odor
| ?
| ?
| ?
|-
| '''Sebaceous gland'''
| clusters of cells side-by-side, pale fluffy cytoplasm
| grease hair, sexual lubrication
| ?
| assoc. with hair follicle
| ?
|-
| '''Hair follicle'''
| linear structure
| keep individual warm
| ?
| assoc. with sebaceous glands
| ?
|-
| '''Nail'''
| epidermal structure
| weapon (claw-like), look pretty?
| ?
| ?
| [http://histology.osumc.edu/histology/HumanHisto/Integumentary/Img/17B-23_001.html (osumc.edu)], [http://ctrgenpath.net/static/atlas/mousehistology/Windows/integumentary/nail20.html (ctrgenpath.net)]
|-
|}

Ducts vs. glands:<ref>HJ. 27 Feb 2009.</ref>
*Eccrine glands - spindle-shaped myoepithelial cells surround luminal cells.
*Eccrine ducts - cuboidal type subepithelial cells.

=Common terms=
==Clinical descriptors==
There are multitude of clinical descriptors - common ones are:<ref>URL: [http://www.pediatrics.wisc.edu/education/derm/text.html http://www.pediatrics.wisc.edu/education/derm/text.html]. Accessed on: 18 September 2012.</ref>
{| class="wikitable sortable"
! '''Name'''
! '''Size †'''
! '''Description'''
! '''Other'''
! '''Image'''
|-
| Macule
| <= 10 mm
| flat + change of colour
| if > 10 mm --> patch
| [[Image:Macule_and_Patch.svg|thumb|center|150px| Macule (WC)]]
|-
| Patch
| > 10 mm
| flat + change of colour
| if <= 10 mm --> macule
| [[Image:Macule_and_Patch.svg|thumb|center|150px| Patch (WC)]]
|-
| Papule
| <= 10 mm
| raised
| if > 10 mm --> nodule
| [[Image:Papule_and_Plaque.svg|thumb|center|150px| Papule (WC)]]
|-
| Nodule
| > 10 mm
| raised
| if <= 10 mm --> papule
| [[Image:Nodules.svg|thumb|center|150px| Nodule (WC)]]
|-
| Plaque
| > 10 mm
| raised, flat-top
| plateau-like
| [[Image:Papule_and_Plaque.svg|thumb|center|150px| Plaque (WC)]]
|-
| Vesicle
| <= 10 mm
| raised, fluid filled
| if > 10 mm --> bulla
| [[Image:Vesicles_and_Bulla.svg |thumb|center|150px| Vesicle (WC)]]
|-
| Bulla
| > 10 mm
| raised, fluid filled
| if <= 10 mm --> vesicle
| [[Image:Vesicles_and_Bulla.svg |thumb|center|150px| Bulla (WC)]]
|}
Note:
* † Definitions vary -- some authors use a 5 mm cut-off.

==Histologic descriptors==
Dermatopathology doesn't have intuitive terms, e.g. thickening of the stratum spinosum isn't ''spinosum hyperplasia''. The terms have to committed to memory.

===Common terms in a table===
{| class="wikitable sortable"
! Term
! Meaning
! Reference
|-
|Acanthosis
| thickening of the prickle layer (stratum spinosum) of epidermis
| <ref>[http://dictionary.reference.com/browse/acanthosis http://dictionary.reference.com/browse/acanthosis]</ref>
|-
|Acantholysis
| loss of intercellular connections in the epidermis
|
|-
|Dyskeratosis
| abnormal keratinization, often refers to keratinization below the stratum granulosum; keratinization above may be abnormal (dependent on body site)
|
|-
|Parakeratosis
| retention of nuclei in the stratum corneum, normal in mucous membranes
|
|-
|Spongiosis
| epidermal intercellular edema; cells appear to have a clear halo around 'em
| <ref>{{Ref PBoD|1230}}</ref>
|-
|Basketweave stratum corneum
| appearance of the normal stratum corneum; presence in the context of pathology suggests an acute process
|
|-
|Compact hyperkeratosis
| stratum corneum layer is dense and thickened; this suggests a chronic process
| <ref>URL: [http://dermnetnz.org/pathology/pathology-glossary.html http://dermnetnz.org/pathology/pathology-glossary.html]. Accessed on: 8 August 2012.</ref>
|-
| Hyperkeratosis
| thickened stratum corneum - also see ''compact hyperkeratosis'' and ''basketweave stratum corneum''
|
|-
|Epidermotropism †
| intraepithelial lymphocytes in [[CTCL]]; how to remember: epidermotropis''m'' = ''m''alignant
| <ref name=pmid20132423>{{Cite journal | last1 = Fung | first1 = MA. | title = 'Epidermotropism' vs. 'exocytosis' of lymphocytes 101: definition of terms. | journal = J Cutan Pathol | volume = 37 | issue = 5 | pages = 525-9 | month = May | year = 2010 | doi = 10.1111/j.1600-0560.2010.01515.x | PMID = 20132423 }}</ref>
|-
|Exocytosis †
| intraepithelial lymphocytes in benign conditions
| <ref name=pmid20132423>{{Cite journal | last1 = Fung | first1 = MA. | title = 'Epidermotropism' vs. 'exocytosis' of lymphocytes 101: definition of terms. | journal = J Cutan Pathol | volume = 37 | issue = 5 | pages = 525-9 | month = May | year = 2010 | doi = 10.1111/j.1600-0560.2010.01515.x | PMID = 20132423 }}</ref>
|-
|Orthokeratosis
| anuclear keratin layer is present (stratum corneum) - seen in normal skin; ''ortho-'' means ''correct''
| <ref>URL: [http://www.medilexicon.com/medicaldictionary.php?t=63448 http://www.medilexicon.com/medicaldictionary.php?t=63448]. Accessed on: 13 March 2013.</ref><ref>URL: [http://dictionary.reference.com/browse/ortho- http://dictionary.reference.com/browse/ortho-]. Accessed on: 13 March 2013.</ref>
|}
Note:
* † These definitions are not universally accepted. ''Epidermotropism'' is sometimes used in the context of benign disease.<ref name=pmid9537476>{{Cite journal | last1 = Fung | first1 = MA. | last2 = LeBoit | first2 = PE. | title = Light microscopic criteria for the diagnosis of early vulvar lichen sclerosus: a comparison with lichen planus. | journal = Am J Surg Pathol | volume = 22 | issue = 4 | pages = 473-8 | month = Apr | year = 1998 | doi = | PMID = 9537476 }}</ref>

Image:
*[http://commons.wikimedia.org/wiki/File:Spongiotic_dermatitis_%282%29_Dyshidrotic_.JPG Spongiosis (WC)].

===Others terms===
*Crust = epithelial elements, blood.

Image:
*[http://www.eplasty.com/article_images/eplasty10e60_fig3.gif Crust (eplasty.com)].<ref>URL: [http://www.eplasty.com/index.php?option=com_content&view=article&id=492&catid=171:volume-10-eplasty-2010&Itemid=121 http://www.eplasty.com/index.php?option=com_content&view=article&id=492&catid=171:volume-10-eplasty-2010&Itemid=121]. Accessed on: 16 October 2012.</ref>

=Skin diseases=
==Neoplasms==
{{main|Dermatologic neoplasms}}

===Malignant===
Skin cancer is very common. The basic DDx of a malignant skin lesion is:
*[[Squamous cell carcinoma]] (SCC).
*[[Basal cell carcinoma]] (BCC).
*[[Malignant melanoma]].
*Metstases.

==Non-malignant disease==
{{main|Non-malignant skin disease}}
Non-malignant skin disease is common. It is the domain of dermatologists. It can be scary for general anatomical pathologists because the differential diagnosis is often broad, and, it's generally not something the general anatomical pathologist sees a lot of.

===Subarticles===
*[[Dermal cysts]], e.g. [[epidermal cyst]], [[pilar cyst]].
*[[Epidermal necrosis]], e.g. [[erythema multiforme]], [[toxic epidermal necrolysis]].
*[[Inflammatory skin diseases]].
**[[Bullous diseases]], e.g. [[pemphigus vulgaris]].
**[[Panniculitis]].

=Common entities in tables=
==Non-malignant non-cystic - very common==
{| class="wikitable sortable" style="margin-left:auto;margin-right:auto"
! Entity
! Key histologic feature
! Other features
! Clinical
! Stains/IHC
! DDx
! Other
! Image
|-
| [[Seborrheic keratosis]] (SK)
| horn cysts (intraepidermal collections of keratin)
| hyperkeratosis, brown granular material at the DE junction, sharply demarcated
| stuck on appearance
| none
| [[fibroepithelial polyp]]
| Leser–Trélat sign = many SKs in malignancy
| [[Image:Seborrheic_keratosis_(1).jpg |thumb|center|150px| SK (WC)]]
|-
| [[Dermatofibroma]]
| fibrous bundles esp. at edge of lesion
| "dirty fingers" = acanthosis + basal keratinocyte hyperpigmentation
| +/-trauma Hx
| CD34-, Factor XIIIa+
| [[DFSP]]
| very common
| [[Image:SkinTumors-P9280848.jpg|thumb|center|150px|DF (WC)]]
|-
| [[Fibroepithelial polyp]] (skin tag)
| on a stalk (epithelium on 3+ sides)
| no horn nests, no hyperkeratosis
| raised lesion
| none
| [[seborrheic keratosis]]
| very common
| [[Image:SkinTumors-P9250819.jpg|thumb|center|150px|Skin tag (WC)]]
|-
| [[Lipoma]]
| mature adipocytes - uniform size
| var. of size may be seen, should prompt search for lipoblasts
| mobile subcutaneous mass
| S100 (???)
| [[liposarcoma]]
| variants: angiolipoma (blood vessels), myolipoma (muscle)
| [[Image: Lipoma -- high mag.jpg|thumb|center|150px|Lipoma (WC)]]
|-
| [[Cicatrix]] (dermal scar)
| dense collagen bundles running parallel to DE junction, loss of dermal papillae
| loss of adnexal structures, +/-[[giant cells]], +/-foreign material, +/-inflammatory cells
| site of previous trauma/surgery
| usu. none; S-100 (to exclude melanoma)
| residual disease, [[hypertrophic scar]], (desmoplastic) [[melanoma]]
|
| [[Image:ScarHistology.JPG |thumb|center|150px| Scar (WC)]]
|- 
|}

==Non-malignant non-cystic - common==
{| class="wikitable sortable" style="margin-left:auto;margin-right:auto"
! Entity
! Key histologic feature
! Other features
! Clinical
! Stains/IHC
! DDx
! Other
! Image
|-
| [[Neurofibroma]]
| bland spindle cells
| mast cells, mixed with collagen, assoc. with a nerve
| may be associated with [[neurofibromatosis]], esp. plexiform type
| S100+, GFAP+
| neurotized [[melanocytic nevus]]
| may develop into [[MPNST]]
| [[Image:Neurofibroma_%281%29.jpg |thumb|center|150px| Neurofibroma (WC)]]
|-
| [[Keratoacanthoma]]
| keratin plug, glassy pink cytoplasm, pushing downward growth
| minimal/no nuclear atypia
| grow rapidly then involute
| none
| [[squamous cell carcinoma]]
| some don't believe in the entity
| [[Image:Skin_keratoacanthoma_whole_slide.jpg |thumb|center|150px| Keratoacathoma (WC)]]
|-
| [[Molluscum contagiosum]]
| suprabasilar cells with abundant granular eosinophilic cytoplasm
| small peripheral nucleus
| polypoid lesion; mushroom-like (?)
| none (?)
| DDx (?)
| favourite exam case
| [[Image:Molluscum_contagiosum_high_mag.jpg |thumb|center|150px|Molluscum contagiosum (WC)]]
|-
| [[Verruca vulgaris]]
| hypergranulosis (thick granular layer) + keratohyaline granules
| hyperkeratosis (thick s. corneum), acanthosis (thick s. spinosum), rete ridges lengthened (~7-10x normal), large vessels at DE junction, koilocytic change (???)
| raised lesions, classically on hand
| none (p16+?)
| [[squamous cell carcinoma of the skin|squamous cell carcinoma]]
| caused by [[HPV]]
| [[Image:Verruca_vulgaris_-_very_low_mag.jpg |thumb|center|150px| Verruca vulgaris (WC)]]
|-
| [[Condyloma acuminatum]]
| koilocytes
| parakeratosis, long folded rete ridges (papillomatosis) - pseudopapillary look
| genital lesion
| none (p16+)
| [[fibroepithelial polyp]]
| caused by [[HPV]]
| [[Image:Anal_condyloma_%282%29.jpg |thumb|center|150px| Condyloma acuminatum (WC)]]
|-
| [[Granuloma annulare]]
| dermal palisading [[granuloma]] around necrotic collagen
| mucin in centre of lesion, (peripheral) lymphocytes, usu. more superficial than necrobiosis lipoidica
| benign, self-limited
| none (CD68?)
| [[necrobiosis lipoidica]], [[rheumatoid nodule]], [[epithelioid sarcoma]]
| Other ?
| [[Image:Granuloma_annulare_-_add_-_high_mag.jpg |thumb|center|150px| GA (WC)]]
|-
| [[Necrobiosis lipoidica]]
| dermal palisading [[granuloma]] around necrotic collagen, plasma cells
| mucin in centre of lesion, (peripheral) chronic inflammatory cells
| may be assoc. [[diabetes mellitus]]
| none (CD68?)
| [[granuloma annulare]], [[rheumatoid nodule]]
| histology identical to ''necrobiosis lipoidica diabeticorum''
| [http://www.drmihm.com/cases/casefigure.cfm?figID=942&CaseID=53 (drmihm.com)]
|-
| [[Angiofibroma]]
| fibrotic dermis, dilated capillaries
| enlarged (stellate fibroblasts)
| dome-shaped - face, boys & nosebleeds ([[nasopharyngeal angiofibroma]])
| Stains/IHC
| DDx
| may be associated with [[tuberous sclerosis]]
| [[Image:Nasopharyngeal angiofibroma - 2 - high mag.jpg|thumb|150px|Angiofibroma (WC)]]
|-
| [[Keloid]]
| thick collagen bundles - surrounded by paler staining fibroblasts
| replaces adnexal structures
| site of previous trauma, esp. in blacks
| none
| [[dermatofibroma]] (???)
| [[hypertrophic scar]]
| [[Image:Keloid_-_high_mag.jpg|thumb|center|150px|Keloid (WC)]]
|-
| [[Eccrine poroma]]
| abundant basaloid cells with (small) ductal structures
| incloses islands of sclerotic stroma with edema
| erythematous lesions
| Stains/IHC ?
| DDx ?
| Other ?
| [[Image:SkinTumors-P7150495.JPG|thumb|center|150px|EP (WC)]]
|-
| [[Syringoma]]
| bilayered ducts, occasionally tadpole like shape
|
| usu. close to [[eyelid]]
| Stains/IHC ?
| DDx ?
| Other ?
| [http://dermatology.cdlib.org/144/tumors/axillary_syringoma/2.jpg (cdlib.org)]
|-
| [[Chondroid syringoma]] (mixed tumour of skin)
| [[chondromyxoid stroma]], epithelial component
| epithelial component in nests with eosinophilic cytoplasm, round/ovoid nuclei with nucleoli
| Clinical ?
| Stains/IHC ?
| DDx ?
| related to [[pleomorphic adenoma]] (???)
| Image ?
|-
| [[Angiokeratoma]]
| ectatic superficial dermal vessels + overlying hyperkeratosis
| -
| may be seen in [[Fabry disease]]
| Stains/IHC ?
| [[venous lake]]
| Other ?
| [[Image:Angiokeratoma_-_low_mag.jpg |thumb|center|150px| Angiokeratoma (WC)]]
|- 
|}

==Non-malignant non-cystic - children==
{| class="wikitable sortable" style="margin-left:auto;margin-right:auto"
! Entity
! Key histologic feature
! Other features
! Clinical
! Stains/IHC
! DDx
! Other
! Image
|-
| [[Pilomatricoma]]
| anucleate squamous cells (ghost cells), giant cells
| bland basaloid cells
| common in children
| none
| [[squamous cell carcinoma of the skin|squamous cell carcinoma]]
| mutations of CTNNB1 gene
| [[Image:Pilomatrixoma_-_intermed_mag.jpg |thumb|center|150px| Pilomatrixcoma (WC)]]
|-
| [[Juvenile xanthogranuloma]] (JXG)
| Touton giant cells - multi-nucleated cells where nuclei are distributed around the cell periphery forming a ring
| abundant cytoplasm
| children
| CD68+, CD1a-, CD207-
| [[Langerhans cell histiocytosis]]
| may be seen in adults, known as '''adult xanthogranuloma'''
| [[Image:Juvenile_xanthogranuloma_-_high_mag.jpg |thumb|center|150px| JXG (WC)]]
|}

==Non-malignant cystic==
{| class="wikitable sortable" style="margin-left:auto;margin-right:auto"
! Entity
! Key histologic feature
! Other features
! Clinical
! Stains/IHC
! DDx
! Other
! Image
|-
| [[Epidermal cyst]]
| cyst lined by squamous epithelium '''with''' a granular layer
| keratinous debris, no skin adnexal structures
| cyst
| none
| [[pilar cyst]], [[dermoid cyst]]
| Other?
| [[Image:Epidermal inclusion cyst -- high mag.jpg |thumb|center|150px| Epidermal inclusion cyst (WC)]]
|-
| [[Pilar cyst]] (trichilemmal cyst)
| cyst lined by squamous epithelium '''without''' a granular layer
| keratinous debris
| cyst
| none
| [[epidermal cyst]]
| Other?
| [[Image:Trichilemmal_cyst_-_very_high_mag.jpg |thumb|center|100px| Pilar cyst (WC)]]
|-
| [[Steatocystoma]]
| cyst lined by squamous epithelium with a corrugated eosinophilic lining
| epidermis has '''no''' granular layer
| cyst
| none
| [[dermoid cyst]], follicular cyst
| Other?
| [[Image:Steatocystoma_-_high_mag.jpg |thumb|center|150px| Steatocystoma (WC)]]
|-
| [[Dermoid cyst]]
| cyst lined by keratinizing squamous epithelium with adnexal structures
| adnexal structure = hair, sebaceous gland, sweat glands
| cyst
| none
| [[epidermal cyst]]
| may be seen in the [[ovary]]
| [http://webeye.ophth.uiowa.edu/eyeforum/cases-i/case115/larger/Figure4.jpg (uiowa.edu)]
|}

==Pre-malignant==
{| class="wikitable sortable" style="margin-left:auto;margin-right:auto"
! Entity
! Key histologic feature
! Other features
! Clinical
! Stains/IHC
! DDx
! Other
! Image
|-
| [[Actinic keratosis]]
| epidermal atypia, esp. (basal) nuclear enlargement
| var. of nuclear size, shape and staining, parakeratosis (important in early lesions); does ''not'' involves adnexal epithelium and follicular epithelium
| yellow-brown scaly
| none
| [[squamous carcinoma]], [[Bowen disease]]
| seen with [[solar elastosis]]
| [[Image:Actinic_Keratosis,_H%26E.jpg |thumb|center|150px| AK (WC)]]
|-
| [[Bowen disease]] (squamous cell carcinoma in situ)
| epidermal atypia, esp. suprabasal nuclear enlargement
| var. of nuclear size, shape and staining; usually full thickness involvement; involve adnexal epithelium and follicular epithelium
|
| none
| [[squamous carcinoma]], [[actinic keratosis]]
| typically seen with solar elastosis
| [[Image:Bowen_disease_%281%29.jpg |thumb|center|100px| Bowen's disease (WC)]]
|}

==Common malignant==
{| class="wikitable sortable" style="margin-left:auto;margin-right:auto"
! Entity
! Key histologic feature
! Other features
! Clinical
! Stains/IHC
! DDx
! Other
! Image
|-
| [[Basal cell carcinoma]] (BCC)
| basaloid cells with peripheral palisading, artificial cleft
| [[myxoid]] stroma
| raised, pearly, telangiectasia
| usu. none req., [[CK5/6]]+
| [[trichoepithelioma]], [[basaloid squamous cell carcinoma]]
| assoc. [[nevoid basal cell carcinoma syndrome]], [[Bazex syndrome]]
| [[Image:Basal cell carcinoma - high mag.jpg| thumb| center|150px|BCC (WC)]]
|-
| [[Squamous cell carcinoma]] (SCC)
| nuclear enlargement, eosinophilic cytoplasm, central nucleus
| small nucleolus, intercellular bridges
| flaky appearance
| usu. none req., p63+, HMWK+
| [[keratoacanthoma]], [[Paget disease]] ([[EMPD]] & [[PDB]]), [[malignant melanoma]], Toker cell hyperplasia
| Other
| [[Image:Oral_cancer_%281%29_squamous_cell_carcinoma_histopathology.jpg|thumb|center|150px|SCC (WC)]]
|-
| [[Malignant melanoma]]
| spindle and/or epithelioid morphology +/-nuclear atypia (esp. nucleoli)
| mitoses (esp. deep), +/-pigment, +/-nested arch., asymmetry, upward spread (into epidermis), epithelioid m. deep, +/-single cells, +/-sheets of cells
| ABCD = Asymmetry, Borders poor demarc., Colour dark, Diameter large
| S100+, Melan A+, HMB-45+, microphthalmia+, tyrosinase+
| [[melanocytic lesions]] esp. [[Spitz nevus]], [[Bowen's disease]]
| may be familial, [[dysplastic nevus]]
| [[Image:Malignant_melanoma_%281%29_at_thigh_Case_01.jpg |thumb|center|150px|Melanoma (WC)]]
|- 
|}

==Less common malignant==
{| class="wikitable sortable" style="margin-left:auto;margin-right:auto"
! Entity
! Key histologic feature
! Other features
! Clinical
! Stains/IHC
! DDx
! Other
! Image
|-
| [[Kaposi sarcoma]]
| vascular spindle cell lesion
| [[hyaline globules]] (intracytoplasmic)
| often HIV/AIDS
| [[HHV-8]]
| [[Masson's hemangioma]], [[angiosarcoma]], [[Kaposiform hemangioendothelioma]]
| stages: patch stage, plaque stage, nodular stage, exophytic, infiltrative, lymphadenopathic
| [[Image:Kaposi_sarcoma_low_intermed_mag.jpg |thumb|center|150px| Kaposi sarcoma (WC)]]
|-
| [[Cutaneous T-cell lymphoma]] (includes ''mycosis fungoides'')
| single lymphocytes in epidermis ("lymphocyte exocytosis")
| lymphocyte nests in the epidermis ("Pautrier microabscesses"), short arrays of lymphocytes along the basal layer of the epidermis ("epidermotropism")
| Clinical
| CD45, CD4
| B cell lymphoma (?)
| Other
| [[Image:Cutaneous_T-cell_lymphoma_-_intermed_mag.jpg |thumb|center|150px| CTCL (WC)]]
|-
| [[Atypical fibroxanthoma]]
| dermal lesion with marked nuclear atypia
| multinucleated cells, mitoses, vacuolated cytoplasm
| old men, head and neck
| p63-, 34betaE12-, S100-, desmin-
| sarcomatoid squamous carcinoma, [[melanoma]], [[leiomyosarcoma]]
| some classify this as '''benign'''; thought to be related to [[undifferentiated pleomorphic sarcoma]]
| [[Image:SkinTumors-P9280874.jpg|thumb|center|150px| AFX (WC)]]
|-
| [[Merkel cell carcinoma]]
| neuroendocrine nuclear features (stippled chromatin, no nucleolus), scant cytoplasm
| +/-nuclear moulding, usu. intermediate cell size
| Merkel cell polyomavirus associated, usu. head & neck or extremities
| CK20+, EMA+
| cutaneous [[Ewing sarcoma]], [[basal cell carcinoma]], (dermal) [[lymphoma]], metastatic small cell carcinoma (e.g. [[Lung tumours#Small cell carcinoma|lung]])
| rare, aggressive
| [[Image:Merkel_cell_carcinoma_-_very_high_mag.jpg |thumb|center|100px| MCC (WC)]]
|-
| [[Dermatofibrosarcoma protuberans]] (DFSP)
| spindle cell tumour with storiform pattern, tumour often contains adipocytes
| dermal tumour with preserved adnexal structures
| locally aggressive
| CD34+, factor XIIIa-
| [[dermatofibroma]], [[solitary fibrous tumour]] (usu. deeper)
| rarely metastases, characteristic [[translocation]]: t(17;22)(q22;q15) COLA1/PDGFB; may transform to [[fibrosarcoma]]
| [[Image:Storiform_pattern_-_intermed_mag.jpg |thumb|center|150px| DFSP (WC)]]
|- 
|}

=Presentations=
==Leukoplakia==
{{Main|Leukoplakia}}

DDx:<ref>{{Ref PBoD|1065}}</ref>
*Vitiligo (loss of pigment).
*Inflammation.
**Chronic dermatitis.
**[[Psoriasis]].
*Neoplasia.
**[[Vulvar intraepithelial neoplasia]].
**[[Invasive_breast_cancer#Paget.27s_disease|Paget disease]].
**Invasive carcinoma.
*Other.
**[[Lichen sclerosus]].
**[[Lichen simplex chronicus]].

=Skin disease and systemic conditions=
==Tabular list==
{| class="wikitable sortable" style="margin-left:auto;margin-right:auto"
! Entity
! Disease/syndrome
! Key histologic feature
! Image
|-
| [[Acanthosis nigricans]]
| [[diabetes mellitus]], malignancy
| basal cell hyperpigmentation, hyperkeratosis, prominent rete ridges
| [http://dermatology.cdlib.org/149/reviews/acanthosisnigricans/higgins.html (cdlib.org)]
|-
| [[Trichilemmoma]]
| [[Cowden disease]]
| "hyperkeratosis"
| [http://ccr.cancer.gov/staff/images/9033_12822_Lee_1520.jpg (cancer.gov)]<ref>URL: [http://ccr.cancer.gov/staff/gallery.asp?profileid=12822 http://ccr.cancer.gov/staff/gallery.asp?profileid=12822]. Accessed on: 14 December 2011.</ref>
|-
| [[Angiokeratoma]]
| [[Fabry disease]]
| hyperkeratosis + vessels in superficial dermis
| [http://commons.wikimedia.org/wiki/File:Angiokeratoma_-_low_mag.jpg (WC)]
|-
| [[Dermatitis herpetiformis]]
| [[Celiac disease]]
| subepidermal [[bullous disease]], papillary abscesses
| [http://www.lampyris101.com/L101/gallery1/12_JPG.html (lampyris101.com)]
|-
| [[Angiofibroma]]
| [[tuberous sclerosis]]
| fibrotic dermis + dilated blood vessels
| [http://www.drdittmar.lu/images/sce/angiofibroma-s.jpg (drdittmar.lu)]
|-
| [[Sebaceous adenoma]]
| [[Muir-Torre syndrome]]
| abundant sebaceous glands with abn. arch.
| [http://commons.wikimedia.org/wiki/File:Sebaceous_adenoma_-_low_mag.jpg (WC)]
|-
| [[Seborrheic keratosis]], multiple with explosive onset
| Leser–Trélat sign (malignancy)
| horn cysts, hyperkeratosis
| [http://commons.wikimedia.org/wiki/File:IMG_1724.JPG gross (WC)], [http://commons.wikimedia.org/wiki/File:Seborrheic_keratosis_%281%29.jpg micro. (WC)]
|- 
|}

==Acanthosis nigricans==
===General===
Associated with:
*[[Diabetes mellitus]].<ref>URL: [http://www.emedicine.com/derm/topic1.htm http://www.emedicine.com/derm/topic1.htm], URL: [http://dermatlas.med.jhmi.edu/derm/indexDisplay.cfm?ImageID=1943559504].</ref>
*Malignancy.<ref name=Ref_PCPBoD8|596>{{Ref PCPBoD8|596}}</ref>

===Microscopic===
Features (memory device ''BPH''):<ref name=Ref_PCPBoD8|596>{{Ref PCPBoD8|596}}</ref>
*Basal cell hyperpigmentation.
*Prominent rete ridges.
*Hyperkeratosis.

DDx:
*[[Seborrheic keratosis]] - typically has more hyperkeratosis, pseudohorn cysts.

Images:
*[http://dermatology.cdlib.org/149/reviews/acanthosisnigricans/higgins.html AN (cdlib.org)].

==Others==
*[[Dermatitis herpetiformis]]: gluten enteropathy ([[celiac disease]]), [[thyroid]] disease, intestinal [[lymphoma]].<ref name=Ref_TN2007_D23>{{Ref TN2007|D23}}</ref>
*[[Pemphigus vulgaris]]: [[thymoma]], myasthenia gravis, malignancy.<ref name=Ref_TN2007_D23>{{Ref TN2007|D23}}</ref>
 
[[File:3767 dp sl 1.png |Lipoid proteinosis]]
[[File:3767 dp sl 2.png |Lipoid proteinosis]] 
Lipoid proteinosis. A. Inner labial biopsy shows subepithelial hyalinized pink/red material, about blood vessels and in general. B. The particularly glassy appearance of the material in areas is evident at high power.
 
[[File:DP16MR17 sl 1.png| Xanthogranuloma in scrotal skin.]]
[[File:DP16MR17 sl 2.png| Xanthogranuloma in scrotal skin.]]
[[File:DP16MR17 sl 3.png| Xanthogranuloma in scrotal skin.]]
[[File:DP16MR17 sl 4.png| Xanthogranuloma in scrotal skin.]]
 
Xanthogranuloma in scrotal skin. A. Pseudoepitheliomatous hyperplasia seemingly forms a dermal mass. B. Parakeratosis tops epidermis. C. Neutrophils lie in the center of the apparent mass. D. Diagnostic xanthoma cells lie in dermal papillae.
 
[[File:DP13AP17 sl1.png| Silicone granuloma]]
[[File:DP13AP17 sl2.png| Silicone granuloma]]
[[File:DP13AP17 sl3.png| Silicone granuloma]]
[[File:DP13AP17 sl4.png| Silicone granuloma]]
 
Silicone granuloma. A. The dermis resembles Swiss cheese. B. Macrophages, some with more than one nucleus, accompany empty ovoid spaces. C. Some macrophages resemble Teuton body giant cells. D. An admixture of lymphocytes is not at all unusual.

=References=
{{reflist|2}}

[[Category:Dermatopathology]]

Bullous diseases

2017-03-31T18:20:53Z

Mitchell: /* Pemphigoid gestationis */ added a case

'''Bullous diseases''' are a subset of the large [[inflammatory skin diseases]] category. Dermatopathologists help diagnose it.

An introduction to skin pathology is in the ''[[dermatopathology]]'' article. An introduction to inflammatory skin lesions in the ''[[non-malignant skin disease]]'' article.

Bullous disease of the [[lung]] is dealt with in ''[[lung bullae]]''.

=Overview=
==DDx based on type==
===Subcorneal bullous disorders===
DDx '''with''' acantholysis:<ref name=pmid18418089>{{cite journal |author=Brinster NK |title=Dermatopathology for the surgical pathologist: a pattern based approach to the diagnosis of inflammatory skin disorders (part I) |journal=Adv Anat Pathol |volume=15 |issue=2 |pages=76–96 |year=2008 |month=March |pmid=18418089 |doi=10.1097/PAP.0b013e3181664e8d |url=}}</ref>
*[[Pemphigus foliaceus]].
*[[Bullous impetigo]].
*[[Staphylococcal scalded skin syndrome]].

DDx '''without''' acantholysis:DDx:<ref name=pmid18418089/>
*Subcorneal pustular dermatosis (Sneddon-Wilkinson disease)
*Pustular psoriasis.
*Pustular drug eruption ([[acute generalized exanthematous pustulosis]]).

===Suprabasilar bullous disorders===
DDx:<ref name=pmid18418089/>
*[[Pemphigus vulgaris]].
*[[Hailey-Hailey disease]] (benign familial pemphigus).
*[[Darier disease]].
*[[Grover disease]] (transient acantholytic dermatosis).

Memory device - ''PhD'' + ''Grover'' = '''P'''emphigus vulgaris, '''H'''ailey-Hailey, '''D'''arier, '''G'''rover.

===Subepidermal bullous disorders===
DDx:<ref name=pmid18418089/>
*[[Bullous pemphigoid]].
*[[Cicatricial pemphigoid]].
*[[Porphyria cutanea tarda]].
*[[Epidermolysis bullosa acquista]].
*[[Dermatitis herpetiformis]].
*Linear IgA disease.

Others:
*Insect bite.
*Coma blister.
*Bullous [[systemic lupus erythematosus]].

Mnemonic ''DELPHI'':
*[[dermatitis herpetiformis|'''D'''ermatitis herpetiformis]].
*'''E'''pidermolysis bullosa acquisita.
*Bullous '''l'''upus erythematosis.
*'''P'''emphigoid, bullous.
*'''H'''erpes gestationis (now called ''[[pemphigoid gestationis]]'') - rare autoimmune bullous dermatosis of pregnancy, not related to HSV.<ref>URL: [http://emedicine.medscape.com/article/1063499-overview http://emedicine.medscape.com/article/1063499-overview]. Accessed on: 23 September 2011.</ref>
*Linear '''I'''gA disease.

=Specific diseases=
==Pemphigus foliaceus==
===General===
*Autoimmune disease.<ref name=pmid21605805>{{Cite journal | last1 = James | first1 = KA. | last2 = Culton | first2 = DA. | last3 = Diaz | first3 = LA. | title = Diagnosis and clinical features of pemphigus foliaceus. | journal = Dermatol Clin | volume = 29 | issue = 3 | pages = 405-12, viii | month = Jul | year = 2011 | doi = 10.1016/j.det.2011.03.012 | PMID = 21605805 }}</ref>
**Autoantibodies against ''desmoglein 1'' only.

Note:
*[[Pemphigus vulgaris]] has autoantibodies against ''desmoglein 1'' and ''desmoglein 3''.<ref name=omim169615>{{OMIM|169615}}</ref>

===Microscopic===
Features:
*Subcorneal separation.
*[[Acantholysis]].
**Separation of keratinocytes.

DDx:
*[[Staphylococcal scalded skin syndrome]].
*[[Bullous impetigo]].

===IF===
*Desmoglein 1 - abnormal.

==Bullous pemphigoid==
===General===
*Less serious than ''pemphigus vulgaris''.

Epidemiology:
*Old people (60-80 year olds).

Clinical:
*Extreme pruritis.

Etiology:
*Antibodies to BPAG2 (a hemidesmosome protein).<ref name=Ref_PCPBoD8_607>{{Ref PCPBoD8|607}}</ref>

Notes:
*[[Pemphigus vulgaris]] = subepidermal.
*[[Pemphigus foliaceus]] = intraepidermal.

===Microscopic===
Features:<ref name=Ref_PBoD8_1195>{{Ref PBoD8|1195}}</ref>
*Subepidermal blisters.
*+/-Lymphocytes.
*+/-Eosinophils.
*+/-Neutrophils.

Notes:
*Epidermis not affect, i.e. non-acantholytic.
*Linear Ig deposits along basement membrane.
*Early changes may be that of a ''[[dermal perivascular lymphoeosinophilic infiltration]]''.

Images:
*[http://dermatology.cdlib.org/94/NYU/Feb2002/021202-8b.jpg BP (dermatology.cdlib.org)].<ref>URL: [http://dermatology.cdlib.org/94/NYU/Feb2002/8.html http://dermatology.cdlib.org/94/NYU/Feb2002/8.html]. Accessed on: 20 March 2011.</ref>
*[http://missinglink.ucsf.edu/lm/DermatologyGlossary/img/Dermatology%20Glossary/Glossary%20Histo%20Images/bullous_pemphigoid_higher_power.jpg BP (ucsf.edu)].<ref>URL: [http://missinglink.ucsf.edu/lm/DermatologyGlossary/bullous_pemphigoid.html http://missinglink.ucsf.edu/lm/DermatologyGlossary/bullous_pemphigoid.html]. Accessed on: 20 March 2011.</ref>

DDx:
*Bullous lupus.
*[[Dermal perivascular lymphoeosinophilic infiltration]].

==Pemphigus vulgaris==
*[[AKA]] ''pemphigus''.
===General===
*May lead to blindness.
*Oral lesion is classically: ''first to show & last to go''.
**Oral lesions usually precede the skin lesions.

Classic presentation:
*Mouth lesions.
*Non-pruritic.

Treatment:
*Prednisone then steroid sparing agent.

Epidemiology:
*Associated with [[thymoma]], myasthenia gravis, malignancy & D-penicillamine (used to Tx [[Wilson's disease]]).
*Middle age.

Etiology:
*Autoimmune disease.
**Antibodies against: ''desmoglein 1'' (DSG1)<ref name=omim125670>{{OMIM|125670}}</ref> and ''desmoglein 3'' (DSG3).<ref name=omim169615>{{OMIM|169615}}</ref>

===Microscopic===
Features:<ref>{{Ref PBoD8|1193}}</ref>
*Suprabasilar blistering.

DDx:
*[[Hailey-Hailey disease]].
*[[Darier disease]].
*[[Grover disease]].

Images:
*[http://www.dermpedia.org/files/images/pemphigus_vulgaris_3.jpg PV (dermpedia.org)].<ref>URL: [http://www.dermpedia.org/baby-dermpedia-for-beginners/pemphigus-vulgaris http://www.dermpedia.org/baby-dermpedia-for-beginners/pemphigus-vulgaris]. Accessed on: 20 March 2011.</ref>
*[http://commons.wikimedia.org/wiki/File:Pemphigus_vulgaris_-_intermed_mag.jpg Pemphigus vulgaris - intermed. mag. (WC)].
*[http://commons.wikimedia.org/wiki/File:Pemphigus_vulgaris_-_high_mag.jpg Pemphigus vulgaris - high mag. (WC)].

===IF===
*Desmoglein 1 - abnormal.
*Desmoglein 3 - abnormal.

==Familial benign pemphigus==
*AKA ''Hailey-Hailey disease''. Was described by two brothers - that's why it is ''Hailey-Hailey''.<ref name=emed_hailey>URL: [http://emedicine.medscape.com/article/1063224-overview http://emedicine.medscape.com/article/1063224-overview]. Accessed on: 9 September 2011.</ref>

===General===
*Genetic - autosomal dominant with incomplete penetration.<ref name=emed_hailey/>
**Desmosomal defect - due to mutation in the gene ''ATP2C1''.<ref name=emed_hailey/>

Clinical:
*Chest.
*Intertriginous regions (only) - where skin rubs together, e.g. skin folds of the breast, axilla.
*Typically presents individual in their 30s and 40s.<ref name=emed_hailey/>

===Microscopic===
Features:
*Suprabasilar blistering.
*[[Acanthosis]] (thick epidermis).

Notes:
*Hair folicles spared.

DDx:
*[[Pemphigus vulgaris]].

==Dermatitis herpetiformis==
===General===
*Associated with [[celiac sprue]].

Clinical:
*Pruritis - intense.

===Microscopic===
Features:<ref>{{Ref PBoD8|1196}}</ref>
*Subepidermal blistering.
*Clusters of neurophils (microabscesses) - at tips of dermal papillae - '''key feature'''.
*Basal cell injury (vacuolization).

Notes:
*Immunofluorescence - IgA deposits at dermal papillae.

Images:
*[http://dermatology.cdlib.org/94/NYU/Nov2001/112001-9b.jpg DH (dermatology.cdlib.org)].<ref>URL: [http://dermatology.cdlib.org/94/NYU/Nov2001/9.html http://dermatology.cdlib.org/94/NYU/Nov2001/9.html]. Accessed on: 21 March 2011.</ref>
*[http://www.dermpedia.org/files/images/Image49_HE.jpg DH (dermpedia.org)].

==Porphyria cutanea tarda==
===General===
Etiology:
*Genetic, autosomal dominant.

Treatment:
*D/C aggravating substances (see below) - phlebotomy, hydroxychloroquine if phlebotomy contraindicated.

Note:
*Fits into a larger category of ''porphyria''.
====Associations====
Medications/substances:
*[[EtOH]], Rx (estrogen, [[NSAID]]s).

Non-infection chronic conditions:
*[[DM]].

Infections:
*[[HIV]], [[hepatitis C]].

===Gross===
*In photoexposed areas subjected to trauma.

===Microscopic===
Features:<ref>{{Ref PBoD8|1197}}</ref>
*Subepidermal vesicles.
*Thickening of superficial dermal blood vessels.

Images:
*[http://www.dermpedia.org/files/images/Image1_4.jpg Subepidermal blistering with thick vessels (dermpedia.org)].

==Epidermolysis bullosa acquisita==
*Abbreviated ''EBA''

===General===
*Autoimmune disease.
**Antibodies to collagen type VII.<ref>URL: [http://emedicine.medscape.com/article/1063083-overview http://emedicine.medscape.com/article/1063083-overview]. Accessed on: 25 September 2011.</ref>

===Microscopic===
Features:
*Subepidermal bullae.

==Epidermolysis bullosa==
===General===
*A group of inherited, bullous disorders.
*Bullae form due to slight mechanical trauma.

Three major groupings:<ref>URL: [http://emedicine.medscape.com/article/1062939-overview http://emedicine.medscape.com/article/1062939-overview]. Accessed on: 25 September 2011.</ref>
#Epidermolysis bullosa simplex (intraepidermal disease).
#Junctional epidermolysis bullosa (separation at DE junction; specifically central portion (lamina lucida)).
#Dystrophic epidermolysis bullosa (separation at DE junction; specifically deep to lamina densa).

===Microscopic===
Depends on subtype - either intraepidermal ''or'' subepidermal.

==Grover disease==
*[[AKA]] ''transient acantholytic dermatosis''.

===General===
*Cause not known.
*Associated with sun damaged skin, hospitalization and fever.<ref name=pmid15068451>{{Cite journal | last1 = Quirk | first1 = CJ. | last2 = Heenan | first2 = PJ. | title = Grover's disease: 34 years on. | journal = Australas J Dermatol | volume = 45 | issue = 2 | pages = 83-6; quiz 87-8 | month = May | year = 2004 | doi = 10.1111/j.1440-0960.2004.054_1.x | PMID = 15068451 }}</ref>

Clinical:<ref name=pmid16939188>{{Cite journal | last1 = Hanson | first1 = M. | last2 = Hsu | first2 = S. | title = Pruritic papules on the chest and back. Grover's disease. | journal = Am Fam Physician | volume = 74 | issue = 4 | pages = 641-2 | month = Aug | year = 2006 | doi = | PMID = 16939188 | url = http://www.aafp.org/afp/2006/0815/p641.html }}</ref>
*Pruritis (itchy).
*Usually self-limited.
*Treatment for symptoms.

===Gross===
*Usually small ~ 50% less than 2 mm.<ref name=pmid20526170>{{Cite journal | last1 = Fernández-Figueras | first1 = MT. | last2 = Puig | first2 = L. | last3 = Cannata | first3 = P. | last4 = Cuatrecases | first4 = M. | last5 = Quer | first5 = A. | last6 = Ferrándiz | first6 = C. | last7 = Ariza | first7 = A. | title = Grover disease: a reappraisal of histopathological diagnostic criteria in 120 cases. | journal = Am J Dermatopathol | volume = 32 | issue = 6 | pages = 541-9 | month = Aug | year = 2010 | doi = 10.1097/DAD.0b013e3181c80cf9 | PMID = 20526170 }}</ref>
*Typically chest and back.<ref>{{Ref APBR|344 Q2</ref>

===Microscopic===
Features:<ref>S. Sade. 8 September 2011.</ref>
*Subcorneal bullous disease.
*Acanthosis.
*Dyskeratosis.

DDx:<ref name=pmid10089990>{{Cite journal | last1 = Davis | first1 = MD. | last2 = Dinneen | first2 = AM. | last3 = Landa | first3 = N. | last4 = Gibson | first4 = LE. | title = Grover's disease: clinicopathologic review of 72 cases. | journal = Mayo Clin Proc | volume = 74 | issue = 3 | pages = 229-34 | month = Mar | year = 1999 | doi = 10.4065/74.3.229 | PMID = 10089990 }}</ref>
#[[Pemphigus vulgaris]].
#[[Darier disease]].

====Images====
<gallery>
Image:Transient acantholytic dermatosis - intermed mag.jpg | Grover disease - intermed. mag. (WC)
Image:Transient_acantholytic_dermatosis_-_high_mag.jpg | Grover disease - high mag. (WC)
Image:Transient_acantholytic_dermatosis_-_very_high_mag.jpg | Grover disease - very high mag. (WC)
</gallery>

==Acute generalized exanthematous pustulosis==
*Abbreviated ''AGEP''.
*[[AKA]] pustular drug eruption.

===General===
*Drug reaction.

Clinical DDx:
*[[Erythema multiforme]].
*[[Stevens-Johnson syndrome]] (SJS) / [[toxic epidermal necrolysis]] (TEN).

===Microscopic===
Features:
*Superficial dermis separates from underlying tissue. (???)

DDx:
*[[Staphylococcal scalded skin syndrome]].

Images:
*[http://www.dermpedia.org/case/acute-generalized-exanthematous-pustulosis AGEP (dermpedia.org)].

==Pemphigoid gestationis==
*[[AKA]] ''gestational pemphigoid''.
*Previously ''herpes gestationis''.

===General===
*Autoimmune condition in pregnancy.
**Autoantibodies against XVII collagen.<ref name=pmid21605810>{{Cite journal | last1 = Intong | first1 = LR. | last2 = Murrell | first2 = DF. | title = Pemphigoid gestationis: pathogenesis and clinical features. | journal = Dermatol Clin | volume = 29 | issue = 3 | pages = 447-52, ix | month = Jul | year = 2011 | doi = 10.1016/j.det.2011.03.002 | PMID = 21605810 }}</ref>
**Fetus affected in ~5-10% of cases.<ref name=pmid17263216>{{Cite journal | last1 = Tunzi | first1 = M. | last2 = Gray | first2 = GR. | title = Common skin conditions during pregnancy. | journal = Am Fam Physician | volume = 75 | issue = 2 | pages = 211-8 | month = Jan | year = 2007 | doi = | PMID = 17263216 | URL = http://www.aafp.org/afp/2007/0115/p211.html }}</ref>
*Rare - est. 1/50,000 pregnancies.<ref name=pmid18506459>{{Cite journal | last1 = Bedocs | first1 = PM. | last2 = Kumar | first2 = V. | last3 = Mahon | first3 = MJ. | title = Pemphigoid gestationis: a rare case and review. | journal = Arch Gynecol Obstet | volume = 279 | issue = 2 | pages = 235-8 | month = Feb | year = 2009 | doi = 10.1007/s00404-008-0687-3 | PMID = 18506459 }}</ref>

Treatment:
*Corticosteroids.<ref name=pmid21877502/>
===Microscopic===
Features:
*Subepidermal bullous disease.<ref>{{Cite journal | last1 = Kolanko | first1 = E. | last2 = Bickle | first2 = K. | last3 = Keehn | first3 = C. | last4 = Glass | first4 = LF. | title = Subepidermal blistering disorders: a clinical and histopathologic review. | journal = Semin Cutan Med Surg | volume = 23 | issue = 1 | pages = 10-8 | month = Mar | year = 2004 | doi = | PMID = 15095911 }}</ref>
*Eosinophils - abundant.

====Images====
<gallery>
Image:Pemphigoid_gestationis_-_low_mag.jpg | PG - low mag. (WC)
Image:Pemphigoid_gestationis_-_high_mag.jpg | PG - high mag. (WC)
Image:Pemphigoid_gestationis_-_very_high_mag.jpg | PG - very high mag. (WC)
</gallery>

===IF===
*C3 linear pattern at DE junction - diagnostic.<ref name=pmid21877502>{{Cite journal | last1 = Campbell | first1 = SM. | last2 = Balazs | first2 = K. | last3 = Conroy | first3 = M. | title = Pemphigoid gestationis: a case report and review of the literature. | journal = Cutis | volume = 88 | issue = 1 | pages = 21-6 | month = Jul | year = 2011 | doi = | PMID = 21877502 }}</ref>

==Bullous Arthropod Assault==
[[File:30MR17 dp sl 1.png|Bullous arthropod assault]]
[[File:30MR17 dp sl 2.png|Bullous arthropod assault]]
[[File:30MR17 dp sl 3.png|Bullous arthropod assault]] 
Bullous arthropod assault. A. Beneath intraepidermal blistering lies superficial and deep inflammation with extension into fat. B. The vesicle shows spongiotic epidermis at base and multiple eosinophils. C. Eosinophils are prominent in dermal and adipose tissue inflammation.

=See also=
*[[Non-malignant skin disease]].
*[[Dermatopathology introduction]].
*[[Dermal cysts]].

=References=
{{reflist|2}}

[[Category:Non-malignant skin disease]]
[[Category:Dermatopathology]]

Dermatopathology

2017-03-16T19:21:55Z

Mitchell: /* Others */ Added case

'''Dermatopathology''' is the pathology of skin.

Pathology is a significant part of dermatology and dermatologists spend five years in residency. So, it is a huge area.

=Specimens=
*Shave biopsy = done for what is presumed to be benign disease - classically exophytic lesions, e.g. [[seborrheic keratosis]].
*Saucerization = scooped shave biopsy.<ref>{{Cite journal | last1 = Elston | first1 = D. | title = Practical advice regarding problematic pigmented lesions. | journal = J Am Acad Dermatol | volume = 67 | issue = 1 | pages = 148-55 | month = Jul | year = 2012 | doi = 10.1016/j.jaad.2012.04.006 | PMID = 22703907 }}
</ref>
*Punch biopsy = cylindrical piece of skin, usu. epidermis and dermis - suspicious lesions/malignant lesions, e.g. [[basal cell carcinoma]].
*Incisional biopsy = a piece of the lesion for pathologic assessment; lesion not completely removed.
*Excision = lesion cut-out with intent for complete removal - usual has a generous margin, e.g. [[malignant melanoma]] excision.
*Re-excision = done to get a wider margin ''or'' remove part of a lesion that was incompletely removed in a prior excision.
**Conservative re-excision = cut-out more with a minimal rim of normal tissue.<ref>URL: [http://www.nedermatology.com/skin-cancer-treatments.php http://www.nedermatology.com/skin-cancer-treatments.php]. Accessed on: 26 February 2013.</ref>
*[[Sentinel lymph node]] removal = a special type of lymphadenectomy usu. done for [[cancer staging|staging]], esp. [[malignant melanoma]].

=Histology=
==Layers of the skin==
[[Image:Skin.png|thumb|Schematic showing the layers and structures of skin. (WC/cancer.gov)]]
*Epidermis - outer most layer, avascular, separated from dermis by a basement membrane, epithelial tissue.
*Dermis - below the epidermis, vascular, separated from the epidermis by a basement membrane, connective tissue.

Note:
*The layer below the skin is the ''subdermis'' ([[AKA]] hypodermis, [[AKA]] subcutaneous tissue).
**It is below the dermis and consists of adipose tissue.<ref>URL: [http://histologyolm.stevegallik.org/node/119 http://histologyolm.stevegallik.org/node/119]. Accessed on: 5 November 2013.</ref>

Image:
*[http://histologyolm.stevegallik.org/node/119 Dermis and hypodermis (stevegallik.org)].

===Epidermis===
====Layers of the epidermis====
[[Image:Epidermal layers.png|thumb|right|Layers of the epidermis. (WC/Wbensmith)]]
Epidermis layers - from the surface to epidermal-dermal junction:
*Stratum corneum.
*Stratum lucidum.
**Present only in "thick" skin.<ref name=Ref_Derm1>{{Ref Derm|1}}</ref>
*Stratum granulosum.
*Stratum spinosum (aka prickle layer).
*Stratum basale (germinativum).
Mnemonic: ''Corn Lovers Grow Several Bales''.

====Cells of the epidermis====
*Keratinocytes.
**Usually eosinophilic cytoplasm - '''important feature'''.
**May have clear perinuclear halo (glycogenated keratinocytes).
**Intercellular bridges (high power) - '''key feature'''.
*Melanocytes.
**Usuallly basal location.
**Epithelioid or dentritic morphology.
**Pericellular clearing - '''key feature'''.
**Clear cytoplasm.
**+/-Pigmentation.
*Other:
**Toker cell.
**Neutrophils.
***Trilobated nuclei - 2-3 little dots - '''key feature'''.
**Lymphocytes.
***Small (round) nucleus.
***Scant/indistinct cytoplasm.
**Other foreign cells:
***[[Paget disease]]: large cells with clear cytoplasm, may cluster, above basal layer.

====Normal histology====
Features:
*Keratinocytes:
**Basal ~ 2x [[RBC]].
***May palisade focally ~ 1:2 = width: height.
*Melanocytes < 25 melanocytes / 0.5 mm of basal layer.<ref name=pmid21549242>{{Cite journal | last1 = Trotter | first1 = MJ. | title = Melanoma margin assessment. | journal = Clin Lab Med | volume = 31 | issue = 2 | pages = 289-300 | month = Jun | year = 2011 | doi = 10.1016/j.cll.2011.03.006 | PMID = 21549242 }}</ref>
*Basket weave stratum corneum (non-acral skin).

===Dermis===
Subdivided into layers:
#Papillary dermis.
#*Location: superficial - opposed to the deep aspect of the epidermis.
#*Appearance: dense, thick collagen bundles.
#Reticular dermis.
#*Location: deep - between papillary dermis and subdermis.
#*Appearance: loose connective tissue.

Images:
*[http://www.biology-online.org/user_files/Image/Anatomy/AN-fibroblastF02.gif Layers of the dermis - labelled (biology-online.org)].<ref>URL: [http://www.biology-online.org/articles/fibroblast_heterogeneity_skin_deep/figures.html http://www.biology-online.org/articles/fibroblast_heterogeneity_skin_deep/figures.html]. Accessed on: 29 March 2012.</ref>
*[http://melanoma.blogsome.com/wp-admin/images/skinstr.jpg Layers of the skin (melanoma.blogsome.com)].<ref>URL: [http://melanoma.blogsome.com/category/skin-structure/ http://melanoma.blogsome.com/category/skin-structure/]. Accessed on: 29 March 2012.</ref>

===Adnexal structures===
The top five structures of the skin:<ref>{{Ref Derm|4-8}}</ref>
{| class="wikitable sortable"
! Structure / Attribute
! Histomorphology
! Function
! [[IHC]]
! Other
! Image
|-
| '''Eccrine gland'''
| clusters of tubular structures, pale cytoplasm
| thermoregulation (cooling) - produce sweat
| [[CK7]]+, [[CEA]]+, CAM5.2+, [[EMA]]+
| ?
| ?
|-
| '''Apocrine gland'''
| apical snouts, tubular structures
| ear wax, body odor
| ?
| ?
| ?
|-
| '''Sebaceous gland'''
| clusters of cells side-by-side, pale fluffy cytoplasm
| grease hair, sexual lubrication
| ?
| assoc. with hair follicle
| ?
|-
| '''Hair follicle'''
| linear structure
| keep individual warm
| ?
| assoc. with sebaceous glands
| ?
|-
| '''Nail'''
| epidermal structure
| weapon (claw-like), look pretty?
| ?
| ?
| [http://histology.osumc.edu/histology/HumanHisto/Integumentary/Img/17B-23_001.html (osumc.edu)], [http://ctrgenpath.net/static/atlas/mousehistology/Windows/integumentary/nail20.html (ctrgenpath.net)]
|-
|}

Ducts vs. glands:<ref>HJ. 27 Feb 2009.</ref>
*Eccrine glands - spindle-shaped myoepithelial cells surround luminal cells.
*Eccrine ducts - cuboidal type subepithelial cells.

=Common terms=
==Clinical descriptors==
There are multitude of clinical descriptors - common ones are:<ref>URL: [http://www.pediatrics.wisc.edu/education/derm/text.html http://www.pediatrics.wisc.edu/education/derm/text.html]. Accessed on: 18 September 2012.</ref>
{| class="wikitable sortable"
! '''Name'''
! '''Size †'''
! '''Description'''
! '''Other'''
! '''Image'''
|-
| Macule
| <= 10 mm
| flat + change of colour
| if > 10 mm --> patch
| [[Image:Macule_and_Patch.svg|thumb|center|150px| Macule (WC)]]
|-
| Patch
| > 10 mm
| flat + change of colour
| if <= 10 mm --> macule
| [[Image:Macule_and_Patch.svg|thumb|center|150px| Patch (WC)]]
|-
| Papule
| <= 10 mm
| raised
| if > 10 mm --> nodule
| [[Image:Papule_and_Plaque.svg|thumb|center|150px| Papule (WC)]]
|-
| Nodule
| > 10 mm
| raised
| if <= 10 mm --> papule
| [[Image:Nodules.svg|thumb|center|150px| Nodule (WC)]]
|-
| Plaque
| > 10 mm
| raised, flat-top
| plateau-like
| [[Image:Papule_and_Plaque.svg|thumb|center|150px| Plaque (WC)]]
|-
| Vesicle
| <= 10 mm
| raised, fluid filled
| if > 10 mm --> bulla
| [[Image:Vesicles_and_Bulla.svg |thumb|center|150px| Vesicle (WC)]]
|-
| Bulla
| > 10 mm
| raised, fluid filled
| if <= 10 mm --> vesicle
| [[Image:Vesicles_and_Bulla.svg |thumb|center|150px| Bulla (WC)]]
|}
Note:
* † Definitions vary -- some authors use a 5 mm cut-off.

==Histologic descriptors==
Dermatopathology doesn't have intuitive terms, e.g. thickening of the stratum spinosum isn't ''spinosum hyperplasia''. The terms have to committed to memory.

===Common terms in a table===
{| class="wikitable sortable"
! Term
! Meaning
! Reference
|-
|Acanthosis
| thickening of the prickle layer (stratum spinosum) of epidermis
| <ref>[http://dictionary.reference.com/browse/acanthosis http://dictionary.reference.com/browse/acanthosis]</ref>
|-
|Acantholysis
| loss of intercellular connections in the epidermis
|
|-
|Dyskeratosis
| abnormal keratinization, often refers to keratinization below the stratum granulosum; keratinization above may be abnormal (dependent on body site)
|
|-
|Parakeratosis
| retention of nuclei in the stratum corneum, normal in mucous membranes
|
|-
|Spongiosis
| epidermal intercellular edema; cells appear to have a clear halo around 'em
| <ref>{{Ref PBoD|1230}}</ref>
|-
|Basketweave stratum corneum
| appearance of the normal stratum corneum; presence in the context of pathology suggests an acute process
|
|-
|Compact hyperkeratosis
| stratum corneum layer is dense and thickened; this suggests a chronic process
| <ref>URL: [http://dermnetnz.org/pathology/pathology-glossary.html http://dermnetnz.org/pathology/pathology-glossary.html]. Accessed on: 8 August 2012.</ref>
|-
| Hyperkeratosis
| thickened stratum corneum - also see ''compact hyperkeratosis'' and ''basketweave stratum corneum''
|
|-
|Epidermotropism †
| intraepithelial lymphocytes in [[CTCL]]; how to remember: epidermotropis''m'' = ''m''alignant
| <ref name=pmid20132423>{{Cite journal | last1 = Fung | first1 = MA. | title = 'Epidermotropism' vs. 'exocytosis' of lymphocytes 101: definition of terms. | journal = J Cutan Pathol | volume = 37 | issue = 5 | pages = 525-9 | month = May | year = 2010 | doi = 10.1111/j.1600-0560.2010.01515.x | PMID = 20132423 }}</ref>
|-
|Exocytosis †
| intraepithelial lymphocytes in benign conditions
| <ref name=pmid20132423>{{Cite journal | last1 = Fung | first1 = MA. | title = 'Epidermotropism' vs. 'exocytosis' of lymphocytes 101: definition of terms. | journal = J Cutan Pathol | volume = 37 | issue = 5 | pages = 525-9 | month = May | year = 2010 | doi = 10.1111/j.1600-0560.2010.01515.x | PMID = 20132423 }}</ref>
|-
|Orthokeratosis
| anuclear keratin layer is present (stratum corneum) - seen in normal skin; ''ortho-'' means ''correct''
| <ref>URL: [http://www.medilexicon.com/medicaldictionary.php?t=63448 http://www.medilexicon.com/medicaldictionary.php?t=63448]. Accessed on: 13 March 2013.</ref><ref>URL: [http://dictionary.reference.com/browse/ortho- http://dictionary.reference.com/browse/ortho-]. Accessed on: 13 March 2013.</ref>
|}
Note:
* † These definitions are not universally accepted. ''Epidermotropism'' is sometimes used in the context of benign disease.<ref name=pmid9537476>{{Cite journal | last1 = Fung | first1 = MA. | last2 = LeBoit | first2 = PE. | title = Light microscopic criteria for the diagnosis of early vulvar lichen sclerosus: a comparison with lichen planus. | journal = Am J Surg Pathol | volume = 22 | issue = 4 | pages = 473-8 | month = Apr | year = 1998 | doi = | PMID = 9537476 }}</ref>

Image:
*[http://commons.wikimedia.org/wiki/File:Spongiotic_dermatitis_%282%29_Dyshidrotic_.JPG Spongiosis (WC)].

===Others terms===
*Crust = epithelial elements, blood.

Image:
*[http://www.eplasty.com/article_images/eplasty10e60_fig3.gif Crust (eplasty.com)].<ref>URL: [http://www.eplasty.com/index.php?option=com_content&view=article&id=492&catid=171:volume-10-eplasty-2010&Itemid=121 http://www.eplasty.com/index.php?option=com_content&view=article&id=492&catid=171:volume-10-eplasty-2010&Itemid=121]. Accessed on: 16 October 2012.</ref>

=Skin diseases=
==Neoplasms==
{{main|Dermatologic neoplasms}}

===Malignant===
Skin cancer is very common. The basic DDx of a malignant skin lesion is:
*[[Squamous cell carcinoma]] (SCC).
*[[Basal cell carcinoma]] (BCC).
*[[Malignant melanoma]].
*Metstases.

==Non-malignant disease==
{{main|Non-malignant skin disease}}
Non-malignant skin disease is common. It is the domain of dermatologists. It can be scary for general anatomical pathologists because the differential diagnosis is often broad, and, it's generally not something the general anatomical pathologist sees a lot of.

===Subarticles===
*[[Dermal cysts]], e.g. [[epidermal cyst]], [[pilar cyst]].
*[[Epidermal necrosis]], e.g. [[erythema multiforme]], [[toxic epidermal necrolysis]].
*[[Inflammatory skin diseases]].
**[[Bullous diseases]], e.g. [[pemphigus vulgaris]].
**[[Panniculitis]].

=Common entities in tables=
==Non-malignant non-cystic - very common==
{| class="wikitable sortable" style="margin-left:auto;margin-right:auto"
! Entity
! Key histologic feature
! Other features
! Clinical
! Stains/IHC
! DDx
! Other
! Image
|-
| [[Seborrheic keratosis]] (SK)
| horn cysts (intraepidermal collections of keratin)
| hyperkeratosis, brown granular material at the DE junction, sharply demarcated
| stuck on appearance
| none
| [[fibroepithelial polyp]]
| Leser–Trélat sign = many SKs in malignancy
| [[Image:Seborrheic_keratosis_(1).jpg |thumb|center|150px| SK (WC)]]
|-
| [[Dermatofibroma]]
| fibrous bundles esp. at edge of lesion
| "dirty fingers" = acanthosis + basal keratinocyte hyperpigmentation
| +/-trauma Hx
| CD34-, Factor XIIIa+
| [[DFSP]]
| very common
| [[Image:SkinTumors-P9280848.jpg|thumb|center|150px|DF (WC)]]
|-
| [[Fibroepithelial polyp]] (skin tag)
| on a stalk (epithelium on 3+ sides)
| no horn nests, no hyperkeratosis
| raised lesion
| none
| [[seborrheic keratosis]]
| very common
| [[Image:SkinTumors-P9250819.jpg|thumb|center|150px|Skin tag (WC)]]
|-
| [[Lipoma]]
| mature adipocytes - uniform size
| var. of size may be seen, should prompt search for lipoblasts
| mobile subcutaneous mass
| S100 (???)
| [[liposarcoma]]
| variants: angiolipoma (blood vessels), myolipoma (muscle)
| [[Image: Lipoma -- high mag.jpg|thumb|center|150px|Lipoma (WC)]]
|-
| [[Cicatrix]] (dermal scar)
| dense collagen bundles running parallel to DE junction, loss of dermal papillae
| loss of adnexal structures, +/-[[giant cells]], +/-foreign material, +/-inflammatory cells
| site of previous trauma/surgery
| usu. none; S-100 (to exclude melanoma)
| residual disease, [[hypertrophic scar]], (desmoplastic) [[melanoma]]
|
| [[Image:ScarHistology.JPG |thumb|center|150px| Scar (WC)]]
|- 
|}

==Non-malignant non-cystic - common==
{| class="wikitable sortable" style="margin-left:auto;margin-right:auto"
! Entity
! Key histologic feature
! Other features
! Clinical
! Stains/IHC
! DDx
! Other
! Image
|-
| [[Neurofibroma]]
| bland spindle cells
| mast cells, mixed with collagen, assoc. with a nerve
| may be associated with [[neurofibromatosis]], esp. plexiform type
| S100+, GFAP+
| neurotized [[melanocytic nevus]]
| may develop into [[MPNST]]
| [[Image:Neurofibroma_%281%29.jpg |thumb|center|150px| Neurofibroma (WC)]]
|-
| [[Keratoacanthoma]]
| keratin plug, glassy pink cytoplasm, pushing downward growth
| minimal/no nuclear atypia
| grow rapidly then involute
| none
| [[squamous cell carcinoma]]
| some don't believe in the entity
| [[Image:Skin_keratoacanthoma_whole_slide.jpg |thumb|center|150px| Keratoacathoma (WC)]]
|-
| [[Molluscum contagiosum]]
| suprabasilar cells with abundant granular eosinophilic cytoplasm
| small peripheral nucleus
| polypoid lesion; mushroom-like (?)
| none (?)
| DDx (?)
| favourite exam case
| [[Image:Molluscum_contagiosum_high_mag.jpg |thumb|center|150px|Molluscum contagiosum (WC)]]
|-
| [[Verruca vulgaris]]
| hypergranulosis (thick granular layer) + keratohyaline granules
| hyperkeratosis (thick s. corneum), acanthosis (thick s. spinosum), rete ridges lengthened (~7-10x normal), large vessels at DE junction, koilocytic change (???)
| raised lesions, classically on hand
| none (p16+?)
| [[squamous cell carcinoma of the skin|squamous cell carcinoma]]
| caused by [[HPV]]
| [[Image:Verruca_vulgaris_-_very_low_mag.jpg |thumb|center|150px| Verruca vulgaris (WC)]]
|-
| [[Condyloma acuminatum]]
| koilocytes
| parakeratosis, long folded rete ridges (papillomatosis) - pseudopapillary look
| genital lesion
| none (p16+)
| [[fibroepithelial polyp]]
| caused by [[HPV]]
| [[Image:Anal_condyloma_%282%29.jpg |thumb|center|150px| Condyloma acuminatum (WC)]]
|-
| [[Granuloma annulare]]
| dermal palisading [[granuloma]] around necrotic collagen
| mucin in centre of lesion, (peripheral) lymphocytes, usu. more superficial than necrobiosis lipoidica
| benign, self-limited
| none (CD68?)
| [[necrobiosis lipoidica]], [[rheumatoid nodule]], [[epithelioid sarcoma]]
| Other ?
| [[Image:Granuloma_annulare_-_add_-_high_mag.jpg |thumb|center|150px| GA (WC)]]
|-
| [[Necrobiosis lipoidica]]
| dermal palisading [[granuloma]] around necrotic collagen, plasma cells
| mucin in centre of lesion, (peripheral) chronic inflammatory cells
| may be assoc. [[diabetes mellitus]]
| none (CD68?)
| [[granuloma annulare]], [[rheumatoid nodule]]
| histology identical to ''necrobiosis lipoidica diabeticorum''
| [http://www.drmihm.com/cases/casefigure.cfm?figID=942&CaseID=53 (drmihm.com)]
|-
| [[Angiofibroma]]
| fibrotic dermis, dilated capillaries
| enlarged (stellate fibroblasts)
| dome-shaped - face, boys & nosebleeds ([[nasopharyngeal angiofibroma]])
| Stains/IHC
| DDx
| may be associated with [[tuberous sclerosis]]
| [[Image:Nasopharyngeal angiofibroma - 2 - high mag.jpg|thumb|150px|Angiofibroma (WC)]]
|-
| [[Keloid]]
| thick collagen bundles - surrounded by paler staining fibroblasts
| replaces adnexal structures
| site of previous trauma, esp. in blacks
| none
| [[dermatofibroma]] (???)
| [[hypertrophic scar]]
| [[Image:Keloid_-_high_mag.jpg|thumb|center|150px|Keloid (WC)]]
|-
| [[Eccrine poroma]]
| abundant basaloid cells with (small) ductal structures
| incloses islands of sclerotic stroma with edema
| erythematous lesions
| Stains/IHC ?
| DDx ?
| Other ?
| [[Image:SkinTumors-P7150495.JPG|thumb|center|150px|EP (WC)]]
|-
| [[Syringoma]]
| bilayered ducts, occasionally tadpole like shape
|
| usu. close to [[eyelid]]
| Stains/IHC ?
| DDx ?
| Other ?
| [http://dermatology.cdlib.org/144/tumors/axillary_syringoma/2.jpg (cdlib.org)]
|-
| [[Chondroid syringoma]] (mixed tumour of skin)
| [[chondromyxoid stroma]], epithelial component
| epithelial component in nests with eosinophilic cytoplasm, round/ovoid nuclei with nucleoli
| Clinical ?
| Stains/IHC ?
| DDx ?
| related to [[pleomorphic adenoma]] (???)
| Image ?
|-
| [[Angiokeratoma]]
| ectatic superficial dermal vessels + overlying hyperkeratosis
| -
| may be seen in [[Fabry disease]]
| Stains/IHC ?
| [[venous lake]]
| Other ?
| [[Image:Angiokeratoma_-_low_mag.jpg |thumb|center|150px| Angiokeratoma (WC)]]
|- 
|}

==Non-malignant non-cystic - children==
{| class="wikitable sortable" style="margin-left:auto;margin-right:auto"
! Entity
! Key histologic feature
! Other features
! Clinical
! Stains/IHC
! DDx
! Other
! Image
|-
| [[Pilomatricoma]]
| anucleate squamous cells (ghost cells), giant cells
| bland basaloid cells
| common in children
| none
| [[squamous cell carcinoma of the skin|squamous cell carcinoma]]
| mutations of CTNNB1 gene
| [[Image:Pilomatrixoma_-_intermed_mag.jpg |thumb|center|150px| Pilomatrixcoma (WC)]]
|-
| [[Juvenile xanthogranuloma]] (JXG)
| Touton giant cells - multi-nucleated cells where nuclei are distributed around the cell periphery forming a ring
| abundant cytoplasm
| children
| CD68+, CD1a-, CD207-
| [[Langerhans cell histiocytosis]]
| may be seen in adults, known as '''adult xanthogranuloma'''
| [[Image:Juvenile_xanthogranuloma_-_high_mag.jpg |thumb|center|150px| JXG (WC)]]
|}

==Non-malignant cystic==
{| class="wikitable sortable" style="margin-left:auto;margin-right:auto"
! Entity
! Key histologic feature
! Other features
! Clinical
! Stains/IHC
! DDx
! Other
! Image
|-
| [[Epidermal cyst]]
| cyst lined by squamous epithelium '''with''' a granular layer
| keratinous debris, no skin adnexal structures
| cyst
| none
| [[pilar cyst]], [[dermoid cyst]]
| Other?
| [[Image:Epidermal inclusion cyst -- high mag.jpg |thumb|center|150px| Epidermal inclusion cyst (WC)]]
|-
| [[Pilar cyst]] (trichilemmal cyst)
| cyst lined by squamous epithelium '''without''' a granular layer
| keratinous debris
| cyst
| none
| [[epidermal cyst]]
| Other?
| [[Image:Trichilemmal_cyst_-_very_high_mag.jpg |thumb|center|100px| Pilar cyst (WC)]]
|-
| [[Steatocystoma]]
| cyst lined by squamous epithelium with a corrugated eosinophilic lining
| epidermis has '''no''' granular layer
| cyst
| none
| [[dermoid cyst]], follicular cyst
| Other?
| [[Image:Steatocystoma_-_high_mag.jpg |thumb|center|150px| Steatocystoma (WC)]]
|-
| [[Dermoid cyst]]
| cyst lined by keratinizing squamous epithelium with adnexal structures
| adnexal structure = hair, sebaceous gland, sweat glands
| cyst
| none
| [[epidermal cyst]]
| may be seen in the [[ovary]]
| [http://webeye.ophth.uiowa.edu/eyeforum/cases-i/case115/larger/Figure4.jpg (uiowa.edu)]
|}

==Pre-malignant==
{| class="wikitable sortable" style="margin-left:auto;margin-right:auto"
! Entity
! Key histologic feature
! Other features
! Clinical
! Stains/IHC
! DDx
! Other
! Image
|-
| [[Actinic keratosis]]
| epidermal atypia, esp. (basal) nuclear enlargement
| var. of nuclear size, shape and staining, parakeratosis (important in early lesions); does ''not'' involves adnexal epithelium and follicular epithelium
| yellow-brown scaly
| none
| [[squamous carcinoma]], [[Bowen disease]]
| seen with [[solar elastosis]]
| [[Image:Actinic_Keratosis,_H%26E.jpg |thumb|center|150px| AK (WC)]]
|-
| [[Bowen disease]] (squamous cell carcinoma in situ)
| epidermal atypia, esp. suprabasal nuclear enlargement
| var. of nuclear size, shape and staining; usually full thickness involvement; involve adnexal epithelium and follicular epithelium
|
| none
| [[squamous carcinoma]], [[actinic keratosis]]
| typically seen with solar elastosis
| [[Image:Bowen_disease_%281%29.jpg |thumb|center|100px| Bowen's disease (WC)]]
|}

==Common malignant==
{| class="wikitable sortable" style="margin-left:auto;margin-right:auto"
! Entity
! Key histologic feature
! Other features
! Clinical
! Stains/IHC
! DDx
! Other
! Image
|-
| [[Basal cell carcinoma]] (BCC)
| basaloid cells with peripheral palisading, artificial cleft
| [[myxoid]] stroma
| raised, pearly, telangiectasia
| usu. none req., [[CK5/6]]+
| [[trichoepithelioma]], [[basaloid squamous cell carcinoma]]
| assoc. [[nevoid basal cell carcinoma syndrome]], [[Bazex syndrome]]
| [[Image:Basal cell carcinoma - high mag.jpg| thumb| center|150px|BCC (WC)]]
|-
| [[Squamous cell carcinoma]] (SCC)
| nuclear enlargement, eosinophilic cytoplasm, central nucleus
| small nucleolus, intercellular bridges
| flaky appearance
| usu. none req., p63+, HMWK+
| [[keratoacanthoma]], [[Paget disease]] ([[EMPD]] & [[PDB]]), [[malignant melanoma]], Toker cell hyperplasia
| Other
| [[Image:Oral_cancer_%281%29_squamous_cell_carcinoma_histopathology.jpg|thumb|center|150px|SCC (WC)]]
|-
| [[Malignant melanoma]]
| spindle and/or epithelioid morphology +/-nuclear atypia (esp. nucleoli)
| mitoses (esp. deep), +/-pigment, +/-nested arch., asymmetry, upward spread (into epidermis), epithelioid m. deep, +/-single cells, +/-sheets of cells
| ABCD = Asymmetry, Borders poor demarc., Colour dark, Diameter large
| S100+, Melan A+, HMB-45+, microphthalmia+, tyrosinase+
| [[melanocytic lesions]] esp. [[Spitz nevus]], [[Bowen's disease]]
| may be familial, [[dysplastic nevus]]
| [[Image:Malignant_melanoma_%281%29_at_thigh_Case_01.jpg |thumb|center|150px|Melanoma (WC)]]
|- 
|}

==Less common malignant==
{| class="wikitable sortable" style="margin-left:auto;margin-right:auto"
! Entity
! Key histologic feature
! Other features
! Clinical
! Stains/IHC
! DDx
! Other
! Image
|-
| [[Kaposi sarcoma]]
| vascular spindle cell lesion
| [[hyaline globules]] (intracytoplasmic)
| often HIV/AIDS
| [[HHV-8]]
| [[Masson's hemangioma]], [[angiosarcoma]], [[Kaposiform hemangioendothelioma]]
| stages: patch stage, plaque stage, nodular stage, exophytic, infiltrative, lymphadenopathic
| [[Image:Kaposi_sarcoma_low_intermed_mag.jpg |thumb|center|150px| Kaposi sarcoma (WC)]]
|-
| [[Cutaneous T-cell lymphoma]] (includes ''mycosis fungoides'')
| single lymphocytes in epidermis ("lymphocyte exocytosis")
| lymphocyte nests in the epidermis ("Pautrier microabscesses"), short arrays of lymphocytes along the basal layer of the epidermis ("epidermotropism")
| Clinical
| CD45, CD4
| B cell lymphoma (?)
| Other
| [[Image:Cutaneous_T-cell_lymphoma_-_intermed_mag.jpg |thumb|center|150px| CTCL (WC)]]
|-
| [[Atypical fibroxanthoma]]
| dermal lesion with marked nuclear atypia
| multinucleated cells, mitoses, vacuolated cytoplasm
| old men, head and neck
| p63-, 34betaE12-, S100-, desmin-
| sarcomatoid squamous carcinoma, [[melanoma]], [[leiomyosarcoma]]
| some classify this as '''benign'''; thought to be related to [[undifferentiated pleomorphic sarcoma]]
| [[Image:SkinTumors-P9280874.jpg|thumb|center|150px| AFX (WC)]]
|-
| [[Merkel cell carcinoma]]
| neuroendocrine nuclear features (stippled chromatin, no nucleolus), scant cytoplasm
| +/-nuclear moulding, usu. intermediate cell size
| Merkel cell polyomavirus associated, usu. head & neck or extremities
| CK20+, EMA+
| cutaneous [[Ewing sarcoma]], [[basal cell carcinoma]], (dermal) [[lymphoma]], metastatic small cell carcinoma (e.g. [[Lung tumours#Small cell carcinoma|lung]])
| rare, aggressive
| [[Image:Merkel_cell_carcinoma_-_very_high_mag.jpg |thumb|center|100px| MCC (WC)]]
|-
| [[Dermatofibrosarcoma protuberans]] (DFSP)
| spindle cell tumour with storiform pattern, tumour often contains adipocytes
| dermal tumour with preserved adnexal structures
| locally aggressive
| CD34+, factor XIIIa-
| [[dermatofibroma]], [[solitary fibrous tumour]] (usu. deeper)
| rarely metastases, characteristic [[translocation]]: t(17;22)(q22;q15) COLA1/PDGFB; may transform to [[fibrosarcoma]]
| [[Image:Storiform_pattern_-_intermed_mag.jpg |thumb|center|150px| DFSP (WC)]]
|- 
|}

=Presentations=
==Leukoplakia==
{{Main|Leukoplakia}}

DDx:<ref>{{Ref PBoD|1065}}</ref>
*Vitiligo (loss of pigment).
*Inflammation.
**Chronic dermatitis.
**[[Psoriasis]].
*Neoplasia.
**[[Vulvar intraepithelial neoplasia]].
**[[Invasive_breast_cancer#Paget.27s_disease|Paget disease]].
**Invasive carcinoma.
*Other.
**[[Lichen sclerosus]].
**[[Lichen simplex chronicus]].

=Skin disease and systemic conditions=
==Tabular list==
{| class="wikitable sortable" style="margin-left:auto;margin-right:auto"
! Entity
! Disease/syndrome
! Key histologic feature
! Image
|-
| [[Acanthosis nigricans]]
| [[diabetes mellitus]], malignancy
| basal cell hyperpigmentation, hyperkeratosis, prominent rete ridges
| [http://dermatology.cdlib.org/149/reviews/acanthosisnigricans/higgins.html (cdlib.org)]
|-
| [[Trichilemmoma]]
| [[Cowden disease]]
| "hyperkeratosis"
| [http://ccr.cancer.gov/staff/images/9033_12822_Lee_1520.jpg (cancer.gov)]<ref>URL: [http://ccr.cancer.gov/staff/gallery.asp?profileid=12822 http://ccr.cancer.gov/staff/gallery.asp?profileid=12822]. Accessed on: 14 December 2011.</ref>
|-
| [[Angiokeratoma]]
| [[Fabry disease]]
| hyperkeratosis + vessels in superficial dermis
| [http://commons.wikimedia.org/wiki/File:Angiokeratoma_-_low_mag.jpg (WC)]
|-
| [[Dermatitis herpetiformis]]
| [[Celiac disease]]
| subepidermal [[bullous disease]], papillary abscesses
| [http://www.lampyris101.com/L101/gallery1/12_JPG.html (lampyris101.com)]
|-
| [[Angiofibroma]]
| [[tuberous sclerosis]]
| fibrotic dermis + dilated blood vessels
| [http://www.drdittmar.lu/images/sce/angiofibroma-s.jpg (drdittmar.lu)]
|-
| [[Sebaceous adenoma]]
| [[Muir-Torre syndrome]]
| abundant sebaceous glands with abn. arch.
| [http://commons.wikimedia.org/wiki/File:Sebaceous_adenoma_-_low_mag.jpg (WC)]
|-
| [[Seborrheic keratosis]], multiple with explosive onset
| Leser–Trélat sign (malignancy)
| horn cysts, hyperkeratosis
| [http://commons.wikimedia.org/wiki/File:IMG_1724.JPG gross (WC)], [http://commons.wikimedia.org/wiki/File:Seborrheic_keratosis_%281%29.jpg micro. (WC)]
|- 
|}

==Acanthosis nigricans==
===General===
Associated with:
*[[Diabetes mellitus]].<ref>URL: [http://www.emedicine.com/derm/topic1.htm http://www.emedicine.com/derm/topic1.htm], URL: [http://dermatlas.med.jhmi.edu/derm/indexDisplay.cfm?ImageID=1943559504].</ref>
*Malignancy.<ref name=Ref_PCPBoD8|596>{{Ref PCPBoD8|596}}</ref>

===Microscopic===
Features (memory device ''BPH''):<ref name=Ref_PCPBoD8|596>{{Ref PCPBoD8|596}}</ref>
*Basal cell hyperpigmentation.
*Prominent rete ridges.
*Hyperkeratosis.

DDx:
*[[Seborrheic keratosis]] - typically has more hyperkeratosis, pseudohorn cysts.

Images:
*[http://dermatology.cdlib.org/149/reviews/acanthosisnigricans/higgins.html AN (cdlib.org)].

==Others==
*[[Dermatitis herpetiformis]]: gluten enteropathy ([[celiac disease]]), [[thyroid]] disease, intestinal [[lymphoma]].<ref name=Ref_TN2007_D23>{{Ref TN2007|D23}}</ref>
*[[Pemphigus vulgaris]]: [[thymoma]], myasthenia gravis, malignancy.<ref name=Ref_TN2007_D23>{{Ref TN2007|D23}}</ref>
 
[[File:3767 dp sl 1.png |Lipoid proteinosis]]
[[File:3767 dp sl 2.png |Lipoid proteinosis]] 
Lipoid proteinosis. A. Inner labial biopsy shows subepithelial hyalinized pink/red material, about blood vessels and in general. B. The particularly glassy appearance of the material in areas is evident at high power.
 
[[File:DP16MR17 sl 1.png| Xanthogranuloma in scrotal skin.]]
[[File:DP16MR17 sl 2.png| Xanthogranuloma in scrotal skin.]]
[[File:DP16MR17 sl 3.png| Xanthogranuloma in scrotal skin.]]
[[File:DP16MR17 sl 4.png| Xanthogranuloma in scrotal skin.]]
 
Xanthogranuloma in scrotal skin. A. Pseudoepitheliomatous hyperplasia seemingly forms a dermal mass. B. Parakeratosis tops epidermis. C. Neutrophils lie in the center of the apparent mass. D. Diagnostic xanthoma cells lie in dermal papillae.
 

=References=
{{reflist|2}}

[[Category:Dermatopathology]]

Medical liver disease

2017-03-07T23:11:42Z

Mitchell: /* Other */ Added a casepf PSS

[[Image:Ground glass hepatocytes high mag cropped 2.jpg|thumb|right|[[Micrograph]] showing ground glass hepatocytes, as seen in chronic [[hepatitis B]]. [[H&E stain]].]]
This article deals with '''medical [[liver]] disease'''. An introduction to the liver and approach is found in the ''[[liver]]'' article.

Every differential in liver pathology has "drugs"<ref>{{Ref PCPBoD8|448}}</ref> -- if it isn't clearly malignancy.

Liver neoplasms are dealt with in the ''[[liver neoplasms]]'' article.

Medical liver biopsies are often non-specific, as the liver has the same appearance for many mechanisms of injury, especially when the injury is marked. The clinical history, serology and imaging are essential for proper interpretations in this domain of pathology.

=Review of liver blood work=
===Inflammation activity===
*ALT.
*AST.

===Cholestatic markers===
*ALP.
*GGT - used to assess whether the ALP is an "honest" value, elevated in cirrhosis.

===Cirrhosis/decompensation===
*PLT - low is suggestive of dysfunction.
*INR - high is bad, unless anticoagulated.

===Other===
*Bilirubin.
**Direct (AKA conjugated).
**Indirect (AKA unconjugated).

A short DDx of elevated:<ref>{{Ref PCPBoD8|441}}</ref>
*Indirect:
**[[Gilbert syndrome]].
**Crigler-Najjar syndrome type 1.
**Crigler-Najjar syndrome type 2.
*Direct:
**Rotor syndrome.
**Dubin-Johnson syndomre.

===Viral hepatitis===
*HBV DNA.
*HCV RNA.
*HBs Ag, HBs Ab, HBe Ag, HBe Ab.
*HCV Ab.

Others:
*[[Epstein-Barr virus]] (EBV).
*[[Cytomegalovirus]] (CMV) - especially in the immune incompetent.

====Hepatitis B====
Meaning & utility of the various [[Hepatitis B]] tests:<ref>URL: [http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/hepatology/hepatitis-B/ http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/hepatology/hepatitis-B/]. Accessed on: 16 May 2011.</ref><ref name=lto_hepb>URL: [http://www.labtestsonline.org/understanding/analytes/hepatitis_b/test.html http://www.labtestsonline.org/understanding/analytes/hepatitis_b/test.html]. Accessed on: 16 May 2011.</ref>
{| class="wikitable sortable" border="1"
! Test name
! Location
! Positive test
! Negative test
! Usual question
|-
| HBs Ag||Surface||Virus active||No active infection||Active infection?
|-
| HBs Ab||Surface||Exposed OR vaccinated||No exposure OR no vaccine OR loss of Ab||Immunization status?
|-
| HBe Ag||Virus core||Infect. w/ viral replication||No active infection||Active infect. w/ viral replication?
|-
| HBe Ab||Virus core||Exposed to virus||Infect. w/o antibody response OR not exposed||Immune response to infection?
|-
| HBV DNA||-||Active||Not active/no exposure||Viral load/how active?
|-
| HBc Ab||Virus core||Virus active/previous exposure||No exposure||Early active infection?
|}
Notes:
*''HBc Ab'' may test for acute (IgM) or chronic infection - dependent on specific antibody test; it is often used to look for early infection.<ref name=lto_hepb>URL: [http://www.labtestsonline.org/understanding/analytes/hepatitis_b/test.html http://www.labtestsonline.org/understanding/analytes/hepatitis_b/test.html]. Accessed on: 16 May 2011.</ref>
*''Carriers of hepatitis B'': HBs Ag +ve, HBs Ab -ve, HBc Ag -ve, HBc Ab +ve, HBe Ag -ve, HBe Ab +ve.<ref>URL: [http://labtestsonline.org/understanding/analytes/hepatitis-b/tab/test http://labtestsonline.org/understanding/analytes/hepatitis-b/tab/test]. Accessed on: 3 May 2012.</ref>

===Markers for rare liver diseases===
*Ceruloplasm - low think ''[[Wilson's disease]]''; typical value for Wilson's ~ 0.12 g/L.
**<0.20 g/L is a criteria for Wilson's disease.<ref name=pmid18556333>Diagnostic accuracy of serum ceruloplasmin in Wilson disease: determination of sensitivity and specificity by ROC curve analysis among ATP7B-genotyped subjects. Mak CM, Lam CW, Tam S. Clin Chem. 2008 Aug;54(8):1356-62. Epub 2008 Jun 12. PMID 18556333. URL: [http://www.clinchem.org/cgi/reprint/54/8/1356.pdf http://www.clinchem.org/cgi/reprint/54/8/1356.pdf]. Accessed on: 28 September 2009.</ref>
*Alpha-1 antitrypsin - if low think ''deficiency''.

===Hemosiderosis===
*Ferritin - high.
*Iron saturation - high.

Causes:
*Hemochromatosis.
*Hemolysis, chronic.
*Cirrhosis.

=Medical imaging=
Blood flow:<ref>URL: [http://insidesurgery.com/2010/12/hepatopedal-hepatofugal-flow/ http://insidesurgery.com/2010/12/hepatopedal-hepatofugal-flow/]. Accessed on: 2 December 2011.</ref>
*Hepatopedal flow = normal portal vein flow.
*Hepatofugal flow = reversed portal vein flow.

==Interventional measurements==
Wedged to free hepatic venous pressure:<ref name=pmid1864548>{{Cite journal | last1 = Bion | first1 = E. | last2 = Brenard | first2 = R. | last3 = Pariente | first3 = EA. | last4 = Lebrec | first4 = D. | last5 = Degott | first5 = C. | last6 = Maitre | first6 = F. | last7 = Benhamou | first7 = JP. | title = Sinusoidal portal hypertension in hepatic amyloidosis. | journal = Gut | volume = 32 | issue = 2 | pages = 227-30 | month = Feb | year = 1991 | doi = | PMID = 1864548 | PMC = 1378815 | URL = http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1378815/?tool=pubmed }}</ref>
*Normal = 1-4 mmHg.
**Elevated in [[portal hypertension]].

=Liver biopsy=
==Medical liver biopsy adequacy==
Liver biopsy specimens should be:<ref>{{Ref MacSween|418}}</ref>
*2.0 cm in length and contain 11-15 portal tracts,
*The core should be deeper than 1.0 cm from the liver capsule; specimens close to the capsule may lead to over grading of fibrosis.

==Reporting==
{{Main|Pathology reports}}
<pre>
Specimen, procedure:
- Diagnosis.
</pre>
The diagnosis usually contains grading and staging information, e.g. ''activity 2 /4, Laennec fibrosis stage 1 /4''.

In the context of medical liver disease:
*Grade = inflammation/activity.
*Stage = severity of fibrosis/architectural changes.

Notes:
*The term "acute" is infrequently used in liver pathology.
*In the liver: neutrophils ''is not'' acute -- unlike most elsewhere in the body.<ref>OA. September 2009.</ref>

===A microscopic checklist===
<pre>
Size of biopsy: Adequate
Fragmentation: Absent
Fibrosis: Stage 2-3/4, mostly stage 2
Fibrous septa: Present
Septa with curved contours: Present – focally only
Large droplet steatosis (% of hepatocytes): Present, moderate 60%
Ballooning of hepatocytes: Present, rare
Mallory-Denk bodies: Present, rare
Portal inflammation: Present
Interface activity: Minimal (0-1/4)
Lobular necroinflammation: Minimal
Ducts: Present in normal numbers
Duct injury: Absent
Ductular reaction: Absent
Cholestasis: Absent
Terminal hepatic venules: Present
Iron stain: Absent
Ground glass cells with routine stains: Absent
PASD for alpha-1 antitrypsin droplets: Negative
</pre>

=Viral hepatitis=
These are common. The diagnoses are based on serology. The serology is covered in the ''[[Liver_pathology#Viral_hepatitis|viral hepatitis]]'' section in the ''[[liver pathology]]'' article.

Typically classified as:<ref name=pmid8048409>{{Cite journal | title = Terminology of chronic hepatitis, hepatic allograft rejection, and nodular lesions of the liver: summary of recommendations developed by an international working party, supported by the World Congresses of Gastroenterology, Los Angeles, 1994. | journal = Am J Gastroenterol | volume = 89 | issue = 8 Suppl | pages = S177-81 | month = Aug | year = 1994 | doi = | PMID = 8048409 }}</ref><ref>URL: [http://familydoctor.org/familydoctor/en/diseases-conditions/hepatitis-b.html http://familydoctor.org/familydoctor/en/diseases-conditions/hepatitis-b.html]. Accessed on: 2 May 2012.</ref>
#Acute < 6 months duration.
#Chronic > 6 months duration.

==Hepatitis A==
*Infection is self-limited, i.e. not persistent.
**May present as ''[[fulminant hepatic necrosis]]''.
*Usually asymptomatic in children.<ref name=pmid20068336>{{cite journal |author=Jeong SH, Lee HS |title=Hepatitis A: clinical manifestations and management |journal=Intervirology |volume=53 |issue=1 |pages=15–9 |year=2010 |pmid=20068336 |doi=10.1159/000252779 |url=}}</ref>
*Serology is diagnostic.

==Hepatitis B==
:''Hepatitis B virus'', abbreviated ''HBV'', redirects here.
{{Main|Hepatitis B}}

==Hepatitis C==
{{Main|Hepatitis C}}

=Other infections=
*Hydatid disease (Hydatid cyst).
*Ascaris.
*Fasciola

==Hydatid disease==
*[[AKA]] ''hydatid cyst''.
===General===
*Etiology: ''[[Echinococcus]]''.

===Microscopic===
Features:
*Laminated wall +/- calcification.<ref name=Ref_PBPoD8_448>{{Ref PCPBoD8|448}}</ref>
*Organisms -- see ''[[Echinococcus]]''.

====Images====
<gallery>
Image:Liver_cyst_wall_-_intermed_mag.jpg | Liver cyst wall - intermed. mag. (WC)
Image:Liver_cyst_wall_-_high_mag.jpg | Liver cyst wall - high mag. (WC)
Image: Laminated liver cyst wall - intermed mag.jpg | Characteristic laminated portion - intermed. mag. (WC)
Image: Laminated liver cyst wall - high mag.jpg | Characteristic laminated portion - high mag. (WC)
</gallery>
[[www]]:
*[http://pathmicro.med.sc.edu/parasitology/hydatid-hist1.jpg Hydatid cyst (med.sc.edu)].
*[http://www.atlas.or.kr/atlas/include/viewImg.html?uid=645 Hydatid cyst (atlas.or.kr)].
*[http://casereports.bmj.com/content/2009/bcr.04.2009.1798.full Hydatid cyst (casereports.bmj.com)].

==Abscess==
A. [[File:1 ABS 1 680x512px.tif|A process replaces most of the liver parenchyma (20X).]]
 
B. [[File:2 ABS 1 680x512px.tif|Fibrinopurulent exudate apposes granulation tissue (200X).]]
 
C. [[File:3 ABS 1 680x512px.tif|Neutrophils lie in widened sinusoids (200X)..]]
 
D. [[File:4 ABS 1 680x512px.tif|Trichrome shows collagenization of spaces of Disse. Scarring about an abscess or other mass lesion should not be interpreted as reflective of the liver in general (200X).]]
 
Abscess. A. A process replaces most of the liver parenchyma. B. Fibrinopurulent exudate apposes granulation tissue. C. Neutrophils lie in widened sinusoids. D. Trichrome shows collagenization of spaces of Disse. Scarring about an abscess or other mass lesion should not be interpreted as reflective of the liver in general (LR 200X).

==Coccidiomycosis==
A. [[File:Coccidiomycosis - 1 - 40X 680x512px shot.tif|500x500px Granulomas at low power]]
 
B. [[File:Coccidiomycosis - 1 - 200X 680x513px shot.tif|500x500px Granulomas with centrally crowded cells & lady slipper macrophage nuclei]]
 
C. [[File:Coccidiomycosis - 1 - 400X 1369x1024px shot.tif|500x500px Center of previous granuloma showing pyknotic macrophage nuclei]]
 
D. [[File:Coccidiomycosis - 1 - GMS 400X 1369x1024px shot.tif|500x500px Four Coccidiomycotic spherules]]
 
Coccidiomycosis. A. Note the granulomas in otherwise undisturbed liver (UL). B. Granuloma with centrally crowded cells & lady slipper macrophage nuclei. C. Center of granuloma with pyknotic macrophage nuclei, "necrotizing". D. Organisms on GMS stain.

=Metabolic and toxic=
==Alcoholic liver disease==
===General===
*Acute and/or chronic liver changes due to excessive [[alcohol]] use - includes:
**''[[Alcoholic steatohepatitis]]'' (ASH), [[AKA]] ''alcoholic hepatitis''.<ref>URL: [http://emedicine.medscape.com/article/170539-overview http://emedicine.medscape.com/article/170539-overview]. Accessed on: 3 May 2012.</ref>
***Alcoholic hepatitis can be with minimal steatosis.<ref>STC. 6 December 2010.</ref>
**[[Steatosis]] - classically macrovescicular and centrilobular.
**Alcoholic [[cirrhosis]].

====Classic lab findings in EtOH abusers====
*AST & ALT elevated with AST:ALT=2:1.
*GGT elevated.
*MCV increased.

===Gross pathology/radiologic findings===
*Classically micronodular pattern.
**May be macronodular.

===Microscopic===
See:
*''[[Steatohepatitis]]'' section and ''[[ballooning degeneration]]'' section.

Features:
*Often zone III damage.
*Cholestatsis common, i.e. yellow staining.
**NASH (non-alcoholic steatohepatitis) usu. does not have cholestasis.<ref>STC. 6 December 2010.</ref>
*Fibrosis starts at central veins.
*Neutrophils (often helpful) -- few other things have PMNs. (???)
**Neutrophils cluster around cells with Mallory hyaline.

====Images====

A. [[File:1 etoh 3 680x512px.tif| Alcoholic hepatitis with Metavir stage IV fibrosis (advanced fibrosis/cirrhosis).]]
 
B. [[File:2 etoh 3 680x512px.tif| Alcoholic hepatitis with Metavir stage IV fibrosis (advanced fibrosis/cirrhosis).]]
 
C. [[File:3 etoh 3 680x512px.tif| Alcoholic hepatitis with Metavir stage IV fibrosis (advanced fibrosis/cirrhosis).]]
 
D. [[File:4 etoh 3 680x512px.tif| Alcoholic hepatitis with Metavir stage IV fibrosis (advanced fibrosis/cirrhosis).]]
 
E. [[File:5 etoh 3 680x512px.tif| Alcoholic hepatitis with Metavir stage IV fibrosis (advanced fibrosis/cirrhosis).]]
 
F. [[File:6 etoh 3 680x512px.tif| Alcoholic hepatitis with Metavir stage IV fibrosis (advanced fibrosis/cirrhosis).]]
 

Alcoholic hepatitis with Metavir stage IV fibrosis (advanced fibrosis/cirrhosis).
A. Trichrome shows relatively non-inflamed fibrous bands, as well as [between green dots] nodules. The lack of regeneration throughout might have precluded a diagnosis of cirrhosis, but stage IV fibrosis under the Metavir system is justified. B. Reticulin shows regenerative nodules [left] with mostly two or more nuclei between black lines juxtaposed to non-regenerative hepatocytes on the right, without piecemeal necrosis. C. Regenerative nodules show occasional neutrophils [red arrow] and cytoplasmic tufts of ballooned cells, sometimes possibly Mallory hyalin [green arrows]. D. Triads (note vein [green arrow], artery [yellow arrow], and interlobular bile duct [blue arrow]) generally showed little or no interface hepatitis, even when expanded by fibrosis and inflamed. E. Occasional foci of spotty necrosis were seen. F. This edge of an inflamed triads shows neutrophils about proliferated bile ducts [red arrows], as well as Mallory-Denk bodies [blue arrows].
 
A. [[File:1 etoh 4 680x512px.tif| Cirrhosis in an alcoholic.]]
 
B. [[File:2 etoh 4 680x512px.tif| Cirrhosis in an alcoholic.]]
 
C. [[File:3 etoh 4 680x512px.tif| Cirrhosis in an alcoholic.]]
 
D. [[File:4 etoh 4 680x512px.tif| Cirrhosis in an alcoholic.]]
 
E. [[File:5 etoh 4 680x512px.tif| Cirrhosis in an alcoholic.]]
 
F. [[File:6 etoh 4 680x512px.tif| Cirrhosis in an alcoholic.]]
 
Definite cirrhosis in an alcoholic. A. Hepatocyte free bands parse tissue, with occasional definite islands [arrows]. B. Trichrome establishes blue fibrosis about isles [arrows]. C. Reticulin stain shows nodules with regeneration, wherein a large proportion of them are at least two nuclei thick [arrows]. D. Bile duct proliferation can be difficult, sometimes mimicking cholangiocarcinoma. Follow the double headed arrows to see how the ductules can be seen to proliferate from a single sources, with all ducts being complete, without necrotic epithelial cells. E. PAS with distase can help, as cholangiocarcinoma generally lacks the red rim of proliferating bile ductules [arrows]; again note the connections that can be made between the ductule openings by the blue double headed arrows. The cyan double headed arrows show general parallelism, consistent with uniform directionality induced by extrinsic force, not a neoplastic spread. F. Trichrome shows the most difficult focus. Double headed arrows display the connectivity seen before of the proliferated bile ductules. Note that numerous pairs of adjacent perpendicular glands without a head to foot appearance are not seen that would indicate the disorderly spread of cholangiocarcinoma.
 
A. [[File:1 ALC 2 680x512px.tif|Expanded, inflamed triads with increased bile duct/vascular openings. Mild steatosis (40X).]]
 
B. [[File:2 ALC 2 680x512px.tif|Trichrome stain shows periportal fibrosis [red arrowheads] (200X).]]
 
C. [[File:3 ALC 2 680x512px.tif|PAS with diastase stain shows proliferated bile ductules [blue arrowheads] in stroma with mixed inflammatory infiltrate (400X)]]
 
D. [[File:4 ALC 2 680x512px.tif|Neutrophils about ballooned hepatocyte (satellitosis) [yellow arrowheads]. Councilman bodies [green arrowheads] (400X).]]
 
Alcoholic hepatitis without cirrhosis. No history of viral disease. AMA negative. A. Expanded, inflamed triads with increased bile duct/vascular openings. Mild steatosis. B. Trichrome stain shows periportal fibrosis [red arrowheads]. C. PAS with diastase stain shows proliferated bile ductules [blue arrowheads] in stroma with mixed inflammatory infiltrate. D. Neutrophils about ballooned hepatocyte (satellitosis) [yellow arrowheads]. Councilman bodies [green arrowheads].

Notes:
*If portal inflammatory infiltrates more than mild, r/o other causes i.e. [[viral hepatitis]].
*Mallory bodies once thought to be characteristic; now considered non-specific and generally poorly understood.<ref>{{cite journal |author=Jensen K, Gluud C |title=The Mallory body: theories on development and pathological significance (Part 2 of a literature survey) |journal=Hepatology |volume=20 |issue=5 |pages=1330-42 |year=1994 |month=November |pmid=7927269 |doi= |url=}}</ref>
*Some consider ''alcoholic liver disease'' a clinical diagnosis, i.e. as a pathologist one does not diagnose it.<ref>MG. September 2009.</ref>

==Non-alcoholic fatty liver disease==
*Abbreviated ''NAFLD''.
*Fatty liver that is not due to alcohol; includes obesity-related fatty liver, metabolic disease/diabetes-related fatty liver.

===NASH===
*Non-alcoholic steatohepatitis - see ''steatohepatitis'' section.
*Histologically indistinguishable from ASH.
*NASH is a ''clinical diagnosis'' based on exclusion of alcohol.

==Steatohepatitis==
{{Main|Steatohepatitis}}

=Autoimmune=
==Autoimmune hepatitis==
*Abbreviated ''AIH''.
{{Main|Autoimmune hepatitis}}

==Primary biliary cirrhosis==
*Abbreviated PBC.
{{Main|Primary biliary cirrhosis}}

==Autoimmune hepatitis with obstruction - combined changes==
A. [[File:1 AIH OBS 1.tif|Low power shows inflammation; portal triads, lobules, central veins cannot be distinguished (40X).]]
 
B. [[File:2 AIH OBS 1.tif|Trichrome shows central venous sclerosis (red arrowhead), periportal fibrosis (green arrowhead), & space of Disse collagenization (yellow arrowhead); juxtaposition of central vein & portal tract indicates collapse, no definite bridging was seen (100X)]]
 
C. [[File:3 AIH OBS 1.tif|Central vein is inflamed with a rare plasma cell (cyan arrowhead) (400X).]]
 
D. [[File:4 AIH OBS 1.tif|Interface hepatitis with plasma cells (yellow arrows) and ballooned hepatocytes (red arrows). Lobule is disorganized (400X).]]
 
E. [[File:5 AIH OBS 1.tif|Proliferating bile ductules (blue arrows) with occasional neutrophils (fucsia arrows), indicative of obstruction, but not acute cholangitis, which requires inflamed bile duct itself, best diagnosed with associated blood vessel (400X).]]
 
F. [[File:6 AIH OBS 1.tif|Rare distorted rosettes with greenish brown strands of bile (left arrow) or bile plugs (right arrow) (400X).]]
 
Patient with SLE and obstructive jaundice that resolved with apparent passage of stone. A. Low power shows inflammation; portal triads, lobules, central veins cannot be distinguished. B. Trichrome shows central venous sclerosis (red arrowhead), periportal fibrosis (green arrowhead), & space of Disse collagenization (yellow arrowhead); juxtaposition of central vein & portal tract indicates collapse, no definite bridging was seen. C. Central vein is inflamed with a rare plasma cell (cyan arrowhead). D. Interface hepatitis with plasma cells (yellow arrows) and ballooned hepatocytes (red arrows). Lobule is disorganized. E. Proliferating bile ductules (blue arrows) with occasional neutrophils (fucsia arrows), indicative of obstruction, but not acute cholangitis, which requires inflamed bile duct itself, best diagnosed with associated blood vessel. F. Rare distorted rosettes with greenish brown strands of bile (left arrow) or bile plugs (right arrow).

==Autoimmune hepatitis-primary biliary cirrhosis overlap syndrome==
*Abbreviation ''AIH-PBC OS''.
===General===
Epidemiology:
*Rare.

Serology:<ref name=pmid19491855>{{Cite journal | last1 = Muratori | first1 = P. | last2 = Granito | first2 = A. | last3 = Pappas | first3 = G. | last4 = Pendino | first4 = GM. | last5 = Quarneti | first5 = C. | last6 = Cicola | first6 = R. | last7 = Menichella | first7 = R. | last8 = Ferri | first8 = S. | last9 = Cassani | first9 = F. | title = The serological profile of the autoimmune hepatitis/primary biliary cirrhosis overlap syndrome. | journal = Am J Gastroenterol | volume = 104 | issue = 6 | pages = 1420-5 | month = Jun | year = 2009 | doi = 10.1038/ajg.2009.126 | PMID = 19491855 }}</ref>
*AMA +ve.
*Anti-dsDNA +ve.

===Microscopic===
:See: ''[[autoimmune hepatitis]]'' and ''[[primary biliary cirrhosis]]''.
A. [[File:1 AIH PBC 1 680x512px.tif|Expanded portal tracts with fuzzy edges (40X).]]
 
B. [[File:2 AIH PBC 1 680x512px.tif|Interface hepatitis with plasma cells (400X).]]
 
C. [[File:3 AIH PBC 1 680x512px.tif|Loose granuloma (400X).]]
 
D. [[File:4 AIH PBC 1 680x512px.tif|Damaged bile duct (400X).]]
 
AIH/PBC overlap. AMA & ANA positive with Alkaline phosphatase > 2 upper limit of normal & one ALT > 5 times upper limit of normal. A. Expanded portal tracts with fuzzy edges. B. Interface hepatitis with plasma cells. C. Loose granuloma. D. Damaged bile duct.

==Primary sclerosing cholangitis==
*Abbreviated ''PSC''.
{{Main|Primary sclerosing cholangitis}}

=Hereditary=
==Caroli disease==
===General===
*Genetic disease.
**Frequently associated with [[autosomal recessive polycystic kidney disease]] (ARPKD).<ref name=omim263200>{{OMIM|263200}}</ref>
**May be seen in isolation.<ref name=omim600643>{{OMIM|600643}}</ref>

Clinical:<ref name=pmid17461493>{{Cite journal | last1 = Yonem | first1 = O. | last2 = Bayraktar | first2 = Y. | title = Clinical characteristics of Caroli's syndrome. | journal = World J Gastroenterol | volume = 13 | issue = 13 | pages = 1934-7 | month = Apr | year = 2007 | doi = | PMID = 17461493 }}</ref>
*Recurrent [[cholangitis]].
*Recurrent [[cholelithiasis]].
*[[Cholangiocarcinoma]]<ref name=pmid17461492>{{Cite journal | last1 = Yonem | first1 = O. | last2 = Bayraktar | first2 = Y. | title = Clinical characteristics of Caroli's disease. | journal = World J Gastroenterol | volume = 13 | issue = 13 | pages = 1930-3 | month = Apr | year = 2007 | doi = | PMID = 17461492 }}</ref> - seen in ~7% of cases.<ref name=pmid15347876>{{Cite journal | last1 = Karim | first1 = AS. | title = Caroli's disease. | journal = Indian Pediatr | volume = 41 | issue = 8 | pages = 848-50 | month = Aug | year = 2004 | doi = | PMID = 15347876 }}</ref>

Note:
*''Caroli syndrome'' = Caroli disease + congenital hepatic fibrosis.<ref name=pmid15888616>{{Cite journal | last1 = Brancatelli | first1 = G. | last2 = Federle | first2 = MP. | last3 = Vilgrain | first3 = V. | last4 = Vullierme | first4 = MP. | last5 = Marin | first5 = D. | last6 = Lagalla | first6 = R. | title = Fibropolycystic liver disease: CT and MR imaging findings. | journal = Radiographics | volume = 25 | issue = 3 | pages = 659-70 | month = | year = | doi = 10.1148/rg.253045114 | PMID = 15888616 | URL = http://radiographics.rsna.org/content/25/3/659.long }}</ref>

===Gross===
*Dilated bile ducts.<ref name=omim263200/>

===Microscopic===
Features:<ref name=pmid17461493/>
*Dilated bile ducts.
*Periductal fibrosis. (???)
*+/-Fibrosis.

Image:
*[http://www.meddean.luc.edu/lumen/MedEd/orfpath/11-3-10.jpg Caroli disease (meddean.luc.edu)].<ref>URL: [http://www.meddean.luc.edu/lumen/MedEd/orfpath/develop.htm http://www.meddean.luc.edu/lumen/MedEd/orfpath/develop.htm]. Accessed on: 1 December 2011.</ref>

==Hereditary hemochromatosis==
:''For secondary causes see [[secondary hemochromatosis]]''.
{{Main|Hereditary hemochromatosis}}

==Wilson disease==
{{Main|Wilson's disease}}

==Alpha-1 antitrypsin deficiency==
*[[AKA]] ''alpha1-antiprotease inhibitor deficiency''.
{{Main|Alpha-1 antitrypsin deficiency }}

=Other=
==Primary Systemic Sclerosis==
[[File:5 05168051 sl 1.png |Primary systemic sclerosis in the liver]]
[[File:5 05168051 sl 2.png |Primary systemic sclerosis in the liver]]
[[File:5 05168051 sl 3.png |Primary systemic sclerosis in the liver]]
[[File:5 05168051 sl 4.png |Primary systemic sclerosis in the liver]]
[[File:5 05168051 sl 5.png |Primary systemic sclerosis in the liver]]
[[File:5 05168051 sl 6.png |Primary systemic sclerosis in the liver]]
 
Primary systemic sclerosis in a 67 year old White, non-Hispanic man who had undergone renal transplantation for idiopathic nodular glomerusclerosis, which had recurred in 2013. He had been scheduled to receive a second transplantation, but had not yet received one. The patient had a positive anti-nuclear antigen study, with a positive scleroderma antibody (SCL-70), a high SCL-70 antibody index of 3.9, and negative DNA, Chromatin, Anti-Riboscomal P, SS-A, SS-B, anti Smith, RNP, JO-1, anticentromere antibody and rheumatoid factor serologic studies. Hepatitis A, B, and C serologic studies were negative. Liver function tests showed normal albumin and total bilirubin levels with alkaline phosphatase of 712 IU/L (35-129 normal range), alanine aminotransferase 59 IU/L (5-41 normal range), and aspartate aminotransferase 68 IU/L (5-37 normal range). This case provisions many of the features known to be present in primary systemic sclerosis as seen in the skin. A. At low power, triads appear almost as white ghosts against a relatively normal set of hepatocyte lobules. B. Closer examination reveals some triads to be expanded, with peripheral bile ductular proliferation and modest associated chronic inflammation without interface hepatitis. C. Portal arterioles had thick walls; inflammation included lymphocytes and occasional plasma cells. D. Trichrome failed to stain the material in the triads blue, but did show space of Disse collagenization. E. PAS with diastase showed positive staining of the material with emphasis on the arteriole walls. F. Hemosiderosis was seen on iron stain.

==Budd-Chiari syndrome==
*[[AKA]] ''hepatic vein obstruction''.
===General===
*Hepatic outflow obstruction.

Clinical triad:<ref name=pmid21573256>{{Cite journal | last1 = Fox | first1 = MA. | last2 = Fox | first2 = JA. | last3 = Davies | first3 = MH. | title = Budd-Chiari syndrome--a review of the diagnosis and management. | journal = Acute Med | volume = 10 | issue = 1 | pages = 5-9 | month = | year = 2011 | doi = | PMID = 21573256 }}</ref>
*Ascites.
*Abdominal pain.
*Hepatomegaly.

Etiology:
*~50% have a [[myeloproliferative disease]].<ref name=pmid18814079>{{Cite journal | last1 = Plessier | first1 = A. | last2 = Valla | first2 = DC. | title = Budd-Chiari syndrome. | journal = Semin Liver Dis | volume = 28 | issue = 3 | pages = 259-69 | month = Aug | year = 2008 | doi = 10.1055/s-0028-1085094 | PMID = 18814079 }}</ref>
*May be due to mass effect from a tumour.

Clinical DDx:
*[[Hepatic veno-occlusive disease]].

===Microscopic===
Features:<ref name=pmid17569137>{{Cite journal | last1 = Aydinli | first1 = M. | last2 = Bayraktar | first2 = Y. | title = Budd-Chiari syndrome: etiology, pathogenesis and diagnosis. | journal = World J Gastroenterol | volume = 13 | issue = 19 | pages = 2693-6 | month = May | year = 2007 | doi = | PMID = 17569137 | url=http://www.wjgnet.com/1007-9327/full/v13/i19/2693.htm }}</ref>
*Sinusoidal dilation in zone III (congestion).
*+/-Hepatocyte drop-out.
*+/-Centrilobular fibrosis.

DDx congestion:
*Congestive heart failure ([[congestive hepatopathy]]).
*Constrictive pericarditis.

==Vanishing bile duct syndrome==
*[[AKA]] ''bile duct loss'', [[AKA]] ''ductopenia''.<ref name=pmid11521176/>
===General===
*Fatal.

DDx:<ref name=pmid18242505/>
*[[Primary biliary cirrhosis]].
*[[Primary sclerosing cholangitis]].
*[[GVHD]].<ref name=pmid7994249>{{Cite journal | last1 = Yeh | first1 = KH. | last2 = Hsieh | first2 = HC. | last3 = Tang | first3 = JL. | last4 = Lin | first4 = MT. | last5 = Yang | first5 = CH. | last6 = Chen | first6 = YC. | title = Severe isolated acute hepatic graft-versus-host disease with vanishing bile duct syndrome. | journal = Bone Marrow Transplant | volume = 14 | issue = 2 | pages = 319-21 | month = Aug | year = 1994 | doi = | PMID = 7994249 }}</ref>
*[[Drug-induced liver disease|Drugs]].<ref name=pmid11352118>{{Cite journal | last1 = Chitturi | first1 = S. | last2 = Farrell | first2 = GC. | title = Drug-induced cholestasis. | journal = Semin Gastrointest Dis | volume = 12 | issue = 2 | pages = 113-24 | month = Apr | year = 2001 | doi = | PMID = 11352118 }}</ref>
*Chronic rejection.<ref name=pmid11521176>{{Cite journal | last1 = Inomata | first1 = Y. | last2 = Tanaka | first2 = K. | title = Pathogenesis and treatment of bile duct loss after liver transplantation. | journal = J Hepatobiliary Pancreat Surg | volume = 8 | issue = 4 | pages = 316-22 | month = | year = 2001 | doi = 10.1007/s0053410080316 | PMID = 11521176 }}</ref>

===Microscopic===
Features:<ref name=pmid18242505>{{Cite journal | last1 = Reau | first1 = NS. | last2 = Jensen | first2 = DM. | title = Vanishing bile duct syndrome. | journal = Clin Liver Dis | volume = 12 | issue = 1 | pages = 203-17, x | month = Feb | year = 2008 | doi = 10.1016/j.cld.2007.11.007 | PMID = 18242505 }}</ref>
*Loss of intrahepatitic bile ducts - '''key feature'''.
*Cholestasis.

Note:
*May occur without fibrosis and inflammation; thus, can be easy to miss.

===IHC===
*[[CK7]] -ve.
**Marks bile ducts.

==Extrahepatic biliary obstruction==
A. [[File:1 OBS 3 680x512px.tif|Sinusoidal dilatation, circular spaces of hepatocytes, small portal triads(40X).]]
 
B. [[File:2 OBS 3 680x512px.tif|Bile in hepatocytes about central vein & in plugs in canaliculi [yellow arrowhead] (400X).]]
 
C. [[File:3 OBS 3 680x512px.tif|Trichrome shows fibrosis about central vein (400X).]]
 
D. [[File:4 OBS 3 680x512px.tif|PAS with diastase shows portal triads with mild edema and chronic inflammation, without tortuous bile duct (400X).]]
 
Early extrahepatic biliary obstruction, demonstrated radiographically, transient, with rise in bilirubin, alkaline phosphatase, and transaminases. Pure canalicular cholestasis near terminal hepatic venules also seen in acute hepatitis, drug reactions, benign recurrent cholestasis, pregnancy, sepsis, & lymphomas. A. Sinusoidal dilatation, circular spaces of hepatocytes, small portal triads. B. Bile in hepatocytes about central vein & in plugs in canaliculi [yellow arrowhead]. C. Trichrome shows fibrosis about central vein. D. PAS with diastase shows portal triads with mild edema and chronic inflammation, without tortuous bile duct.
 
A. [[File:1 OBS 2 680x512px.tif|Expanded inflamed portal triads, swollen hepatocytes (40X)]]
 
B. [[File:2 OBS 2 680x512px.tif|Edematous stroma, proliferating ductules [yellow arrowheads], PAS-D macrophages [red arrowhead] (PAS with diastasse, 200X)]]
 
C. [[File:3 OBS 2 680x512px.tif|Disordered, often swollen hepatocytes,some with feathery degeneration (net like spaces in cytoplasm [blue arrowhead], rare Councilman body [green arrowhead] (400X)]]
 
D. [[File:4 OBS 2 1360x1024px.tif|Bile in hepatocytes [cyan arrrowhead] & in canaliculi [purple arrowheads]. Empty acinar spaces bounded by hepatocytes [orange arrowhead] (400X, higher pixel),]]
 
Changes of extrahepatic biliary obstruction, months duration. A. Expanded inflamed portal triads, swollen hepatocytes. B. Edematous stroma, proliferating ductules [yellow arrowheads], PAS-D macrophages [red arrowhead]. C. Disordered, often swollen hepatocytes,some with feathery degeneration (net like spaces in cytoplasm) [blue arrowhead], rare Councilman body [green arrowhead]. D. Bile in hepatocytes [cyan arrrowhead] & in canaliculi [purple arrowheads]. Empty acinar spaces bounded by hepatocytes [orange arrowhead].
 
A. [[File:1 Bd obs 4 680x512px.tif|Expanded, light colored portal triads (arrows)(20X).]]
 
B. [[File:2 Bd obs 4 680x512px.tif|Proliferating bile ductules (cyan arrows) with neutrophils (yellow arrows), not specific for acute cholangitis, of assistance with large bile duct obstruction (400X)..]]
 
C. [[File:3 Bd obs 4 680x512px.tif|Uninflamed interlobular duct (yellow arrow) with, accompanying blood vessel (red arrow) (400X)]]
 
D. [[File:4 Bd obs 4 680x512px.tif|Bile infarct with pyknotic nuclei (arrows)(400X).]]
 
E. [[File:5 Bd obs 4 680x512px.tif|Bile (arrow) in interlobular bile duct with disordered nuclei (400X).]]
 
F. [[File:6 Bd obs 4 680x512px.tif|Bile plugs in cannaliculi (red arrows), feathery degeneration producing foamy macrophage like hepatocytes (yellow arrows)(400X).]]
 
Large bile duct obstruction. A. Expanded, light colored portal triads (arrows). B. Proliferating bile ductules (cyan arrows) with neutrophils (yellow arrows), not specific for acute cholangitis, of assistance with large bile duct obstruction. C. Uninflamed interlobular duct (yellow arrow) with, accompanying blood vessel (red arrow). D. Bile infarct with pyknotic nuclei (arrows). E. Bile (arrow) in interlobular bile duct with disordered nuclei. F. Bile plugs in cannaliculi (red arrows), feathery degeneration producing foamy macrophage-like hepatocytes (yellow arrows).

==Congestive hepatopathy==
===General===
*Liver failure due to (right) heart failure.
*AKA ''cardiac cirrhosis'' - a term used by clinicians.
**Generally, it does not satisfy pathologic criteria for cirrhosis.<ref>URL: [http://emedicine.medscape.com/article/151792-overview http://emedicine.medscape.com/article/151792-overview]. Accessed on: 17 June 2010.</ref>

===Gross===
*"Nutmeg" liver - yellow spotted appearance.

===Microscopic===
Features:<ref>URL: [http://emedicine.medscape.com/article/151792-diagnosis http://emedicine.medscape.com/article/151792-diagnosis]. Accessed on: 17 June 2010.</ref>
*Zone III atrophy.
*Portal venule (central vein) distension.
*Perisinusoidal fibrosis - progresses to centrilobular fibrosis and then diffuse fibrosis.
*Dilation of sinusoids in ''all'' zone III areas - '''key feature'''.<ref>Suggested by OA. September 2009.</ref>

DDx:
*[[Hemangioma of the liver]] - should be focal lesion.
Cardiac (congestive) hepatopathy, wherein outflow obstruction occurs secondary to backflow from a failing heart, and Budd Chiari syndrome, wherein obstruction of outflow occurs secondary to obstruction, usually thrombotic, have overlapping features, including sinusoidal dilation with emphasis upon the central vein, space of Disse erythrocytes, centrilobular inflammation, hemorrhage, bile ductules, and hemosiderin, and portal inflammation, fibrosis and bile ductular reaction. Centrilobular dropout/necrosis is more common in Budd Chiari syndrome, while peri-central venous and sinusoidal fibrosis are more common in cardiac hepatopathy. In end stage liver, fibrosis for cardiac hepatopathy comprises stellate centrizonal fibrous with haphazard spread, as opposed to the more frequent nodular cirrhosis in Budd-Chiari. Clinical findings are important to take into account, as cardiac failure is usually well known at the time of diagnosis as are the clinical predictors of Budd Chiari syndrome, prothrombotic states, myeloproliferative diseases, and oral contraceptive use. <ref name=pmid27681331 >{{cite journal |author=Gonzalez RS, Gilger MA, Huh WJ, Washington MK |title=The spectrum of histologic findings in hepatic outflow obstruction |journal= Arch Pathol Lab Med |volume=141 |issue= |pages=98 |year=2017 |pmid= 27681331 ||doi= 10.5858/arpa.2015-0388-OA |url=http http://www.archivesofpathology.org/doi/10.5858/arpa.2015-0388-OA?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%3dpubmed&code=coap-site }}</ref>
====Images====
<gallery>
Image:Congestive_hepatopathy_high_mag.jpg | Mild congestive hepatopathy. (WC) 
A.[[File:1 CEN NEC 1 680x512px.tif|PAS without diastase shows ovoids of necrosis {40X).]] 
B. [[File:2 CEN NEC 1 680x512px.tif|Necrosis with central vein [yellow arrowhead], inflammatory cells, residual Councilman body [green arrowhead], and hepatocyte with mitotic figure [red arrowhead] (400X).]]
 
C. [[File:3 CEN NEC 1 680x512px.tif|Trichrome highlights fibrosis about central vein [yellow arrowhead] & shows beginning scar formation [green arrowheads]. Note residual atrophic hepatocytes [blue arrowheads] (400X).]]
 
D. [[File:4 CEN NEC 1 680x512px.tif|Portal triads are largely unaffected (400X).]]
|} 
Centrilobular necrosis (seen in circulatory failure and with toxins/drugs). A. PAS without diastase shows ovoids of necrosis. B. Necrosis with central vein [yellow arrowhead], inflammatory cells, residual Councilman body [green arrowhead], and hepatocyte with mitotic figure [red arrowhead]. C. Trichrome highlights fibrosis about central vein [yellow arrowhead] & shows beginning scar formation [green arrowheads]. Note residual atrophic hepatocytes [blue arrowheads]. D. Portal triads are largely unaffected (LR 400X)
 
A. [[File:1 CHF 1 680x512px.tif|Dilated and undilated sinusoidal regions (40X).]]
 
B. [[File:2 CHF 1 680x512px.tif|Thrombi in sinusoids; glycogenated nuclei likely reflect patient’s diabetes mellitus (400X).]]
 
C. [[File:3 CHF 1 680x512px.tif|Dilated portal vein (400X).]]
 
D. [[File:4 CHF 1 680x512px.tif|Reticulin shows collapse (thick black lines) as well as a dilated portal vein (200X).]]
 
E. [[File:5 CHF 1 680x512px.tif|Trichrome shows space of Disse collagenization (pericellular fibrosis) (200X).]]
 
F. [[File:6 CHF 1 680x512px.tif|Trichrome shows periportal fibrosis; no bridging was seen (200X).]]

Patient with congestive heart failure and stage I fibrosis. A. Dilated and undilated sinusoidal regions. B. Thrombi in sinusoids; glycogenated nuclei likely reflect patient’s diabetes mellitus. C. Dilated portal vein. D. Reticulin shows black lines of bridging, too thick for collapse. E. Trichrome shows space of Disse collagenization (pericellular fibrosis). F. Trichrome shows bridge beginning off to right; when it is more than a mere spike, it is a bridge.

==Drug-induced liver disease==
*[[AKA]] ''drug-induced liver toxicity''.
{{Main|Drug-induced liver disease}}

==Focal nodular hyperplasia==
*Abbreviated ''FNH''.
{{Main|Focal nodular hyperplasia}}

==Nodular regenerative hyperplasia==
===General===
*Associated with renal transplants, [[bone marrow transplant]]s and [[vasculitides]].<ref name=Ref_PBoD922>{{Ref PBoD|922}}</ref>
*Can lead to [[portal hypertension]] and many of the associated complications.<ref name=pmid22554152>{{Cite journal | last1 = Bissonnette | first1 = J. | last2 = Généreux | first2 = A. | last3 = Côté | first3 = J. | last4 = Nguyen | first4 = B. | last5 = Perreault | first5 = P. | last6 = Bouchard | first6 = L. | last7 = Pomier-Layrargues | first7 = G. | title = Hepatic hemodynamics in 24 patients with nodular regenerative hyperplasia and symptomatic portal hypertension. | journal = J Gastroenterol Hepatol | volume = 27 | issue = 8 | pages = 1336-40 | month = Aug | year = 2012 | doi = 10.1111/j.1440-1746.2012.07168.x | PMID = 22554152 }}
</ref>

====Etiology====
*Arterial hypervascularity secondary to loss of hepatic vein radicles (loss of central venule in hepatic lobule).<ref name=Ref_PBoD922>{{Ref PBoD|922}}</ref>

ASIDE: radicle = ramulus - smallest branch or vessel or nerve.<ref name=Dorlands2>Dorland's Medical Dictionary. 30th Ed.</ref>

===Gross===
*Diffuse nodularity - whole liver.

===Microscopic===
Features:<ref name=Ref_PBoD922>{{Ref PBoD|922}}</ref>
*"Plump" hepatocytes surrounded by atrophic ones.
*No fibrosis.

==Sinuosoidal obstruction syndrome==
*May be referred to as ''Hepatic veno-occlusive disease''.<ref name=pmid11928077>{{Cite journal | last1 = DeLeve | first1 = LD. | last2 = Shulman | first2 = HM. | last3 = McDonald | first3 = GB. | title = Toxic injury to hepatic sinusoids: sinusoidal obstruction syndrome (veno-occlusive disease). | journal = Semin Liver Dis | volume = 22 | issue = 1 | pages = 27-42 | month = Feb | year = 2002 | doi = 10.1055/s-2002-23204 | PMID = 11928077 }}.</ref>
===General===
*Term for obstruction due to toxicity from a chemotherapeutic agent.<ref name=pmid16393276>{{Cite journal | last1 = Helmy | first1 = A. | title = Review article: updates in the pathogenesis and therapy of hepatic sinusoidal obstruction syndrome. | journal = Aliment Pharmacol Ther | volume = 23 | issue = 1 | pages = 11-25 | month = Jan | year = 2006 | doi = 10.1111/j.1365-2036.2006.02742.x | PMID = 16393276 }}</ref><ref name=pmid17569137>{{Cite journal | last1 = Aydinli | first1 = M. | last2 = Bayraktar | first2 = Y. | title = Budd-Chiari syndrome: etiology, pathogenesis and diagnosis. | journal = World J Gastroenterol | volume = 13 | issue = 19 | pages = 2693-6 | month = May | year = 2007 | doi = | PMID = 17569137 | url=http://www.wjgnet.com/1007-9327/full/v13/i19/2693.htm }}</ref>

Clinical DDx:
*[[Budd-Chiari syndrome]].

===Microscopic===
Features:<ref name=pmid17569137>{{Cite journal | last1 = Aydinli | first1 = M. | last2 = Bayraktar | first2 = Y. | title = Budd-Chiari syndrome: etiology, pathogenesis and diagnosis. | journal = World J Gastroenterol | volume = 13 | issue = 19 | pages = 2693-6 | month = May | year = 2007 | doi = | PMID = 17569137 | url=http://www.wjgnet.com/1007-9327/full/v13/i19/2693.htm }}</ref>
*Subendothelial swelling in hepatic venules.

Negatives:
*No thrombosis.

==Ascending Cholangitis (Acute Cholangitis)==
===General===
*Term for infection of bile ducts, usually due to obstruction

Clinical DDx:

===Microscopic===
====Images====

A. [[File:1 asc chol 1 680x512px.tif|Rounded, clear (edematous) portal tracts (arrows) separated by hepatocytes with dilated sinusoids (Row 1 Left 40X).]]
 
B. [[File:2 asc chol 1 680x512px.tif|Neutrophils about hepatocytes (arrows) have spilled into the lobule from a portal tract (Row 1 Right 200X).]]
 
C. [[File:3 asc chol 1 680x512px.tif|Proliferated bile ductules (arrows) bearing neutrophils within epithelium and lumens are features of obstruction that should prompt a search for interlobular ducts with acute inflammation (Row 2 Left 400X).]]
 
D. [[File:4 asc chol 1 680x512px.tif|The epithelium of the ducts can be severely degenerated. Neutrophils (cyan arrows) invade epithelium of an interlobular duct that are recognizable mainly as a circle of rounded nuclei; the associated arteriole (red arrow) should be identified to ensure an interlobular duct is being evaluated. Note the proliferated bile ductules (blue arrows) (Row 2 Right 400X).]]
 
E. [[File:5 asc chol 1 680x512px.tif|A PAS without diastase stain colors the arteriole (blue arrow), as well as the rim of the interlobular duct within which lies a neutrophil (cyan arrow) (Row 2 Right 400X). .]]
 
F. [[File:6 asc chol 1 680x512px.tif|A PAS with diastase stain colors the arteriole (red arrow), as well as the rim of the interlobular duct within which lies a neutrophil (cyan arrow) (Row 1 Right 400X)]]
 
Acute cholangitis in a patient with multiple bile duct procedures. After the biopsy, removal of bile duct stones released pus. A. Rounded, clear (edematous) portal tracts (arrows) separated by hepatocytes with dilated sinusoids. B. Neutrophils about hepatocytes (arrows) have spilled into the lobule from a portal tract. C, Proliferated bile ductules (arrows) bearing neutrophils within epithelium and lumens are features of obstruction that should prompt a search for interlobular ducts with acute inflammation. D. The epithelium of the ducts can be severely degenerated. Neutrophils (cyan arrows) invade epithelium of an interlobular duct that are recognizable mainly as a circle of rounded nuclei; the associated arteriole (red arrow) should be identified to ensure an interlobular duct is being evaluated. Note the proliferated bile ductules (blue arrows). E. A PAS without diastase stain colors the arteriole (blue arrow), as well as the rim of the interlobular duct within which lies a neutrophil (cyan arrow). F. A PAS with diastase stain colors the arteriole (red arrow), as well as the rim of the interlobular duct within which lies a neutrophil (cyan arrow).

A.[[File:1 Sep Acu Cho 1 680x512px.tif|Low power shows variably sized inflamed portal tracts (40X)]]
 
B. [[File:2 Sep Acu Cho 1 680x512px.tif|Trichrome shows dilated sinusoids and space of Disse collagenization (200X)]]
 
C. [[File:3 Sep Acu Cho 1 680x512px.tif|Inflammatory focus with macrophages and neutrophils (400X).]]
 
D. [[File:4 Sep Acu Cho 1 680x512px.tif|PAS with diastase shows proliferated bile ductules at edge of triad with neutrophils, which should not be used to make a definite diagnosis of acute cholangitis (400X).]]
 
E. [[File:5 Sep Acu Cho 1 680x512px.tif|PAS without diastase showing acutely inflamed bile duct, with accompanying blood vessel of similar size, diagnostic of acute cholangitis (400X).]]
 
F. [[File:6 Sep Acu Cho 1 680x512px.tif|PAS with diastase showing neutrophil in bille duct lumen, diagnostic of acute cholangitis (400X).]]
 
Patient with sepsis and acute cholangitis. A. Low power shows variably sized inflamed portal tracts. B. Trichrome shows dilated sinusoids and space of Disse collagenization. C. Inflammatory focus with macrophages and neutrophils. D. PAS with diastase shows proliferated bile ductules at edge of triad with neutrophils, which should not be used to make a definite diagnosis of acute cholangitis. E. PAS without diastase showing acutely inflamed bile duct, with accompanying blood vessel of similar size, diagnostic of acute cholangitis. F. PAS with diastase showing neutrophil in bille duct lumen, diagnostic of acute cholangitis.

==Polycystic kidney disease and the liver==
{{Main|Cystic kidney disease}}
===General===
Complications of PKD in the liver:<ref>{{Ref MacSween|174-5}}</ref>
#Infected cyst.
#Cholangiocarcinoma.
#Cholestasis/obstruction due to duct compression.<ref>URL: [http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=9184868 http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=9184868]. Accessed on: 23 September 2009.</ref>

Cysts:
*Cysts in the liver, like the kidney, are thought to enlarge with age.

===Microscopic===
Features:<ref>{{Ref MacSween|176}}</ref>
*''Von Meyenburg complexes'' ([[bile duct hamartoma]]):
**Cluster of dilated ducts with "altered" bile.
**Surrounded by collagenous stroma.
**Separate from the portal areas.<ref>Meyenburg complex. Stedman's Medical Dictionary. 27th Ed.</reF>

Images:
*[http://commons.wikimedia.org/wiki/File:Von_Meyenburg_complex_low_mag.jpg Von Meyenburg complex - bile duct hamartoma (WC)].
*[http://commons.wikimedia.org/wiki/File:Bile_duct_hamartoma_intermed_mag.jpg Bile duct hamartoma (WC)].

Notes:
*Appearance on ultrasound<ref name=pmid17287178>Bile duct hamartomas--the von Meyenburg complex. Salles VJ, Marotta A, Netto JM, Speranzini MB, Martins MR. Hepatobiliary Pancreat Dis Int. 2007 Feb;6(1):108-9. PMID 17287178.</ref> and CT (hypodense)<ref name=pmid19294869>[The von Meyenburg complex] Schwab SA, Bautz W, Uder M, Kuefner MA. Rontgenpraxis. 2008;56(6):241-4. German. PMID 19294869.</ref> - similar to metastases.

==Peliosis hepatis==
===General===
*Associated with:
**Infections.
**Malignancy.
**Other stuff.
*Rarely biopsied.

===Microscopic===
Features:
*Cyst lined by endothelium.
**Usu. incomplete.
*Blood.
A. [[File:1 PEL 1 680x512px.tif|Hemorrhage at left end, dilated sinusoids elsewhere (20X).]]
 
B. [[File:2 PEL 1 680x512px.tif|Ramifying dilated sinusoidal spaces (100X).]]
 
C. [[File:3 PEL 1 680x512px.tif|PAS with diastase shows flat lining (400X).]]
 
D. [[File:4 PEL 1 680x512px.tif|Necrotic hepatocytes in cords, presumably due to pressure (400X).]]
 
Peliosis hepatis. A. Hemorrhage at left end, dilated sinusoids elsewhere. B. Ramifying dilated sinusoidal spaces. C. PAS with diastase shows flat lining. D. Necrotic hepatocytes in cords, presumably due to pressure.

==Total parenteral nutrition==
*Abbreviated ''TPN''.

===General===
*Indication: short gut syndrome, others.

===Microscopic===
Variable - may range from: steatosis, steatohepatitis, cholestasis, fibrosis and cirrhosis.<ref name=pmid16766237>{{cite journal |author=Guglielmi FW, Boggio-Bertinet D, Federico A, ''et al.'' |title=Total parenteral nutrition-related gastroenterological complications |journal=Dig Liver Dis |volume=38 |issue=9 |pages=623–42 |year=2006 |month=September |pmid=16766237 |doi=10.1016/j.dld.2006.04.002 |url=}}</ref>

Features (classic):<ref>{{Cite journal | last1 = Li | first1 = SJ. | last2 = Nussbaum | first2 = MS. | last3 = McFadden | first3 = DW. | last4 = Gapen | first4 = CL. | last5 = Dayal | first5 = R. | last6 = Fischer | first6 = JE. | title = Addition of glucagon to total parenteral nutrition (TPN) prevents hepatic steatosis in rats. | journal = Surgery | volume = 104 | issue = 2 | pages = 350-7 | month = Aug | year = 1988 | doi = | PMID = 3135627 }}</ref><ref>{{Cite journal | last1 = Stanko | first1 = RT. | last2 = Nathan | first2 = G. | last3 = Mendelow | first3 = H. | last4 = Adibi | first4 = SA. | title = Development of hepatic cholestasis and fibrosis in patients with massive loss of intestine supported by prolonged parenteral nutrition. | journal = Gastroenterology | volume = 92 | issue = 1 | pages = 197-202 | month = Jan | year = 1987 | doi = | PMID = 3096806 }}
</ref>
*[[Steatosis]] (periportal) - early.
*Cholestasis - late.

==Giant cell hepatitis==
*[[AKA]] ''neonatal giant cell hepatitis''.

:See: ''[[Giant cell hepatitis]]''.

==Hepatic amyloidosis==
{{Main|Amyloidosis}}
*[[AKA]] ''liver amyloidosis''.
*[[AKA]] ''amyloidosis of the liver''.
===General===
*Diffuse abundant amyloid within the space of Disse is associated with [[portal hypertension]].<ref name=pmid1864548>{{Cite journal | last1 = Bion | first1 = E. | last2 = Brenard | first2 = R. | last3 = Pariente | first3 = EA. | last4 = Lebrec | first4 = D. | last5 = Degott | first5 = C. | last6 = Maitre | first6 = F. | last7 = Benhamou | first7 = JP. | title = Sinusoidal portal hypertension in hepatic amyloidosis. | journal = Gut | volume = 32 | issue = 2 | pages = 227-30 | month = Feb | year = 1991 | doi = | PMID = 1864548 | PMC = 1378815 | URL = http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1378815/?tool=pubmed }}</ref>

===Microscopic===
Features:
*Amorphous extracellular pink stuff on H&E - see ''[[amyloid]]'' article.

DDx:
*[[Fibrolamellar hepatocellular carcinoma]].

====Images====
<gallery>
Image:Hepatic_amyloidosis_-_low_mag.jpg | Amyloidosis of the liver - low mag. (WC)
Image:Hepatic_amyloidosis_-_intermed_mag.jpg | Amyloidosis of the liver - intermed. mag. (WC)
Image:Hepatic_amyloidosis_-_high_mag.jpg | Amyloidosis of the liver - high mag. (WC)
Image:Hepatic_amyloidosis_-_very_high_mag.jpg | Amyloidosis of the liver - very high mag. (WC)
</gallery>
A. [[File:1 AMY 1 680x512px.tif|Amorphous material replaces hepatic parenchyma [4X]]]
 
B. [[File:2 AMY 1 680x512px.tif|Material barely stains blue on trichrome [10X]]]
 
C. [[File:3 AMY 1 680x512px.tif|Material stains red on unpolarized Congo Red [40X]]]
 
D. [[File:4 AMY 1 680x512px.tif|Material stains apple green on polarized Congo Red [40X]]]
 
Amyloidosis. A. Amorphous material replaces hepatic parenchyma. B. Material barely stains blue on trichrome. C. Material stains red on unpolarized Congo Red. D. Material stains apple green on polarized Congo Red.

===Stains===
*[[Congo red]] +ve.

==Fulminant hepatic necrosis==
===General===
Etiology:
*Viral, i.e. [[Hepatitis A]], [[Hepatitis B]]; [[Hepatitis C]] - extremely rare.
*Trauma.
*Shock.

===Microscopic===

A. [[File:1 Necrosis 2 680x512px.tif| Submassive hepatic necrosis.]]
 
B. [[File:2 Necrosis 2 680x512px.tif| Submassive hepatic necrosis.]]
 
C. [[File:3 Necrosis 2 680x512px.tif| Submassive hepatic necrosis.]]
 
D. [[File:4 Necrosis 2 680x512px.tif| Submassive hepatic necrosis.]]
 
E. [[File:5 Necrosis 2 680x512px.tif| Submassive hepatic necrosis.]]
 
F. [[File:6 Necrosis 2 680x512px.tif| Submassive hepatic necrosis.]]
 
Submassive hepatic necrosis. Patient had transaminases in the thousands that rapidly dropped to normal. A/ Pink preserved parenchyma strews empty necrotic spaces. B. Focus of necrosis with no apparent hepatocytes macrophages abuts apparently normal liver. C. Iron stain shows the macrophages bear hemosiderin. D. Reticulin stain highlights the recently dead liver cells. E. Reticulin stain shows a necrotic bridge forming; the multiple small black circles preclude diagnosis of a fibrous bridge. F. Trichrome shows the necrotic bridge (“collapse”) lacks much collagen deposition, as would be expected for bridging fibrosis.

Features:
*Hepatocyte [[necrosis]].
*Bile duct proliferation.

DDx:
*[[Cholangiocarcinoma]].
*[[Angiosarcoma]].

==Secondary hemochromatosis==
:''For the hereditary one see [[hereditary hemochromatosis]]''.
===General===
*Iron overload secondary to blood transfusions for hereditary or acquired anemia.<ref name=pmid19727383/>
**Primary hemochromatosis due to a defect in iron processing - called ''[[hereditary hemochromatosis]]''.
*Imaging considered the best test, as iron deposition is patchy.<ref name=pmid19727383/>

Selected hereditary causes:<ref name=pmid19727383>{{Cite journal | last1 = Gattermann | first1 = N. | title = The treatment of secondary hemochromatosis. | journal = Dtsch Arztebl Int | volume = 106 | issue = 30 | pages = 499-504, I | month = Jul | year = 2009 | doi = 10.3238/arztebl.2009.0499 | PMID = 19727383 | PMC = 2735704 | URL = http://www.ncbi.nlm.nih.gov.myaccess.library.utoronto.ca/pmc/articles/PMC2735704/?tool=pubmed}}</ref>
*Thalassemia.
*[[Sickle cell anemia]].
*Hereditary sideroblastic anemia.

Selected acquired causes:<ref name=pmid19727383/>
*[[Myelodysplastic syndromes]]
*Myelofibrosis
*Aplastic anemia, intractable.

===Microscopic===
:See ''[[hereditary hemochromatosis]]''.

==Hepatic sarcoidosis==
{{Main|Hepatic sarcoidosis}}
==Overlapping Disorders==

[[File:1 Mixed Disorder 1 680x512px.tif|Changes of steatohepatitis and interface hepatitis, with granuloma. Patient with diabetes was ANA, AMA, HCV, HBV negative, without drugs known to produce granulomas or interface hepatitis. This may be a case of AMA negative primary biliary cirrhosis, but studies to determine that with certainty were not performed.]]
[[File:2 Mixed Disorder 1 680x512px.tif|Changes of steatohepatitis and interface hepatitis, with granuloma. Patient with diabetes was ANA, AMA, HCV, HBV negative, without drugs known to produce granulomas or interface hepatitis. This may be a case of AMA negative primary biliary cirrhosis, but studies to determine that with certainty were not performed.]]
[[File:3 Mixed Disorder 1 680x512px.tif|Changes of steatohepatitis and interface hepatitis, with granuloma. Patient with diabetes was ANA, AMA, HCV, HBV negative, without drugs known to produce granulomas or interface hepatitis. This may be a case of AMA negative primary biliary cirrhosis, but studies to determine that with certainty were not performed.]]
[[File:4 Mixed Disorder 1 680x512px.tif|Changes of steatohepatitis and interface hepatitis, with granuloma. Patient with diabetes was ANA, AMA, HCV, HBV negative, without drugs known to produce granulomas or interface hepatitis. This may be a case of AMA negative primary biliary cirrhosis, but studies to determine that with certainty were not performed.]]
[[File:5 Mixed Disorder 1 680x512px.tif|Changes of steatohepatitis and interface hepatitis, with granuloma. Patient with diabetes was ANA, AMA, HCV, HBV negative, without drugs known to produce granulomas or interface hepatitis. This may be a case of AMA negative primary biliary cirrhosis, but studies to determine that with certainty were not performed.]]
[[File:6 Mixed Disorder 1 680x512px.tif|Changes of steatohepatitis and interface hepatitis, with granuloma. Patient with diabetes was ANA, AMA, HCV, HBV negative, without drugs known to produce granulomas or interface hepatitis. This may be a case of AMA negative primary biliary cirrhosis, but studies to determine that with certainty were not performed.]] 
Changes of steatohepatitis and interface hepatitis, with granuloma. Patient with diabetes was ANA, AMA, HCV, HBV negative, without drugs known to produce granulomas or interface hepatitis. This may be a case of AMA negative primary biliary cirrhosis, but studies to determine that with certainty were not performed. A. Low power shows hepatocytes afflicted by steatosis and an inflamed portal tract. B. In a region of fatty change lie cytoplasmic tufts of ballooning degeneration (green arrows) and a lipogranuloma (black arrow). C. At the portal-hepatocyte junction lies interface hepatitis (black arrows), as well as extension of inflammation into the lobule (green arrows). D. Red hepatocytes bounded by inflammation denote piecemeal necrosis [PAS without diastase]. E. Giant cells intermixed with lymphocytes prove a portal granuloma [PAS without diastase]. F. A blue fibrous bridge extends from a triad [Trichrome].

[[File:4 95599552608917 sl 1.png|Acute obstructive changes and changes of recurrent acute injury]]
[[File:4 95599552608917 sl 2.png|Acute obstructive changes and changes of recurrent acute injury]]
[[File:4 95599552608917 sl 3.png|Acute obstructive changes and changes of recurrent acute injury]]
[[File:4 95599552608917 sl 4.png|Acute obstructive changes and changes of recurrent acute injury]]
[[File:4 95599552608917 sl 5.png|Acute obstructive changes and changes of recurrent acute injury]]
[[File:4 95599552608917 sl 6.png|Acute obstructive changes and changes of recurrent acute injury]]
[[File:4 95599552608917 sl 7.png|Acute obstructive changes and changes of recurrent acute injury]] 
Acute obstructive changes and changes of recurrent injury in 46 yo man with Clostridium perfringens positive blood culture, an ERCP that showed duodenal compression by the pancreas with resultant bile duct dilatation. The patient had had and continued to have multiple bouts of acute pancreatitis. At the time of biopsy, decreased platelet count/hemoglobin/albumin, elevated lipase/amylase/PT/PTT, normal alkaline phosphatase, bilirubin, AST/ALT, AMA, hepatitis virus serology, ANA. A. Fragment biopsy shows inflamed triads and bridges. B. Trichrome shows bridges without nodules, evidence of prior injury; the patient subsequently developed multiple episodes of pancreatitis. C. Reticulin shows piecemeal necrosis, with black lines bounding individual hepatocytes at interface (arrows). D. Collapse is shown by closly approximated thick black lines; one cannot call portal-central collapse without seeing a central vein. Note on this and the other reticulin image that regeneration, two cell thick cords, is not prominent. E. PAS D of two portal triads, far nearer than normal, both expanded. Note increased number of ducts/ductules (red arrows), neutrophils, and PAS-D macrophages. F. PAS D shows collapse extending from a triad to a portion of a lobule with steatosis. No feathery degeneration or bile duct plugs were seen. Neither were foci of spotty necrosis or abscess seen. G. Other triads, again edematous, showed more of a chronic inflammatory response, with occasional plasma cells (black arrows). Also present are neutrophils (red arrows). The bile duct (grey arrow) near the artery (brown arrow) shows mildly disturbed nuclei. Note early proliferated bile ductules (cyan arrows).

[[File:6 17281676469188 sl 1.png| Hepatitis B virus with steatohepatitis]]
[[File:6 17281676469188 sl 2.png| Hepatitis B virus with steatohepatitis]]
[[File:6 17281676469188 sl 3.png| Hepatitis B virus with steatohepatitis]]
[[File:6 17281676469188 sl 4.png| Hepatitis B virus with steatohepatitis]]
[[File:6 17281676469188 sl 5.png| Hepatitis B virus with steatohepatitis]]
[[File:6 17281676469188 sl 6.png| Hepatitis B virus with steatohepatitis]] 
Hepatitis B virus with steatohepatitis in a 36 year old man with hepatitis B surface antigen and hepatitis Be antigen positivity, Hepatitis be QTPC of 1750 cop/mL, an occasionally mildly elevated (42) ALT, and normal glucose, alkaline phosphatase, bilirubin, and other transaminases. He had a history of alcohol abuse, which became controlled. A. Triads show scant inflammation without definite interface hepatitis. About one-fourth of the lobule, not pan-acinar, is afflicted by steatosis. B. Occasional tufts are seen (arrow), indicating focal ballooning sufficient for a diagnosis of steatohepatitis. C. Glycogenated nuclei (black arrows) and hepatocytes with feathery degeneration (red arrows) are seen. D. Very rare foci of spotty necrosis were seen. E. Apart from this triad and the one in the trichrome stain in F, which had moderate inflammation comprising lymphocytes and macrophages, all triads were small, most without any inflammation at all. Neither collapse nor piecemeal necrosis were seen on reticulin stain. F. Trichrome stain showed only portal fibrosis. The interhepatocyte fibrosis required for brunt fibrosis stage I was not seen. Hence, one would grade this as follows: A) Chronic hepatitis (history of hepatitis B), Metavir activity index 1, Piecemeal necrosis 0, Lobular necrosis 1, Metavir fibrosis stage 1, B) Steatohepaitits, Brunt necroinflammatory grade 1, Brunt fibrosis stage 0.

=See also=
*[[Pancreas]].
*[[Gastrointestinal pathology]].
*[[Liver neoplasms]].
*[[Liver]].

=References=
{{reflist|2}}

[[Category:Gastrointestinal pathology]]
[[Category:Liver pathology]]
[[Category:Medical liver disease]]

Dermatopathology

2017-02-24T20:31:19Z

Mitchell: /* Others */ added a case

'''Dermatopathology''' is the pathology of skin.

Pathology is a significant part of dermatology and dermatologists spend five years in residency. So, it is a huge area.

=Specimens=
*Shave biopsy = done for what is presumed to be benign disease - classically exophytic lesions, e.g. [[seborrheic keratosis]].
*Saucerization = scooped shave biopsy.<ref>{{Cite journal | last1 = Elston | first1 = D. | title = Practical advice regarding problematic pigmented lesions. | journal = J Am Acad Dermatol | volume = 67 | issue = 1 | pages = 148-55 | month = Jul | year = 2012 | doi = 10.1016/j.jaad.2012.04.006 | PMID = 22703907 }}
</ref>
*Punch biopsy = cylindrical piece of skin, usu. epidermis and dermis - suspicious lesions/malignant lesions, e.g. [[basal cell carcinoma]].
*Incisional biopsy = a piece of the lesion for pathologic assessment; lesion not completely removed.
*Excision = lesion cut-out with intent for complete removal - usual has a generous margin, e.g. [[malignant melanoma]] excision.
*Re-excision = done to get a wider margin ''or'' remove part of a lesion that was incompletely removed in a prior excision.
**Conservative re-excision = cut-out more with a minimal rim of normal tissue.<ref>URL: [http://www.nedermatology.com/skin-cancer-treatments.php http://www.nedermatology.com/skin-cancer-treatments.php]. Accessed on: 26 February 2013.</ref>
*[[Sentinel lymph node]] removal = a special type of lymphadenectomy usu. done for [[cancer staging|staging]], esp. [[malignant melanoma]].

=Histology=
==Layers of the skin==
[[Image:Skin.png|thumb|Schematic showing the layers and structures of skin. (WC/cancer.gov)]]
*Epidermis - outer most layer, avascular, separated from dermis by a basement membrane, epithelial tissue.
*Dermis - below the epidermis, vascular, separated from the epidermis by a basement membrane, connective tissue.

Note:
*The layer below the skin is the ''subdermis'' ([[AKA]] hypodermis, [[AKA]] subcutaneous tissue).
**It is below the dermis and consists of adipose tissue.<ref>URL: [http://histologyolm.stevegallik.org/node/119 http://histologyolm.stevegallik.org/node/119]. Accessed on: 5 November 2013.</ref>

Image:
*[http://histologyolm.stevegallik.org/node/119 Dermis and hypodermis (stevegallik.org)].

===Epidermis===
====Layers of the epidermis====
[[Image:Epidermal layers.png|thumb|right|Layers of the epidermis. (WC/Wbensmith)]]
Epidermis layers - from the surface to epidermal-dermal junction:
*Stratum corneum.
*Stratum lucidum.
**Present only in "thick" skin.<ref name=Ref_Derm1>{{Ref Derm|1}}</ref>
*Stratum granulosum.
*Stratum spinosum (aka prickle layer).
*Stratum basale (germinativum).
Mnemonic: ''Corn Lovers Grow Several Bales''.

====Cells of the epidermis====
*Keratinocytes.
**Usually eosinophilic cytoplasm - '''important feature'''.
**May have clear perinuclear halo (glycogenated keratinocytes).
**Intercellular bridges (high power) - '''key feature'''.
*Melanocytes.
**Usuallly basal location.
**Epithelioid or dentritic morphology.
**Pericellular clearing - '''key feature'''.
**Clear cytoplasm.
**+/-Pigmentation.
*Other:
**Toker cell.
**Neutrophils.
***Trilobated nuclei - 2-3 little dots - '''key feature'''.
**Lymphocytes.
***Small (round) nucleus.
***Scant/indistinct cytoplasm.
**Other foreign cells:
***[[Paget disease]]: large cells with clear cytoplasm, may cluster, above basal layer.

====Normal histology====
Features:
*Keratinocytes:
**Basal ~ 2x [[RBC]].
***May palisade focally ~ 1:2 = width: height.
*Melanocytes < 25 melanocytes / 0.5 mm of basal layer.<ref name=pmid21549242>{{Cite journal | last1 = Trotter | first1 = MJ. | title = Melanoma margin assessment. | journal = Clin Lab Med | volume = 31 | issue = 2 | pages = 289-300 | month = Jun | year = 2011 | doi = 10.1016/j.cll.2011.03.006 | PMID = 21549242 }}</ref>
*Basket weave stratum corneum (non-acral skin).

===Dermis===
Subdivided into layers:
#Papillary dermis.
#*Location: superficial - opposed to the deep aspect of the epidermis.
#*Appearance: dense, thick collagen bundles.
#Reticular dermis.
#*Location: deep - between papillary dermis and subdermis.
#*Appearance: loose connective tissue.

Images:
*[http://www.biology-online.org/user_files/Image/Anatomy/AN-fibroblastF02.gif Layers of the dermis - labelled (biology-online.org)].<ref>URL: [http://www.biology-online.org/articles/fibroblast_heterogeneity_skin_deep/figures.html http://www.biology-online.org/articles/fibroblast_heterogeneity_skin_deep/figures.html]. Accessed on: 29 March 2012.</ref>
*[http://melanoma.blogsome.com/wp-admin/images/skinstr.jpg Layers of the skin (melanoma.blogsome.com)].<ref>URL: [http://melanoma.blogsome.com/category/skin-structure/ http://melanoma.blogsome.com/category/skin-structure/]. Accessed on: 29 March 2012.</ref>

===Adnexal structures===
The top five structures of the skin:<ref>{{Ref Derm|4-8}}</ref>
{| class="wikitable sortable"
! Structure / Attribute
! Histomorphology
! Function
! [[IHC]]
! Other
! Image
|-
| '''Eccrine gland'''
| clusters of tubular structures, pale cytoplasm
| thermoregulation (cooling) - produce sweat
| [[CK7]]+, [[CEA]]+, CAM5.2+, [[EMA]]+
| ?
| ?
|-
| '''Apocrine gland'''
| apical snouts, tubular structures
| ear wax, body odor
| ?
| ?
| ?
|-
| '''Sebaceous gland'''
| clusters of cells side-by-side, pale fluffy cytoplasm
| grease hair, sexual lubrication
| ?
| assoc. with hair follicle
| ?
|-
| '''Hair follicle'''
| linear structure
| keep individual warm
| ?
| assoc. with sebaceous glands
| ?
|-
| '''Nail'''
| epidermal structure
| weapon (claw-like), look pretty?
| ?
| ?
| [http://histology.osumc.edu/histology/HumanHisto/Integumentary/Img/17B-23_001.html (osumc.edu)], [http://ctrgenpath.net/static/atlas/mousehistology/Windows/integumentary/nail20.html (ctrgenpath.net)]
|-
|}

Ducts vs. glands:<ref>HJ. 27 Feb 2009.</ref>
*Eccrine glands - spindle-shaped myoepithelial cells surround luminal cells.
*Eccrine ducts - cuboidal type subepithelial cells.

=Common terms=
==Clinical descriptors==
There are multitude of clinical descriptors - common ones are:<ref>URL: [http://www.pediatrics.wisc.edu/education/derm/text.html http://www.pediatrics.wisc.edu/education/derm/text.html]. Accessed on: 18 September 2012.</ref>
{| class="wikitable sortable"
! '''Name'''
! '''Size †'''
! '''Description'''
! '''Other'''
! '''Image'''
|-
| Macule
| <= 10 mm
| flat + change of colour
| if > 10 mm --> patch
| [[Image:Macule_and_Patch.svg|thumb|center|150px| Macule (WC)]]
|-
| Patch
| > 10 mm
| flat + change of colour
| if <= 10 mm --> macule
| [[Image:Macule_and_Patch.svg|thumb|center|150px| Patch (WC)]]
|-
| Papule
| <= 10 mm
| raised
| if > 10 mm --> nodule
| [[Image:Papule_and_Plaque.svg|thumb|center|150px| Papule (WC)]]
|-
| Nodule
| > 10 mm
| raised
| if <= 10 mm --> papule
| [[Image:Nodules.svg|thumb|center|150px| Nodule (WC)]]
|-
| Plaque
| > 10 mm
| raised, flat-top
| plateau-like
| [[Image:Papule_and_Plaque.svg|thumb|center|150px| Plaque (WC)]]
|-
| Vesicle
| <= 10 mm
| raised, fluid filled
| if > 10 mm --> bulla
| [[Image:Vesicles_and_Bulla.svg |thumb|center|150px| Vesicle (WC)]]
|-
| Bulla
| > 10 mm
| raised, fluid filled
| if <= 10 mm --> vesicle
| [[Image:Vesicles_and_Bulla.svg |thumb|center|150px| Bulla (WC)]]
|}
Note:
* † Definitions vary -- some authors use a 5 mm cut-off.

==Histologic descriptors==
Dermatopathology doesn't have intuitive terms, e.g. thickening of the stratum spinosum isn't ''spinosum hyperplasia''. The terms have to committed to memory.

===Common terms in a table===
{| class="wikitable sortable"
! Term
! Meaning
! Reference
|-
|Acanthosis
| thickening of the prickle layer (stratum spinosum) of epidermis
| <ref>[http://dictionary.reference.com/browse/acanthosis http://dictionary.reference.com/browse/acanthosis]</ref>
|-
|Acantholysis
| loss of intercellular connections in the epidermis
|
|-
|Dyskeratosis
| abnormal keratinization, often refers to keratinization below the stratum granulosum; keratinization above may be abnormal (dependent on body site)
|
|-
|Parakeratosis
| retention of nuclei in the stratum corneum, normal in mucous membranes
|
|-
|Spongiosis
| epidermal intercellular edema; cells appear to have a clear halo around 'em
| <ref>{{Ref PBoD|1230}}</ref>
|-
|Basketweave stratum corneum
| appearance of the normal stratum corneum; presence in the context of pathology suggests an acute process
|
|-
|Compact hyperkeratosis
| stratum corneum layer is dense and thickened; this suggests a chronic process
| <ref>URL: [http://dermnetnz.org/pathology/pathology-glossary.html http://dermnetnz.org/pathology/pathology-glossary.html]. Accessed on: 8 August 2012.</ref>
|-
| Hyperkeratosis
| thickened stratum corneum - also see ''compact hyperkeratosis'' and ''basketweave stratum corneum''
|
|-
|Epidermotropism †
| intraepithelial lymphocytes in [[CTCL]]; how to remember: epidermotropis''m'' = ''m''alignant
| <ref name=pmid20132423>{{Cite journal | last1 = Fung | first1 = MA. | title = 'Epidermotropism' vs. 'exocytosis' of lymphocytes 101: definition of terms. | journal = J Cutan Pathol | volume = 37 | issue = 5 | pages = 525-9 | month = May | year = 2010 | doi = 10.1111/j.1600-0560.2010.01515.x | PMID = 20132423 }}</ref>
|-
|Exocytosis †
| intraepithelial lymphocytes in benign conditions
| <ref name=pmid20132423>{{Cite journal | last1 = Fung | first1 = MA. | title = 'Epidermotropism' vs. 'exocytosis' of lymphocytes 101: definition of terms. | journal = J Cutan Pathol | volume = 37 | issue = 5 | pages = 525-9 | month = May | year = 2010 | doi = 10.1111/j.1600-0560.2010.01515.x | PMID = 20132423 }}</ref>
|-
|Orthokeratosis
| anuclear keratin layer is present (stratum corneum) - seen in normal skin; ''ortho-'' means ''correct''
| <ref>URL: [http://www.medilexicon.com/medicaldictionary.php?t=63448 http://www.medilexicon.com/medicaldictionary.php?t=63448]. Accessed on: 13 March 2013.</ref><ref>URL: [http://dictionary.reference.com/browse/ortho- http://dictionary.reference.com/browse/ortho-]. Accessed on: 13 March 2013.</ref>
|}
Note:
* † These definitions are not universally accepted. ''Epidermotropism'' is sometimes used in the context of benign disease.<ref name=pmid9537476>{{Cite journal | last1 = Fung | first1 = MA. | last2 = LeBoit | first2 = PE. | title = Light microscopic criteria for the diagnosis of early vulvar lichen sclerosus: a comparison with lichen planus. | journal = Am J Surg Pathol | volume = 22 | issue = 4 | pages = 473-8 | month = Apr | year = 1998 | doi = | PMID = 9537476 }}</ref>

Image:
*[http://commons.wikimedia.org/wiki/File:Spongiotic_dermatitis_%282%29_Dyshidrotic_.JPG Spongiosis (WC)].

===Others terms===
*Crust = epithelial elements, blood.

Image:
*[http://www.eplasty.com/article_images/eplasty10e60_fig3.gif Crust (eplasty.com)].<ref>URL: [http://www.eplasty.com/index.php?option=com_content&view=article&id=492&catid=171:volume-10-eplasty-2010&Itemid=121 http://www.eplasty.com/index.php?option=com_content&view=article&id=492&catid=171:volume-10-eplasty-2010&Itemid=121]. Accessed on: 16 October 2012.</ref>

=Skin diseases=
==Neoplasms==
{{main|Dermatologic neoplasms}}

===Malignant===
Skin cancer is very common. The basic DDx of a malignant skin lesion is:
*[[Squamous cell carcinoma]] (SCC).
*[[Basal cell carcinoma]] (BCC).
*[[Malignant melanoma]].
*Metstases.

==Non-malignant disease==
{{main|Non-malignant skin disease}}
Non-malignant skin disease is common. It is the domain of dermatologists. It can be scary for general anatomical pathologists because the differential diagnosis is often broad, and, it's generally not something the general anatomical pathologist sees a lot of.

===Subarticles===
*[[Dermal cysts]], e.g. [[epidermal cyst]], [[pilar cyst]].
*[[Epidermal necrosis]], e.g. [[erythema multiforme]], [[toxic epidermal necrolysis]].
*[[Inflammatory skin diseases]].
**[[Bullous diseases]], e.g. [[pemphigus vulgaris]].
**[[Panniculitis]].

=Common entities in tables=
==Non-malignant non-cystic - very common==
{| class="wikitable sortable" style="margin-left:auto;margin-right:auto"
! Entity
! Key histologic feature
! Other features
! Clinical
! Stains/IHC
! DDx
! Other
! Image
|-
| [[Seborrheic keratosis]] (SK)
| horn cysts (intraepidermal collections of keratin)
| hyperkeratosis, brown granular material at the DE junction, sharply demarcated
| stuck on appearance
| none
| [[fibroepithelial polyp]]
| Leser–Trélat sign = many SKs in malignancy
| [[Image:Seborrheic_keratosis_(1).jpg |thumb|center|150px| SK (WC)]]
|-
| [[Dermatofibroma]]
| fibrous bundles esp. at edge of lesion
| "dirty fingers" = acanthosis + basal keratinocyte hyperpigmentation
| +/-trauma Hx
| CD34-, Factor XIIIa+
| [[DFSP]]
| very common
| [[Image:SkinTumors-P9280848.jpg|thumb|center|150px|DF (WC)]]
|-
| [[Fibroepithelial polyp]] (skin tag)
| on a stalk (epithelium on 3+ sides)
| no horn nests, no hyperkeratosis
| raised lesion
| none
| [[seborrheic keratosis]]
| very common
| [[Image:SkinTumors-P9250819.jpg|thumb|center|150px|Skin tag (WC)]]
|-
| [[Lipoma]]
| mature adipocytes - uniform size
| var. of size may be seen, should prompt search for lipoblasts
| mobile subcutaneous mass
| S100 (???)
| [[liposarcoma]]
| variants: angiolipoma (blood vessels), myolipoma (muscle)
| [[Image: Lipoma -- high mag.jpg|thumb|center|150px|Lipoma (WC)]]
|-
| [[Cicatrix]] (dermal scar)
| dense collagen bundles running parallel to DE junction, loss of dermal papillae
| loss of adnexal structures, +/-[[giant cells]], +/-foreign material, +/-inflammatory cells
| site of previous trauma/surgery
| usu. none; S-100 (to exclude melanoma)
| residual disease, [[hypertrophic scar]], (desmoplastic) [[melanoma]]
|
| [[Image:ScarHistology.JPG |thumb|center|150px| Scar (WC)]]
|- 
|}

==Non-malignant non-cystic - common==
{| class="wikitable sortable" style="margin-left:auto;margin-right:auto"
! Entity
! Key histologic feature
! Other features
! Clinical
! Stains/IHC
! DDx
! Other
! Image
|-
| [[Neurofibroma]]
| bland spindle cells
| mast cells, mixed with collagen, assoc. with a nerve
| may be associated with [[neurofibromatosis]], esp. plexiform type
| S100+, GFAP+
| neurotized [[melanocytic nevus]]
| may develop into [[MPNST]]
| [[Image:Neurofibroma_%281%29.jpg |thumb|center|150px| Neurofibroma (WC)]]
|-
| [[Keratoacanthoma]]
| keratin plug, glassy pink cytoplasm, pushing downward growth
| minimal/no nuclear atypia
| grow rapidly then involute
| none
| [[squamous cell carcinoma]]
| some don't believe in the entity
| [[Image:Skin_keratoacanthoma_whole_slide.jpg |thumb|center|150px| Keratoacathoma (WC)]]
|-
| [[Molluscum contagiosum]]
| suprabasilar cells with abundant granular eosinophilic cytoplasm
| small peripheral nucleus
| polypoid lesion; mushroom-like (?)
| none (?)
| DDx (?)
| favourite exam case
| [[Image:Molluscum_contagiosum_high_mag.jpg |thumb|center|150px|Molluscum contagiosum (WC)]]
|-
| [[Verruca vulgaris]]
| hypergranulosis (thick granular layer) + keratohyaline granules
| hyperkeratosis (thick s. corneum), acanthosis (thick s. spinosum), rete ridges lengthened (~7-10x normal), large vessels at DE junction, koilocytic change (???)
| raised lesions, classically on hand
| none (p16+?)
| [[squamous cell carcinoma of the skin|squamous cell carcinoma]]
| caused by [[HPV]]
| [[Image:Verruca_vulgaris_-_very_low_mag.jpg |thumb|center|150px| Verruca vulgaris (WC)]]
|-
| [[Condyloma acuminatum]]
| koilocytes
| parakeratosis, long folded rete ridges (papillomatosis) - pseudopapillary look
| genital lesion
| none (p16+)
| [[fibroepithelial polyp]]
| caused by [[HPV]]
| [[Image:Anal_condyloma_%282%29.jpg |thumb|center|150px| Condyloma acuminatum (WC)]]
|-
| [[Granuloma annulare]]
| dermal palisading [[granuloma]] around necrotic collagen
| mucin in centre of lesion, (peripheral) lymphocytes, usu. more superficial than necrobiosis lipoidica
| benign, self-limited
| none (CD68?)
| [[necrobiosis lipoidica]], [[rheumatoid nodule]], [[epithelioid sarcoma]]
| Other ?
| [[Image:Granuloma_annulare_-_add_-_high_mag.jpg |thumb|center|150px| GA (WC)]]
|-
| [[Necrobiosis lipoidica]]
| dermal palisading [[granuloma]] around necrotic collagen, plasma cells
| mucin in centre of lesion, (peripheral) chronic inflammatory cells
| may be assoc. [[diabetes mellitus]]
| none (CD68?)
| [[granuloma annulare]], [[rheumatoid nodule]]
| histology identical to ''necrobiosis lipoidica diabeticorum''
| [http://www.drmihm.com/cases/casefigure.cfm?figID=942&CaseID=53 (drmihm.com)]
|-
| [[Angiofibroma]]
| fibrotic dermis, dilated capillaries
| enlarged (stellate fibroblasts)
| dome-shaped - face, boys & nosebleeds ([[nasopharyngeal angiofibroma]])
| Stains/IHC
| DDx
| may be associated with [[tuberous sclerosis]]
| [[Image:Nasopharyngeal angiofibroma - 2 - high mag.jpg|thumb|150px|Angiofibroma (WC)]]
|-
| [[Keloid]]
| thick collagen bundles - surrounded by paler staining fibroblasts
| replaces adnexal structures
| site of previous trauma, esp. in blacks
| none
| [[dermatofibroma]] (???)
| [[hypertrophic scar]]
| [[Image:Keloid_-_high_mag.jpg|thumb|center|150px|Keloid (WC)]]
|-
| [[Eccrine poroma]]
| abundant basaloid cells with (small) ductal structures
| incloses islands of sclerotic stroma with edema
| erythematous lesions
| Stains/IHC ?
| DDx ?
| Other ?
| [[Image:SkinTumors-P7150495.JPG|thumb|center|150px|EP (WC)]]
|-
| [[Syringoma]]
| bilayered ducts, occasionally tadpole like shape
|
| usu. close to [[eyelid]]
| Stains/IHC ?
| DDx ?
| Other ?
| [http://dermatology.cdlib.org/144/tumors/axillary_syringoma/2.jpg (cdlib.org)]
|-
| [[Chondroid syringoma]] (mixed tumour of skin)
| [[chondromyxoid stroma]], epithelial component
| epithelial component in nests with eosinophilic cytoplasm, round/ovoid nuclei with nucleoli
| Clinical ?
| Stains/IHC ?
| DDx ?
| related to [[pleomorphic adenoma]] (???)
| Image ?
|-
| [[Angiokeratoma]]
| ectatic superficial dermal vessels + overlying hyperkeratosis
| -
| may be seen in [[Fabry disease]]
| Stains/IHC ?
| [[venous lake]]
| Other ?
| [[Image:Angiokeratoma_-_low_mag.jpg |thumb|center|150px| Angiokeratoma (WC)]]
|- 
|}

==Non-malignant non-cystic - children==
{| class="wikitable sortable" style="margin-left:auto;margin-right:auto"
! Entity
! Key histologic feature
! Other features
! Clinical
! Stains/IHC
! DDx
! Other
! Image
|-
| [[Pilomatricoma]]
| anucleate squamous cells (ghost cells), giant cells
| bland basaloid cells
| common in children
| none
| [[squamous cell carcinoma of the skin|squamous cell carcinoma]]
| mutations of CTNNB1 gene
| [[Image:Pilomatrixoma_-_intermed_mag.jpg |thumb|center|150px| Pilomatrixcoma (WC)]]
|-
| [[Juvenile xanthogranuloma]] (JXG)
| Touton giant cells - multi-nucleated cells where nuclei are distributed around the cell periphery forming a ring
| abundant cytoplasm
| children
| CD68+, CD1a-, CD207-
| [[Langerhans cell histiocytosis]]
| may be seen in adults, known as '''adult xanthogranuloma'''
| [[Image:Juvenile_xanthogranuloma_-_high_mag.jpg |thumb|center|150px| JXG (WC)]]
|}

==Non-malignant cystic==
{| class="wikitable sortable" style="margin-left:auto;margin-right:auto"
! Entity
! Key histologic feature
! Other features
! Clinical
! Stains/IHC
! DDx
! Other
! Image
|-
| [[Epidermal cyst]]
| cyst lined by squamous epithelium '''with''' a granular layer
| keratinous debris, no skin adnexal structures
| cyst
| none
| [[pilar cyst]], [[dermoid cyst]]
| Other?
| [[Image:Epidermal inclusion cyst -- high mag.jpg |thumb|center|150px| Epidermal inclusion cyst (WC)]]
|-
| [[Pilar cyst]] (trichilemmal cyst)
| cyst lined by squamous epithelium '''without''' a granular layer
| keratinous debris
| cyst
| none
| [[epidermal cyst]]
| Other?
| [[Image:Trichilemmal_cyst_-_very_high_mag.jpg |thumb|center|100px| Pilar cyst (WC)]]
|-
| [[Steatocystoma]]
| cyst lined by squamous epithelium with a corrugated eosinophilic lining
| epidermis has '''no''' granular layer
| cyst
| none
| [[dermoid cyst]], follicular cyst
| Other?
| [[Image:Steatocystoma_-_high_mag.jpg |thumb|center|150px| Steatocystoma (WC)]]
|-
| [[Dermoid cyst]]
| cyst lined by keratinizing squamous epithelium with adnexal structures
| adnexal structure = hair, sebaceous gland, sweat glands
| cyst
| none
| [[epidermal cyst]]
| may be seen in the [[ovary]]
| [http://webeye.ophth.uiowa.edu/eyeforum/cases-i/case115/larger/Figure4.jpg (uiowa.edu)]
|}

==Pre-malignant==
{| class="wikitable sortable" style="margin-left:auto;margin-right:auto"
! Entity
! Key histologic feature
! Other features
! Clinical
! Stains/IHC
! DDx
! Other
! Image
|-
| [[Actinic keratosis]]
| epidermal atypia, esp. (basal) nuclear enlargement
| var. of nuclear size, shape and staining, parakeratosis (important in early lesions); does ''not'' involves adnexal epithelium and follicular epithelium
| yellow-brown scaly
| none
| [[squamous carcinoma]], [[Bowen disease]]
| seen with [[solar elastosis]]
| [[Image:Actinic_Keratosis,_H%26E.jpg |thumb|center|150px| AK (WC)]]
|-
| [[Bowen disease]] (squamous cell carcinoma in situ)
| epidermal atypia, esp. suprabasal nuclear enlargement
| var. of nuclear size, shape and staining; usually full thickness involvement; involve adnexal epithelium and follicular epithelium
|
| none
| [[squamous carcinoma]], [[actinic keratosis]]
| typically seen with solar elastosis
| [[Image:Bowen_disease_%281%29.jpg |thumb|center|100px| Bowen's disease (WC)]]
|}

==Common malignant==
{| class="wikitable sortable" style="margin-left:auto;margin-right:auto"
! Entity
! Key histologic feature
! Other features
! Clinical
! Stains/IHC
! DDx
! Other
! Image
|-
| [[Basal cell carcinoma]] (BCC)
| basaloid cells with peripheral palisading, artificial cleft
| [[myxoid]] stroma
| raised, pearly, telangiectasia
| usu. none req., [[CK5/6]]+
| [[trichoepithelioma]], [[basaloid squamous cell carcinoma]]
| assoc. [[nevoid basal cell carcinoma syndrome]], [[Bazex syndrome]]
| [[Image:Basal cell carcinoma - high mag.jpg| thumb| center|150px|BCC (WC)]]
|-
| [[Squamous cell carcinoma]] (SCC)
| nuclear enlargement, eosinophilic cytoplasm, central nucleus
| small nucleolus, intercellular bridges
| flaky appearance
| usu. none req., p63+, HMWK+
| [[keratoacanthoma]], [[Paget disease]] ([[EMPD]] & [[PDB]]), [[malignant melanoma]], Toker cell hyperplasia
| Other
| [[Image:Oral_cancer_%281%29_squamous_cell_carcinoma_histopathology.jpg|thumb|center|150px|SCC (WC)]]
|-
| [[Malignant melanoma]]
| spindle and/or epithelioid morphology +/-nuclear atypia (esp. nucleoli)
| mitoses (esp. deep), +/-pigment, +/-nested arch., asymmetry, upward spread (into epidermis), epithelioid m. deep, +/-single cells, +/-sheets of cells
| ABCD = Asymmetry, Borders poor demarc., Colour dark, Diameter large
| S100+, Melan A+, HMB-45+, microphthalmia+, tyrosinase+
| [[melanocytic lesions]] esp. [[Spitz nevus]], [[Bowen's disease]]
| may be familial, [[dysplastic nevus]]
| [[Image:Malignant_melanoma_%281%29_at_thigh_Case_01.jpg |thumb|center|150px|Melanoma (WC)]]
|- 
|}

==Less common malignant==
{| class="wikitable sortable" style="margin-left:auto;margin-right:auto"
! Entity
! Key histologic feature
! Other features
! Clinical
! Stains/IHC
! DDx
! Other
! Image
|-
| [[Kaposi sarcoma]]
| vascular spindle cell lesion
| [[hyaline globules]] (intracytoplasmic)
| often HIV/AIDS
| [[HHV-8]]
| [[Masson's hemangioma]], [[angiosarcoma]], [[Kaposiform hemangioendothelioma]]
| stages: patch stage, plaque stage, nodular stage, exophytic, infiltrative, lymphadenopathic
| [[Image:Kaposi_sarcoma_low_intermed_mag.jpg |thumb|center|150px| Kaposi sarcoma (WC)]]
|-
| [[Cutaneous T-cell lymphoma]] (includes ''mycosis fungoides'')
| single lymphocytes in epidermis ("lymphocyte exocytosis")
| lymphocyte nests in the epidermis ("Pautrier microabscesses"), short arrays of lymphocytes along the basal layer of the epidermis ("epidermotropism")
| Clinical
| CD45, CD4
| B cell lymphoma (?)
| Other
| [[Image:Cutaneous_T-cell_lymphoma_-_intermed_mag.jpg |thumb|center|150px| CTCL (WC)]]
|-
| [[Atypical fibroxanthoma]]
| dermal lesion with marked nuclear atypia
| multinucleated cells, mitoses, vacuolated cytoplasm
| old men, head and neck
| p63-, 34betaE12-, S100-, desmin-
| sarcomatoid squamous carcinoma, [[melanoma]], [[leiomyosarcoma]]
| some classify this as '''benign'''; thought to be related to [[undifferentiated pleomorphic sarcoma]]
| [[Image:SkinTumors-P9280874.jpg|thumb|center|150px| AFX (WC)]]
|-
| [[Merkel cell carcinoma]]
| neuroendocrine nuclear features (stippled chromatin, no nucleolus), scant cytoplasm
| +/-nuclear moulding, usu. intermediate cell size
| Merkel cell polyomavirus associated, usu. head & neck or extremities
| CK20+, EMA+
| cutaneous [[Ewing sarcoma]], [[basal cell carcinoma]], (dermal) [[lymphoma]], metastatic small cell carcinoma (e.g. [[Lung tumours#Small cell carcinoma|lung]])
| rare, aggressive
| [[Image:Merkel_cell_carcinoma_-_very_high_mag.jpg |thumb|center|100px| MCC (WC)]]
|-
| [[Dermatofibrosarcoma protuberans]] (DFSP)
| spindle cell tumour with storiform pattern, tumour often contains adipocytes
| dermal tumour with preserved adnexal structures
| locally aggressive
| CD34+, factor XIIIa-
| [[dermatofibroma]], [[solitary fibrous tumour]] (usu. deeper)
| rarely metastases, characteristic [[translocation]]: t(17;22)(q22;q15) COLA1/PDGFB; may transform to [[fibrosarcoma]]
| [[Image:Storiform_pattern_-_intermed_mag.jpg |thumb|center|150px| DFSP (WC)]]
|- 
|}

=Presentations=
==Leukoplakia==
{{Main|Leukoplakia}}

DDx:<ref>{{Ref PBoD|1065}}</ref>
*Vitiligo (loss of pigment).
*Inflammation.
**Chronic dermatitis.
**[[Psoriasis]].
*Neoplasia.
**[[Vulvar intraepithelial neoplasia]].
**[[Invasive_breast_cancer#Paget.27s_disease|Paget disease]].
**Invasive carcinoma.
*Other.
**[[Lichen sclerosus]].
**[[Lichen simplex chronicus]].

=Skin disease and systemic conditions=
==Tabular list==
{| class="wikitable sortable" style="margin-left:auto;margin-right:auto"
! Entity
! Disease/syndrome
! Key histologic feature
! Image
|-
| [[Acanthosis nigricans]]
| [[diabetes mellitus]], malignancy
| basal cell hyperpigmentation, hyperkeratosis, prominent rete ridges
| [http://dermatology.cdlib.org/149/reviews/acanthosisnigricans/higgins.html (cdlib.org)]
|-
| [[Trichilemmoma]]
| [[Cowden disease]]
| "hyperkeratosis"
| [http://ccr.cancer.gov/staff/images/9033_12822_Lee_1520.jpg (cancer.gov)]<ref>URL: [http://ccr.cancer.gov/staff/gallery.asp?profileid=12822 http://ccr.cancer.gov/staff/gallery.asp?profileid=12822]. Accessed on: 14 December 2011.</ref>
|-
| [[Angiokeratoma]]
| [[Fabry disease]]
| hyperkeratosis + vessels in superficial dermis
| [http://commons.wikimedia.org/wiki/File:Angiokeratoma_-_low_mag.jpg (WC)]
|-
| [[Dermatitis herpetiformis]]
| [[Celiac disease]]
| subepidermal [[bullous disease]], papillary abscesses
| [http://www.lampyris101.com/L101/gallery1/12_JPG.html (lampyris101.com)]
|-
| [[Angiofibroma]]
| [[tuberous sclerosis]]
| fibrotic dermis + dilated blood vessels
| [http://www.drdittmar.lu/images/sce/angiofibroma-s.jpg (drdittmar.lu)]
|-
| [[Sebaceous adenoma]]
| [[Muir-Torre syndrome]]
| abundant sebaceous glands with abn. arch.
| [http://commons.wikimedia.org/wiki/File:Sebaceous_adenoma_-_low_mag.jpg (WC)]
|-
| [[Seborrheic keratosis]], multiple with explosive onset
| Leser–Trélat sign (malignancy)
| horn cysts, hyperkeratosis
| [http://commons.wikimedia.org/wiki/File:IMG_1724.JPG gross (WC)], [http://commons.wikimedia.org/wiki/File:Seborrheic_keratosis_%281%29.jpg micro. (WC)]
|- 
|}

==Acanthosis nigricans==
===General===
Associated with:
*[[Diabetes mellitus]].<ref>URL: [http://www.emedicine.com/derm/topic1.htm http://www.emedicine.com/derm/topic1.htm], URL: [http://dermatlas.med.jhmi.edu/derm/indexDisplay.cfm?ImageID=1943559504].</ref>
*Malignancy.<ref name=Ref_PCPBoD8|596>{{Ref PCPBoD8|596}}</ref>

===Microscopic===
Features (memory device ''BPH''):<ref name=Ref_PCPBoD8|596>{{Ref PCPBoD8|596}}</ref>
*Basal cell hyperpigmentation.
*Prominent rete ridges.
*Hyperkeratosis.

DDx:
*[[Seborrheic keratosis]] - typically has more hyperkeratosis, pseudohorn cysts.

Images:
*[http://dermatology.cdlib.org/149/reviews/acanthosisnigricans/higgins.html AN (cdlib.org)].

==Others==
*[[Dermatitis herpetiformis]]: gluten enteropathy ([[celiac disease]]), [[thyroid]] disease, intestinal [[lymphoma]].<ref name=Ref_TN2007_D23>{{Ref TN2007|D23}}</ref>
*[[Pemphigus vulgaris]]: [[thymoma]], myasthenia gravis, malignancy.<ref name=Ref_TN2007_D23>{{Ref TN2007|D23}}</ref>
[[File:3767 dp sl 1.png |Lipoid proteinosis]]
[[File:3767 dp sl 2.png |Lipoid proteinosis]]
Lipoid proteinosis. A. Inner labial biopsy shows subepithelial hyalinized pink/red material, about blood vessels and in general. B. The particularly glassy appearance of the material in areas is evident at high power.

=References=
{{reflist|2}}

[[Category:Dermatopathology]]

Mantle cell lymphoma

2017-02-24T20:28:31Z

Mitchell: /* Images */ added a case

{{ Infobox diagnosis
| Name = {{PAGENAME}}
| Image = Mantle cell lymphoma - intermed mag.jpg
| Width =
| Caption = Mantle cell lymphoma. [[H&E stain]].
| Synonyms =
| Micro = small monomorphic (uniform size, shape and staining) lymphoid population with abundant mitoses, +/-scattered epithelioid histiocytes (should not be confused with tingible-body macrophages), +/-sclerosed blood vessels
| Subtypes = blastic variant
| LMDDx = other [[small cell lymphomas]] (esp. [[MALT lymphoma]]), [[Burkitt lymphoma]]
| Stains =
| IHC = cyclin D1 +ve, CD5 +ve, CD43 +ve, CD20 +ve, CD23 -ve
| EM =
| Molecular = t(11;14)(q13;q32) / IGH-CCND1
| IF =
| Gross =
| Grossing =
| Site = [[lymph node]], GI tract, other sites
| Assdx =
| Syndromes =
| Clinicalhx =
| Signs =
| Symptoms =
| Prevalence = not common
| Bloodwork =
| Rads =
| Endoscopy =
| Prognosis = moderately aggressive to poor
| Other =
| ClinDDx =
| Tx =
}}
'''Mantle cell lymphoma''', abbreviated '''MCL''', is less common [[small cell lymphoma]] that is relatively aggressive when compared to other small cell lymphomas.

==General==
*Relatively aggressive - guarded prognosis.<ref name=pmid10583923>{{Cite journal | last1 = Hankin | first1 = RC. | last2 = Hunter | first2 = SV. | title = Mantle cell lymphoma. | journal = Arch Pathol Lab Med | volume = 123 | issue = 12 | pages = 1182-8 | month = Dec | year = 1999 | doi = 10.1043/0003-9985(1999)1231182:MCL2.0.CO;2 | PMID = 10583923 }}</ref>
*Rare ~ 2% of non-Hogkin's lymphoma in a series of over 4000 patients.<ref name=pmid18723950>{{cite journal |author=Gujral S, Agarwal A, Gota V, ''et al.'' |title=A clinicopathologic study of mantle cell lymphoma in a single center study in India |journal=Indian J Pathol Microbiol |volume=51 |issue=3 |pages=315–22 |year=2008 |pmid=18723950 |doi= |url=}}</ref>
GI tract - typically:<ref name=pmid22236942/>
*Abdominal pain (~37% of cases) or GI bleeding (~26% of cases).

==Gross==
*GI tract: polypoid lesions (~50% of cases).<ref name=pmid22236942>{{Cite journal | last1 = Kim | first1 = JH. | last2 = Jung | first2 = HW. | last3 = Kang | first3 = KJ. | last4 = Min | first4 = BH. | last5 = Lee | first5 = JH. | last6 = Chang | first6 = DK. | last7 = Kim | first7 = YH. | last8 = Son | first8 = HJ. | last9 = Rhee | first9 = PL. | title = Endoscopic findings in mantle cell lymphoma with gastrointestinal tract involvement. | journal = Acta Haematol | volume = 127 | issue = 3 | pages = 129-34 | month = | year = 2012 | doi = 10.1159/000333139 | PMID = 22236942 }}</ref>

==Microscopic==
Features:<ref>Good, D. 17 August 2010.</ref>
*Typically a small monomorphic (uniform size, shape and staining) lymphoid population.
**May be "large" (blastic variant of mantle cell lymphoma) with 1 or 2 nucleoli.<ref name=pmid17917091>{{cite journal |author=Todorovic M, Pavlovic M, Balint B, ''et al.'' |title=Immunophenotypic profile and clinical characteristics in patients with advanced stage mantle cell lymphoma |journal=Med. Oncol. |volume=24 |issue=4 |pages=413–8 |year=2007 |pmid=17917091 |doi= |url=}}</ref>
*Abundant mitoses.
*Scattered epithelioid histiocytes (should not be confused with tingible-body macrophages).
*Sclerosed blood vessels.

DDx:
*Other [[small cell lymphomas]], esp. [[marginal zone lymphoma]].
*[[Burkitt's lymphoma]].
*Large B-cell lymphoma - for blastic variant of MCL.<ref name=pmid11681422>{{cite journal |author=Bernard M, Gressin R, Lefrère F, ''et al.'' |title=Blastic variant of mantle cell lymphoma: a rare but highly aggressive subtype |journal=Leukemia |volume=15 |issue=11 |pages=1785–91 |year=2001 |month=November |pmid=11681422 |doi= |url=}}</ref>

===Images===
<gallery>
Image:Mantle cell lymphoma - low mag.jpg | MCL - low mag. (WC)
Image:Mantle cell lymphoma - intermed mag.jpg | MCL - intermed. mag. (WC)
Image:Mantle cell lymphoma - low mag - cyclin D1.jpg | MCL - low mag. - cyclin D1. (WC)
Image:Mantle cell lymphoma - intermed mag - cyclin D1.jpg | MCL - intermed. mag. - cyclin D1. (WC)
</gallery>
www:
*[http://path.upmc.edu/cases/case441.html MCL - several images (upmc.edu)].
[[File:4 718053471 sl 1.png|Mantle cell lymphoma]]
[[File:4 718053471 sl 2.png|Mantle cell lymphoma]]
[[File:4 718053471 sl 3.png|Mantle cell lymphoma]]
[[File:4 718053471 sl 4.png|Mantle cell lymphoma]]
[[File:4 718053471 sl 5.png|Mantle cell lymphoma]]
[[File:4 718053471 sl 6.png|Mantle cell lymphoma]]
[[File:4 718053471 sl 7.png|Mantle cell lymphoma]] 
Mantle cell lymphoma in a 56 year old woman. A. A blue sea of cells spares a lymphoid follicle in the upper right corner. B. Small, round to reniform cells contrast with the larger tingible body macrophage (arrow). C-F. Tumor cells are Cyclin D1. CD20, BCL2, and CD5 positive positive. G. About 60% of tumor cells were positive for Ki67. Tumor cells were negative for CD3, CD10, and BCL6.

==IHC==
*CD45 +ve.
*CD20 +ve.
*CD79a +ve.
*CD5 +ve -- '''important'''.
**Negative in case reports.<ref>URL: [http://path.upmc.edu/cases/case308/dx.html http://path.upmc.edu/cases/case308/dx.html]. Accessed on: 14 January 2012.</ref>
*CD43 +ve.
*Cyclin D1 +ve -- '''key immunostain'''.
**[[AKA]] BCL1, AKA CCND1.<ref name=omim168461>{{OMIM|168461}}</ref>

Others:
*CD23 -ve.
**Positive in [[CLL]].

==Molecular==
*t(11;14)(q13;q32) / IGH-CCND1.<ref>URL: [http://atlasgeneticsoncology.org/Anomalies/t1114ID2021.html http://atlasgeneticsoncology.org/Anomalies/t1114ID2021.html]. Accessed on: 10 August 2010.</ref>

==Sign out==
<pre>
TERMINAL ILEUM, BIOPSY:
- MANTLE CELL LYMPHOMA.

COMMENT:
The tumour consists of small lymphoid cells in sheets.

The tumour stains as follows:
POSITIVE: CD20, CD5, BCL2, cyclin D1.
NEGATIVE: CD23, BCL6, CD10.
PROLIFERATION (Ki-67): 25%.
</pre>

==See also==
*[[Small cell lymphomas]].
*[[Ileal nodular lymphoid hyperplasia]].

==References==
{{Reflist|2}}

[[Category:Diagnosis]]
[[Category:Small cell lymphomas]]

Endocervical adenocarcinoma in situ

2017-02-14T18:38:16Z

Mitchell: /* Microscopic */ Put in ioffe scoring system

{{ Infobox diagnosis
| Name = {{PAGENAME}}
| Image = Endocervical adenocarcinoma in situ -- very high mag.jpg
| Width =
| Caption = Endocervical adenocarcinoma in situ. [[H&E stain]].
| Synonyms =
| Micro = Nuclear changes (nuclear crowding/pseudostratification, nuclear enlargement (often cigar-shaped nuclei), coarse chromatin, small nucleolus or nucleoli), +/-mitoses, +/-reduced cytoplasmic mucin, preservation of glandular architecture
| Subtypes =
| LMDDx = [[Tubal metaplasia of the uterine cervix|tubal metaplasia]], [[Arias-Stella reaction]], [[endometriosis]], lower uterine segment epithelium (esp. [[proliferative phase endometrium]]), [[endocervical adenocarcinoma]], [[metastasis|metastatic]] adenocarcinoma
| Stains =
| IHC = p16 +ve
| EM =
| Molecular =
| IF =
| Gross =
| Grossing =
| Site = [[uterine cervix]] - endocervical canal
| Assdx = squamous lesions ([[LSIL]], [[HSIL]])
| Syndromes =
| Clinicalhx = +/-[[HPV]]
| Signs =
| Symptoms = asymptomatic
| Prevalence = uncommon
| Bloodwork =
| Rads =
| Endoscopy =
| Prognosis =
| Other =
| ClinDDx = [[endocervical adenocarcinoma]] (invasive), [[endometrial carcinoma]], squamous cervical lesions
| Tx = typically [[LEEP]]
}}
:''For the cytology see [[Gynecologic cytopathology#Endocervical adenocarcinoma in situ|Endocervical adenocarcinoma in situ (cytology)]]''
'''Endocervical adenocarcinoma in situ''', also '''adenocarcinoma in situ of the uterine endocervix''', is pre-invasive change of the [[uterine cervix|uterine endocervix]]. It is closely tied to [[HPV]] infection.

If the context is clear, it may be referred to as '''[[adenocarcinoma in situ]]''', abbreviated '''AIS'''.

==General==
*Usually due to [[HPV]].
*May be found together with squamous neoplasias of the cervix.
*AIS of the cervix is much less common than squamous dysplasia of the cervix/SCC of the cervix.
*Generally, definitely diagnosed with an ''endocervical curettage'' (ECC).

==Gross==
*Not apparent at colposcopy.

==Microscopic==
Features:<ref name=pmid10757337>{{Cite journal | last1 = Zaino | first1 = RJ. | title = Glandular lesions of the uterine cervix. | journal = Mod Pathol | volume = 13 | issue = 3 | pages = 261-74 | month = Mar | year = 2000 | doi = 10.1038/modpathol.3880047 | PMID = 10757337 | url = http://www.nature.com/modpathol/journal/v13/n3/full/3880047a.html }}</ref>
#Nuclear changes - '''key feature''':
#*Variable nuclear stratification.
#**Nuclear crowding/pseudostratification.
#*Nuclear enlargement.
#**Often cigar-shaped nuclei.
#*Coarse chromatin.
#*Small nucleolus or [[nucleoli]].
#+/-Mitoses.
#+/-Reduced cytoplasmic mucin.
#Preservation of glandular architecture.
#*Normal gland spacing - lack of complexity ("lobular pattern").
#*Normal gland depth (subjective).

Ioffe, et al, :<ref name=pmid12657929>{{cite journal |author=Ioffe OB, Sagae S, Moritani S, Dahmoush L, Chen TT, Silverberg SG. |title=Proposal of a new scoring scheme for the diagnosis of noninvasive endocervical glandular lesions |journal=Am J Surg Pathol | volume=27 | issue=4| pages=452–460 | year=2003 | pmid=12657929 |pmc= |doi= |url= }}</ref> devised a reproducible schema by which one might discern reactive glandular atypia, glandular dysplasia, and adenocarcinoma in situ, summarized in the table below from the article:

Sum the scores for stratification, nuclear atypia, and mitoses/apoptotic bodies 
 
Stratification 
None (0 points) 
Mild (1 point) 
Moderate (2 points) 
Up to the luminal surface (3 points) 
 
Nuclear atypia 
As normal (0 points) 
Small (size of normal) or slightly enlarged uniform nuclei, minimal hyperchromasia, little dispolarity, no nucleoli (1 point) 
Nuclear enlargement (≤3× normal), moderate anisocytosis/hyperchromasia/dispolarity, occasional small nucleoli (2 points) 
Large nuclei (>3× normal), marked anisocytosis, marked hyperchromasia, severe dispolarity, frequent prominent nucleoli (3 points) 
 
Mitoses and apoptoses in two most active glands, number per gland (average between two glands) 
None (0 points) 
Less than 0.5 per gland (1 point) 
0.6–3.0 per gland (2 points) 
>3.0 per gland (3 points) 
 
Total score 0–3 = benign 4–5 = endocervical glandular dysplasia (EGD) 6–9 = adenocarcinoma in situ

DDx:
*[[Tubal metaplasia of the uterine cervix|Tubal metaplasia]].
*[[Arias-Stella reaction]].
*[[Endometriosis]].
*Lower uterine segment epithelium<ref name=Ref_GP167>{{Ref GP|167}}</ref> - esp. [[proliferative phase endometrium]] - mitoses rare, NC ratio normal, stroma different.
*[[Endocervical adenocarcinoma]] - often has paradoxical maturation... paler cytoplasm & nuclei than adjacent AIS.
*[[metastasis|Metastatic]] adenocarcinoma.
*[[Proliferative phase endometrium]] - endometrial type stroma, cytoplasm not pale staining, no nuclear atypia (smooth nuclear contour, stratified).

===Images===
====Case - ECC====
<gallery>
Image: Endocervical adenocarcinoma in situ -- intermed mag.jpg | AIS - intermed. mag.
Image: Endocervical adenocarcinoma in situ -- high mag.jpg | AIS - high mag.
Image: Endocervical adenocarcinoma in situ -- very high mag.jpg | AIS - very high mag.
Image: Endocervical adenocarcinoma in situ 2 -- intermed mag.jpg | AIS - intermed. mag.
Image: Endocervical adenocarcinoma in situ 2 -- high mag.jpg | AIS - high mag.
Image: Endocervical adenocarcinoma in situ 2a -- very high mag.jpg | AIS - very high mag.
Image: Endocervical adenocarcinoma in situ 2b -- very high mag.jpg | AIS - very high mag.
</gallery>
====Case - biopsy====
<gallery>
Image: Endocervical adenocarcinoma in situ --- intermed mag.jpg | AIS - intermed. mag.
Image: Endocervical adenocarcinoma in situ --- high mag.jpg | AIS - high mag.
Image: Endocervical adenocarcinoma in situ --- very high mag.jpg | AIS - very high mag.

Image: Endocervical adenocarcinoma in situ - alt --- intermed mag.jpg | AIS - intermed. mag.
Image: Endocervical adenocarcinoma in situ - alt --- high mag.jpg | AIS - high mag.
Image: Endocervical adenocarcinoma in situ - alt --- very high mag.jpg | AIS - very high mag.

Image: Endocervical adenocarcinoma in situ - p16 --- intermed mag.jpg | AIS - p16 - intermed. mag.
Image: Endocervical adenocarcinoma in situ - p16 --- high mag.jpg | AIS - p16 - high mag.
Image: Endocervical adenocarcinoma in situ - p16 --- very high mag.jpg | AIS - p16 - very high mag.

Image: Endocervical adenocarcinoma in situ - ki67 --- intermed mag.jpg | AIS - Ki-67 - intermed. mag.
Image: Endocervical adenocarcinoma in situ - ki67 --- high mag.jpg | AIS - Ki-67 - high mag.
Image: Endocervical adenocarcinoma in situ - ki67 --- very high mag.jpg | AIS - Ki-67 - very high mag.
</gallery>
====www====
*[https://www.flickr.com/photos/euthman/1799754415 Endocervical AIS adjacent to normal (flickr.com/euthman)].
*[http://nih.techriver.net/view.php?patientId=99 Endocervical adenocarcinoma in situ (techriver.net)].
*[http://womenshealthsection.com/content/gynpc/gynpc006d.jpg Endocervical adenocarcinoma in situ (womenshealthsection.com)].<ref>URL: [http://www.womenshealthsection.com/content/print.php3?title=gynpc006&cat=60&lng=english http://www.womenshealthsection.com/content/print.php3?title=gynpc006&cat=60&lng=english]. Accessed on: 20 March 2013.</ref>
*[http://nih.techriver.net/view.php?patientId=67 Endocervical adenocarcinoma in situ - cytology (techriver.net)].

==IHC==
*p16 +ve.
*CEA +ve.
*Vimentin -ve.

==Sign out==
<pre>
UTERINE CERVIX, BIOPSY:
- HIGH-GRADE SQUAMOUS INTRAEPITHELIAL LESION (HSIL).
- ENDOCERVICAL ADENOCARCINOMA IN SITU (AIS).
- ACUTE AND CHRONIC INFLAMMATION.

COMMENT:
A p16 immunostain marks the full thickness of the squamous epithelium and is
strong. A Ki-67 immunostain marks increased numbers of superficial squamous cells.

The atypical endocervical epithelium (interpreted as AIS) is strongly p16 positive
and has an increased proliferative activity with Ki-67 staining.
</pre>

===Micro===
The atypical endocervical epithelium (interpreted as AIS) shows marked hyperchromasia, nuclear crowding and moderate nuclear atypia with a relatively abundant cytoplasm ( nucleus to cell size = 1:2 ).

==See also==
*[[Endocervical adenocarcinoma]].
*[[Uterine cervix]].

==References==
{{Reflist|2}}

[[Category:Diagnosis]]
[[Category:Uterine cervix]]

Serous cystadenoma of the pancreas

2017-02-13T19:09:35Z

Mitchell: /* Images */ Added a case

{{ Infobox diagnosis
| Name = {{PAGENAME}}
| Image = Pancreatic_serous_cystadenoma_-_intermed_mag.jpg
| Width =
| Caption = Pancreatic serous cystadenoma. [[H&E stain]].
| Synonyms = serous microcystic adenoma
| Micro = small cystic spaces lined by cytologically bland cuboidal cells
| Subtypes =
| LMDDx = cystic [[renal cell carcinoma]], [[lymphangioma]], [[hemangioma]]
| Stains = PAS +ve, PASD -ve
| IHC =
| EM =
| Molecular =
| IF =
| Gross = lobulated appearance, no cysts apparent
| Grossing =
| Site = [[pancreas]] - body and tail
| Assdx =
| Syndromes = [[von Hippel-Lindau disease]]
| Clinicalhx =
| Signs =
| Symptoms =
| Prevalence = uncommon
| Bloodwork =
| Rads = honey comb-like appearance, Well-demarcated border - may be described as a "coin lesion"
| Endoscopy =
| Prognosis = benign
| Other =
| ClinDDx =
| Tx =
}}
'''Serous cystadenoma of the pancreas''' is a benign cystic lesion of the [[pancreas]].

It is also known as '''serous microcystic adenoma''',<ref name=Ref_Sternberg4_1630>{{Ref Sternberg4|1630}}</ref> and '''pancreatic serous cystadenoma'''.

It is unrelated to the [[ovarian serous cystadenoma]].

==General==
*1-2% of all exocrine pancreatic tumours.
*Female > male.
*Mean age 66 years.
*Truly benign with no malignant potenial.
*May be part of [[von Hippel-Lindau syndrome]].

Management:
*Observe or resect.

==Gross==
Features:
*Classically has a characteristic central scar.<ref name=pmid15888617>{{cite journal |author=Kim YH, Saini S, Sahani D, Hahn PF, Mueller PR, Auh YH |title=Imaging diagnosis of cystic pancreatic lesions: pseudocyst versus nonpseudocyst |journal=Radiographics |volume=25 |issue=3 |pages=671–85 |year=2005 |pmid=15888617 |doi=10.1148/rg.253045104 |url=http://radiographics.rsna.org/content/25/3/671.abstract}}</ref>
*Bosulated surface.
*Lobulated.
*No (macroscopic) cysts apparent on gross.
*Location: 50-70% occur in the body and tail.
*Size: average size 11 cm.

Radiologic appearance:
*Honey comb-like appearance.
*Well demarcated border - may be described as a "coin lesion".

Image:
*[http://www.joplink.net/prev/200905/25_fig06.jpg Serous microcystic adenoma (joplink.net)].<ref name=pmid19454830>{{Cite journal | last1 = Vernadakis | first1 = S. | last2 = Kaiser | first2 = GM. | last3 = Christodoulou | first3 = E. | last4 = Mathe | first4 = Z. | last5 = Troullinakis | first5 = M. | last6 = Bankfalvi | first6 = A. | last7 = Paul | first7 = A. | title = Enormous serous microcystic adenoma of the pancreas. | journal = JOP | volume = 10 | issue = 3 | pages = 332-4 | month = | year = 2009 | doi = | PMID = 19454830 |URL = http://www.joplink.net/prev/200905/25.html }}</ref>

==Microscopic==
Features:
*Cystic spaces lined by cuboidal cells.
**Glycogen rich.
**Cilia. (???)

DDx:
*[[Renal cell carcinoma]].
*[[Lymphangioma]].
*[[Hemangioma]].
*Oligocystic mucinous cystic tumors and pseudocysts.
**Have mucin; PAS-D could be used to demonstrate its presence.

Notes:
*Serous adenoma may coexist with aggressive tumours.

===Images===
<gallery>
Image:Pancreatic_serous_cystadenoma_-_low_mag.jpg | PSC - low mag. (WC)
Image:Pancreatic_serous_cystadenoma_-_intermed_mag.jpg | PSC - intermed. mag. (WC)
Image:Pancreatic_serous_cystadenoma_-_high_mag.jpg | PSC - high mag. (WC)
Image:Pancreatic_serous_cystadenoma_-_very_high_mag.jpg | PSC - very high mag. (WC)
</gallery>
<gallery>
Image: Pancreatic serous cystadenoma (1).jpg |PSC. (WC/KGH)
Image: Pancreatic serous cystadenoma (2).jpg |PSC. (WC/KGH)
</gallery>
[[File:4 691589031 sl 1.png| Microcystic serous cystadenoma of pancreas]]
[[File:4 691589031 sl 2.png| Microcystic serous cystadenoma of pancreas]]
[[File:4 691589031 sl 3.png| Microcystic serous cystadenoma of pancreas]]
[[File:4 691589031 sl 4.png| Microcystic serous cystadenoma of pancreas]]
[[File:4 691589031 sl 5.png| Microcystic serous cystadenoma of pancreas]]
[[File:4 691589031 sl 6.png| Microcystic serous cystadenoma of pancreas]]
 Microcystic serous cystadenoma of pancreas in a 62 year old woman. A. The tumor showed a central scar with multiple minute cysts; slight pressure yielded clear fluid. B. The mass comprises microcysts numberless. C. Cysts bear single cell linings with bland, amitotic nuclei. D. PAS without diastase shows positive cytoplasmic material. E. PAS with diastase shows the cytoplasmic material has been digested away. F. Keratin shows positive staining lining cells.

==Stains==
*PAS +ve.
*PASD -ve.

==See also==
*[[Pancreas]].
*[[Serous cystadenoma]].

==References==
{{Reflist|2}}

[[Category:Pancreas]]
[[Category:Diagnosis]]

Medical liver disease

2017-02-10T19:01:09Z

Mitchell: /* Microscopic */

[[Image:Ground glass hepatocytes high mag cropped 2.jpg|thumb|right|[[Micrograph]] showing ground glass hepatocytes, as seen in chronic [[hepatitis B]]. [[H&E stain]].]]
This article deals with '''medical [[liver]] disease'''. An introduction to the liver and approach is found in the ''[[liver]]'' article.

Every differential in liver pathology has "drugs"<ref>{{Ref PCPBoD8|448}}</ref> -- if it isn't clearly malignancy.

Liver neoplasms are dealt with in the ''[[liver neoplasms]]'' article.

Medical liver biopsies are often non-specific, as the liver has the same appearance for many mechanisms of injury, especially when the injury is marked. The clinical history, serology and imaging are essential for proper interpretations in this domain of pathology.

=Review of liver blood work=
===Inflammation activity===
*ALT.
*AST.

===Cholestatic markers===
*ALP.
*GGT - used to assess whether the ALP is an "honest" value, elevated in cirrhosis.

===Cirrhosis/decompensation===
*PLT - low is suggestive of dysfunction.
*INR - high is bad, unless anticoagulated.

===Other===
*Bilirubin.
**Direct (AKA conjugated).
**Indirect (AKA unconjugated).

A short DDx of elevated:<ref>{{Ref PCPBoD8|441}}</ref>
*Indirect:
**[[Gilbert syndrome]].
**Crigler-Najjar syndrome type 1.
**Crigler-Najjar syndrome type 2.
*Direct:
**Rotor syndrome.
**Dubin-Johnson syndomre.

===Viral hepatitis===
*HBV DNA.
*HCV RNA.
*HBs Ag, HBs Ab, HBe Ag, HBe Ab.
*HCV Ab.

Others:
*[[Epstein-Barr virus]] (EBV).
*[[Cytomegalovirus]] (CMV) - especially in the immune incompetent.

====Hepatitis B====
Meaning & utility of the various [[Hepatitis B]] tests:<ref>URL: [http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/hepatology/hepatitis-B/ http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/hepatology/hepatitis-B/]. Accessed on: 16 May 2011.</ref><ref name=lto_hepb>URL: [http://www.labtestsonline.org/understanding/analytes/hepatitis_b/test.html http://www.labtestsonline.org/understanding/analytes/hepatitis_b/test.html]. Accessed on: 16 May 2011.</ref>
{| class="wikitable sortable" border="1"
! Test name
! Location
! Positive test
! Negative test
! Usual question
|-
| HBs Ag||Surface||Virus active||No active infection||Active infection?
|-
| HBs Ab||Surface||Exposed OR vaccinated||No exposure OR no vaccine OR loss of Ab||Immunization status?
|-
| HBe Ag||Virus core||Infect. w/ viral replication||No active infection||Active infect. w/ viral replication?
|-
| HBe Ab||Virus core||Exposed to virus||Infect. w/o antibody response OR not exposed||Immune response to infection?
|-
| HBV DNA||-||Active||Not active/no exposure||Viral load/how active?
|-
| HBc Ab||Virus core||Virus active/previous exposure||No exposure||Early active infection?
|}
Notes:
*''HBc Ab'' may test for acute (IgM) or chronic infection - dependent on specific antibody test; it is often used to look for early infection.<ref name=lto_hepb>URL: [http://www.labtestsonline.org/understanding/analytes/hepatitis_b/test.html http://www.labtestsonline.org/understanding/analytes/hepatitis_b/test.html]. Accessed on: 16 May 2011.</ref>
*''Carriers of hepatitis B'': HBs Ag +ve, HBs Ab -ve, HBc Ag -ve, HBc Ab +ve, HBe Ag -ve, HBe Ab +ve.<ref>URL: [http://labtestsonline.org/understanding/analytes/hepatitis-b/tab/test http://labtestsonline.org/understanding/analytes/hepatitis-b/tab/test]. Accessed on: 3 May 2012.</ref>

===Markers for rare liver diseases===
*Ceruloplasm - low think ''[[Wilson's disease]]''; typical value for Wilson's ~ 0.12 g/L.
**<0.20 g/L is a criteria for Wilson's disease.<ref name=pmid18556333>Diagnostic accuracy of serum ceruloplasmin in Wilson disease: determination of sensitivity and specificity by ROC curve analysis among ATP7B-genotyped subjects. Mak CM, Lam CW, Tam S. Clin Chem. 2008 Aug;54(8):1356-62. Epub 2008 Jun 12. PMID 18556333. URL: [http://www.clinchem.org/cgi/reprint/54/8/1356.pdf http://www.clinchem.org/cgi/reprint/54/8/1356.pdf]. Accessed on: 28 September 2009.</ref>
*Alpha-1 antitrypsin - if low think ''deficiency''.

===Hemosiderosis===
*Ferritin - high.
*Iron saturation - high.

Causes:
*Hemochromatosis.
*Hemolysis, chronic.
*Cirrhosis.

=Medical imaging=
Blood flow:<ref>URL: [http://insidesurgery.com/2010/12/hepatopedal-hepatofugal-flow/ http://insidesurgery.com/2010/12/hepatopedal-hepatofugal-flow/]. Accessed on: 2 December 2011.</ref>
*Hepatopedal flow = normal portal vein flow.
*Hepatofugal flow = reversed portal vein flow.

==Interventional measurements==
Wedged to free hepatic venous pressure:<ref name=pmid1864548>{{Cite journal | last1 = Bion | first1 = E. | last2 = Brenard | first2 = R. | last3 = Pariente | first3 = EA. | last4 = Lebrec | first4 = D. | last5 = Degott | first5 = C. | last6 = Maitre | first6 = F. | last7 = Benhamou | first7 = JP. | title = Sinusoidal portal hypertension in hepatic amyloidosis. | journal = Gut | volume = 32 | issue = 2 | pages = 227-30 | month = Feb | year = 1991 | doi = | PMID = 1864548 | PMC = 1378815 | URL = http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1378815/?tool=pubmed }}</ref>
*Normal = 1-4 mmHg.
**Elevated in [[portal hypertension]].

=Liver biopsy=
==Medical liver biopsy adequacy==
Liver biopsy specimens should be:<ref>{{Ref MacSween|418}}</ref>
*2.0 cm in length and contain 11-15 portal tracts,
*The core should be deeper than 1.0 cm from the liver capsule; specimens close to the capsule may lead to over grading of fibrosis.

==Reporting==
{{Main|Pathology reports}}
<pre>
Specimen, procedure:
- Diagnosis.
</pre>
The diagnosis usually contains grading and staging information, e.g. ''activity 2 /4, Laennec fibrosis stage 1 /4''.

In the context of medical liver disease:
*Grade = inflammation/activity.
*Stage = severity of fibrosis/architectural changes.

Notes:
*The term "acute" is infrequently used in liver pathology.
*In the liver: neutrophils ''is not'' acute -- unlike most elsewhere in the body.<ref>OA. September 2009.</ref>

===A microscopic checklist===
<pre>
Size of biopsy: Adequate
Fragmentation: Absent
Fibrosis: Stage 2-3/4, mostly stage 2
Fibrous septa: Present
Septa with curved contours: Present – focally only
Large droplet steatosis (% of hepatocytes): Present, moderate 60%
Ballooning of hepatocytes: Present, rare
Mallory-Denk bodies: Present, rare
Portal inflammation: Present
Interface activity: Minimal (0-1/4)
Lobular necroinflammation: Minimal
Ducts: Present in normal numbers
Duct injury: Absent
Ductular reaction: Absent
Cholestasis: Absent
Terminal hepatic venules: Present
Iron stain: Absent
Ground glass cells with routine stains: Absent
PASD for alpha-1 antitrypsin droplets: Negative
</pre>

=Viral hepatitis=
These are common. The diagnoses are based on serology. The serology is covered in the ''[[Liver_pathology#Viral_hepatitis|viral hepatitis]]'' section in the ''[[liver pathology]]'' article.

Typically classified as:<ref name=pmid8048409>{{Cite journal | title = Terminology of chronic hepatitis, hepatic allograft rejection, and nodular lesions of the liver: summary of recommendations developed by an international working party, supported by the World Congresses of Gastroenterology, Los Angeles, 1994. | journal = Am J Gastroenterol | volume = 89 | issue = 8 Suppl | pages = S177-81 | month = Aug | year = 1994 | doi = | PMID = 8048409 }}</ref><ref>URL: [http://familydoctor.org/familydoctor/en/diseases-conditions/hepatitis-b.html http://familydoctor.org/familydoctor/en/diseases-conditions/hepatitis-b.html]. Accessed on: 2 May 2012.</ref>
#Acute < 6 months duration.
#Chronic > 6 months duration.

==Hepatitis A==
*Infection is self-limited, i.e. not persistent.
**May present as ''[[fulminant hepatic necrosis]]''.
*Usually asymptomatic in children.<ref name=pmid20068336>{{cite journal |author=Jeong SH, Lee HS |title=Hepatitis A: clinical manifestations and management |journal=Intervirology |volume=53 |issue=1 |pages=15–9 |year=2010 |pmid=20068336 |doi=10.1159/000252779 |url=}}</ref>
*Serology is diagnostic.

==Hepatitis B==
:''Hepatitis B virus'', abbreviated ''HBV'', redirects here.
{{Main|Hepatitis B}}

==Hepatitis C==
{{Main|Hepatitis C}}

=Other infections=
*Hydatid disease (Hydatid cyst).
*Ascaris.
*Fasciola

==Hydatid disease==
*[[AKA]] ''hydatid cyst''.
===General===
*Etiology: ''[[Echinococcus]]''.

===Microscopic===
Features:
*Laminated wall +/- calcification.<ref name=Ref_PBPoD8_448>{{Ref PCPBoD8|448}}</ref>
*Organisms -- see ''[[Echinococcus]]''.

====Images====
<gallery>
Image:Liver_cyst_wall_-_intermed_mag.jpg | Liver cyst wall - intermed. mag. (WC)
Image:Liver_cyst_wall_-_high_mag.jpg | Liver cyst wall - high mag. (WC)
Image: Laminated liver cyst wall - intermed mag.jpg | Characteristic laminated portion - intermed. mag. (WC)
Image: Laminated liver cyst wall - high mag.jpg | Characteristic laminated portion - high mag. (WC)
</gallery>
[[www]]:
*[http://pathmicro.med.sc.edu/parasitology/hydatid-hist1.jpg Hydatid cyst (med.sc.edu)].
*[http://www.atlas.or.kr/atlas/include/viewImg.html?uid=645 Hydatid cyst (atlas.or.kr)].
*[http://casereports.bmj.com/content/2009/bcr.04.2009.1798.full Hydatid cyst (casereports.bmj.com)].

==Abscess==
A. [[File:1 ABS 1 680x512px.tif|A process replaces most of the liver parenchyma (20X).]]
 
B. [[File:2 ABS 1 680x512px.tif|Fibrinopurulent exudate apposes granulation tissue (200X).]]
 
C. [[File:3 ABS 1 680x512px.tif|Neutrophils lie in widened sinusoids (200X)..]]
 
D. [[File:4 ABS 1 680x512px.tif|Trichrome shows collagenization of spaces of Disse. Scarring about an abscess or other mass lesion should not be interpreted as reflective of the liver in general (200X).]]
 
Abscess. A. A process replaces most of the liver parenchyma. B. Fibrinopurulent exudate apposes granulation tissue. C. Neutrophils lie in widened sinusoids. D. Trichrome shows collagenization of spaces of Disse. Scarring about an abscess or other mass lesion should not be interpreted as reflective of the liver in general (LR 200X).

==Coccidiomycosis==
A. [[File:Coccidiomycosis - 1 - 40X 680x512px shot.tif|500x500px Granulomas at low power]]
 
B. [[File:Coccidiomycosis - 1 - 200X 680x513px shot.tif|500x500px Granulomas with centrally crowded cells & lady slipper macrophage nuclei]]
 
C. [[File:Coccidiomycosis - 1 - 400X 1369x1024px shot.tif|500x500px Center of previous granuloma showing pyknotic macrophage nuclei]]
 
D. [[File:Coccidiomycosis - 1 - GMS 400X 1369x1024px shot.tif|500x500px Four Coccidiomycotic spherules]]
 
Coccidiomycosis. A. Note the granulomas in otherwise undisturbed liver (UL). B. Granuloma with centrally crowded cells & lady slipper macrophage nuclei. C. Center of granuloma with pyknotic macrophage nuclei, "necrotizing". D. Organisms on GMS stain.

=Metabolic and toxic=
==Alcoholic liver disease==
===General===
*Acute and/or chronic liver changes due to excessive [[alcohol]] use - includes:
**''[[Alcoholic steatohepatitis]]'' (ASH), [[AKA]] ''alcoholic hepatitis''.<ref>URL: [http://emedicine.medscape.com/article/170539-overview http://emedicine.medscape.com/article/170539-overview]. Accessed on: 3 May 2012.</ref>
***Alcoholic hepatitis can be with minimal steatosis.<ref>STC. 6 December 2010.</ref>
**[[Steatosis]] - classically macrovescicular and centrilobular.
**Alcoholic [[cirrhosis]].

====Classic lab findings in EtOH abusers====
*AST & ALT elevated with AST:ALT=2:1.
*GGT elevated.
*MCV increased.

===Gross pathology/radiologic findings===
*Classically micronodular pattern.
**May be macronodular.

===Microscopic===
See:
*''[[Steatohepatitis]]'' section and ''[[ballooning degeneration]]'' section.

Features:
*Often zone III damage.
*Cholestatsis common, i.e. yellow staining.
**NASH (non-alcoholic steatohepatitis) usu. does not have cholestasis.<ref>STC. 6 December 2010.</ref>
*Fibrosis starts at central veins.
*Neutrophils (often helpful) -- few other things have PMNs. (???)
**Neutrophils cluster around cells with Mallory hyaline.

====Images====

A. [[File:1 etoh 3 680x512px.tif| Alcoholic hepatitis with Metavir stage IV fibrosis (advanced fibrosis/cirrhosis).]]
 
B. [[File:2 etoh 3 680x512px.tif| Alcoholic hepatitis with Metavir stage IV fibrosis (advanced fibrosis/cirrhosis).]]
 
C. [[File:3 etoh 3 680x512px.tif| Alcoholic hepatitis with Metavir stage IV fibrosis (advanced fibrosis/cirrhosis).]]
 
D. [[File:4 etoh 3 680x512px.tif| Alcoholic hepatitis with Metavir stage IV fibrosis (advanced fibrosis/cirrhosis).]]
 
E. [[File:5 etoh 3 680x512px.tif| Alcoholic hepatitis with Metavir stage IV fibrosis (advanced fibrosis/cirrhosis).]]
 
F. [[File:6 etoh 3 680x512px.tif| Alcoholic hepatitis with Metavir stage IV fibrosis (advanced fibrosis/cirrhosis).]]
 

Alcoholic hepatitis with Metavir stage IV fibrosis (advanced fibrosis/cirrhosis).
A. Trichrome shows relatively non-inflamed fibrous bands, as well as [between green dots] nodules. The lack of regeneration throughout might have precluded a diagnosis of cirrhosis, but stage IV fibrosis under the Metavir system is justified. B. Reticulin shows regenerative nodules [left] with mostly two or more nuclei between black lines juxtaposed to non-regenerative hepatocytes on the right, without piecemeal necrosis. C. Regenerative nodules show occasional neutrophils [red arrow] and cytoplasmic tufts of ballooned cells, sometimes possibly Mallory hyalin [green arrows]. D. Triads (note vein [green arrow], artery [yellow arrow], and interlobular bile duct [blue arrow]) generally showed little or no interface hepatitis, even when expanded by fibrosis and inflamed. E. Occasional foci of spotty necrosis were seen. F. This edge of an inflamed triads shows neutrophils about proliferated bile ducts [red arrows], as well as Mallory-Denk bodies [blue arrows].
 
A. [[File:1 etoh 4 680x512px.tif| Cirrhosis in an alcoholic.]]
 
B. [[File:2 etoh 4 680x512px.tif| Cirrhosis in an alcoholic.]]
 
C. [[File:3 etoh 4 680x512px.tif| Cirrhosis in an alcoholic.]]
 
D. [[File:4 etoh 4 680x512px.tif| Cirrhosis in an alcoholic.]]
 
E. [[File:5 etoh 4 680x512px.tif| Cirrhosis in an alcoholic.]]
 
F. [[File:6 etoh 4 680x512px.tif| Cirrhosis in an alcoholic.]]
 
Definite cirrhosis in an alcoholic. A. Hepatocyte free bands parse tissue, with occasional definite islands [arrows]. B. Trichrome establishes blue fibrosis about isles [arrows]. C. Reticulin stain shows nodules with regeneration, wherein a large proportion of them are at least two nuclei thick [arrows]. D. Bile duct proliferation can be difficult, sometimes mimicking cholangiocarcinoma. Follow the double headed arrows to see how the ductules can be seen to proliferate from a single sources, with all ducts being complete, without necrotic epithelial cells. E. PAS with distase can help, as cholangiocarcinoma generally lacks the red rim of proliferating bile ductules [arrows]; again note the connections that can be made between the ductule openings by the blue double headed arrows. The cyan double headed arrows show general parallelism, consistent with uniform directionality induced by extrinsic force, not a neoplastic spread. F. Trichrome shows the most difficult focus. Double headed arrows display the connectivity seen before of the proliferated bile ductules. Note that numerous pairs of adjacent perpendicular glands without a head to foot appearance are not seen that would indicate the disorderly spread of cholangiocarcinoma.
 
A. [[File:1 ALC 2 680x512px.tif|Expanded, inflamed triads with increased bile duct/vascular openings. Mild steatosis (40X).]]
 
B. [[File:2 ALC 2 680x512px.tif|Trichrome stain shows periportal fibrosis [red arrowheads] (200X).]]
 
C. [[File:3 ALC 2 680x512px.tif|PAS with diastase stain shows proliferated bile ductules [blue arrowheads] in stroma with mixed inflammatory infiltrate (400X)]]
 
D. [[File:4 ALC 2 680x512px.tif|Neutrophils about ballooned hepatocyte (satellitosis) [yellow arrowheads]. Councilman bodies [green arrowheads] (400X).]]
 
Alcoholic hepatitis without cirrhosis. No history of viral disease. AMA negative. A. Expanded, inflamed triads with increased bile duct/vascular openings. Mild steatosis. B. Trichrome stain shows periportal fibrosis [red arrowheads]. C. PAS with diastase stain shows proliferated bile ductules [blue arrowheads] in stroma with mixed inflammatory infiltrate. D. Neutrophils about ballooned hepatocyte (satellitosis) [yellow arrowheads]. Councilman bodies [green arrowheads].

Notes:
*If portal inflammatory infiltrates more than mild, r/o other causes i.e. [[viral hepatitis]].
*Mallory bodies once thought to be characteristic; now considered non-specific and generally poorly understood.<ref>{{cite journal |author=Jensen K, Gluud C |title=The Mallory body: theories on development and pathological significance (Part 2 of a literature survey) |journal=Hepatology |volume=20 |issue=5 |pages=1330-42 |year=1994 |month=November |pmid=7927269 |doi= |url=}}</ref>
*Some consider ''alcoholic liver disease'' a clinical diagnosis, i.e. as a pathologist one does not diagnose it.<ref>MG. September 2009.</ref>

==Non-alcoholic fatty liver disease==
*Abbreviated ''NAFLD''.
*Fatty liver that is not due to alcohol; includes obesity-related fatty liver, metabolic disease/diabetes-related fatty liver.

===NASH===
*Non-alcoholic steatohepatitis - see ''steatohepatitis'' section.
*Histologically indistinguishable from ASH.
*NASH is a ''clinical diagnosis'' based on exclusion of alcohol.

==Steatohepatitis==
{{Main|Steatohepatitis}}

=Autoimmune=
==Autoimmune hepatitis==
*Abbreviated ''AIH''.
{{Main|Autoimmune hepatitis}}

==Primary biliary cirrhosis==
*Abbreviated PBC.
{{Main|Primary biliary cirrhosis}}

==Autoimmune hepatitis with obstruction - combined changes==
A. [[File:1 AIH OBS 1.tif|Low power shows inflammation; portal triads, lobules, central veins cannot be distinguished (40X).]]
 
B. [[File:2 AIH OBS 1.tif|Trichrome shows central venous sclerosis (red arrowhead), periportal fibrosis (green arrowhead), & space of Disse collagenization (yellow arrowhead); juxtaposition of central vein & portal tract indicates collapse, no definite bridging was seen (100X)]]
 
C. [[File:3 AIH OBS 1.tif|Central vein is inflamed with a rare plasma cell (cyan arrowhead) (400X).]]
 
D. [[File:4 AIH OBS 1.tif|Interface hepatitis with plasma cells (yellow arrows) and ballooned hepatocytes (red arrows). Lobule is disorganized (400X).]]
 
E. [[File:5 AIH OBS 1.tif|Proliferating bile ductules (blue arrows) with occasional neutrophils (fucsia arrows), indicative of obstruction, but not acute cholangitis, which requires inflamed bile duct itself, best diagnosed with associated blood vessel (400X).]]
 
F. [[File:6 AIH OBS 1.tif|Rare distorted rosettes with greenish brown strands of bile (left arrow) or bile plugs (right arrow) (400X).]]
 
Patient with SLE and obstructive jaundice that resolved with apparent passage of stone. A. Low power shows inflammation; portal triads, lobules, central veins cannot be distinguished. B. Trichrome shows central venous sclerosis (red arrowhead), periportal fibrosis (green arrowhead), & space of Disse collagenization (yellow arrowhead); juxtaposition of central vein & portal tract indicates collapse, no definite bridging was seen. C. Central vein is inflamed with a rare plasma cell (cyan arrowhead). D. Interface hepatitis with plasma cells (yellow arrows) and ballooned hepatocytes (red arrows). Lobule is disorganized. E. Proliferating bile ductules (blue arrows) with occasional neutrophils (fucsia arrows), indicative of obstruction, but not acute cholangitis, which requires inflamed bile duct itself, best diagnosed with associated blood vessel. F. Rare distorted rosettes with greenish brown strands of bile (left arrow) or bile plugs (right arrow).

==Autoimmune hepatitis-primary biliary cirrhosis overlap syndrome==
*Abbreviation ''AIH-PBC OS''.
===General===
Epidemiology:
*Rare.

Serology:<ref name=pmid19491855>{{Cite journal | last1 = Muratori | first1 = P. | last2 = Granito | first2 = A. | last3 = Pappas | first3 = G. | last4 = Pendino | first4 = GM. | last5 = Quarneti | first5 = C. | last6 = Cicola | first6 = R. | last7 = Menichella | first7 = R. | last8 = Ferri | first8 = S. | last9 = Cassani | first9 = F. | title = The serological profile of the autoimmune hepatitis/primary biliary cirrhosis overlap syndrome. | journal = Am J Gastroenterol | volume = 104 | issue = 6 | pages = 1420-5 | month = Jun | year = 2009 | doi = 10.1038/ajg.2009.126 | PMID = 19491855 }}</ref>
*AMA +ve.
*Anti-dsDNA +ve.

===Microscopic===
:See: ''[[autoimmune hepatitis]]'' and ''[[primary biliary cirrhosis]]''.
A. [[File:1 AIH PBC 1 680x512px.tif|Expanded portal tracts with fuzzy edges (40X).]]
 
B. [[File:2 AIH PBC 1 680x512px.tif|Interface hepatitis with plasma cells (400X).]]
 
C. [[File:3 AIH PBC 1 680x512px.tif|Loose granuloma (400X).]]
 
D. [[File:4 AIH PBC 1 680x512px.tif|Damaged bile duct (400X).]]
 
AIH/PBC overlap. AMA & ANA positive with Alkaline phosphatase > 2 upper limit of normal & one ALT > 5 times upper limit of normal. A. Expanded portal tracts with fuzzy edges. B. Interface hepatitis with plasma cells. C. Loose granuloma. D. Damaged bile duct.

==Primary sclerosing cholangitis==
*Abbreviated ''PSC''.
{{Main|Primary sclerosing cholangitis}}

=Hereditary=
==Caroli disease==
===General===
*Genetic disease.
**Frequently associated with [[autosomal recessive polycystic kidney disease]] (ARPKD).<ref name=omim263200>{{OMIM|263200}}</ref>
**May be seen in isolation.<ref name=omim600643>{{OMIM|600643}}</ref>

Clinical:<ref name=pmid17461493>{{Cite journal | last1 = Yonem | first1 = O. | last2 = Bayraktar | first2 = Y. | title = Clinical characteristics of Caroli's syndrome. | journal = World J Gastroenterol | volume = 13 | issue = 13 | pages = 1934-7 | month = Apr | year = 2007 | doi = | PMID = 17461493 }}</ref>
*Recurrent [[cholangitis]].
*Recurrent [[cholelithiasis]].
*[[Cholangiocarcinoma]]<ref name=pmid17461492>{{Cite journal | last1 = Yonem | first1 = O. | last2 = Bayraktar | first2 = Y. | title = Clinical characteristics of Caroli's disease. | journal = World J Gastroenterol | volume = 13 | issue = 13 | pages = 1930-3 | month = Apr | year = 2007 | doi = | PMID = 17461492 }}</ref> - seen in ~7% of cases.<ref name=pmid15347876>{{Cite journal | last1 = Karim | first1 = AS. | title = Caroli's disease. | journal = Indian Pediatr | volume = 41 | issue = 8 | pages = 848-50 | month = Aug | year = 2004 | doi = | PMID = 15347876 }}</ref>

Note:
*''Caroli syndrome'' = Caroli disease + congenital hepatic fibrosis.<ref name=pmid15888616>{{Cite journal | last1 = Brancatelli | first1 = G. | last2 = Federle | first2 = MP. | last3 = Vilgrain | first3 = V. | last4 = Vullierme | first4 = MP. | last5 = Marin | first5 = D. | last6 = Lagalla | first6 = R. | title = Fibropolycystic liver disease: CT and MR imaging findings. | journal = Radiographics | volume = 25 | issue = 3 | pages = 659-70 | month = | year = | doi = 10.1148/rg.253045114 | PMID = 15888616 | URL = http://radiographics.rsna.org/content/25/3/659.long }}</ref>

===Gross===
*Dilated bile ducts.<ref name=omim263200/>

===Microscopic===
Features:<ref name=pmid17461493/>
*Dilated bile ducts.
*Periductal fibrosis. (???)
*+/-Fibrosis.

Image:
*[http://www.meddean.luc.edu/lumen/MedEd/orfpath/11-3-10.jpg Caroli disease (meddean.luc.edu)].<ref>URL: [http://www.meddean.luc.edu/lumen/MedEd/orfpath/develop.htm http://www.meddean.luc.edu/lumen/MedEd/orfpath/develop.htm]. Accessed on: 1 December 2011.</ref>

==Hereditary hemochromatosis==
:''For secondary causes see [[secondary hemochromatosis]]''.
{{Main|Hereditary hemochromatosis}}

==Wilson disease==
{{Main|Wilson's disease}}

==Alpha-1 antitrypsin deficiency==
*[[AKA]] ''alpha1-antiprotease inhibitor deficiency''.
{{Main|Alpha-1 antitrypsin deficiency }}

=Other=
==Budd-Chiari syndrome==
*[[AKA]] ''hepatic vein obstruction''.
===General===
*Hepatic outflow obstruction.

Clinical triad:<ref name=pmid21573256>{{Cite journal | last1 = Fox | first1 = MA. | last2 = Fox | first2 = JA. | last3 = Davies | first3 = MH. | title = Budd-Chiari syndrome--a review of the diagnosis and management. | journal = Acute Med | volume = 10 | issue = 1 | pages = 5-9 | month = | year = 2011 | doi = | PMID = 21573256 }}</ref>
*Ascites.
*Abdominal pain.
*Hepatomegaly.

Etiology:
*~50% have a [[myeloproliferative disease]].<ref name=pmid18814079>{{Cite journal | last1 = Plessier | first1 = A. | last2 = Valla | first2 = DC. | title = Budd-Chiari syndrome. | journal = Semin Liver Dis | volume = 28 | issue = 3 | pages = 259-69 | month = Aug | year = 2008 | doi = 10.1055/s-0028-1085094 | PMID = 18814079 }}</ref>
*May be due to mass effect from a tumour.

Clinical DDx:
*[[Hepatic veno-occlusive disease]].

===Microscopic===
Features:<ref name=pmid17569137>{{Cite journal | last1 = Aydinli | first1 = M. | last2 = Bayraktar | first2 = Y. | title = Budd-Chiari syndrome: etiology, pathogenesis and diagnosis. | journal = World J Gastroenterol | volume = 13 | issue = 19 | pages = 2693-6 | month = May | year = 2007 | doi = | PMID = 17569137 | url=http://www.wjgnet.com/1007-9327/full/v13/i19/2693.htm }}</ref>
*Sinusoidal dilation in zone III (congestion).
*+/-Hepatocyte drop-out.
*+/-Centrilobular fibrosis.

DDx congestion:
*Congestive heart failure ([[congestive hepatopathy]]).
*Constrictive pericarditis.

==Vanishing bile duct syndrome==
*[[AKA]] ''bile duct loss'', [[AKA]] ''ductopenia''.<ref name=pmid11521176/>
===General===
*Fatal.

DDx:<ref name=pmid18242505/>
*[[Primary biliary cirrhosis]].
*[[Primary sclerosing cholangitis]].
*[[GVHD]].<ref name=pmid7994249>{{Cite journal | last1 = Yeh | first1 = KH. | last2 = Hsieh | first2 = HC. | last3 = Tang | first3 = JL. | last4 = Lin | first4 = MT. | last5 = Yang | first5 = CH. | last6 = Chen | first6 = YC. | title = Severe isolated acute hepatic graft-versus-host disease with vanishing bile duct syndrome. | journal = Bone Marrow Transplant | volume = 14 | issue = 2 | pages = 319-21 | month = Aug | year = 1994 | doi = | PMID = 7994249 }}</ref>
*[[Drug-induced liver disease|Drugs]].<ref name=pmid11352118>{{Cite journal | last1 = Chitturi | first1 = S. | last2 = Farrell | first2 = GC. | title = Drug-induced cholestasis. | journal = Semin Gastrointest Dis | volume = 12 | issue = 2 | pages = 113-24 | month = Apr | year = 2001 | doi = | PMID = 11352118 }}</ref>
*Chronic rejection.<ref name=pmid11521176>{{Cite journal | last1 = Inomata | first1 = Y. | last2 = Tanaka | first2 = K. | title = Pathogenesis and treatment of bile duct loss after liver transplantation. | journal = J Hepatobiliary Pancreat Surg | volume = 8 | issue = 4 | pages = 316-22 | month = | year = 2001 | doi = 10.1007/s0053410080316 | PMID = 11521176 }}</ref>

===Microscopic===
Features:<ref name=pmid18242505>{{Cite journal | last1 = Reau | first1 = NS. | last2 = Jensen | first2 = DM. | title = Vanishing bile duct syndrome. | journal = Clin Liver Dis | volume = 12 | issue = 1 | pages = 203-17, x | month = Feb | year = 2008 | doi = 10.1016/j.cld.2007.11.007 | PMID = 18242505 }}</ref>
*Loss of intrahepatitic bile ducts - '''key feature'''.
*Cholestasis.

Note:
*May occur without fibrosis and inflammation; thus, can be easy to miss.

===IHC===
*[[CK7]] -ve.
**Marks bile ducts.

==Extrahepatic biliary obstruction==
A. [[File:1 OBS 3 680x512px.tif|Sinusoidal dilatation, circular spaces of hepatocytes, small portal triads(40X).]]
 
B. [[File:2 OBS 3 680x512px.tif|Bile in hepatocytes about central vein & in plugs in canaliculi [yellow arrowhead] (400X).]]
 
C. [[File:3 OBS 3 680x512px.tif|Trichrome shows fibrosis about central vein (400X).]]
 
D. [[File:4 OBS 3 680x512px.tif|PAS with diastase shows portal triads with mild edema and chronic inflammation, without tortuous bile duct (400X).]]
 
Early extrahepatic biliary obstruction, demonstrated radiographically, transient, with rise in bilirubin, alkaline phosphatase, and transaminases. Pure canalicular cholestasis near terminal hepatic venules also seen in acute hepatitis, drug reactions, benign recurrent cholestasis, pregnancy, sepsis, & lymphomas. A. Sinusoidal dilatation, circular spaces of hepatocytes, small portal triads. B. Bile in hepatocytes about central vein & in plugs in canaliculi [yellow arrowhead]. C. Trichrome shows fibrosis about central vein. D. PAS with diastase shows portal triads with mild edema and chronic inflammation, without tortuous bile duct.
 
A. [[File:1 OBS 2 680x512px.tif|Expanded inflamed portal triads, swollen hepatocytes (40X)]]
 
B. [[File:2 OBS 2 680x512px.tif|Edematous stroma, proliferating ductules [yellow arrowheads], PAS-D macrophages [red arrowhead] (PAS with diastasse, 200X)]]
 
C. [[File:3 OBS 2 680x512px.tif|Disordered, often swollen hepatocytes,some with feathery degeneration (net like spaces in cytoplasm [blue arrowhead], rare Councilman body [green arrowhead] (400X)]]
 
D. [[File:4 OBS 2 1360x1024px.tif|Bile in hepatocytes [cyan arrrowhead] & in canaliculi [purple arrowheads]. Empty acinar spaces bounded by hepatocytes [orange arrowhead] (400X, higher pixel),]]
 
Changes of extrahepatic biliary obstruction, months duration. A. Expanded inflamed portal triads, swollen hepatocytes. B. Edematous stroma, proliferating ductules [yellow arrowheads], PAS-D macrophages [red arrowhead]. C. Disordered, often swollen hepatocytes,some with feathery degeneration (net like spaces in cytoplasm) [blue arrowhead], rare Councilman body [green arrowhead]. D. Bile in hepatocytes [cyan arrrowhead] & in canaliculi [purple arrowheads]. Empty acinar spaces bounded by hepatocytes [orange arrowhead].
 
A. [[File:1 Bd obs 4 680x512px.tif|Expanded, light colored portal triads (arrows)(20X).]]
 
B. [[File:2 Bd obs 4 680x512px.tif|Proliferating bile ductules (cyan arrows) with neutrophils (yellow arrows), not specific for acute cholangitis, of assistance with large bile duct obstruction (400X)..]]
 
C. [[File:3 Bd obs 4 680x512px.tif|Uninflamed interlobular duct (yellow arrow) with, accompanying blood vessel (red arrow) (400X)]]
 
D. [[File:4 Bd obs 4 680x512px.tif|Bile infarct with pyknotic nuclei (arrows)(400X).]]
 
E. [[File:5 Bd obs 4 680x512px.tif|Bile (arrow) in interlobular bile duct with disordered nuclei (400X).]]
 
F. [[File:6 Bd obs 4 680x512px.tif|Bile plugs in cannaliculi (red arrows), feathery degeneration producing foamy macrophage like hepatocytes (yellow arrows)(400X).]]
 
Large bile duct obstruction. A. Expanded, light colored portal triads (arrows). B. Proliferating bile ductules (cyan arrows) with neutrophils (yellow arrows), not specific for acute cholangitis, of assistance with large bile duct obstruction. C. Uninflamed interlobular duct (yellow arrow) with, accompanying blood vessel (red arrow). D. Bile infarct with pyknotic nuclei (arrows). E. Bile (arrow) in interlobular bile duct with disordered nuclei. F. Bile plugs in cannaliculi (red arrows), feathery degeneration producing foamy macrophage-like hepatocytes (yellow arrows).

==Congestive hepatopathy==
===General===
*Liver failure due to (right) heart failure.
*AKA ''cardiac cirrhosis'' - a term used by clinicians.
**Generally, it does not satisfy pathologic criteria for cirrhosis.<ref>URL: [http://emedicine.medscape.com/article/151792-overview http://emedicine.medscape.com/article/151792-overview]. Accessed on: 17 June 2010.</ref>

===Gross===
*"Nutmeg" liver - yellow spotted appearance.

===Microscopic===
Features:<ref>URL: [http://emedicine.medscape.com/article/151792-diagnosis http://emedicine.medscape.com/article/151792-diagnosis]. Accessed on: 17 June 2010.</ref>
*Zone III atrophy.
*Portal venule (central vein) distension.
*Perisinusoidal fibrosis - progresses to centrilobular fibrosis and then diffuse fibrosis.
*Dilation of sinusoids in ''all'' zone III areas - '''key feature'''.<ref>Suggested by OA. September 2009.</ref>

DDx:
*[[Hemangioma of the liver]] - should be focal lesion.
Cardiac (congestive) hepatopathy, wherein outflow obstruction occurs secondary to backflow from a failing heart, and Budd Chiari syndrome, wherein obstruction of outflow occurs secondary to obstruction, usually thrombotic, have overlapping features, including sinusoidal dilation with emphasis upon the central vein, space of Disse erythrocytes, centrilobular inflammation, hemorrhage, bile ductules, and hemosiderin, and portal inflammation, fibrosis and bile ductular reaction. Centrilobular dropout/necrosis is more common in Budd Chiari syndrome, while peri-central venous and sinusoidal fibrosis are more common in cardiac hepatopathy. In end stage liver, fibrosis for cardiac hepatopathy comprises stellate centrizonal fibrous with haphazard spread, as opposed to the more frequent nodular cirrhosis in Budd-Chiari. Clinical findings are important to take into account, as cardiac failure is usually well known at the time of diagnosis as are the clinical predictors of Budd Chiari syndrome, prothrombotic states, myeloproliferative diseases, and oral contraceptive use. <ref name=pmid27681331 >{{cite journal |author=Gonzalez RS, Gilger MA, Huh WJ, Washington MK |title=The spectrum of histologic findings in hepatic outflow obstruction |journal= Arch Pathol Lab Med |volume=141 |issue= |pages=98 |year=2017 |pmid= 27681331 ||doi= 10.5858/arpa.2015-0388-OA |url=http http://www.archivesofpathology.org/doi/10.5858/arpa.2015-0388-OA?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%3dpubmed&code=coap-site }}</ref>
====Images====
<gallery>
Image:Congestive_hepatopathy_high_mag.jpg | Mild congestive hepatopathy. (WC) 
A.[[File:1 CEN NEC 1 680x512px.tif|PAS without diastase shows ovoids of necrosis {40X).]] 
B. [[File:2 CEN NEC 1 680x512px.tif|Necrosis with central vein [yellow arrowhead], inflammatory cells, residual Councilman body [green arrowhead], and hepatocyte with mitotic figure [red arrowhead] (400X).]]
 
C. [[File:3 CEN NEC 1 680x512px.tif|Trichrome highlights fibrosis about central vein [yellow arrowhead] & shows beginning scar formation [green arrowheads]. Note residual atrophic hepatocytes [blue arrowheads] (400X).]]
 
D. [[File:4 CEN NEC 1 680x512px.tif|Portal triads are largely unaffected (400X).]]
|} 
Centrilobular necrosis (seen in circulatory failure and with toxins/drugs). A. PAS without diastase shows ovoids of necrosis. B. Necrosis with central vein [yellow arrowhead], inflammatory cells, residual Councilman body [green arrowhead], and hepatocyte with mitotic figure [red arrowhead]. C. Trichrome highlights fibrosis about central vein [yellow arrowhead] & shows beginning scar formation [green arrowheads]. Note residual atrophic hepatocytes [blue arrowheads]. D. Portal triads are largely unaffected (LR 400X)
 
A. [[File:1 CHF 1 680x512px.tif|Dilated and undilated sinusoidal regions (40X).]]
 
B. [[File:2 CHF 1 680x512px.tif|Thrombi in sinusoids; glycogenated nuclei likely reflect patient’s diabetes mellitus (400X).]]
 
C. [[File:3 CHF 1 680x512px.tif|Dilated portal vein (400X).]]
 
D. [[File:4 CHF 1 680x512px.tif|Reticulin shows collapse (thick black lines) as well as a dilated portal vein (200X).]]
 
E. [[File:5 CHF 1 680x512px.tif|Trichrome shows space of Disse collagenization (pericellular fibrosis) (200X).]]
 
F. [[File:6 CHF 1 680x512px.tif|Trichrome shows periportal fibrosis; no bridging was seen (200X).]]

Patient with congestive heart failure and stage I fibrosis. A. Dilated and undilated sinusoidal regions. B. Thrombi in sinusoids; glycogenated nuclei likely reflect patient’s diabetes mellitus. C. Dilated portal vein. D. Reticulin shows black lines of bridging, too thick for collapse. E. Trichrome shows space of Disse collagenization (pericellular fibrosis). F. Trichrome shows bridge beginning off to right; when it is more than a mere spike, it is a bridge.

==Drug-induced liver disease==
*[[AKA]] ''drug-induced liver toxicity''.
{{Main|Drug-induced liver disease}}

==Focal nodular hyperplasia==
*Abbreviated ''FNH''.
{{Main|Focal nodular hyperplasia}}

==Nodular regenerative hyperplasia==
===General===
*Associated with renal transplants, [[bone marrow transplant]]s and [[vasculitides]].<ref name=Ref_PBoD922>{{Ref PBoD|922}}</ref>
*Can lead to [[portal hypertension]] and many of the associated complications.<ref name=pmid22554152>{{Cite journal | last1 = Bissonnette | first1 = J. | last2 = Généreux | first2 = A. | last3 = Côté | first3 = J. | last4 = Nguyen | first4 = B. | last5 = Perreault | first5 = P. | last6 = Bouchard | first6 = L. | last7 = Pomier-Layrargues | first7 = G. | title = Hepatic hemodynamics in 24 patients with nodular regenerative hyperplasia and symptomatic portal hypertension. | journal = J Gastroenterol Hepatol | volume = 27 | issue = 8 | pages = 1336-40 | month = Aug | year = 2012 | doi = 10.1111/j.1440-1746.2012.07168.x | PMID = 22554152 }}
</ref>

====Etiology====
*Arterial hypervascularity secondary to loss of hepatic vein radicles (loss of central venule in hepatic lobule).<ref name=Ref_PBoD922>{{Ref PBoD|922}}</ref>

ASIDE: radicle = ramulus - smallest branch or vessel or nerve.<ref name=Dorlands2>Dorland's Medical Dictionary. 30th Ed.</ref>

===Gross===
*Diffuse nodularity - whole liver.

===Microscopic===
Features:<ref name=Ref_PBoD922>{{Ref PBoD|922}}</ref>
*"Plump" hepatocytes surrounded by atrophic ones.
*No fibrosis.

==Sinuosoidal obstruction syndrome==
*May be referred to as ''Hepatic veno-occlusive disease''.<ref name=pmid11928077>{{Cite journal | last1 = DeLeve | first1 = LD. | last2 = Shulman | first2 = HM. | last3 = McDonald | first3 = GB. | title = Toxic injury to hepatic sinusoids: sinusoidal obstruction syndrome (veno-occlusive disease). | journal = Semin Liver Dis | volume = 22 | issue = 1 | pages = 27-42 | month = Feb | year = 2002 | doi = 10.1055/s-2002-23204 | PMID = 11928077 }}.</ref>
===General===
*Term for obstruction due to toxicity from a chemotherapeutic agent.<ref name=pmid16393276>{{Cite journal | last1 = Helmy | first1 = A. | title = Review article: updates in the pathogenesis and therapy of hepatic sinusoidal obstruction syndrome. | journal = Aliment Pharmacol Ther | volume = 23 | issue = 1 | pages = 11-25 | month = Jan | year = 2006 | doi = 10.1111/j.1365-2036.2006.02742.x | PMID = 16393276 }}</ref><ref name=pmid17569137>{{Cite journal | last1 = Aydinli | first1 = M. | last2 = Bayraktar | first2 = Y. | title = Budd-Chiari syndrome: etiology, pathogenesis and diagnosis. | journal = World J Gastroenterol | volume = 13 | issue = 19 | pages = 2693-6 | month = May | year = 2007 | doi = | PMID = 17569137 | url=http://www.wjgnet.com/1007-9327/full/v13/i19/2693.htm }}</ref>

Clinical DDx:
*[[Budd-Chiari syndrome]].

===Microscopic===
Features:<ref name=pmid17569137>{{Cite journal | last1 = Aydinli | first1 = M. | last2 = Bayraktar | first2 = Y. | title = Budd-Chiari syndrome: etiology, pathogenesis and diagnosis. | journal = World J Gastroenterol | volume = 13 | issue = 19 | pages = 2693-6 | month = May | year = 2007 | doi = | PMID = 17569137 | url=http://www.wjgnet.com/1007-9327/full/v13/i19/2693.htm }}</ref>
*Subendothelial swelling in hepatic venules.

Negatives:
*No thrombosis.

==Ascending Cholangitis (Acute Cholangitis)==
===General===
*Term for infection of bile ducts, usually due to obstruction

Clinical DDx:

===Microscopic===
====Images====

A. [[File:1 asc chol 1 680x512px.tif|Rounded, clear (edematous) portal tracts (arrows) separated by hepatocytes with dilated sinusoids (Row 1 Left 40X).]]
 
B. [[File:2 asc chol 1 680x512px.tif|Neutrophils about hepatocytes (arrows) have spilled into the lobule from a portal tract (Row 1 Right 200X).]]
 
C. [[File:3 asc chol 1 680x512px.tif|Proliferated bile ductules (arrows) bearing neutrophils within epithelium and lumens are features of obstruction that should prompt a search for interlobular ducts with acute inflammation (Row 2 Left 400X).]]
 
D. [[File:4 asc chol 1 680x512px.tif|The epithelium of the ducts can be severely degenerated. Neutrophils (cyan arrows) invade epithelium of an interlobular duct that are recognizable mainly as a circle of rounded nuclei; the associated arteriole (red arrow) should be identified to ensure an interlobular duct is being evaluated. Note the proliferated bile ductules (blue arrows) (Row 2 Right 400X).]]
 
E. [[File:5 asc chol 1 680x512px.tif|A PAS without diastase stain colors the arteriole (blue arrow), as well as the rim of the interlobular duct within which lies a neutrophil (cyan arrow) (Row 2 Right 400X). .]]
 
F. [[File:6 asc chol 1 680x512px.tif|A PAS with diastase stain colors the arteriole (red arrow), as well as the rim of the interlobular duct within which lies a neutrophil (cyan arrow) (Row 1 Right 400X)]]
 
Acute cholangitis in a patient with multiple bile duct procedures. After the biopsy, removal of bile duct stones released pus. A. Rounded, clear (edematous) portal tracts (arrows) separated by hepatocytes with dilated sinusoids. B. Neutrophils about hepatocytes (arrows) have spilled into the lobule from a portal tract. C, Proliferated bile ductules (arrows) bearing neutrophils within epithelium and lumens are features of obstruction that should prompt a search for interlobular ducts with acute inflammation. D. The epithelium of the ducts can be severely degenerated. Neutrophils (cyan arrows) invade epithelium of an interlobular duct that are recognizable mainly as a circle of rounded nuclei; the associated arteriole (red arrow) should be identified to ensure an interlobular duct is being evaluated. Note the proliferated bile ductules (blue arrows). E. A PAS without diastase stain colors the arteriole (blue arrow), as well as the rim of the interlobular duct within which lies a neutrophil (cyan arrow). F. A PAS with diastase stain colors the arteriole (red arrow), as well as the rim of the interlobular duct within which lies a neutrophil (cyan arrow).

A.[[File:1 Sep Acu Cho 1 680x512px.tif|Low power shows variably sized inflamed portal tracts (40X)]]
 
B. [[File:2 Sep Acu Cho 1 680x512px.tif|Trichrome shows dilated sinusoids and space of Disse collagenization (200X)]]
 
C. [[File:3 Sep Acu Cho 1 680x512px.tif|Inflammatory focus with macrophages and neutrophils (400X).]]
 
D. [[File:4 Sep Acu Cho 1 680x512px.tif|PAS with diastase shows proliferated bile ductules at edge of triad with neutrophils, which should not be used to make a definite diagnosis of acute cholangitis (400X).]]
 
E. [[File:5 Sep Acu Cho 1 680x512px.tif|PAS without diastase showing acutely inflamed bile duct, with accompanying blood vessel of similar size, diagnostic of acute cholangitis (400X).]]
 
F. [[File:6 Sep Acu Cho 1 680x512px.tif|PAS with diastase showing neutrophil in bille duct lumen, diagnostic of acute cholangitis (400X).]]
 
Patient with sepsis and acute cholangitis. A. Low power shows variably sized inflamed portal tracts. B. Trichrome shows dilated sinusoids and space of Disse collagenization. C. Inflammatory focus with macrophages and neutrophils. D. PAS with diastase shows proliferated bile ductules at edge of triad with neutrophils, which should not be used to make a definite diagnosis of acute cholangitis. E. PAS without diastase showing acutely inflamed bile duct, with accompanying blood vessel of similar size, diagnostic of acute cholangitis. F. PAS with diastase showing neutrophil in bille duct lumen, diagnostic of acute cholangitis.

==Polycystic kidney disease and the liver==
{{Main|Cystic kidney disease}}
===General===
Complications of PKD in the liver:<ref>{{Ref MacSween|174-5}}</ref>
#Infected cyst.
#Cholangiocarcinoma.
#Cholestasis/obstruction due to duct compression.<ref>URL: [http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=9184868 http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=9184868]. Accessed on: 23 September 2009.</ref>

Cysts:
*Cysts in the liver, like the kidney, are thought to enlarge with age.

===Microscopic===
Features:<ref>{{Ref MacSween|176}}</ref>
*''Von Meyenburg complexes'' ([[bile duct hamartoma]]):
**Cluster of dilated ducts with "altered" bile.
**Surrounded by collagenous stroma.
**Separate from the portal areas.<ref>Meyenburg complex. Stedman's Medical Dictionary. 27th Ed.</reF>

Images:
*[http://commons.wikimedia.org/wiki/File:Von_Meyenburg_complex_low_mag.jpg Von Meyenburg complex - bile duct hamartoma (WC)].
*[http://commons.wikimedia.org/wiki/File:Bile_duct_hamartoma_intermed_mag.jpg Bile duct hamartoma (WC)].

Notes:
*Appearance on ultrasound<ref name=pmid17287178>Bile duct hamartomas--the von Meyenburg complex. Salles VJ, Marotta A, Netto JM, Speranzini MB, Martins MR. Hepatobiliary Pancreat Dis Int. 2007 Feb;6(1):108-9. PMID 17287178.</ref> and CT (hypodense)<ref name=pmid19294869>[The von Meyenburg complex] Schwab SA, Bautz W, Uder M, Kuefner MA. Rontgenpraxis. 2008;56(6):241-4. German. PMID 19294869.</ref> - similar to metastases.

==Peliosis hepatis==
===General===
*Associated with:
**Infections.
**Malignancy.
**Other stuff.
*Rarely biopsied.

===Microscopic===
Features:
*Cyst lined by endothelium.
**Usu. incomplete.
*Blood.
A. [[File:1 PEL 1 680x512px.tif|Hemorrhage at left end, dilated sinusoids elsewhere (20X).]]
 
B. [[File:2 PEL 1 680x512px.tif|Ramifying dilated sinusoidal spaces (100X).]]
 
C. [[File:3 PEL 1 680x512px.tif|PAS with diastase shows flat lining (400X).]]
 
D. [[File:4 PEL 1 680x512px.tif|Necrotic hepatocytes in cords, presumably due to pressure (400X).]]
 
Peliosis hepatis. A. Hemorrhage at left end, dilated sinusoids elsewhere. B. Ramifying dilated sinusoidal spaces. C. PAS with diastase shows flat lining. D. Necrotic hepatocytes in cords, presumably due to pressure.

==Total parenteral nutrition==
*Abbreviated ''TPN''.

===General===
*Indication: short gut syndrome, others.

===Microscopic===
Variable - may range from: steatosis, steatohepatitis, cholestasis, fibrosis and cirrhosis.<ref name=pmid16766237>{{cite journal |author=Guglielmi FW, Boggio-Bertinet D, Federico A, ''et al.'' |title=Total parenteral nutrition-related gastroenterological complications |journal=Dig Liver Dis |volume=38 |issue=9 |pages=623–42 |year=2006 |month=September |pmid=16766237 |doi=10.1016/j.dld.2006.04.002 |url=}}</ref>

Features (classic):<ref>{{Cite journal | last1 = Li | first1 = SJ. | last2 = Nussbaum | first2 = MS. | last3 = McFadden | first3 = DW. | last4 = Gapen | first4 = CL. | last5 = Dayal | first5 = R. | last6 = Fischer | first6 = JE. | title = Addition of glucagon to total parenteral nutrition (TPN) prevents hepatic steatosis in rats. | journal = Surgery | volume = 104 | issue = 2 | pages = 350-7 | month = Aug | year = 1988 | doi = | PMID = 3135627 }}</ref><ref>{{Cite journal | last1 = Stanko | first1 = RT. | last2 = Nathan | first2 = G. | last3 = Mendelow | first3 = H. | last4 = Adibi | first4 = SA. | title = Development of hepatic cholestasis and fibrosis in patients with massive loss of intestine supported by prolonged parenteral nutrition. | journal = Gastroenterology | volume = 92 | issue = 1 | pages = 197-202 | month = Jan | year = 1987 | doi = | PMID = 3096806 }}
</ref>
*[[Steatosis]] (periportal) - early.
*Cholestasis - late.

==Giant cell hepatitis==
*[[AKA]] ''neonatal giant cell hepatitis''.

:See: ''[[Giant cell hepatitis]]''.

==Hepatic amyloidosis==
{{Main|Amyloidosis}}
*[[AKA]] ''liver amyloidosis''.
*[[AKA]] ''amyloidosis of the liver''.
===General===
*Diffuse abundant amyloid within the space of Disse is associated with [[portal hypertension]].<ref name=pmid1864548>{{Cite journal | last1 = Bion | first1 = E. | last2 = Brenard | first2 = R. | last3 = Pariente | first3 = EA. | last4 = Lebrec | first4 = D. | last5 = Degott | first5 = C. | last6 = Maitre | first6 = F. | last7 = Benhamou | first7 = JP. | title = Sinusoidal portal hypertension in hepatic amyloidosis. | journal = Gut | volume = 32 | issue = 2 | pages = 227-30 | month = Feb | year = 1991 | doi = | PMID = 1864548 | PMC = 1378815 | URL = http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1378815/?tool=pubmed }}</ref>

===Microscopic===
Features:
*Amorphous extracellular pink stuff on H&E - see ''[[amyloid]]'' article.

DDx:
*[[Fibrolamellar hepatocellular carcinoma]].

====Images====
<gallery>
Image:Hepatic_amyloidosis_-_low_mag.jpg | Amyloidosis of the liver - low mag. (WC)
Image:Hepatic_amyloidosis_-_intermed_mag.jpg | Amyloidosis of the liver - intermed. mag. (WC)
Image:Hepatic_amyloidosis_-_high_mag.jpg | Amyloidosis of the liver - high mag. (WC)
Image:Hepatic_amyloidosis_-_very_high_mag.jpg | Amyloidosis of the liver - very high mag. (WC)
</gallery>
A. [[File:1 AMY 1 680x512px.tif|Amorphous material replaces hepatic parenchyma [4X]]]
 
B. [[File:2 AMY 1 680x512px.tif|Material barely stains blue on trichrome [10X]]]
 
C. [[File:3 AMY 1 680x512px.tif|Material stains red on unpolarized Congo Red [40X]]]
 
D. [[File:4 AMY 1 680x512px.tif|Material stains apple green on polarized Congo Red [40X]]]
 
Amyloidosis. A. Amorphous material replaces hepatic parenchyma. B. Material barely stains blue on trichrome. C. Material stains red on unpolarized Congo Red. D. Material stains apple green on polarized Congo Red.

===Stains===
*[[Congo red]] +ve.

==Fulminant hepatic necrosis==
===General===
Etiology:
*Viral, i.e. [[Hepatitis A]], [[Hepatitis B]]; [[Hepatitis C]] - extremely rare.
*Trauma.
*Shock.

===Microscopic===

A. [[File:1 Necrosis 2 680x512px.tif| Submassive hepatic necrosis.]]
 
B. [[File:2 Necrosis 2 680x512px.tif| Submassive hepatic necrosis.]]
 
C. [[File:3 Necrosis 2 680x512px.tif| Submassive hepatic necrosis.]]
 
D. [[File:4 Necrosis 2 680x512px.tif| Submassive hepatic necrosis.]]
 
E. [[File:5 Necrosis 2 680x512px.tif| Submassive hepatic necrosis.]]
 
F. [[File:6 Necrosis 2 680x512px.tif| Submassive hepatic necrosis.]]
 
Submassive hepatic necrosis. Patient had transaminases in the thousands that rapidly dropped to normal. A/ Pink preserved parenchyma strews empty necrotic spaces. B. Focus of necrosis with no apparent hepatocytes macrophages abuts apparently normal liver. C. Iron stain shows the macrophages bear hemosiderin. D. Reticulin stain highlights the recently dead liver cells. E. Reticulin stain shows a necrotic bridge forming; the multiple small black circles preclude diagnosis of a fibrous bridge. F. Trichrome shows the necrotic bridge (“collapse”) lacks much collagen deposition, as would be expected for bridging fibrosis.

Features:
*Hepatocyte [[necrosis]].
*Bile duct proliferation.

DDx:
*[[Cholangiocarcinoma]].
*[[Angiosarcoma]].

==Secondary hemochromatosis==
:''For the hereditary one see [[hereditary hemochromatosis]]''.
===General===
*Iron overload secondary to blood transfusions for hereditary or acquired anemia.<ref name=pmid19727383/>
**Primary hemochromatosis due to a defect in iron processing - called ''[[hereditary hemochromatosis]]''.
*Imaging considered the best test, as iron deposition is patchy.<ref name=pmid19727383/>

Selected hereditary causes:<ref name=pmid19727383>{{Cite journal | last1 = Gattermann | first1 = N. | title = The treatment of secondary hemochromatosis. | journal = Dtsch Arztebl Int | volume = 106 | issue = 30 | pages = 499-504, I | month = Jul | year = 2009 | doi = 10.3238/arztebl.2009.0499 | PMID = 19727383 | PMC = 2735704 | URL = http://www.ncbi.nlm.nih.gov.myaccess.library.utoronto.ca/pmc/articles/PMC2735704/?tool=pubmed}}</ref>
*Thalassemia.
*[[Sickle cell anemia]].
*Hereditary sideroblastic anemia.

Selected acquired causes:<ref name=pmid19727383/>
*[[Myelodysplastic syndromes]]
*Myelofibrosis
*Aplastic anemia, intractable.

===Microscopic===
:See ''[[hereditary hemochromatosis]]''.

==Hepatic sarcoidosis==
{{Main|Hepatic sarcoidosis}}
==Overlapping Disorders==

[[File:1 Mixed Disorder 1 680x512px.tif|Changes of steatohepatitis and interface hepatitis, with granuloma. Patient with diabetes was ANA, AMA, HCV, HBV negative, without drugs known to produce granulomas or interface hepatitis. This may be a case of AMA negative primary biliary cirrhosis, but studies to determine that with certainty were not performed.]]
[[File:2 Mixed Disorder 1 680x512px.tif|Changes of steatohepatitis and interface hepatitis, with granuloma. Patient with diabetes was ANA, AMA, HCV, HBV negative, without drugs known to produce granulomas or interface hepatitis. This may be a case of AMA negative primary biliary cirrhosis, but studies to determine that with certainty were not performed.]]
[[File:3 Mixed Disorder 1 680x512px.tif|Changes of steatohepatitis and interface hepatitis, with granuloma. Patient with diabetes was ANA, AMA, HCV, HBV negative, without drugs known to produce granulomas or interface hepatitis. This may be a case of AMA negative primary biliary cirrhosis, but studies to determine that with certainty were not performed.]]
[[File:4 Mixed Disorder 1 680x512px.tif|Changes of steatohepatitis and interface hepatitis, with granuloma. Patient with diabetes was ANA, AMA, HCV, HBV negative, without drugs known to produce granulomas or interface hepatitis. This may be a case of AMA negative primary biliary cirrhosis, but studies to determine that with certainty were not performed.]]
[[File:5 Mixed Disorder 1 680x512px.tif|Changes of steatohepatitis and interface hepatitis, with granuloma. Patient with diabetes was ANA, AMA, HCV, HBV negative, without drugs known to produce granulomas or interface hepatitis. This may be a case of AMA negative primary biliary cirrhosis, but studies to determine that with certainty were not performed.]]
[[File:6 Mixed Disorder 1 680x512px.tif|Changes of steatohepatitis and interface hepatitis, with granuloma. Patient with diabetes was ANA, AMA, HCV, HBV negative, without drugs known to produce granulomas or interface hepatitis. This may be a case of AMA negative primary biliary cirrhosis, but studies to determine that with certainty were not performed.]] 
Changes of steatohepatitis and interface hepatitis, with granuloma. Patient with diabetes was ANA, AMA, HCV, HBV negative, without drugs known to produce granulomas or interface hepatitis. This may be a case of AMA negative primary biliary cirrhosis, but studies to determine that with certainty were not performed. A. Low power shows hepatocytes afflicted by steatosis and an inflamed portal tract. B. In a region of fatty change lie cytoplasmic tufts of ballooning degeneration (green arrows) and a lipogranuloma (black arrow). C. At the portal-hepatocyte junction lies interface hepatitis (black arrows), as well as extension of inflammation into the lobule (green arrows). D. Red hepatocytes bounded by inflammation denote piecemeal necrosis [PAS without diastase]. E. Giant cells intermixed with lymphocytes prove a portal granuloma [PAS without diastase]. F. A blue fibrous bridge extends from a triad [Trichrome].

[[File:4 95599552608917 sl 1.png|Acute obstructive changes and changes of recurrent acute injury]]
[[File:4 95599552608917 sl 2.png|Acute obstructive changes and changes of recurrent acute injury]]
[[File:4 95599552608917 sl 3.png|Acute obstructive changes and changes of recurrent acute injury]]
[[File:4 95599552608917 sl 4.png|Acute obstructive changes and changes of recurrent acute injury]]
[[File:4 95599552608917 sl 5.png|Acute obstructive changes and changes of recurrent acute injury]]
[[File:4 95599552608917 sl 6.png|Acute obstructive changes and changes of recurrent acute injury]]
[[File:4 95599552608917 sl 7.png|Acute obstructive changes and changes of recurrent acute injury]] 
Acute obstructive changes and changes of recurrent injury in 46 yo man with Clostridium perfringens positive blood culture, an ERCP that showed duodenal compression by the pancreas with resultant bile duct dilatation. The patient had had and continued to have multiple bouts of acute pancreatitis. At the time of biopsy, decreased platelet count/hemoglobin/albumin, elevated lipase/amylase/PT/PTT, normal alkaline phosphatase, bilirubin, AST/ALT, AMA, hepatitis virus serology, ANA. A. Fragment biopsy shows inflamed triads and bridges. B. Trichrome shows bridges without nodules, evidence of prior injury; the patient subsequently developed multiple episodes of pancreatitis. C. Reticulin shows piecemeal necrosis, with black lines bounding individual hepatocytes at interface (arrows). D. Collapse is shown by closly approximated thick black lines; one cannot call portal-central collapse without seeing a central vein. Note on this and the other reticulin image that regeneration, two cell thick cords, is not prominent. E. PAS D of two portal triads, far nearer than normal, both expanded. Note increased number of ducts/ductules (red arrows), neutrophils, and PAS-D macrophages. F. PAS D shows collapse extending from a triad to a portion of a lobule with steatosis. No feathery degeneration or bile duct plugs were seen. Neither were foci of spotty necrosis or abscess seen. G. Other triads, again edematous, showed more of a chronic inflammatory response, with occasional plasma cells (black arrows). Also present are neutrophils (red arrows). The bile duct (grey arrow) near the artery (brown arrow) shows mildly disturbed nuclei. Note early proliferated bile ductules (cyan arrows).

[[File:6 17281676469188 sl 1.png| Hepatitis B virus with steatohepatitis]]
[[File:6 17281676469188 sl 2.png| Hepatitis B virus with steatohepatitis]]
[[File:6 17281676469188 sl 3.png| Hepatitis B virus with steatohepatitis]]
[[File:6 17281676469188 sl 4.png| Hepatitis B virus with steatohepatitis]]
[[File:6 17281676469188 sl 5.png| Hepatitis B virus with steatohepatitis]]
[[File:6 17281676469188 sl 6.png| Hepatitis B virus with steatohepatitis]] 
Hepatitis B virus with steatohepatitis in a 36 year old man with hepatitis B surface antigen and hepatitis Be antigen positivity, Hepatitis be QTPC of 1750 cop/mL, an occasionally mildly elevated (42) ALT, and normal glucose, alkaline phosphatase, bilirubin, and other transaminases. He had a history of alcohol abuse, which became controlled. A. Triads show scant inflammation without definite interface hepatitis. About one-fourth of the lobule, not pan-acinar, is afflicted by steatosis. B. Occasional tufts are seen (arrow), indicating focal ballooning sufficient for a diagnosis of steatohepatitis. C. Glycogenated nuclei (black arrows) and hepatocytes with feathery degeneration (red arrows) are seen. D. Very rare foci of spotty necrosis were seen. E. Apart from this triad and the one in the trichrome stain in F, which had moderate inflammation comprising lymphocytes and macrophages, all triads were small, most without any inflammation at all. Neither collapse nor piecemeal necrosis were seen on reticulin stain. F. Trichrome stain showed only portal fibrosis. The interhepatocyte fibrosis required for brunt fibrosis stage I was not seen. Hence, one would grade this as follows: A) Chronic hepatitis (history of hepatitis B), Metavir activity index 1, Piecemeal necrosis 0, Lobular necrosis 1, Metavir fibrosis stage 1, B) Steatohepaitits, Brunt necroinflammatory grade 1, Brunt fibrosis stage 0.

=See also=
*[[Pancreas]].
*[[Gastrointestinal pathology]].
*[[Liver neoplasms]].
*[[Liver]].

=References=
{{reflist|2}}

[[Category:Gastrointestinal pathology]]
[[Category:Liver pathology]]
[[Category:Medical liver disease]]

Medical liver disease

2017-02-10T18:58:40Z

Mitchell: /* Images */ improved appearance of images

[[Image:Ground glass hepatocytes high mag cropped 2.jpg|thumb|right|[[Micrograph]] showing ground glass hepatocytes, as seen in chronic [[hepatitis B]]. [[H&E stain]].]]
This article deals with '''medical [[liver]] disease'''. An introduction to the liver and approach is found in the ''[[liver]]'' article.

Every differential in liver pathology has "drugs"<ref>{{Ref PCPBoD8|448}}</ref> -- if it isn't clearly malignancy.

Liver neoplasms are dealt with in the ''[[liver neoplasms]]'' article.

Medical liver biopsies are often non-specific, as the liver has the same appearance for many mechanisms of injury, especially when the injury is marked. The clinical history, serology and imaging are essential for proper interpretations in this domain of pathology.

=Review of liver blood work=
===Inflammation activity===
*ALT.
*AST.

===Cholestatic markers===
*ALP.
*GGT - used to assess whether the ALP is an "honest" value, elevated in cirrhosis.

===Cirrhosis/decompensation===
*PLT - low is suggestive of dysfunction.
*INR - high is bad, unless anticoagulated.

===Other===
*Bilirubin.
**Direct (AKA conjugated).
**Indirect (AKA unconjugated).

A short DDx of elevated:<ref>{{Ref PCPBoD8|441}}</ref>
*Indirect:
**[[Gilbert syndrome]].
**Crigler-Najjar syndrome type 1.
**Crigler-Najjar syndrome type 2.
*Direct:
**Rotor syndrome.
**Dubin-Johnson syndomre.

===Viral hepatitis===
*HBV DNA.
*HCV RNA.
*HBs Ag, HBs Ab, HBe Ag, HBe Ab.
*HCV Ab.

Others:
*[[Epstein-Barr virus]] (EBV).
*[[Cytomegalovirus]] (CMV) - especially in the immune incompetent.

====Hepatitis B====
Meaning & utility of the various [[Hepatitis B]] tests:<ref>URL: [http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/hepatology/hepatitis-B/ http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/hepatology/hepatitis-B/]. Accessed on: 16 May 2011.</ref><ref name=lto_hepb>URL: [http://www.labtestsonline.org/understanding/analytes/hepatitis_b/test.html http://www.labtestsonline.org/understanding/analytes/hepatitis_b/test.html]. Accessed on: 16 May 2011.</ref>
{| class="wikitable sortable" border="1"
! Test name
! Location
! Positive test
! Negative test
! Usual question
|-
| HBs Ag||Surface||Virus active||No active infection||Active infection?
|-
| HBs Ab||Surface||Exposed OR vaccinated||No exposure OR no vaccine OR loss of Ab||Immunization status?
|-
| HBe Ag||Virus core||Infect. w/ viral replication||No active infection||Active infect. w/ viral replication?
|-
| HBe Ab||Virus core||Exposed to virus||Infect. w/o antibody response OR not exposed||Immune response to infection?
|-
| HBV DNA||-||Active||Not active/no exposure||Viral load/how active?
|-
| HBc Ab||Virus core||Virus active/previous exposure||No exposure||Early active infection?
|}
Notes:
*''HBc Ab'' may test for acute (IgM) or chronic infection - dependent on specific antibody test; it is often used to look for early infection.<ref name=lto_hepb>URL: [http://www.labtestsonline.org/understanding/analytes/hepatitis_b/test.html http://www.labtestsonline.org/understanding/analytes/hepatitis_b/test.html]. Accessed on: 16 May 2011.</ref>
*''Carriers of hepatitis B'': HBs Ag +ve, HBs Ab -ve, HBc Ag -ve, HBc Ab +ve, HBe Ag -ve, HBe Ab +ve.<ref>URL: [http://labtestsonline.org/understanding/analytes/hepatitis-b/tab/test http://labtestsonline.org/understanding/analytes/hepatitis-b/tab/test]. Accessed on: 3 May 2012.</ref>

===Markers for rare liver diseases===
*Ceruloplasm - low think ''[[Wilson's disease]]''; typical value for Wilson's ~ 0.12 g/L.
**<0.20 g/L is a criteria for Wilson's disease.<ref name=pmid18556333>Diagnostic accuracy of serum ceruloplasmin in Wilson disease: determination of sensitivity and specificity by ROC curve analysis among ATP7B-genotyped subjects. Mak CM, Lam CW, Tam S. Clin Chem. 2008 Aug;54(8):1356-62. Epub 2008 Jun 12. PMID 18556333. URL: [http://www.clinchem.org/cgi/reprint/54/8/1356.pdf http://www.clinchem.org/cgi/reprint/54/8/1356.pdf]. Accessed on: 28 September 2009.</ref>
*Alpha-1 antitrypsin - if low think ''deficiency''.

===Hemosiderosis===
*Ferritin - high.
*Iron saturation - high.

Causes:
*Hemochromatosis.
*Hemolysis, chronic.
*Cirrhosis.

=Medical imaging=
Blood flow:<ref>URL: [http://insidesurgery.com/2010/12/hepatopedal-hepatofugal-flow/ http://insidesurgery.com/2010/12/hepatopedal-hepatofugal-flow/]. Accessed on: 2 December 2011.</ref>
*Hepatopedal flow = normal portal vein flow.
*Hepatofugal flow = reversed portal vein flow.

==Interventional measurements==
Wedged to free hepatic venous pressure:<ref name=pmid1864548>{{Cite journal | last1 = Bion | first1 = E. | last2 = Brenard | first2 = R. | last3 = Pariente | first3 = EA. | last4 = Lebrec | first4 = D. | last5 = Degott | first5 = C. | last6 = Maitre | first6 = F. | last7 = Benhamou | first7 = JP. | title = Sinusoidal portal hypertension in hepatic amyloidosis. | journal = Gut | volume = 32 | issue = 2 | pages = 227-30 | month = Feb | year = 1991 | doi = | PMID = 1864548 | PMC = 1378815 | URL = http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1378815/?tool=pubmed }}</ref>
*Normal = 1-4 mmHg.
**Elevated in [[portal hypertension]].

=Liver biopsy=
==Medical liver biopsy adequacy==
Liver biopsy specimens should be:<ref>{{Ref MacSween|418}}</ref>
*2.0 cm in length and contain 11-15 portal tracts,
*The core should be deeper than 1.0 cm from the liver capsule; specimens close to the capsule may lead to over grading of fibrosis.

==Reporting==
{{Main|Pathology reports}}
<pre>
Specimen, procedure:
- Diagnosis.
</pre>
The diagnosis usually contains grading and staging information, e.g. ''activity 2 /4, Laennec fibrosis stage 1 /4''.

In the context of medical liver disease:
*Grade = inflammation/activity.
*Stage = severity of fibrosis/architectural changes.

Notes:
*The term "acute" is infrequently used in liver pathology.
*In the liver: neutrophils ''is not'' acute -- unlike most elsewhere in the body.<ref>OA. September 2009.</ref>

===A microscopic checklist===
<pre>
Size of biopsy: Adequate
Fragmentation: Absent
Fibrosis: Stage 2-3/4, mostly stage 2
Fibrous septa: Present
Septa with curved contours: Present – focally only
Large droplet steatosis (% of hepatocytes): Present, moderate 60%
Ballooning of hepatocytes: Present, rare
Mallory-Denk bodies: Present, rare
Portal inflammation: Present
Interface activity: Minimal (0-1/4)
Lobular necroinflammation: Minimal
Ducts: Present in normal numbers
Duct injury: Absent
Ductular reaction: Absent
Cholestasis: Absent
Terminal hepatic venules: Present
Iron stain: Absent
Ground glass cells with routine stains: Absent
PASD for alpha-1 antitrypsin droplets: Negative
</pre>

=Viral hepatitis=
These are common. The diagnoses are based on serology. The serology is covered in the ''[[Liver_pathology#Viral_hepatitis|viral hepatitis]]'' section in the ''[[liver pathology]]'' article.

Typically classified as:<ref name=pmid8048409>{{Cite journal | title = Terminology of chronic hepatitis, hepatic allograft rejection, and nodular lesions of the liver: summary of recommendations developed by an international working party, supported by the World Congresses of Gastroenterology, Los Angeles, 1994. | journal = Am J Gastroenterol | volume = 89 | issue = 8 Suppl | pages = S177-81 | month = Aug | year = 1994 | doi = | PMID = 8048409 }}</ref><ref>URL: [http://familydoctor.org/familydoctor/en/diseases-conditions/hepatitis-b.html http://familydoctor.org/familydoctor/en/diseases-conditions/hepatitis-b.html]. Accessed on: 2 May 2012.</ref>
#Acute < 6 months duration.
#Chronic > 6 months duration.

==Hepatitis A==
*Infection is self-limited, i.e. not persistent.
**May present as ''[[fulminant hepatic necrosis]]''.
*Usually asymptomatic in children.<ref name=pmid20068336>{{cite journal |author=Jeong SH, Lee HS |title=Hepatitis A: clinical manifestations and management |journal=Intervirology |volume=53 |issue=1 |pages=15–9 |year=2010 |pmid=20068336 |doi=10.1159/000252779 |url=}}</ref>
*Serology is diagnostic.

==Hepatitis B==
:''Hepatitis B virus'', abbreviated ''HBV'', redirects here.
{{Main|Hepatitis B}}

==Hepatitis C==
{{Main|Hepatitis C}}

=Other infections=
*Hydatid disease (Hydatid cyst).
*Ascaris.
*Fasciola

==Hydatid disease==
*[[AKA]] ''hydatid cyst''.
===General===
*Etiology: ''[[Echinococcus]]''.

===Microscopic===
Features:
*Laminated wall +/- calcification.<ref name=Ref_PBPoD8_448>{{Ref PCPBoD8|448}}</ref>
*Organisms -- see ''[[Echinococcus]]''.

====Images====
<gallery>
Image:Liver_cyst_wall_-_intermed_mag.jpg | Liver cyst wall - intermed. mag. (WC)
Image:Liver_cyst_wall_-_high_mag.jpg | Liver cyst wall - high mag. (WC)
Image: Laminated liver cyst wall - intermed mag.jpg | Characteristic laminated portion - intermed. mag. (WC)
Image: Laminated liver cyst wall - high mag.jpg | Characteristic laminated portion - high mag. (WC)
</gallery>
[[www]]:
*[http://pathmicro.med.sc.edu/parasitology/hydatid-hist1.jpg Hydatid cyst (med.sc.edu)].
*[http://www.atlas.or.kr/atlas/include/viewImg.html?uid=645 Hydatid cyst (atlas.or.kr)].
*[http://casereports.bmj.com/content/2009/bcr.04.2009.1798.full Hydatid cyst (casereports.bmj.com)].

==Abscess==
A. [[File:1 ABS 1 680x512px.tif|A process replaces most of the liver parenchyma (20X).]]
 
B. [[File:2 ABS 1 680x512px.tif|Fibrinopurulent exudate apposes granulation tissue (200X).]]
 
C. [[File:3 ABS 1 680x512px.tif|Neutrophils lie in widened sinusoids (200X)..]]
 
D. [[File:4 ABS 1 680x512px.tif|Trichrome shows collagenization of spaces of Disse. Scarring about an abscess or other mass lesion should not be interpreted as reflective of the liver in general (200X).]]
 
Abscess. A. A process replaces most of the liver parenchyma. B. Fibrinopurulent exudate apposes granulation tissue. C. Neutrophils lie in widened sinusoids. D. Trichrome shows collagenization of spaces of Disse. Scarring about an abscess or other mass lesion should not be interpreted as reflective of the liver in general (LR 200X).

==Coccidiomycosis==
A. [[File:Coccidiomycosis - 1 - 40X 680x512px shot.tif|500x500px Granulomas at low power]]
 
B. [[File:Coccidiomycosis - 1 - 200X 680x513px shot.tif|500x500px Granulomas with centrally crowded cells & lady slipper macrophage nuclei]]
 
C. [[File:Coccidiomycosis - 1 - 400X 1369x1024px shot.tif|500x500px Center of previous granuloma showing pyknotic macrophage nuclei]]
 
D. [[File:Coccidiomycosis - 1 - GMS 400X 1369x1024px shot.tif|500x500px Four Coccidiomycotic spherules]]
 
Coccidiomycosis. A. Note the granulomas in otherwise undisturbed liver (UL). B. Granuloma with centrally crowded cells & lady slipper macrophage nuclei. C. Center of granuloma with pyknotic macrophage nuclei, "necrotizing". D. Organisms on GMS stain.

=Metabolic and toxic=
==Alcoholic liver disease==
===General===
*Acute and/or chronic liver changes due to excessive [[alcohol]] use - includes:
**''[[Alcoholic steatohepatitis]]'' (ASH), [[AKA]] ''alcoholic hepatitis''.<ref>URL: [http://emedicine.medscape.com/article/170539-overview http://emedicine.medscape.com/article/170539-overview]. Accessed on: 3 May 2012.</ref>
***Alcoholic hepatitis can be with minimal steatosis.<ref>STC. 6 December 2010.</ref>
**[[Steatosis]] - classically macrovescicular and centrilobular.
**Alcoholic [[cirrhosis]].

====Classic lab findings in EtOH abusers====
*AST & ALT elevated with AST:ALT=2:1.
*GGT elevated.
*MCV increased.

===Gross pathology/radiologic findings===
*Classically micronodular pattern.
**May be macronodular.

===Microscopic===
See:
*''[[Steatohepatitis]]'' section and ''[[ballooning degeneration]]'' section.

Features:
*Often zone III damage.
*Cholestatsis common, i.e. yellow staining.
**NASH (non-alcoholic steatohepatitis) usu. does not have cholestasis.<ref>STC. 6 December 2010.</ref>
*Fibrosis starts at central veins.
*Neutrophils (often helpful) -- few other things have PMNs. (???)
**Neutrophils cluster around cells with Mallory hyaline.

====Images====

A. [[File:1 etoh 3 680x512px.tif| Alcoholic hepatitis with Metavir stage IV fibrosis (advanced fibrosis/cirrhosis).]]
 
B. [[File:2 etoh 3 680x512px.tif| Alcoholic hepatitis with Metavir stage IV fibrosis (advanced fibrosis/cirrhosis).]]
 
C. [[File:3 etoh 3 680x512px.tif| Alcoholic hepatitis with Metavir stage IV fibrosis (advanced fibrosis/cirrhosis).]]
 
D. [[File:4 etoh 3 680x512px.tif| Alcoholic hepatitis with Metavir stage IV fibrosis (advanced fibrosis/cirrhosis).]]
 
E. [[File:5 etoh 3 680x512px.tif| Alcoholic hepatitis with Metavir stage IV fibrosis (advanced fibrosis/cirrhosis).]]
 
F. [[File:6 etoh 3 680x512px.tif| Alcoholic hepatitis with Metavir stage IV fibrosis (advanced fibrosis/cirrhosis).]]
 

Alcoholic hepatitis with Metavir stage IV fibrosis (advanced fibrosis/cirrhosis).
A. Trichrome shows relatively non-inflamed fibrous bands, as well as [between green dots] nodules. The lack of regeneration throughout might have precluded a diagnosis of cirrhosis, but stage IV fibrosis under the Metavir system is justified. B. Reticulin shows regenerative nodules [left] with mostly two or more nuclei between black lines juxtaposed to non-regenerative hepatocytes on the right, without piecemeal necrosis. C. Regenerative nodules show occasional neutrophils [red arrow] and cytoplasmic tufts of ballooned cells, sometimes possibly Mallory hyalin [green arrows]. D. Triads (note vein [green arrow], artery [yellow arrow], and interlobular bile duct [blue arrow]) generally showed little or no interface hepatitis, even when expanded by fibrosis and inflamed. E. Occasional foci of spotty necrosis were seen. F. This edge of an inflamed triads shows neutrophils about proliferated bile ducts [red arrows], as well as Mallory-Denk bodies [blue arrows].
 
A. [[File:1 etoh 4 680x512px.tif| Cirrhosis in an alcoholic.]]
 
B. [[File:2 etoh 4 680x512px.tif| Cirrhosis in an alcoholic.]]
 
C. [[File:3 etoh 4 680x512px.tif| Cirrhosis in an alcoholic.]]
 
D. [[File:4 etoh 4 680x512px.tif| Cirrhosis in an alcoholic.]]
 
E. [[File:5 etoh 4 680x512px.tif| Cirrhosis in an alcoholic.]]
 
F. [[File:6 etoh 4 680x512px.tif| Cirrhosis in an alcoholic.]]
 
Definite cirrhosis in an alcoholic. A. Hepatocyte free bands parse tissue, with occasional definite islands [arrows]. B. Trichrome establishes blue fibrosis about isles [arrows]. C. Reticulin stain shows nodules with regeneration, wherein a large proportion of them are at least two nuclei thick [arrows]. D. Bile duct proliferation can be difficult, sometimes mimicking cholangiocarcinoma. Follow the double headed arrows to see how the ductules can be seen to proliferate from a single sources, with all ducts being complete, without necrotic epithelial cells. E. PAS with distase can help, as cholangiocarcinoma generally lacks the red rim of proliferating bile ductules [arrows]; again note the connections that can be made between the ductule openings by the blue double headed arrows. The cyan double headed arrows show general parallelism, consistent with uniform directionality induced by extrinsic force, not a neoplastic spread. F. Trichrome shows the most difficult focus. Double headed arrows display the connectivity seen before of the proliferated bile ductules. Note that numerous pairs of adjacent perpendicular glands without a head to foot appearance are not seen that would indicate the disorderly spread of cholangiocarcinoma.
 
A. [[File:1 ALC 2 680x512px.tif|Expanded, inflamed triads with increased bile duct/vascular openings. Mild steatosis (40X).]]
 
B. [[File:2 ALC 2 680x512px.tif|Trichrome stain shows periportal fibrosis [red arrowheads] (200X).]]
 
C. [[File:3 ALC 2 680x512px.tif|PAS with diastase stain shows proliferated bile ductules [blue arrowheads] in stroma with mixed inflammatory infiltrate (400X)]]
 
D. [[File:4 ALC 2 680x512px.tif|Neutrophils about ballooned hepatocyte (satellitosis) [yellow arrowheads]. Councilman bodies [green arrowheads] (400X).]]
 
Alcoholic hepatitis without cirrhosis. No history of viral disease. AMA negative. A. Expanded, inflamed triads with increased bile duct/vascular openings. Mild steatosis. B. Trichrome stain shows periportal fibrosis [red arrowheads]. C. PAS with diastase stain shows proliferated bile ductules [blue arrowheads] in stroma with mixed inflammatory infiltrate. D. Neutrophils about ballooned hepatocyte (satellitosis) [yellow arrowheads]. Councilman bodies [green arrowheads].

Notes:
*If portal inflammatory infiltrates more than mild, r/o other causes i.e. [[viral hepatitis]].
*Mallory bodies once thought to be characteristic; now considered non-specific and generally poorly understood.<ref>{{cite journal |author=Jensen K, Gluud C |title=The Mallory body: theories on development and pathological significance (Part 2 of a literature survey) |journal=Hepatology |volume=20 |issue=5 |pages=1330-42 |year=1994 |month=November |pmid=7927269 |doi= |url=}}</ref>
*Some consider ''alcoholic liver disease'' a clinical diagnosis, i.e. as a pathologist one does not diagnose it.<ref>MG. September 2009.</ref>

==Non-alcoholic fatty liver disease==
*Abbreviated ''NAFLD''.
*Fatty liver that is not due to alcohol; includes obesity-related fatty liver, metabolic disease/diabetes-related fatty liver.

===NASH===
*Non-alcoholic steatohepatitis - see ''steatohepatitis'' section.
*Histologically indistinguishable from ASH.
*NASH is a ''clinical diagnosis'' based on exclusion of alcohol.

==Steatohepatitis==
{{Main|Steatohepatitis}}

=Autoimmune=
==Autoimmune hepatitis==
*Abbreviated ''AIH''.
{{Main|Autoimmune hepatitis}}

==Primary biliary cirrhosis==
*Abbreviated PBC.
{{Main|Primary biliary cirrhosis}}

==Autoimmune hepatitis with obstruction - combined changes==
A. [[File:1 AIH OBS 1.tif|Low power shows inflammation; portal triads, lobules, central veins cannot be distinguished (40X).]]
 
B. [[File:2 AIH OBS 1.tif|Trichrome shows central venous sclerosis (red arrowhead), periportal fibrosis (green arrowhead), & space of Disse collagenization (yellow arrowhead); juxtaposition of central vein & portal tract indicates collapse, no definite bridging was seen (100X)]]
 
C. [[File:3 AIH OBS 1.tif|Central vein is inflamed with a rare plasma cell (cyan arrowhead) (400X).]]
 
D. [[File:4 AIH OBS 1.tif|Interface hepatitis with plasma cells (yellow arrows) and ballooned hepatocytes (red arrows). Lobule is disorganized (400X).]]
 
E. [[File:5 AIH OBS 1.tif|Proliferating bile ductules (blue arrows) with occasional neutrophils (fucsia arrows), indicative of obstruction, but not acute cholangitis, which requires inflamed bile duct itself, best diagnosed with associated blood vessel (400X).]]
 
F. [[File:6 AIH OBS 1.tif|Rare distorted rosettes with greenish brown strands of bile (left arrow) or bile plugs (right arrow) (400X).]]
 
Patient with SLE and obstructive jaundice that resolved with apparent passage of stone. A. Low power shows inflammation; portal triads, lobules, central veins cannot be distinguished. B. Trichrome shows central venous sclerosis (red arrowhead), periportal fibrosis (green arrowhead), & space of Disse collagenization (yellow arrowhead); juxtaposition of central vein & portal tract indicates collapse, no definite bridging was seen. C. Central vein is inflamed with a rare plasma cell (cyan arrowhead). D. Interface hepatitis with plasma cells (yellow arrows) and ballooned hepatocytes (red arrows). Lobule is disorganized. E. Proliferating bile ductules (blue arrows) with occasional neutrophils (fucsia arrows), indicative of obstruction, but not acute cholangitis, which requires inflamed bile duct itself, best diagnosed with associated blood vessel. F. Rare distorted rosettes with greenish brown strands of bile (left arrow) or bile plugs (right arrow).

==Autoimmune hepatitis-primary biliary cirrhosis overlap syndrome==
*Abbreviation ''AIH-PBC OS''.
===General===
Epidemiology:
*Rare.

Serology:<ref name=pmid19491855>{{Cite journal | last1 = Muratori | first1 = P. | last2 = Granito | first2 = A. | last3 = Pappas | first3 = G. | last4 = Pendino | first4 = GM. | last5 = Quarneti | first5 = C. | last6 = Cicola | first6 = R. | last7 = Menichella | first7 = R. | last8 = Ferri | first8 = S. | last9 = Cassani | first9 = F. | title = The serological profile of the autoimmune hepatitis/primary biliary cirrhosis overlap syndrome. | journal = Am J Gastroenterol | volume = 104 | issue = 6 | pages = 1420-5 | month = Jun | year = 2009 | doi = 10.1038/ajg.2009.126 | PMID = 19491855 }}</ref>
*AMA +ve.
*Anti-dsDNA +ve.

===Microscopic===
:See: ''[[autoimmune hepatitis]]'' and ''[[primary biliary cirrhosis]]''.
A. [[File:1 AIH PBC 1 680x512px.tif|Expanded portal tracts with fuzzy edges (40X).]]
 
B. [[File:2 AIH PBC 1 680x512px.tif|Interface hepatitis with plasma cells (400X).]]
 
C. [[File:3 AIH PBC 1 680x512px.tif|Loose granuloma (400X).]]
 
D. [[File:4 AIH PBC 1 680x512px.tif|Damaged bile duct (400X).]]
 
AIH/PBC overlap. AMA & ANA positive with Alkaline phosphatase > 2 upper limit of normal & one ALT > 5 times upper limit of normal. A. Expanded portal tracts with fuzzy edges. B. Interface hepatitis with plasma cells. C. Loose granuloma. D. Damaged bile duct.

==Primary sclerosing cholangitis==
*Abbreviated ''PSC''.
{{Main|Primary sclerosing cholangitis}}

=Hereditary=
==Caroli disease==
===General===
*Genetic disease.
**Frequently associated with [[autosomal recessive polycystic kidney disease]] (ARPKD).<ref name=omim263200>{{OMIM|263200}}</ref>
**May be seen in isolation.<ref name=omim600643>{{OMIM|600643}}</ref>

Clinical:<ref name=pmid17461493>{{Cite journal | last1 = Yonem | first1 = O. | last2 = Bayraktar | first2 = Y. | title = Clinical characteristics of Caroli's syndrome. | journal = World J Gastroenterol | volume = 13 | issue = 13 | pages = 1934-7 | month = Apr | year = 2007 | doi = | PMID = 17461493 }}</ref>
*Recurrent [[cholangitis]].
*Recurrent [[cholelithiasis]].
*[[Cholangiocarcinoma]]<ref name=pmid17461492>{{Cite journal | last1 = Yonem | first1 = O. | last2 = Bayraktar | first2 = Y. | title = Clinical characteristics of Caroli's disease. | journal = World J Gastroenterol | volume = 13 | issue = 13 | pages = 1930-3 | month = Apr | year = 2007 | doi = | PMID = 17461492 }}</ref> - seen in ~7% of cases.<ref name=pmid15347876>{{Cite journal | last1 = Karim | first1 = AS. | title = Caroli's disease. | journal = Indian Pediatr | volume = 41 | issue = 8 | pages = 848-50 | month = Aug | year = 2004 | doi = | PMID = 15347876 }}</ref>

Note:
*''Caroli syndrome'' = Caroli disease + congenital hepatic fibrosis.<ref name=pmid15888616>{{Cite journal | last1 = Brancatelli | first1 = G. | last2 = Federle | first2 = MP. | last3 = Vilgrain | first3 = V. | last4 = Vullierme | first4 = MP. | last5 = Marin | first5 = D. | last6 = Lagalla | first6 = R. | title = Fibropolycystic liver disease: CT and MR imaging findings. | journal = Radiographics | volume = 25 | issue = 3 | pages = 659-70 | month = | year = | doi = 10.1148/rg.253045114 | PMID = 15888616 | URL = http://radiographics.rsna.org/content/25/3/659.long }}</ref>

===Gross===
*Dilated bile ducts.<ref name=omim263200/>

===Microscopic===
Features:<ref name=pmid17461493/>
*Dilated bile ducts.
*Periductal fibrosis. (???)
*+/-Fibrosis.

Image:
*[http://www.meddean.luc.edu/lumen/MedEd/orfpath/11-3-10.jpg Caroli disease (meddean.luc.edu)].<ref>URL: [http://www.meddean.luc.edu/lumen/MedEd/orfpath/develop.htm http://www.meddean.luc.edu/lumen/MedEd/orfpath/develop.htm]. Accessed on: 1 December 2011.</ref>

==Hereditary hemochromatosis==
:''For secondary causes see [[secondary hemochromatosis]]''.
{{Main|Hereditary hemochromatosis}}

==Wilson disease==
{{Main|Wilson's disease}}

==Alpha-1 antitrypsin deficiency==
*[[AKA]] ''alpha1-antiprotease inhibitor deficiency''.
{{Main|Alpha-1 antitrypsin deficiency }}

=Other=
==Budd-Chiari syndrome==
*[[AKA]] ''hepatic vein obstruction''.
===General===
*Hepatic outflow obstruction.

Clinical triad:<ref name=pmid21573256>{{Cite journal | last1 = Fox | first1 = MA. | last2 = Fox | first2 = JA. | last3 = Davies | first3 = MH. | title = Budd-Chiari syndrome--a review of the diagnosis and management. | journal = Acute Med | volume = 10 | issue = 1 | pages = 5-9 | month = | year = 2011 | doi = | PMID = 21573256 }}</ref>
*Ascites.
*Abdominal pain.
*Hepatomegaly.

Etiology:
*~50% have a [[myeloproliferative disease]].<ref name=pmid18814079>{{Cite journal | last1 = Plessier | first1 = A. | last2 = Valla | first2 = DC. | title = Budd-Chiari syndrome. | journal = Semin Liver Dis | volume = 28 | issue = 3 | pages = 259-69 | month = Aug | year = 2008 | doi = 10.1055/s-0028-1085094 | PMID = 18814079 }}</ref>
*May be due to mass effect from a tumour.

Clinical DDx:
*[[Hepatic veno-occlusive disease]].

===Microscopic===
Features:<ref name=pmid17569137>{{Cite journal | last1 = Aydinli | first1 = M. | last2 = Bayraktar | first2 = Y. | title = Budd-Chiari syndrome: etiology, pathogenesis and diagnosis. | journal = World J Gastroenterol | volume = 13 | issue = 19 | pages = 2693-6 | month = May | year = 2007 | doi = | PMID = 17569137 | url=http://www.wjgnet.com/1007-9327/full/v13/i19/2693.htm }}</ref>
*Sinusoidal dilation in zone III (congestion).
*+/-Hepatocyte drop-out.
*+/-Centrilobular fibrosis.

DDx congestion:
*Congestive heart failure ([[congestive hepatopathy]]).
*Constrictive pericarditis.

==Vanishing bile duct syndrome==
*[[AKA]] ''bile duct loss'', [[AKA]] ''ductopenia''.<ref name=pmid11521176/>
===General===
*Fatal.

DDx:<ref name=pmid18242505/>
*[[Primary biliary cirrhosis]].
*[[Primary sclerosing cholangitis]].
*[[GVHD]].<ref name=pmid7994249>{{Cite journal | last1 = Yeh | first1 = KH. | last2 = Hsieh | first2 = HC. | last3 = Tang | first3 = JL. | last4 = Lin | first4 = MT. | last5 = Yang | first5 = CH. | last6 = Chen | first6 = YC. | title = Severe isolated acute hepatic graft-versus-host disease with vanishing bile duct syndrome. | journal = Bone Marrow Transplant | volume = 14 | issue = 2 | pages = 319-21 | month = Aug | year = 1994 | doi = | PMID = 7994249 }}</ref>
*[[Drug-induced liver disease|Drugs]].<ref name=pmid11352118>{{Cite journal | last1 = Chitturi | first1 = S. | last2 = Farrell | first2 = GC. | title = Drug-induced cholestasis. | journal = Semin Gastrointest Dis | volume = 12 | issue = 2 | pages = 113-24 | month = Apr | year = 2001 | doi = | PMID = 11352118 }}</ref>
*Chronic rejection.<ref name=pmid11521176>{{Cite journal | last1 = Inomata | first1 = Y. | last2 = Tanaka | first2 = K. | title = Pathogenesis and treatment of bile duct loss after liver transplantation. | journal = J Hepatobiliary Pancreat Surg | volume = 8 | issue = 4 | pages = 316-22 | month = | year = 2001 | doi = 10.1007/s0053410080316 | PMID = 11521176 }}</ref>

===Microscopic===
Features:<ref name=pmid18242505>{{Cite journal | last1 = Reau | first1 = NS. | last2 = Jensen | first2 = DM. | title = Vanishing bile duct syndrome. | journal = Clin Liver Dis | volume = 12 | issue = 1 | pages = 203-17, x | month = Feb | year = 2008 | doi = 10.1016/j.cld.2007.11.007 | PMID = 18242505 }}</ref>
*Loss of intrahepatitic bile ducts - '''key feature'''.
*Cholestasis.

Note:
*May occur without fibrosis and inflammation; thus, can be easy to miss.

===IHC===
*[[CK7]] -ve.
**Marks bile ducts.

==Extrahepatic biliary obstruction==
A. [[File:1 OBS 3 680x512px.tif|Sinusoidal dilatation, circular spaces of hepatocytes, small portal triads(40X).]]
 
B. [[File:2 OBS 3 680x512px.tif|Bile in hepatocytes about central vein & in plugs in canaliculi [yellow arrowhead] (400X).]]
 
C. [[File:3 OBS 3 680x512px.tif|Trichrome shows fibrosis about central vein (400X).]]
 
D. [[File:4 OBS 3 680x512px.tif|PAS with diastase shows portal triads with mild edema and chronic inflammation, without tortuous bile duct (400X).]]
 
Early extrahepatic biliary obstruction, demonstrated radiographically, transient, with rise in bilirubin, alkaline phosphatase, and transaminases. Pure canalicular cholestasis near terminal hepatic venules also seen in acute hepatitis, drug reactions, benign recurrent cholestasis, pregnancy, sepsis, & lymphomas. A. Sinusoidal dilatation, circular spaces of hepatocytes, small portal triads. B. Bile in hepatocytes about central vein & in plugs in canaliculi [yellow arrowhead]. C. Trichrome shows fibrosis about central vein. D. PAS with diastase shows portal triads with mild edema and chronic inflammation, without tortuous bile duct.
 
A. [[File:1 OBS 2 680x512px.tif|Expanded inflamed portal triads, swollen hepatocytes (40X)]]
 
B. [[File:2 OBS 2 680x512px.tif|Edematous stroma, proliferating ductules [yellow arrowheads], PAS-D macrophages [red arrowhead] (PAS with diastasse, 200X)]]
 
C. [[File:3 OBS 2 680x512px.tif|Disordered, often swollen hepatocytes,some with feathery degeneration (net like spaces in cytoplasm [blue arrowhead], rare Councilman body [green arrowhead] (400X)]]
 
D. [[File:4 OBS 2 1360x1024px.tif|Bile in hepatocytes [cyan arrrowhead] & in canaliculi [purple arrowheads]. Empty acinar spaces bounded by hepatocytes [orange arrowhead] (400X, higher pixel),]]
 
Changes of extrahepatic biliary obstruction, months duration. A. Expanded inflamed portal triads, swollen hepatocytes. B. Edematous stroma, proliferating ductules [yellow arrowheads], PAS-D macrophages [red arrowhead]. C. Disordered, often swollen hepatocytes,some with feathery degeneration (net like spaces in cytoplasm) [blue arrowhead], rare Councilman body [green arrowhead]. D. Bile in hepatocytes [cyan arrrowhead] & in canaliculi [purple arrowheads]. Empty acinar spaces bounded by hepatocytes [orange arrowhead].
 
A. [[File:1 Bd obs 4 680x512px.tif|Expanded, light colored portal triads (arrows)(20X).]]
 
B. [[File:2 Bd obs 4 680x512px.tif|Proliferating bile ductules (cyan arrows) with neutrophils (yellow arrows), not specific for acute cholangitis, of assistance with large bile duct obstruction (400X)..]]
 
C. [[File:3 Bd obs 4 680x512px.tif|Uninflamed interlobular duct (yellow arrow) with, accompanying blood vessel (red arrow) (400X)]]
 
D. [[File:4 Bd obs 4 680x512px.tif|Bile infarct with pyknotic nuclei (arrows)(400X).]]
 
E. [[File:5 Bd obs 4 680x512px.tif|Bile (arrow) in interlobular bile duct with disordered nuclei (400X).]]
 
F. [[File:6 Bd obs 4 680x512px.tif|Bile plugs in cannaliculi (red arrows), feathery degeneration producing foamy macrophage like hepatocytes (yellow arrows)(400X).]]
 
Large bile duct obstruction. A. Expanded, light colored portal triads (arrows). B. Proliferating bile ductules (cyan arrows) with neutrophils (yellow arrows), not specific for acute cholangitis, of assistance with large bile duct obstruction. C. Uninflamed interlobular duct (yellow arrow) with, accompanying blood vessel (red arrow). D. Bile infarct with pyknotic nuclei (arrows). E. Bile (arrow) in interlobular bile duct with disordered nuclei. F. Bile plugs in cannaliculi (red arrows), feathery degeneration producing foamy macrophage-like hepatocytes (yellow arrows).

==Congestive hepatopathy==
===General===
*Liver failure due to (right) heart failure.
*AKA ''cardiac cirrhosis'' - a term used by clinicians.
**Generally, it does not satisfy pathologic criteria for cirrhosis.<ref>URL: [http://emedicine.medscape.com/article/151792-overview http://emedicine.medscape.com/article/151792-overview]. Accessed on: 17 June 2010.</ref>

===Gross===
*"Nutmeg" liver - yellow spotted appearance.

===Microscopic===
Features:<ref>URL: [http://emedicine.medscape.com/article/151792-diagnosis http://emedicine.medscape.com/article/151792-diagnosis]. Accessed on: 17 June 2010.</ref>
*Zone III atrophy.
*Portal venule (central vein) distension.
*Perisinusoidal fibrosis - progresses to centrilobular fibrosis and then diffuse fibrosis.
*Dilation of sinusoids in ''all'' zone III areas - '''key feature'''.<ref>Suggested by OA. September 2009.</ref>

DDx:
*[[Hemangioma of the liver]] - should be focal lesion.
Cardiac (congestive) hepatopathy, wherein outflow obstruction occurs secondary to backflow from a failing heart, and Budd Chiari syndrome, wherein obstruction of outflow occurs secondary to obstruction, usually thrombotic, have overlapping features, including sinusoidal dilation with emphasis upon the central vein, space of Disse erythrocytes, centrilobular inflammation, hemorrhage, bile ductules, and hemosiderin, and portal inflammation, fibrosis and bile ductular reaction. Centrilobular dropout/necrosis is more common in Budd Chiari syndrome, while peri-central venous and sinusoidal fibrosis are more common in cardiac hepatopathy. In end stage liver, fibrosis for cardiac hepatopathy comprises stellate centrizonal fibrous with haphazard spread, as opposed to the more frequent nodular cirrhosis in Budd-Chiari. Clinical findings are important to take into account, as cardiac failure is usually well known at the time of diagnosis as are the clinical predictors of Budd Chiari syndrome, prothrombotic states, myeloproliferative diseases, and oral contraceptive use. <ref name=pmid27681331 >{{cite journal |author=Gonzalez RS, Gilger MA, Huh WJ, Washington MK |title=The spectrum of histologic findings in hepatic outflow obstruction |journal= Arch Pathol Lab Med |volume=141 |issue= |pages=98 |year=2017 |pmid= 27681331 ||doi= 10.5858/arpa.2015-0388-OA |url=http http://www.archivesofpathology.org/doi/10.5858/arpa.2015-0388-OA?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%3dpubmed&code=coap-site }}</ref>
====Images====
<gallery>
Image:Congestive_hepatopathy_high_mag.jpg | Mild congestive hepatopathy. (WC) 
A.[[File:1 CEN NEC 1 680x512px.tif|PAS without diastase shows ovoids of necrosis {40X).]] 
B. [[File:2 CEN NEC 1 680x512px.tif|Necrosis with central vein [yellow arrowhead], inflammatory cells, residual Councilman body [green arrowhead], and hepatocyte with mitotic figure [red arrowhead] (400X).]]
 
C. [[File:3 CEN NEC 1 680x512px.tif|Trichrome highlights fibrosis about central vein [yellow arrowhead] & shows beginning scar formation [green arrowheads]. Note residual atrophic hepatocytes [blue arrowheads] (400X).]]
 
D. [[File:4 CEN NEC 1 680x512px.tif|Portal triads are largely unaffected (400X).]]
|} 
Centrilobular necrosis (seen in circulatory failure and with toxins/drugs). A. PAS without diastase shows ovoids of necrosis. B. Necrosis with central vein [yellow arrowhead], inflammatory cells, residual Councilman body [green arrowhead], and hepatocyte with mitotic figure [red arrowhead]. C. Trichrome highlights fibrosis about central vein [yellow arrowhead] & shows beginning scar formation [green arrowheads]. Note residual atrophic hepatocytes [blue arrowheads]. D. Portal triads are largely unaffected (LR 400X)
 
A. [[File:1 CHF 1 680x512px.tif|Dilated and undilated sinusoidal regions (40X).]]
 
B. [[File:2 CHF 1 680x512px.tif|Thrombi in sinusoids; glycogenated nuclei likely reflect patient’s diabetes mellitus (400X).]]
 
C. [[File:3 CHF 1 680x512px.tif|Dilated portal vein (400X).]]
 
D. [[File:4 CHF 1 680x512px.tif|Reticulin shows collapse (thick black lines) as well as a dilated portal vein (200X).]]
 
E. [[File:5 CHF 1 680x512px.tif|Trichrome shows space of Disse collagenization (pericellular fibrosis) (200X).]]
 
F. [[File:6 CHF 1 680x512px.tif|Trichrome shows periportal fibrosis; no bridging was seen (200X).]]

Patient with congestive heart failure and stage I fibrosis. A. Dilated and undilated sinusoidal regions. B. Thrombi in sinusoids; glycogenated nuclei likely reflect patient’s diabetes mellitus. C. Dilated portal vein. D. Reticulin shows black lines of bridging, too thick for collapse. E. Trichrome shows space of Disse collagenization (pericellular fibrosis). F. Trichrome shows bridge beginning off to right; when it is more than a mere spike, it is a bridge.

==Drug-induced liver disease==
*[[AKA]] ''drug-induced liver toxicity''.
{{Main|Drug-induced liver disease}}

==Focal nodular hyperplasia==
*Abbreviated ''FNH''.
{{Main|Focal nodular hyperplasia}}

==Nodular regenerative hyperplasia==
===General===
*Associated with renal transplants, [[bone marrow transplant]]s and [[vasculitides]].<ref name=Ref_PBoD922>{{Ref PBoD|922}}</ref>
*Can lead to [[portal hypertension]] and many of the associated complications.<ref name=pmid22554152>{{Cite journal | last1 = Bissonnette | first1 = J. | last2 = Généreux | first2 = A. | last3 = Côté | first3 = J. | last4 = Nguyen | first4 = B. | last5 = Perreault | first5 = P. | last6 = Bouchard | first6 = L. | last7 = Pomier-Layrargues | first7 = G. | title = Hepatic hemodynamics in 24 patients with nodular regenerative hyperplasia and symptomatic portal hypertension. | journal = J Gastroenterol Hepatol | volume = 27 | issue = 8 | pages = 1336-40 | month = Aug | year = 2012 | doi = 10.1111/j.1440-1746.2012.07168.x | PMID = 22554152 }}
</ref>

====Etiology====
*Arterial hypervascularity secondary to loss of hepatic vein radicles (loss of central venule in hepatic lobule).<ref name=Ref_PBoD922>{{Ref PBoD|922}}</ref>

ASIDE: radicle = ramulus - smallest branch or vessel or nerve.<ref name=Dorlands2>Dorland's Medical Dictionary. 30th Ed.</ref>

===Gross===
*Diffuse nodularity - whole liver.

===Microscopic===
Features:<ref name=Ref_PBoD922>{{Ref PBoD|922}}</ref>
*"Plump" hepatocytes surrounded by atrophic ones.
*No fibrosis.

==Sinuosoidal obstruction syndrome==
*May be referred to as ''Hepatic veno-occlusive disease''.<ref name=pmid11928077>{{Cite journal | last1 = DeLeve | first1 = LD. | last2 = Shulman | first2 = HM. | last3 = McDonald | first3 = GB. | title = Toxic injury to hepatic sinusoids: sinusoidal obstruction syndrome (veno-occlusive disease). | journal = Semin Liver Dis | volume = 22 | issue = 1 | pages = 27-42 | month = Feb | year = 2002 | doi = 10.1055/s-2002-23204 | PMID = 11928077 }}.</ref>
===General===
*Term for obstruction due to toxicity from a chemotherapeutic agent.<ref name=pmid16393276>{{Cite journal | last1 = Helmy | first1 = A. | title = Review article: updates in the pathogenesis and therapy of hepatic sinusoidal obstruction syndrome. | journal = Aliment Pharmacol Ther | volume = 23 | issue = 1 | pages = 11-25 | month = Jan | year = 2006 | doi = 10.1111/j.1365-2036.2006.02742.x | PMID = 16393276 }}</ref><ref name=pmid17569137>{{Cite journal | last1 = Aydinli | first1 = M. | last2 = Bayraktar | first2 = Y. | title = Budd-Chiari syndrome: etiology, pathogenesis and diagnosis. | journal = World J Gastroenterol | volume = 13 | issue = 19 | pages = 2693-6 | month = May | year = 2007 | doi = | PMID = 17569137 | url=http://www.wjgnet.com/1007-9327/full/v13/i19/2693.htm }}</ref>

Clinical DDx:
*[[Budd-Chiari syndrome]].

===Microscopic===
Features:<ref name=pmid17569137>{{Cite journal | last1 = Aydinli | first1 = M. | last2 = Bayraktar | first2 = Y. | title = Budd-Chiari syndrome: etiology, pathogenesis and diagnosis. | journal = World J Gastroenterol | volume = 13 | issue = 19 | pages = 2693-6 | month = May | year = 2007 | doi = | PMID = 17569137 | url=http://www.wjgnet.com/1007-9327/full/v13/i19/2693.htm }}</ref>
*Subendothelial swelling in hepatic venules.

Negatives:
*No thrombosis.

==Ascending Cholangitis (Acute Cholangitis)==
===General===
*Term for infection of bile ducts, usually due to obstruction

Clinical DDx:

===Microscopic===
====Images====

A. [[File:1 asc chol 1 680x512px.tif|Rounded, clear (edematous) portal tracts (arrows) separated by hepatocytes with dilated sinusoids (Row 1 Left 40X).]]
 
B. [[File:2 asc chol 1 680x512px.tif|Neutrophils about hepatocytes (arrows) have spilled into the lobule from a portal tract (Row 1 Right 200X).]]
 
C. [[File:3 asc chol 1 680x512px.tif|Proliferated bile ductules (arrows) bearing neutrophils within epithelium and lumens are features of obstruction that should prompt a search for interlobular ducts with acute inflammation (Row 2 Left 400X).]]
 
D. [[File:4 asc chol 1 680x512px.tif|The epithelium of the ducts can be severely degenerated. Neutrophils (cyan arrows) invade epithelium of an interlobular duct that are recognizable mainly as a circle of rounded nuclei; the associated arteriole (red arrow) should be identified to ensure an interlobular duct is being evaluated. Note the proliferated bile ductules (blue arrows) (Row 2 Right 400X).]]
 
E. [[File:5 asc chol 1 680x512px.tif|A PAS without diastase stain colors the arteriole (blue arrow), as well as the rim of the interlobular duct within which lies a neutrophil (cyan arrow) (Row 2 Right 400X). .]]
 
F. [[File:6 asc chol 1 680x512px.tif|A PAS with diastase stain colors the arteriole (red arrow), as well as the rim of the interlobular duct within which lies a neutrophil (cyan arrow) (Row 1 Right 400X)]]
 
Acute cholangitis in a patient with multiple bile duct procedures. After the biopsy, removal of bile duct stones released pus. A. Rounded, clear (edematous) portal tracts (arrows) separated by hepatocytes with dilated sinusoids. B. Neutrophils about hepatocytes (arrows) have spilled into the lobule from a portal tract. C, Proliferated bile ductules (arrows) bearing neutrophils within epithelium and lumens are features of obstruction that should prompt a search for interlobular ducts with acute inflammation. D. The epithelium of the ducts can be severely degenerated. Neutrophils (cyan arrows) invade epithelium of an interlobular duct that are recognizable mainly as a circle of rounded nuclei; the associated arteriole (red arrow) should be identified to ensure an interlobular duct is being evaluated. Note the proliferated bile ductules (blue arrows). E. A PAS without diastase stain colors the arteriole (blue arrow), as well as the rim of the interlobular duct within which lies a neutrophil (cyan arrow). F. A PAS with diastase stain colors the arteriole (red arrow), as well as the rim of the interlobular duct within which lies a neutrophil (cyan arrow).

A.[[File:1 Sep Acu Cho 1 680x512px.tif|Low power shows variably sized inflamed portal tracts (40X)]]
 
B. [[File:2 Sep Acu Cho 1 680x512px.tif|Trichrome shows dilated sinusoids and space of Disse collagenization (200X)]]
 
C. [[File:3 Sep Acu Cho 1 680x512px.tif|Inflammatory focus with macrophages and neutrophils (400X).]]
 
D. [[File:4 Sep Acu Cho 1 680x512px.tif|PAS with diastase shows proliferated bile ductules at edge of triad with neutrophils, which should not be used to make a definite diagnosis of acute cholangitis (400X).]]
 
E. [[File:5 Sep Acu Cho 1 680x512px.tif|PAS without diastase showing acutely inflamed bile duct, with accompanying blood vessel of similar size, diagnostic of acute cholangitis (400X).]]
 
F. [[File:6 Sep Acu Cho 1 680x512px.tif|PAS with diastase showing neutrophil in bille duct lumen, diagnostic of acute cholangitis (400X).]]
 
Patient with sepsis and acute cholangitis. A. Low power shows variably sized inflamed portal tracts. B. Trichrome shows dilated sinusoids and space of Disse collagenization. C. Inflammatory focus with macrophages and neutrophils. D. PAS with diastase shows proliferated bile ductules at edge of triad with neutrophils, which should not be used to make a definite diagnosis of acute cholangitis. E. PAS without diastase showing acutely inflamed bile duct, with accompanying blood vessel of similar size, diagnostic of acute cholangitis. F. PAS with diastase showing neutrophil in bille duct lumen, diagnostic of acute cholangitis.

==Polycystic kidney disease and the liver==
{{Main|Cystic kidney disease}}
===General===
Complications of PKD in the liver:<ref>{{Ref MacSween|174-5}}</ref>
#Infected cyst.
#Cholangiocarcinoma.
#Cholestasis/obstruction due to duct compression.<ref>URL: [http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=9184868 http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=9184868]. Accessed on: 23 September 2009.</ref>

Cysts:
*Cysts in the liver, like the kidney, are thought to enlarge with age.

===Microscopic===
Features:<ref>{{Ref MacSween|176}}</ref>
*''Von Meyenburg complexes'' ([[bile duct hamartoma]]):
**Cluster of dilated ducts with "altered" bile.
**Surrounded by collagenous stroma.
**Separate from the portal areas.<ref>Meyenburg complex. Stedman's Medical Dictionary. 27th Ed.</reF>

Images:
*[http://commons.wikimedia.org/wiki/File:Von_Meyenburg_complex_low_mag.jpg Von Meyenburg complex - bile duct hamartoma (WC)].
*[http://commons.wikimedia.org/wiki/File:Bile_duct_hamartoma_intermed_mag.jpg Bile duct hamartoma (WC)].

Notes:
*Appearance on ultrasound<ref name=pmid17287178>Bile duct hamartomas--the von Meyenburg complex. Salles VJ, Marotta A, Netto JM, Speranzini MB, Martins MR. Hepatobiliary Pancreat Dis Int. 2007 Feb;6(1):108-9. PMID 17287178.</ref> and CT (hypodense)<ref name=pmid19294869>[The von Meyenburg complex] Schwab SA, Bautz W, Uder M, Kuefner MA. Rontgenpraxis. 2008;56(6):241-4. German. PMID 19294869.</ref> - similar to metastases.

==Peliosis hepatis==
===General===
*Associated with:
**Infections.
**Malignancy.
**Other stuff.
*Rarely biopsied.

===Microscopic===
Features:
*Cyst lined by endothelium.
**Usu. incomplete.
*Blood.
A. [[File:1 PEL 1 680x512px.tif|Hemorrhage at left end, dilated sinusoids elsewhere (20X).]]
 
B. [[File:2 PEL 1 680x512px.tif|Ramifying dilated sinusoidal spaces (100X).]]
 
C. [[File:3 PEL 1 680x512px.tif|PAS with diastase shows flat lining (400X).]]
 
D. [[File:4 PEL 1 680x512px.tif|Necrotic hepatocytes in cords, presumably due to pressure (400X).]]
 
Peliosis hepatis. A. Hemorrhage at left end, dilated sinusoids elsewhere. B. Ramifying dilated sinusoidal spaces. C. PAS with diastase shows flat lining. D. Necrotic hepatocytes in cords, presumably due to pressure.

==Total parenteral nutrition==
*Abbreviated ''TPN''.

===General===
*Indication: short gut syndrome, others.

===Microscopic===
Variable - may range from: steatosis, steatohepatitis, cholestasis, fibrosis and cirrhosis.<ref name=pmid16766237>{{cite journal |author=Guglielmi FW, Boggio-Bertinet D, Federico A, ''et al.'' |title=Total parenteral nutrition-related gastroenterological complications |journal=Dig Liver Dis |volume=38 |issue=9 |pages=623–42 |year=2006 |month=September |pmid=16766237 |doi=10.1016/j.dld.2006.04.002 |url=}}</ref>

Features (classic):<ref>{{Cite journal | last1 = Li | first1 = SJ. | last2 = Nussbaum | first2 = MS. | last3 = McFadden | first3 = DW. | last4 = Gapen | first4 = CL. | last5 = Dayal | first5 = R. | last6 = Fischer | first6 = JE. | title = Addition of glucagon to total parenteral nutrition (TPN) prevents hepatic steatosis in rats. | journal = Surgery | volume = 104 | issue = 2 | pages = 350-7 | month = Aug | year = 1988 | doi = | PMID = 3135627 }}</ref><ref>{{Cite journal | last1 = Stanko | first1 = RT. | last2 = Nathan | first2 = G. | last3 = Mendelow | first3 = H. | last4 = Adibi | first4 = SA. | title = Development of hepatic cholestasis and fibrosis in patients with massive loss of intestine supported by prolonged parenteral nutrition. | journal = Gastroenterology | volume = 92 | issue = 1 | pages = 197-202 | month = Jan | year = 1987 | doi = | PMID = 3096806 }}
</ref>
*[[Steatosis]] (periportal) - early.
*Cholestasis - late.

==Giant cell hepatitis==
*[[AKA]] ''neonatal giant cell hepatitis''.

:See: ''[[Giant cell hepatitis]]''.

==Hepatic amyloidosis==
{{Main|Amyloidosis}}
*[[AKA]] ''liver amyloidosis''.
*[[AKA]] ''amyloidosis of the liver''.
===General===
*Diffuse abundant amyloid within the space of Disse is associated with [[portal hypertension]].<ref name=pmid1864548>{{Cite journal | last1 = Bion | first1 = E. | last2 = Brenard | first2 = R. | last3 = Pariente | first3 = EA. | last4 = Lebrec | first4 = D. | last5 = Degott | first5 = C. | last6 = Maitre | first6 = F. | last7 = Benhamou | first7 = JP. | title = Sinusoidal portal hypertension in hepatic amyloidosis. | journal = Gut | volume = 32 | issue = 2 | pages = 227-30 | month = Feb | year = 1991 | doi = | PMID = 1864548 | PMC = 1378815 | URL = http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1378815/?tool=pubmed }}</ref>

===Microscopic===
Features:
*Amorphous extracellular pink stuff on H&E - see ''[[amyloid]]'' article.

DDx:
*[[Fibrolamellar hepatocellular carcinoma]].

====Images====
<gallery>
Image:Hepatic_amyloidosis_-_low_mag.jpg | Amyloidosis of the liver - low mag. (WC)
Image:Hepatic_amyloidosis_-_intermed_mag.jpg | Amyloidosis of the liver - intermed. mag. (WC)
Image:Hepatic_amyloidosis_-_high_mag.jpg | Amyloidosis of the liver - high mag. (WC)
Image:Hepatic_amyloidosis_-_very_high_mag.jpg | Amyloidosis of the liver - very high mag. (WC)
</gallery>
A. [[File:1 AMY 1 680x512px.tif|Amorphous material replaces hepatic parenchyma [4X]]]
 
B. [[File:2 AMY 1 680x512px.tif|Material barely stains blue on trichrome [10X]]]
 
C. [[File:3 AMY 1 680x512px.tif|Material stains red on unpolarized Congo Red [40X]]]
 
D. [[File:4 AMY 1 680x512px.tif|Material stains apple green on polarized Congo Red [40X]]]
 
Amyloidosis. A. Amorphous material replaces hepatic parenchyma. B. Material barely stains blue on trichrome. C. Material stains red on unpolarized Congo Red. D. Material stains apple green on polarized Congo Red.

===Stains===
*[[Congo red]] +ve.

==Fulminant hepatic necrosis==
===General===
Etiology:
*Viral, i.e. [[Hepatitis A]], [[Hepatitis B]]; [[Hepatitis C]] - extremely rare.
*Trauma.
*Shock.

===Microscopic===
{|
[[File:1 Necrosis 2 680x512px.tif| Submassive hepatic necrosis.]]
[[File:2 Necrosis 2 680x512px.tif| Submassive hepatic necrosis.]]
 
[[File:3 Necrosis 2 680x512px.tif| Submassive hepatic necrosis.]]
[[File:4 Necrosis 2 680x512px.tif| Submassive hepatic necrosis.]]
 
[[File:5 Necrosis 2 680x512px.tif| Submassive hepatic necrosis.]]
[[File:6 Necrosis 2 680x512px.tif| Submassive hepatic necrosis.]]
|}
Submassive hepatic necrosis. Patient had transaminases in the thousands that rapidly dropped to normal. Pink preserved parenchyma strews empty necrotic spaces (Row 1 Left 20X). Focus of necrosis with no apparent hepatocytes macrophages abuts apparently normal liver (Row 1 Right 200X). Iron stain shows the macrophages bear hemosiderin (Row 2 Left 200X). Reticulin stain highlights the recently dead liver cells (Row 2 Right 200X). Reticulin stain shows a necrotic bridge forming; the multiple small black circles preclude diagnosis of a fibrous bridge (Row 3 Left 200X). Trichrome shows the necrotic bridge (“collapse”) lacks much collagen deposition, as would be expected for bridging fibrosis (Row 3 Right 200X).

Features:
*Hepatocyte [[necrosis]].
*Bile duct proliferation.

DDx:
*[[Cholangiocarcinoma]].
*[[Angiosarcoma]].

==Secondary hemochromatosis==
:''For the hereditary one see [[hereditary hemochromatosis]]''.
===General===
*Iron overload secondary to blood transfusions for hereditary or acquired anemia.<ref name=pmid19727383/>
**Primary hemochromatosis due to a defect in iron processing - called ''[[hereditary hemochromatosis]]''.
*Imaging considered the best test, as iron deposition is patchy.<ref name=pmid19727383/>

Selected hereditary causes:<ref name=pmid19727383>{{Cite journal | last1 = Gattermann | first1 = N. | title = The treatment of secondary hemochromatosis. | journal = Dtsch Arztebl Int | volume = 106 | issue = 30 | pages = 499-504, I | month = Jul | year = 2009 | doi = 10.3238/arztebl.2009.0499 | PMID = 19727383 | PMC = 2735704 | URL = http://www.ncbi.nlm.nih.gov.myaccess.library.utoronto.ca/pmc/articles/PMC2735704/?tool=pubmed}}</ref>
*Thalassemia.
*[[Sickle cell anemia]].
*Hereditary sideroblastic anemia.

Selected acquired causes:<ref name=pmid19727383/>
*[[Myelodysplastic syndromes]]
*Myelofibrosis
*Aplastic anemia, intractable.

===Microscopic===
:See ''[[hereditary hemochromatosis]]''.

==Hepatic sarcoidosis==
{{Main|Hepatic sarcoidosis}}
==Overlapping Disorders==

[[File:1 Mixed Disorder 1 680x512px.tif|Changes of steatohepatitis and interface hepatitis, with granuloma. Patient with diabetes was ANA, AMA, HCV, HBV negative, without drugs known to produce granulomas or interface hepatitis. This may be a case of AMA negative primary biliary cirrhosis, but studies to determine that with certainty were not performed.]]
[[File:2 Mixed Disorder 1 680x512px.tif|Changes of steatohepatitis and interface hepatitis, with granuloma. Patient with diabetes was ANA, AMA, HCV, HBV negative, without drugs known to produce granulomas or interface hepatitis. This may be a case of AMA negative primary biliary cirrhosis, but studies to determine that with certainty were not performed.]]
[[File:3 Mixed Disorder 1 680x512px.tif|Changes of steatohepatitis and interface hepatitis, with granuloma. Patient with diabetes was ANA, AMA, HCV, HBV negative, without drugs known to produce granulomas or interface hepatitis. This may be a case of AMA negative primary biliary cirrhosis, but studies to determine that with certainty were not performed.]]
[[File:4 Mixed Disorder 1 680x512px.tif|Changes of steatohepatitis and interface hepatitis, with granuloma. Patient with diabetes was ANA, AMA, HCV, HBV negative, without drugs known to produce granulomas or interface hepatitis. This may be a case of AMA negative primary biliary cirrhosis, but studies to determine that with certainty were not performed.]]
[[File:5 Mixed Disorder 1 680x512px.tif|Changes of steatohepatitis and interface hepatitis, with granuloma. Patient with diabetes was ANA, AMA, HCV, HBV negative, without drugs known to produce granulomas or interface hepatitis. This may be a case of AMA negative primary biliary cirrhosis, but studies to determine that with certainty were not performed.]]
[[File:6 Mixed Disorder 1 680x512px.tif|Changes of steatohepatitis and interface hepatitis, with granuloma. Patient with diabetes was ANA, AMA, HCV, HBV negative, without drugs known to produce granulomas or interface hepatitis. This may be a case of AMA negative primary biliary cirrhosis, but studies to determine that with certainty were not performed.]] 
Changes of steatohepatitis and interface hepatitis, with granuloma. Patient with diabetes was ANA, AMA, HCV, HBV negative, without drugs known to produce granulomas or interface hepatitis. This may be a case of AMA negative primary biliary cirrhosis, but studies to determine that with certainty were not performed. A. Low power shows hepatocytes afflicted by steatosis and an inflamed portal tract. B. In a region of fatty change lie cytoplasmic tufts of ballooning degeneration (green arrows) and a lipogranuloma (black arrow). C. At the portal-hepatocyte junction lies interface hepatitis (black arrows), as well as extension of inflammation into the lobule (green arrows). D. Red hepatocytes bounded by inflammation denote piecemeal necrosis [PAS without diastase]. E. Giant cells intermixed with lymphocytes prove a portal granuloma [PAS without diastase]. F. A blue fibrous bridge extends from a triad [Trichrome].

[[File:4 95599552608917 sl 1.png|Acute obstructive changes and changes of recurrent acute injury]]
[[File:4 95599552608917 sl 2.png|Acute obstructive changes and changes of recurrent acute injury]]
[[File:4 95599552608917 sl 3.png|Acute obstructive changes and changes of recurrent acute injury]]
[[File:4 95599552608917 sl 4.png|Acute obstructive changes and changes of recurrent acute injury]]
[[File:4 95599552608917 sl 5.png|Acute obstructive changes and changes of recurrent acute injury]]
[[File:4 95599552608917 sl 6.png|Acute obstructive changes and changes of recurrent acute injury]]
[[File:4 95599552608917 sl 7.png|Acute obstructive changes and changes of recurrent acute injury]] 
Acute obstructive changes and changes of recurrent injury in 46 yo man with Clostridium perfringens positive blood culture, an ERCP that showed duodenal compression by the pancreas with resultant bile duct dilatation. The patient had had and continued to have multiple bouts of acute pancreatitis. At the time of biopsy, decreased platelet count/hemoglobin/albumin, elevated lipase/amylase/PT/PTT, normal alkaline phosphatase, bilirubin, AST/ALT, AMA, hepatitis virus serology, ANA. A. Fragment biopsy shows inflamed triads and bridges. B. Trichrome shows bridges without nodules, evidence of prior injury; the patient subsequently developed multiple episodes of pancreatitis. C. Reticulin shows piecemeal necrosis, with black lines bounding individual hepatocytes at interface (arrows). D. Collapse is shown by closly approximated thick black lines; one cannot call portal-central collapse without seeing a central vein. Note on this and the other reticulin image that regeneration, two cell thick cords, is not prominent. E. PAS D of two portal triads, far nearer than normal, both expanded. Note increased number of ducts/ductules (red arrows), neutrophils, and PAS-D macrophages. F. PAS D shows collapse extending from a triad to a portion of a lobule with steatosis. No feathery degeneration or bile duct plugs were seen. Neither were foci of spotty necrosis or abscess seen. G. Other triads, again edematous, showed more of a chronic inflammatory response, with occasional plasma cells (black arrows). Also present are neutrophils (red arrows). The bile duct (grey arrow) near the artery (brown arrow) shows mildly disturbed nuclei. Note early proliferated bile ductules (cyan arrows).

[[File:6 17281676469188 sl 1.png| Hepatitis B virus with steatohepatitis]]
[[File:6 17281676469188 sl 2.png| Hepatitis B virus with steatohepatitis]]
[[File:6 17281676469188 sl 3.png| Hepatitis B virus with steatohepatitis]]
[[File:6 17281676469188 sl 4.png| Hepatitis B virus with steatohepatitis]]
[[File:6 17281676469188 sl 5.png| Hepatitis B virus with steatohepatitis]]
[[File:6 17281676469188 sl 6.png| Hepatitis B virus with steatohepatitis]] 
Hepatitis B virus with steatohepatitis in a 36 year old man with hepatitis B surface antigen and hepatitis Be antigen positivity, Hepatitis be QTPC of 1750 cop/mL, an occasionally mildly elevated (42) ALT, and normal glucose, alkaline phosphatase, bilirubin, and other transaminases. He had a history of alcohol abuse, which became controlled. A. Triads show scant inflammation without definite interface hepatitis. About one-fourth of the lobule, not pan-acinar, is afflicted by steatosis. B. Occasional tufts are seen (arrow), indicating focal ballooning sufficient for a diagnosis of steatohepatitis. C. Glycogenated nuclei (black arrows) and hepatocytes with feathery degeneration (red arrows) are seen. D. Very rare foci of spotty necrosis were seen. E. Apart from this triad and the one in the trichrome stain in F, which had moderate inflammation comprising lymphocytes and macrophages, all triads were small, most without any inflammation at all. Neither collapse nor piecemeal necrosis were seen on reticulin stain. F. Trichrome stain showed only portal fibrosis. The interhepatocyte fibrosis required for brunt fibrosis stage I was not seen. Hence, one would grade this as follows: A) Chronic hepatitis (history of hepatitis B), Metavir activity index 1, Piecemeal necrosis 0, Lobular necrosis 1, Metavir fibrosis stage 1, B) Steatohepaitits, Brunt necroinflammatory grade 1, Brunt fibrosis stage 0.

=See also=
*[[Pancreas]].
*[[Gastrointestinal pathology]].
*[[Liver neoplasms]].
*[[Liver]].

=References=
{{reflist|2}}

[[Category:Gastrointestinal pathology]]
[[Category:Liver pathology]]
[[Category:Medical liver disease]]

Medical liver disease

2017-02-10T18:52:54Z

Mitchell: /* Extrahepatic biliary obstruction */ Improved appearances of image notation

[[Image:Ground glass hepatocytes high mag cropped 2.jpg|thumb|right|[[Micrograph]] showing ground glass hepatocytes, as seen in chronic [[hepatitis B]]. [[H&E stain]].]]
This article deals with '''medical [[liver]] disease'''. An introduction to the liver and approach is found in the ''[[liver]]'' article.

Every differential in liver pathology has "drugs"<ref>{{Ref PCPBoD8|448}}</ref> -- if it isn't clearly malignancy.

Liver neoplasms are dealt with in the ''[[liver neoplasms]]'' article.

Medical liver biopsies are often non-specific, as the liver has the same appearance for many mechanisms of injury, especially when the injury is marked. The clinical history, serology and imaging are essential for proper interpretations in this domain of pathology.

=Review of liver blood work=
===Inflammation activity===
*ALT.
*AST.

===Cholestatic markers===
*ALP.
*GGT - used to assess whether the ALP is an "honest" value, elevated in cirrhosis.

===Cirrhosis/decompensation===
*PLT - low is suggestive of dysfunction.
*INR - high is bad, unless anticoagulated.

===Other===
*Bilirubin.
**Direct (AKA conjugated).
**Indirect (AKA unconjugated).

A short DDx of elevated:<ref>{{Ref PCPBoD8|441}}</ref>
*Indirect:
**[[Gilbert syndrome]].
**Crigler-Najjar syndrome type 1.
**Crigler-Najjar syndrome type 2.
*Direct:
**Rotor syndrome.
**Dubin-Johnson syndomre.

===Viral hepatitis===
*HBV DNA.
*HCV RNA.
*HBs Ag, HBs Ab, HBe Ag, HBe Ab.
*HCV Ab.

Others:
*[[Epstein-Barr virus]] (EBV).
*[[Cytomegalovirus]] (CMV) - especially in the immune incompetent.

====Hepatitis B====
Meaning & utility of the various [[Hepatitis B]] tests:<ref>URL: [http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/hepatology/hepatitis-B/ http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/hepatology/hepatitis-B/]. Accessed on: 16 May 2011.</ref><ref name=lto_hepb>URL: [http://www.labtestsonline.org/understanding/analytes/hepatitis_b/test.html http://www.labtestsonline.org/understanding/analytes/hepatitis_b/test.html]. Accessed on: 16 May 2011.</ref>
{| class="wikitable sortable" border="1"
! Test name
! Location
! Positive test
! Negative test
! Usual question
|-
| HBs Ag||Surface||Virus active||No active infection||Active infection?
|-
| HBs Ab||Surface||Exposed OR vaccinated||No exposure OR no vaccine OR loss of Ab||Immunization status?
|-
| HBe Ag||Virus core||Infect. w/ viral replication||No active infection||Active infect. w/ viral replication?
|-
| HBe Ab||Virus core||Exposed to virus||Infect. w/o antibody response OR not exposed||Immune response to infection?
|-
| HBV DNA||-||Active||Not active/no exposure||Viral load/how active?
|-
| HBc Ab||Virus core||Virus active/previous exposure||No exposure||Early active infection?
|}
Notes:
*''HBc Ab'' may test for acute (IgM) or chronic infection - dependent on specific antibody test; it is often used to look for early infection.<ref name=lto_hepb>URL: [http://www.labtestsonline.org/understanding/analytes/hepatitis_b/test.html http://www.labtestsonline.org/understanding/analytes/hepatitis_b/test.html]. Accessed on: 16 May 2011.</ref>
*''Carriers of hepatitis B'': HBs Ag +ve, HBs Ab -ve, HBc Ag -ve, HBc Ab +ve, HBe Ag -ve, HBe Ab +ve.<ref>URL: [http://labtestsonline.org/understanding/analytes/hepatitis-b/tab/test http://labtestsonline.org/understanding/analytes/hepatitis-b/tab/test]. Accessed on: 3 May 2012.</ref>

===Markers for rare liver diseases===
*Ceruloplasm - low think ''[[Wilson's disease]]''; typical value for Wilson's ~ 0.12 g/L.
**<0.20 g/L is a criteria for Wilson's disease.<ref name=pmid18556333>Diagnostic accuracy of serum ceruloplasmin in Wilson disease: determination of sensitivity and specificity by ROC curve analysis among ATP7B-genotyped subjects. Mak CM, Lam CW, Tam S. Clin Chem. 2008 Aug;54(8):1356-62. Epub 2008 Jun 12. PMID 18556333. URL: [http://www.clinchem.org/cgi/reprint/54/8/1356.pdf http://www.clinchem.org/cgi/reprint/54/8/1356.pdf]. Accessed on: 28 September 2009.</ref>
*Alpha-1 antitrypsin - if low think ''deficiency''.

===Hemosiderosis===
*Ferritin - high.
*Iron saturation - high.

Causes:
*Hemochromatosis.
*Hemolysis, chronic.
*Cirrhosis.

=Medical imaging=
Blood flow:<ref>URL: [http://insidesurgery.com/2010/12/hepatopedal-hepatofugal-flow/ http://insidesurgery.com/2010/12/hepatopedal-hepatofugal-flow/]. Accessed on: 2 December 2011.</ref>
*Hepatopedal flow = normal portal vein flow.
*Hepatofugal flow = reversed portal vein flow.

==Interventional measurements==
Wedged to free hepatic venous pressure:<ref name=pmid1864548>{{Cite journal | last1 = Bion | first1 = E. | last2 = Brenard | first2 = R. | last3 = Pariente | first3 = EA. | last4 = Lebrec | first4 = D. | last5 = Degott | first5 = C. | last6 = Maitre | first6 = F. | last7 = Benhamou | first7 = JP. | title = Sinusoidal portal hypertension in hepatic amyloidosis. | journal = Gut | volume = 32 | issue = 2 | pages = 227-30 | month = Feb | year = 1991 | doi = | PMID = 1864548 | PMC = 1378815 | URL = http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1378815/?tool=pubmed }}</ref>
*Normal = 1-4 mmHg.
**Elevated in [[portal hypertension]].

=Liver biopsy=
==Medical liver biopsy adequacy==
Liver biopsy specimens should be:<ref>{{Ref MacSween|418}}</ref>
*2.0 cm in length and contain 11-15 portal tracts,
*The core should be deeper than 1.0 cm from the liver capsule; specimens close to the capsule may lead to over grading of fibrosis.

==Reporting==
{{Main|Pathology reports}}
<pre>
Specimen, procedure:
- Diagnosis.
</pre>
The diagnosis usually contains grading and staging information, e.g. ''activity 2 /4, Laennec fibrosis stage 1 /4''.

In the context of medical liver disease:
*Grade = inflammation/activity.
*Stage = severity of fibrosis/architectural changes.

Notes:
*The term "acute" is infrequently used in liver pathology.
*In the liver: neutrophils ''is not'' acute -- unlike most elsewhere in the body.<ref>OA. September 2009.</ref>

===A microscopic checklist===
<pre>
Size of biopsy: Adequate
Fragmentation: Absent
Fibrosis: Stage 2-3/4, mostly stage 2
Fibrous septa: Present
Septa with curved contours: Present – focally only
Large droplet steatosis (% of hepatocytes): Present, moderate 60%
Ballooning of hepatocytes: Present, rare
Mallory-Denk bodies: Present, rare
Portal inflammation: Present
Interface activity: Minimal (0-1/4)
Lobular necroinflammation: Minimal
Ducts: Present in normal numbers
Duct injury: Absent
Ductular reaction: Absent
Cholestasis: Absent
Terminal hepatic venules: Present
Iron stain: Absent
Ground glass cells with routine stains: Absent
PASD for alpha-1 antitrypsin droplets: Negative
</pre>

=Viral hepatitis=
These are common. The diagnoses are based on serology. The serology is covered in the ''[[Liver_pathology#Viral_hepatitis|viral hepatitis]]'' section in the ''[[liver pathology]]'' article.

Typically classified as:<ref name=pmid8048409>{{Cite journal | title = Terminology of chronic hepatitis, hepatic allograft rejection, and nodular lesions of the liver: summary of recommendations developed by an international working party, supported by the World Congresses of Gastroenterology, Los Angeles, 1994. | journal = Am J Gastroenterol | volume = 89 | issue = 8 Suppl | pages = S177-81 | month = Aug | year = 1994 | doi = | PMID = 8048409 }}</ref><ref>URL: [http://familydoctor.org/familydoctor/en/diseases-conditions/hepatitis-b.html http://familydoctor.org/familydoctor/en/diseases-conditions/hepatitis-b.html]. Accessed on: 2 May 2012.</ref>
#Acute < 6 months duration.
#Chronic > 6 months duration.

==Hepatitis A==
*Infection is self-limited, i.e. not persistent.
**May present as ''[[fulminant hepatic necrosis]]''.
*Usually asymptomatic in children.<ref name=pmid20068336>{{cite journal |author=Jeong SH, Lee HS |title=Hepatitis A: clinical manifestations and management |journal=Intervirology |volume=53 |issue=1 |pages=15–9 |year=2010 |pmid=20068336 |doi=10.1159/000252779 |url=}}</ref>
*Serology is diagnostic.

==Hepatitis B==
:''Hepatitis B virus'', abbreviated ''HBV'', redirects here.
{{Main|Hepatitis B}}

==Hepatitis C==
{{Main|Hepatitis C}}

=Other infections=
*Hydatid disease (Hydatid cyst).
*Ascaris.
*Fasciola

==Hydatid disease==
*[[AKA]] ''hydatid cyst''.
===General===
*Etiology: ''[[Echinococcus]]''.

===Microscopic===
Features:
*Laminated wall +/- calcification.<ref name=Ref_PBPoD8_448>{{Ref PCPBoD8|448}}</ref>
*Organisms -- see ''[[Echinococcus]]''.

====Images====
<gallery>
Image:Liver_cyst_wall_-_intermed_mag.jpg | Liver cyst wall - intermed. mag. (WC)
Image:Liver_cyst_wall_-_high_mag.jpg | Liver cyst wall - high mag. (WC)
Image: Laminated liver cyst wall - intermed mag.jpg | Characteristic laminated portion - intermed. mag. (WC)
Image: Laminated liver cyst wall - high mag.jpg | Characteristic laminated portion - high mag. (WC)
</gallery>
[[www]]:
*[http://pathmicro.med.sc.edu/parasitology/hydatid-hist1.jpg Hydatid cyst (med.sc.edu)].
*[http://www.atlas.or.kr/atlas/include/viewImg.html?uid=645 Hydatid cyst (atlas.or.kr)].
*[http://casereports.bmj.com/content/2009/bcr.04.2009.1798.full Hydatid cyst (casereports.bmj.com)].

==Abscess==
A. [[File:1 ABS 1 680x512px.tif|A process replaces most of the liver parenchyma (20X).]]
 
B. [[File:2 ABS 1 680x512px.tif|Fibrinopurulent exudate apposes granulation tissue (200X).]]
 
C. [[File:3 ABS 1 680x512px.tif|Neutrophils lie in widened sinusoids (200X)..]]
 
D. [[File:4 ABS 1 680x512px.tif|Trichrome shows collagenization of spaces of Disse. Scarring about an abscess or other mass lesion should not be interpreted as reflective of the liver in general (200X).]]
 
Abscess. A. A process replaces most of the liver parenchyma. B. Fibrinopurulent exudate apposes granulation tissue. C. Neutrophils lie in widened sinusoids. D. Trichrome shows collagenization of spaces of Disse. Scarring about an abscess or other mass lesion should not be interpreted as reflective of the liver in general (LR 200X).

==Coccidiomycosis==
A. [[File:Coccidiomycosis - 1 - 40X 680x512px shot.tif|500x500px Granulomas at low power]]
 
B. [[File:Coccidiomycosis - 1 - 200X 680x513px shot.tif|500x500px Granulomas with centrally crowded cells & lady slipper macrophage nuclei]]
 
C. [[File:Coccidiomycosis - 1 - 400X 1369x1024px shot.tif|500x500px Center of previous granuloma showing pyknotic macrophage nuclei]]
 
D. [[File:Coccidiomycosis - 1 - GMS 400X 1369x1024px shot.tif|500x500px Four Coccidiomycotic spherules]]
 
Coccidiomycosis. A. Note the granulomas in otherwise undisturbed liver (UL). B. Granuloma with centrally crowded cells & lady slipper macrophage nuclei. C. Center of granuloma with pyknotic macrophage nuclei, "necrotizing". D. Organisms on GMS stain.

=Metabolic and toxic=
==Alcoholic liver disease==
===General===
*Acute and/or chronic liver changes due to excessive [[alcohol]] use - includes:
**''[[Alcoholic steatohepatitis]]'' (ASH), [[AKA]] ''alcoholic hepatitis''.<ref>URL: [http://emedicine.medscape.com/article/170539-overview http://emedicine.medscape.com/article/170539-overview]. Accessed on: 3 May 2012.</ref>
***Alcoholic hepatitis can be with minimal steatosis.<ref>STC. 6 December 2010.</ref>
**[[Steatosis]] - classically macrovescicular and centrilobular.
**Alcoholic [[cirrhosis]].

====Classic lab findings in EtOH abusers====
*AST & ALT elevated with AST:ALT=2:1.
*GGT elevated.
*MCV increased.

===Gross pathology/radiologic findings===
*Classically micronodular pattern.
**May be macronodular.

===Microscopic===
See:
*''[[Steatohepatitis]]'' section and ''[[ballooning degeneration]]'' section.

Features:
*Often zone III damage.
*Cholestatsis common, i.e. yellow staining.
**NASH (non-alcoholic steatohepatitis) usu. does not have cholestasis.<ref>STC. 6 December 2010.</ref>
*Fibrosis starts at central veins.
*Neutrophils (often helpful) -- few other things have PMNs. (???)
**Neutrophils cluster around cells with Mallory hyaline.

====Images====

A. [[File:1 etoh 3 680x512px.tif| Alcoholic hepatitis with Metavir stage IV fibrosis (advanced fibrosis/cirrhosis).]]
 
B. [[File:2 etoh 3 680x512px.tif| Alcoholic hepatitis with Metavir stage IV fibrosis (advanced fibrosis/cirrhosis).]]
 
C. [[File:3 etoh 3 680x512px.tif| Alcoholic hepatitis with Metavir stage IV fibrosis (advanced fibrosis/cirrhosis).]]
 
D. [[File:4 etoh 3 680x512px.tif| Alcoholic hepatitis with Metavir stage IV fibrosis (advanced fibrosis/cirrhosis).]]
 
E. [[File:5 etoh 3 680x512px.tif| Alcoholic hepatitis with Metavir stage IV fibrosis (advanced fibrosis/cirrhosis).]]
 
F. [[File:6 etoh 3 680x512px.tif| Alcoholic hepatitis with Metavir stage IV fibrosis (advanced fibrosis/cirrhosis).]]
 

Alcoholic hepatitis with Metavir stage IV fibrosis (advanced fibrosis/cirrhosis).
A. Trichrome shows relatively non-inflamed fibrous bands, as well as [between green dots] nodules. The lack of regeneration throughout might have precluded a diagnosis of cirrhosis, but stage IV fibrosis under the Metavir system is justified. B. Reticulin shows regenerative nodules [left] with mostly two or more nuclei between black lines juxtaposed to non-regenerative hepatocytes on the right, without piecemeal necrosis. C. Regenerative nodules show occasional neutrophils [red arrow] and cytoplasmic tufts of ballooned cells, sometimes possibly Mallory hyalin [green arrows]. D. Triads (note vein [green arrow], artery [yellow arrow], and interlobular bile duct [blue arrow]) generally showed little or no interface hepatitis, even when expanded by fibrosis and inflamed. E. Occasional foci of spotty necrosis were seen. F. This edge of an inflamed triads shows neutrophils about proliferated bile ducts [red arrows], as well as Mallory-Denk bodies [blue arrows].
 
A. [[File:1 etoh 4 680x512px.tif| Cirrhosis in an alcoholic.]]
 
B. [[File:2 etoh 4 680x512px.tif| Cirrhosis in an alcoholic.]]
 
C. [[File:3 etoh 4 680x512px.tif| Cirrhosis in an alcoholic.]]
 
D. [[File:4 etoh 4 680x512px.tif| Cirrhosis in an alcoholic.]]
 
E. [[File:5 etoh 4 680x512px.tif| Cirrhosis in an alcoholic.]]
 
F. [[File:6 etoh 4 680x512px.tif| Cirrhosis in an alcoholic.]]
 
Definite cirrhosis in an alcoholic. A. Hepatocyte free bands parse tissue, with occasional definite islands [arrows]. B. Trichrome establishes blue fibrosis about isles [arrows]. C. Reticulin stain shows nodules with regeneration, wherein a large proportion of them are at least two nuclei thick [arrows]. D. Bile duct proliferation can be difficult, sometimes mimicking cholangiocarcinoma. Follow the double headed arrows to see how the ductules can be seen to proliferate from a single sources, with all ducts being complete, without necrotic epithelial cells. E. PAS with distase can help, as cholangiocarcinoma generally lacks the red rim of proliferating bile ductules [arrows]; again note the connections that can be made between the ductule openings by the blue double headed arrows. The cyan double headed arrows show general parallelism, consistent with uniform directionality induced by extrinsic force, not a neoplastic spread. F. Trichrome shows the most difficult focus. Double headed arrows display the connectivity seen before of the proliferated bile ductules. Note that numerous pairs of adjacent perpendicular glands without a head to foot appearance are not seen that would indicate the disorderly spread of cholangiocarcinoma.
 
A. [[File:1 ALC 2 680x512px.tif|Expanded, inflamed triads with increased bile duct/vascular openings. Mild steatosis (40X).]]
 
B. [[File:2 ALC 2 680x512px.tif|Trichrome stain shows periportal fibrosis [red arrowheads] (200X).]]
 
C. [[File:3 ALC 2 680x512px.tif|PAS with diastase stain shows proliferated bile ductules [blue arrowheads] in stroma with mixed inflammatory infiltrate (400X)]]
 
D. [[File:4 ALC 2 680x512px.tif|Neutrophils about ballooned hepatocyte (satellitosis) [yellow arrowheads]. Councilman bodies [green arrowheads] (400X).]]
 
Alcoholic hepatitis without cirrhosis. No history of viral disease. AMA negative. A. Expanded, inflamed triads with increased bile duct/vascular openings. Mild steatosis. B. Trichrome stain shows periportal fibrosis [red arrowheads]. C. PAS with diastase stain shows proliferated bile ductules [blue arrowheads] in stroma with mixed inflammatory infiltrate. D. Neutrophils about ballooned hepatocyte (satellitosis) [yellow arrowheads]. Councilman bodies [green arrowheads].

Notes:
*If portal inflammatory infiltrates more than mild, r/o other causes i.e. [[viral hepatitis]].
*Mallory bodies once thought to be characteristic; now considered non-specific and generally poorly understood.<ref>{{cite journal |author=Jensen K, Gluud C |title=The Mallory body: theories on development and pathological significance (Part 2 of a literature survey) |journal=Hepatology |volume=20 |issue=5 |pages=1330-42 |year=1994 |month=November |pmid=7927269 |doi= |url=}}</ref>
*Some consider ''alcoholic liver disease'' a clinical diagnosis, i.e. as a pathologist one does not diagnose it.<ref>MG. September 2009.</ref>

==Non-alcoholic fatty liver disease==
*Abbreviated ''NAFLD''.
*Fatty liver that is not due to alcohol; includes obesity-related fatty liver, metabolic disease/diabetes-related fatty liver.

===NASH===
*Non-alcoholic steatohepatitis - see ''steatohepatitis'' section.
*Histologically indistinguishable from ASH.
*NASH is a ''clinical diagnosis'' based on exclusion of alcohol.

==Steatohepatitis==
{{Main|Steatohepatitis}}

=Autoimmune=
==Autoimmune hepatitis==
*Abbreviated ''AIH''.
{{Main|Autoimmune hepatitis}}

==Primary biliary cirrhosis==
*Abbreviated PBC.
{{Main|Primary biliary cirrhosis}}

==Autoimmune hepatitis with obstruction - combined changes==
A. [[File:1 AIH OBS 1.tif|Low power shows inflammation; portal triads, lobules, central veins cannot be distinguished (40X).]]
 
B. [[File:2 AIH OBS 1.tif|Trichrome shows central venous sclerosis (red arrowhead), periportal fibrosis (green arrowhead), & space of Disse collagenization (yellow arrowhead); juxtaposition of central vein & portal tract indicates collapse, no definite bridging was seen (100X)]]
 
C. [[File:3 AIH OBS 1.tif|Central vein is inflamed with a rare plasma cell (cyan arrowhead) (400X).]]
 
D. [[File:4 AIH OBS 1.tif|Interface hepatitis with plasma cells (yellow arrows) and ballooned hepatocytes (red arrows). Lobule is disorganized (400X).]]
 
E. [[File:5 AIH OBS 1.tif|Proliferating bile ductules (blue arrows) with occasional neutrophils (fucsia arrows), indicative of obstruction, but not acute cholangitis, which requires inflamed bile duct itself, best diagnosed with associated blood vessel (400X).]]
 
F. [[File:6 AIH OBS 1.tif|Rare distorted rosettes with greenish brown strands of bile (left arrow) or bile plugs (right arrow) (400X).]]
 
Patient with SLE and obstructive jaundice that resolved with apparent passage of stone. A. Low power shows inflammation; portal triads, lobules, central veins cannot be distinguished. B. Trichrome shows central venous sclerosis (red arrowhead), periportal fibrosis (green arrowhead), & space of Disse collagenization (yellow arrowhead); juxtaposition of central vein & portal tract indicates collapse, no definite bridging was seen. C. Central vein is inflamed with a rare plasma cell (cyan arrowhead). D. Interface hepatitis with plasma cells (yellow arrows) and ballooned hepatocytes (red arrows). Lobule is disorganized. E. Proliferating bile ductules (blue arrows) with occasional neutrophils (fucsia arrows), indicative of obstruction, but not acute cholangitis, which requires inflamed bile duct itself, best diagnosed with associated blood vessel. F. Rare distorted rosettes with greenish brown strands of bile (left arrow) or bile plugs (right arrow).

==Autoimmune hepatitis-primary biliary cirrhosis overlap syndrome==
*Abbreviation ''AIH-PBC OS''.
===General===
Epidemiology:
*Rare.

Serology:<ref name=pmid19491855>{{Cite journal | last1 = Muratori | first1 = P. | last2 = Granito | first2 = A. | last3 = Pappas | first3 = G. | last4 = Pendino | first4 = GM. | last5 = Quarneti | first5 = C. | last6 = Cicola | first6 = R. | last7 = Menichella | first7 = R. | last8 = Ferri | first8 = S. | last9 = Cassani | first9 = F. | title = The serological profile of the autoimmune hepatitis/primary biliary cirrhosis overlap syndrome. | journal = Am J Gastroenterol | volume = 104 | issue = 6 | pages = 1420-5 | month = Jun | year = 2009 | doi = 10.1038/ajg.2009.126 | PMID = 19491855 }}</ref>
*AMA +ve.
*Anti-dsDNA +ve.

===Microscopic===
:See: ''[[autoimmune hepatitis]]'' and ''[[primary biliary cirrhosis]]''.
A. [[File:1 AIH PBC 1 680x512px.tif|Expanded portal tracts with fuzzy edges (40X).]]
 
B. [[File:2 AIH PBC 1 680x512px.tif|Interface hepatitis with plasma cells (400X).]]
 
C. [[File:3 AIH PBC 1 680x512px.tif|Loose granuloma (400X).]]
 
D. [[File:4 AIH PBC 1 680x512px.tif|Damaged bile duct (400X).]]
 
AIH/PBC overlap. AMA & ANA positive with Alkaline phosphatase > 2 upper limit of normal & one ALT > 5 times upper limit of normal. A. Expanded portal tracts with fuzzy edges. B. Interface hepatitis with plasma cells. C. Loose granuloma. D. Damaged bile duct.

==Primary sclerosing cholangitis==
*Abbreviated ''PSC''.
{{Main|Primary sclerosing cholangitis}}

=Hereditary=
==Caroli disease==
===General===
*Genetic disease.
**Frequently associated with [[autosomal recessive polycystic kidney disease]] (ARPKD).<ref name=omim263200>{{OMIM|263200}}</ref>
**May be seen in isolation.<ref name=omim600643>{{OMIM|600643}}</ref>

Clinical:<ref name=pmid17461493>{{Cite journal | last1 = Yonem | first1 = O. | last2 = Bayraktar | first2 = Y. | title = Clinical characteristics of Caroli's syndrome. | journal = World J Gastroenterol | volume = 13 | issue = 13 | pages = 1934-7 | month = Apr | year = 2007 | doi = | PMID = 17461493 }}</ref>
*Recurrent [[cholangitis]].
*Recurrent [[cholelithiasis]].
*[[Cholangiocarcinoma]]<ref name=pmid17461492>{{Cite journal | last1 = Yonem | first1 = O. | last2 = Bayraktar | first2 = Y. | title = Clinical characteristics of Caroli's disease. | journal = World J Gastroenterol | volume = 13 | issue = 13 | pages = 1930-3 | month = Apr | year = 2007 | doi = | PMID = 17461492 }}</ref> - seen in ~7% of cases.<ref name=pmid15347876>{{Cite journal | last1 = Karim | first1 = AS. | title = Caroli's disease. | journal = Indian Pediatr | volume = 41 | issue = 8 | pages = 848-50 | month = Aug | year = 2004 | doi = | PMID = 15347876 }}</ref>

Note:
*''Caroli syndrome'' = Caroli disease + congenital hepatic fibrosis.<ref name=pmid15888616>{{Cite journal | last1 = Brancatelli | first1 = G. | last2 = Federle | first2 = MP. | last3 = Vilgrain | first3 = V. | last4 = Vullierme | first4 = MP. | last5 = Marin | first5 = D. | last6 = Lagalla | first6 = R. | title = Fibropolycystic liver disease: CT and MR imaging findings. | journal = Radiographics | volume = 25 | issue = 3 | pages = 659-70 | month = | year = | doi = 10.1148/rg.253045114 | PMID = 15888616 | URL = http://radiographics.rsna.org/content/25/3/659.long }}</ref>

===Gross===
*Dilated bile ducts.<ref name=omim263200/>

===Microscopic===
Features:<ref name=pmid17461493/>
*Dilated bile ducts.
*Periductal fibrosis. (???)
*+/-Fibrosis.

Image:
*[http://www.meddean.luc.edu/lumen/MedEd/orfpath/11-3-10.jpg Caroli disease (meddean.luc.edu)].<ref>URL: [http://www.meddean.luc.edu/lumen/MedEd/orfpath/develop.htm http://www.meddean.luc.edu/lumen/MedEd/orfpath/develop.htm]. Accessed on: 1 December 2011.</ref>

==Hereditary hemochromatosis==
:''For secondary causes see [[secondary hemochromatosis]]''.
{{Main|Hereditary hemochromatosis}}

==Wilson disease==
{{Main|Wilson's disease}}

==Alpha-1 antitrypsin deficiency==
*[[AKA]] ''alpha1-antiprotease inhibitor deficiency''.
{{Main|Alpha-1 antitrypsin deficiency }}

=Other=
==Budd-Chiari syndrome==
*[[AKA]] ''hepatic vein obstruction''.
===General===
*Hepatic outflow obstruction.

Clinical triad:<ref name=pmid21573256>{{Cite journal | last1 = Fox | first1 = MA. | last2 = Fox | first2 = JA. | last3 = Davies | first3 = MH. | title = Budd-Chiari syndrome--a review of the diagnosis and management. | journal = Acute Med | volume = 10 | issue = 1 | pages = 5-9 | month = | year = 2011 | doi = | PMID = 21573256 }}</ref>
*Ascites.
*Abdominal pain.
*Hepatomegaly.

Etiology:
*~50% have a [[myeloproliferative disease]].<ref name=pmid18814079>{{Cite journal | last1 = Plessier | first1 = A. | last2 = Valla | first2 = DC. | title = Budd-Chiari syndrome. | journal = Semin Liver Dis | volume = 28 | issue = 3 | pages = 259-69 | month = Aug | year = 2008 | doi = 10.1055/s-0028-1085094 | PMID = 18814079 }}</ref>
*May be due to mass effect from a tumour.

Clinical DDx:
*[[Hepatic veno-occlusive disease]].

===Microscopic===
Features:<ref name=pmid17569137>{{Cite journal | last1 = Aydinli | first1 = M. | last2 = Bayraktar | first2 = Y. | title = Budd-Chiari syndrome: etiology, pathogenesis and diagnosis. | journal = World J Gastroenterol | volume = 13 | issue = 19 | pages = 2693-6 | month = May | year = 2007 | doi = | PMID = 17569137 | url=http://www.wjgnet.com/1007-9327/full/v13/i19/2693.htm }}</ref>
*Sinusoidal dilation in zone III (congestion).
*+/-Hepatocyte drop-out.
*+/-Centrilobular fibrosis.

DDx congestion:
*Congestive heart failure ([[congestive hepatopathy]]).
*Constrictive pericarditis.

==Vanishing bile duct syndrome==
*[[AKA]] ''bile duct loss'', [[AKA]] ''ductopenia''.<ref name=pmid11521176/>
===General===
*Fatal.

DDx:<ref name=pmid18242505/>
*[[Primary biliary cirrhosis]].
*[[Primary sclerosing cholangitis]].
*[[GVHD]].<ref name=pmid7994249>{{Cite journal | last1 = Yeh | first1 = KH. | last2 = Hsieh | first2 = HC. | last3 = Tang | first3 = JL. | last4 = Lin | first4 = MT. | last5 = Yang | first5 = CH. | last6 = Chen | first6 = YC. | title = Severe isolated acute hepatic graft-versus-host disease with vanishing bile duct syndrome. | journal = Bone Marrow Transplant | volume = 14 | issue = 2 | pages = 319-21 | month = Aug | year = 1994 | doi = | PMID = 7994249 }}</ref>
*[[Drug-induced liver disease|Drugs]].<ref name=pmid11352118>{{Cite journal | last1 = Chitturi | first1 = S. | last2 = Farrell | first2 = GC. | title = Drug-induced cholestasis. | journal = Semin Gastrointest Dis | volume = 12 | issue = 2 | pages = 113-24 | month = Apr | year = 2001 | doi = | PMID = 11352118 }}</ref>
*Chronic rejection.<ref name=pmid11521176>{{Cite journal | last1 = Inomata | first1 = Y. | last2 = Tanaka | first2 = K. | title = Pathogenesis and treatment of bile duct loss after liver transplantation. | journal = J Hepatobiliary Pancreat Surg | volume = 8 | issue = 4 | pages = 316-22 | month = | year = 2001 | doi = 10.1007/s0053410080316 | PMID = 11521176 }}</ref>

===Microscopic===
Features:<ref name=pmid18242505>{{Cite journal | last1 = Reau | first1 = NS. | last2 = Jensen | first2 = DM. | title = Vanishing bile duct syndrome. | journal = Clin Liver Dis | volume = 12 | issue = 1 | pages = 203-17, x | month = Feb | year = 2008 | doi = 10.1016/j.cld.2007.11.007 | PMID = 18242505 }}</ref>
*Loss of intrahepatitic bile ducts - '''key feature'''.
*Cholestasis.

Note:
*May occur without fibrosis and inflammation; thus, can be easy to miss.

===IHC===
*[[CK7]] -ve.
**Marks bile ducts.

==Extrahepatic biliary obstruction==
A. [[File:1 OBS 3 680x512px.tif|Sinusoidal dilatation, circular spaces of hepatocytes, small portal triads(40X).]]
 
B. [[File:2 OBS 3 680x512px.tif|Bile in hepatocytes about central vein & in plugs in canaliculi [yellow arrowhead] (400X).]]
 
C. [[File:3 OBS 3 680x512px.tif|Trichrome shows fibrosis about central vein (400X).]]
 
D. [[File:4 OBS 3 680x512px.tif|PAS with diastase shows portal triads with mild edema and chronic inflammation, without tortuous bile duct (400X).]]
 
Early extrahepatic biliary obstruction, demonstrated radiographically, transient, with rise in bilirubin, alkaline phosphatase, and transaminases. Pure canalicular cholestasis near terminal hepatic venules also seen in acute hepatitis, drug reactions, benign recurrent cholestasis, pregnancy, sepsis, & lymphomas. A. Sinusoidal dilatation, circular spaces of hepatocytes, small portal triads. B. Bile in hepatocytes about central vein & in plugs in canaliculi [yellow arrowhead]. C. Trichrome shows fibrosis about central vein. D. PAS with diastase shows portal triads with mild edema and chronic inflammation, without tortuous bile duct.
 
A. [[File:1 OBS 2 680x512px.tif|Expanded inflamed portal triads, swollen hepatocytes (40X)]]
 
B. [[File:2 OBS 2 680x512px.tif|Edematous stroma, proliferating ductules [yellow arrowheads], PAS-D macrophages [red arrowhead] (PAS with diastasse, 200X)]]
 
C. [[File:3 OBS 2 680x512px.tif|Disordered, often swollen hepatocytes,some with feathery degeneration (net like spaces in cytoplasm [blue arrowhead], rare Councilman body [green arrowhead] (400X)]]
 
D. [[File:4 OBS 2 1360x1024px.tif|Bile in hepatocytes [cyan arrrowhead] & in canaliculi [purple arrowheads]. Empty acinar spaces bounded by hepatocytes [orange arrowhead] (400X, higher pixel),]]
 
Changes of extrahepatic biliary obstruction, months duration. A. Expanded inflamed portal triads, swollen hepatocytes. B. Edematous stroma, proliferating ductules [yellow arrowheads], PAS-D macrophages [red arrowhead]. C. Disordered, often swollen hepatocytes,some with feathery degeneration (net like spaces in cytoplasm) [blue arrowhead], rare Councilman body [green arrowhead]. D. Bile in hepatocytes [cyan arrrowhead] & in canaliculi [purple arrowheads]. Empty acinar spaces bounded by hepatocytes [orange arrowhead].
 
A. [[File:1 Bd obs 4 680x512px.tif|Expanded, light colored portal triads (arrows)(20X).]]
 
B. [[File:2 Bd obs 4 680x512px.tif|Proliferating bile ductules (cyan arrows) with neutrophils (yellow arrows), not specific for acute cholangitis, of assistance with large bile duct obstruction (400X)..]]
 
C. [[File:3 Bd obs 4 680x512px.tif|Uninflamed interlobular duct (yellow arrow) with, accompanying blood vessel (red arrow) (400X)]]
 
D. [[File:4 Bd obs 4 680x512px.tif|Bile infarct with pyknotic nuclei (arrows)(400X).]]
 
E. [[File:5 Bd obs 4 680x512px.tif|Bile (arrow) in interlobular bile duct with disordered nuclei (400X).]]
 
F. [[File:6 Bd obs 4 680x512px.tif|Bile plugs in cannaliculi (red arrows), feathery degeneration producing foamy macrophage like hepatocytes (yellow arrows)(400X).]]
 
Large bile duct obstruction. A. Expanded, light colored portal triads (arrows). B. Proliferating bile ductules (cyan arrows) with neutrophils (yellow arrows), not specific for acute cholangitis, of assistance with large bile duct obstruction. C. Uninflamed interlobular duct (yellow arrow) with, accompanying blood vessel (red arrow). D. Bile infarct with pyknotic nuclei (arrows). E. Bile (arrow) in interlobular bile duct with disordered nuclei. F. Bile plugs in cannaliculi (red arrows), feathery degeneration producing foamy macrophage-like hepatocytes (yellow arrows).

==Congestive hepatopathy==
===General===
*Liver failure due to (right) heart failure.
*AKA ''cardiac cirrhosis'' - a term used by clinicians.
**Generally, it does not satisfy pathologic criteria for cirrhosis.<ref>URL: [http://emedicine.medscape.com/article/151792-overview http://emedicine.medscape.com/article/151792-overview]. Accessed on: 17 June 2010.</ref>

===Gross===
*"Nutmeg" liver - yellow spotted appearance.

===Microscopic===
Features:<ref>URL: [http://emedicine.medscape.com/article/151792-diagnosis http://emedicine.medscape.com/article/151792-diagnosis]. Accessed on: 17 June 2010.</ref>
*Zone III atrophy.
*Portal venule (central vein) distension.
*Perisinusoidal fibrosis - progresses to centrilobular fibrosis and then diffuse fibrosis.
*Dilation of sinusoids in ''all'' zone III areas - '''key feature'''.<ref>Suggested by OA. September 2009.</ref>

DDx:
*[[Hemangioma of the liver]] - should be focal lesion.
Cardiac (congestive) hepatopathy, wherein outflow obstruction occurs secondary to backflow from a failing heart, and Budd Chiari syndrome, wherein obstruction of outflow occurs secondary to obstruction, usually thrombotic, have overlapping features, including sinusoidal dilation with emphasis upon the central vein, space of Disse erythrocytes, centrilobular inflammation, hemorrhage, bile ductules, and hemosiderin, and portal inflammation, fibrosis and bile ductular reaction. Centrilobular dropout/necrosis is more common in Budd Chiari syndrome, while peri-central venous and sinusoidal fibrosis are more common in cardiac hepatopathy. In end stage liver, fibrosis for cardiac hepatopathy comprises stellate centrizonal fibrous with haphazard spread, as opposed to the more frequent nodular cirrhosis in Budd-Chiari. Clinical findings are important to take into account, as cardiac failure is usually well known at the time of diagnosis as are the clinical predictors of Budd Chiari syndrome, prothrombotic states, myeloproliferative diseases, and oral contraceptive use. <ref name=pmid27681331 >{{cite journal |author=Gonzalez RS, Gilger MA, Huh WJ, Washington MK |title=The spectrum of histologic findings in hepatic outflow obstruction |journal= Arch Pathol Lab Med |volume=141 |issue= |pages=98 |year=2017 |pmid= 27681331 ||doi= 10.5858/arpa.2015-0388-OA |url=http http://www.archivesofpathology.org/doi/10.5858/arpa.2015-0388-OA?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%3dpubmed&code=coap-site }}</ref>
====Images====
<gallery>
Image:Congestive_hepatopathy_high_mag.jpg | Mild congestive hepatopathy. (WC) 
A.[[File:1 CEN NEC 1 680x512px.tif|PAS without diastase shows ovoids of necrosis {40X).]] 
B. [[File:2 CEN NEC 1 680x512px.tif|Necrosis with central vein [yellow arrowhead], inflammatory cells, residual Councilman body [green arrowhead], and hepatocyte with mitotic figure [red arrowhead] (400X).]]
 
C. [[File:3 CEN NEC 1 680x512px.tif|Trichrome highlights fibrosis about central vein [yellow arrowhead] & shows beginning scar formation [green arrowheads]. Note residual atrophic hepatocytes [blue arrowheads] (400X).]]
 
D. [[File:4 CEN NEC 1 680x512px.tif|Portal triads are largely unaffected (400X).]]
|} 
Centrilobular necrosis (seen in circulatory failure and with toxins/drugs). A. PAS without diastase shows ovoids of necrosis. B. Necrosis with central vein [yellow arrowhead], inflammatory cells, residual Councilman body [green arrowhead], and hepatocyte with mitotic figure [red arrowhead]. C. Trichrome highlights fibrosis about central vein [yellow arrowhead] & shows beginning scar formation [green arrowheads]. Note residual atrophic hepatocytes [blue arrowheads]. D. Portal triads are largely unaffected (LR 400X)
 
A. [[File:1 CHF 1 680x512px.tif|Dilated and undilated sinusoidal regions (40X).]]
 
B. [[File:2 CHF 1 680x512px.tif|Thrombi in sinusoids; glycogenated nuclei likely reflect patient’s diabetes mellitus (400X).]]
 
C. [[File:3 CHF 1 680x512px.tif|Dilated portal vein (400X).]]
 
D. [[File:4 CHF 1 680x512px.tif|Reticulin shows collapse (thick black lines) as well as a dilated portal vein (200X).]]
 
E. [[File:5 CHF 1 680x512px.tif|Trichrome shows space of Disse collagenization (pericellular fibrosis) (200X).]]
 
F. [[File:6 CHF 1 680x512px.tif|Trichrome shows periportal fibrosis; no bridging was seen (200X).]]

Patient with congestive heart failure and stage I fibrosis. A. Dilated and undilated sinusoidal regions. B. Thrombi in sinusoids; glycogenated nuclei likely reflect patient’s diabetes mellitus. C. Dilated portal vein. D. Reticulin shows black lines of bridging, too thick for collapse. E. Trichrome shows space of Disse collagenization (pericellular fibrosis). F. Trichrome shows bridge beginning off to right; when it is more than a mere spike, it is a bridge.

==Drug-induced liver disease==
*[[AKA]] ''drug-induced liver toxicity''.
{{Main|Drug-induced liver disease}}

==Focal nodular hyperplasia==
*Abbreviated ''FNH''.
{{Main|Focal nodular hyperplasia}}

==Nodular regenerative hyperplasia==
===General===
*Associated with renal transplants, [[bone marrow transplant]]s and [[vasculitides]].<ref name=Ref_PBoD922>{{Ref PBoD|922}}</ref>
*Can lead to [[portal hypertension]] and many of the associated complications.<ref name=pmid22554152>{{Cite journal | last1 = Bissonnette | first1 = J. | last2 = Généreux | first2 = A. | last3 = Côté | first3 = J. | last4 = Nguyen | first4 = B. | last5 = Perreault | first5 = P. | last6 = Bouchard | first6 = L. | last7 = Pomier-Layrargues | first7 = G. | title = Hepatic hemodynamics in 24 patients with nodular regenerative hyperplasia and symptomatic portal hypertension. | journal = J Gastroenterol Hepatol | volume = 27 | issue = 8 | pages = 1336-40 | month = Aug | year = 2012 | doi = 10.1111/j.1440-1746.2012.07168.x | PMID = 22554152 }}
</ref>

====Etiology====
*Arterial hypervascularity secondary to loss of hepatic vein radicles (loss of central venule in hepatic lobule).<ref name=Ref_PBoD922>{{Ref PBoD|922}}</ref>

ASIDE: radicle = ramulus - smallest branch or vessel or nerve.<ref name=Dorlands2>Dorland's Medical Dictionary. 30th Ed.</ref>

===Gross===
*Diffuse nodularity - whole liver.

===Microscopic===
Features:<ref name=Ref_PBoD922>{{Ref PBoD|922}}</ref>
*"Plump" hepatocytes surrounded by atrophic ones.
*No fibrosis.

==Sinuosoidal obstruction syndrome==
*May be referred to as ''Hepatic veno-occlusive disease''.<ref name=pmid11928077>{{Cite journal | last1 = DeLeve | first1 = LD. | last2 = Shulman | first2 = HM. | last3 = McDonald | first3 = GB. | title = Toxic injury to hepatic sinusoids: sinusoidal obstruction syndrome (veno-occlusive disease). | journal = Semin Liver Dis | volume = 22 | issue = 1 | pages = 27-42 | month = Feb | year = 2002 | doi = 10.1055/s-2002-23204 | PMID = 11928077 }}.</ref>
===General===
*Term for obstruction due to toxicity from a chemotherapeutic agent.<ref name=pmid16393276>{{Cite journal | last1 = Helmy | first1 = A. | title = Review article: updates in the pathogenesis and therapy of hepatic sinusoidal obstruction syndrome. | journal = Aliment Pharmacol Ther | volume = 23 | issue = 1 | pages = 11-25 | month = Jan | year = 2006 | doi = 10.1111/j.1365-2036.2006.02742.x | PMID = 16393276 }}</ref><ref name=pmid17569137>{{Cite journal | last1 = Aydinli | first1 = M. | last2 = Bayraktar | first2 = Y. | title = Budd-Chiari syndrome: etiology, pathogenesis and diagnosis. | journal = World J Gastroenterol | volume = 13 | issue = 19 | pages = 2693-6 | month = May | year = 2007 | doi = | PMID = 17569137 | url=http://www.wjgnet.com/1007-9327/full/v13/i19/2693.htm }}</ref>

Clinical DDx:
*[[Budd-Chiari syndrome]].

===Microscopic===
Features:<ref name=pmid17569137>{{Cite journal | last1 = Aydinli | first1 = M. | last2 = Bayraktar | first2 = Y. | title = Budd-Chiari syndrome: etiology, pathogenesis and diagnosis. | journal = World J Gastroenterol | volume = 13 | issue = 19 | pages = 2693-6 | month = May | year = 2007 | doi = | PMID = 17569137 | url=http://www.wjgnet.com/1007-9327/full/v13/i19/2693.htm }}</ref>
*Subendothelial swelling in hepatic venules.

Negatives:
*No thrombosis.

==Ascending Cholangitis (Acute Cholangitis)==
===General===
*Term for infection of bile ducts, usually due to obstruction

Clinical DDx:

===Microscopic===
====Images====

A. [[File:1 asc chol 1 680x512px.tif|Rounded, clear (edematous) portal tracts (arrows) separated by hepatocytes with dilated sinusoids (Row 1 Left 40X).]]
 
B. [[File:2 asc chol 1 680x512px.tif|Neutrophils about hepatocytes (arrows) have spilled into the lobule from a portal tract (Row 1 Right 200X).]]
 
C. [[File:3 asc chol 1 680x512px.tif|Proliferated bile ductules (arrows) bearing neutrophils within epithelium and lumens are features of obstruction that should prompt a search for interlobular ducts with acute inflammation (Row 2 Left 400X).]]
 
D. [[File:4 asc chol 1 680x512px.tif|The epithelium of the ducts can be severely degenerated. Neutrophils (cyan arrows) invade epithelium of an interlobular duct that are recognizable mainly as a circle of rounded nuclei; the associated arteriole (red arrow) should be identified to ensure an interlobular duct is being evaluated. Note the proliferated bile ductules (blue arrows) (Row 2 Right 400X).]]
 
E. [[File:5 asc chol 1 680x512px.tif|A PAS without diastase stain colors the arteriole (blue arrow), as well as the rim of the interlobular duct within which lies a neutrophil (cyan arrow) (Row 2 Right 400X). .]]
 
F. [[File:6 asc chol 1 680x512px.tif|A PAS with diastase stain colors the arteriole (red arrow), as well as the rim of the interlobular duct within which lies a neutrophil (cyan arrow) (Row 1 Right 400X)]]
 
Acute cholangitis in a patient with multiple bile duct procedures. After the biopsy, removal of bile duct stones released pus. A. Rounded, clear (edematous) portal tracts (arrows) separated by hepatocytes with dilated sinusoids. B. Neutrophils about hepatocytes (arrows) have spilled into the lobule from a portal tract. C, Proliferated bile ductules (arrows) bearing neutrophils within epithelium and lumens are features of obstruction that should prompt a search for interlobular ducts with acute inflammation. D. The epithelium of the ducts can be severely degenerated. Neutrophils (cyan arrows) invade epithelium of an interlobular duct that are recognizable mainly as a circle of rounded nuclei; the associated arteriole (red arrow) should be identified to ensure an interlobular duct is being evaluated. Note the proliferated bile ductules (blue arrows). E. A PAS without diastase stain colors the arteriole (blue arrow), as well as the rim of the interlobular duct within which lies a neutrophil (cyan arrow). F. A PAS with diastase stain colors the arteriole (red arrow), as well as the rim of the interlobular duct within which lies a neutrophil (cyan arrow).

A.[[File:1 Sep Acu Cho 1 680x512px.tif|Low power shows variably sized inflamed portal tracts (40X)]]
 
B. [[File:2 Sep Acu Cho 1 680x512px.tif|Trichrome shows dilated sinusoids and space of Disse collagenization (200X)]]
 
C. [[File:3 Sep Acu Cho 1 680x512px.tif|Inflammatory focus with macrophages and neutrophils (400X).]]
 
D. [[File:4 Sep Acu Cho 1 680x512px.tif|PAS with diastase shows proliferated bile ductules at edge of triad with neutrophils, which should not be used to make a definite diagnosis of acute cholangitis (400X).]]
 
E. [[File:5 Sep Acu Cho 1 680x512px.tif|PAS without diastase showing acutely inflamed bile duct, with accompanying blood vessel of similar size, diagnostic of acute cholangitis (400X).]]
 
F. [[File:6 Sep Acu Cho 1 680x512px.tif|PAS with diastase showing neutrophil in bille duct lumen, diagnostic of acute cholangitis (400X).]]
 
Patient with sepsis and acute cholangitis. A. Low power shows variably sized inflamed portal tracts. B. Trichrome shows dilated sinusoids and space of Disse collagenization. C. Inflammatory focus with macrophages and neutrophils. D. PAS with diastase shows proliferated bile ductules at edge of triad with neutrophils, which should not be used to make a definite diagnosis of acute cholangitis. E. PAS without diastase showing acutely inflamed bile duct, with accompanying blood vessel of similar size, diagnostic of acute cholangitis. F. PAS with diastase showing neutrophil in bille duct lumen, diagnostic of acute cholangitis.

==Polycystic kidney disease and the liver==
{{Main|Cystic kidney disease}}
===General===
Complications of PKD in the liver:<ref>{{Ref MacSween|174-5}}</ref>
#Infected cyst.
#Cholangiocarcinoma.
#Cholestasis/obstruction due to duct compression.<ref>URL: [http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=9184868 http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=9184868]. Accessed on: 23 September 2009.</ref>

Cysts:
*Cysts in the liver, like the kidney, are thought to enlarge with age.

===Microscopic===
Features:<ref>{{Ref MacSween|176}}</ref>
*''Von Meyenburg complexes'' ([[bile duct hamartoma]]):
**Cluster of dilated ducts with "altered" bile.
**Surrounded by collagenous stroma.
**Separate from the portal areas.<ref>Meyenburg complex. Stedman's Medical Dictionary. 27th Ed.</reF>

Images:
*[http://commons.wikimedia.org/wiki/File:Von_Meyenburg_complex_low_mag.jpg Von Meyenburg complex - bile duct hamartoma (WC)].
*[http://commons.wikimedia.org/wiki/File:Bile_duct_hamartoma_intermed_mag.jpg Bile duct hamartoma (WC)].

Notes:
*Appearance on ultrasound<ref name=pmid17287178>Bile duct hamartomas--the von Meyenburg complex. Salles VJ, Marotta A, Netto JM, Speranzini MB, Martins MR. Hepatobiliary Pancreat Dis Int. 2007 Feb;6(1):108-9. PMID 17287178.</ref> and CT (hypodense)<ref name=pmid19294869>[The von Meyenburg complex] Schwab SA, Bautz W, Uder M, Kuefner MA. Rontgenpraxis. 2008;56(6):241-4. German. PMID 19294869.</ref> - similar to metastases.

==Peliosis hepatis==
===General===
*Associated with:
**Infections.
**Malignancy.
**Other stuff.
*Rarely biopsied.

===Microscopic===
Features:
*Cyst lined by endothelium.
**Usu. incomplete.
*Blood.
{|
[[File:1 PEL 1 680x512px.tif|Hemorrhage at left end, dilated sinusoids elsewhere (20X).]]
[[File:2 PEL 1 680x512px.tif|Ramifying dilated sinusoidal spaces (100X).]]
 
[[File:3 PEL 1 680x512px.tif|PAS with diastase shows flat lining (400X).]]
[[File:4 PEL 1 680x512px.tif|Necrotic hepatocytes in cords, presumably due to pressure (400X).]]
|}
Peliosis hepatis. Hemorrhage at left end, dilated sinusoids elsewhere (UL 20X). Ramifying dilated sinusoidal spaces (UR 100X). PAS with diastase shows flat lining (LL 400X). Necrotic hepatocytes in cords, presumably due to pressure (LR 400X).

==Total parenteral nutrition==
*Abbreviated ''TPN''.

===General===
*Indication: short gut syndrome, others.

===Microscopic===
Variable - may range from: steatosis, steatohepatitis, cholestasis, fibrosis and cirrhosis.<ref name=pmid16766237>{{cite journal |author=Guglielmi FW, Boggio-Bertinet D, Federico A, ''et al.'' |title=Total parenteral nutrition-related gastroenterological complications |journal=Dig Liver Dis |volume=38 |issue=9 |pages=623–42 |year=2006 |month=September |pmid=16766237 |doi=10.1016/j.dld.2006.04.002 |url=}}</ref>

Features (classic):<ref>{{Cite journal | last1 = Li | first1 = SJ. | last2 = Nussbaum | first2 = MS. | last3 = McFadden | first3 = DW. | last4 = Gapen | first4 = CL. | last5 = Dayal | first5 = R. | last6 = Fischer | first6 = JE. | title = Addition of glucagon to total parenteral nutrition (TPN) prevents hepatic steatosis in rats. | journal = Surgery | volume = 104 | issue = 2 | pages = 350-7 | month = Aug | year = 1988 | doi = | PMID = 3135627 }}</ref><ref>{{Cite journal | last1 = Stanko | first1 = RT. | last2 = Nathan | first2 = G. | last3 = Mendelow | first3 = H. | last4 = Adibi | first4 = SA. | title = Development of hepatic cholestasis and fibrosis in patients with massive loss of intestine supported by prolonged parenteral nutrition. | journal = Gastroenterology | volume = 92 | issue = 1 | pages = 197-202 | month = Jan | year = 1987 | doi = | PMID = 3096806 }}
</ref>
*[[Steatosis]] (periportal) - early.
*Cholestasis - late.

==Giant cell hepatitis==
*[[AKA]] ''neonatal giant cell hepatitis''.

:See: ''[[Giant cell hepatitis]]''.

==Hepatic amyloidosis==
{{Main|Amyloidosis}}
*[[AKA]] ''liver amyloidosis''.
*[[AKA]] ''amyloidosis of the liver''.
===General===
*Diffuse abundant amyloid within the space of Disse is associated with [[portal hypertension]].<ref name=pmid1864548>{{Cite journal | last1 = Bion | first1 = E. | last2 = Brenard | first2 = R. | last3 = Pariente | first3 = EA. | last4 = Lebrec | first4 = D. | last5 = Degott | first5 = C. | last6 = Maitre | first6 = F. | last7 = Benhamou | first7 = JP. | title = Sinusoidal portal hypertension in hepatic amyloidosis. | journal = Gut | volume = 32 | issue = 2 | pages = 227-30 | month = Feb | year = 1991 | doi = | PMID = 1864548 | PMC = 1378815 | URL = http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1378815/?tool=pubmed }}</ref>

===Microscopic===
Features:
*Amorphous extracellular pink stuff on H&E - see ''[[amyloid]]'' article.

DDx:
*[[Fibrolamellar hepatocellular carcinoma]].

====Images====
<gallery>
Image:Hepatic_amyloidosis_-_low_mag.jpg | Amyloidosis of the liver - low mag. (WC)
Image:Hepatic_amyloidosis_-_intermed_mag.jpg | Amyloidosis of the liver - intermed. mag. (WC)
Image:Hepatic_amyloidosis_-_high_mag.jpg | Amyloidosis of the liver - high mag. (WC)
Image:Hepatic_amyloidosis_-_very_high_mag.jpg | Amyloidosis of the liver - very high mag. (WC)
</gallery>
{|
[[File:1 AMY 1 680x512px.tif|Amorphous material replaces hepatic parenchyma [4X]]]
[[File:2 AMY 1 680x512px.tif|Material barely stains blue on trichrome [10X]]]
 
[[File:3 AMY 1 680x512px.tif|Material stains red on unpolarized Congo Red [40X]]]
[[File:4 AMY 1 680x512px.tif|Material stains apple green on polarized Congo Red [40X]]]
|}
Amyloidosis. Amorphous material replaces hepatic parenchyma [UL 4X]. Material barely stains blue on trichrome [UR 10X] Material stains red on unpolarized Congo Red [LL 40X] Material stains apple green on polarized Congo Red [LR 40X]

===Stains===
*[[Congo red]] +ve.

==Fulminant hepatic necrosis==
===General===
Etiology:
*Viral, i.e. [[Hepatitis A]], [[Hepatitis B]]; [[Hepatitis C]] - extremely rare.
*Trauma.
*Shock.

===Microscopic===
{|
[[File:1 Necrosis 2 680x512px.tif| Submassive hepatic necrosis.]]
[[File:2 Necrosis 2 680x512px.tif| Submassive hepatic necrosis.]]
 
[[File:3 Necrosis 2 680x512px.tif| Submassive hepatic necrosis.]]
[[File:4 Necrosis 2 680x512px.tif| Submassive hepatic necrosis.]]
 
[[File:5 Necrosis 2 680x512px.tif| Submassive hepatic necrosis.]]
[[File:6 Necrosis 2 680x512px.tif| Submassive hepatic necrosis.]]
|}
Submassive hepatic necrosis. Patient had transaminases in the thousands that rapidly dropped to normal. Pink preserved parenchyma strews empty necrotic spaces (Row 1 Left 20X). Focus of necrosis with no apparent hepatocytes macrophages abuts apparently normal liver (Row 1 Right 200X). Iron stain shows the macrophages bear hemosiderin (Row 2 Left 200X). Reticulin stain highlights the recently dead liver cells (Row 2 Right 200X). Reticulin stain shows a necrotic bridge forming; the multiple small black circles preclude diagnosis of a fibrous bridge (Row 3 Left 200X). Trichrome shows the necrotic bridge (“collapse”) lacks much collagen deposition, as would be expected for bridging fibrosis (Row 3 Right 200X).

Features:
*Hepatocyte [[necrosis]].
*Bile duct proliferation.

DDx:
*[[Cholangiocarcinoma]].
*[[Angiosarcoma]].

==Secondary hemochromatosis==
:''For the hereditary one see [[hereditary hemochromatosis]]''.
===General===
*Iron overload secondary to blood transfusions for hereditary or acquired anemia.<ref name=pmid19727383/>
**Primary hemochromatosis due to a defect in iron processing - called ''[[hereditary hemochromatosis]]''.
*Imaging considered the best test, as iron deposition is patchy.<ref name=pmid19727383/>

Selected hereditary causes:<ref name=pmid19727383>{{Cite journal | last1 = Gattermann | first1 = N. | title = The treatment of secondary hemochromatosis. | journal = Dtsch Arztebl Int | volume = 106 | issue = 30 | pages = 499-504, I | month = Jul | year = 2009 | doi = 10.3238/arztebl.2009.0499 | PMID = 19727383 | PMC = 2735704 | URL = http://www.ncbi.nlm.nih.gov.myaccess.library.utoronto.ca/pmc/articles/PMC2735704/?tool=pubmed}}</ref>
*Thalassemia.
*[[Sickle cell anemia]].
*Hereditary sideroblastic anemia.

Selected acquired causes:<ref name=pmid19727383/>
*[[Myelodysplastic syndromes]]
*Myelofibrosis
*Aplastic anemia, intractable.

===Microscopic===
:See ''[[hereditary hemochromatosis]]''.

==Hepatic sarcoidosis==
{{Main|Hepatic sarcoidosis}}
==Overlapping Disorders==

[[File:1 Mixed Disorder 1 680x512px.tif|Changes of steatohepatitis and interface hepatitis, with granuloma. Patient with diabetes was ANA, AMA, HCV, HBV negative, without drugs known to produce granulomas or interface hepatitis. This may be a case of AMA negative primary biliary cirrhosis, but studies to determine that with certainty were not performed.]]
[[File:2 Mixed Disorder 1 680x512px.tif|Changes of steatohepatitis and interface hepatitis, with granuloma. Patient with diabetes was ANA, AMA, HCV, HBV negative, without drugs known to produce granulomas or interface hepatitis. This may be a case of AMA negative primary biliary cirrhosis, but studies to determine that with certainty were not performed.]]
[[File:3 Mixed Disorder 1 680x512px.tif|Changes of steatohepatitis and interface hepatitis, with granuloma. Patient with diabetes was ANA, AMA, HCV, HBV negative, without drugs known to produce granulomas or interface hepatitis. This may be a case of AMA negative primary biliary cirrhosis, but studies to determine that with certainty were not performed.]]
[[File:4 Mixed Disorder 1 680x512px.tif|Changes of steatohepatitis and interface hepatitis, with granuloma. Patient with diabetes was ANA, AMA, HCV, HBV negative, without drugs known to produce granulomas or interface hepatitis. This may be a case of AMA negative primary biliary cirrhosis, but studies to determine that with certainty were not performed.]]
[[File:5 Mixed Disorder 1 680x512px.tif|Changes of steatohepatitis and interface hepatitis, with granuloma. Patient with diabetes was ANA, AMA, HCV, HBV negative, without drugs known to produce granulomas or interface hepatitis. This may be a case of AMA negative primary biliary cirrhosis, but studies to determine that with certainty were not performed.]]
[[File:6 Mixed Disorder 1 680x512px.tif|Changes of steatohepatitis and interface hepatitis, with granuloma. Patient with diabetes was ANA, AMA, HCV, HBV negative, without drugs known to produce granulomas or interface hepatitis. This may be a case of AMA negative primary biliary cirrhosis, but studies to determine that with certainty were not performed.]] 
Changes of steatohepatitis and interface hepatitis, with granuloma. Patient with diabetes was ANA, AMA, HCV, HBV negative, without drugs known to produce granulomas or interface hepatitis. This may be a case of AMA negative primary biliary cirrhosis, but studies to determine that with certainty were not performed. A. Low power shows hepatocytes afflicted by steatosis and an inflamed portal tract. B. In a region of fatty change lie cytoplasmic tufts of ballooning degeneration (green arrows) and a lipogranuloma (black arrow). C. At the portal-hepatocyte junction lies interface hepatitis (black arrows), as well as extension of inflammation into the lobule (green arrows). D. Red hepatocytes bounded by inflammation denote piecemeal necrosis [PAS without diastase]. E. Giant cells intermixed with lymphocytes prove a portal granuloma [PAS without diastase]. F. A blue fibrous bridge extends from a triad [Trichrome].

[[File:4 95599552608917 sl 1.png|Acute obstructive changes and changes of recurrent acute injury]]
[[File:4 95599552608917 sl 2.png|Acute obstructive changes and changes of recurrent acute injury]]
[[File:4 95599552608917 sl 3.png|Acute obstructive changes and changes of recurrent acute injury]]
[[File:4 95599552608917 sl 4.png|Acute obstructive changes and changes of recurrent acute injury]]
[[File:4 95599552608917 sl 5.png|Acute obstructive changes and changes of recurrent acute injury]]
[[File:4 95599552608917 sl 6.png|Acute obstructive changes and changes of recurrent acute injury]]
[[File:4 95599552608917 sl 7.png|Acute obstructive changes and changes of recurrent acute injury]] 
Acute obstructive changes and changes of recurrent injury in 46 yo man with Clostridium perfringens positive blood culture, an ERCP that showed duodenal compression by the pancreas with resultant bile duct dilatation. The patient had had and continued to have multiple bouts of acute pancreatitis. At the time of biopsy, decreased platelet count/hemoglobin/albumin, elevated lipase/amylase/PT/PTT, normal alkaline phosphatase, bilirubin, AST/ALT, AMA, hepatitis virus serology, ANA. A. Fragment biopsy shows inflamed triads and bridges. B. Trichrome shows bridges without nodules, evidence of prior injury; the patient subsequently developed multiple episodes of pancreatitis. C. Reticulin shows piecemeal necrosis, with black lines bounding individual hepatocytes at interface (arrows). D. Collapse is shown by closly approximated thick black lines; one cannot call portal-central collapse without seeing a central vein. Note on this and the other reticulin image that regeneration, two cell thick cords, is not prominent. E. PAS D of two portal triads, far nearer than normal, both expanded. Note increased number of ducts/ductules (red arrows), neutrophils, and PAS-D macrophages. F. PAS D shows collapse extending from a triad to a portion of a lobule with steatosis. No feathery degeneration or bile duct plugs were seen. Neither were foci of spotty necrosis or abscess seen. G. Other triads, again edematous, showed more of a chronic inflammatory response, with occasional plasma cells (black arrows). Also present are neutrophils (red arrows). The bile duct (grey arrow) near the artery (brown arrow) shows mildly disturbed nuclei. Note early proliferated bile ductules (cyan arrows).

[[File:6 17281676469188 sl 1.png| Hepatitis B virus with steatohepatitis]]
[[File:6 17281676469188 sl 2.png| Hepatitis B virus with steatohepatitis]]
[[File:6 17281676469188 sl 3.png| Hepatitis B virus with steatohepatitis]]
[[File:6 17281676469188 sl 4.png| Hepatitis B virus with steatohepatitis]]
[[File:6 17281676469188 sl 5.png| Hepatitis B virus with steatohepatitis]]
[[File:6 17281676469188 sl 6.png| Hepatitis B virus with steatohepatitis]] 
Hepatitis B virus with steatohepatitis in a 36 year old man with hepatitis B surface antigen and hepatitis Be antigen positivity, Hepatitis be QTPC of 1750 cop/mL, an occasionally mildly elevated (42) ALT, and normal glucose, alkaline phosphatase, bilirubin, and other transaminases. He had a history of alcohol abuse, which became controlled. A. Triads show scant inflammation without definite interface hepatitis. About one-fourth of the lobule, not pan-acinar, is afflicted by steatosis. B. Occasional tufts are seen (arrow), indicating focal ballooning sufficient for a diagnosis of steatohepatitis. C. Glycogenated nuclei (black arrows) and hepatocytes with feathery degeneration (red arrows) are seen. D. Very rare foci of spotty necrosis were seen. E. Apart from this triad and the one in the trichrome stain in F, which had moderate inflammation comprising lymphocytes and macrophages, all triads were small, most without any inflammation at all. Neither collapse nor piecemeal necrosis were seen on reticulin stain. F. Trichrome stain showed only portal fibrosis. The interhepatocyte fibrosis required for brunt fibrosis stage I was not seen. Hence, one would grade this as follows: A) Chronic hepatitis (history of hepatitis B), Metavir activity index 1, Piecemeal necrosis 0, Lobular necrosis 1, Metavir fibrosis stage 1, B) Steatohepaitits, Brunt necroinflammatory grade 1, Brunt fibrosis stage 0.

=See also=
*[[Pancreas]].
*[[Gastrointestinal pathology]].
*[[Liver neoplasms]].
*[[Liver]].

=References=
{{reflist|2}}

[[Category:Gastrointestinal pathology]]
[[Category:Liver pathology]]
[[Category:Medical liver disease]]

Medical liver disease

2017-02-10T18:43:21Z

Mitchell: /* Microscopic */ Improved image labelling

[[Image:Ground glass hepatocytes high mag cropped 2.jpg|thumb|right|[[Micrograph]] showing ground glass hepatocytes, as seen in chronic [[hepatitis B]]. [[H&E stain]].]]
This article deals with '''medical [[liver]] disease'''. An introduction to the liver and approach is found in the ''[[liver]]'' article.

Every differential in liver pathology has "drugs"<ref>{{Ref PCPBoD8|448}}</ref> -- if it isn't clearly malignancy.

Liver neoplasms are dealt with in the ''[[liver neoplasms]]'' article.

Medical liver biopsies are often non-specific, as the liver has the same appearance for many mechanisms of injury, especially when the injury is marked. The clinical history, serology and imaging are essential for proper interpretations in this domain of pathology.

=Review of liver blood work=
===Inflammation activity===
*ALT.
*AST.

===Cholestatic markers===
*ALP.
*GGT - used to assess whether the ALP is an "honest" value, elevated in cirrhosis.

===Cirrhosis/decompensation===
*PLT - low is suggestive of dysfunction.
*INR - high is bad, unless anticoagulated.

===Other===
*Bilirubin.
**Direct (AKA conjugated).
**Indirect (AKA unconjugated).

A short DDx of elevated:<ref>{{Ref PCPBoD8|441}}</ref>
*Indirect:
**[[Gilbert syndrome]].
**Crigler-Najjar syndrome type 1.
**Crigler-Najjar syndrome type 2.
*Direct:
**Rotor syndrome.
**Dubin-Johnson syndomre.

===Viral hepatitis===
*HBV DNA.
*HCV RNA.
*HBs Ag, HBs Ab, HBe Ag, HBe Ab.
*HCV Ab.

Others:
*[[Epstein-Barr virus]] (EBV).
*[[Cytomegalovirus]] (CMV) - especially in the immune incompetent.

====Hepatitis B====
Meaning & utility of the various [[Hepatitis B]] tests:<ref>URL: [http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/hepatology/hepatitis-B/ http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/hepatology/hepatitis-B/]. Accessed on: 16 May 2011.</ref><ref name=lto_hepb>URL: [http://www.labtestsonline.org/understanding/analytes/hepatitis_b/test.html http://www.labtestsonline.org/understanding/analytes/hepatitis_b/test.html]. Accessed on: 16 May 2011.</ref>
{| class="wikitable sortable" border="1"
! Test name
! Location
! Positive test
! Negative test
! Usual question
|-
| HBs Ag||Surface||Virus active||No active infection||Active infection?
|-
| HBs Ab||Surface||Exposed OR vaccinated||No exposure OR no vaccine OR loss of Ab||Immunization status?
|-
| HBe Ag||Virus core||Infect. w/ viral replication||No active infection||Active infect. w/ viral replication?
|-
| HBe Ab||Virus core||Exposed to virus||Infect. w/o antibody response OR not exposed||Immune response to infection?
|-
| HBV DNA||-||Active||Not active/no exposure||Viral load/how active?
|-
| HBc Ab||Virus core||Virus active/previous exposure||No exposure||Early active infection?
|}
Notes:
*''HBc Ab'' may test for acute (IgM) or chronic infection - dependent on specific antibody test; it is often used to look for early infection.<ref name=lto_hepb>URL: [http://www.labtestsonline.org/understanding/analytes/hepatitis_b/test.html http://www.labtestsonline.org/understanding/analytes/hepatitis_b/test.html]. Accessed on: 16 May 2011.</ref>
*''Carriers of hepatitis B'': HBs Ag +ve, HBs Ab -ve, HBc Ag -ve, HBc Ab +ve, HBe Ag -ve, HBe Ab +ve.<ref>URL: [http://labtestsonline.org/understanding/analytes/hepatitis-b/tab/test http://labtestsonline.org/understanding/analytes/hepatitis-b/tab/test]. Accessed on: 3 May 2012.</ref>

===Markers for rare liver diseases===
*Ceruloplasm - low think ''[[Wilson's disease]]''; typical value for Wilson's ~ 0.12 g/L.
**<0.20 g/L is a criteria for Wilson's disease.<ref name=pmid18556333>Diagnostic accuracy of serum ceruloplasmin in Wilson disease: determination of sensitivity and specificity by ROC curve analysis among ATP7B-genotyped subjects. Mak CM, Lam CW, Tam S. Clin Chem. 2008 Aug;54(8):1356-62. Epub 2008 Jun 12. PMID 18556333. URL: [http://www.clinchem.org/cgi/reprint/54/8/1356.pdf http://www.clinchem.org/cgi/reprint/54/8/1356.pdf]. Accessed on: 28 September 2009.</ref>
*Alpha-1 antitrypsin - if low think ''deficiency''.

===Hemosiderosis===
*Ferritin - high.
*Iron saturation - high.

Causes:
*Hemochromatosis.
*Hemolysis, chronic.
*Cirrhosis.

=Medical imaging=
Blood flow:<ref>URL: [http://insidesurgery.com/2010/12/hepatopedal-hepatofugal-flow/ http://insidesurgery.com/2010/12/hepatopedal-hepatofugal-flow/]. Accessed on: 2 December 2011.</ref>
*Hepatopedal flow = normal portal vein flow.
*Hepatofugal flow = reversed portal vein flow.

==Interventional measurements==
Wedged to free hepatic venous pressure:<ref name=pmid1864548>{{Cite journal | last1 = Bion | first1 = E. | last2 = Brenard | first2 = R. | last3 = Pariente | first3 = EA. | last4 = Lebrec | first4 = D. | last5 = Degott | first5 = C. | last6 = Maitre | first6 = F. | last7 = Benhamou | first7 = JP. | title = Sinusoidal portal hypertension in hepatic amyloidosis. | journal = Gut | volume = 32 | issue = 2 | pages = 227-30 | month = Feb | year = 1991 | doi = | PMID = 1864548 | PMC = 1378815 | URL = http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1378815/?tool=pubmed }}</ref>
*Normal = 1-4 mmHg.
**Elevated in [[portal hypertension]].

=Liver biopsy=
==Medical liver biopsy adequacy==
Liver biopsy specimens should be:<ref>{{Ref MacSween|418}}</ref>
*2.0 cm in length and contain 11-15 portal tracts,
*The core should be deeper than 1.0 cm from the liver capsule; specimens close to the capsule may lead to over grading of fibrosis.

==Reporting==
{{Main|Pathology reports}}
<pre>
Specimen, procedure:
- Diagnosis.
</pre>
The diagnosis usually contains grading and staging information, e.g. ''activity 2 /4, Laennec fibrosis stage 1 /4''.

In the context of medical liver disease:
*Grade = inflammation/activity.
*Stage = severity of fibrosis/architectural changes.

Notes:
*The term "acute" is infrequently used in liver pathology.
*In the liver: neutrophils ''is not'' acute -- unlike most elsewhere in the body.<ref>OA. September 2009.</ref>

===A microscopic checklist===
<pre>
Size of biopsy: Adequate
Fragmentation: Absent
Fibrosis: Stage 2-3/4, mostly stage 2
Fibrous septa: Present
Septa with curved contours: Present – focally only
Large droplet steatosis (% of hepatocytes): Present, moderate 60%
Ballooning of hepatocytes: Present, rare
Mallory-Denk bodies: Present, rare
Portal inflammation: Present
Interface activity: Minimal (0-1/4)
Lobular necroinflammation: Minimal
Ducts: Present in normal numbers
Duct injury: Absent
Ductular reaction: Absent
Cholestasis: Absent
Terminal hepatic venules: Present
Iron stain: Absent
Ground glass cells with routine stains: Absent
PASD for alpha-1 antitrypsin droplets: Negative
</pre>

=Viral hepatitis=
These are common. The diagnoses are based on serology. The serology is covered in the ''[[Liver_pathology#Viral_hepatitis|viral hepatitis]]'' section in the ''[[liver pathology]]'' article.

Typically classified as:<ref name=pmid8048409>{{Cite journal | title = Terminology of chronic hepatitis, hepatic allograft rejection, and nodular lesions of the liver: summary of recommendations developed by an international working party, supported by the World Congresses of Gastroenterology, Los Angeles, 1994. | journal = Am J Gastroenterol | volume = 89 | issue = 8 Suppl | pages = S177-81 | month = Aug | year = 1994 | doi = | PMID = 8048409 }}</ref><ref>URL: [http://familydoctor.org/familydoctor/en/diseases-conditions/hepatitis-b.html http://familydoctor.org/familydoctor/en/diseases-conditions/hepatitis-b.html]. Accessed on: 2 May 2012.</ref>
#Acute < 6 months duration.
#Chronic > 6 months duration.

==Hepatitis A==
*Infection is self-limited, i.e. not persistent.
**May present as ''[[fulminant hepatic necrosis]]''.
*Usually asymptomatic in children.<ref name=pmid20068336>{{cite journal |author=Jeong SH, Lee HS |title=Hepatitis A: clinical manifestations and management |journal=Intervirology |volume=53 |issue=1 |pages=15–9 |year=2010 |pmid=20068336 |doi=10.1159/000252779 |url=}}</ref>
*Serology is diagnostic.

==Hepatitis B==
:''Hepatitis B virus'', abbreviated ''HBV'', redirects here.
{{Main|Hepatitis B}}

==Hepatitis C==
{{Main|Hepatitis C}}

=Other infections=
*Hydatid disease (Hydatid cyst).
*Ascaris.
*Fasciola

==Hydatid disease==
*[[AKA]] ''hydatid cyst''.
===General===
*Etiology: ''[[Echinococcus]]''.

===Microscopic===
Features:
*Laminated wall +/- calcification.<ref name=Ref_PBPoD8_448>{{Ref PCPBoD8|448}}</ref>
*Organisms -- see ''[[Echinococcus]]''.

====Images====
<gallery>
Image:Liver_cyst_wall_-_intermed_mag.jpg | Liver cyst wall - intermed. mag. (WC)
Image:Liver_cyst_wall_-_high_mag.jpg | Liver cyst wall - high mag. (WC)
Image: Laminated liver cyst wall - intermed mag.jpg | Characteristic laminated portion - intermed. mag. (WC)
Image: Laminated liver cyst wall - high mag.jpg | Characteristic laminated portion - high mag. (WC)
</gallery>
[[www]]:
*[http://pathmicro.med.sc.edu/parasitology/hydatid-hist1.jpg Hydatid cyst (med.sc.edu)].
*[http://www.atlas.or.kr/atlas/include/viewImg.html?uid=645 Hydatid cyst (atlas.or.kr)].
*[http://casereports.bmj.com/content/2009/bcr.04.2009.1798.full Hydatid cyst (casereports.bmj.com)].

==Abscess==
A. [[File:1 ABS 1 680x512px.tif|A process replaces most of the liver parenchyma (20X).]]
 
B. [[File:2 ABS 1 680x512px.tif|Fibrinopurulent exudate apposes granulation tissue (200X).]]
 
C. [[File:3 ABS 1 680x512px.tif|Neutrophils lie in widened sinusoids (200X)..]]
 
D. [[File:4 ABS 1 680x512px.tif|Trichrome shows collagenization of spaces of Disse. Scarring about an abscess or other mass lesion should not be interpreted as reflective of the liver in general (200X).]]
 
Abscess. A. A process replaces most of the liver parenchyma. B. Fibrinopurulent exudate apposes granulation tissue. C. Neutrophils lie in widened sinusoids. D. Trichrome shows collagenization of spaces of Disse. Scarring about an abscess or other mass lesion should not be interpreted as reflective of the liver in general (LR 200X).

==Coccidiomycosis==
A. [[File:Coccidiomycosis - 1 - 40X 680x512px shot.tif|500x500px Granulomas at low power]]
 
B. [[File:Coccidiomycosis - 1 - 200X 680x513px shot.tif|500x500px Granulomas with centrally crowded cells & lady slipper macrophage nuclei]]
 
C. [[File:Coccidiomycosis - 1 - 400X 1369x1024px shot.tif|500x500px Center of previous granuloma showing pyknotic macrophage nuclei]]
 
D. [[File:Coccidiomycosis - 1 - GMS 400X 1369x1024px shot.tif|500x500px Four Coccidiomycotic spherules]]
 
Coccidiomycosis. A. Note the granulomas in otherwise undisturbed liver (UL). B. Granuloma with centrally crowded cells & lady slipper macrophage nuclei. C. Center of granuloma with pyknotic macrophage nuclei, "necrotizing". D. Organisms on GMS stain.

=Metabolic and toxic=
==Alcoholic liver disease==
===General===
*Acute and/or chronic liver changes due to excessive [[alcohol]] use - includes:
**''[[Alcoholic steatohepatitis]]'' (ASH), [[AKA]] ''alcoholic hepatitis''.<ref>URL: [http://emedicine.medscape.com/article/170539-overview http://emedicine.medscape.com/article/170539-overview]. Accessed on: 3 May 2012.</ref>
***Alcoholic hepatitis can be with minimal steatosis.<ref>STC. 6 December 2010.</ref>
**[[Steatosis]] - classically macrovescicular and centrilobular.
**Alcoholic [[cirrhosis]].

====Classic lab findings in EtOH abusers====
*AST & ALT elevated with AST:ALT=2:1.
*GGT elevated.
*MCV increased.

===Gross pathology/radiologic findings===
*Classically micronodular pattern.
**May be macronodular.

===Microscopic===
See:
*''[[Steatohepatitis]]'' section and ''[[ballooning degeneration]]'' section.

Features:
*Often zone III damage.
*Cholestatsis common, i.e. yellow staining.
**NASH (non-alcoholic steatohepatitis) usu. does not have cholestasis.<ref>STC. 6 December 2010.</ref>
*Fibrosis starts at central veins.
*Neutrophils (often helpful) -- few other things have PMNs. (???)
**Neutrophils cluster around cells with Mallory hyaline.

====Images====

A. [[File:1 etoh 3 680x512px.tif| Alcoholic hepatitis with Metavir stage IV fibrosis (advanced fibrosis/cirrhosis).]]
 
B. [[File:2 etoh 3 680x512px.tif| Alcoholic hepatitis with Metavir stage IV fibrosis (advanced fibrosis/cirrhosis).]]
 
C. [[File:3 etoh 3 680x512px.tif| Alcoholic hepatitis with Metavir stage IV fibrosis (advanced fibrosis/cirrhosis).]]
 
D. [[File:4 etoh 3 680x512px.tif| Alcoholic hepatitis with Metavir stage IV fibrosis (advanced fibrosis/cirrhosis).]]
 
E. [[File:5 etoh 3 680x512px.tif| Alcoholic hepatitis with Metavir stage IV fibrosis (advanced fibrosis/cirrhosis).]]
 
F. [[File:6 etoh 3 680x512px.tif| Alcoholic hepatitis with Metavir stage IV fibrosis (advanced fibrosis/cirrhosis).]]
 

Alcoholic hepatitis with Metavir stage IV fibrosis (advanced fibrosis/cirrhosis).
A. Trichrome shows relatively non-inflamed fibrous bands, as well as [between green dots] nodules. The lack of regeneration throughout might have precluded a diagnosis of cirrhosis, but stage IV fibrosis under the Metavir system is justified. B. Reticulin shows regenerative nodules [left] with mostly two or more nuclei between black lines juxtaposed to non-regenerative hepatocytes on the right, without piecemeal necrosis. C. Regenerative nodules show occasional neutrophils [red arrow] and cytoplasmic tufts of ballooned cells, sometimes possibly Mallory hyalin [green arrows]. D. Triads (note vein [green arrow], artery [yellow arrow], and interlobular bile duct [blue arrow]) generally showed little or no interface hepatitis, even when expanded by fibrosis and inflamed. E. Occasional foci of spotty necrosis were seen. F. This edge of an inflamed triads shows neutrophils about proliferated bile ducts [red arrows], as well as Mallory-Denk bodies [blue arrows].
 
A. [[File:1 etoh 4 680x512px.tif| Cirrhosis in an alcoholic.]]
 
B. [[File:2 etoh 4 680x512px.tif| Cirrhosis in an alcoholic.]]
 
C. [[File:3 etoh 4 680x512px.tif| Cirrhosis in an alcoholic.]]
 
D. [[File:4 etoh 4 680x512px.tif| Cirrhosis in an alcoholic.]]
 
E. [[File:5 etoh 4 680x512px.tif| Cirrhosis in an alcoholic.]]
 
F. [[File:6 etoh 4 680x512px.tif| Cirrhosis in an alcoholic.]]
 
Definite cirrhosis in an alcoholic. A. Hepatocyte free bands parse tissue, with occasional definite islands [arrows]. B. Trichrome establishes blue fibrosis about isles [arrows]. C. Reticulin stain shows nodules with regeneration, wherein a large proportion of them are at least two nuclei thick [arrows]. D. Bile duct proliferation can be difficult, sometimes mimicking cholangiocarcinoma. Follow the double headed arrows to see how the ductules can be seen to proliferate from a single sources, with all ducts being complete, without necrotic epithelial cells. E. PAS with distase can help, as cholangiocarcinoma generally lacks the red rim of proliferating bile ductules [arrows]; again note the connections that can be made between the ductule openings by the blue double headed arrows. The cyan double headed arrows show general parallelism, consistent with uniform directionality induced by extrinsic force, not a neoplastic spread. F. Trichrome shows the most difficult focus. Double headed arrows display the connectivity seen before of the proliferated bile ductules. Note that numerous pairs of adjacent perpendicular glands without a head to foot appearance are not seen that would indicate the disorderly spread of cholangiocarcinoma.
 
A. [[File:1 ALC 2 680x512px.tif|Expanded, inflamed triads with increased bile duct/vascular openings. Mild steatosis (40X).]]
 
B. [[File:2 ALC 2 680x512px.tif|Trichrome stain shows periportal fibrosis [red arrowheads] (200X).]]
 
C. [[File:3 ALC 2 680x512px.tif|PAS with diastase stain shows proliferated bile ductules [blue arrowheads] in stroma with mixed inflammatory infiltrate (400X)]]
 
D. [[File:4 ALC 2 680x512px.tif|Neutrophils about ballooned hepatocyte (satellitosis) [yellow arrowheads]. Councilman bodies [green arrowheads] (400X).]]
 
Alcoholic hepatitis without cirrhosis. No history of viral disease. AMA negative. A. Expanded, inflamed triads with increased bile duct/vascular openings. Mild steatosis. B. Trichrome stain shows periportal fibrosis [red arrowheads]. C. PAS with diastase stain shows proliferated bile ductules [blue arrowheads] in stroma with mixed inflammatory infiltrate. D. Neutrophils about ballooned hepatocyte (satellitosis) [yellow arrowheads]. Councilman bodies [green arrowheads].

Notes:
*If portal inflammatory infiltrates more than mild, r/o other causes i.e. [[viral hepatitis]].
*Mallory bodies once thought to be characteristic; now considered non-specific and generally poorly understood.<ref>{{cite journal |author=Jensen K, Gluud C |title=The Mallory body: theories on development and pathological significance (Part 2 of a literature survey) |journal=Hepatology |volume=20 |issue=5 |pages=1330-42 |year=1994 |month=November |pmid=7927269 |doi= |url=}}</ref>
*Some consider ''alcoholic liver disease'' a clinical diagnosis, i.e. as a pathologist one does not diagnose it.<ref>MG. September 2009.</ref>

==Non-alcoholic fatty liver disease==
*Abbreviated ''NAFLD''.
*Fatty liver that is not due to alcohol; includes obesity-related fatty liver, metabolic disease/diabetes-related fatty liver.

===NASH===
*Non-alcoholic steatohepatitis - see ''steatohepatitis'' section.
*Histologically indistinguishable from ASH.
*NASH is a ''clinical diagnosis'' based on exclusion of alcohol.

==Steatohepatitis==
{{Main|Steatohepatitis}}

=Autoimmune=
==Autoimmune hepatitis==
*Abbreviated ''AIH''.
{{Main|Autoimmune hepatitis}}

==Primary biliary cirrhosis==
*Abbreviated PBC.
{{Main|Primary biliary cirrhosis}}

==Autoimmune hepatitis with obstruction - combined changes==
A. [[File:1 AIH OBS 1.tif|Low power shows inflammation; portal triads, lobules, central veins cannot be distinguished (40X).]]
 
B. [[File:2 AIH OBS 1.tif|Trichrome shows central venous sclerosis (red arrowhead), periportal fibrosis (green arrowhead), & space of Disse collagenization (yellow arrowhead); juxtaposition of central vein & portal tract indicates collapse, no definite bridging was seen (100X)]]
 
C. [[File:3 AIH OBS 1.tif|Central vein is inflamed with a rare plasma cell (cyan arrowhead) (400X).]]
 
D. [[File:4 AIH OBS 1.tif|Interface hepatitis with plasma cells (yellow arrows) and ballooned hepatocytes (red arrows). Lobule is disorganized (400X).]]
 
E. [[File:5 AIH OBS 1.tif|Proliferating bile ductules (blue arrows) with occasional neutrophils (fucsia arrows), indicative of obstruction, but not acute cholangitis, which requires inflamed bile duct itself, best diagnosed with associated blood vessel (400X).]]
 
F. [[File:6 AIH OBS 1.tif|Rare distorted rosettes with greenish brown strands of bile (left arrow) or bile plugs (right arrow) (400X).]]
 
Patient with SLE and obstructive jaundice that resolved with apparent passage of stone. A. Low power shows inflammation; portal triads, lobules, central veins cannot be distinguished. B. Trichrome shows central venous sclerosis (red arrowhead), periportal fibrosis (green arrowhead), & space of Disse collagenization (yellow arrowhead); juxtaposition of central vein & portal tract indicates collapse, no definite bridging was seen. C. Central vein is inflamed with a rare plasma cell (cyan arrowhead). D. Interface hepatitis with plasma cells (yellow arrows) and ballooned hepatocytes (red arrows). Lobule is disorganized. E. Proliferating bile ductules (blue arrows) with occasional neutrophils (fucsia arrows), indicative of obstruction, but not acute cholangitis, which requires inflamed bile duct itself, best diagnosed with associated blood vessel. F. Rare distorted rosettes with greenish brown strands of bile (left arrow) or bile plugs (right arrow).

==Autoimmune hepatitis-primary biliary cirrhosis overlap syndrome==
*Abbreviation ''AIH-PBC OS''.
===General===
Epidemiology:
*Rare.

Serology:<ref name=pmid19491855>{{Cite journal | last1 = Muratori | first1 = P. | last2 = Granito | first2 = A. | last3 = Pappas | first3 = G. | last4 = Pendino | first4 = GM. | last5 = Quarneti | first5 = C. | last6 = Cicola | first6 = R. | last7 = Menichella | first7 = R. | last8 = Ferri | first8 = S. | last9 = Cassani | first9 = F. | title = The serological profile of the autoimmune hepatitis/primary biliary cirrhosis overlap syndrome. | journal = Am J Gastroenterol | volume = 104 | issue = 6 | pages = 1420-5 | month = Jun | year = 2009 | doi = 10.1038/ajg.2009.126 | PMID = 19491855 }}</ref>
*AMA +ve.
*Anti-dsDNA +ve.

===Microscopic===
:See: ''[[autoimmune hepatitis]]'' and ''[[primary biliary cirrhosis]]''.
A. [[File:1 AIH PBC 1 680x512px.tif|Expanded portal tracts with fuzzy edges (40X).]]
 
B. [[File:2 AIH PBC 1 680x512px.tif|Interface hepatitis with plasma cells (400X).]]
 
C. [[File:3 AIH PBC 1 680x512px.tif|Loose granuloma (400X).]]
 
D. [[File:4 AIH PBC 1 680x512px.tif|Damaged bile duct (400X).]]
 
AIH/PBC overlap. AMA & ANA positive with Alkaline phosphatase > 2 upper limit of normal & one ALT > 5 times upper limit of normal. A. Expanded portal tracts with fuzzy edges. B. Interface hepatitis with plasma cells. C. Loose granuloma. D. Damaged bile duct.

==Primary sclerosing cholangitis==
*Abbreviated ''PSC''.
{{Main|Primary sclerosing cholangitis}}

=Hereditary=
==Caroli disease==
===General===
*Genetic disease.
**Frequently associated with [[autosomal recessive polycystic kidney disease]] (ARPKD).<ref name=omim263200>{{OMIM|263200}}</ref>
**May be seen in isolation.<ref name=omim600643>{{OMIM|600643}}</ref>

Clinical:<ref name=pmid17461493>{{Cite journal | last1 = Yonem | first1 = O. | last2 = Bayraktar | first2 = Y. | title = Clinical characteristics of Caroli's syndrome. | journal = World J Gastroenterol | volume = 13 | issue = 13 | pages = 1934-7 | month = Apr | year = 2007 | doi = | PMID = 17461493 }}</ref>
*Recurrent [[cholangitis]].
*Recurrent [[cholelithiasis]].
*[[Cholangiocarcinoma]]<ref name=pmid17461492>{{Cite journal | last1 = Yonem | first1 = O. | last2 = Bayraktar | first2 = Y. | title = Clinical characteristics of Caroli's disease. | journal = World J Gastroenterol | volume = 13 | issue = 13 | pages = 1930-3 | month = Apr | year = 2007 | doi = | PMID = 17461492 }}</ref> - seen in ~7% of cases.<ref name=pmid15347876>{{Cite journal | last1 = Karim | first1 = AS. | title = Caroli's disease. | journal = Indian Pediatr | volume = 41 | issue = 8 | pages = 848-50 | month = Aug | year = 2004 | doi = | PMID = 15347876 }}</ref>

Note:
*''Caroli syndrome'' = Caroli disease + congenital hepatic fibrosis.<ref name=pmid15888616>{{Cite journal | last1 = Brancatelli | first1 = G. | last2 = Federle | first2 = MP. | last3 = Vilgrain | first3 = V. | last4 = Vullierme | first4 = MP. | last5 = Marin | first5 = D. | last6 = Lagalla | first6 = R. | title = Fibropolycystic liver disease: CT and MR imaging findings. | journal = Radiographics | volume = 25 | issue = 3 | pages = 659-70 | month = | year = | doi = 10.1148/rg.253045114 | PMID = 15888616 | URL = http://radiographics.rsna.org/content/25/3/659.long }}</ref>

===Gross===
*Dilated bile ducts.<ref name=omim263200/>

===Microscopic===
Features:<ref name=pmid17461493/>
*Dilated bile ducts.
*Periductal fibrosis. (???)
*+/-Fibrosis.

Image:
*[http://www.meddean.luc.edu/lumen/MedEd/orfpath/11-3-10.jpg Caroli disease (meddean.luc.edu)].<ref>URL: [http://www.meddean.luc.edu/lumen/MedEd/orfpath/develop.htm http://www.meddean.luc.edu/lumen/MedEd/orfpath/develop.htm]. Accessed on: 1 December 2011.</ref>

==Hereditary hemochromatosis==
:''For secondary causes see [[secondary hemochromatosis]]''.
{{Main|Hereditary hemochromatosis}}

==Wilson disease==
{{Main|Wilson's disease}}

==Alpha-1 antitrypsin deficiency==
*[[AKA]] ''alpha1-antiprotease inhibitor deficiency''.
{{Main|Alpha-1 antitrypsin deficiency }}

=Other=
==Budd-Chiari syndrome==
*[[AKA]] ''hepatic vein obstruction''.
===General===
*Hepatic outflow obstruction.

Clinical triad:<ref name=pmid21573256>{{Cite journal | last1 = Fox | first1 = MA. | last2 = Fox | first2 = JA. | last3 = Davies | first3 = MH. | title = Budd-Chiari syndrome--a review of the diagnosis and management. | journal = Acute Med | volume = 10 | issue = 1 | pages = 5-9 | month = | year = 2011 | doi = | PMID = 21573256 }}</ref>
*Ascites.
*Abdominal pain.
*Hepatomegaly.

Etiology:
*~50% have a [[myeloproliferative disease]].<ref name=pmid18814079>{{Cite journal | last1 = Plessier | first1 = A. | last2 = Valla | first2 = DC. | title = Budd-Chiari syndrome. | journal = Semin Liver Dis | volume = 28 | issue = 3 | pages = 259-69 | month = Aug | year = 2008 | doi = 10.1055/s-0028-1085094 | PMID = 18814079 }}</ref>
*May be due to mass effect from a tumour.

Clinical DDx:
*[[Hepatic veno-occlusive disease]].

===Microscopic===
Features:<ref name=pmid17569137>{{Cite journal | last1 = Aydinli | first1 = M. | last2 = Bayraktar | first2 = Y. | title = Budd-Chiari syndrome: etiology, pathogenesis and diagnosis. | journal = World J Gastroenterol | volume = 13 | issue = 19 | pages = 2693-6 | month = May | year = 2007 | doi = | PMID = 17569137 | url=http://www.wjgnet.com/1007-9327/full/v13/i19/2693.htm }}</ref>
*Sinusoidal dilation in zone III (congestion).
*+/-Hepatocyte drop-out.
*+/-Centrilobular fibrosis.

DDx congestion:
*Congestive heart failure ([[congestive hepatopathy]]).
*Constrictive pericarditis.

==Vanishing bile duct syndrome==
*[[AKA]] ''bile duct loss'', [[AKA]] ''ductopenia''.<ref name=pmid11521176/>
===General===
*Fatal.

DDx:<ref name=pmid18242505/>
*[[Primary biliary cirrhosis]].
*[[Primary sclerosing cholangitis]].
*[[GVHD]].<ref name=pmid7994249>{{Cite journal | last1 = Yeh | first1 = KH. | last2 = Hsieh | first2 = HC. | last3 = Tang | first3 = JL. | last4 = Lin | first4 = MT. | last5 = Yang | first5 = CH. | last6 = Chen | first6 = YC. | title = Severe isolated acute hepatic graft-versus-host disease with vanishing bile duct syndrome. | journal = Bone Marrow Transplant | volume = 14 | issue = 2 | pages = 319-21 | month = Aug | year = 1994 | doi = | PMID = 7994249 }}</ref>
*[[Drug-induced liver disease|Drugs]].<ref name=pmid11352118>{{Cite journal | last1 = Chitturi | first1 = S. | last2 = Farrell | first2 = GC. | title = Drug-induced cholestasis. | journal = Semin Gastrointest Dis | volume = 12 | issue = 2 | pages = 113-24 | month = Apr | year = 2001 | doi = | PMID = 11352118 }}</ref>
*Chronic rejection.<ref name=pmid11521176>{{Cite journal | last1 = Inomata | first1 = Y. | last2 = Tanaka | first2 = K. | title = Pathogenesis and treatment of bile duct loss after liver transplantation. | journal = J Hepatobiliary Pancreat Surg | volume = 8 | issue = 4 | pages = 316-22 | month = | year = 2001 | doi = 10.1007/s0053410080316 | PMID = 11521176 }}</ref>

===Microscopic===
Features:<ref name=pmid18242505>{{Cite journal | last1 = Reau | first1 = NS. | last2 = Jensen | first2 = DM. | title = Vanishing bile duct syndrome. | journal = Clin Liver Dis | volume = 12 | issue = 1 | pages = 203-17, x | month = Feb | year = 2008 | doi = 10.1016/j.cld.2007.11.007 | PMID = 18242505 }}</ref>
*Loss of intrahepatitic bile ducts - '''key feature'''.
*Cholestasis.

Note:
*May occur without fibrosis and inflammation; thus, can be easy to miss.

===IHC===
*[[CK7]] -ve.
**Marks bile ducts.

==Extrahepatic biliary obstruction==
{|
[[File:1 OBS 3 680x512px.tif|Sinusoidal dilatation, circular spaces of hepatocytes, small portal triads(40X).]]
[[File:2 OBS 3 680x512px.tif|Bile in hepatocytes about central vein & in plugs in canaliculi [yellow arrowhead] (400X).]]
 
[[File:3 OBS 3 680x512px.tif|Trichrome shows fibrosis about central vein (400X).]]
[[File:4 OBS 3 680x512px.tif|PAS with diastase shows portal triads with mild edema and chronic inflammation, without tortuous bile duct (400X).]]
|}
Early extrahepatic biliary obstruction, demonstrated radiographically, transient, with rise in bilirubin, alkaline phosphatase, and transaminases. Pure canalicular cholestasis near terminal hepatic venules also seen in acute hepatitis, drug reactions, benign recurrent cholestasis, pregnancy, sepsis, & lymphomas. Sinusoidal dilatation, circular spaces of hepatocytes, small portal triads(UL 40X). Bile in hepatocytes about central vein & in plugs in canaliculi [yellow arrowhead] (UR 400X). Trichrome shows fibrosis about central vein (LL 400X). PAS with diastase shows portal triads with mild edema and chronic inflammation, without tortuous bile duct (LR 400X).

{|
[[File:1 OBS 2 680x512px.tif|Expanded inflamed portal triads, swollen hepatocytes (40X)]]
[[File:2 OBS 2 680x512px.tif|Edematous stroma, proliferating ductules [yellow arrowheads], PAS-D macrophages [red arrowhead] (PAS with diastasse, 200X)]]
 
[[File:3 OBS 2 680x512px.tif|Disordered, often swollen hepatocytes,some with feathery degeneration (net like spaces in cytoplasm [blue arrowhead], rare Councilman body [green arrowhead] (400X)]]
[[File:4 OBS 2 1360x1024px.tif|Bile in hepatocytes [cyan arrrowhead] & in canaliculi [purple arrowheads]. Empty acinar spaces bounded by hepatocytes [orange arrowhead] (400X, higher pixel),]]
|}
Changes of extrahepatic biliary obstruction, months duration. Expanded inflamed portal triads, swollen hepatocytes (UL 40X). Edematous stroma, proliferating ductules [yellow arrowheads], PAS-D macrophages [red arrowhead] (UR PAS with diastasse, 200X). Disordered, often swollen hepatocytes,some with feathery degeneration (net like spaces in cytoplasm) [blue arrowhead], rare Councilman body [green arrowhead] (LL 400X). Bile in hepatocytes [cyan arrrowhead] & in canaliculi [purple arrowheads]. Empty acinar spaces bounded by hepatocytes [orange arrowhead] (LR 400X).
{|
[[File:1 Bd obs 4 680x512px.tif|Expanded, light colored portal triads (arrows)(20X).]]
[[File:2 Bd obs 4 680x512px.tif|Proliferating bile ductules (cyan arrows) with neutrophils (yellow arrows), not specific for acute cholangitis, of assistance with large bile duct obstruction (400X)..]]
 
[[File:3 Bd obs 4 680x512px.tif|Uninflamed interlobular duct (yellow arrow) with, accompanying blood vessel (red arrow) (400X)]]
[[File:4 Bd obs 4 680x512px.tif|Bile infarct with pyknotic nuclei (arrows)(400X).]]
 
[[File:5 Bd obs 4 680x512px.tif|Bile (arrow) in interlobular bile duct with disordered nuclei (400X).]]
[[File:6 Bd obs 4 680x512px.tif|Bile plugs in cannaliculi (red arrows), feathery degeneration producing foamy macrophage like hepatocytes (yellow arrows)(400X).]]
|}
Large bile duct obstruction. Expanded, light colored portal triads (arrows)(Row 1 Left 20X). Proliferating bile ductules (cyan arrows) with neutrophils (yellow arrows), not specific for acute cholangitis, of assistance with large bile duct obstruction (Row 1 Right 400X). Uninflamed interlobular duct (yellow arrow) with, accompanying blood vessel (red arrow) (Row 2 Left 400X). Bile infarct with pyknotic nuclei (arrows)(Row 2 Right 400X). Bile (arrow) in interlobular bile duct with disordered nuclei (Row 3 Left 400X). Bile plugs in cannaliculi (red arrows), feathery degeneration producing foamy macrophage-like hepatocytes (yellow arrows)(Row 3 Right 400X).

==Congestive hepatopathy==
===General===
*Liver failure due to (right) heart failure.
*AKA ''cardiac cirrhosis'' - a term used by clinicians.
**Generally, it does not satisfy pathologic criteria for cirrhosis.<ref>URL: [http://emedicine.medscape.com/article/151792-overview http://emedicine.medscape.com/article/151792-overview]. Accessed on: 17 June 2010.</ref>

===Gross===
*"Nutmeg" liver - yellow spotted appearance.

===Microscopic===
Features:<ref>URL: [http://emedicine.medscape.com/article/151792-diagnosis http://emedicine.medscape.com/article/151792-diagnosis]. Accessed on: 17 June 2010.</ref>
*Zone III atrophy.
*Portal venule (central vein) distension.
*Perisinusoidal fibrosis - progresses to centrilobular fibrosis and then diffuse fibrosis.
*Dilation of sinusoids in ''all'' zone III areas - '''key feature'''.<ref>Suggested by OA. September 2009.</ref>

DDx:
*[[Hemangioma of the liver]] - should be focal lesion.
Cardiac (congestive) hepatopathy, wherein outflow obstruction occurs secondary to backflow from a failing heart, and Budd Chiari syndrome, wherein obstruction of outflow occurs secondary to obstruction, usually thrombotic, have overlapping features, including sinusoidal dilation with emphasis upon the central vein, space of Disse erythrocytes, centrilobular inflammation, hemorrhage, bile ductules, and hemosiderin, and portal inflammation, fibrosis and bile ductular reaction. Centrilobular dropout/necrosis is more common in Budd Chiari syndrome, while peri-central venous and sinusoidal fibrosis are more common in cardiac hepatopathy. In end stage liver, fibrosis for cardiac hepatopathy comprises stellate centrizonal fibrous with haphazard spread, as opposed to the more frequent nodular cirrhosis in Budd-Chiari. Clinical findings are important to take into account, as cardiac failure is usually well known at the time of diagnosis as are the clinical predictors of Budd Chiari syndrome, prothrombotic states, myeloproliferative diseases, and oral contraceptive use. <ref name=pmid27681331 >{{cite journal |author=Gonzalez RS, Gilger MA, Huh WJ, Washington MK |title=The spectrum of histologic findings in hepatic outflow obstruction |journal= Arch Pathol Lab Med |volume=141 |issue= |pages=98 |year=2017 |pmid= 27681331 ||doi= 10.5858/arpa.2015-0388-OA |url=http http://www.archivesofpathology.org/doi/10.5858/arpa.2015-0388-OA?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%3dpubmed&code=coap-site }}</ref>
====Images====
<gallery>
Image:Congestive_hepatopathy_high_mag.jpg | Mild congestive hepatopathy. (WC) 
A.[[File:1 CEN NEC 1 680x512px.tif|PAS without diastase shows ovoids of necrosis {40X).]] 
B. [[File:2 CEN NEC 1 680x512px.tif|Necrosis with central vein [yellow arrowhead], inflammatory cells, residual Councilman body [green arrowhead], and hepatocyte with mitotic figure [red arrowhead] (400X).]]
 
C. [[File:3 CEN NEC 1 680x512px.tif|Trichrome highlights fibrosis about central vein [yellow arrowhead] & shows beginning scar formation [green arrowheads]. Note residual atrophic hepatocytes [blue arrowheads] (400X).]]
 
D. [[File:4 CEN NEC 1 680x512px.tif|Portal triads are largely unaffected (400X).]]
|} 
Centrilobular necrosis (seen in circulatory failure and with toxins/drugs). A. PAS without diastase shows ovoids of necrosis. B. Necrosis with central vein [yellow arrowhead], inflammatory cells, residual Councilman body [green arrowhead], and hepatocyte with mitotic figure [red arrowhead]. C. Trichrome highlights fibrosis about central vein [yellow arrowhead] & shows beginning scar formation [green arrowheads]. Note residual atrophic hepatocytes [blue arrowheads]. D. Portal triads are largely unaffected (LR 400X)
 
A. [[File:1 CHF 1 680x512px.tif|Dilated and undilated sinusoidal regions (40X).]]
 
B. [[File:2 CHF 1 680x512px.tif|Thrombi in sinusoids; glycogenated nuclei likely reflect patient’s diabetes mellitus (400X).]]
 
C. [[File:3 CHF 1 680x512px.tif|Dilated portal vein (400X).]]
 
D. [[File:4 CHF 1 680x512px.tif|Reticulin shows collapse (thick black lines) as well as a dilated portal vein (200X).]]
 
E. [[File:5 CHF 1 680x512px.tif|Trichrome shows space of Disse collagenization (pericellular fibrosis) (200X).]]
 
F. [[File:6 CHF 1 680x512px.tif|Trichrome shows periportal fibrosis; no bridging was seen (200X).]]

Patient with congestive heart failure and stage I fibrosis. A. Dilated and undilated sinusoidal regions. B. Thrombi in sinusoids; glycogenated nuclei likely reflect patient’s diabetes mellitus. C. Dilated portal vein. D. Reticulin shows black lines of bridging, too thick for collapse. E. Trichrome shows space of Disse collagenization (pericellular fibrosis). F. Trichrome shows bridge beginning off to right; when it is more than a mere spike, it is a bridge.

==Drug-induced liver disease==
*[[AKA]] ''drug-induced liver toxicity''.
{{Main|Drug-induced liver disease}}

==Focal nodular hyperplasia==
*Abbreviated ''FNH''.
{{Main|Focal nodular hyperplasia}}

==Nodular regenerative hyperplasia==
===General===
*Associated with renal transplants, [[bone marrow transplant]]s and [[vasculitides]].<ref name=Ref_PBoD922>{{Ref PBoD|922}}</ref>
*Can lead to [[portal hypertension]] and many of the associated complications.<ref name=pmid22554152>{{Cite journal | last1 = Bissonnette | first1 = J. | last2 = Généreux | first2 = A. | last3 = Côté | first3 = J. | last4 = Nguyen | first4 = B. | last5 = Perreault | first5 = P. | last6 = Bouchard | first6 = L. | last7 = Pomier-Layrargues | first7 = G. | title = Hepatic hemodynamics in 24 patients with nodular regenerative hyperplasia and symptomatic portal hypertension. | journal = J Gastroenterol Hepatol | volume = 27 | issue = 8 | pages = 1336-40 | month = Aug | year = 2012 | doi = 10.1111/j.1440-1746.2012.07168.x | PMID = 22554152 }}
</ref>

====Etiology====
*Arterial hypervascularity secondary to loss of hepatic vein radicles (loss of central venule in hepatic lobule).<ref name=Ref_PBoD922>{{Ref PBoD|922}}</ref>

ASIDE: radicle = ramulus - smallest branch or vessel or nerve.<ref name=Dorlands2>Dorland's Medical Dictionary. 30th Ed.</ref>

===Gross===
*Diffuse nodularity - whole liver.

===Microscopic===
Features:<ref name=Ref_PBoD922>{{Ref PBoD|922}}</ref>
*"Plump" hepatocytes surrounded by atrophic ones.
*No fibrosis.

==Sinuosoidal obstruction syndrome==
*May be referred to as ''Hepatic veno-occlusive disease''.<ref name=pmid11928077>{{Cite journal | last1 = DeLeve | first1 = LD. | last2 = Shulman | first2 = HM. | last3 = McDonald | first3 = GB. | title = Toxic injury to hepatic sinusoids: sinusoidal obstruction syndrome (veno-occlusive disease). | journal = Semin Liver Dis | volume = 22 | issue = 1 | pages = 27-42 | month = Feb | year = 2002 | doi = 10.1055/s-2002-23204 | PMID = 11928077 }}.</ref>
===General===
*Term for obstruction due to toxicity from a chemotherapeutic agent.<ref name=pmid16393276>{{Cite journal | last1 = Helmy | first1 = A. | title = Review article: updates in the pathogenesis and therapy of hepatic sinusoidal obstruction syndrome. | journal = Aliment Pharmacol Ther | volume = 23 | issue = 1 | pages = 11-25 | month = Jan | year = 2006 | doi = 10.1111/j.1365-2036.2006.02742.x | PMID = 16393276 }}</ref><ref name=pmid17569137>{{Cite journal | last1 = Aydinli | first1 = M. | last2 = Bayraktar | first2 = Y. | title = Budd-Chiari syndrome: etiology, pathogenesis and diagnosis. | journal = World J Gastroenterol | volume = 13 | issue = 19 | pages = 2693-6 | month = May | year = 2007 | doi = | PMID = 17569137 | url=http://www.wjgnet.com/1007-9327/full/v13/i19/2693.htm }}</ref>

Clinical DDx:
*[[Budd-Chiari syndrome]].

===Microscopic===
Features:<ref name=pmid17569137>{{Cite journal | last1 = Aydinli | first1 = M. | last2 = Bayraktar | first2 = Y. | title = Budd-Chiari syndrome: etiology, pathogenesis and diagnosis. | journal = World J Gastroenterol | volume = 13 | issue = 19 | pages = 2693-6 | month = May | year = 2007 | doi = | PMID = 17569137 | url=http://www.wjgnet.com/1007-9327/full/v13/i19/2693.htm }}</ref>
*Subendothelial swelling in hepatic venules.

Negatives:
*No thrombosis.

==Ascending Cholangitis (Acute Cholangitis)==
===General===
*Term for infection of bile ducts, usually due to obstruction

Clinical DDx:

===Microscopic===
====Images====

A. [[File:1 asc chol 1 680x512px.tif|Rounded, clear (edematous) portal tracts (arrows) separated by hepatocytes with dilated sinusoids (Row 1 Left 40X).]]
 
B. [[File:2 asc chol 1 680x512px.tif|Neutrophils about hepatocytes (arrows) have spilled into the lobule from a portal tract (Row 1 Right 200X).]]
 
C. [[File:3 asc chol 1 680x512px.tif|Proliferated bile ductules (arrows) bearing neutrophils within epithelium and lumens are features of obstruction that should prompt a search for interlobular ducts with acute inflammation (Row 2 Left 400X).]]
 
D. [[File:4 asc chol 1 680x512px.tif|The epithelium of the ducts can be severely degenerated. Neutrophils (cyan arrows) invade epithelium of an interlobular duct that are recognizable mainly as a circle of rounded nuclei; the associated arteriole (red arrow) should be identified to ensure an interlobular duct is being evaluated. Note the proliferated bile ductules (blue arrows) (Row 2 Right 400X).]]
 
E. [[File:5 asc chol 1 680x512px.tif|A PAS without diastase stain colors the arteriole (blue arrow), as well as the rim of the interlobular duct within which lies a neutrophil (cyan arrow) (Row 2 Right 400X). .]]
 
F. [[File:6 asc chol 1 680x512px.tif|A PAS with diastase stain colors the arteriole (red arrow), as well as the rim of the interlobular duct within which lies a neutrophil (cyan arrow) (Row 1 Right 400X)]]
 
Acute cholangitis in a patient with multiple bile duct procedures. After the biopsy, removal of bile duct stones released pus. A. Rounded, clear (edematous) portal tracts (arrows) separated by hepatocytes with dilated sinusoids. B. Neutrophils about hepatocytes (arrows) have spilled into the lobule from a portal tract. C, Proliferated bile ductules (arrows) bearing neutrophils within epithelium and lumens are features of obstruction that should prompt a search for interlobular ducts with acute inflammation. D. The epithelium of the ducts can be severely degenerated. Neutrophils (cyan arrows) invade epithelium of an interlobular duct that are recognizable mainly as a circle of rounded nuclei; the associated arteriole (red arrow) should be identified to ensure an interlobular duct is being evaluated. Note the proliferated bile ductules (blue arrows). E. A PAS without diastase stain colors the arteriole (blue arrow), as well as the rim of the interlobular duct within which lies a neutrophil (cyan arrow). F. A PAS with diastase stain colors the arteriole (red arrow), as well as the rim of the interlobular duct within which lies a neutrophil (cyan arrow).

A.[[File:1 Sep Acu Cho 1 680x512px.tif|Low power shows variably sized inflamed portal tracts (40X)]]
 
B. [[File:2 Sep Acu Cho 1 680x512px.tif|Trichrome shows dilated sinusoids and space of Disse collagenization (200X)]]
 
C. [[File:3 Sep Acu Cho 1 680x512px.tif|Inflammatory focus with macrophages and neutrophils (400X).]]
 
D. [[File:4 Sep Acu Cho 1 680x512px.tif|PAS with diastase shows proliferated bile ductules at edge of triad with neutrophils, which should not be used to make a definite diagnosis of acute cholangitis (400X).]]
 
E. [[File:5 Sep Acu Cho 1 680x512px.tif|PAS without diastase showing acutely inflamed bile duct, with accompanying blood vessel of similar size, diagnostic of acute cholangitis (400X).]]
 
F. [[File:6 Sep Acu Cho 1 680x512px.tif|PAS with diastase showing neutrophil in bille duct lumen, diagnostic of acute cholangitis (400X).]]
 
Patient with sepsis and acute cholangitis. A. Low power shows variably sized inflamed portal tracts. B. Trichrome shows dilated sinusoids and space of Disse collagenization. C. Inflammatory focus with macrophages and neutrophils. D. PAS with diastase shows proliferated bile ductules at edge of triad with neutrophils, which should not be used to make a definite diagnosis of acute cholangitis. E. PAS without diastase showing acutely inflamed bile duct, with accompanying blood vessel of similar size, diagnostic of acute cholangitis. F. PAS with diastase showing neutrophil in bille duct lumen, diagnostic of acute cholangitis.

==Polycystic kidney disease and the liver==
{{Main|Cystic kidney disease}}
===General===
Complications of PKD in the liver:<ref>{{Ref MacSween|174-5}}</ref>
#Infected cyst.
#Cholangiocarcinoma.
#Cholestasis/obstruction due to duct compression.<ref>URL: [http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=9184868 http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=9184868]. Accessed on: 23 September 2009.</ref>

Cysts:
*Cysts in the liver, like the kidney, are thought to enlarge with age.

===Microscopic===
Features:<ref>{{Ref MacSween|176}}</ref>
*''Von Meyenburg complexes'' ([[bile duct hamartoma]]):
**Cluster of dilated ducts with "altered" bile.
**Surrounded by collagenous stroma.
**Separate from the portal areas.<ref>Meyenburg complex. Stedman's Medical Dictionary. 27th Ed.</reF>

Images:
*[http://commons.wikimedia.org/wiki/File:Von_Meyenburg_complex_low_mag.jpg Von Meyenburg complex - bile duct hamartoma (WC)].
*[http://commons.wikimedia.org/wiki/File:Bile_duct_hamartoma_intermed_mag.jpg Bile duct hamartoma (WC)].

Notes:
*Appearance on ultrasound<ref name=pmid17287178>Bile duct hamartomas--the von Meyenburg complex. Salles VJ, Marotta A, Netto JM, Speranzini MB, Martins MR. Hepatobiliary Pancreat Dis Int. 2007 Feb;6(1):108-9. PMID 17287178.</ref> and CT (hypodense)<ref name=pmid19294869>[The von Meyenburg complex] Schwab SA, Bautz W, Uder M, Kuefner MA. Rontgenpraxis. 2008;56(6):241-4. German. PMID 19294869.</ref> - similar to metastases.

==Peliosis hepatis==
===General===
*Associated with:
**Infections.
**Malignancy.
**Other stuff.
*Rarely biopsied.

===Microscopic===
Features:
*Cyst lined by endothelium.
**Usu. incomplete.
*Blood.
{|
[[File:1 PEL 1 680x512px.tif|Hemorrhage at left end, dilated sinusoids elsewhere (20X).]]
[[File:2 PEL 1 680x512px.tif|Ramifying dilated sinusoidal spaces (100X).]]
 
[[File:3 PEL 1 680x512px.tif|PAS with diastase shows flat lining (400X).]]
[[File:4 PEL 1 680x512px.tif|Necrotic hepatocytes in cords, presumably due to pressure (400X).]]
|}
Peliosis hepatis. Hemorrhage at left end, dilated sinusoids elsewhere (UL 20X). Ramifying dilated sinusoidal spaces (UR 100X). PAS with diastase shows flat lining (LL 400X). Necrotic hepatocytes in cords, presumably due to pressure (LR 400X).

==Total parenteral nutrition==
*Abbreviated ''TPN''.

===General===
*Indication: short gut syndrome, others.

===Microscopic===
Variable - may range from: steatosis, steatohepatitis, cholestasis, fibrosis and cirrhosis.<ref name=pmid16766237>{{cite journal |author=Guglielmi FW, Boggio-Bertinet D, Federico A, ''et al.'' |title=Total parenteral nutrition-related gastroenterological complications |journal=Dig Liver Dis |volume=38 |issue=9 |pages=623–42 |year=2006 |month=September |pmid=16766237 |doi=10.1016/j.dld.2006.04.002 |url=}}</ref>

Features (classic):<ref>{{Cite journal | last1 = Li | first1 = SJ. | last2 = Nussbaum | first2 = MS. | last3 = McFadden | first3 = DW. | last4 = Gapen | first4 = CL. | last5 = Dayal | first5 = R. | last6 = Fischer | first6 = JE. | title = Addition of glucagon to total parenteral nutrition (TPN) prevents hepatic steatosis in rats. | journal = Surgery | volume = 104 | issue = 2 | pages = 350-7 | month = Aug | year = 1988 | doi = | PMID = 3135627 }}</ref><ref>{{Cite journal | last1 = Stanko | first1 = RT. | last2 = Nathan | first2 = G. | last3 = Mendelow | first3 = H. | last4 = Adibi | first4 = SA. | title = Development of hepatic cholestasis and fibrosis in patients with massive loss of intestine supported by prolonged parenteral nutrition. | journal = Gastroenterology | volume = 92 | issue = 1 | pages = 197-202 | month = Jan | year = 1987 | doi = | PMID = 3096806 }}
</ref>
*[[Steatosis]] (periportal) - early.
*Cholestasis - late.

==Giant cell hepatitis==
*[[AKA]] ''neonatal giant cell hepatitis''.

:See: ''[[Giant cell hepatitis]]''.

==Hepatic amyloidosis==
{{Main|Amyloidosis}}
*[[AKA]] ''liver amyloidosis''.
*[[AKA]] ''amyloidosis of the liver''.
===General===
*Diffuse abundant amyloid within the space of Disse is associated with [[portal hypertension]].<ref name=pmid1864548>{{Cite journal | last1 = Bion | first1 = E. | last2 = Brenard | first2 = R. | last3 = Pariente | first3 = EA. | last4 = Lebrec | first4 = D. | last5 = Degott | first5 = C. | last6 = Maitre | first6 = F. | last7 = Benhamou | first7 = JP. | title = Sinusoidal portal hypertension in hepatic amyloidosis. | journal = Gut | volume = 32 | issue = 2 | pages = 227-30 | month = Feb | year = 1991 | doi = | PMID = 1864548 | PMC = 1378815 | URL = http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1378815/?tool=pubmed }}</ref>

===Microscopic===
Features:
*Amorphous extracellular pink stuff on H&E - see ''[[amyloid]]'' article.

DDx:
*[[Fibrolamellar hepatocellular carcinoma]].

====Images====
<gallery>
Image:Hepatic_amyloidosis_-_low_mag.jpg | Amyloidosis of the liver - low mag. (WC)
Image:Hepatic_amyloidosis_-_intermed_mag.jpg | Amyloidosis of the liver - intermed. mag. (WC)
Image:Hepatic_amyloidosis_-_high_mag.jpg | Amyloidosis of the liver - high mag. (WC)
Image:Hepatic_amyloidosis_-_very_high_mag.jpg | Amyloidosis of the liver - very high mag. (WC)
</gallery>
{|
[[File:1 AMY 1 680x512px.tif|Amorphous material replaces hepatic parenchyma [4X]]]
[[File:2 AMY 1 680x512px.tif|Material barely stains blue on trichrome [10X]]]
 
[[File:3 AMY 1 680x512px.tif|Material stains red on unpolarized Congo Red [40X]]]
[[File:4 AMY 1 680x512px.tif|Material stains apple green on polarized Congo Red [40X]]]
|}
Amyloidosis. Amorphous material replaces hepatic parenchyma [UL 4X]. Material barely stains blue on trichrome [UR 10X] Material stains red on unpolarized Congo Red [LL 40X] Material stains apple green on polarized Congo Red [LR 40X]

===Stains===
*[[Congo red]] +ve.

==Fulminant hepatic necrosis==
===General===
Etiology:
*Viral, i.e. [[Hepatitis A]], [[Hepatitis B]]; [[Hepatitis C]] - extremely rare.
*Trauma.
*Shock.

===Microscopic===
{|
[[File:1 Necrosis 2 680x512px.tif| Submassive hepatic necrosis.]]
[[File:2 Necrosis 2 680x512px.tif| Submassive hepatic necrosis.]]
 
[[File:3 Necrosis 2 680x512px.tif| Submassive hepatic necrosis.]]
[[File:4 Necrosis 2 680x512px.tif| Submassive hepatic necrosis.]]
 
[[File:5 Necrosis 2 680x512px.tif| Submassive hepatic necrosis.]]
[[File:6 Necrosis 2 680x512px.tif| Submassive hepatic necrosis.]]
|}
Submassive hepatic necrosis. Patient had transaminases in the thousands that rapidly dropped to normal. Pink preserved parenchyma strews empty necrotic spaces (Row 1 Left 20X). Focus of necrosis with no apparent hepatocytes macrophages abuts apparently normal liver (Row 1 Right 200X). Iron stain shows the macrophages bear hemosiderin (Row 2 Left 200X). Reticulin stain highlights the recently dead liver cells (Row 2 Right 200X). Reticulin stain shows a necrotic bridge forming; the multiple small black circles preclude diagnosis of a fibrous bridge (Row 3 Left 200X). Trichrome shows the necrotic bridge (“collapse”) lacks much collagen deposition, as would be expected for bridging fibrosis (Row 3 Right 200X).

Features:
*Hepatocyte [[necrosis]].
*Bile duct proliferation.

DDx:
*[[Cholangiocarcinoma]].
*[[Angiosarcoma]].

==Secondary hemochromatosis==
:''For the hereditary one see [[hereditary hemochromatosis]]''.
===General===
*Iron overload secondary to blood transfusions for hereditary or acquired anemia.<ref name=pmid19727383/>
**Primary hemochromatosis due to a defect in iron processing - called ''[[hereditary hemochromatosis]]''.
*Imaging considered the best test, as iron deposition is patchy.<ref name=pmid19727383/>

Selected hereditary causes:<ref name=pmid19727383>{{Cite journal | last1 = Gattermann | first1 = N. | title = The treatment of secondary hemochromatosis. | journal = Dtsch Arztebl Int | volume = 106 | issue = 30 | pages = 499-504, I | month = Jul | year = 2009 | doi = 10.3238/arztebl.2009.0499 | PMID = 19727383 | PMC = 2735704 | URL = http://www.ncbi.nlm.nih.gov.myaccess.library.utoronto.ca/pmc/articles/PMC2735704/?tool=pubmed}}</ref>
*Thalassemia.
*[[Sickle cell anemia]].
*Hereditary sideroblastic anemia.

Selected acquired causes:<ref name=pmid19727383/>
*[[Myelodysplastic syndromes]]
*Myelofibrosis
*Aplastic anemia, intractable.

===Microscopic===
:See ''[[hereditary hemochromatosis]]''.

==Hepatic sarcoidosis==
{{Main|Hepatic sarcoidosis}}
==Overlapping Disorders==

[[File:1 Mixed Disorder 1 680x512px.tif|Changes of steatohepatitis and interface hepatitis, with granuloma. Patient with diabetes was ANA, AMA, HCV, HBV negative, without drugs known to produce granulomas or interface hepatitis. This may be a case of AMA negative primary biliary cirrhosis, but studies to determine that with certainty were not performed.]]
[[File:2 Mixed Disorder 1 680x512px.tif|Changes of steatohepatitis and interface hepatitis, with granuloma. Patient with diabetes was ANA, AMA, HCV, HBV negative, without drugs known to produce granulomas or interface hepatitis. This may be a case of AMA negative primary biliary cirrhosis, but studies to determine that with certainty were not performed.]]
[[File:3 Mixed Disorder 1 680x512px.tif|Changes of steatohepatitis and interface hepatitis, with granuloma. Patient with diabetes was ANA, AMA, HCV, HBV negative, without drugs known to produce granulomas or interface hepatitis. This may be a case of AMA negative primary biliary cirrhosis, but studies to determine that with certainty were not performed.]]
[[File:4 Mixed Disorder 1 680x512px.tif|Changes of steatohepatitis and interface hepatitis, with granuloma. Patient with diabetes was ANA, AMA, HCV, HBV negative, without drugs known to produce granulomas or interface hepatitis. This may be a case of AMA negative primary biliary cirrhosis, but studies to determine that with certainty were not performed.]]
[[File:5 Mixed Disorder 1 680x512px.tif|Changes of steatohepatitis and interface hepatitis, with granuloma. Patient with diabetes was ANA, AMA, HCV, HBV negative, without drugs known to produce granulomas or interface hepatitis. This may be a case of AMA negative primary biliary cirrhosis, but studies to determine that with certainty were not performed.]]
[[File:6 Mixed Disorder 1 680x512px.tif|Changes of steatohepatitis and interface hepatitis, with granuloma. Patient with diabetes was ANA, AMA, HCV, HBV negative, without drugs known to produce granulomas or interface hepatitis. This may be a case of AMA negative primary biliary cirrhosis, but studies to determine that with certainty were not performed.]] 
Changes of steatohepatitis and interface hepatitis, with granuloma. Patient with diabetes was ANA, AMA, HCV, HBV negative, without drugs known to produce granulomas or interface hepatitis. This may be a case of AMA negative primary biliary cirrhosis, but studies to determine that with certainty were not performed. A. Low power shows hepatocytes afflicted by steatosis and an inflamed portal tract. B. In a region of fatty change lie cytoplasmic tufts of ballooning degeneration (green arrows) and a lipogranuloma (black arrow). C. At the portal-hepatocyte junction lies interface hepatitis (black arrows), as well as extension of inflammation into the lobule (green arrows). D. Red hepatocytes bounded by inflammation denote piecemeal necrosis [PAS without diastase]. E. Giant cells intermixed with lymphocytes prove a portal granuloma [PAS without diastase]. F. A blue fibrous bridge extends from a triad [Trichrome].

[[File:4 95599552608917 sl 1.png|Acute obstructive changes and changes of recurrent acute injury]]
[[File:4 95599552608917 sl 2.png|Acute obstructive changes and changes of recurrent acute injury]]
[[File:4 95599552608917 sl 3.png|Acute obstructive changes and changes of recurrent acute injury]]
[[File:4 95599552608917 sl 4.png|Acute obstructive changes and changes of recurrent acute injury]]
[[File:4 95599552608917 sl 5.png|Acute obstructive changes and changes of recurrent acute injury]]
[[File:4 95599552608917 sl 6.png|Acute obstructive changes and changes of recurrent acute injury]]
[[File:4 95599552608917 sl 7.png|Acute obstructive changes and changes of recurrent acute injury]] 
Acute obstructive changes and changes of recurrent injury in 46 yo man with Clostridium perfringens positive blood culture, an ERCP that showed duodenal compression by the pancreas with resultant bile duct dilatation. The patient had had and continued to have multiple bouts of acute pancreatitis. At the time of biopsy, decreased platelet count/hemoglobin/albumin, elevated lipase/amylase/PT/PTT, normal alkaline phosphatase, bilirubin, AST/ALT, AMA, hepatitis virus serology, ANA. A. Fragment biopsy shows inflamed triads and bridges. B. Trichrome shows bridges without nodules, evidence of prior injury; the patient subsequently developed multiple episodes of pancreatitis. C. Reticulin shows piecemeal necrosis, with black lines bounding individual hepatocytes at interface (arrows). D. Collapse is shown by closly approximated thick black lines; one cannot call portal-central collapse without seeing a central vein. Note on this and the other reticulin image that regeneration, two cell thick cords, is not prominent. E. PAS D of two portal triads, far nearer than normal, both expanded. Note increased number of ducts/ductules (red arrows), neutrophils, and PAS-D macrophages. F. PAS D shows collapse extending from a triad to a portion of a lobule with steatosis. No feathery degeneration or bile duct plugs were seen. Neither were foci of spotty necrosis or abscess seen. G. Other triads, again edematous, showed more of a chronic inflammatory response, with occasional plasma cells (black arrows). Also present are neutrophils (red arrows). The bile duct (grey arrow) near the artery (brown arrow) shows mildly disturbed nuclei. Note early proliferated bile ductules (cyan arrows).

[[File:6 17281676469188 sl 1.png| Hepatitis B virus with steatohepatitis]]
[[File:6 17281676469188 sl 2.png| Hepatitis B virus with steatohepatitis]]
[[File:6 17281676469188 sl 3.png| Hepatitis B virus with steatohepatitis]]
[[File:6 17281676469188 sl 4.png| Hepatitis B virus with steatohepatitis]]
[[File:6 17281676469188 sl 5.png| Hepatitis B virus with steatohepatitis]]
[[File:6 17281676469188 sl 6.png| Hepatitis B virus with steatohepatitis]] 
Hepatitis B virus with steatohepatitis in a 36 year old man with hepatitis B surface antigen and hepatitis Be antigen positivity, Hepatitis be QTPC of 1750 cop/mL, an occasionally mildly elevated (42) ALT, and normal glucose, alkaline phosphatase, bilirubin, and other transaminases. He had a history of alcohol abuse, which became controlled. A. Triads show scant inflammation without definite interface hepatitis. About one-fourth of the lobule, not pan-acinar, is afflicted by steatosis. B. Occasional tufts are seen (arrow), indicating focal ballooning sufficient for a diagnosis of steatohepatitis. C. Glycogenated nuclei (black arrows) and hepatocytes with feathery degeneration (red arrows) are seen. D. Very rare foci of spotty necrosis were seen. E. Apart from this triad and the one in the trichrome stain in F, which had moderate inflammation comprising lymphocytes and macrophages, all triads were small, most without any inflammation at all. Neither collapse nor piecemeal necrosis were seen on reticulin stain. F. Trichrome stain showed only portal fibrosis. The interhepatocyte fibrosis required for brunt fibrosis stage I was not seen. Hence, one would grade this as follows: A) Chronic hepatitis (history of hepatitis B), Metavir activity index 1, Piecemeal necrosis 0, Lobular necrosis 1, Metavir fibrosis stage 1, B) Steatohepaitits, Brunt necroinflammatory grade 1, Brunt fibrosis stage 0.

=See also=
*[[Pancreas]].
*[[Gastrointestinal pathology]].
*[[Liver neoplasms]].
*[[Liver]].

=References=
{{reflist|2}}

[[Category:Gastrointestinal pathology]]
[[Category:Liver pathology]]
[[Category:Medical liver disease]]

Medical liver disease

2017-02-10T18:41:28Z

Mitchell: /* Autoimmune hepatitis with obstruction - combined changes */ Improved appearances

[[Image:Ground glass hepatocytes high mag cropped 2.jpg|thumb|right|[[Micrograph]] showing ground glass hepatocytes, as seen in chronic [[hepatitis B]]. [[H&E stain]].]]
This article deals with '''medical [[liver]] disease'''. An introduction to the liver and approach is found in the ''[[liver]]'' article.

Every differential in liver pathology has "drugs"<ref>{{Ref PCPBoD8|448}}</ref> -- if it isn't clearly malignancy.

Liver neoplasms are dealt with in the ''[[liver neoplasms]]'' article.

Medical liver biopsies are often non-specific, as the liver has the same appearance for many mechanisms of injury, especially when the injury is marked. The clinical history, serology and imaging are essential for proper interpretations in this domain of pathology.

=Review of liver blood work=
===Inflammation activity===
*ALT.
*AST.

===Cholestatic markers===
*ALP.
*GGT - used to assess whether the ALP is an "honest" value, elevated in cirrhosis.

===Cirrhosis/decompensation===
*PLT - low is suggestive of dysfunction.
*INR - high is bad, unless anticoagulated.

===Other===
*Bilirubin.
**Direct (AKA conjugated).
**Indirect (AKA unconjugated).

A short DDx of elevated:<ref>{{Ref PCPBoD8|441}}</ref>
*Indirect:
**[[Gilbert syndrome]].
**Crigler-Najjar syndrome type 1.
**Crigler-Najjar syndrome type 2.
*Direct:
**Rotor syndrome.
**Dubin-Johnson syndomre.

===Viral hepatitis===
*HBV DNA.
*HCV RNA.
*HBs Ag, HBs Ab, HBe Ag, HBe Ab.
*HCV Ab.

Others:
*[[Epstein-Barr virus]] (EBV).
*[[Cytomegalovirus]] (CMV) - especially in the immune incompetent.

====Hepatitis B====
Meaning & utility of the various [[Hepatitis B]] tests:<ref>URL: [http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/hepatology/hepatitis-B/ http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/hepatology/hepatitis-B/]. Accessed on: 16 May 2011.</ref><ref name=lto_hepb>URL: [http://www.labtestsonline.org/understanding/analytes/hepatitis_b/test.html http://www.labtestsonline.org/understanding/analytes/hepatitis_b/test.html]. Accessed on: 16 May 2011.</ref>
{| class="wikitable sortable" border="1"
! Test name
! Location
! Positive test
! Negative test
! Usual question
|-
| HBs Ag||Surface||Virus active||No active infection||Active infection?
|-
| HBs Ab||Surface||Exposed OR vaccinated||No exposure OR no vaccine OR loss of Ab||Immunization status?
|-
| HBe Ag||Virus core||Infect. w/ viral replication||No active infection||Active infect. w/ viral replication?
|-
| HBe Ab||Virus core||Exposed to virus||Infect. w/o antibody response OR not exposed||Immune response to infection?
|-
| HBV DNA||-||Active||Not active/no exposure||Viral load/how active?
|-
| HBc Ab||Virus core||Virus active/previous exposure||No exposure||Early active infection?
|}
Notes:
*''HBc Ab'' may test for acute (IgM) or chronic infection - dependent on specific antibody test; it is often used to look for early infection.<ref name=lto_hepb>URL: [http://www.labtestsonline.org/understanding/analytes/hepatitis_b/test.html http://www.labtestsonline.org/understanding/analytes/hepatitis_b/test.html]. Accessed on: 16 May 2011.</ref>
*''Carriers of hepatitis B'': HBs Ag +ve, HBs Ab -ve, HBc Ag -ve, HBc Ab +ve, HBe Ag -ve, HBe Ab +ve.<ref>URL: [http://labtestsonline.org/understanding/analytes/hepatitis-b/tab/test http://labtestsonline.org/understanding/analytes/hepatitis-b/tab/test]. Accessed on: 3 May 2012.</ref>

===Markers for rare liver diseases===
*Ceruloplasm - low think ''[[Wilson's disease]]''; typical value for Wilson's ~ 0.12 g/L.
**<0.20 g/L is a criteria for Wilson's disease.<ref name=pmid18556333>Diagnostic accuracy of serum ceruloplasmin in Wilson disease: determination of sensitivity and specificity by ROC curve analysis among ATP7B-genotyped subjects. Mak CM, Lam CW, Tam S. Clin Chem. 2008 Aug;54(8):1356-62. Epub 2008 Jun 12. PMID 18556333. URL: [http://www.clinchem.org/cgi/reprint/54/8/1356.pdf http://www.clinchem.org/cgi/reprint/54/8/1356.pdf]. Accessed on: 28 September 2009.</ref>
*Alpha-1 antitrypsin - if low think ''deficiency''.

===Hemosiderosis===
*Ferritin - high.
*Iron saturation - high.

Causes:
*Hemochromatosis.
*Hemolysis, chronic.
*Cirrhosis.

=Medical imaging=
Blood flow:<ref>URL: [http://insidesurgery.com/2010/12/hepatopedal-hepatofugal-flow/ http://insidesurgery.com/2010/12/hepatopedal-hepatofugal-flow/]. Accessed on: 2 December 2011.</ref>
*Hepatopedal flow = normal portal vein flow.
*Hepatofugal flow = reversed portal vein flow.

==Interventional measurements==
Wedged to free hepatic venous pressure:<ref name=pmid1864548>{{Cite journal | last1 = Bion | first1 = E. | last2 = Brenard | first2 = R. | last3 = Pariente | first3 = EA. | last4 = Lebrec | first4 = D. | last5 = Degott | first5 = C. | last6 = Maitre | first6 = F. | last7 = Benhamou | first7 = JP. | title = Sinusoidal portal hypertension in hepatic amyloidosis. | journal = Gut | volume = 32 | issue = 2 | pages = 227-30 | month = Feb | year = 1991 | doi = | PMID = 1864548 | PMC = 1378815 | URL = http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1378815/?tool=pubmed }}</ref>
*Normal = 1-4 mmHg.
**Elevated in [[portal hypertension]].

=Liver biopsy=
==Medical liver biopsy adequacy==
Liver biopsy specimens should be:<ref>{{Ref MacSween|418}}</ref>
*2.0 cm in length and contain 11-15 portal tracts,
*The core should be deeper than 1.0 cm from the liver capsule; specimens close to the capsule may lead to over grading of fibrosis.

==Reporting==
{{Main|Pathology reports}}
<pre>
Specimen, procedure:
- Diagnosis.
</pre>
The diagnosis usually contains grading and staging information, e.g. ''activity 2 /4, Laennec fibrosis stage 1 /4''.

In the context of medical liver disease:
*Grade = inflammation/activity.
*Stage = severity of fibrosis/architectural changes.

Notes:
*The term "acute" is infrequently used in liver pathology.
*In the liver: neutrophils ''is not'' acute -- unlike most elsewhere in the body.<ref>OA. September 2009.</ref>

===A microscopic checklist===
<pre>
Size of biopsy: Adequate
Fragmentation: Absent
Fibrosis: Stage 2-3/4, mostly stage 2
Fibrous septa: Present
Septa with curved contours: Present – focally only
Large droplet steatosis (% of hepatocytes): Present, moderate 60%
Ballooning of hepatocytes: Present, rare
Mallory-Denk bodies: Present, rare
Portal inflammation: Present
Interface activity: Minimal (0-1/4)
Lobular necroinflammation: Minimal
Ducts: Present in normal numbers
Duct injury: Absent
Ductular reaction: Absent
Cholestasis: Absent
Terminal hepatic venules: Present
Iron stain: Absent
Ground glass cells with routine stains: Absent
PASD for alpha-1 antitrypsin droplets: Negative
</pre>

=Viral hepatitis=
These are common. The diagnoses are based on serology. The serology is covered in the ''[[Liver_pathology#Viral_hepatitis|viral hepatitis]]'' section in the ''[[liver pathology]]'' article.

Typically classified as:<ref name=pmid8048409>{{Cite journal | title = Terminology of chronic hepatitis, hepatic allograft rejection, and nodular lesions of the liver: summary of recommendations developed by an international working party, supported by the World Congresses of Gastroenterology, Los Angeles, 1994. | journal = Am J Gastroenterol | volume = 89 | issue = 8 Suppl | pages = S177-81 | month = Aug | year = 1994 | doi = | PMID = 8048409 }}</ref><ref>URL: [http://familydoctor.org/familydoctor/en/diseases-conditions/hepatitis-b.html http://familydoctor.org/familydoctor/en/diseases-conditions/hepatitis-b.html]. Accessed on: 2 May 2012.</ref>
#Acute < 6 months duration.
#Chronic > 6 months duration.

==Hepatitis A==
*Infection is self-limited, i.e. not persistent.
**May present as ''[[fulminant hepatic necrosis]]''.
*Usually asymptomatic in children.<ref name=pmid20068336>{{cite journal |author=Jeong SH, Lee HS |title=Hepatitis A: clinical manifestations and management |journal=Intervirology |volume=53 |issue=1 |pages=15–9 |year=2010 |pmid=20068336 |doi=10.1159/000252779 |url=}}</ref>
*Serology is diagnostic.

==Hepatitis B==
:''Hepatitis B virus'', abbreviated ''HBV'', redirects here.
{{Main|Hepatitis B}}

==Hepatitis C==
{{Main|Hepatitis C}}

=Other infections=
*Hydatid disease (Hydatid cyst).
*Ascaris.
*Fasciola

==Hydatid disease==
*[[AKA]] ''hydatid cyst''.
===General===
*Etiology: ''[[Echinococcus]]''.

===Microscopic===
Features:
*Laminated wall +/- calcification.<ref name=Ref_PBPoD8_448>{{Ref PCPBoD8|448}}</ref>
*Organisms -- see ''[[Echinococcus]]''.

====Images====
<gallery>
Image:Liver_cyst_wall_-_intermed_mag.jpg | Liver cyst wall - intermed. mag. (WC)
Image:Liver_cyst_wall_-_high_mag.jpg | Liver cyst wall - high mag. (WC)
Image: Laminated liver cyst wall - intermed mag.jpg | Characteristic laminated portion - intermed. mag. (WC)
Image: Laminated liver cyst wall - high mag.jpg | Characteristic laminated portion - high mag. (WC)
</gallery>
[[www]]:
*[http://pathmicro.med.sc.edu/parasitology/hydatid-hist1.jpg Hydatid cyst (med.sc.edu)].
*[http://www.atlas.or.kr/atlas/include/viewImg.html?uid=645 Hydatid cyst (atlas.or.kr)].
*[http://casereports.bmj.com/content/2009/bcr.04.2009.1798.full Hydatid cyst (casereports.bmj.com)].

==Abscess==
A. [[File:1 ABS 1 680x512px.tif|A process replaces most of the liver parenchyma (20X).]]
 
B. [[File:2 ABS 1 680x512px.tif|Fibrinopurulent exudate apposes granulation tissue (200X).]]
 
C. [[File:3 ABS 1 680x512px.tif|Neutrophils lie in widened sinusoids (200X)..]]
 
D. [[File:4 ABS 1 680x512px.tif|Trichrome shows collagenization of spaces of Disse. Scarring about an abscess or other mass lesion should not be interpreted as reflective of the liver in general (200X).]]
 
Abscess. A. A process replaces most of the liver parenchyma. B. Fibrinopurulent exudate apposes granulation tissue. C. Neutrophils lie in widened sinusoids. D. Trichrome shows collagenization of spaces of Disse. Scarring about an abscess or other mass lesion should not be interpreted as reflective of the liver in general (LR 200X).

==Coccidiomycosis==
A. [[File:Coccidiomycosis - 1 - 40X 680x512px shot.tif|500x500px Granulomas at low power]]
 
B. [[File:Coccidiomycosis - 1 - 200X 680x513px shot.tif|500x500px Granulomas with centrally crowded cells & lady slipper macrophage nuclei]]
 
C. [[File:Coccidiomycosis - 1 - 400X 1369x1024px shot.tif|500x500px Center of previous granuloma showing pyknotic macrophage nuclei]]
 
D. [[File:Coccidiomycosis - 1 - GMS 400X 1369x1024px shot.tif|500x500px Four Coccidiomycotic spherules]]
 
Coccidiomycosis. A. Note the granulomas in otherwise undisturbed liver (UL). B. Granuloma with centrally crowded cells & lady slipper macrophage nuclei. C. Center of granuloma with pyknotic macrophage nuclei, "necrotizing". D. Organisms on GMS stain.

=Metabolic and toxic=
==Alcoholic liver disease==
===General===
*Acute and/or chronic liver changes due to excessive [[alcohol]] use - includes:
**''[[Alcoholic steatohepatitis]]'' (ASH), [[AKA]] ''alcoholic hepatitis''.<ref>URL: [http://emedicine.medscape.com/article/170539-overview http://emedicine.medscape.com/article/170539-overview]. Accessed on: 3 May 2012.</ref>
***Alcoholic hepatitis can be with minimal steatosis.<ref>STC. 6 December 2010.</ref>
**[[Steatosis]] - classically macrovescicular and centrilobular.
**Alcoholic [[cirrhosis]].

====Classic lab findings in EtOH abusers====
*AST & ALT elevated with AST:ALT=2:1.
*GGT elevated.
*MCV increased.

===Gross pathology/radiologic findings===
*Classically micronodular pattern.
**May be macronodular.

===Microscopic===
See:
*''[[Steatohepatitis]]'' section and ''[[ballooning degeneration]]'' section.

Features:
*Often zone III damage.
*Cholestatsis common, i.e. yellow staining.
**NASH (non-alcoholic steatohepatitis) usu. does not have cholestasis.<ref>STC. 6 December 2010.</ref>
*Fibrosis starts at central veins.
*Neutrophils (often helpful) -- few other things have PMNs. (???)
**Neutrophils cluster around cells with Mallory hyaline.

====Images====

A. [[File:1 etoh 3 680x512px.tif| Alcoholic hepatitis with Metavir stage IV fibrosis (advanced fibrosis/cirrhosis).]]
 
B. [[File:2 etoh 3 680x512px.tif| Alcoholic hepatitis with Metavir stage IV fibrosis (advanced fibrosis/cirrhosis).]]
 
C. [[File:3 etoh 3 680x512px.tif| Alcoholic hepatitis with Metavir stage IV fibrosis (advanced fibrosis/cirrhosis).]]
 
D. [[File:4 etoh 3 680x512px.tif| Alcoholic hepatitis with Metavir stage IV fibrosis (advanced fibrosis/cirrhosis).]]
 
E. [[File:5 etoh 3 680x512px.tif| Alcoholic hepatitis with Metavir stage IV fibrosis (advanced fibrosis/cirrhosis).]]
 
F. [[File:6 etoh 3 680x512px.tif| Alcoholic hepatitis with Metavir stage IV fibrosis (advanced fibrosis/cirrhosis).]]
 

Alcoholic hepatitis with Metavir stage IV fibrosis (advanced fibrosis/cirrhosis).
A. Trichrome shows relatively non-inflamed fibrous bands, as well as [between green dots] nodules. The lack of regeneration throughout might have precluded a diagnosis of cirrhosis, but stage IV fibrosis under the Metavir system is justified. B. Reticulin shows regenerative nodules [left] with mostly two or more nuclei between black lines juxtaposed to non-regenerative hepatocytes on the right, without piecemeal necrosis. C. Regenerative nodules show occasional neutrophils [red arrow] and cytoplasmic tufts of ballooned cells, sometimes possibly Mallory hyalin [green arrows]. D. Triads (note vein [green arrow], artery [yellow arrow], and interlobular bile duct [blue arrow]) generally showed little or no interface hepatitis, even when expanded by fibrosis and inflamed. E. Occasional foci of spotty necrosis were seen. F. This edge of an inflamed triads shows neutrophils about proliferated bile ducts [red arrows], as well as Mallory-Denk bodies [blue arrows].
 
A. [[File:1 etoh 4 680x512px.tif| Cirrhosis in an alcoholic.]]
 
B. [[File:2 etoh 4 680x512px.tif| Cirrhosis in an alcoholic.]]
 
C. [[File:3 etoh 4 680x512px.tif| Cirrhosis in an alcoholic.]]
 
D. [[File:4 etoh 4 680x512px.tif| Cirrhosis in an alcoholic.]]
 
E. [[File:5 etoh 4 680x512px.tif| Cirrhosis in an alcoholic.]]
 
F. [[File:6 etoh 4 680x512px.tif| Cirrhosis in an alcoholic.]]
 
Definite cirrhosis in an alcoholic. A. Hepatocyte free bands parse tissue, with occasional definite islands [arrows]. B. Trichrome establishes blue fibrosis about isles [arrows]. C. Reticulin stain shows nodules with regeneration, wherein a large proportion of them are at least two nuclei thick [arrows]. D. Bile duct proliferation can be difficult, sometimes mimicking cholangiocarcinoma. Follow the double headed arrows to see how the ductules can be seen to proliferate from a single sources, with all ducts being complete, without necrotic epithelial cells. E. PAS with distase can help, as cholangiocarcinoma generally lacks the red rim of proliferating bile ductules [arrows]; again note the connections that can be made between the ductule openings by the blue double headed arrows. The cyan double headed arrows show general parallelism, consistent with uniform directionality induced by extrinsic force, not a neoplastic spread. F. Trichrome shows the most difficult focus. Double headed arrows display the connectivity seen before of the proliferated bile ductules. Note that numerous pairs of adjacent perpendicular glands without a head to foot appearance are not seen that would indicate the disorderly spread of cholangiocarcinoma.
 
A. [[File:1 ALC 2 680x512px.tif|Expanded, inflamed triads with increased bile duct/vascular openings. Mild steatosis (40X).]]
 
B. [[File:2 ALC 2 680x512px.tif|Trichrome stain shows periportal fibrosis [red arrowheads] (200X).]]
 
C. [[File:3 ALC 2 680x512px.tif|PAS with diastase stain shows proliferated bile ductules [blue arrowheads] in stroma with mixed inflammatory infiltrate (400X)]]
 
D. [[File:4 ALC 2 680x512px.tif|Neutrophils about ballooned hepatocyte (satellitosis) [yellow arrowheads]. Councilman bodies [green arrowheads] (400X).]]
 
Alcoholic hepatitis without cirrhosis. No history of viral disease. AMA negative. A. Expanded, inflamed triads with increased bile duct/vascular openings. Mild steatosis. B. Trichrome stain shows periportal fibrosis [red arrowheads]. C. PAS with diastase stain shows proliferated bile ductules [blue arrowheads] in stroma with mixed inflammatory infiltrate. D. Neutrophils about ballooned hepatocyte (satellitosis) [yellow arrowheads]. Councilman bodies [green arrowheads].

Notes:
*If portal inflammatory infiltrates more than mild, r/o other causes i.e. [[viral hepatitis]].
*Mallory bodies once thought to be characteristic; now considered non-specific and generally poorly understood.<ref>{{cite journal |author=Jensen K, Gluud C |title=The Mallory body: theories on development and pathological significance (Part 2 of a literature survey) |journal=Hepatology |volume=20 |issue=5 |pages=1330-42 |year=1994 |month=November |pmid=7927269 |doi= |url=}}</ref>
*Some consider ''alcoholic liver disease'' a clinical diagnosis, i.e. as a pathologist one does not diagnose it.<ref>MG. September 2009.</ref>

==Non-alcoholic fatty liver disease==
*Abbreviated ''NAFLD''.
*Fatty liver that is not due to alcohol; includes obesity-related fatty liver, metabolic disease/diabetes-related fatty liver.

===NASH===
*Non-alcoholic steatohepatitis - see ''steatohepatitis'' section.
*Histologically indistinguishable from ASH.
*NASH is a ''clinical diagnosis'' based on exclusion of alcohol.

==Steatohepatitis==
{{Main|Steatohepatitis}}

=Autoimmune=
==Autoimmune hepatitis==
*Abbreviated ''AIH''.
{{Main|Autoimmune hepatitis}}

==Primary biliary cirrhosis==
*Abbreviated PBC.
{{Main|Primary biliary cirrhosis}}

==Autoimmune hepatitis with obstruction - combined changes==
A. [[File:1 AIH OBS 1.tif|Low power shows inflammation; portal triads, lobules, central veins cannot be distinguished (40X).]]
 
B. [[File:2 AIH OBS 1.tif|Trichrome shows central venous sclerosis (red arrowhead), periportal fibrosis (green arrowhead), & space of Disse collagenization (yellow arrowhead); juxtaposition of central vein & portal tract indicates collapse, no definite bridging was seen (100X)]]
 
C. [[File:3 AIH OBS 1.tif|Central vein is inflamed with a rare plasma cell (cyan arrowhead) (400X).]]
 
D. [[File:4 AIH OBS 1.tif|Interface hepatitis with plasma cells (yellow arrows) and ballooned hepatocytes (red arrows). Lobule is disorganized (400X).]]
 
E. [[File:5 AIH OBS 1.tif|Proliferating bile ductules (blue arrows) with occasional neutrophils (fucsia arrows), indicative of obstruction, but not acute cholangitis, which requires inflamed bile duct itself, best diagnosed with associated blood vessel (400X).]]
 
F. [[File:6 AIH OBS 1.tif|Rare distorted rosettes with greenish brown strands of bile (left arrow) or bile plugs (right arrow) (400X).]]
 
Patient with SLE and obstructive jaundice that resolved with apparent passage of stone. A. Low power shows inflammation; portal triads, lobules, central veins cannot be distinguished. B. Trichrome shows central venous sclerosis (red arrowhead), periportal fibrosis (green arrowhead), & space of Disse collagenization (yellow arrowhead); juxtaposition of central vein & portal tract indicates collapse, no definite bridging was seen. C. Central vein is inflamed with a rare plasma cell (cyan arrowhead). D. Interface hepatitis with plasma cells (yellow arrows) and ballooned hepatocytes (red arrows). Lobule is disorganized. E. Proliferating bile ductules (blue arrows) with occasional neutrophils (fucsia arrows), indicative of obstruction, but not acute cholangitis, which requires inflamed bile duct itself, best diagnosed with associated blood vessel. F. Rare distorted rosettes with greenish brown strands of bile (left arrow) or bile plugs (right arrow).

==Autoimmune hepatitis-primary biliary cirrhosis overlap syndrome==
*Abbreviation ''AIH-PBC OS''.
===General===
Epidemiology:
*Rare.

Serology:<ref name=pmid19491855>{{Cite journal | last1 = Muratori | first1 = P. | last2 = Granito | first2 = A. | last3 = Pappas | first3 = G. | last4 = Pendino | first4 = GM. | last5 = Quarneti | first5 = C. | last6 = Cicola | first6 = R. | last7 = Menichella | first7 = R. | last8 = Ferri | first8 = S. | last9 = Cassani | first9 = F. | title = The serological profile of the autoimmune hepatitis/primary biliary cirrhosis overlap syndrome. | journal = Am J Gastroenterol | volume = 104 | issue = 6 | pages = 1420-5 | month = Jun | year = 2009 | doi = 10.1038/ajg.2009.126 | PMID = 19491855 }}</ref>
*AMA +ve.
*Anti-dsDNA +ve.

===Microscopic===
:See: ''[[autoimmune hepatitis]]'' and ''[[primary biliary cirrhosis]]''.
{|
[[File:1 AIH PBC 1 680x512px.tif|Expanded portal tracts with fuzzy edges (40X).]]
[[File:2 AIH PBC 1 680x512px.tif|Interface hepatitis with plasma cells (400X).]]
 
[[File:3 AIH PBC 1 680x512px.tif|Loose granuloma (400X).]]
[[File:4 AIH PBC 1 680x512px.tif|Damaged bile duct (400X).]]
|}

AIH/PBC overlap. AMA & ANA positive with Alkaline phosphatase > 2 upper limit of normal & one ALT > 5 times upper limit of normal. Expanded portal tracts with fuzzy edges (UL 40X). IInterface hepatitis with plasma cells (UR 400X). Loose granuloma (LL 400X). Damaged bile duct (LR 400X).

==Primary sclerosing cholangitis==
*Abbreviated ''PSC''.
{{Main|Primary sclerosing cholangitis}}

=Hereditary=
==Caroli disease==
===General===
*Genetic disease.
**Frequently associated with [[autosomal recessive polycystic kidney disease]] (ARPKD).<ref name=omim263200>{{OMIM|263200}}</ref>
**May be seen in isolation.<ref name=omim600643>{{OMIM|600643}}</ref>

Clinical:<ref name=pmid17461493>{{Cite journal | last1 = Yonem | first1 = O. | last2 = Bayraktar | first2 = Y. | title = Clinical characteristics of Caroli's syndrome. | journal = World J Gastroenterol | volume = 13 | issue = 13 | pages = 1934-7 | month = Apr | year = 2007 | doi = | PMID = 17461493 }}</ref>
*Recurrent [[cholangitis]].
*Recurrent [[cholelithiasis]].
*[[Cholangiocarcinoma]]<ref name=pmid17461492>{{Cite journal | last1 = Yonem | first1 = O. | last2 = Bayraktar | first2 = Y. | title = Clinical characteristics of Caroli's disease. | journal = World J Gastroenterol | volume = 13 | issue = 13 | pages = 1930-3 | month = Apr | year = 2007 | doi = | PMID = 17461492 }}</ref> - seen in ~7% of cases.<ref name=pmid15347876>{{Cite journal | last1 = Karim | first1 = AS. | title = Caroli's disease. | journal = Indian Pediatr | volume = 41 | issue = 8 | pages = 848-50 | month = Aug | year = 2004 | doi = | PMID = 15347876 }}</ref>

Note:
*''Caroli syndrome'' = Caroli disease + congenital hepatic fibrosis.<ref name=pmid15888616>{{Cite journal | last1 = Brancatelli | first1 = G. | last2 = Federle | first2 = MP. | last3 = Vilgrain | first3 = V. | last4 = Vullierme | first4 = MP. | last5 = Marin | first5 = D. | last6 = Lagalla | first6 = R. | title = Fibropolycystic liver disease: CT and MR imaging findings. | journal = Radiographics | volume = 25 | issue = 3 | pages = 659-70 | month = | year = | doi = 10.1148/rg.253045114 | PMID = 15888616 | URL = http://radiographics.rsna.org/content/25/3/659.long }}</ref>

===Gross===
*Dilated bile ducts.<ref name=omim263200/>

===Microscopic===
Features:<ref name=pmid17461493/>
*Dilated bile ducts.
*Periductal fibrosis. (???)
*+/-Fibrosis.

Image:
*[http://www.meddean.luc.edu/lumen/MedEd/orfpath/11-3-10.jpg Caroli disease (meddean.luc.edu)].<ref>URL: [http://www.meddean.luc.edu/lumen/MedEd/orfpath/develop.htm http://www.meddean.luc.edu/lumen/MedEd/orfpath/develop.htm]. Accessed on: 1 December 2011.</ref>

==Hereditary hemochromatosis==
:''For secondary causes see [[secondary hemochromatosis]]''.
{{Main|Hereditary hemochromatosis}}

==Wilson disease==
{{Main|Wilson's disease}}

==Alpha-1 antitrypsin deficiency==
*[[AKA]] ''alpha1-antiprotease inhibitor deficiency''.
{{Main|Alpha-1 antitrypsin deficiency }}

=Other=
==Budd-Chiari syndrome==
*[[AKA]] ''hepatic vein obstruction''.
===General===
*Hepatic outflow obstruction.

Clinical triad:<ref name=pmid21573256>{{Cite journal | last1 = Fox | first1 = MA. | last2 = Fox | first2 = JA. | last3 = Davies | first3 = MH. | title = Budd-Chiari syndrome--a review of the diagnosis and management. | journal = Acute Med | volume = 10 | issue = 1 | pages = 5-9 | month = | year = 2011 | doi = | PMID = 21573256 }}</ref>
*Ascites.
*Abdominal pain.
*Hepatomegaly.

Etiology:
*~50% have a [[myeloproliferative disease]].<ref name=pmid18814079>{{Cite journal | last1 = Plessier | first1 = A. | last2 = Valla | first2 = DC. | title = Budd-Chiari syndrome. | journal = Semin Liver Dis | volume = 28 | issue = 3 | pages = 259-69 | month = Aug | year = 2008 | doi = 10.1055/s-0028-1085094 | PMID = 18814079 }}</ref>
*May be due to mass effect from a tumour.

Clinical DDx:
*[[Hepatic veno-occlusive disease]].

===Microscopic===
Features:<ref name=pmid17569137>{{Cite journal | last1 = Aydinli | first1 = M. | last2 = Bayraktar | first2 = Y. | title = Budd-Chiari syndrome: etiology, pathogenesis and diagnosis. | journal = World J Gastroenterol | volume = 13 | issue = 19 | pages = 2693-6 | month = May | year = 2007 | doi = | PMID = 17569137 | url=http://www.wjgnet.com/1007-9327/full/v13/i19/2693.htm }}</ref>
*Sinusoidal dilation in zone III (congestion).
*+/-Hepatocyte drop-out.
*+/-Centrilobular fibrosis.

DDx congestion:
*Congestive heart failure ([[congestive hepatopathy]]).
*Constrictive pericarditis.

==Vanishing bile duct syndrome==
*[[AKA]] ''bile duct loss'', [[AKA]] ''ductopenia''.<ref name=pmid11521176/>
===General===
*Fatal.

DDx:<ref name=pmid18242505/>
*[[Primary biliary cirrhosis]].
*[[Primary sclerosing cholangitis]].
*[[GVHD]].<ref name=pmid7994249>{{Cite journal | last1 = Yeh | first1 = KH. | last2 = Hsieh | first2 = HC. | last3 = Tang | first3 = JL. | last4 = Lin | first4 = MT. | last5 = Yang | first5 = CH. | last6 = Chen | first6 = YC. | title = Severe isolated acute hepatic graft-versus-host disease with vanishing bile duct syndrome. | journal = Bone Marrow Transplant | volume = 14 | issue = 2 | pages = 319-21 | month = Aug | year = 1994 | doi = | PMID = 7994249 }}</ref>
*[[Drug-induced liver disease|Drugs]].<ref name=pmid11352118>{{Cite journal | last1 = Chitturi | first1 = S. | last2 = Farrell | first2 = GC. | title = Drug-induced cholestasis. | journal = Semin Gastrointest Dis | volume = 12 | issue = 2 | pages = 113-24 | month = Apr | year = 2001 | doi = | PMID = 11352118 }}</ref>
*Chronic rejection.<ref name=pmid11521176>{{Cite journal | last1 = Inomata | first1 = Y. | last2 = Tanaka | first2 = K. | title = Pathogenesis and treatment of bile duct loss after liver transplantation. | journal = J Hepatobiliary Pancreat Surg | volume = 8 | issue = 4 | pages = 316-22 | month = | year = 2001 | doi = 10.1007/s0053410080316 | PMID = 11521176 }}</ref>

===Microscopic===
Features:<ref name=pmid18242505>{{Cite journal | last1 = Reau | first1 = NS. | last2 = Jensen | first2 = DM. | title = Vanishing bile duct syndrome. | journal = Clin Liver Dis | volume = 12 | issue = 1 | pages = 203-17, x | month = Feb | year = 2008 | doi = 10.1016/j.cld.2007.11.007 | PMID = 18242505 }}</ref>
*Loss of intrahepatitic bile ducts - '''key feature'''.
*Cholestasis.

Note:
*May occur without fibrosis and inflammation; thus, can be easy to miss.

===IHC===
*[[CK7]] -ve.
**Marks bile ducts.

==Extrahepatic biliary obstruction==
{|
[[File:1 OBS 3 680x512px.tif|Sinusoidal dilatation, circular spaces of hepatocytes, small portal triads(40X).]]
[[File:2 OBS 3 680x512px.tif|Bile in hepatocytes about central vein & in plugs in canaliculi [yellow arrowhead] (400X).]]
 
[[File:3 OBS 3 680x512px.tif|Trichrome shows fibrosis about central vein (400X).]]
[[File:4 OBS 3 680x512px.tif|PAS with diastase shows portal triads with mild edema and chronic inflammation, without tortuous bile duct (400X).]]
|}
Early extrahepatic biliary obstruction, demonstrated radiographically, transient, with rise in bilirubin, alkaline phosphatase, and transaminases. Pure canalicular cholestasis near terminal hepatic venules also seen in acute hepatitis, drug reactions, benign recurrent cholestasis, pregnancy, sepsis, & lymphomas. Sinusoidal dilatation, circular spaces of hepatocytes, small portal triads(UL 40X). Bile in hepatocytes about central vein & in plugs in canaliculi [yellow arrowhead] (UR 400X). Trichrome shows fibrosis about central vein (LL 400X). PAS with diastase shows portal triads with mild edema and chronic inflammation, without tortuous bile duct (LR 400X).

{|
[[File:1 OBS 2 680x512px.tif|Expanded inflamed portal triads, swollen hepatocytes (40X)]]
[[File:2 OBS 2 680x512px.tif|Edematous stroma, proliferating ductules [yellow arrowheads], PAS-D macrophages [red arrowhead] (PAS with diastasse, 200X)]]
 
[[File:3 OBS 2 680x512px.tif|Disordered, often swollen hepatocytes,some with feathery degeneration (net like spaces in cytoplasm [blue arrowhead], rare Councilman body [green arrowhead] (400X)]]
[[File:4 OBS 2 1360x1024px.tif|Bile in hepatocytes [cyan arrrowhead] & in canaliculi [purple arrowheads]. Empty acinar spaces bounded by hepatocytes [orange arrowhead] (400X, higher pixel),]]
|}
Changes of extrahepatic biliary obstruction, months duration. Expanded inflamed portal triads, swollen hepatocytes (UL 40X). Edematous stroma, proliferating ductules [yellow arrowheads], PAS-D macrophages [red arrowhead] (UR PAS with diastasse, 200X). Disordered, often swollen hepatocytes,some with feathery degeneration (net like spaces in cytoplasm) [blue arrowhead], rare Councilman body [green arrowhead] (LL 400X). Bile in hepatocytes [cyan arrrowhead] & in canaliculi [purple arrowheads]. Empty acinar spaces bounded by hepatocytes [orange arrowhead] (LR 400X).
{|
[[File:1 Bd obs 4 680x512px.tif|Expanded, light colored portal triads (arrows)(20X).]]
[[File:2 Bd obs 4 680x512px.tif|Proliferating bile ductules (cyan arrows) with neutrophils (yellow arrows), not specific for acute cholangitis, of assistance with large bile duct obstruction (400X)..]]
 
[[File:3 Bd obs 4 680x512px.tif|Uninflamed interlobular duct (yellow arrow) with, accompanying blood vessel (red arrow) (400X)]]
[[File:4 Bd obs 4 680x512px.tif|Bile infarct with pyknotic nuclei (arrows)(400X).]]
 
[[File:5 Bd obs 4 680x512px.tif|Bile (arrow) in interlobular bile duct with disordered nuclei (400X).]]
[[File:6 Bd obs 4 680x512px.tif|Bile plugs in cannaliculi (red arrows), feathery degeneration producing foamy macrophage like hepatocytes (yellow arrows)(400X).]]
|}
Large bile duct obstruction. Expanded, light colored portal triads (arrows)(Row 1 Left 20X). Proliferating bile ductules (cyan arrows) with neutrophils (yellow arrows), not specific for acute cholangitis, of assistance with large bile duct obstruction (Row 1 Right 400X). Uninflamed interlobular duct (yellow arrow) with, accompanying blood vessel (red arrow) (Row 2 Left 400X). Bile infarct with pyknotic nuclei (arrows)(Row 2 Right 400X). Bile (arrow) in interlobular bile duct with disordered nuclei (Row 3 Left 400X). Bile plugs in cannaliculi (red arrows), feathery degeneration producing foamy macrophage-like hepatocytes (yellow arrows)(Row 3 Right 400X).

==Congestive hepatopathy==
===General===
*Liver failure due to (right) heart failure.
*AKA ''cardiac cirrhosis'' - a term used by clinicians.
**Generally, it does not satisfy pathologic criteria for cirrhosis.<ref>URL: [http://emedicine.medscape.com/article/151792-overview http://emedicine.medscape.com/article/151792-overview]. Accessed on: 17 June 2010.</ref>

===Gross===
*"Nutmeg" liver - yellow spotted appearance.

===Microscopic===
Features:<ref>URL: [http://emedicine.medscape.com/article/151792-diagnosis http://emedicine.medscape.com/article/151792-diagnosis]. Accessed on: 17 June 2010.</ref>
*Zone III atrophy.
*Portal venule (central vein) distension.
*Perisinusoidal fibrosis - progresses to centrilobular fibrosis and then diffuse fibrosis.
*Dilation of sinusoids in ''all'' zone III areas - '''key feature'''.<ref>Suggested by OA. September 2009.</ref>

DDx:
*[[Hemangioma of the liver]] - should be focal lesion.
Cardiac (congestive) hepatopathy, wherein outflow obstruction occurs secondary to backflow from a failing heart, and Budd Chiari syndrome, wherein obstruction of outflow occurs secondary to obstruction, usually thrombotic, have overlapping features, including sinusoidal dilation with emphasis upon the central vein, space of Disse erythrocytes, centrilobular inflammation, hemorrhage, bile ductules, and hemosiderin, and portal inflammation, fibrosis and bile ductular reaction. Centrilobular dropout/necrosis is more common in Budd Chiari syndrome, while peri-central venous and sinusoidal fibrosis are more common in cardiac hepatopathy. In end stage liver, fibrosis for cardiac hepatopathy comprises stellate centrizonal fibrous with haphazard spread, as opposed to the more frequent nodular cirrhosis in Budd-Chiari. Clinical findings are important to take into account, as cardiac failure is usually well known at the time of diagnosis as are the clinical predictors of Budd Chiari syndrome, prothrombotic states, myeloproliferative diseases, and oral contraceptive use. <ref name=pmid27681331 >{{cite journal |author=Gonzalez RS, Gilger MA, Huh WJ, Washington MK |title=The spectrum of histologic findings in hepatic outflow obstruction |journal= Arch Pathol Lab Med |volume=141 |issue= |pages=98 |year=2017 |pmid= 27681331 ||doi= 10.5858/arpa.2015-0388-OA |url=http http://www.archivesofpathology.org/doi/10.5858/arpa.2015-0388-OA?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%3dpubmed&code=coap-site }}</ref>
====Images====
<gallery>
Image:Congestive_hepatopathy_high_mag.jpg | Mild congestive hepatopathy. (WC) 
A.[[File:1 CEN NEC 1 680x512px.tif|PAS without diastase shows ovoids of necrosis {40X).]] 
B. [[File:2 CEN NEC 1 680x512px.tif|Necrosis with central vein [yellow arrowhead], inflammatory cells, residual Councilman body [green arrowhead], and hepatocyte with mitotic figure [red arrowhead] (400X).]]
 
C. [[File:3 CEN NEC 1 680x512px.tif|Trichrome highlights fibrosis about central vein [yellow arrowhead] & shows beginning scar formation [green arrowheads]. Note residual atrophic hepatocytes [blue arrowheads] (400X).]]
 
D. [[File:4 CEN NEC 1 680x512px.tif|Portal triads are largely unaffected (400X).]]
|} 
Centrilobular necrosis (seen in circulatory failure and with toxins/drugs). A. PAS without diastase shows ovoids of necrosis. B. Necrosis with central vein [yellow arrowhead], inflammatory cells, residual Councilman body [green arrowhead], and hepatocyte with mitotic figure [red arrowhead]. C. Trichrome highlights fibrosis about central vein [yellow arrowhead] & shows beginning scar formation [green arrowheads]. Note residual atrophic hepatocytes [blue arrowheads]. D. Portal triads are largely unaffected (LR 400X)
 
A. [[File:1 CHF 1 680x512px.tif|Dilated and undilated sinusoidal regions (40X).]]
 
B. [[File:2 CHF 1 680x512px.tif|Thrombi in sinusoids; glycogenated nuclei likely reflect patient’s diabetes mellitus (400X).]]
 
C. [[File:3 CHF 1 680x512px.tif|Dilated portal vein (400X).]]
 
D. [[File:4 CHF 1 680x512px.tif|Reticulin shows collapse (thick black lines) as well as a dilated portal vein (200X).]]
 
E. [[File:5 CHF 1 680x512px.tif|Trichrome shows space of Disse collagenization (pericellular fibrosis) (200X).]]
 
F. [[File:6 CHF 1 680x512px.tif|Trichrome shows periportal fibrosis; no bridging was seen (200X).]]

Patient with congestive heart failure and stage I fibrosis. A. Dilated and undilated sinusoidal regions. B. Thrombi in sinusoids; glycogenated nuclei likely reflect patient’s diabetes mellitus. C. Dilated portal vein. D. Reticulin shows black lines of bridging, too thick for collapse. E. Trichrome shows space of Disse collagenization (pericellular fibrosis). F. Trichrome shows bridge beginning off to right; when it is more than a mere spike, it is a bridge.

==Drug-induced liver disease==
*[[AKA]] ''drug-induced liver toxicity''.
{{Main|Drug-induced liver disease}}

==Focal nodular hyperplasia==
*Abbreviated ''FNH''.
{{Main|Focal nodular hyperplasia}}

==Nodular regenerative hyperplasia==
===General===
*Associated with renal transplants, [[bone marrow transplant]]s and [[vasculitides]].<ref name=Ref_PBoD922>{{Ref PBoD|922}}</ref>
*Can lead to [[portal hypertension]] and many of the associated complications.<ref name=pmid22554152>{{Cite journal | last1 = Bissonnette | first1 = J. | last2 = Généreux | first2 = A. | last3 = Côté | first3 = J. | last4 = Nguyen | first4 = B. | last5 = Perreault | first5 = P. | last6 = Bouchard | first6 = L. | last7 = Pomier-Layrargues | first7 = G. | title = Hepatic hemodynamics in 24 patients with nodular regenerative hyperplasia and symptomatic portal hypertension. | journal = J Gastroenterol Hepatol | volume = 27 | issue = 8 | pages = 1336-40 | month = Aug | year = 2012 | doi = 10.1111/j.1440-1746.2012.07168.x | PMID = 22554152 }}
</ref>

====Etiology====
*Arterial hypervascularity secondary to loss of hepatic vein radicles (loss of central venule in hepatic lobule).<ref name=Ref_PBoD922>{{Ref PBoD|922}}</ref>

ASIDE: radicle = ramulus - smallest branch or vessel or nerve.<ref name=Dorlands2>Dorland's Medical Dictionary. 30th Ed.</ref>

===Gross===
*Diffuse nodularity - whole liver.

===Microscopic===
Features:<ref name=Ref_PBoD922>{{Ref PBoD|922}}</ref>
*"Plump" hepatocytes surrounded by atrophic ones.
*No fibrosis.

==Sinuosoidal obstruction syndrome==
*May be referred to as ''Hepatic veno-occlusive disease''.<ref name=pmid11928077>{{Cite journal | last1 = DeLeve | first1 = LD. | last2 = Shulman | first2 = HM. | last3 = McDonald | first3 = GB. | title = Toxic injury to hepatic sinusoids: sinusoidal obstruction syndrome (veno-occlusive disease). | journal = Semin Liver Dis | volume = 22 | issue = 1 | pages = 27-42 | month = Feb | year = 2002 | doi = 10.1055/s-2002-23204 | PMID = 11928077 }}.</ref>
===General===
*Term for obstruction due to toxicity from a chemotherapeutic agent.<ref name=pmid16393276>{{Cite journal | last1 = Helmy | first1 = A. | title = Review article: updates in the pathogenesis and therapy of hepatic sinusoidal obstruction syndrome. | journal = Aliment Pharmacol Ther | volume = 23 | issue = 1 | pages = 11-25 | month = Jan | year = 2006 | doi = 10.1111/j.1365-2036.2006.02742.x | PMID = 16393276 }}</ref><ref name=pmid17569137>{{Cite journal | last1 = Aydinli | first1 = M. | last2 = Bayraktar | first2 = Y. | title = Budd-Chiari syndrome: etiology, pathogenesis and diagnosis. | journal = World J Gastroenterol | volume = 13 | issue = 19 | pages = 2693-6 | month = May | year = 2007 | doi = | PMID = 17569137 | url=http://www.wjgnet.com/1007-9327/full/v13/i19/2693.htm }}</ref>

Clinical DDx:
*[[Budd-Chiari syndrome]].

===Microscopic===
Features:<ref name=pmid17569137>{{Cite journal | last1 = Aydinli | first1 = M. | last2 = Bayraktar | first2 = Y. | title = Budd-Chiari syndrome: etiology, pathogenesis and diagnosis. | journal = World J Gastroenterol | volume = 13 | issue = 19 | pages = 2693-6 | month = May | year = 2007 | doi = | PMID = 17569137 | url=http://www.wjgnet.com/1007-9327/full/v13/i19/2693.htm }}</ref>
*Subendothelial swelling in hepatic venules.

Negatives:
*No thrombosis.

==Ascending Cholangitis (Acute Cholangitis)==
===General===
*Term for infection of bile ducts, usually due to obstruction

Clinical DDx:

===Microscopic===
====Images====

A. [[File:1 asc chol 1 680x512px.tif|Rounded, clear (edematous) portal tracts (arrows) separated by hepatocytes with dilated sinusoids (Row 1 Left 40X).]]
 
B. [[File:2 asc chol 1 680x512px.tif|Neutrophils about hepatocytes (arrows) have spilled into the lobule from a portal tract (Row 1 Right 200X).]]
 
C. [[File:3 asc chol 1 680x512px.tif|Proliferated bile ductules (arrows) bearing neutrophils within epithelium and lumens are features of obstruction that should prompt a search for interlobular ducts with acute inflammation (Row 2 Left 400X).]]
 
D. [[File:4 asc chol 1 680x512px.tif|The epithelium of the ducts can be severely degenerated. Neutrophils (cyan arrows) invade epithelium of an interlobular duct that are recognizable mainly as a circle of rounded nuclei; the associated arteriole (red arrow) should be identified to ensure an interlobular duct is being evaluated. Note the proliferated bile ductules (blue arrows) (Row 2 Right 400X).]]
 
E. [[File:5 asc chol 1 680x512px.tif|A PAS without diastase stain colors the arteriole (blue arrow), as well as the rim of the interlobular duct within which lies a neutrophil (cyan arrow) (Row 2 Right 400X). .]]
 
F. [[File:6 asc chol 1 680x512px.tif|A PAS with diastase stain colors the arteriole (red arrow), as well as the rim of the interlobular duct within which lies a neutrophil (cyan arrow) (Row 1 Right 400X)]]
 
Acute cholangitis in a patient with multiple bile duct procedures. After the biopsy, removal of bile duct stones released pus. A. Rounded, clear (edematous) portal tracts (arrows) separated by hepatocytes with dilated sinusoids. B. Neutrophils about hepatocytes (arrows) have spilled into the lobule from a portal tract. C, Proliferated bile ductules (arrows) bearing neutrophils within epithelium and lumens are features of obstruction that should prompt a search for interlobular ducts with acute inflammation. D. The epithelium of the ducts can be severely degenerated. Neutrophils (cyan arrows) invade epithelium of an interlobular duct that are recognizable mainly as a circle of rounded nuclei; the associated arteriole (red arrow) should be identified to ensure an interlobular duct is being evaluated. Note the proliferated bile ductules (blue arrows). E. A PAS without diastase stain colors the arteriole (blue arrow), as well as the rim of the interlobular duct within which lies a neutrophil (cyan arrow). F. A PAS with diastase stain colors the arteriole (red arrow), as well as the rim of the interlobular duct within which lies a neutrophil (cyan arrow).

A.[[File:1 Sep Acu Cho 1 680x512px.tif|Low power shows variably sized inflamed portal tracts (40X)]]
 
B. [[File:2 Sep Acu Cho 1 680x512px.tif|Trichrome shows dilated sinusoids and space of Disse collagenization (200X)]]
 
C. [[File:3 Sep Acu Cho 1 680x512px.tif|Inflammatory focus with macrophages and neutrophils (400X).]]
 
D. [[File:4 Sep Acu Cho 1 680x512px.tif|PAS with diastase shows proliferated bile ductules at edge of triad with neutrophils, which should not be used to make a definite diagnosis of acute cholangitis (400X).]]
 
E. [[File:5 Sep Acu Cho 1 680x512px.tif|PAS without diastase showing acutely inflamed bile duct, with accompanying blood vessel of similar size, diagnostic of acute cholangitis (400X).]]
 
F. [[File:6 Sep Acu Cho 1 680x512px.tif|PAS with diastase showing neutrophil in bille duct lumen, diagnostic of acute cholangitis (400X).]]
 
Patient with sepsis and acute cholangitis. A. Low power shows variably sized inflamed portal tracts. B. Trichrome shows dilated sinusoids and space of Disse collagenization. C. Inflammatory focus with macrophages and neutrophils. D. PAS with diastase shows proliferated bile ductules at edge of triad with neutrophils, which should not be used to make a definite diagnosis of acute cholangitis. E. PAS without diastase showing acutely inflamed bile duct, with accompanying blood vessel of similar size, diagnostic of acute cholangitis. F. PAS with diastase showing neutrophil in bille duct lumen, diagnostic of acute cholangitis.

==Polycystic kidney disease and the liver==
{{Main|Cystic kidney disease}}
===General===
Complications of PKD in the liver:<ref>{{Ref MacSween|174-5}}</ref>
#Infected cyst.
#Cholangiocarcinoma.
#Cholestasis/obstruction due to duct compression.<ref>URL: [http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=9184868 http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=9184868]. Accessed on: 23 September 2009.</ref>

Cysts:
*Cysts in the liver, like the kidney, are thought to enlarge with age.

===Microscopic===
Features:<ref>{{Ref MacSween|176}}</ref>
*''Von Meyenburg complexes'' ([[bile duct hamartoma]]):
**Cluster of dilated ducts with "altered" bile.
**Surrounded by collagenous stroma.
**Separate from the portal areas.<ref>Meyenburg complex. Stedman's Medical Dictionary. 27th Ed.</reF>

Images:
*[http://commons.wikimedia.org/wiki/File:Von_Meyenburg_complex_low_mag.jpg Von Meyenburg complex - bile duct hamartoma (WC)].
*[http://commons.wikimedia.org/wiki/File:Bile_duct_hamartoma_intermed_mag.jpg Bile duct hamartoma (WC)].

Notes:
*Appearance on ultrasound<ref name=pmid17287178>Bile duct hamartomas--the von Meyenburg complex. Salles VJ, Marotta A, Netto JM, Speranzini MB, Martins MR. Hepatobiliary Pancreat Dis Int. 2007 Feb;6(1):108-9. PMID 17287178.</ref> and CT (hypodense)<ref name=pmid19294869>[The von Meyenburg complex] Schwab SA, Bautz W, Uder M, Kuefner MA. Rontgenpraxis. 2008;56(6):241-4. German. PMID 19294869.</ref> - similar to metastases.

==Peliosis hepatis==
===General===
*Associated with:
**Infections.
**Malignancy.
**Other stuff.
*Rarely biopsied.

===Microscopic===
Features:
*Cyst lined by endothelium.
**Usu. incomplete.
*Blood.
{|
[[File:1 PEL 1 680x512px.tif|Hemorrhage at left end, dilated sinusoids elsewhere (20X).]]
[[File:2 PEL 1 680x512px.tif|Ramifying dilated sinusoidal spaces (100X).]]
 
[[File:3 PEL 1 680x512px.tif|PAS with diastase shows flat lining (400X).]]
[[File:4 PEL 1 680x512px.tif|Necrotic hepatocytes in cords, presumably due to pressure (400X).]]
|}
Peliosis hepatis. Hemorrhage at left end, dilated sinusoids elsewhere (UL 20X). Ramifying dilated sinusoidal spaces (UR 100X). PAS with diastase shows flat lining (LL 400X). Necrotic hepatocytes in cords, presumably due to pressure (LR 400X).

==Total parenteral nutrition==
*Abbreviated ''TPN''.

===General===
*Indication: short gut syndrome, others.

===Microscopic===
Variable - may range from: steatosis, steatohepatitis, cholestasis, fibrosis and cirrhosis.<ref name=pmid16766237>{{cite journal |author=Guglielmi FW, Boggio-Bertinet D, Federico A, ''et al.'' |title=Total parenteral nutrition-related gastroenterological complications |journal=Dig Liver Dis |volume=38 |issue=9 |pages=623–42 |year=2006 |month=September |pmid=16766237 |doi=10.1016/j.dld.2006.04.002 |url=}}</ref>

Features (classic):<ref>{{Cite journal | last1 = Li | first1 = SJ. | last2 = Nussbaum | first2 = MS. | last3 = McFadden | first3 = DW. | last4 = Gapen | first4 = CL. | last5 = Dayal | first5 = R. | last6 = Fischer | first6 = JE. | title = Addition of glucagon to total parenteral nutrition (TPN) prevents hepatic steatosis in rats. | journal = Surgery | volume = 104 | issue = 2 | pages = 350-7 | month = Aug | year = 1988 | doi = | PMID = 3135627 }}</ref><ref>{{Cite journal | last1 = Stanko | first1 = RT. | last2 = Nathan | first2 = G. | last3 = Mendelow | first3 = H. | last4 = Adibi | first4 = SA. | title = Development of hepatic cholestasis and fibrosis in patients with massive loss of intestine supported by prolonged parenteral nutrition. | journal = Gastroenterology | volume = 92 | issue = 1 | pages = 197-202 | month = Jan | year = 1987 | doi = | PMID = 3096806 }}
</ref>
*[[Steatosis]] (periportal) - early.
*Cholestasis - late.

==Giant cell hepatitis==
*[[AKA]] ''neonatal giant cell hepatitis''.

:See: ''[[Giant cell hepatitis]]''.

==Hepatic amyloidosis==
{{Main|Amyloidosis}}
*[[AKA]] ''liver amyloidosis''.
*[[AKA]] ''amyloidosis of the liver''.
===General===
*Diffuse abundant amyloid within the space of Disse is associated with [[portal hypertension]].<ref name=pmid1864548>{{Cite journal | last1 = Bion | first1 = E. | last2 = Brenard | first2 = R. | last3 = Pariente | first3 = EA. | last4 = Lebrec | first4 = D. | last5 = Degott | first5 = C. | last6 = Maitre | first6 = F. | last7 = Benhamou | first7 = JP. | title = Sinusoidal portal hypertension in hepatic amyloidosis. | journal = Gut | volume = 32 | issue = 2 | pages = 227-30 | month = Feb | year = 1991 | doi = | PMID = 1864548 | PMC = 1378815 | URL = http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1378815/?tool=pubmed }}</ref>

===Microscopic===
Features:
*Amorphous extracellular pink stuff on H&E - see ''[[amyloid]]'' article.

DDx:
*[[Fibrolamellar hepatocellular carcinoma]].

====Images====
<gallery>
Image:Hepatic_amyloidosis_-_low_mag.jpg | Amyloidosis of the liver - low mag. (WC)
Image:Hepatic_amyloidosis_-_intermed_mag.jpg | Amyloidosis of the liver - intermed. mag. (WC)
Image:Hepatic_amyloidosis_-_high_mag.jpg | Amyloidosis of the liver - high mag. (WC)
Image:Hepatic_amyloidosis_-_very_high_mag.jpg | Amyloidosis of the liver - very high mag. (WC)
</gallery>
{|
[[File:1 AMY 1 680x512px.tif|Amorphous material replaces hepatic parenchyma [4X]]]
[[File:2 AMY 1 680x512px.tif|Material barely stains blue on trichrome [10X]]]
 
[[File:3 AMY 1 680x512px.tif|Material stains red on unpolarized Congo Red [40X]]]
[[File:4 AMY 1 680x512px.tif|Material stains apple green on polarized Congo Red [40X]]]
|}
Amyloidosis. Amorphous material replaces hepatic parenchyma [UL 4X]. Material barely stains blue on trichrome [UR 10X] Material stains red on unpolarized Congo Red [LL 40X] Material stains apple green on polarized Congo Red [LR 40X]

===Stains===
*[[Congo red]] +ve.

==Fulminant hepatic necrosis==
===General===
Etiology:
*Viral, i.e. [[Hepatitis A]], [[Hepatitis B]]; [[Hepatitis C]] - extremely rare.
*Trauma.
*Shock.

===Microscopic===
{|
[[File:1 Necrosis 2 680x512px.tif| Submassive hepatic necrosis.]]
[[File:2 Necrosis 2 680x512px.tif| Submassive hepatic necrosis.]]
 
[[File:3 Necrosis 2 680x512px.tif| Submassive hepatic necrosis.]]
[[File:4 Necrosis 2 680x512px.tif| Submassive hepatic necrosis.]]
 
[[File:5 Necrosis 2 680x512px.tif| Submassive hepatic necrosis.]]
[[File:6 Necrosis 2 680x512px.tif| Submassive hepatic necrosis.]]
|}
Submassive hepatic necrosis. Patient had transaminases in the thousands that rapidly dropped to normal. Pink preserved parenchyma strews empty necrotic spaces (Row 1 Left 20X). Focus of necrosis with no apparent hepatocytes macrophages abuts apparently normal liver (Row 1 Right 200X). Iron stain shows the macrophages bear hemosiderin (Row 2 Left 200X). Reticulin stain highlights the recently dead liver cells (Row 2 Right 200X). Reticulin stain shows a necrotic bridge forming; the multiple small black circles preclude diagnosis of a fibrous bridge (Row 3 Left 200X). Trichrome shows the necrotic bridge (“collapse”) lacks much collagen deposition, as would be expected for bridging fibrosis (Row 3 Right 200X).

Features:
*Hepatocyte [[necrosis]].
*Bile duct proliferation.

DDx:
*[[Cholangiocarcinoma]].
*[[Angiosarcoma]].

==Secondary hemochromatosis==
:''For the hereditary one see [[hereditary hemochromatosis]]''.
===General===
*Iron overload secondary to blood transfusions for hereditary or acquired anemia.<ref name=pmid19727383/>
**Primary hemochromatosis due to a defect in iron processing - called ''[[hereditary hemochromatosis]]''.
*Imaging considered the best test, as iron deposition is patchy.<ref name=pmid19727383/>

Selected hereditary causes:<ref name=pmid19727383>{{Cite journal | last1 = Gattermann | first1 = N. | title = The treatment of secondary hemochromatosis. | journal = Dtsch Arztebl Int | volume = 106 | issue = 30 | pages = 499-504, I | month = Jul | year = 2009 | doi = 10.3238/arztebl.2009.0499 | PMID = 19727383 | PMC = 2735704 | URL = http://www.ncbi.nlm.nih.gov.myaccess.library.utoronto.ca/pmc/articles/PMC2735704/?tool=pubmed}}</ref>
*Thalassemia.
*[[Sickle cell anemia]].
*Hereditary sideroblastic anemia.

Selected acquired causes:<ref name=pmid19727383/>
*[[Myelodysplastic syndromes]]
*Myelofibrosis
*Aplastic anemia, intractable.

===Microscopic===
:See ''[[hereditary hemochromatosis]]''.

==Hepatic sarcoidosis==
{{Main|Hepatic sarcoidosis}}
==Overlapping Disorders==

[[File:1 Mixed Disorder 1 680x512px.tif|Changes of steatohepatitis and interface hepatitis, with granuloma. Patient with diabetes was ANA, AMA, HCV, HBV negative, without drugs known to produce granulomas or interface hepatitis. This may be a case of AMA negative primary biliary cirrhosis, but studies to determine that with certainty were not performed.]]
[[File:2 Mixed Disorder 1 680x512px.tif|Changes of steatohepatitis and interface hepatitis, with granuloma. Patient with diabetes was ANA, AMA, HCV, HBV negative, without drugs known to produce granulomas or interface hepatitis. This may be a case of AMA negative primary biliary cirrhosis, but studies to determine that with certainty were not performed.]]
[[File:3 Mixed Disorder 1 680x512px.tif|Changes of steatohepatitis and interface hepatitis, with granuloma. Patient with diabetes was ANA, AMA, HCV, HBV negative, without drugs known to produce granulomas or interface hepatitis. This may be a case of AMA negative primary biliary cirrhosis, but studies to determine that with certainty were not performed.]]
[[File:4 Mixed Disorder 1 680x512px.tif|Changes of steatohepatitis and interface hepatitis, with granuloma. Patient with diabetes was ANA, AMA, HCV, HBV negative, without drugs known to produce granulomas or interface hepatitis. This may be a case of AMA negative primary biliary cirrhosis, but studies to determine that with certainty were not performed.]]
[[File:5 Mixed Disorder 1 680x512px.tif|Changes of steatohepatitis and interface hepatitis, with granuloma. Patient with diabetes was ANA, AMA, HCV, HBV negative, without drugs known to produce granulomas or interface hepatitis. This may be a case of AMA negative primary biliary cirrhosis, but studies to determine that with certainty were not performed.]]
[[File:6 Mixed Disorder 1 680x512px.tif|Changes of steatohepatitis and interface hepatitis, with granuloma. Patient with diabetes was ANA, AMA, HCV, HBV negative, without drugs known to produce granulomas or interface hepatitis. This may be a case of AMA negative primary biliary cirrhosis, but studies to determine that with certainty were not performed.]] 
Changes of steatohepatitis and interface hepatitis, with granuloma. Patient with diabetes was ANA, AMA, HCV, HBV negative, without drugs known to produce granulomas or interface hepatitis. This may be a case of AMA negative primary biliary cirrhosis, but studies to determine that with certainty were not performed. A. Low power shows hepatocytes afflicted by steatosis and an inflamed portal tract. B. In a region of fatty change lie cytoplasmic tufts of ballooning degeneration (green arrows) and a lipogranuloma (black arrow). C. At the portal-hepatocyte junction lies interface hepatitis (black arrows), as well as extension of inflammation into the lobule (green arrows). D. Red hepatocytes bounded by inflammation denote piecemeal necrosis [PAS without diastase]. E. Giant cells intermixed with lymphocytes prove a portal granuloma [PAS without diastase]. F. A blue fibrous bridge extends from a triad [Trichrome].

[[File:4 95599552608917 sl 1.png|Acute obstructive changes and changes of recurrent acute injury]]
[[File:4 95599552608917 sl 2.png|Acute obstructive changes and changes of recurrent acute injury]]
[[File:4 95599552608917 sl 3.png|Acute obstructive changes and changes of recurrent acute injury]]
[[File:4 95599552608917 sl 4.png|Acute obstructive changes and changes of recurrent acute injury]]
[[File:4 95599552608917 sl 5.png|Acute obstructive changes and changes of recurrent acute injury]]
[[File:4 95599552608917 sl 6.png|Acute obstructive changes and changes of recurrent acute injury]]
[[File:4 95599552608917 sl 7.png|Acute obstructive changes and changes of recurrent acute injury]] 
Acute obstructive changes and changes of recurrent injury in 46 yo man with Clostridium perfringens positive blood culture, an ERCP that showed duodenal compression by the pancreas with resultant bile duct dilatation. The patient had had and continued to have multiple bouts of acute pancreatitis. At the time of biopsy, decreased platelet count/hemoglobin/albumin, elevated lipase/amylase/PT/PTT, normal alkaline phosphatase, bilirubin, AST/ALT, AMA, hepatitis virus serology, ANA. A. Fragment biopsy shows inflamed triads and bridges. B. Trichrome shows bridges without nodules, evidence of prior injury; the patient subsequently developed multiple episodes of pancreatitis. C. Reticulin shows piecemeal necrosis, with black lines bounding individual hepatocytes at interface (arrows). D. Collapse is shown by closly approximated thick black lines; one cannot call portal-central collapse without seeing a central vein. Note on this and the other reticulin image that regeneration, two cell thick cords, is not prominent. E. PAS D of two portal triads, far nearer than normal, both expanded. Note increased number of ducts/ductules (red arrows), neutrophils, and PAS-D macrophages. F. PAS D shows collapse extending from a triad to a portion of a lobule with steatosis. No feathery degeneration or bile duct plugs were seen. Neither were foci of spotty necrosis or abscess seen. G. Other triads, again edematous, showed more of a chronic inflammatory response, with occasional plasma cells (black arrows). Also present are neutrophils (red arrows). The bile duct (grey arrow) near the artery (brown arrow) shows mildly disturbed nuclei. Note early proliferated bile ductules (cyan arrows).

[[File:6 17281676469188 sl 1.png| Hepatitis B virus with steatohepatitis]]
[[File:6 17281676469188 sl 2.png| Hepatitis B virus with steatohepatitis]]
[[File:6 17281676469188 sl 3.png| Hepatitis B virus with steatohepatitis]]
[[File:6 17281676469188 sl 4.png| Hepatitis B virus with steatohepatitis]]
[[File:6 17281676469188 sl 5.png| Hepatitis B virus with steatohepatitis]]
[[File:6 17281676469188 sl 6.png| Hepatitis B virus with steatohepatitis]] 
Hepatitis B virus with steatohepatitis in a 36 year old man with hepatitis B surface antigen and hepatitis Be antigen positivity, Hepatitis be QTPC of 1750 cop/mL, an occasionally mildly elevated (42) ALT, and normal glucose, alkaline phosphatase, bilirubin, and other transaminases. He had a history of alcohol abuse, which became controlled. A. Triads show scant inflammation without definite interface hepatitis. About one-fourth of the lobule, not pan-acinar, is afflicted by steatosis. B. Occasional tufts are seen (arrow), indicating focal ballooning sufficient for a diagnosis of steatohepatitis. C. Glycogenated nuclei (black arrows) and hepatocytes with feathery degeneration (red arrows) are seen. D. Very rare foci of spotty necrosis were seen. E. Apart from this triad and the one in the trichrome stain in F, which had moderate inflammation comprising lymphocytes and macrophages, all triads were small, most without any inflammation at all. Neither collapse nor piecemeal necrosis were seen on reticulin stain. F. Trichrome stain showed only portal fibrosis. The interhepatocyte fibrosis required for brunt fibrosis stage I was not seen. Hence, one would grade this as follows: A) Chronic hepatitis (history of hepatitis B), Metavir activity index 1, Piecemeal necrosis 0, Lobular necrosis 1, Metavir fibrosis stage 1, B) Steatohepaitits, Brunt necroinflammatory grade 1, Brunt fibrosis stage 0.

=See also=
*[[Pancreas]].
*[[Gastrointestinal pathology]].
*[[Liver neoplasms]].
*[[Liver]].

=References=
{{reflist|2}}

[[Category:Gastrointestinal pathology]]
[[Category:Liver pathology]]
[[Category:Medical liver disease]]

Medical liver disease

2017-02-10T18:38:05Z

Mitchell: /* Images */ altered image notation

[[Image:Ground glass hepatocytes high mag cropped 2.jpg|thumb|right|[[Micrograph]] showing ground glass hepatocytes, as seen in chronic [[hepatitis B]]. [[H&E stain]].]]
This article deals with '''medical [[liver]] disease'''. An introduction to the liver and approach is found in the ''[[liver]]'' article.

Every differential in liver pathology has "drugs"<ref>{{Ref PCPBoD8|448}}</ref> -- if it isn't clearly malignancy.

Liver neoplasms are dealt with in the ''[[liver neoplasms]]'' article.

Medical liver biopsies are often non-specific, as the liver has the same appearance for many mechanisms of injury, especially when the injury is marked. The clinical history, serology and imaging are essential for proper interpretations in this domain of pathology.

=Review of liver blood work=
===Inflammation activity===
*ALT.
*AST.

===Cholestatic markers===
*ALP.
*GGT - used to assess whether the ALP is an "honest" value, elevated in cirrhosis.

===Cirrhosis/decompensation===
*PLT - low is suggestive of dysfunction.
*INR - high is bad, unless anticoagulated.

===Other===
*Bilirubin.
**Direct (AKA conjugated).
**Indirect (AKA unconjugated).

A short DDx of elevated:<ref>{{Ref PCPBoD8|441}}</ref>
*Indirect:
**[[Gilbert syndrome]].
**Crigler-Najjar syndrome type 1.
**Crigler-Najjar syndrome type 2.
*Direct:
**Rotor syndrome.
**Dubin-Johnson syndomre.

===Viral hepatitis===
*HBV DNA.
*HCV RNA.
*HBs Ag, HBs Ab, HBe Ag, HBe Ab.
*HCV Ab.

Others:
*[[Epstein-Barr virus]] (EBV).
*[[Cytomegalovirus]] (CMV) - especially in the immune incompetent.

====Hepatitis B====
Meaning & utility of the various [[Hepatitis B]] tests:<ref>URL: [http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/hepatology/hepatitis-B/ http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/hepatology/hepatitis-B/]. Accessed on: 16 May 2011.</ref><ref name=lto_hepb>URL: [http://www.labtestsonline.org/understanding/analytes/hepatitis_b/test.html http://www.labtestsonline.org/understanding/analytes/hepatitis_b/test.html]. Accessed on: 16 May 2011.</ref>
{| class="wikitable sortable" border="1"
! Test name
! Location
! Positive test
! Negative test
! Usual question
|-
| HBs Ag||Surface||Virus active||No active infection||Active infection?
|-
| HBs Ab||Surface||Exposed OR vaccinated||No exposure OR no vaccine OR loss of Ab||Immunization status?
|-
| HBe Ag||Virus core||Infect. w/ viral replication||No active infection||Active infect. w/ viral replication?
|-
| HBe Ab||Virus core||Exposed to virus||Infect. w/o antibody response OR not exposed||Immune response to infection?
|-
| HBV DNA||-||Active||Not active/no exposure||Viral load/how active?
|-
| HBc Ab||Virus core||Virus active/previous exposure||No exposure||Early active infection?
|}
Notes:
*''HBc Ab'' may test for acute (IgM) or chronic infection - dependent on specific antibody test; it is often used to look for early infection.<ref name=lto_hepb>URL: [http://www.labtestsonline.org/understanding/analytes/hepatitis_b/test.html http://www.labtestsonline.org/understanding/analytes/hepatitis_b/test.html]. Accessed on: 16 May 2011.</ref>
*''Carriers of hepatitis B'': HBs Ag +ve, HBs Ab -ve, HBc Ag -ve, HBc Ab +ve, HBe Ag -ve, HBe Ab +ve.<ref>URL: [http://labtestsonline.org/understanding/analytes/hepatitis-b/tab/test http://labtestsonline.org/understanding/analytes/hepatitis-b/tab/test]. Accessed on: 3 May 2012.</ref>

===Markers for rare liver diseases===
*Ceruloplasm - low think ''[[Wilson's disease]]''; typical value for Wilson's ~ 0.12 g/L.
**<0.20 g/L is a criteria for Wilson's disease.<ref name=pmid18556333>Diagnostic accuracy of serum ceruloplasmin in Wilson disease: determination of sensitivity and specificity by ROC curve analysis among ATP7B-genotyped subjects. Mak CM, Lam CW, Tam S. Clin Chem. 2008 Aug;54(8):1356-62. Epub 2008 Jun 12. PMID 18556333. URL: [http://www.clinchem.org/cgi/reprint/54/8/1356.pdf http://www.clinchem.org/cgi/reprint/54/8/1356.pdf]. Accessed on: 28 September 2009.</ref>
*Alpha-1 antitrypsin - if low think ''deficiency''.

===Hemosiderosis===
*Ferritin - high.
*Iron saturation - high.

Causes:
*Hemochromatosis.
*Hemolysis, chronic.
*Cirrhosis.

=Medical imaging=
Blood flow:<ref>URL: [http://insidesurgery.com/2010/12/hepatopedal-hepatofugal-flow/ http://insidesurgery.com/2010/12/hepatopedal-hepatofugal-flow/]. Accessed on: 2 December 2011.</ref>
*Hepatopedal flow = normal portal vein flow.
*Hepatofugal flow = reversed portal vein flow.

==Interventional measurements==
Wedged to free hepatic venous pressure:<ref name=pmid1864548>{{Cite journal | last1 = Bion | first1 = E. | last2 = Brenard | first2 = R. | last3 = Pariente | first3 = EA. | last4 = Lebrec | first4 = D. | last5 = Degott | first5 = C. | last6 = Maitre | first6 = F. | last7 = Benhamou | first7 = JP. | title = Sinusoidal portal hypertension in hepatic amyloidosis. | journal = Gut | volume = 32 | issue = 2 | pages = 227-30 | month = Feb | year = 1991 | doi = | PMID = 1864548 | PMC = 1378815 | URL = http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1378815/?tool=pubmed }}</ref>
*Normal = 1-4 mmHg.
**Elevated in [[portal hypertension]].

=Liver biopsy=
==Medical liver biopsy adequacy==
Liver biopsy specimens should be:<ref>{{Ref MacSween|418}}</ref>
*2.0 cm in length and contain 11-15 portal tracts,
*The core should be deeper than 1.0 cm from the liver capsule; specimens close to the capsule may lead to over grading of fibrosis.

==Reporting==
{{Main|Pathology reports}}
<pre>
Specimen, procedure:
- Diagnosis.
</pre>
The diagnosis usually contains grading and staging information, e.g. ''activity 2 /4, Laennec fibrosis stage 1 /4''.

In the context of medical liver disease:
*Grade = inflammation/activity.
*Stage = severity of fibrosis/architectural changes.

Notes:
*The term "acute" is infrequently used in liver pathology.
*In the liver: neutrophils ''is not'' acute -- unlike most elsewhere in the body.<ref>OA. September 2009.</ref>

===A microscopic checklist===
<pre>
Size of biopsy: Adequate
Fragmentation: Absent
Fibrosis: Stage 2-3/4, mostly stage 2
Fibrous septa: Present
Septa with curved contours: Present – focally only
Large droplet steatosis (% of hepatocytes): Present, moderate 60%
Ballooning of hepatocytes: Present, rare
Mallory-Denk bodies: Present, rare
Portal inflammation: Present
Interface activity: Minimal (0-1/4)
Lobular necroinflammation: Minimal
Ducts: Present in normal numbers
Duct injury: Absent
Ductular reaction: Absent
Cholestasis: Absent
Terminal hepatic venules: Present
Iron stain: Absent
Ground glass cells with routine stains: Absent
PASD for alpha-1 antitrypsin droplets: Negative
</pre>

=Viral hepatitis=
These are common. The diagnoses are based on serology. The serology is covered in the ''[[Liver_pathology#Viral_hepatitis|viral hepatitis]]'' section in the ''[[liver pathology]]'' article.

Typically classified as:<ref name=pmid8048409>{{Cite journal | title = Terminology of chronic hepatitis, hepatic allograft rejection, and nodular lesions of the liver: summary of recommendations developed by an international working party, supported by the World Congresses of Gastroenterology, Los Angeles, 1994. | journal = Am J Gastroenterol | volume = 89 | issue = 8 Suppl | pages = S177-81 | month = Aug | year = 1994 | doi = | PMID = 8048409 }}</ref><ref>URL: [http://familydoctor.org/familydoctor/en/diseases-conditions/hepatitis-b.html http://familydoctor.org/familydoctor/en/diseases-conditions/hepatitis-b.html]. Accessed on: 2 May 2012.</ref>
#Acute < 6 months duration.
#Chronic > 6 months duration.

==Hepatitis A==
*Infection is self-limited, i.e. not persistent.
**May present as ''[[fulminant hepatic necrosis]]''.
*Usually asymptomatic in children.<ref name=pmid20068336>{{cite journal |author=Jeong SH, Lee HS |title=Hepatitis A: clinical manifestations and management |journal=Intervirology |volume=53 |issue=1 |pages=15–9 |year=2010 |pmid=20068336 |doi=10.1159/000252779 |url=}}</ref>
*Serology is diagnostic.

==Hepatitis B==
:''Hepatitis B virus'', abbreviated ''HBV'', redirects here.
{{Main|Hepatitis B}}

==Hepatitis C==
{{Main|Hepatitis C}}

=Other infections=
*Hydatid disease (Hydatid cyst).
*Ascaris.
*Fasciola

==Hydatid disease==
*[[AKA]] ''hydatid cyst''.
===General===
*Etiology: ''[[Echinococcus]]''.

===Microscopic===
Features:
*Laminated wall +/- calcification.<ref name=Ref_PBPoD8_448>{{Ref PCPBoD8|448}}</ref>
*Organisms -- see ''[[Echinococcus]]''.

====Images====
<gallery>
Image:Liver_cyst_wall_-_intermed_mag.jpg | Liver cyst wall - intermed. mag. (WC)
Image:Liver_cyst_wall_-_high_mag.jpg | Liver cyst wall - high mag. (WC)
Image: Laminated liver cyst wall - intermed mag.jpg | Characteristic laminated portion - intermed. mag. (WC)
Image: Laminated liver cyst wall - high mag.jpg | Characteristic laminated portion - high mag. (WC)
</gallery>
[[www]]:
*[http://pathmicro.med.sc.edu/parasitology/hydatid-hist1.jpg Hydatid cyst (med.sc.edu)].
*[http://www.atlas.or.kr/atlas/include/viewImg.html?uid=645 Hydatid cyst (atlas.or.kr)].
*[http://casereports.bmj.com/content/2009/bcr.04.2009.1798.full Hydatid cyst (casereports.bmj.com)].

==Abscess==
A. [[File:1 ABS 1 680x512px.tif|A process replaces most of the liver parenchyma (20X).]]
 
B. [[File:2 ABS 1 680x512px.tif|Fibrinopurulent exudate apposes granulation tissue (200X).]]
 
C. [[File:3 ABS 1 680x512px.tif|Neutrophils lie in widened sinusoids (200X)..]]
 
D. [[File:4 ABS 1 680x512px.tif|Trichrome shows collagenization of spaces of Disse. Scarring about an abscess or other mass lesion should not be interpreted as reflective of the liver in general (200X).]]
 
Abscess. A. A process replaces most of the liver parenchyma. B. Fibrinopurulent exudate apposes granulation tissue. C. Neutrophils lie in widened sinusoids. D. Trichrome shows collagenization of spaces of Disse. Scarring about an abscess or other mass lesion should not be interpreted as reflective of the liver in general (LR 200X).

==Coccidiomycosis==
A. [[File:Coccidiomycosis - 1 - 40X 680x512px shot.tif|500x500px Granulomas at low power]]
 
B. [[File:Coccidiomycosis - 1 - 200X 680x513px shot.tif|500x500px Granulomas with centrally crowded cells & lady slipper macrophage nuclei]]
 
C. [[File:Coccidiomycosis - 1 - 400X 1369x1024px shot.tif|500x500px Center of previous granuloma showing pyknotic macrophage nuclei]]
 
D. [[File:Coccidiomycosis - 1 - GMS 400X 1369x1024px shot.tif|500x500px Four Coccidiomycotic spherules]]
 
Coccidiomycosis. A. Note the granulomas in otherwise undisturbed liver (UL). B. Granuloma with centrally crowded cells & lady slipper macrophage nuclei. C. Center of granuloma with pyknotic macrophage nuclei, "necrotizing". D. Organisms on GMS stain.

=Metabolic and toxic=
==Alcoholic liver disease==
===General===
*Acute and/or chronic liver changes due to excessive [[alcohol]] use - includes:
**''[[Alcoholic steatohepatitis]]'' (ASH), [[AKA]] ''alcoholic hepatitis''.<ref>URL: [http://emedicine.medscape.com/article/170539-overview http://emedicine.medscape.com/article/170539-overview]. Accessed on: 3 May 2012.</ref>
***Alcoholic hepatitis can be with minimal steatosis.<ref>STC. 6 December 2010.</ref>
**[[Steatosis]] - classically macrovescicular and centrilobular.
**Alcoholic [[cirrhosis]].

====Classic lab findings in EtOH abusers====
*AST & ALT elevated with AST:ALT=2:1.
*GGT elevated.
*MCV increased.

===Gross pathology/radiologic findings===
*Classically micronodular pattern.
**May be macronodular.

===Microscopic===
See:
*''[[Steatohepatitis]]'' section and ''[[ballooning degeneration]]'' section.

Features:
*Often zone III damage.
*Cholestatsis common, i.e. yellow staining.
**NASH (non-alcoholic steatohepatitis) usu. does not have cholestasis.<ref>STC. 6 December 2010.</ref>
*Fibrosis starts at central veins.
*Neutrophils (often helpful) -- few other things have PMNs. (???)
**Neutrophils cluster around cells with Mallory hyaline.

====Images====

A. [[File:1 etoh 3 680x512px.tif| Alcoholic hepatitis with Metavir stage IV fibrosis (advanced fibrosis/cirrhosis).]]
 
B. [[File:2 etoh 3 680x512px.tif| Alcoholic hepatitis with Metavir stage IV fibrosis (advanced fibrosis/cirrhosis).]]
 
C. [[File:3 etoh 3 680x512px.tif| Alcoholic hepatitis with Metavir stage IV fibrosis (advanced fibrosis/cirrhosis).]]
 
D. [[File:4 etoh 3 680x512px.tif| Alcoholic hepatitis with Metavir stage IV fibrosis (advanced fibrosis/cirrhosis).]]
 
E. [[File:5 etoh 3 680x512px.tif| Alcoholic hepatitis with Metavir stage IV fibrosis (advanced fibrosis/cirrhosis).]]
 
F. [[File:6 etoh 3 680x512px.tif| Alcoholic hepatitis with Metavir stage IV fibrosis (advanced fibrosis/cirrhosis).]]
 

Alcoholic hepatitis with Metavir stage IV fibrosis (advanced fibrosis/cirrhosis).
A. Trichrome shows relatively non-inflamed fibrous bands, as well as [between green dots] nodules. The lack of regeneration throughout might have precluded a diagnosis of cirrhosis, but stage IV fibrosis under the Metavir system is justified. B. Reticulin shows regenerative nodules [left] with mostly two or more nuclei between black lines juxtaposed to non-regenerative hepatocytes on the right, without piecemeal necrosis. C. Regenerative nodules show occasional neutrophils [red arrow] and cytoplasmic tufts of ballooned cells, sometimes possibly Mallory hyalin [green arrows]. D. Triads (note vein [green arrow], artery [yellow arrow], and interlobular bile duct [blue arrow]) generally showed little or no interface hepatitis, even when expanded by fibrosis and inflamed. E. Occasional foci of spotty necrosis were seen. F. This edge of an inflamed triads shows neutrophils about proliferated bile ducts [red arrows], as well as Mallory-Denk bodies [blue arrows].
 
A. [[File:1 etoh 4 680x512px.tif| Cirrhosis in an alcoholic.]]
 
B. [[File:2 etoh 4 680x512px.tif| Cirrhosis in an alcoholic.]]
 
C. [[File:3 etoh 4 680x512px.tif| Cirrhosis in an alcoholic.]]
 
D. [[File:4 etoh 4 680x512px.tif| Cirrhosis in an alcoholic.]]
 
E. [[File:5 etoh 4 680x512px.tif| Cirrhosis in an alcoholic.]]
 
F. [[File:6 etoh 4 680x512px.tif| Cirrhosis in an alcoholic.]]
 
Definite cirrhosis in an alcoholic. A. Hepatocyte free bands parse tissue, with occasional definite islands [arrows]. B. Trichrome establishes blue fibrosis about isles [arrows]. C. Reticulin stain shows nodules with regeneration, wherein a large proportion of them are at least two nuclei thick [arrows]. D. Bile duct proliferation can be difficult, sometimes mimicking cholangiocarcinoma. Follow the double headed arrows to see how the ductules can be seen to proliferate from a single sources, with all ducts being complete, without necrotic epithelial cells. E. PAS with distase can help, as cholangiocarcinoma generally lacks the red rim of proliferating bile ductules [arrows]; again note the connections that can be made between the ductule openings by the blue double headed arrows. The cyan double headed arrows show general parallelism, consistent with uniform directionality induced by extrinsic force, not a neoplastic spread. F. Trichrome shows the most difficult focus. Double headed arrows display the connectivity seen before of the proliferated bile ductules. Note that numerous pairs of adjacent perpendicular glands without a head to foot appearance are not seen that would indicate the disorderly spread of cholangiocarcinoma.
 
A. [[File:1 ALC 2 680x512px.tif|Expanded, inflamed triads with increased bile duct/vascular openings. Mild steatosis (40X).]]
 
B. [[File:2 ALC 2 680x512px.tif|Trichrome stain shows periportal fibrosis [red arrowheads] (200X).]]
 
C. [[File:3 ALC 2 680x512px.tif|PAS with diastase stain shows proliferated bile ductules [blue arrowheads] in stroma with mixed inflammatory infiltrate (400X)]]
 
D. [[File:4 ALC 2 680x512px.tif|Neutrophils about ballooned hepatocyte (satellitosis) [yellow arrowheads]. Councilman bodies [green arrowheads] (400X).]]
 
Alcoholic hepatitis without cirrhosis. No history of viral disease. AMA negative. A. Expanded, inflamed triads with increased bile duct/vascular openings. Mild steatosis. B. Trichrome stain shows periportal fibrosis [red arrowheads]. C. PAS with diastase stain shows proliferated bile ductules [blue arrowheads] in stroma with mixed inflammatory infiltrate. D. Neutrophils about ballooned hepatocyte (satellitosis) [yellow arrowheads]. Councilman bodies [green arrowheads].

Notes:
*If portal inflammatory infiltrates more than mild, r/o other causes i.e. [[viral hepatitis]].
*Mallory bodies once thought to be characteristic; now considered non-specific and generally poorly understood.<ref>{{cite journal |author=Jensen K, Gluud C |title=The Mallory body: theories on development and pathological significance (Part 2 of a literature survey) |journal=Hepatology |volume=20 |issue=5 |pages=1330-42 |year=1994 |month=November |pmid=7927269 |doi= |url=}}</ref>
*Some consider ''alcoholic liver disease'' a clinical diagnosis, i.e. as a pathologist one does not diagnose it.<ref>MG. September 2009.</ref>

==Non-alcoholic fatty liver disease==
*Abbreviated ''NAFLD''.
*Fatty liver that is not due to alcohol; includes obesity-related fatty liver, metabolic disease/diabetes-related fatty liver.

===NASH===
*Non-alcoholic steatohepatitis - see ''steatohepatitis'' section.
*Histologically indistinguishable from ASH.
*NASH is a ''clinical diagnosis'' based on exclusion of alcohol.

==Steatohepatitis==
{{Main|Steatohepatitis}}

=Autoimmune=
==Autoimmune hepatitis==
*Abbreviated ''AIH''.
{{Main|Autoimmune hepatitis}}

==Primary biliary cirrhosis==
*Abbreviated PBC.
{{Main|Primary biliary cirrhosis}}

==Autoimmune hepatitis with obstruction - combined changes==
{|
[[File:1 AIH OBS 1.tif|Low power shows inflammation; portal triads, lobules, central veins cannot be distinguished (40X).]]
[[File:2 AIH OBS 1.tif|Trichrome shows central venous sclerosis (red arrowhead), periportal fibrosis (green arrowhead), & space of Disse collagenization (yellow arrowhead); juxtaposition of central vein & portal tract indicates collapse, no definite bridging was seen (100X)]]
 
[[File:3 AIH OBS 1.tif|Central vein is inflamed with a rare plasma cell (cyan arrowhead) (400X).]]
[[File:4 AIH OBS 1.tif|Interface hepatitis with plasma cells (yellow arrows) and ballooned hepatocytes (red arrows). Lobule is disorganized (400X).]]
 
[[File:5 AIH OBS 1.tif|Proliferating bile ductules (blue arrows) with occasional neutrophils (fucsia arrows), indicative of obstruction, but not acute cholangitis, which requires inflamed bile duct itself, best diagnosed with associated blood vessel (400X).]]
[[File:6 AIH OBS 1.tif|Rare distorted rosettes with greenish brown strands of bile (left arrow) or bile plugs (right arrow) (400X).]]
|}
Patient with SLE and obstructive jaundice that resolved with apparent passage of stone. Low power shows inflammation; portal triads, lobules, central veins cannot be distinguished (left row 1 40X). Trichrome shows central venous sclerosis (red arrowhead), periportal fibrosis (green arrowhead), & space of Disse collagenization (yellow arrowhead); juxtaposition of central vein & portal tract indicates collapse, no definite bridging was seen (right row 1 100X). Central vein is inflamed with a rare plasma cell (cyan arrowhead) (left row 2 400X). Interface hepatitis with plasma cells (yellow arrows) and ballooned hepatocytes (red arrows). Lobule is disorganized (right row 2 400X). Proliferating bile ductules (blue arrows) with occasional neutrophils (fucsia arrows), indicative of obstruction, but not acute cholangitis, which requires inflamed bile duct itself, best diagnosed with associated blood vessel (left row 3 400X). Rare distorted rosettes with greenish brown strands of bile (left arrow) or bile plugs (right arrow) (right row 3 400X).

==Autoimmune hepatitis-primary biliary cirrhosis overlap syndrome==
*Abbreviation ''AIH-PBC OS''.
===General===
Epidemiology:
*Rare.

Serology:<ref name=pmid19491855>{{Cite journal | last1 = Muratori | first1 = P. | last2 = Granito | first2 = A. | last3 = Pappas | first3 = G. | last4 = Pendino | first4 = GM. | last5 = Quarneti | first5 = C. | last6 = Cicola | first6 = R. | last7 = Menichella | first7 = R. | last8 = Ferri | first8 = S. | last9 = Cassani | first9 = F. | title = The serological profile of the autoimmune hepatitis/primary biliary cirrhosis overlap syndrome. | journal = Am J Gastroenterol | volume = 104 | issue = 6 | pages = 1420-5 | month = Jun | year = 2009 | doi = 10.1038/ajg.2009.126 | PMID = 19491855 }}</ref>
*AMA +ve.
*Anti-dsDNA +ve.

===Microscopic===
:See: ''[[autoimmune hepatitis]]'' and ''[[primary biliary cirrhosis]]''.
{|
[[File:1 AIH PBC 1 680x512px.tif|Expanded portal tracts with fuzzy edges (40X).]]
[[File:2 AIH PBC 1 680x512px.tif|Interface hepatitis with plasma cells (400X).]]
 
[[File:3 AIH PBC 1 680x512px.tif|Loose granuloma (400X).]]
[[File:4 AIH PBC 1 680x512px.tif|Damaged bile duct (400X).]]
|}

AIH/PBC overlap. AMA & ANA positive with Alkaline phosphatase > 2 upper limit of normal & one ALT > 5 times upper limit of normal. Expanded portal tracts with fuzzy edges (UL 40X). IInterface hepatitis with plasma cells (UR 400X). Loose granuloma (LL 400X). Damaged bile duct (LR 400X).

==Primary sclerosing cholangitis==
*Abbreviated ''PSC''.
{{Main|Primary sclerosing cholangitis}}

=Hereditary=
==Caroli disease==
===General===
*Genetic disease.
**Frequently associated with [[autosomal recessive polycystic kidney disease]] (ARPKD).<ref name=omim263200>{{OMIM|263200}}</ref>
**May be seen in isolation.<ref name=omim600643>{{OMIM|600643}}</ref>

Clinical:<ref name=pmid17461493>{{Cite journal | last1 = Yonem | first1 = O. | last2 = Bayraktar | first2 = Y. | title = Clinical characteristics of Caroli's syndrome. | journal = World J Gastroenterol | volume = 13 | issue = 13 | pages = 1934-7 | month = Apr | year = 2007 | doi = | PMID = 17461493 }}</ref>
*Recurrent [[cholangitis]].
*Recurrent [[cholelithiasis]].
*[[Cholangiocarcinoma]]<ref name=pmid17461492>{{Cite journal | last1 = Yonem | first1 = O. | last2 = Bayraktar | first2 = Y. | title = Clinical characteristics of Caroli's disease. | journal = World J Gastroenterol | volume = 13 | issue = 13 | pages = 1930-3 | month = Apr | year = 2007 | doi = | PMID = 17461492 }}</ref> - seen in ~7% of cases.<ref name=pmid15347876>{{Cite journal | last1 = Karim | first1 = AS. | title = Caroli's disease. | journal = Indian Pediatr | volume = 41 | issue = 8 | pages = 848-50 | month = Aug | year = 2004 | doi = | PMID = 15347876 }}</ref>

Note:
*''Caroli syndrome'' = Caroli disease + congenital hepatic fibrosis.<ref name=pmid15888616>{{Cite journal | last1 = Brancatelli | first1 = G. | last2 = Federle | first2 = MP. | last3 = Vilgrain | first3 = V. | last4 = Vullierme | first4 = MP. | last5 = Marin | first5 = D. | last6 = Lagalla | first6 = R. | title = Fibropolycystic liver disease: CT and MR imaging findings. | journal = Radiographics | volume = 25 | issue = 3 | pages = 659-70 | month = | year = | doi = 10.1148/rg.253045114 | PMID = 15888616 | URL = http://radiographics.rsna.org/content/25/3/659.long }}</ref>

===Gross===
*Dilated bile ducts.<ref name=omim263200/>

===Microscopic===
Features:<ref name=pmid17461493/>
*Dilated bile ducts.
*Periductal fibrosis. (???)
*+/-Fibrosis.

Image:
*[http://www.meddean.luc.edu/lumen/MedEd/orfpath/11-3-10.jpg Caroli disease (meddean.luc.edu)].<ref>URL: [http://www.meddean.luc.edu/lumen/MedEd/orfpath/develop.htm http://www.meddean.luc.edu/lumen/MedEd/orfpath/develop.htm]. Accessed on: 1 December 2011.</ref>

==Hereditary hemochromatosis==
:''For secondary causes see [[secondary hemochromatosis]]''.
{{Main|Hereditary hemochromatosis}}

==Wilson disease==
{{Main|Wilson's disease}}

==Alpha-1 antitrypsin deficiency==
*[[AKA]] ''alpha1-antiprotease inhibitor deficiency''.
{{Main|Alpha-1 antitrypsin deficiency }}

=Other=
==Budd-Chiari syndrome==
*[[AKA]] ''hepatic vein obstruction''.
===General===
*Hepatic outflow obstruction.

Clinical triad:<ref name=pmid21573256>{{Cite journal | last1 = Fox | first1 = MA. | last2 = Fox | first2 = JA. | last3 = Davies | first3 = MH. | title = Budd-Chiari syndrome--a review of the diagnosis and management. | journal = Acute Med | volume = 10 | issue = 1 | pages = 5-9 | month = | year = 2011 | doi = | PMID = 21573256 }}</ref>
*Ascites.
*Abdominal pain.
*Hepatomegaly.

Etiology:
*~50% have a [[myeloproliferative disease]].<ref name=pmid18814079>{{Cite journal | last1 = Plessier | first1 = A. | last2 = Valla | first2 = DC. | title = Budd-Chiari syndrome. | journal = Semin Liver Dis | volume = 28 | issue = 3 | pages = 259-69 | month = Aug | year = 2008 | doi = 10.1055/s-0028-1085094 | PMID = 18814079 }}</ref>
*May be due to mass effect from a tumour.

Clinical DDx:
*[[Hepatic veno-occlusive disease]].

===Microscopic===
Features:<ref name=pmid17569137>{{Cite journal | last1 = Aydinli | first1 = M. | last2 = Bayraktar | first2 = Y. | title = Budd-Chiari syndrome: etiology, pathogenesis and diagnosis. | journal = World J Gastroenterol | volume = 13 | issue = 19 | pages = 2693-6 | month = May | year = 2007 | doi = | PMID = 17569137 | url=http://www.wjgnet.com/1007-9327/full/v13/i19/2693.htm }}</ref>
*Sinusoidal dilation in zone III (congestion).
*+/-Hepatocyte drop-out.
*+/-Centrilobular fibrosis.

DDx congestion:
*Congestive heart failure ([[congestive hepatopathy]]).
*Constrictive pericarditis.

==Vanishing bile duct syndrome==
*[[AKA]] ''bile duct loss'', [[AKA]] ''ductopenia''.<ref name=pmid11521176/>
===General===
*Fatal.

DDx:<ref name=pmid18242505/>
*[[Primary biliary cirrhosis]].
*[[Primary sclerosing cholangitis]].
*[[GVHD]].<ref name=pmid7994249>{{Cite journal | last1 = Yeh | first1 = KH. | last2 = Hsieh | first2 = HC. | last3 = Tang | first3 = JL. | last4 = Lin | first4 = MT. | last5 = Yang | first5 = CH. | last6 = Chen | first6 = YC. | title = Severe isolated acute hepatic graft-versus-host disease with vanishing bile duct syndrome. | journal = Bone Marrow Transplant | volume = 14 | issue = 2 | pages = 319-21 | month = Aug | year = 1994 | doi = | PMID = 7994249 }}</ref>
*[[Drug-induced liver disease|Drugs]].<ref name=pmid11352118>{{Cite journal | last1 = Chitturi | first1 = S. | last2 = Farrell | first2 = GC. | title = Drug-induced cholestasis. | journal = Semin Gastrointest Dis | volume = 12 | issue = 2 | pages = 113-24 | month = Apr | year = 2001 | doi = | PMID = 11352118 }}</ref>
*Chronic rejection.<ref name=pmid11521176>{{Cite journal | last1 = Inomata | first1 = Y. | last2 = Tanaka | first2 = K. | title = Pathogenesis and treatment of bile duct loss after liver transplantation. | journal = J Hepatobiliary Pancreat Surg | volume = 8 | issue = 4 | pages = 316-22 | month = | year = 2001 | doi = 10.1007/s0053410080316 | PMID = 11521176 }}</ref>

===Microscopic===
Features:<ref name=pmid18242505>{{Cite journal | last1 = Reau | first1 = NS. | last2 = Jensen | first2 = DM. | title = Vanishing bile duct syndrome. | journal = Clin Liver Dis | volume = 12 | issue = 1 | pages = 203-17, x | month = Feb | year = 2008 | doi = 10.1016/j.cld.2007.11.007 | PMID = 18242505 }}</ref>
*Loss of intrahepatitic bile ducts - '''key feature'''.
*Cholestasis.

Note:
*May occur without fibrosis and inflammation; thus, can be easy to miss.

===IHC===
*[[CK7]] -ve.
**Marks bile ducts.

==Extrahepatic biliary obstruction==
{|
[[File:1 OBS 3 680x512px.tif|Sinusoidal dilatation, circular spaces of hepatocytes, small portal triads(40X).]]
[[File:2 OBS 3 680x512px.tif|Bile in hepatocytes about central vein & in plugs in canaliculi [yellow arrowhead] (400X).]]
 
[[File:3 OBS 3 680x512px.tif|Trichrome shows fibrosis about central vein (400X).]]
[[File:4 OBS 3 680x512px.tif|PAS with diastase shows portal triads with mild edema and chronic inflammation, without tortuous bile duct (400X).]]
|}
Early extrahepatic biliary obstruction, demonstrated radiographically, transient, with rise in bilirubin, alkaline phosphatase, and transaminases. Pure canalicular cholestasis near terminal hepatic venules also seen in acute hepatitis, drug reactions, benign recurrent cholestasis, pregnancy, sepsis, & lymphomas. Sinusoidal dilatation, circular spaces of hepatocytes, small portal triads(UL 40X). Bile in hepatocytes about central vein & in plugs in canaliculi [yellow arrowhead] (UR 400X). Trichrome shows fibrosis about central vein (LL 400X). PAS with diastase shows portal triads with mild edema and chronic inflammation, without tortuous bile duct (LR 400X).

{|
[[File:1 OBS 2 680x512px.tif|Expanded inflamed portal triads, swollen hepatocytes (40X)]]
[[File:2 OBS 2 680x512px.tif|Edematous stroma, proliferating ductules [yellow arrowheads], PAS-D macrophages [red arrowhead] (PAS with diastasse, 200X)]]
 
[[File:3 OBS 2 680x512px.tif|Disordered, often swollen hepatocytes,some with feathery degeneration (net like spaces in cytoplasm [blue arrowhead], rare Councilman body [green arrowhead] (400X)]]
[[File:4 OBS 2 1360x1024px.tif|Bile in hepatocytes [cyan arrrowhead] & in canaliculi [purple arrowheads]. Empty acinar spaces bounded by hepatocytes [orange arrowhead] (400X, higher pixel),]]
|}
Changes of extrahepatic biliary obstruction, months duration. Expanded inflamed portal triads, swollen hepatocytes (UL 40X). Edematous stroma, proliferating ductules [yellow arrowheads], PAS-D macrophages [red arrowhead] (UR PAS with diastasse, 200X). Disordered, often swollen hepatocytes,some with feathery degeneration (net like spaces in cytoplasm) [blue arrowhead], rare Councilman body [green arrowhead] (LL 400X). Bile in hepatocytes [cyan arrrowhead] & in canaliculi [purple arrowheads]. Empty acinar spaces bounded by hepatocytes [orange arrowhead] (LR 400X).
{|
[[File:1 Bd obs 4 680x512px.tif|Expanded, light colored portal triads (arrows)(20X).]]
[[File:2 Bd obs 4 680x512px.tif|Proliferating bile ductules (cyan arrows) with neutrophils (yellow arrows), not specific for acute cholangitis, of assistance with large bile duct obstruction (400X)..]]
 
[[File:3 Bd obs 4 680x512px.tif|Uninflamed interlobular duct (yellow arrow) with, accompanying blood vessel (red arrow) (400X)]]
[[File:4 Bd obs 4 680x512px.tif|Bile infarct with pyknotic nuclei (arrows)(400X).]]
 
[[File:5 Bd obs 4 680x512px.tif|Bile (arrow) in interlobular bile duct with disordered nuclei (400X).]]
[[File:6 Bd obs 4 680x512px.tif|Bile plugs in cannaliculi (red arrows), feathery degeneration producing foamy macrophage like hepatocytes (yellow arrows)(400X).]]
|}
Large bile duct obstruction. Expanded, light colored portal triads (arrows)(Row 1 Left 20X). Proliferating bile ductules (cyan arrows) with neutrophils (yellow arrows), not specific for acute cholangitis, of assistance with large bile duct obstruction (Row 1 Right 400X). Uninflamed interlobular duct (yellow arrow) with, accompanying blood vessel (red arrow) (Row 2 Left 400X). Bile infarct with pyknotic nuclei (arrows)(Row 2 Right 400X). Bile (arrow) in interlobular bile duct with disordered nuclei (Row 3 Left 400X). Bile plugs in cannaliculi (red arrows), feathery degeneration producing foamy macrophage-like hepatocytes (yellow arrows)(Row 3 Right 400X).

==Congestive hepatopathy==
===General===
*Liver failure due to (right) heart failure.
*AKA ''cardiac cirrhosis'' - a term used by clinicians.
**Generally, it does not satisfy pathologic criteria for cirrhosis.<ref>URL: [http://emedicine.medscape.com/article/151792-overview http://emedicine.medscape.com/article/151792-overview]. Accessed on: 17 June 2010.</ref>

===Gross===
*"Nutmeg" liver - yellow spotted appearance.

===Microscopic===
Features:<ref>URL: [http://emedicine.medscape.com/article/151792-diagnosis http://emedicine.medscape.com/article/151792-diagnosis]. Accessed on: 17 June 2010.</ref>
*Zone III atrophy.
*Portal venule (central vein) distension.
*Perisinusoidal fibrosis - progresses to centrilobular fibrosis and then diffuse fibrosis.
*Dilation of sinusoids in ''all'' zone III areas - '''key feature'''.<ref>Suggested by OA. September 2009.</ref>

DDx:
*[[Hemangioma of the liver]] - should be focal lesion.
Cardiac (congestive) hepatopathy, wherein outflow obstruction occurs secondary to backflow from a failing heart, and Budd Chiari syndrome, wherein obstruction of outflow occurs secondary to obstruction, usually thrombotic, have overlapping features, including sinusoidal dilation with emphasis upon the central vein, space of Disse erythrocytes, centrilobular inflammation, hemorrhage, bile ductules, and hemosiderin, and portal inflammation, fibrosis and bile ductular reaction. Centrilobular dropout/necrosis is more common in Budd Chiari syndrome, while peri-central venous and sinusoidal fibrosis are more common in cardiac hepatopathy. In end stage liver, fibrosis for cardiac hepatopathy comprises stellate centrizonal fibrous with haphazard spread, as opposed to the more frequent nodular cirrhosis in Budd-Chiari. Clinical findings are important to take into account, as cardiac failure is usually well known at the time of diagnosis as are the clinical predictors of Budd Chiari syndrome, prothrombotic states, myeloproliferative diseases, and oral contraceptive use. <ref name=pmid27681331 >{{cite journal |author=Gonzalez RS, Gilger MA, Huh WJ, Washington MK |title=The spectrum of histologic findings in hepatic outflow obstruction |journal= Arch Pathol Lab Med |volume=141 |issue= |pages=98 |year=2017 |pmid= 27681331 ||doi= 10.5858/arpa.2015-0388-OA |url=http http://www.archivesofpathology.org/doi/10.5858/arpa.2015-0388-OA?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%3dpubmed&code=coap-site }}</ref>
====Images====
<gallery>
Image:Congestive_hepatopathy_high_mag.jpg | Mild congestive hepatopathy. (WC) 
A.[[File:1 CEN NEC 1 680x512px.tif|PAS without diastase shows ovoids of necrosis {40X).]] 
B. [[File:2 CEN NEC 1 680x512px.tif|Necrosis with central vein [yellow arrowhead], inflammatory cells, residual Councilman body [green arrowhead], and hepatocyte with mitotic figure [red arrowhead] (400X).]]
 
C. [[File:3 CEN NEC 1 680x512px.tif|Trichrome highlights fibrosis about central vein [yellow arrowhead] & shows beginning scar formation [green arrowheads]. Note residual atrophic hepatocytes [blue arrowheads] (400X).]]
 
D. [[File:4 CEN NEC 1 680x512px.tif|Portal triads are largely unaffected (400X).]]
|} 
Centrilobular necrosis (seen in circulatory failure and with toxins/drugs). A. PAS without diastase shows ovoids of necrosis. B. Necrosis with central vein [yellow arrowhead], inflammatory cells, residual Councilman body [green arrowhead], and hepatocyte with mitotic figure [red arrowhead]. C. Trichrome highlights fibrosis about central vein [yellow arrowhead] & shows beginning scar formation [green arrowheads]. Note residual atrophic hepatocytes [blue arrowheads]. D. Portal triads are largely unaffected (LR 400X)
 
A. [[File:1 CHF 1 680x512px.tif|Dilated and undilated sinusoidal regions (40X).]]
 
B. [[File:2 CHF 1 680x512px.tif|Thrombi in sinusoids; glycogenated nuclei likely reflect patient’s diabetes mellitus (400X).]]
 
C. [[File:3 CHF 1 680x512px.tif|Dilated portal vein (400X).]]
 
D. [[File:4 CHF 1 680x512px.tif|Reticulin shows collapse (thick black lines) as well as a dilated portal vein (200X).]]
 
E. [[File:5 CHF 1 680x512px.tif|Trichrome shows space of Disse collagenization (pericellular fibrosis) (200X).]]
 
F. [[File:6 CHF 1 680x512px.tif|Trichrome shows periportal fibrosis; no bridging was seen (200X).]]

Patient with congestive heart failure and stage I fibrosis. A. Dilated and undilated sinusoidal regions. B. Thrombi in sinusoids; glycogenated nuclei likely reflect patient’s diabetes mellitus. C. Dilated portal vein. D. Reticulin shows black lines of bridging, too thick for collapse. E. Trichrome shows space of Disse collagenization (pericellular fibrosis). F. Trichrome shows bridge beginning off to right; when it is more than a mere spike, it is a bridge.

==Drug-induced liver disease==
*[[AKA]] ''drug-induced liver toxicity''.
{{Main|Drug-induced liver disease}}

==Focal nodular hyperplasia==
*Abbreviated ''FNH''.
{{Main|Focal nodular hyperplasia}}

==Nodular regenerative hyperplasia==
===General===
*Associated with renal transplants, [[bone marrow transplant]]s and [[vasculitides]].<ref name=Ref_PBoD922>{{Ref PBoD|922}}</ref>
*Can lead to [[portal hypertension]] and many of the associated complications.<ref name=pmid22554152>{{Cite journal | last1 = Bissonnette | first1 = J. | last2 = Généreux | first2 = A. | last3 = Côté | first3 = J. | last4 = Nguyen | first4 = B. | last5 = Perreault | first5 = P. | last6 = Bouchard | first6 = L. | last7 = Pomier-Layrargues | first7 = G. | title = Hepatic hemodynamics in 24 patients with nodular regenerative hyperplasia and symptomatic portal hypertension. | journal = J Gastroenterol Hepatol | volume = 27 | issue = 8 | pages = 1336-40 | month = Aug | year = 2012 | doi = 10.1111/j.1440-1746.2012.07168.x | PMID = 22554152 }}
</ref>

====Etiology====
*Arterial hypervascularity secondary to loss of hepatic vein radicles (loss of central venule in hepatic lobule).<ref name=Ref_PBoD922>{{Ref PBoD|922}}</ref>

ASIDE: radicle = ramulus - smallest branch or vessel or nerve.<ref name=Dorlands2>Dorland's Medical Dictionary. 30th Ed.</ref>

===Gross===
*Diffuse nodularity - whole liver.

===Microscopic===
Features:<ref name=Ref_PBoD922>{{Ref PBoD|922}}</ref>
*"Plump" hepatocytes surrounded by atrophic ones.
*No fibrosis.

==Sinuosoidal obstruction syndrome==
*May be referred to as ''Hepatic veno-occlusive disease''.<ref name=pmid11928077>{{Cite journal | last1 = DeLeve | first1 = LD. | last2 = Shulman | first2 = HM. | last3 = McDonald | first3 = GB. | title = Toxic injury to hepatic sinusoids: sinusoidal obstruction syndrome (veno-occlusive disease). | journal = Semin Liver Dis | volume = 22 | issue = 1 | pages = 27-42 | month = Feb | year = 2002 | doi = 10.1055/s-2002-23204 | PMID = 11928077 }}.</ref>
===General===
*Term for obstruction due to toxicity from a chemotherapeutic agent.<ref name=pmid16393276>{{Cite journal | last1 = Helmy | first1 = A. | title = Review article: updates in the pathogenesis and therapy of hepatic sinusoidal obstruction syndrome. | journal = Aliment Pharmacol Ther | volume = 23 | issue = 1 | pages = 11-25 | month = Jan | year = 2006 | doi = 10.1111/j.1365-2036.2006.02742.x | PMID = 16393276 }}</ref><ref name=pmid17569137>{{Cite journal | last1 = Aydinli | first1 = M. | last2 = Bayraktar | first2 = Y. | title = Budd-Chiari syndrome: etiology, pathogenesis and diagnosis. | journal = World J Gastroenterol | volume = 13 | issue = 19 | pages = 2693-6 | month = May | year = 2007 | doi = | PMID = 17569137 | url=http://www.wjgnet.com/1007-9327/full/v13/i19/2693.htm }}</ref>

Clinical DDx:
*[[Budd-Chiari syndrome]].

===Microscopic===
Features:<ref name=pmid17569137>{{Cite journal | last1 = Aydinli | first1 = M. | last2 = Bayraktar | first2 = Y. | title = Budd-Chiari syndrome: etiology, pathogenesis and diagnosis. | journal = World J Gastroenterol | volume = 13 | issue = 19 | pages = 2693-6 | month = May | year = 2007 | doi = | PMID = 17569137 | url=http://www.wjgnet.com/1007-9327/full/v13/i19/2693.htm }}</ref>
*Subendothelial swelling in hepatic venules.

Negatives:
*No thrombosis.

==Ascending Cholangitis (Acute Cholangitis)==
===General===
*Term for infection of bile ducts, usually due to obstruction

Clinical DDx:

===Microscopic===
====Images====

A. [[File:1 asc chol 1 680x512px.tif|Rounded, clear (edematous) portal tracts (arrows) separated by hepatocytes with dilated sinusoids (Row 1 Left 40X).]]
 
B. [[File:2 asc chol 1 680x512px.tif|Neutrophils about hepatocytes (arrows) have spilled into the lobule from a portal tract (Row 1 Right 200X).]]
 
C. [[File:3 asc chol 1 680x512px.tif|Proliferated bile ductules (arrows) bearing neutrophils within epithelium and lumens are features of obstruction that should prompt a search for interlobular ducts with acute inflammation (Row 2 Left 400X).]]
 
D. [[File:4 asc chol 1 680x512px.tif|The epithelium of the ducts can be severely degenerated. Neutrophils (cyan arrows) invade epithelium of an interlobular duct that are recognizable mainly as a circle of rounded nuclei; the associated arteriole (red arrow) should be identified to ensure an interlobular duct is being evaluated. Note the proliferated bile ductules (blue arrows) (Row 2 Right 400X).]]
 
E. [[File:5 asc chol 1 680x512px.tif|A PAS without diastase stain colors the arteriole (blue arrow), as well as the rim of the interlobular duct within which lies a neutrophil (cyan arrow) (Row 2 Right 400X). .]]
 
F. [[File:6 asc chol 1 680x512px.tif|A PAS with diastase stain colors the arteriole (red arrow), as well as the rim of the interlobular duct within which lies a neutrophil (cyan arrow) (Row 1 Right 400X)]]
 
Acute cholangitis in a patient with multiple bile duct procedures. After the biopsy, removal of bile duct stones released pus. A. Rounded, clear (edematous) portal tracts (arrows) separated by hepatocytes with dilated sinusoids. B. Neutrophils about hepatocytes (arrows) have spilled into the lobule from a portal tract. C, Proliferated bile ductules (arrows) bearing neutrophils within epithelium and lumens are features of obstruction that should prompt a search for interlobular ducts with acute inflammation. D. The epithelium of the ducts can be severely degenerated. Neutrophils (cyan arrows) invade epithelium of an interlobular duct that are recognizable mainly as a circle of rounded nuclei; the associated arteriole (red arrow) should be identified to ensure an interlobular duct is being evaluated. Note the proliferated bile ductules (blue arrows). E. A PAS without diastase stain colors the arteriole (blue arrow), as well as the rim of the interlobular duct within which lies a neutrophil (cyan arrow). F. A PAS with diastase stain colors the arteriole (red arrow), as well as the rim of the interlobular duct within which lies a neutrophil (cyan arrow).

A.[[File:1 Sep Acu Cho 1 680x512px.tif|Low power shows variably sized inflamed portal tracts (40X)]]
 
B. [[File:2 Sep Acu Cho 1 680x512px.tif|Trichrome shows dilated sinusoids and space of Disse collagenization (200X)]]
 
C. [[File:3 Sep Acu Cho 1 680x512px.tif|Inflammatory focus with macrophages and neutrophils (400X).]]
 
D. [[File:4 Sep Acu Cho 1 680x512px.tif|PAS with diastase shows proliferated bile ductules at edge of triad with neutrophils, which should not be used to make a definite diagnosis of acute cholangitis (400X).]]
 
E. [[File:5 Sep Acu Cho 1 680x512px.tif|PAS without diastase showing acutely inflamed bile duct, with accompanying blood vessel of similar size, diagnostic of acute cholangitis (400X).]]
 
F. [[File:6 Sep Acu Cho 1 680x512px.tif|PAS with diastase showing neutrophil in bille duct lumen, diagnostic of acute cholangitis (400X).]]
 
Patient with sepsis and acute cholangitis. A. Low power shows variably sized inflamed portal tracts. B. Trichrome shows dilated sinusoids and space of Disse collagenization. C. Inflammatory focus with macrophages and neutrophils. D. PAS with diastase shows proliferated bile ductules at edge of triad with neutrophils, which should not be used to make a definite diagnosis of acute cholangitis. E. PAS without diastase showing acutely inflamed bile duct, with accompanying blood vessel of similar size, diagnostic of acute cholangitis. F. PAS with diastase showing neutrophil in bille duct lumen, diagnostic of acute cholangitis.

==Polycystic kidney disease and the liver==
{{Main|Cystic kidney disease}}
===General===
Complications of PKD in the liver:<ref>{{Ref MacSween|174-5}}</ref>
#Infected cyst.
#Cholangiocarcinoma.
#Cholestasis/obstruction due to duct compression.<ref>URL: [http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=9184868 http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=9184868]. Accessed on: 23 September 2009.</ref>

Cysts:
*Cysts in the liver, like the kidney, are thought to enlarge with age.

===Microscopic===
Features:<ref>{{Ref MacSween|176}}</ref>
*''Von Meyenburg complexes'' ([[bile duct hamartoma]]):
**Cluster of dilated ducts with "altered" bile.
**Surrounded by collagenous stroma.
**Separate from the portal areas.<ref>Meyenburg complex. Stedman's Medical Dictionary. 27th Ed.</reF>

Images:
*[http://commons.wikimedia.org/wiki/File:Von_Meyenburg_complex_low_mag.jpg Von Meyenburg complex - bile duct hamartoma (WC)].
*[http://commons.wikimedia.org/wiki/File:Bile_duct_hamartoma_intermed_mag.jpg Bile duct hamartoma (WC)].

Notes:
*Appearance on ultrasound<ref name=pmid17287178>Bile duct hamartomas--the von Meyenburg complex. Salles VJ, Marotta A, Netto JM, Speranzini MB, Martins MR. Hepatobiliary Pancreat Dis Int. 2007 Feb;6(1):108-9. PMID 17287178.</ref> and CT (hypodense)<ref name=pmid19294869>[The von Meyenburg complex] Schwab SA, Bautz W, Uder M, Kuefner MA. Rontgenpraxis. 2008;56(6):241-4. German. PMID 19294869.</ref> - similar to metastases.

==Peliosis hepatis==
===General===
*Associated with:
**Infections.
**Malignancy.
**Other stuff.
*Rarely biopsied.

===Microscopic===
Features:
*Cyst lined by endothelium.
**Usu. incomplete.
*Blood.
{|
[[File:1 PEL 1 680x512px.tif|Hemorrhage at left end, dilated sinusoids elsewhere (20X).]]
[[File:2 PEL 1 680x512px.tif|Ramifying dilated sinusoidal spaces (100X).]]
 
[[File:3 PEL 1 680x512px.tif|PAS with diastase shows flat lining (400X).]]
[[File:4 PEL 1 680x512px.tif|Necrotic hepatocytes in cords, presumably due to pressure (400X).]]
|}
Peliosis hepatis. Hemorrhage at left end, dilated sinusoids elsewhere (UL 20X). Ramifying dilated sinusoidal spaces (UR 100X). PAS with diastase shows flat lining (LL 400X). Necrotic hepatocytes in cords, presumably due to pressure (LR 400X).

==Total parenteral nutrition==
*Abbreviated ''TPN''.

===General===
*Indication: short gut syndrome, others.

===Microscopic===
Variable - may range from: steatosis, steatohepatitis, cholestasis, fibrosis and cirrhosis.<ref name=pmid16766237>{{cite journal |author=Guglielmi FW, Boggio-Bertinet D, Federico A, ''et al.'' |title=Total parenteral nutrition-related gastroenterological complications |journal=Dig Liver Dis |volume=38 |issue=9 |pages=623–42 |year=2006 |month=September |pmid=16766237 |doi=10.1016/j.dld.2006.04.002 |url=}}</ref>

Features (classic):<ref>{{Cite journal | last1 = Li | first1 = SJ. | last2 = Nussbaum | first2 = MS. | last3 = McFadden | first3 = DW. | last4 = Gapen | first4 = CL. | last5 = Dayal | first5 = R. | last6 = Fischer | first6 = JE. | title = Addition of glucagon to total parenteral nutrition (TPN) prevents hepatic steatosis in rats. | journal = Surgery | volume = 104 | issue = 2 | pages = 350-7 | month = Aug | year = 1988 | doi = | PMID = 3135627 }}</ref><ref>{{Cite journal | last1 = Stanko | first1 = RT. | last2 = Nathan | first2 = G. | last3 = Mendelow | first3 = H. | last4 = Adibi | first4 = SA. | title = Development of hepatic cholestasis and fibrosis in patients with massive loss of intestine supported by prolonged parenteral nutrition. | journal = Gastroenterology | volume = 92 | issue = 1 | pages = 197-202 | month = Jan | year = 1987 | doi = | PMID = 3096806 }}
</ref>
*[[Steatosis]] (periportal) - early.
*Cholestasis - late.

==Giant cell hepatitis==
*[[AKA]] ''neonatal giant cell hepatitis''.

:See: ''[[Giant cell hepatitis]]''.

==Hepatic amyloidosis==
{{Main|Amyloidosis}}
*[[AKA]] ''liver amyloidosis''.
*[[AKA]] ''amyloidosis of the liver''.
===General===
*Diffuse abundant amyloid within the space of Disse is associated with [[portal hypertension]].<ref name=pmid1864548>{{Cite journal | last1 = Bion | first1 = E. | last2 = Brenard | first2 = R. | last3 = Pariente | first3 = EA. | last4 = Lebrec | first4 = D. | last5 = Degott | first5 = C. | last6 = Maitre | first6 = F. | last7 = Benhamou | first7 = JP. | title = Sinusoidal portal hypertension in hepatic amyloidosis. | journal = Gut | volume = 32 | issue = 2 | pages = 227-30 | month = Feb | year = 1991 | doi = | PMID = 1864548 | PMC = 1378815 | URL = http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1378815/?tool=pubmed }}</ref>

===Microscopic===
Features:
*Amorphous extracellular pink stuff on H&E - see ''[[amyloid]]'' article.

DDx:
*[[Fibrolamellar hepatocellular carcinoma]].

====Images====
<gallery>
Image:Hepatic_amyloidosis_-_low_mag.jpg | Amyloidosis of the liver - low mag. (WC)
Image:Hepatic_amyloidosis_-_intermed_mag.jpg | Amyloidosis of the liver - intermed. mag. (WC)
Image:Hepatic_amyloidosis_-_high_mag.jpg | Amyloidosis of the liver - high mag. (WC)
Image:Hepatic_amyloidosis_-_very_high_mag.jpg | Amyloidosis of the liver - very high mag. (WC)
</gallery>
{|
[[File:1 AMY 1 680x512px.tif|Amorphous material replaces hepatic parenchyma [4X]]]
[[File:2 AMY 1 680x512px.tif|Material barely stains blue on trichrome [10X]]]
 
[[File:3 AMY 1 680x512px.tif|Material stains red on unpolarized Congo Red [40X]]]
[[File:4 AMY 1 680x512px.tif|Material stains apple green on polarized Congo Red [40X]]]
|}
Amyloidosis. Amorphous material replaces hepatic parenchyma [UL 4X]. Material barely stains blue on trichrome [UR 10X] Material stains red on unpolarized Congo Red [LL 40X] Material stains apple green on polarized Congo Red [LR 40X]

===Stains===
*[[Congo red]] +ve.

==Fulminant hepatic necrosis==
===General===
Etiology:
*Viral, i.e. [[Hepatitis A]], [[Hepatitis B]]; [[Hepatitis C]] - extremely rare.
*Trauma.
*Shock.

===Microscopic===
{|
[[File:1 Necrosis 2 680x512px.tif| Submassive hepatic necrosis.]]
[[File:2 Necrosis 2 680x512px.tif| Submassive hepatic necrosis.]]
 
[[File:3 Necrosis 2 680x512px.tif| Submassive hepatic necrosis.]]
[[File:4 Necrosis 2 680x512px.tif| Submassive hepatic necrosis.]]
 
[[File:5 Necrosis 2 680x512px.tif| Submassive hepatic necrosis.]]
[[File:6 Necrosis 2 680x512px.tif| Submassive hepatic necrosis.]]
|}
Submassive hepatic necrosis. Patient had transaminases in the thousands that rapidly dropped to normal. Pink preserved parenchyma strews empty necrotic spaces (Row 1 Left 20X). Focus of necrosis with no apparent hepatocytes macrophages abuts apparently normal liver (Row 1 Right 200X). Iron stain shows the macrophages bear hemosiderin (Row 2 Left 200X). Reticulin stain highlights the recently dead liver cells (Row 2 Right 200X). Reticulin stain shows a necrotic bridge forming; the multiple small black circles preclude diagnosis of a fibrous bridge (Row 3 Left 200X). Trichrome shows the necrotic bridge (“collapse”) lacks much collagen deposition, as would be expected for bridging fibrosis (Row 3 Right 200X).

Features:
*Hepatocyte [[necrosis]].
*Bile duct proliferation.

DDx:
*[[Cholangiocarcinoma]].
*[[Angiosarcoma]].

==Secondary hemochromatosis==
:''For the hereditary one see [[hereditary hemochromatosis]]''.
===General===
*Iron overload secondary to blood transfusions for hereditary or acquired anemia.<ref name=pmid19727383/>
**Primary hemochromatosis due to a defect in iron processing - called ''[[hereditary hemochromatosis]]''.
*Imaging considered the best test, as iron deposition is patchy.<ref name=pmid19727383/>

Selected hereditary causes:<ref name=pmid19727383>{{Cite journal | last1 = Gattermann | first1 = N. | title = The treatment of secondary hemochromatosis. | journal = Dtsch Arztebl Int | volume = 106 | issue = 30 | pages = 499-504, I | month = Jul | year = 2009 | doi = 10.3238/arztebl.2009.0499 | PMID = 19727383 | PMC = 2735704 | URL = http://www.ncbi.nlm.nih.gov.myaccess.library.utoronto.ca/pmc/articles/PMC2735704/?tool=pubmed}}</ref>
*Thalassemia.
*[[Sickle cell anemia]].
*Hereditary sideroblastic anemia.

Selected acquired causes:<ref name=pmid19727383/>
*[[Myelodysplastic syndromes]]
*Myelofibrosis
*Aplastic anemia, intractable.

===Microscopic===
:See ''[[hereditary hemochromatosis]]''.

==Hepatic sarcoidosis==
{{Main|Hepatic sarcoidosis}}
==Overlapping Disorders==

[[File:1 Mixed Disorder 1 680x512px.tif|Changes of steatohepatitis and interface hepatitis, with granuloma. Patient with diabetes was ANA, AMA, HCV, HBV negative, without drugs known to produce granulomas or interface hepatitis. This may be a case of AMA negative primary biliary cirrhosis, but studies to determine that with certainty were not performed.]]
[[File:2 Mixed Disorder 1 680x512px.tif|Changes of steatohepatitis and interface hepatitis, with granuloma. Patient with diabetes was ANA, AMA, HCV, HBV negative, without drugs known to produce granulomas or interface hepatitis. This may be a case of AMA negative primary biliary cirrhosis, but studies to determine that with certainty were not performed.]]
[[File:3 Mixed Disorder 1 680x512px.tif|Changes of steatohepatitis and interface hepatitis, with granuloma. Patient with diabetes was ANA, AMA, HCV, HBV negative, without drugs known to produce granulomas or interface hepatitis. This may be a case of AMA negative primary biliary cirrhosis, but studies to determine that with certainty were not performed.]]
[[File:4 Mixed Disorder 1 680x512px.tif|Changes of steatohepatitis and interface hepatitis, with granuloma. Patient with diabetes was ANA, AMA, HCV, HBV negative, without drugs known to produce granulomas or interface hepatitis. This may be a case of AMA negative primary biliary cirrhosis, but studies to determine that with certainty were not performed.]]
[[File:5 Mixed Disorder 1 680x512px.tif|Changes of steatohepatitis and interface hepatitis, with granuloma. Patient with diabetes was ANA, AMA, HCV, HBV negative, without drugs known to produce granulomas or interface hepatitis. This may be a case of AMA negative primary biliary cirrhosis, but studies to determine that with certainty were not performed.]]
[[File:6 Mixed Disorder 1 680x512px.tif|Changes of steatohepatitis and interface hepatitis, with granuloma. Patient with diabetes was ANA, AMA, HCV, HBV negative, without drugs known to produce granulomas or interface hepatitis. This may be a case of AMA negative primary biliary cirrhosis, but studies to determine that with certainty were not performed.]] 
Changes of steatohepatitis and interface hepatitis, with granuloma. Patient with diabetes was ANA, AMA, HCV, HBV negative, without drugs known to produce granulomas or interface hepatitis. This may be a case of AMA negative primary biliary cirrhosis, but studies to determine that with certainty were not performed. A. Low power shows hepatocytes afflicted by steatosis and an inflamed portal tract. B. In a region of fatty change lie cytoplasmic tufts of ballooning degeneration (green arrows) and a lipogranuloma (black arrow). C. At the portal-hepatocyte junction lies interface hepatitis (black arrows), as well as extension of inflammation into the lobule (green arrows). D. Red hepatocytes bounded by inflammation denote piecemeal necrosis [PAS without diastase]. E. Giant cells intermixed with lymphocytes prove a portal granuloma [PAS without diastase]. F. A blue fibrous bridge extends from a triad [Trichrome].

[[File:4 95599552608917 sl 1.png|Acute obstructive changes and changes of recurrent acute injury]]
[[File:4 95599552608917 sl 2.png|Acute obstructive changes and changes of recurrent acute injury]]
[[File:4 95599552608917 sl 3.png|Acute obstructive changes and changes of recurrent acute injury]]
[[File:4 95599552608917 sl 4.png|Acute obstructive changes and changes of recurrent acute injury]]
[[File:4 95599552608917 sl 5.png|Acute obstructive changes and changes of recurrent acute injury]]
[[File:4 95599552608917 sl 6.png|Acute obstructive changes and changes of recurrent acute injury]]
[[File:4 95599552608917 sl 7.png|Acute obstructive changes and changes of recurrent acute injury]] 
Acute obstructive changes and changes of recurrent injury in 46 yo man with Clostridium perfringens positive blood culture, an ERCP that showed duodenal compression by the pancreas with resultant bile duct dilatation. The patient had had and continued to have multiple bouts of acute pancreatitis. At the time of biopsy, decreased platelet count/hemoglobin/albumin, elevated lipase/amylase/PT/PTT, normal alkaline phosphatase, bilirubin, AST/ALT, AMA, hepatitis virus serology, ANA. A. Fragment biopsy shows inflamed triads and bridges. B. Trichrome shows bridges without nodules, evidence of prior injury; the patient subsequently developed multiple episodes of pancreatitis. C. Reticulin shows piecemeal necrosis, with black lines bounding individual hepatocytes at interface (arrows). D. Collapse is shown by closly approximated thick black lines; one cannot call portal-central collapse without seeing a central vein. Note on this and the other reticulin image that regeneration, two cell thick cords, is not prominent. E. PAS D of two portal triads, far nearer than normal, both expanded. Note increased number of ducts/ductules (red arrows), neutrophils, and PAS-D macrophages. F. PAS D shows collapse extending from a triad to a portion of a lobule with steatosis. No feathery degeneration or bile duct plugs were seen. Neither were foci of spotty necrosis or abscess seen. G. Other triads, again edematous, showed more of a chronic inflammatory response, with occasional plasma cells (black arrows). Also present are neutrophils (red arrows). The bile duct (grey arrow) near the artery (brown arrow) shows mildly disturbed nuclei. Note early proliferated bile ductules (cyan arrows).

[[File:6 17281676469188 sl 1.png| Hepatitis B virus with steatohepatitis]]
[[File:6 17281676469188 sl 2.png| Hepatitis B virus with steatohepatitis]]
[[File:6 17281676469188 sl 3.png| Hepatitis B virus with steatohepatitis]]
[[File:6 17281676469188 sl 4.png| Hepatitis B virus with steatohepatitis]]
[[File:6 17281676469188 sl 5.png| Hepatitis B virus with steatohepatitis]]
[[File:6 17281676469188 sl 6.png| Hepatitis B virus with steatohepatitis]] 
Hepatitis B virus with steatohepatitis in a 36 year old man with hepatitis B surface antigen and hepatitis Be antigen positivity, Hepatitis be QTPC of 1750 cop/mL, an occasionally mildly elevated (42) ALT, and normal glucose, alkaline phosphatase, bilirubin, and other transaminases. He had a history of alcohol abuse, which became controlled. A. Triads show scant inflammation without definite interface hepatitis. About one-fourth of the lobule, not pan-acinar, is afflicted by steatosis. B. Occasional tufts are seen (arrow), indicating focal ballooning sufficient for a diagnosis of steatohepatitis. C. Glycogenated nuclei (black arrows) and hepatocytes with feathery degeneration (red arrows) are seen. D. Very rare foci of spotty necrosis were seen. E. Apart from this triad and the one in the trichrome stain in F, which had moderate inflammation comprising lymphocytes and macrophages, all triads were small, most without any inflammation at all. Neither collapse nor piecemeal necrosis were seen on reticulin stain. F. Trichrome stain showed only portal fibrosis. The interhepatocyte fibrosis required for brunt fibrosis stage I was not seen. Hence, one would grade this as follows: A) Chronic hepatitis (history of hepatitis B), Metavir activity index 1, Piecemeal necrosis 0, Lobular necrosis 1, Metavir fibrosis stage 1, B) Steatohepaitits, Brunt necroinflammatory grade 1, Brunt fibrosis stage 0.

=See also=
*[[Pancreas]].
*[[Gastrointestinal pathology]].
*[[Liver neoplasms]].
*[[Liver]].

=References=
{{reflist|2}}

[[Category:Gastrointestinal pathology]]
[[Category:Liver pathology]]
[[Category:Medical liver disease]]

Medical liver disease

2017-02-10T18:30:37Z

Mitchell: /* Microscopic */ Added a discussion with a reference for outflow obstruction and improved the appearance with letters of the photograph

[[Image:Ground glass hepatocytes high mag cropped 2.jpg|thumb|right|[[Micrograph]] showing ground glass hepatocytes, as seen in chronic [[hepatitis B]]. [[H&E stain]].]]
This article deals with '''medical [[liver]] disease'''. An introduction to the liver and approach is found in the ''[[liver]]'' article.

Every differential in liver pathology has "drugs"<ref>{{Ref PCPBoD8|448}}</ref> -- if it isn't clearly malignancy.

Liver neoplasms are dealt with in the ''[[liver neoplasms]]'' article.

Medical liver biopsies are often non-specific, as the liver has the same appearance for many mechanisms of injury, especially when the injury is marked. The clinical history, serology and imaging are essential for proper interpretations in this domain of pathology.

=Review of liver blood work=
===Inflammation activity===
*ALT.
*AST.

===Cholestatic markers===
*ALP.
*GGT - used to assess whether the ALP is an "honest" value, elevated in cirrhosis.

===Cirrhosis/decompensation===
*PLT - low is suggestive of dysfunction.
*INR - high is bad, unless anticoagulated.

===Other===
*Bilirubin.
**Direct (AKA conjugated).
**Indirect (AKA unconjugated).

A short DDx of elevated:<ref>{{Ref PCPBoD8|441}}</ref>
*Indirect:
**[[Gilbert syndrome]].
**Crigler-Najjar syndrome type 1.
**Crigler-Najjar syndrome type 2.
*Direct:
**Rotor syndrome.
**Dubin-Johnson syndomre.

===Viral hepatitis===
*HBV DNA.
*HCV RNA.
*HBs Ag, HBs Ab, HBe Ag, HBe Ab.
*HCV Ab.

Others:
*[[Epstein-Barr virus]] (EBV).
*[[Cytomegalovirus]] (CMV) - especially in the immune incompetent.

====Hepatitis B====
Meaning & utility of the various [[Hepatitis B]] tests:<ref>URL: [http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/hepatology/hepatitis-B/ http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/hepatology/hepatitis-B/]. Accessed on: 16 May 2011.</ref><ref name=lto_hepb>URL: [http://www.labtestsonline.org/understanding/analytes/hepatitis_b/test.html http://www.labtestsonline.org/understanding/analytes/hepatitis_b/test.html]. Accessed on: 16 May 2011.</ref>
{| class="wikitable sortable" border="1"
! Test name
! Location
! Positive test
! Negative test
! Usual question
|-
| HBs Ag||Surface||Virus active||No active infection||Active infection?
|-
| HBs Ab||Surface||Exposed OR vaccinated||No exposure OR no vaccine OR loss of Ab||Immunization status?
|-
| HBe Ag||Virus core||Infect. w/ viral replication||No active infection||Active infect. w/ viral replication?
|-
| HBe Ab||Virus core||Exposed to virus||Infect. w/o antibody response OR not exposed||Immune response to infection?
|-
| HBV DNA||-||Active||Not active/no exposure||Viral load/how active?
|-
| HBc Ab||Virus core||Virus active/previous exposure||No exposure||Early active infection?
|}
Notes:
*''HBc Ab'' may test for acute (IgM) or chronic infection - dependent on specific antibody test; it is often used to look for early infection.<ref name=lto_hepb>URL: [http://www.labtestsonline.org/understanding/analytes/hepatitis_b/test.html http://www.labtestsonline.org/understanding/analytes/hepatitis_b/test.html]. Accessed on: 16 May 2011.</ref>
*''Carriers of hepatitis B'': HBs Ag +ve, HBs Ab -ve, HBc Ag -ve, HBc Ab +ve, HBe Ag -ve, HBe Ab +ve.<ref>URL: [http://labtestsonline.org/understanding/analytes/hepatitis-b/tab/test http://labtestsonline.org/understanding/analytes/hepatitis-b/tab/test]. Accessed on: 3 May 2012.</ref>

===Markers for rare liver diseases===
*Ceruloplasm - low think ''[[Wilson's disease]]''; typical value for Wilson's ~ 0.12 g/L.
**<0.20 g/L is a criteria for Wilson's disease.<ref name=pmid18556333>Diagnostic accuracy of serum ceruloplasmin in Wilson disease: determination of sensitivity and specificity by ROC curve analysis among ATP7B-genotyped subjects. Mak CM, Lam CW, Tam S. Clin Chem. 2008 Aug;54(8):1356-62. Epub 2008 Jun 12. PMID 18556333. URL: [http://www.clinchem.org/cgi/reprint/54/8/1356.pdf http://www.clinchem.org/cgi/reprint/54/8/1356.pdf]. Accessed on: 28 September 2009.</ref>
*Alpha-1 antitrypsin - if low think ''deficiency''.

===Hemosiderosis===
*Ferritin - high.
*Iron saturation - high.

Causes:
*Hemochromatosis.
*Hemolysis, chronic.
*Cirrhosis.

=Medical imaging=
Blood flow:<ref>URL: [http://insidesurgery.com/2010/12/hepatopedal-hepatofugal-flow/ http://insidesurgery.com/2010/12/hepatopedal-hepatofugal-flow/]. Accessed on: 2 December 2011.</ref>
*Hepatopedal flow = normal portal vein flow.
*Hepatofugal flow = reversed portal vein flow.

==Interventional measurements==
Wedged to free hepatic venous pressure:<ref name=pmid1864548>{{Cite journal | last1 = Bion | first1 = E. | last2 = Brenard | first2 = R. | last3 = Pariente | first3 = EA. | last4 = Lebrec | first4 = D. | last5 = Degott | first5 = C. | last6 = Maitre | first6 = F. | last7 = Benhamou | first7 = JP. | title = Sinusoidal portal hypertension in hepatic amyloidosis. | journal = Gut | volume = 32 | issue = 2 | pages = 227-30 | month = Feb | year = 1991 | doi = | PMID = 1864548 | PMC = 1378815 | URL = http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1378815/?tool=pubmed }}</ref>
*Normal = 1-4 mmHg.
**Elevated in [[portal hypertension]].

=Liver biopsy=
==Medical liver biopsy adequacy==
Liver biopsy specimens should be:<ref>{{Ref MacSween|418}}</ref>
*2.0 cm in length and contain 11-15 portal tracts,
*The core should be deeper than 1.0 cm from the liver capsule; specimens close to the capsule may lead to over grading of fibrosis.

==Reporting==
{{Main|Pathology reports}}
<pre>
Specimen, procedure:
- Diagnosis.
</pre>
The diagnosis usually contains grading and staging information, e.g. ''activity 2 /4, Laennec fibrosis stage 1 /4''.

In the context of medical liver disease:
*Grade = inflammation/activity.
*Stage = severity of fibrosis/architectural changes.

Notes:
*The term "acute" is infrequently used in liver pathology.
*In the liver: neutrophils ''is not'' acute -- unlike most elsewhere in the body.<ref>OA. September 2009.</ref>

===A microscopic checklist===
<pre>
Size of biopsy: Adequate
Fragmentation: Absent
Fibrosis: Stage 2-3/4, mostly stage 2
Fibrous septa: Present
Septa with curved contours: Present – focally only
Large droplet steatosis (% of hepatocytes): Present, moderate 60%
Ballooning of hepatocytes: Present, rare
Mallory-Denk bodies: Present, rare
Portal inflammation: Present
Interface activity: Minimal (0-1/4)
Lobular necroinflammation: Minimal
Ducts: Present in normal numbers
Duct injury: Absent
Ductular reaction: Absent
Cholestasis: Absent
Terminal hepatic venules: Present
Iron stain: Absent
Ground glass cells with routine stains: Absent
PASD for alpha-1 antitrypsin droplets: Negative
</pre>

=Viral hepatitis=
These are common. The diagnoses are based on serology. The serology is covered in the ''[[Liver_pathology#Viral_hepatitis|viral hepatitis]]'' section in the ''[[liver pathology]]'' article.

Typically classified as:<ref name=pmid8048409>{{Cite journal | title = Terminology of chronic hepatitis, hepatic allograft rejection, and nodular lesions of the liver: summary of recommendations developed by an international working party, supported by the World Congresses of Gastroenterology, Los Angeles, 1994. | journal = Am J Gastroenterol | volume = 89 | issue = 8 Suppl | pages = S177-81 | month = Aug | year = 1994 | doi = | PMID = 8048409 }}</ref><ref>URL: [http://familydoctor.org/familydoctor/en/diseases-conditions/hepatitis-b.html http://familydoctor.org/familydoctor/en/diseases-conditions/hepatitis-b.html]. Accessed on: 2 May 2012.</ref>
#Acute < 6 months duration.
#Chronic > 6 months duration.

==Hepatitis A==
*Infection is self-limited, i.e. not persistent.
**May present as ''[[fulminant hepatic necrosis]]''.
*Usually asymptomatic in children.<ref name=pmid20068336>{{cite journal |author=Jeong SH, Lee HS |title=Hepatitis A: clinical manifestations and management |journal=Intervirology |volume=53 |issue=1 |pages=15–9 |year=2010 |pmid=20068336 |doi=10.1159/000252779 |url=}}</ref>
*Serology is diagnostic.

==Hepatitis B==
:''Hepatitis B virus'', abbreviated ''HBV'', redirects here.
{{Main|Hepatitis B}}

==Hepatitis C==
{{Main|Hepatitis C}}

=Other infections=
*Hydatid disease (Hydatid cyst).
*Ascaris.
*Fasciola

==Hydatid disease==
*[[AKA]] ''hydatid cyst''.
===General===
*Etiology: ''[[Echinococcus]]''.

===Microscopic===
Features:
*Laminated wall +/- calcification.<ref name=Ref_PBPoD8_448>{{Ref PCPBoD8|448}}</ref>
*Organisms -- see ''[[Echinococcus]]''.

====Images====
<gallery>
Image:Liver_cyst_wall_-_intermed_mag.jpg | Liver cyst wall - intermed. mag. (WC)
Image:Liver_cyst_wall_-_high_mag.jpg | Liver cyst wall - high mag. (WC)
Image: Laminated liver cyst wall - intermed mag.jpg | Characteristic laminated portion - intermed. mag. (WC)
Image: Laminated liver cyst wall - high mag.jpg | Characteristic laminated portion - high mag. (WC)
</gallery>
[[www]]:
*[http://pathmicro.med.sc.edu/parasitology/hydatid-hist1.jpg Hydatid cyst (med.sc.edu)].
*[http://www.atlas.or.kr/atlas/include/viewImg.html?uid=645 Hydatid cyst (atlas.or.kr)].
*[http://casereports.bmj.com/content/2009/bcr.04.2009.1798.full Hydatid cyst (casereports.bmj.com)].

==Abscess==
A. [[File:1 ABS 1 680x512px.tif|A process replaces most of the liver parenchyma (20X).]]
 
B. [[File:2 ABS 1 680x512px.tif|Fibrinopurulent exudate apposes granulation tissue (200X).]]
 
C. [[File:3 ABS 1 680x512px.tif|Neutrophils lie in widened sinusoids (200X)..]]
 
D. [[File:4 ABS 1 680x512px.tif|Trichrome shows collagenization of spaces of Disse. Scarring about an abscess or other mass lesion should not be interpreted as reflective of the liver in general (200X).]]
 
Abscess. A. A process replaces most of the liver parenchyma. B. Fibrinopurulent exudate apposes granulation tissue. C. Neutrophils lie in widened sinusoids. D. Trichrome shows collagenization of spaces of Disse. Scarring about an abscess or other mass lesion should not be interpreted as reflective of the liver in general (LR 200X).

==Coccidiomycosis==
A. [[File:Coccidiomycosis - 1 - 40X 680x512px shot.tif|500x500px Granulomas at low power]]
 
B. [[File:Coccidiomycosis - 1 - 200X 680x513px shot.tif|500x500px Granulomas with centrally crowded cells & lady slipper macrophage nuclei]]
 
C. [[File:Coccidiomycosis - 1 - 400X 1369x1024px shot.tif|500x500px Center of previous granuloma showing pyknotic macrophage nuclei]]
 
D. [[File:Coccidiomycosis - 1 - GMS 400X 1369x1024px shot.tif|500x500px Four Coccidiomycotic spherules]]
 
Coccidiomycosis. A. Note the granulomas in otherwise undisturbed liver (UL). B. Granuloma with centrally crowded cells & lady slipper macrophage nuclei. C. Center of granuloma with pyknotic macrophage nuclei, "necrotizing". D. Organisms on GMS stain.

=Metabolic and toxic=
==Alcoholic liver disease==
===General===
*Acute and/or chronic liver changes due to excessive [[alcohol]] use - includes:
**''[[Alcoholic steatohepatitis]]'' (ASH), [[AKA]] ''alcoholic hepatitis''.<ref>URL: [http://emedicine.medscape.com/article/170539-overview http://emedicine.medscape.com/article/170539-overview]. Accessed on: 3 May 2012.</ref>
***Alcoholic hepatitis can be with minimal steatosis.<ref>STC. 6 December 2010.</ref>
**[[Steatosis]] - classically macrovescicular and centrilobular.
**Alcoholic [[cirrhosis]].

====Classic lab findings in EtOH abusers====
*AST & ALT elevated with AST:ALT=2:1.
*GGT elevated.
*MCV increased.

===Gross pathology/radiologic findings===
*Classically micronodular pattern.
**May be macronodular.

===Microscopic===
See:
*''[[Steatohepatitis]]'' section and ''[[ballooning degeneration]]'' section.

Features:
*Often zone III damage.
*Cholestatsis common, i.e. yellow staining.
**NASH (non-alcoholic steatohepatitis) usu. does not have cholestasis.<ref>STC. 6 December 2010.</ref>
*Fibrosis starts at central veins.
*Neutrophils (often helpful) -- few other things have PMNs. (???)
**Neutrophils cluster around cells with Mallory hyaline.

====Images====
{|
[[File:1 etoh 3 680x512px.tif| Alcoholic hepatitis with Metavir stage IV fibrosis (advanced fibrosis/cirrhosis).]]
[[File:2 etoh 3 680x512px.tif| Alcoholic hepatitis with Metavir stage IV fibrosis (advanced fibrosis/cirrhosis).]]
 
[[File:3 etoh 3 680x512px.tif| Alcoholic hepatitis with Metavir stage IV fibrosis (advanced fibrosis/cirrhosis).]]
[[File:4 etoh 3 680x512px.tif| Alcoholic hepatitis with Metavir stage IV fibrosis (advanced fibrosis/cirrhosis).]]
 
[[File:5 etoh 3 680x512px.tif| Alcoholic hepatitis with Metavir stage IV fibrosis (advanced fibrosis/cirrhosis).]]
[[File:6 etoh 3 680x512px.tif| Alcoholic hepatitis with Metavir stage IV fibrosis (advanced fibrosis/cirrhosis).]]
|}
Alcoholic hepatitis with Metavir stage IV fibrosis (advanced fibrosis/cirrhosis).
Trichrome shows relatively non-inflamed fibrous bands, as well as [between green dots] nodules. The lack of regeneration throughout might have precluded a diagnosis of cirrhosis, but stage IV fibrosis under the Metavir system is justified (Row 1 Left 20X). Reticulin shows regenerative nodules [left] with mostly two or more nuclei between black lines juxtaposed to non-regenerative hepatocytes on the right, without piecemeal necrosis. (Row 1 Right 100X). Regenerative nodules show occasional neutrophils [red arrow] and cytoplasmic tufts of ballooned cells, sometimes possibly Mallory hyalin [green arrows] (Row 2 Left 200X). Triads (note vein [green arrow], artery [yellow arrow], and interlobular bile duct [blue arrow]) generally showed little or no interface hepatitis, even when expanded by fibrosis and inflamed (Row 2 Right 200X). Occasional foci of spotty necrosis were seen (Row 3 Left 200X). This edge of an inflamed triads shows neutrophils about proliferated bile ducts [red arrows], as well as Mallory-Denk bodies [blue arrows] (Row 4 Left 400X).
{|
[[File:1 etoh 4 680x512px.tif| Cirrhosis in an alcoholic.]]
[[File:2 etoh 4 680x512px.tif| Cirrhosis in an alcoholic.]]
 
[[File:3 etoh 4 680x512px.tif| Cirrhosis in an alcoholic.]]
[[File:4 etoh 4 680x512px.tif| Cirrhosis in an alcoholic.]]
 
[[File:5 etoh 4 680x512px.tif| Cirrhosis in an alcoholic.]]
[[File:6 etoh 4 680x512px.tif| Cirrhosis in an alcoholic.]]
|}
Definite cirrhosis in an alcoholic. Hepatocyte free bands parse tissue, with occasional definite islands [arrows] (Row 1 Left 40X). Trichrome establishes blue fibrosis about isles [arrows] (Row 1 Right 40X). Reticulin stain shows nodules with regeneration, wherein a large proportion of them are at least two nuclei thick [arrows] (Row 2 Left 200X). Bile duct proliferation can be difficult, sometimes mimicking cholangiocarcinoma. Follow the double headed arrows to see how the ductules can be seen to proliferate from a single sources, with all ducts being complete, without necrotic epithelial cells. (Row 2 Right 400X). PAS with distase can help, as cholangiocarcinoma generally lacks the red rim of proliferating bile ductules [arrows]; again note the connections that can be made between the ductule openings by the blue double headed arrows. The cyan double headed arrows show general parallelism, consistent with uniform directionality induced by extrinsic force, not a neoplastic spread (Row 3 Left 400X). Trichrome shows the most difficult focus. Double headed arrows display the connectivity seen before of the proliferated bile ductules. Note that numerous pairs of adjacent perpendicular glands without a head to foot appearance are not seen that would indicate the disorderly spread of cholangiocarcinoma (Row 3 Right 400X).

{|
[[File:1 ALC 2 680x512px.tif|Expanded, inflamed triads with increased bile duct/vascular openings. Mild steatosis (40X).]]
[[File:2 ALC 2 680x512px.tif|Trichrome stain shows periportal fibrosis [red arrowheads] (200X).]]
 
[[File:3 ALC 2 680x512px.tif|PAS with diastase stain shows proliferated bile ductules [blue arrowheads] in stroma with mixed inflammatory infiltrate (400X)]]
[[File:4 ALC 2 680x512px.tif|Neutrophils about ballooned hepatocyte (satellitosis) [yellow arrowheads]. Councilman bodies [green arrowheads] (400X).]]
|}
Alcoholic hepatitis without cirrhosis. No history of viral disease. AMA negative. Expanded, inflamed triads with increased bile duct/vascular openings. Mild steatosis (UL 40X). Trichrome stain shows periportal fibrosis [red arrowheads] (UR 200X). PAS with diastase stain shows proliferated bile ductules [blue arrowheads] in stroma with mixed inflammatory infiltrate (LL 400X) Neutrophils about ballooned hepatocyte (satellitosis) [yellow arrowheads]. Councilman bodies [green arrowheads] (LR 400X).

Notes:
*If portal inflammatory infiltrates more than mild, r/o other causes i.e. [[viral hepatitis]].
*Mallory bodies once thought to be characteristic; now considered non-specific and generally poorly understood.<ref>{{cite journal |author=Jensen K, Gluud C |title=The Mallory body: theories on development and pathological significance (Part 2 of a literature survey) |journal=Hepatology |volume=20 |issue=5 |pages=1330-42 |year=1994 |month=November |pmid=7927269 |doi= |url=}}</ref>
*Some consider ''alcoholic liver disease'' a clinical diagnosis, i.e. as a pathologist one does not diagnose it.<ref>MG. September 2009.</ref>

==Non-alcoholic fatty liver disease==
*Abbreviated ''NAFLD''.
*Fatty liver that is not due to alcohol; includes obesity-related fatty liver, metabolic disease/diabetes-related fatty liver.

===NASH===
*Non-alcoholic steatohepatitis - see ''steatohepatitis'' section.
*Histologically indistinguishable from ASH.
*NASH is a ''clinical diagnosis'' based on exclusion of alcohol.

==Steatohepatitis==
{{Main|Steatohepatitis}}

=Autoimmune=
==Autoimmune hepatitis==
*Abbreviated ''AIH''.
{{Main|Autoimmune hepatitis}}

==Primary biliary cirrhosis==
*Abbreviated PBC.
{{Main|Primary biliary cirrhosis}}

==Autoimmune hepatitis with obstruction - combined changes==
{|
[[File:1 AIH OBS 1.tif|Low power shows inflammation; portal triads, lobules, central veins cannot be distinguished (40X).]]
[[File:2 AIH OBS 1.tif|Trichrome shows central venous sclerosis (red arrowhead), periportal fibrosis (green arrowhead), & space of Disse collagenization (yellow arrowhead); juxtaposition of central vein & portal tract indicates collapse, no definite bridging was seen (100X)]]
 
[[File:3 AIH OBS 1.tif|Central vein is inflamed with a rare plasma cell (cyan arrowhead) (400X).]]
[[File:4 AIH OBS 1.tif|Interface hepatitis with plasma cells (yellow arrows) and ballooned hepatocytes (red arrows). Lobule is disorganized (400X).]]
 
[[File:5 AIH OBS 1.tif|Proliferating bile ductules (blue arrows) with occasional neutrophils (fucsia arrows), indicative of obstruction, but not acute cholangitis, which requires inflamed bile duct itself, best diagnosed with associated blood vessel (400X).]]
[[File:6 AIH OBS 1.tif|Rare distorted rosettes with greenish brown strands of bile (left arrow) or bile plugs (right arrow) (400X).]]
|}
Patient with SLE and obstructive jaundice that resolved with apparent passage of stone. Low power shows inflammation; portal triads, lobules, central veins cannot be distinguished (left row 1 40X). Trichrome shows central venous sclerosis (red arrowhead), periportal fibrosis (green arrowhead), & space of Disse collagenization (yellow arrowhead); juxtaposition of central vein & portal tract indicates collapse, no definite bridging was seen (right row 1 100X). Central vein is inflamed with a rare plasma cell (cyan arrowhead) (left row 2 400X). Interface hepatitis with plasma cells (yellow arrows) and ballooned hepatocytes (red arrows). Lobule is disorganized (right row 2 400X). Proliferating bile ductules (blue arrows) with occasional neutrophils (fucsia arrows), indicative of obstruction, but not acute cholangitis, which requires inflamed bile duct itself, best diagnosed with associated blood vessel (left row 3 400X). Rare distorted rosettes with greenish brown strands of bile (left arrow) or bile plugs (right arrow) (right row 3 400X).

==Autoimmune hepatitis-primary biliary cirrhosis overlap syndrome==
*Abbreviation ''AIH-PBC OS''.
===General===
Epidemiology:
*Rare.

Serology:<ref name=pmid19491855>{{Cite journal | last1 = Muratori | first1 = P. | last2 = Granito | first2 = A. | last3 = Pappas | first3 = G. | last4 = Pendino | first4 = GM. | last5 = Quarneti | first5 = C. | last6 = Cicola | first6 = R. | last7 = Menichella | first7 = R. | last8 = Ferri | first8 = S. | last9 = Cassani | first9 = F. | title = The serological profile of the autoimmune hepatitis/primary biliary cirrhosis overlap syndrome. | journal = Am J Gastroenterol | volume = 104 | issue = 6 | pages = 1420-5 | month = Jun | year = 2009 | doi = 10.1038/ajg.2009.126 | PMID = 19491855 }}</ref>
*AMA +ve.
*Anti-dsDNA +ve.

===Microscopic===
:See: ''[[autoimmune hepatitis]]'' and ''[[primary biliary cirrhosis]]''.
{|
[[File:1 AIH PBC 1 680x512px.tif|Expanded portal tracts with fuzzy edges (40X).]]
[[File:2 AIH PBC 1 680x512px.tif|Interface hepatitis with plasma cells (400X).]]
 
[[File:3 AIH PBC 1 680x512px.tif|Loose granuloma (400X).]]
[[File:4 AIH PBC 1 680x512px.tif|Damaged bile duct (400X).]]
|}

AIH/PBC overlap. AMA & ANA positive with Alkaline phosphatase > 2 upper limit of normal & one ALT > 5 times upper limit of normal. Expanded portal tracts with fuzzy edges (UL 40X). IInterface hepatitis with plasma cells (UR 400X). Loose granuloma (LL 400X). Damaged bile duct (LR 400X).

==Primary sclerosing cholangitis==
*Abbreviated ''PSC''.
{{Main|Primary sclerosing cholangitis}}

=Hereditary=
==Caroli disease==
===General===
*Genetic disease.
**Frequently associated with [[autosomal recessive polycystic kidney disease]] (ARPKD).<ref name=omim263200>{{OMIM|263200}}</ref>
**May be seen in isolation.<ref name=omim600643>{{OMIM|600643}}</ref>

Clinical:<ref name=pmid17461493>{{Cite journal | last1 = Yonem | first1 = O. | last2 = Bayraktar | first2 = Y. | title = Clinical characteristics of Caroli's syndrome. | journal = World J Gastroenterol | volume = 13 | issue = 13 | pages = 1934-7 | month = Apr | year = 2007 | doi = | PMID = 17461493 }}</ref>
*Recurrent [[cholangitis]].
*Recurrent [[cholelithiasis]].
*[[Cholangiocarcinoma]]<ref name=pmid17461492>{{Cite journal | last1 = Yonem | first1 = O. | last2 = Bayraktar | first2 = Y. | title = Clinical characteristics of Caroli's disease. | journal = World J Gastroenterol | volume = 13 | issue = 13 | pages = 1930-3 | month = Apr | year = 2007 | doi = | PMID = 17461492 }}</ref> - seen in ~7% of cases.<ref name=pmid15347876>{{Cite journal | last1 = Karim | first1 = AS. | title = Caroli's disease. | journal = Indian Pediatr | volume = 41 | issue = 8 | pages = 848-50 | month = Aug | year = 2004 | doi = | PMID = 15347876 }}</ref>

Note:
*''Caroli syndrome'' = Caroli disease + congenital hepatic fibrosis.<ref name=pmid15888616>{{Cite journal | last1 = Brancatelli | first1 = G. | last2 = Federle | first2 = MP. | last3 = Vilgrain | first3 = V. | last4 = Vullierme | first4 = MP. | last5 = Marin | first5 = D. | last6 = Lagalla | first6 = R. | title = Fibropolycystic liver disease: CT and MR imaging findings. | journal = Radiographics | volume = 25 | issue = 3 | pages = 659-70 | month = | year = | doi = 10.1148/rg.253045114 | PMID = 15888616 | URL = http://radiographics.rsna.org/content/25/3/659.long }}</ref>

===Gross===
*Dilated bile ducts.<ref name=omim263200/>

===Microscopic===
Features:<ref name=pmid17461493/>
*Dilated bile ducts.
*Periductal fibrosis. (???)
*+/-Fibrosis.

Image:
*[http://www.meddean.luc.edu/lumen/MedEd/orfpath/11-3-10.jpg Caroli disease (meddean.luc.edu)].<ref>URL: [http://www.meddean.luc.edu/lumen/MedEd/orfpath/develop.htm http://www.meddean.luc.edu/lumen/MedEd/orfpath/develop.htm]. Accessed on: 1 December 2011.</ref>

==Hereditary hemochromatosis==
:''For secondary causes see [[secondary hemochromatosis]]''.
{{Main|Hereditary hemochromatosis}}

==Wilson disease==
{{Main|Wilson's disease}}

==Alpha-1 antitrypsin deficiency==
*[[AKA]] ''alpha1-antiprotease inhibitor deficiency''.
{{Main|Alpha-1 antitrypsin deficiency }}

=Other=
==Budd-Chiari syndrome==
*[[AKA]] ''hepatic vein obstruction''.
===General===
*Hepatic outflow obstruction.

Clinical triad:<ref name=pmid21573256>{{Cite journal | last1 = Fox | first1 = MA. | last2 = Fox | first2 = JA. | last3 = Davies | first3 = MH. | title = Budd-Chiari syndrome--a review of the diagnosis and management. | journal = Acute Med | volume = 10 | issue = 1 | pages = 5-9 | month = | year = 2011 | doi = | PMID = 21573256 }}</ref>
*Ascites.
*Abdominal pain.
*Hepatomegaly.

Etiology:
*~50% have a [[myeloproliferative disease]].<ref name=pmid18814079>{{Cite journal | last1 = Plessier | first1 = A. | last2 = Valla | first2 = DC. | title = Budd-Chiari syndrome. | journal = Semin Liver Dis | volume = 28 | issue = 3 | pages = 259-69 | month = Aug | year = 2008 | doi = 10.1055/s-0028-1085094 | PMID = 18814079 }}</ref>
*May be due to mass effect from a tumour.

Clinical DDx:
*[[Hepatic veno-occlusive disease]].

===Microscopic===
Features:<ref name=pmid17569137>{{Cite journal | last1 = Aydinli | first1 = M. | last2 = Bayraktar | first2 = Y. | title = Budd-Chiari syndrome: etiology, pathogenesis and diagnosis. | journal = World J Gastroenterol | volume = 13 | issue = 19 | pages = 2693-6 | month = May | year = 2007 | doi = | PMID = 17569137 | url=http://www.wjgnet.com/1007-9327/full/v13/i19/2693.htm }}</ref>
*Sinusoidal dilation in zone III (congestion).
*+/-Hepatocyte drop-out.
*+/-Centrilobular fibrosis.

DDx congestion:
*Congestive heart failure ([[congestive hepatopathy]]).
*Constrictive pericarditis.

==Vanishing bile duct syndrome==
*[[AKA]] ''bile duct loss'', [[AKA]] ''ductopenia''.<ref name=pmid11521176/>
===General===
*Fatal.

DDx:<ref name=pmid18242505/>
*[[Primary biliary cirrhosis]].
*[[Primary sclerosing cholangitis]].
*[[GVHD]].<ref name=pmid7994249>{{Cite journal | last1 = Yeh | first1 = KH. | last2 = Hsieh | first2 = HC. | last3 = Tang | first3 = JL. | last4 = Lin | first4 = MT. | last5 = Yang | first5 = CH. | last6 = Chen | first6 = YC. | title = Severe isolated acute hepatic graft-versus-host disease with vanishing bile duct syndrome. | journal = Bone Marrow Transplant | volume = 14 | issue = 2 | pages = 319-21 | month = Aug | year = 1994 | doi = | PMID = 7994249 }}</ref>
*[[Drug-induced liver disease|Drugs]].<ref name=pmid11352118>{{Cite journal | last1 = Chitturi | first1 = S. | last2 = Farrell | first2 = GC. | title = Drug-induced cholestasis. | journal = Semin Gastrointest Dis | volume = 12 | issue = 2 | pages = 113-24 | month = Apr | year = 2001 | doi = | PMID = 11352118 }}</ref>
*Chronic rejection.<ref name=pmid11521176>{{Cite journal | last1 = Inomata | first1 = Y. | last2 = Tanaka | first2 = K. | title = Pathogenesis and treatment of bile duct loss after liver transplantation. | journal = J Hepatobiliary Pancreat Surg | volume = 8 | issue = 4 | pages = 316-22 | month = | year = 2001 | doi = 10.1007/s0053410080316 | PMID = 11521176 }}</ref>

===Microscopic===
Features:<ref name=pmid18242505>{{Cite journal | last1 = Reau | first1 = NS. | last2 = Jensen | first2 = DM. | title = Vanishing bile duct syndrome. | journal = Clin Liver Dis | volume = 12 | issue = 1 | pages = 203-17, x | month = Feb | year = 2008 | doi = 10.1016/j.cld.2007.11.007 | PMID = 18242505 }}</ref>
*Loss of intrahepatitic bile ducts - '''key feature'''.
*Cholestasis.

Note:
*May occur without fibrosis and inflammation; thus, can be easy to miss.

===IHC===
*[[CK7]] -ve.
**Marks bile ducts.

==Extrahepatic biliary obstruction==
{|
[[File:1 OBS 3 680x512px.tif|Sinusoidal dilatation, circular spaces of hepatocytes, small portal triads(40X).]]
[[File:2 OBS 3 680x512px.tif|Bile in hepatocytes about central vein & in plugs in canaliculi [yellow arrowhead] (400X).]]
 
[[File:3 OBS 3 680x512px.tif|Trichrome shows fibrosis about central vein (400X).]]
[[File:4 OBS 3 680x512px.tif|PAS with diastase shows portal triads with mild edema and chronic inflammation, without tortuous bile duct (400X).]]
|}
Early extrahepatic biliary obstruction, demonstrated radiographically, transient, with rise in bilirubin, alkaline phosphatase, and transaminases. Pure canalicular cholestasis near terminal hepatic venules also seen in acute hepatitis, drug reactions, benign recurrent cholestasis, pregnancy, sepsis, & lymphomas. Sinusoidal dilatation, circular spaces of hepatocytes, small portal triads(UL 40X). Bile in hepatocytes about central vein & in plugs in canaliculi [yellow arrowhead] (UR 400X). Trichrome shows fibrosis about central vein (LL 400X). PAS with diastase shows portal triads with mild edema and chronic inflammation, without tortuous bile duct (LR 400X).

{|
[[File:1 OBS 2 680x512px.tif|Expanded inflamed portal triads, swollen hepatocytes (40X)]]
[[File:2 OBS 2 680x512px.tif|Edematous stroma, proliferating ductules [yellow arrowheads], PAS-D macrophages [red arrowhead] (PAS with diastasse, 200X)]]
 
[[File:3 OBS 2 680x512px.tif|Disordered, often swollen hepatocytes,some with feathery degeneration (net like spaces in cytoplasm [blue arrowhead], rare Councilman body [green arrowhead] (400X)]]
[[File:4 OBS 2 1360x1024px.tif|Bile in hepatocytes [cyan arrrowhead] & in canaliculi [purple arrowheads]. Empty acinar spaces bounded by hepatocytes [orange arrowhead] (400X, higher pixel),]]
|}
Changes of extrahepatic biliary obstruction, months duration. Expanded inflamed portal triads, swollen hepatocytes (UL 40X). Edematous stroma, proliferating ductules [yellow arrowheads], PAS-D macrophages [red arrowhead] (UR PAS with diastasse, 200X). Disordered, often swollen hepatocytes,some with feathery degeneration (net like spaces in cytoplasm) [blue arrowhead], rare Councilman body [green arrowhead] (LL 400X). Bile in hepatocytes [cyan arrrowhead] & in canaliculi [purple arrowheads]. Empty acinar spaces bounded by hepatocytes [orange arrowhead] (LR 400X).
{|
[[File:1 Bd obs 4 680x512px.tif|Expanded, light colored portal triads (arrows)(20X).]]
[[File:2 Bd obs 4 680x512px.tif|Proliferating bile ductules (cyan arrows) with neutrophils (yellow arrows), not specific for acute cholangitis, of assistance with large bile duct obstruction (400X)..]]
 
[[File:3 Bd obs 4 680x512px.tif|Uninflamed interlobular duct (yellow arrow) with, accompanying blood vessel (red arrow) (400X)]]
[[File:4 Bd obs 4 680x512px.tif|Bile infarct with pyknotic nuclei (arrows)(400X).]]
 
[[File:5 Bd obs 4 680x512px.tif|Bile (arrow) in interlobular bile duct with disordered nuclei (400X).]]
[[File:6 Bd obs 4 680x512px.tif|Bile plugs in cannaliculi (red arrows), feathery degeneration producing foamy macrophage like hepatocytes (yellow arrows)(400X).]]
|}
Large bile duct obstruction. Expanded, light colored portal triads (arrows)(Row 1 Left 20X). Proliferating bile ductules (cyan arrows) with neutrophils (yellow arrows), not specific for acute cholangitis, of assistance with large bile duct obstruction (Row 1 Right 400X). Uninflamed interlobular duct (yellow arrow) with, accompanying blood vessel (red arrow) (Row 2 Left 400X). Bile infarct with pyknotic nuclei (arrows)(Row 2 Right 400X). Bile (arrow) in interlobular bile duct with disordered nuclei (Row 3 Left 400X). Bile plugs in cannaliculi (red arrows), feathery degeneration producing foamy macrophage-like hepatocytes (yellow arrows)(Row 3 Right 400X).

==Congestive hepatopathy==
===General===
*Liver failure due to (right) heart failure.
*AKA ''cardiac cirrhosis'' - a term used by clinicians.
**Generally, it does not satisfy pathologic criteria for cirrhosis.<ref>URL: [http://emedicine.medscape.com/article/151792-overview http://emedicine.medscape.com/article/151792-overview]. Accessed on: 17 June 2010.</ref>

===Gross===
*"Nutmeg" liver - yellow spotted appearance.

===Microscopic===
Features:<ref>URL: [http://emedicine.medscape.com/article/151792-diagnosis http://emedicine.medscape.com/article/151792-diagnosis]. Accessed on: 17 June 2010.</ref>
*Zone III atrophy.
*Portal venule (central vein) distension.
*Perisinusoidal fibrosis - progresses to centrilobular fibrosis and then diffuse fibrosis.
*Dilation of sinusoids in ''all'' zone III areas - '''key feature'''.<ref>Suggested by OA. September 2009.</ref>

DDx:
*[[Hemangioma of the liver]] - should be focal lesion.
Cardiac (congestive) hepatopathy, wherein outflow obstruction occurs secondary to backflow from a failing heart, and Budd Chiari syndrome, wherein obstruction of outflow occurs secondary to obstruction, usually thrombotic, have overlapping features, including sinusoidal dilation with emphasis upon the central vein, space of Disse erythrocytes, centrilobular inflammation, hemorrhage, bile ductules, and hemosiderin, and portal inflammation, fibrosis and bile ductular reaction. Centrilobular dropout/necrosis is more common in Budd Chiari syndrome, while peri-central venous and sinusoidal fibrosis are more common in cardiac hepatopathy. In end stage liver, fibrosis for cardiac hepatopathy comprises stellate centrizonal fibrous with haphazard spread, as opposed to the more frequent nodular cirrhosis in Budd-Chiari. Clinical findings are important to take into account, as cardiac failure is usually well known at the time of diagnosis as are the clinical predictors of Budd Chiari syndrome, prothrombotic states, myeloproliferative diseases, and oral contraceptive use. <ref name=pmid27681331 >{{cite journal |author=Gonzalez RS, Gilger MA, Huh WJ, Washington MK |title=The spectrum of histologic findings in hepatic outflow obstruction |journal= Arch Pathol Lab Med |volume=141 |issue= |pages=98 |year=2017 |pmid= 27681331 ||doi= 10.5858/arpa.2015-0388-OA |url=http http://www.archivesofpathology.org/doi/10.5858/arpa.2015-0388-OA?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%3dpubmed&code=coap-site }}</ref>
====Images====
<gallery>
Image:Congestive_hepatopathy_high_mag.jpg | Mild congestive hepatopathy. (WC) 
A.[[File:1 CEN NEC 1 680x512px.tif|PAS without diastase shows ovoids of necrosis {40X).]] 
B. [[File:2 CEN NEC 1 680x512px.tif|Necrosis with central vein [yellow arrowhead], inflammatory cells, residual Councilman body [green arrowhead], and hepatocyte with mitotic figure [red arrowhead] (400X).]]
 
C. [[File:3 CEN NEC 1 680x512px.tif|Trichrome highlights fibrosis about central vein [yellow arrowhead] & shows beginning scar formation [green arrowheads]. Note residual atrophic hepatocytes [blue arrowheads] (400X).]]
 
D. [[File:4 CEN NEC 1 680x512px.tif|Portal triads are largely unaffected (400X).]]
|} 
Centrilobular necrosis (seen in circulatory failure and with toxins/drugs). A. PAS without diastase shows ovoids of necrosis. B. Necrosis with central vein [yellow arrowhead], inflammatory cells, residual Councilman body [green arrowhead], and hepatocyte with mitotic figure [red arrowhead]. C. Trichrome highlights fibrosis about central vein [yellow arrowhead] & shows beginning scar formation [green arrowheads]. Note residual atrophic hepatocytes [blue arrowheads]. D. Portal triads are largely unaffected (LR 400X)
 
A. [[File:1 CHF 1 680x512px.tif|Dilated and undilated sinusoidal regions (40X).]]
 
B. [[File:2 CHF 1 680x512px.tif|Thrombi in sinusoids; glycogenated nuclei likely reflect patient’s diabetes mellitus (400X).]]
 
C. [[File:3 CHF 1 680x512px.tif|Dilated portal vein (400X).]]
 
D. [[File:4 CHF 1 680x512px.tif|Reticulin shows collapse (thick black lines) as well as a dilated portal vein (200X).]]
 
E. [[File:5 CHF 1 680x512px.tif|Trichrome shows space of Disse collagenization (pericellular fibrosis) (200X).]]
 
F. [[File:6 CHF 1 680x512px.tif|Trichrome shows periportal fibrosis; no bridging was seen (200X).]]

Patient with congestive heart failure and stage I fibrosis. A. Dilated and undilated sinusoidal regions. B. Thrombi in sinusoids; glycogenated nuclei likely reflect patient’s diabetes mellitus. C. Dilated portal vein. D. Reticulin shows black lines of bridging, too thick for collapse. E. Trichrome shows space of Disse collagenization (pericellular fibrosis). F. Trichrome shows bridge beginning off to right; when it is more than a mere spike, it is a bridge.

==Drug-induced liver disease==
*[[AKA]] ''drug-induced liver toxicity''.
{{Main|Drug-induced liver disease}}

==Focal nodular hyperplasia==
*Abbreviated ''FNH''.
{{Main|Focal nodular hyperplasia}}

==Nodular regenerative hyperplasia==
===General===
*Associated with renal transplants, [[bone marrow transplant]]s and [[vasculitides]].<ref name=Ref_PBoD922>{{Ref PBoD|922}}</ref>
*Can lead to [[portal hypertension]] and many of the associated complications.<ref name=pmid22554152>{{Cite journal | last1 = Bissonnette | first1 = J. | last2 = Généreux | first2 = A. | last3 = Côté | first3 = J. | last4 = Nguyen | first4 = B. | last5 = Perreault | first5 = P. | last6 = Bouchard | first6 = L. | last7 = Pomier-Layrargues | first7 = G. | title = Hepatic hemodynamics in 24 patients with nodular regenerative hyperplasia and symptomatic portal hypertension. | journal = J Gastroenterol Hepatol | volume = 27 | issue = 8 | pages = 1336-40 | month = Aug | year = 2012 | doi = 10.1111/j.1440-1746.2012.07168.x | PMID = 22554152 }}
</ref>

====Etiology====
*Arterial hypervascularity secondary to loss of hepatic vein radicles (loss of central venule in hepatic lobule).<ref name=Ref_PBoD922>{{Ref PBoD|922}}</ref>

ASIDE: radicle = ramulus - smallest branch or vessel or nerve.<ref name=Dorlands2>Dorland's Medical Dictionary. 30th Ed.</ref>

===Gross===
*Diffuse nodularity - whole liver.

===Microscopic===
Features:<ref name=Ref_PBoD922>{{Ref PBoD|922}}</ref>
*"Plump" hepatocytes surrounded by atrophic ones.
*No fibrosis.

==Sinuosoidal obstruction syndrome==
*May be referred to as ''Hepatic veno-occlusive disease''.<ref name=pmid11928077>{{Cite journal | last1 = DeLeve | first1 = LD. | last2 = Shulman | first2 = HM. | last3 = McDonald | first3 = GB. | title = Toxic injury to hepatic sinusoids: sinusoidal obstruction syndrome (veno-occlusive disease). | journal = Semin Liver Dis | volume = 22 | issue = 1 | pages = 27-42 | month = Feb | year = 2002 | doi = 10.1055/s-2002-23204 | PMID = 11928077 }}.</ref>
===General===
*Term for obstruction due to toxicity from a chemotherapeutic agent.<ref name=pmid16393276>{{Cite journal | last1 = Helmy | first1 = A. | title = Review article: updates in the pathogenesis and therapy of hepatic sinusoidal obstruction syndrome. | journal = Aliment Pharmacol Ther | volume = 23 | issue = 1 | pages = 11-25 | month = Jan | year = 2006 | doi = 10.1111/j.1365-2036.2006.02742.x | PMID = 16393276 }}</ref><ref name=pmid17569137>{{Cite journal | last1 = Aydinli | first1 = M. | last2 = Bayraktar | first2 = Y. | title = Budd-Chiari syndrome: etiology, pathogenesis and diagnosis. | journal = World J Gastroenterol | volume = 13 | issue = 19 | pages = 2693-6 | month = May | year = 2007 | doi = | PMID = 17569137 | url=http://www.wjgnet.com/1007-9327/full/v13/i19/2693.htm }}</ref>

Clinical DDx:
*[[Budd-Chiari syndrome]].

===Microscopic===
Features:<ref name=pmid17569137>{{Cite journal | last1 = Aydinli | first1 = M. | last2 = Bayraktar | first2 = Y. | title = Budd-Chiari syndrome: etiology, pathogenesis and diagnosis. | journal = World J Gastroenterol | volume = 13 | issue = 19 | pages = 2693-6 | month = May | year = 2007 | doi = | PMID = 17569137 | url=http://www.wjgnet.com/1007-9327/full/v13/i19/2693.htm }}</ref>
*Subendothelial swelling in hepatic venules.

Negatives:
*No thrombosis.

==Ascending Cholangitis (Acute Cholangitis)==
===General===
*Term for infection of bile ducts, usually due to obstruction

Clinical DDx:

===Microscopic===
====Images====

A. [[File:1 asc chol 1 680x512px.tif|Rounded, clear (edematous) portal tracts (arrows) separated by hepatocytes with dilated sinusoids (Row 1 Left 40X).]]
 
B. [[File:2 asc chol 1 680x512px.tif|Neutrophils about hepatocytes (arrows) have spilled into the lobule from a portal tract (Row 1 Right 200X).]]
 
C. [[File:3 asc chol 1 680x512px.tif|Proliferated bile ductules (arrows) bearing neutrophils within epithelium and lumens are features of obstruction that should prompt a search for interlobular ducts with acute inflammation (Row 2 Left 400X).]]
 
D. [[File:4 asc chol 1 680x512px.tif|The epithelium of the ducts can be severely degenerated. Neutrophils (cyan arrows) invade epithelium of an interlobular duct that are recognizable mainly as a circle of rounded nuclei; the associated arteriole (red arrow) should be identified to ensure an interlobular duct is being evaluated. Note the proliferated bile ductules (blue arrows) (Row 2 Right 400X).]]
 
E. [[File:5 asc chol 1 680x512px.tif|A PAS without diastase stain colors the arteriole (blue arrow), as well as the rim of the interlobular duct within which lies a neutrophil (cyan arrow) (Row 2 Right 400X). .]]
 
F. [[File:6 asc chol 1 680x512px.tif|A PAS with diastase stain colors the arteriole (red arrow), as well as the rim of the interlobular duct within which lies a neutrophil (cyan arrow) (Row 1 Right 400X)]]
 
Acute cholangitis in a patient with multiple bile duct procedures. After the biopsy, removal of bile duct stones released pus. A. Rounded, clear (edematous) portal tracts (arrows) separated by hepatocytes with dilated sinusoids. B. Neutrophils about hepatocytes (arrows) have spilled into the lobule from a portal tract. C, Proliferated bile ductules (arrows) bearing neutrophils within epithelium and lumens are features of obstruction that should prompt a search for interlobular ducts with acute inflammation. D. The epithelium of the ducts can be severely degenerated. Neutrophils (cyan arrows) invade epithelium of an interlobular duct that are recognizable mainly as a circle of rounded nuclei; the associated arteriole (red arrow) should be identified to ensure an interlobular duct is being evaluated. Note the proliferated bile ductules (blue arrows). E. A PAS without diastase stain colors the arteriole (blue arrow), as well as the rim of the interlobular duct within which lies a neutrophil (cyan arrow). F. A PAS with diastase stain colors the arteriole (red arrow), as well as the rim of the interlobular duct within which lies a neutrophil (cyan arrow).

A.[[File:1 Sep Acu Cho 1 680x512px.tif|Low power shows variably sized inflamed portal tracts (40X)]]
 
B. [[File:2 Sep Acu Cho 1 680x512px.tif|Trichrome shows dilated sinusoids and space of Disse collagenization (200X)]]
 
C. [[File:3 Sep Acu Cho 1 680x512px.tif|Inflammatory focus with macrophages and neutrophils (400X).]]
 
D. [[File:4 Sep Acu Cho 1 680x512px.tif|PAS with diastase shows proliferated bile ductules at edge of triad with neutrophils, which should not be used to make a definite diagnosis of acute cholangitis (400X).]]
 
E. [[File:5 Sep Acu Cho 1 680x512px.tif|PAS without diastase showing acutely inflamed bile duct, with accompanying blood vessel of similar size, diagnostic of acute cholangitis (400X).]]
 
F. [[File:6 Sep Acu Cho 1 680x512px.tif|PAS with diastase showing neutrophil in bille duct lumen, diagnostic of acute cholangitis (400X).]]
 
Patient with sepsis and acute cholangitis. A. Low power shows variably sized inflamed portal tracts. B. Trichrome shows dilated sinusoids and space of Disse collagenization. C. Inflammatory focus with macrophages and neutrophils. D. PAS with diastase shows proliferated bile ductules at edge of triad with neutrophils, which should not be used to make a definite diagnosis of acute cholangitis. E. PAS without diastase showing acutely inflamed bile duct, with accompanying blood vessel of similar size, diagnostic of acute cholangitis. F. PAS with diastase showing neutrophil in bille duct lumen, diagnostic of acute cholangitis.

==Polycystic kidney disease and the liver==
{{Main|Cystic kidney disease}}
===General===
Complications of PKD in the liver:<ref>{{Ref MacSween|174-5}}</ref>
#Infected cyst.
#Cholangiocarcinoma.
#Cholestasis/obstruction due to duct compression.<ref>URL: [http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=9184868 http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=9184868]. Accessed on: 23 September 2009.</ref>

Cysts:
*Cysts in the liver, like the kidney, are thought to enlarge with age.

===Microscopic===
Features:<ref>{{Ref MacSween|176}}</ref>
*''Von Meyenburg complexes'' ([[bile duct hamartoma]]):
**Cluster of dilated ducts with "altered" bile.
**Surrounded by collagenous stroma.
**Separate from the portal areas.<ref>Meyenburg complex. Stedman's Medical Dictionary. 27th Ed.</reF>

Images:
*[http://commons.wikimedia.org/wiki/File:Von_Meyenburg_complex_low_mag.jpg Von Meyenburg complex - bile duct hamartoma (WC)].
*[http://commons.wikimedia.org/wiki/File:Bile_duct_hamartoma_intermed_mag.jpg Bile duct hamartoma (WC)].

Notes:
*Appearance on ultrasound<ref name=pmid17287178>Bile duct hamartomas--the von Meyenburg complex. Salles VJ, Marotta A, Netto JM, Speranzini MB, Martins MR. Hepatobiliary Pancreat Dis Int. 2007 Feb;6(1):108-9. PMID 17287178.</ref> and CT (hypodense)<ref name=pmid19294869>[The von Meyenburg complex] Schwab SA, Bautz W, Uder M, Kuefner MA. Rontgenpraxis. 2008;56(6):241-4. German. PMID 19294869.</ref> - similar to metastases.

==Peliosis hepatis==
===General===
*Associated with:
**Infections.
**Malignancy.
**Other stuff.
*Rarely biopsied.

===Microscopic===
Features:
*Cyst lined by endothelium.
**Usu. incomplete.
*Blood.
{|
[[File:1 PEL 1 680x512px.tif|Hemorrhage at left end, dilated sinusoids elsewhere (20X).]]
[[File:2 PEL 1 680x512px.tif|Ramifying dilated sinusoidal spaces (100X).]]
 
[[File:3 PEL 1 680x512px.tif|PAS with diastase shows flat lining (400X).]]
[[File:4 PEL 1 680x512px.tif|Necrotic hepatocytes in cords, presumably due to pressure (400X).]]
|}
Peliosis hepatis. Hemorrhage at left end, dilated sinusoids elsewhere (UL 20X). Ramifying dilated sinusoidal spaces (UR 100X). PAS with diastase shows flat lining (LL 400X). Necrotic hepatocytes in cords, presumably due to pressure (LR 400X).

==Total parenteral nutrition==
*Abbreviated ''TPN''.

===General===
*Indication: short gut syndrome, others.

===Microscopic===
Variable - may range from: steatosis, steatohepatitis, cholestasis, fibrosis and cirrhosis.<ref name=pmid16766237>{{cite journal |author=Guglielmi FW, Boggio-Bertinet D, Federico A, ''et al.'' |title=Total parenteral nutrition-related gastroenterological complications |journal=Dig Liver Dis |volume=38 |issue=9 |pages=623–42 |year=2006 |month=September |pmid=16766237 |doi=10.1016/j.dld.2006.04.002 |url=}}</ref>

Features (classic):<ref>{{Cite journal | last1 = Li | first1 = SJ. | last2 = Nussbaum | first2 = MS. | last3 = McFadden | first3 = DW. | last4 = Gapen | first4 = CL. | last5 = Dayal | first5 = R. | last6 = Fischer | first6 = JE. | title = Addition of glucagon to total parenteral nutrition (TPN) prevents hepatic steatosis in rats. | journal = Surgery | volume = 104 | issue = 2 | pages = 350-7 | month = Aug | year = 1988 | doi = | PMID = 3135627 }}</ref><ref>{{Cite journal | last1 = Stanko | first1 = RT. | last2 = Nathan | first2 = G. | last3 = Mendelow | first3 = H. | last4 = Adibi | first4 = SA. | title = Development of hepatic cholestasis and fibrosis in patients with massive loss of intestine supported by prolonged parenteral nutrition. | journal = Gastroenterology | volume = 92 | issue = 1 | pages = 197-202 | month = Jan | year = 1987 | doi = | PMID = 3096806 }}
</ref>
*[[Steatosis]] (periportal) - early.
*Cholestasis - late.

==Giant cell hepatitis==
*[[AKA]] ''neonatal giant cell hepatitis''.

:See: ''[[Giant cell hepatitis]]''.

==Hepatic amyloidosis==
{{Main|Amyloidosis}}
*[[AKA]] ''liver amyloidosis''.
*[[AKA]] ''amyloidosis of the liver''.
===General===
*Diffuse abundant amyloid within the space of Disse is associated with [[portal hypertension]].<ref name=pmid1864548>{{Cite journal | last1 = Bion | first1 = E. | last2 = Brenard | first2 = R. | last3 = Pariente | first3 = EA. | last4 = Lebrec | first4 = D. | last5 = Degott | first5 = C. | last6 = Maitre | first6 = F. | last7 = Benhamou | first7 = JP. | title = Sinusoidal portal hypertension in hepatic amyloidosis. | journal = Gut | volume = 32 | issue = 2 | pages = 227-30 | month = Feb | year = 1991 | doi = | PMID = 1864548 | PMC = 1378815 | URL = http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1378815/?tool=pubmed }}</ref>

===Microscopic===
Features:
*Amorphous extracellular pink stuff on H&E - see ''[[amyloid]]'' article.

DDx:
*[[Fibrolamellar hepatocellular carcinoma]].

====Images====
<gallery>
Image:Hepatic_amyloidosis_-_low_mag.jpg | Amyloidosis of the liver - low mag. (WC)
Image:Hepatic_amyloidosis_-_intermed_mag.jpg | Amyloidosis of the liver - intermed. mag. (WC)
Image:Hepatic_amyloidosis_-_high_mag.jpg | Amyloidosis of the liver - high mag. (WC)
Image:Hepatic_amyloidosis_-_very_high_mag.jpg | Amyloidosis of the liver - very high mag. (WC)
</gallery>
{|
[[File:1 AMY 1 680x512px.tif|Amorphous material replaces hepatic parenchyma [4X]]]
[[File:2 AMY 1 680x512px.tif|Material barely stains blue on trichrome [10X]]]
 
[[File:3 AMY 1 680x512px.tif|Material stains red on unpolarized Congo Red [40X]]]
[[File:4 AMY 1 680x512px.tif|Material stains apple green on polarized Congo Red [40X]]]
|}
Amyloidosis. Amorphous material replaces hepatic parenchyma [UL 4X]. Material barely stains blue on trichrome [UR 10X] Material stains red on unpolarized Congo Red [LL 40X] Material stains apple green on polarized Congo Red [LR 40X]

===Stains===
*[[Congo red]] +ve.

==Fulminant hepatic necrosis==
===General===
Etiology:
*Viral, i.e. [[Hepatitis A]], [[Hepatitis B]]; [[Hepatitis C]] - extremely rare.
*Trauma.
*Shock.

===Microscopic===
{|
[[File:1 Necrosis 2 680x512px.tif| Submassive hepatic necrosis.]]
[[File:2 Necrosis 2 680x512px.tif| Submassive hepatic necrosis.]]
 
[[File:3 Necrosis 2 680x512px.tif| Submassive hepatic necrosis.]]
[[File:4 Necrosis 2 680x512px.tif| Submassive hepatic necrosis.]]
 
[[File:5 Necrosis 2 680x512px.tif| Submassive hepatic necrosis.]]
[[File:6 Necrosis 2 680x512px.tif| Submassive hepatic necrosis.]]
|}
Submassive hepatic necrosis. Patient had transaminases in the thousands that rapidly dropped to normal. Pink preserved parenchyma strews empty necrotic spaces (Row 1 Left 20X). Focus of necrosis with no apparent hepatocytes macrophages abuts apparently normal liver (Row 1 Right 200X). Iron stain shows the macrophages bear hemosiderin (Row 2 Left 200X). Reticulin stain highlights the recently dead liver cells (Row 2 Right 200X). Reticulin stain shows a necrotic bridge forming; the multiple small black circles preclude diagnosis of a fibrous bridge (Row 3 Left 200X). Trichrome shows the necrotic bridge (“collapse”) lacks much collagen deposition, as would be expected for bridging fibrosis (Row 3 Right 200X).

Features:
*Hepatocyte [[necrosis]].
*Bile duct proliferation.

DDx:
*[[Cholangiocarcinoma]].
*[[Angiosarcoma]].

==Secondary hemochromatosis==
:''For the hereditary one see [[hereditary hemochromatosis]]''.
===General===
*Iron overload secondary to blood transfusions for hereditary or acquired anemia.<ref name=pmid19727383/>
**Primary hemochromatosis due to a defect in iron processing - called ''[[hereditary hemochromatosis]]''.
*Imaging considered the best test, as iron deposition is patchy.<ref name=pmid19727383/>

Selected hereditary causes:<ref name=pmid19727383>{{Cite journal | last1 = Gattermann | first1 = N. | title = The treatment of secondary hemochromatosis. | journal = Dtsch Arztebl Int | volume = 106 | issue = 30 | pages = 499-504, I | month = Jul | year = 2009 | doi = 10.3238/arztebl.2009.0499 | PMID = 19727383 | PMC = 2735704 | URL = http://www.ncbi.nlm.nih.gov.myaccess.library.utoronto.ca/pmc/articles/PMC2735704/?tool=pubmed}}</ref>
*Thalassemia.
*[[Sickle cell anemia]].
*Hereditary sideroblastic anemia.

Selected acquired causes:<ref name=pmid19727383/>
*[[Myelodysplastic syndromes]]
*Myelofibrosis
*Aplastic anemia, intractable.

===Microscopic===
:See ''[[hereditary hemochromatosis]]''.

==Hepatic sarcoidosis==
{{Main|Hepatic sarcoidosis}}
==Overlapping Disorders==

[[File:1 Mixed Disorder 1 680x512px.tif|Changes of steatohepatitis and interface hepatitis, with granuloma. Patient with diabetes was ANA, AMA, HCV, HBV negative, without drugs known to produce granulomas or interface hepatitis. This may be a case of AMA negative primary biliary cirrhosis, but studies to determine that with certainty were not performed.]]
[[File:2 Mixed Disorder 1 680x512px.tif|Changes of steatohepatitis and interface hepatitis, with granuloma. Patient with diabetes was ANA, AMA, HCV, HBV negative, without drugs known to produce granulomas or interface hepatitis. This may be a case of AMA negative primary biliary cirrhosis, but studies to determine that with certainty were not performed.]]
[[File:3 Mixed Disorder 1 680x512px.tif|Changes of steatohepatitis and interface hepatitis, with granuloma. Patient with diabetes was ANA, AMA, HCV, HBV negative, without drugs known to produce granulomas or interface hepatitis. This may be a case of AMA negative primary biliary cirrhosis, but studies to determine that with certainty were not performed.]]
[[File:4 Mixed Disorder 1 680x512px.tif|Changes of steatohepatitis and interface hepatitis, with granuloma. Patient with diabetes was ANA, AMA, HCV, HBV negative, without drugs known to produce granulomas or interface hepatitis. This may be a case of AMA negative primary biliary cirrhosis, but studies to determine that with certainty were not performed.]]
[[File:5 Mixed Disorder 1 680x512px.tif|Changes of steatohepatitis and interface hepatitis, with granuloma. Patient with diabetes was ANA, AMA, HCV, HBV negative, without drugs known to produce granulomas or interface hepatitis. This may be a case of AMA negative primary biliary cirrhosis, but studies to determine that with certainty were not performed.]]
[[File:6 Mixed Disorder 1 680x512px.tif|Changes of steatohepatitis and interface hepatitis, with granuloma. Patient with diabetes was ANA, AMA, HCV, HBV negative, without drugs known to produce granulomas or interface hepatitis. This may be a case of AMA negative primary biliary cirrhosis, but studies to determine that with certainty were not performed.]] 
Changes of steatohepatitis and interface hepatitis, with granuloma. Patient with diabetes was ANA, AMA, HCV, HBV negative, without drugs known to produce granulomas or interface hepatitis. This may be a case of AMA negative primary biliary cirrhosis, but studies to determine that with certainty were not performed. A. Low power shows hepatocytes afflicted by steatosis and an inflamed portal tract. B. In a region of fatty change lie cytoplasmic tufts of ballooning degeneration (green arrows) and a lipogranuloma (black arrow). C. At the portal-hepatocyte junction lies interface hepatitis (black arrows), as well as extension of inflammation into the lobule (green arrows). D. Red hepatocytes bounded by inflammation denote piecemeal necrosis [PAS without diastase]. E. Giant cells intermixed with lymphocytes prove a portal granuloma [PAS without diastase]. F. A blue fibrous bridge extends from a triad [Trichrome].

[[File:4 95599552608917 sl 1.png|Acute obstructive changes and changes of recurrent acute injury]]
[[File:4 95599552608917 sl 2.png|Acute obstructive changes and changes of recurrent acute injury]]
[[File:4 95599552608917 sl 3.png|Acute obstructive changes and changes of recurrent acute injury]]
[[File:4 95599552608917 sl 4.png|Acute obstructive changes and changes of recurrent acute injury]]
[[File:4 95599552608917 sl 5.png|Acute obstructive changes and changes of recurrent acute injury]]
[[File:4 95599552608917 sl 6.png|Acute obstructive changes and changes of recurrent acute injury]]
[[File:4 95599552608917 sl 7.png|Acute obstructive changes and changes of recurrent acute injury]] 
Acute obstructive changes and changes of recurrent injury in 46 yo man with Clostridium perfringens positive blood culture, an ERCP that showed duodenal compression by the pancreas with resultant bile duct dilatation. The patient had had and continued to have multiple bouts of acute pancreatitis. At the time of biopsy, decreased platelet count/hemoglobin/albumin, elevated lipase/amylase/PT/PTT, normal alkaline phosphatase, bilirubin, AST/ALT, AMA, hepatitis virus serology, ANA. A. Fragment biopsy shows inflamed triads and bridges. B. Trichrome shows bridges without nodules, evidence of prior injury; the patient subsequently developed multiple episodes of pancreatitis. C. Reticulin shows piecemeal necrosis, with black lines bounding individual hepatocytes at interface (arrows). D. Collapse is shown by closly approximated thick black lines; one cannot call portal-central collapse without seeing a central vein. Note on this and the other reticulin image that regeneration, two cell thick cords, is not prominent. E. PAS D of two portal triads, far nearer than normal, both expanded. Note increased number of ducts/ductules (red arrows), neutrophils, and PAS-D macrophages. F. PAS D shows collapse extending from a triad to a portion of a lobule with steatosis. No feathery degeneration or bile duct plugs were seen. Neither were foci of spotty necrosis or abscess seen. G. Other triads, again edematous, showed more of a chronic inflammatory response, with occasional plasma cells (black arrows). Also present are neutrophils (red arrows). The bile duct (grey arrow) near the artery (brown arrow) shows mildly disturbed nuclei. Note early proliferated bile ductules (cyan arrows).

[[File:6 17281676469188 sl 1.png| Hepatitis B virus with steatohepatitis]]
[[File:6 17281676469188 sl 2.png| Hepatitis B virus with steatohepatitis]]
[[File:6 17281676469188 sl 3.png| Hepatitis B virus with steatohepatitis]]
[[File:6 17281676469188 sl 4.png| Hepatitis B virus with steatohepatitis]]
[[File:6 17281676469188 sl 5.png| Hepatitis B virus with steatohepatitis]]
[[File:6 17281676469188 sl 6.png| Hepatitis B virus with steatohepatitis]] 
Hepatitis B virus with steatohepatitis in a 36 year old man with hepatitis B surface antigen and hepatitis Be antigen positivity, Hepatitis be QTPC of 1750 cop/mL, an occasionally mildly elevated (42) ALT, and normal glucose, alkaline phosphatase, bilirubin, and other transaminases. He had a history of alcohol abuse, which became controlled. A. Triads show scant inflammation without definite interface hepatitis. About one-fourth of the lobule, not pan-acinar, is afflicted by steatosis. B. Occasional tufts are seen (arrow), indicating focal ballooning sufficient for a diagnosis of steatohepatitis. C. Glycogenated nuclei (black arrows) and hepatocytes with feathery degeneration (red arrows) are seen. D. Very rare foci of spotty necrosis were seen. E. Apart from this triad and the one in the trichrome stain in F, which had moderate inflammation comprising lymphocytes and macrophages, all triads were small, most without any inflammation at all. Neither collapse nor piecemeal necrosis were seen on reticulin stain. F. Trichrome stain showed only portal fibrosis. The interhepatocyte fibrosis required for brunt fibrosis stage I was not seen. Hence, one would grade this as follows: A) Chronic hepatitis (history of hepatitis B), Metavir activity index 1, Piecemeal necrosis 0, Lobular necrosis 1, Metavir fibrosis stage 1, B) Steatohepaitits, Brunt necroinflammatory grade 1, Brunt fibrosis stage 0.

=See also=
*[[Pancreas]].
*[[Gastrointestinal pathology]].
*[[Liver neoplasms]].
*[[Liver]].

=References=
{{reflist|2}}

[[Category:Gastrointestinal pathology]]
[[Category:Liver pathology]]
[[Category:Medical liver disease]]

Intraductal papillary mucinous tumour

2017-02-10T17:39:28Z

Mitchell: /* General */ added a sentence about oncocytic type

'''Intraductal papillary mucinous tumour''', abbreviated '''IPMT''', is an uncommon tumour of the [[pancreas]].

It is also known as '''intraductal papillary mucinous neoplasm''' (abbreviated '''IPMN''').

==General==
*Morphologically and biologically distinct from ductal adenocarcinoma, mucinous cystic tumour and ductal papillary hyperplasia.
*Prognosis:
**Favourable if caught early; not much different than ductal adenocarcinoma if caught late.<ref name=pmid12377813>{{cite journal |author=Maire F, Hammel P, Terris B, ''et al.'' |title=Prognosis of malignant intraductal papillary mucinous tumours of the pancreas after surgical resection. Comparison with pancreatic ductal adenocarcinoma |journal=Gut |volume=51 |issue=5 |pages=717–22 |year=2002 |month=November |pmid=12377813 |pmc=1773420 |doi= |url=http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=12377813}}</ref>
**Dependent what is involved:<ref name=pmid20374620>{{cite journal |author=Baiocchi GL, Portolani N, Missale G, ''et al.'' |title=Intraductal papillary mucinous neoplasm of the pancreas (IPMN): clinico-pathological correlations and surgical indications |journal=World J Surg Oncol |volume=8 |issue= |pages=25 |year=2010 |pmid=20374620 |pmc=2858722 |doi=10.1186/1477-7819-8-25 |url=http://wjso.com/content/8/1/25}}</ref>
***Main duct (bad prognosis).
***Branch (good prognosis).

Clinical:
*Patient usually not jaundiced... as no obstruction.
*Often diabetes... as pancreas is destroyed.
*Patients may get a total pancreatectomy - as the disease is often multifocal.

====Epidemiology====
*~1% of all exocrine pancreatic tumours.
*More common in males.
*Mean age at presentation 62 years.
*60-80% occur in the head of the pancreas.
*Average size 4 cm.

===Classification of IMPT===
Commonly classified by the duct involvement:<ref name=pmid20397268>{{Cite journal | last1 = Ikeuchi | first1 = N. | last2 = Itoi | first2 = T. | last3 = Sofuni | first3 = A. | last4 = Itokawa | first4 = F. | last5 = Tsuchiya | first5 = T. | last6 = Kurihara | first6 = T. | last7 = Ishii | first7 = K. | last8 = Tsuji | first8 = S. | last9 = Umeda | first9 = J. | title = Prognosis of cancer with branch duct type IPMN of the pancreas. | journal = World J Gastroenterol | volume = 16 | issue = 15 | pages = 1890-5 | month = Apr | year = 2010 | doi = | PMID = 20397268 PMC = 2856831 | URL = http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2856831/}}</ref>
#Main duct type.
#*Commonly associated with invasive carcinoma.
#Branch duct type.
#*Less commonly associated with invasive carcinoma.

The oncocytic subtype of IPMT is now known to be genetically separate from other types.<ref name=pmid27282351>{{cite journal |author=Basturk O, Tan M, Bhanot U, Allen P, Adsay V, Scott SN, Shah R, Berger MF, Askan G, Dikoglu E, Jobanputra V, Wrzeszczynski KO, Sigel C, Iacobuzio-Donahue C, Klimstra DS. |title=The oncocytic subtype is genetically distinct from other pancreatic intraductal papillary mucinous neoplasm subtypes |journal=Mod Pathol |volume=29 |pages=1058-69 |year=2016 |pmid=27282351 }}</ref>
=====Behaviour=====
*Adenoma.
*Borderline mucinous tumour.
*Carcinoma.

Notes:
*Borderline tumours are rare.
*If intralobular dilated ducts... carcinoma.
*Any margin with mucin cells in thought to be badness!

==Gross==
*May be patchy/multifocal.
*Multiple cystic spaces.

==Microscopic==
Features:
*Pancreatic duct lining cells jut into the duct lumen - papillomatous growth pattern.
*Cytology:
**Cell enlargement.
***Increased mucin production.
**Nuclear changes:
***Increased [[NC ratio]].
***Nuclear crowding and [[nuclear pleomorphism|pleomorphism]].
**Mitotic activity.

Note:
*No ovarian type stroma underneath (as seen in mucinous tumours).

DDx:
*[[PanIN]].
*[[Invasive ductal carcinoma of the pancreas]].
*Intra-ampullary papillary-tubular neoplasm -- see ''[[ampulla of Vater]]''.

==See also==
*[[Pancreas]].

==References==
{{Reflist|1}}
[[Category:Pancreas]]
[[Category:Diagnosis]]

Urothelial carcinoma

2017-02-03T20:44:32Z

Mitchell: /* Images */ add a case

{{ Infobox diagnosis
| Name = {{PAGENAME}}
| Image = Urothelial carcinoma positive margin -- high mag.jpg
| Width =
| Caption = Urothelial carcinoma at a [[surgical margin]]. [[H&E stain]].
| Synonyms = urothelial cell carcinoma
| Micro =
| Subtypes = [[microcystic urothelial carcinoma|microcystic]], [[micropapillary urothelial carcinoma|micropapillary]], glandular, inverted (growth pattern), [[nested urothelial carcinoma|nested]], papillary (dealt with separately in ''[[high-grade papillary urothelial carcinoma]]'' and ''[[low-grade papillary urothelial carcinoma]]''), [[plasmacytoid urothelial carcinoma]], others
| LMDDx = [[urothelial carcinoma in situ]], metastatic carcinoma ([[prostate carcinoma]], [[colorectal carcinoma]]), [[inverted urothelial papilloma]] (for UCC with inverted growth pattern)
| Stains =
| IHC = [[GATA3]] +ve, p63 +ve, CK5/6 +ve, CK34betaE12 +ve, PSA -ve
| EM =
| Molecular = not used for diagnosis; typically: 9p deletions, 17p deletions
| IF =
| Gross =
| Grossing = [[radical cystectomy grossing]], [[cystoprostatectomy grossing]], [[nephroureterectomy grossing]]
| Staging = [[bladder cancer staging]]
| Site = [[urothelium]] - [[ureter]], [[urinary bladder]], proximal [[urethra]] (see [[urothelial carcinoma of the urethra]], renal pelvis
| Assdx =
| Syndromes = [[Lynch syndrome]] - esp. ureters
| Clinicalhx = typically [[smoking|smokers]]
| Signs = hematuria
| Symptoms =
| Prevalence = common
| Bloodwork =
| Rads =
| Endoscopy =
| Prognosis = dependent on grade and stage
| Other =
| ClinDDx =
| Tx = dependent on grade and stage
}}
'''Urothelial carcinoma''', also '''urothelial cell carcinoma''', is a [[malignancy]] that arises from the [[urothelium]]. ''Urothelial carcinoma'' is abbreviated '''UC''' and ''urothelial cell carcinoma'' is abbreviated '''UCC'''.

This article deals with flat invasive urothelial carcinoma. The direct precursor is dealt with in ''[[urothelial carcinoma in situ]]''.

Papillary urothelial carcinomas are dealt with in ''[[low-grade papillary urothelial carcinoma]]'' and ''[[high-grade papillary urothelial carcinoma]]''.

See ''[[Urine_cytopathology#Urothelial_cell_carcinoma|urine cytology]]'' for the [[cytopathology]].

=General=
*These lesions lack papillae and are typical flat.
*Clinically, it may not be possible to differentiate renal pelvis urothelial carcinoma and [[renal cell carcinoma]].
*May be a part of [[Lynch syndrome]].

Prognosis:
*Women often have worse outcomes as they present with more advanced tumours.<ref name=pmid24239476>{{Cite journal | last1 = Mitra | first1 = AP. | last2 = Skinner | first2 = EC. | last3 = Schuckman | first3 = AK. | last4 = Quinn | first4 = DI. | last5 = Dorff | first5 = TB. | last6 = Daneshmand | first6 = S. | title = Effect of gender on outcomes following radical cystectomy for urothelial carcinoma of the bladder: a critical analysis of 1,994 patients. | journal = Urol Oncol | volume = 32 | issue = 1 | pages = 52.e1-9 | month = Jan | year = 2014 | doi = 10.1016/j.urolonc.2013.08.007 | PMID = 24239476 }}</ref>
*Positive soft tissue [[margin status|margin]].<ref name=pmid17936804>{{Cite journal | last1 = Dotan | first1 = ZA. | last2 = Kavanagh | first2 = K. | last3 = Yossepowitch | first3 = O. | last4 = Kaag | first4 = M. | last5 = Olgac | first5 = S. | last6 = Donat | first6 = M. | last7 = Herr | first7 = HW. | title = Positive surgical margins in soft tissue following radical cystectomy for bladder cancer and cancer specific survival. | journal = J Urol | volume = 178 | issue = 6 | pages = 2308-12; discussion 2313 | month = Dec | year = 2007 | doi = 10.1016/j.juro.2007.08.023 | PMID = 17936804 }}</ref>
**Definition (radical cystectomy): tumour touching [[ink]].

Risk factors:
*[[Smoking]].
*Toxins.
*Drugs, e.g. cyclophosphamide.
*Others.

=Microscopic=
Features:
*Nuclear pleomorphism - '''key feature'''.
**Compare nuclei to one another.
*Increased N/C ratio.
*Lack of maturation to surface (important).
*Cells become dyscohesive.

Invasion vs. in situ:
Useful features - present in invasion:<ref>Sternberg, SE. Histology for Pathologists. P.2047.</ref>
*Thin-walled vessels.
*Stromal reaction (hypercellularity).
*Retraction artefact around the tumour cell nests.

Note:
*The presence/absence of muscle should be commented on in biopsy specimens.
*Adipose tissue may be seen in the lamina propria; tumour adjacent to adipose tissue on a biopsy does '''not''' imply invasion deep to the muscularis propria.<ref name=pmid7879346>{{Cite journal | last1 = Bochner | first1 = BH. | last2 = Nichols | first2 = PW. | last3 = Skinner | first3 = DG. | title = Overstaging of transitional cell carcinoma: clinical significance of lamina propria fat within the urinary bladder. | journal = Urology | volume = 45 | issue = 3 | pages = 528-31 | month = Mar | year = 1995 | doi = 10.1016/S0090-4295(99)80030-2 | PMID = 7879346 }}</ref>

DDx:
*[[Pseudocarcinomatous urothelial hyperplasia]].
*[[Urothelial carcinoma in situ]].
*[[High-grade papillary urothelial carcinoma]].
*[[Low-grade papillary urothelial carcinoma]].
*[[Prostate carcinoma]] - may have pseudopapillae<ref name=pmid24503758>{{cite journal |author=Gordetsky J, Epstein JI |title=Pseudopapillary features in prostatic adenocarcinoma mimicking urothelial carcinoma: a diagnostic pitfall |journal=Am. J. Surg. Pathol. |volume=38 |issue=7 |pages=941–5 |year=2014 |month=July |pmid=24503758 |doi=10.1097/PAS.0000000000000178 |url=}}</ref> - see ''[[urothelial carcinoma-like prostatic carcinoma]]''.

==Staging==
{{Main|Bladder cancer staging}}
*T1 - lamina propria.
**Several subdivisions of T1 exist:
***T1a - superficial or in muscularis mucosae.
***T1b - beyond muscularis mucosae - into submucosa.
*T2 - muscularis propria.

Note:
*Approximately 25% of muscle invasive urothelial carcinoma on biopsy is a lower stage in the cystectomy specimen.<ref name=pmid22915241>{{Cite journal | last1 = D'Souza | first1 = AM. | last2 = Pohar | first2 = KS. | last3 = Arif | first3 = T. | last4 = Geyer | first4 = S. | last5 = Zynger | first5 = DL. | title = Retrospective analysis of survival in muscle-invasive bladder cancer: impact of pT classification, node status, lymphovascular invasion, and neoadjuvant chemotherapy. | journal = Virchows Arch | volume = 461 | issue = 4 | pages = 467-74 | month = Oct | year = 2012 | doi = 10.1007/s00428-012-1249-4 | PMID = 22915241 }}</ref>
**In approximately 15% of cases it is pT0 (no primary tumour identified).

===Muscularis propria invasion===
{{Main|Muscularis propria invasion in the urinary bladder}}

==Images==
<gallery>
Image: Urothelial carcinoma positive margin -- intermed mag.jpg | Typical UCC pos. margin - intermed. mag.
Image: Urothelial carcinoma positive margin -- high mag.jpg | Typical UCC pos. margin - high mag.
Image: Urothelial carcinoma positive margin -- very high mag.jpg |Typical UCC pos. margin - very high mag.
Image: Urothelial carcinoma positive margin - alt -- intermed mag.jpg | Typical UCC pos. margin - intermed. mag.
Image: Urothelial carcinoma positive margin - alt -- high mag.jpg | Typical UCC pos. margin - high mag.
</gallery>
www:
*[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3282447/figure/F2/ Several images of NUCC (nih.gov)].<ref name=pmid22355497>{{Cite journal | last1 = Terada | first1 = T. | title = Nested variant of urothelial carcinoma of the urinary bladder. | journal = Rare Tumors | volume = 3 | issue = 4 | pages = e42 | month = Oct | year = 2011 | doi = 10.4081/rt.2011.e42 | PMID = 22355497 | PMC = 3282447 }}</ref>

[[File:5 410253052 sl 1.png| High grade urothelial carcinoma]]
[[File:5 410253052 sl 2.png| High grade urothelial carcinoma]]
[[File:5 410253052 sl 3.png| High grade urothelial carcinoma]]
[[File:5 410253052 sl 4.png| High grade urothelial carcinoma]]
[[File:5 410253052 sl 5.png| High grade urothelial carcinoma]]
[[File:5 410253052 sl 6.png| High grade urothelial carcinoma]]
[[File:5 410253052 sl 7.png| High grade urothelial carcinoma]]
[[File:5 410253052 sl 8.png| High grade urothelial carcinoma]] 
High grade urothelial carcinoma in a 43 year old man. A. At low power, necrosis is seen, luminal, with viable invasive tumor elsewhere. B. Tumor partly fills right ureteral orifice. C. Tumor cells sometimes form Indian files (black arrows), appear to have nuclei that mold (red arrows), and have granular chromatin (cyan arrows), raising possibility of neuroendocrine carcinoma. D. Tumor invades lymphatic spaces. E. Urothelial carcinoma in situ is present. F,G,H. Tumor cells are diffusely positive for CK7, focally positive for CDX2, and diffusely positive for P40, with no positivity for chromogranin or synaptophysin.

=[[IHC]]=
Recommended by [[ISUP]] consensus panel:<ref name=pmid25025364 >{{cite journal |author=Amin MB, Epstein JI, Ulbright TM, ''et al.'' |title=Best practices recommendations in the application of immunohistochemistry in urologic pathology: report from the international society of urological pathology consensus conference |journal=Am. J. Surg. Pathol. |volume=38 |issue=8 |pages=1017–22 |year=2014 |month=August |pmid=25025364 |doi=10.1097/PAS.0000000000000254 |url=}}</ref>
*GATA3 +ve, CK20 +ve, p63 +ve, CK5/6, HMWCK (e.g. CK34betaE12) +ve.

Others:
*CK7 +ve.
*PSA -ve.

Notes:
*CK20 negative in over 50% of cases with metastases.<ref name=pmid11419977>{{Cite journal | last1 = Jiang | first1 = J. | last2 = Ulbright | first2 = TM. | last3 = Younger | first3 = C. | last4 = Sanchez | first4 = K. | last5 = Bostwick | first5 = DG. | last6 = Koch | first6 = MO. | last7 = Eble | first7 = JN. | last8 = Cheng | first8 = L. | title = Cytokeratin 7 and cytokeratin 20 in primary urinary bladder carcinoma and matched lymph node metastasis. | journal = Arch Pathol Lab Med | volume = 125 | issue = 7 | pages = 921-3 | month = Jul | year = 2001 | doi = 10.1043/0003-9985(2001)1250921:CACIPU2.0.CO;2 | PMID = 11419977 }}</ref>

===Reactive changes versus UCIS===
:''See [[urothelial carcinoma in situ]]''.

===UCC versus other cancers===
UCC vs. [[Prostate cancer|prostate]]:
*UCC: GATA3 +ve, PSA -ve, [[p63]] +ve, [[CK20]] +ve.
*Prostate: [[PSA]] +ve, [[GATA3]] -ve, [[PSAP]] +ve, CK7 -ve, CK20 -ve, p63 -ve.

UCC vs. [[renal cell carcinoma|renal cell carcinoma]]:
*UCC: p63 +ve.<ref>{{Cite journal | last1 = Langner | first1 = C. | last2 = Ratschek | first2 = M. | last3 = Tsybrovskyy | first3 = O. | last4 = Schips | first4 = L. | last5 = Zigeuner | first5 = R. | title = P63 immunoreactivity distinguishes upper urinary tract transitional-cell carcinoma and renal-cell carcinoma even in poorly differentiated tumors. | journal = J Histochem Cytochem | volume = 51 | issue = 8 | pages = 1097-9 | month = Aug | year = 2003 | doi = | PMID = 12871991 }}
</ref>

Metastatic UCC versus primary lung squamous cell carcinoma:
:See ''[[Squamous_cell_carcinoma_of_the_lung#Lung_SCC_versus_metastatic_bladder_urothelial_carcinoma]]''.

Note:
*In a large series, PSA positivity is reported in 1.4% bladder UCC.<ref name=pmid19192675>{{Cite journal | last1 = Chen | first1 = JC. | last2 = Ho | first2 = CL. | last3 = Tsai | first3 = HW. | last4 = Tzai | first4 = TS. | last5 = Liu | first5 = HS. | last6 = Chow | first6 = NH. | last7 = Yang | first7 = WH. | last8 = Cheng | first8 = HL. | title = Immunohistochemical detection of prostate-specific antigen expression in primary urothelial carcinoma of the urinary bladder. | journal = Anticancer Res | volume = 28 | issue = 6B | pages = 4149-54 | month = | year = | doi = | PMID = 19192675 }}
</ref>
**In half the cases the staining is weak and in the other half it is strong.<ref name=pmid19192675/>

===IHC for staging===
*''Smoothelin'' immunostain for [[bladder muscularis propria invasion|muscularis propria invasion]] versus muscularis mucosae invasion - see ''[[Muscularis_propria_invasion_in_the_urinary_bladder#IHC]]''.

=Molecular=
Not used for diagnosis.

Changes:
*9p deletion -- site of CDKN2A<ref name=omim600160>{{OMIM|600160}}</ref> (AKA p16).
*17p deletion -- site of PT53 (AKA p53).

=Sign out=
==High grade UC==
<pre>
URINARY BLADDER LESION ("TUMOUR"), TRANSURETHRAL RESECTION URINARY BLADDER TUMOUR (TURBT):
- INVASIVE HIGH-GRADE PAPILLARY UROTHELIAL CARCINOMA WITH SQUAMOUS DIFFERENTIATION AT LEAST
INTO MUSCULARIS PROPRIA.
- LYMPHOVASCULAR INVASION PRESENT.
</pre>

==UCC with some suspicion for muscularis propria invasion==
<pre>
URINARY BLADDER LESION ("TUMOUR"), DEEP, RE-RESECTION (TURBT):
- INVASIVE HIGH-GRADE UROTHELIAL CARCINOMA WITH SQUAMOUS DIFFERENTIATION AT
LEAST INTO THE LAMINA PROPRIA, SEE COMMENT.
- NO DEFINITE LYMPHOVASCULAR INVASION.

COMMENT:
Tumour is seen adjacent to smooth muscle fibres of intermediate thickness. This is
interpreted as thick muscularis mucosae. The tissue orientation is suboptimal.
Definite muscularis propria is not apparent. Levels were cut.

Tumour is abundant in the lamina propria.
</pre>

===Alternate comment===
<pre>
The sections shows thickened muscle bundles with frayed edges between the
tumour cells. The muscle is thought to represent hypertrophic muscularis
mucosae. The large extent of lamina propria invasion raises the possibility
of a higher stage lesion that may not have been sampled.
</pre>

=Subtypes of urothelial carcinoma=
There are numerous subtypes:<ref>URL: [http://www.nature.com/modpathol/journal/v22/n2s/full/modpathol200926a.html http://www.nature.com/modpathol/journal/v22/n2s/full/modpathol200926a.html]. Accessed on: 19 August 2011.</ref>
*Squamous differentiation.
*Clear cell.
*[[Plasmacytoid urothelial carcinoma|Plasmacytoid]].
*[[Micropapillary urothelial carcinoma|Micropapillary]].
**Small nests (< ~10 cells/nest).
*Sarcomatoid.
**Images: [http://path.upmc.edu/cases/case615.html UCC with sarcomatoid differentiation (upmc.edu)].
*Many others...

Benign patterns - mnemonic ''Much GIN'':
*'''M'''icrocystic.
*Small tubular/'''g'''landular.
*'''I'''nverted.
*'''N'''ested.

==Plasmacytoid urothelial cell carcinoma==
{{Main|Plasmacytoid urothelial carcinoma}}

==Microcystic urothelial carcinoma==
{{Main|Microcystic urothelial carcinoma}}

==Micropapillary urothelial carcinoma==
{{Main|Micropapillary urothelial carcinoma}}

==Lymphoepithelioma-like carcinoma==
{{Main|Lymphoepithelioma-like carcinoma of the urinary bladder}}

==Nested urothelial cell carcinoma==
*[[AKA]] ''nested variant of urothelial cell carcinoma''.
{{Main|Nested urothelial carcinoma}}

=See also=
*[[Urothelium]].
*[[Urothelial dysplasia]].
*[[Urothelial carcinoma in situ]].
*[[Prostatic urothelial carcinoma]].

=References=
{{Reflist|2}}

[[Category:Urothelium]]
[[Category:Diagnosis]]

Pancreas

2017-02-03T16:31:51Z

Mitchell: /* Images */

[[Image:Gray 1100 Pancreatic duct.png|thumb|right|250px|A drawing of the pancreas. (WC/Gray's Anatomy)]]
The '''pancreas''' hangs-out in the upper abdomen. It occasionally is afflicited by cancers, the most common of which is very fatal.

Pancreatic cytopathology is dealt with in the ''[[gastrointestinal cytopathology]]'' article.

A general introduction to gastrointestinal pathology is in the ''[[gastrointestinal pathology]]'' article.

=Introduction=
==Normal anatomy==
Divided into three portions: head, body & tail:<ref>URL: [http://www.cap.org/apps/docs/committees/cancer/cancer_protocols/2011/PancreasEndo_11protocol.pdf http://www.cap.org/apps/docs/committees/cancer/cancer_protocols/2011/PancreasEndo_11protocol.pdf]. Accessed on: 29 March 2012.</ref>
*Head:
**Includes unicate process.
**Extends to the left edge of the superior mesenteric vein (SMV) - by definition.
***All of the SMV is with the head.
*Body:
**Right edge of the superior mesenteric vein to the left edge of aorta - by definition.
***All of the aorta is with the body.
*Tail:
**Remainder of pancreas.

==Pancreatic surgeries==
Common pancreatic surgeries include:
*Whipple procedure ([[AKA]] pancreaticoduodenal resection) - includes [[duodenum]] and usually the distal [[stomach]] (antrum).
*Distal pancreatectomy.
**Removal of tail +/- body.
**Specimen usually comes with the [[spleen]].
**Typically done form [[islet cell tumour]]s.
*Total pancreatectomy.
**Specimen usually comes with the spleen.

===Whipple procedure===
*[[AKA]] ''pancreaticoduodenectomy''.

Indications:
*Head of pancreas lesions, duodenal lesions.

[[Margins]]:<ref>URL: [http://www.cap.org/apps/docs/committees/cancer/cancer_protocols/2011/SmallbowelNET_11protocol.pdf http://www.cap.org/apps/docs/committees/cancer/cancer_protocols/2011/SmallbowelNET_11protocol.pdf]. Accessed on: 29 March 2012.</ref>
#Proximal mucosal margin (stomach or duodenum).
#Distal mucosal margin (duodenum or jejunum).
#Bile duct margin.
#Pancreatic retroperitoneal (uncinate process) margin.
#*At SB done ''on edge'' (not ''en face'').
#Pancreatic neck transection margin ([[AKA]] distal pancreatic resection margin);<ref name=pmid20485150>{{Cite journal | last1 = Jamieson | first1 = NB. | last2 = Foulis | first2 = AK. | last3 = Oien | first3 = KA. | last4 = Going | first4 = JJ. | last5 = Glen | first5 = P. | last6 = Dickson | first6 = EJ. | last7 = Imrie | first7 = CW. | last8 = McKay | first8 = CJ. | last9 = Carter | first9 = R. | title = Positive mobilization margins alone do not influence survival following pancreatico-duodenectomy for pancreatic ductal adenocarcinoma. | journal = Ann Surg | volume = 251 | issue = 6 | pages = 1003-10 | month = Jun | year = 2010 | doi = 10.1097/SLA.0b013e3181d77369 | PMID = 20485150 }}</ref> usu. ''en face'' and ''in toto''.<ref>URL: [http://www.cap.org/apps/docs/committees/cancer/cancer_protocols/2011/PancreasEndo_11protocol.pdf http://www.cap.org/apps/docs/committees/cancer/cancer_protocols/2011/PancreasEndo_11protocol.pdf]. Accessed on: 6 April 2012.</ref>
#Sometimes superior mesenteric vein (SMV).
#Rarely superior mesenteric artery (SMA) margin.

[[Opening]]:
#Open the proximal (stomach) and distal (small bowel) stappled margins.
#Open the duodenum along it length on the anterior aspect.
#Open the stomach along the greater curvature.
#Join the cuts that open the stomach and duodenum.

==General classification of pancreatic tumours==
*Metstatses.
**Most common = renal cell carcinoma.
*Primary.
**Endocrine.
***Usually small as hormonally active.
**Exocrine.

===Pancreas neoplasms in a table===
{| class="wikitable sortable"
!| Type
!| Key feature
!| Subtypes
!| Image
!| IHC
!| Detailed microscopic
!| Usual location
!| Other
!| DDx
|-
| Serous tumours
| cuboidal cells, clear cytoplasm
| cystadenoma, borderline t., cystadenocarcinoma
| [http://commons.wikimedia.org/wiki/File:Pancreatic_serous_cystadenoma_%281%29.jpg], [http://commons.wikimedia.org/wiki/File:Pancreatic_serous_cystadenoma_%282%29.jpg (WC)], [http://commons.wikimedia.org/wiki/File:Pancreatic_serous_cystadenoma_-_intermed_mag.jpg (WC)]
| IHC?
| cuboidal cells, clear cytoplasm, central nucleus
| body or tail
| cystadenoma may be assoc. with [[von Hippel-Lindau syndrome]]
| [[clear cell renal cell carcinoma|clear cell RCC]], oligomucinous mucinous tumours
|-
| [[Intraductal papillary mucinous tumour]] (IPMT)
| mucin, no ovarian-like stroma
| clear cell variant
| [http://wjso.com/content/8/1/25/figure/F1 (wjso.com)], [http://path.upmc.edu/cases/case451/images/fig01.jpg (upmc.edu)]
| IHC?
| papillae, tall columnar mucin-producing cells
| head
| -
| mucious neoplasms (other pancreatic, duodenal), intra-ampullary papillary-tubular neoplasm (see [[ampullary carcinoma]])
|-
| Mucinous tumour
| mucin, ovarian-like stroma
| cystadenoma, borderline t., cystadenocarcinoma
| [http://commons.wikimedia.org/w/index.php?title=File:Benign_pancreatic_mucinous_cystic_neoplasm_-_intermed_mag.jpg (WC)], [http://commons.wikimedia.org/w/index.php?title=File:Benign_pancreatic_mucinous_cystic_neoplasm_-_high_mag.jpg (WC)]
| IHC?
| tall columnar mucin-producing cells, ovarian-like stroma
| body or tail
| -
| [[IPMT]], metastatic mucinous tumours
|-
| [[Solid pseudopapillary tumour|Solid pseudopapillary tumour]]
| eosinophilic intracytoplasmic globules
| clear cell variant (cytoplasm clear)
| [http://commons.wikimedia.org/w/index.php?title=File:Solid_pseudopapillary_tumour_-_intermed_mag.jpg (WC)], [http://jcp.bmj.com/content/61/11/1153/F1.large.jpg (bmj.com)]
| beta-catenin +ve, E-cadherin +ve, synaptophysin +ve, chromogranin -ve
| sheets of cells, focally loosely cohesive, eosinophilic cytoplasm, uniform nuclei with grooves
| none (head, body or tail)
| usu. younger women
| [[pancreatic ductal adenocarcinoma|ductal adenocarcinoma]], [[neuroendocrine tumour]]s
|-
| [[Invasive ductal carcinoma of the pancreas|Ductal adenocarcinoma]]
| irregular shaped glands, cytologic atypia
| mucinous, spindle cell, mixed ductal-endocrine
| [http://commons.wikimedia.org/wiki/File:Pancreas_adenocarcinoma_%284%29_Case_01.jpg (WC)], [http://commons.wikimedia.org/wiki/File:Pancreas_adenocarcinoma_%282%29_Case_01.jpg (WC)]
| IHC?
| glands, sheets, single cells, nuc. atypia, +/-mitoses, +/-[[necrosis]]
| head
| arises from the precursor ''PanIN''
| ampullary carcinoma, [[chronic pancreatitis]]
|-
| [[Pancreatoblastoma]]
| squamoid nests, whorling
| -
| [http://www.nature.com/modpathol/journal/v20/n1s/fig_tab/3800686f16.html#figure-title (nature.com)]
| [[CK7]] (acinar comp.), CK8, CK18, [[CK19]]
| squamoid nests of cells, whorling, nested growth, +/-keratinization
| none
| usu. paediatric population
| [[acinar cell carcinoma of the pancreas|acinar cell carcinoma]]
|-
| [[Acinar cell carcinoma of the pancreas|Acinar cell carcinoma]]
| acinar arch.
| -
| [http://commons.wikimedia.org/wiki/File:Acinar_cell_carcinoma_of_the_pancreas_-_very_high_mag.jpg (WC)], [http://www.histopathology-india.net/acinar%20cell%20ca.JPG (histopathology-india.net)]
| trypsin, lipase
| nests or [[trabeculae]], nucleolus, mod. basophilic granular cytoplasm
| head (slight predilection)
| -
| pancreatoblastoma
|-
| Undifferentiated carcinoma with osteoclast-like [[giant cell]]s
| giant cells
| -
| Image?
| IHC?
| giant cells, usu. with AIS or inv. ductal adenocarcinoma
| head
| -
| anaplastic carcinoma
|-
| [[Chronic pancreatitis]]
| fibrosis, loss of acinar tissue, preservation of lobular arch.
| -
| [http://www.pathology.vcu.edu/education/gi/lab1.b.html]
| IHC?
| loss of acinar tissue with preservation of islets, fibrosis
| ?
| not a neoplasm, included here as it is in the (clinical) DDx
| [[pancreatic ductal adenocarcinoma|ductal adenocarcinoma]]
|}

===WHO classification===
Benign epithelial:
*[[Pancreatic serous cystadenoma|Serous cystadenoma]].
*[[Pancreatic mucinous cystadenoma|Mucinous cystadenoma]].
*[[Intraductal papillary mucinous neoplasm|Intraductal papillary mucinous adenoma]].
*[[Mature teratoma]].

Borderline epithelial:
*Mucinous cystic neoplasm with moderate dysplasia.
*[[Intraductal papillary mucinous neoplasm|Intraductal papillary mucinous neoplasm with moderate dysplasia]].
*[[Solid pseudopapillary neoplasm]]

Malignant epithelial:
*[[Pancreatic ductal adenocarcinoma|Ductal adenocarcinoma]].
**Mucinous noncystic carcinoma.
**[[Signet ring cell carcinoma]].
**[[Adenosquamous carcinoma]].
**Undifferentiated carcinoma.
**Undifferentiated carcinoma with osteoclast-like giant cells.
**Mixed ductal-endocrine carcinoma.
*[[Pancreatic serous cystadenocarcinoma|Serous cystadenocarcinoma]].
*[[Pancreatic mucinous cystadenocarcinoma|Mucinous cystadenocarcinoma]].
**Invasive.
**Noninvasive.
*[[Intraductal papillary mucinous neoplasm|Intraductal papillary mucinous carcinoma]].
**Invasive.
**Noninvasive.
*[[Acinar cell carcinoma of the pancreas|Acinar cell carcinoma]].
*[[Pancreatoblastoma]].
*[[Solid pseudopapillary neoplasm|Solid pseudopapillary carcinoma]].

Soft tissue tumours:
*See ''[[soft tissue lesions]]''.

=Ectopic pancreatic tissue=
It comes in two flavours:<ref>URL: [http://test.pathologyportal.org/newindex.htm?92nd/specgasth2.htm http://test.pathologyportal.org/newindex.htm?92nd/specgasth2.htm]. Accessed on: 14 March 2011.</ref>
*Pancreatic ectopia.
*Pancreatic (acinar) metaplasia.

==Pancreatic acinar metaplasia==
*Abbreviated ''PAM''.
*[[AKA]] ''pancreatic metaplasia''.<ref name=pmid8724024>{{Cite journal | last1 = Stachura | first1 = J. | last2 = Konturek | first2 = JW. | last3 = Urbanczyk | first3 = K. | last4 = Bogdal | first4 = J. | last5 = Mach | first5 = T. | last6 = Domschke | first6 = W. | title = Endoscopic and histological appearance of pancreatic metaplasia in the human gastric mucosa: a preliminary report on a recently recognized new type of gastric mucosal metaplasia. | journal = Eur J Gastroenterol Hepatol | volume = 8 | issue = 3 | pages = 239-43 | month = Mar | year = 1996 | doi = | PMID = 8724024 }}</ref>

===General===
*Common in the GI tract.
*Found in ~ 17-19% of [[stomach|gastro]][[esophagus|esophageal]] junction biopsies.<ref name=pmid23989798/><ref name=pmid20012917>{{cite journal |author=Johansson J, Håkansson HO, Mellblom L, ''et al.'' |title=Pancreatic acinar metaplasia in the distal oesophagus and the gastric cardia: prevalence, predictors and relation to GORD |journal=J. Gastroenterol. |volume=45 |issue=3 |pages=291–9 |year=2010 |month=March |pmid=20012917 |doi=10.1007/s00535-009-0161-4 |url=}}</ref>
*Associated with intestinal metaplasis.<ref name=pmid23989798>{{Cite journal | last1 = Schneider | first1 = NI. | last2 = Plieschnegger | first2 = W. | last3 = Geppert | first3 = M. | last4 = Wigginghaus | first4 = B. | last5 = Höss | first5 = GM. | last6 = Eherer | first6 = A. | last7 = Wolf | first7 = EM. | last8 = Rehak | first8 = P. | last9 = Vieth | first9 = M. | title = Pancreatic acinar cells-a normal finding at the gastroesophageal junction? Data from a prospective Central European multicenter study. | journal = Virchows Arch | volume = | issue = | pages = | month = Aug | year = 2013 | doi = 10.1007/s00428-013-1471-8 | PMID = 23989798 }}</ref>
**Not associated with changes of [[GERD]], or [[Helicobacter gastritis]].<ref name=pmid23989798/>

===Gross===
*May be a single lesion or a cluster of lesions.<ref name=pmid8724024/>

Note:
*''Not'' associated with the endoscopic diagnosis of esophagitis or [[Barrett's esophagus]].<ref name=pmid23989798/>

===Microscopic===
Features:
*Pancreatic acini - only.
**Intensely eosinophilic cytoplasm.

Negatives:
*No pancreatic ducts.
*No islets of Langerhans (pancreatic islets).

====Images====
<gallery>
Image:Pancreatic_acinar_metaplasia_-_high_mag.jpg | PAM - high mag. (WC/Nephron)
Image:Pancreatic_acinar_metaplasia_-_low_mag.jpg | PAM - low mag. (WC/Nephron)
</gallery>
===IHC===
Features:<ref>{{Cite journal | last1 = Doglioni | first1 = C. | last2 = Laurino | first2 = L. | last3 = Dei Tos | first3 = AP. | last4 = De Boni | first4 = M. | last5 = Franzin | first5 = G. | last6 = Braidotti | first6 = P. | last7 = Viale | first7 = G. | title = Pancreatic (acinar) metaplasia of the gastric mucosa. Histology, ultrastructure, immunocytochemistry, and clinicopathologic correlations of 101 cases. | journal = Am J Surg Pathol | volume = 17 | issue = 11 | pages = 1134-43 | month = Nov | year = 1993 | doi = | PMID = 8214258 }}</ref>
*Trypase +ve.
*Lipase +ve.

===Sign out===
It can be debated whether it is worth reporting.
<pre>
ESOPHAGUS (DISTAL), BIOPSY:
- COLUMNAR EPITHELIUM WITH MODERATE CHRONIC, FOCALLY ACTIVE, INFLAMMATION, AND
PANCREATIC ACINAR METAPLASIA.
- REACTIVE SQUAMOUS EPITHELIUM.
- NEGATIVE FOR INTESTINAL METAPLASIA.
- NEGATIVE FOR DYSPLASIA AND NEGATIVE FOR MALIGNANCY.
</pre>

==Pancreatic ectopia==
===General===
*May be confused with something pathologic.

===Microscopic===
Features:
*Consists of pancreatic acini ''and'' pancreatic ducts.
*+/-Islets of Langerhans.

=Inflammatory=
==Pancreatitis==
===Classification===
*[[Acute pancreatitis]].
*[[Chronic pancreatitis]].

===Etiology===
Mnemonic ''I GET SMASHED'':
*Idiopathic.
*[[Gallstones]] ~45%.
*Ethanol ~35%.
*Tumours (pancreas, ampulla).
*Scorpion bites, snake bites.
*Microbial - mumps (paramyxovirus), [[Epstein-Barr virus]] (EBV), [[cytomegalovirus]] (CMV), mycoplasma.
*Autoimmune - [[Crohn's disease]], [[polyarteritis nodosa]] (PAN), [[systemic lupus erythematosus]] (SLE).
*Surgery/trauma, e.g. ERCP, motor vehicle collision.
*Hypercalcemia, hyperlipidemia/hypertriglyceridemia, [[hypothermia]].
*Emboli, e.g. post-[[CABG]].
*Drugs - ''SAND'' = steroids & sulfonamides, azathioprine, [[NSAID]]s, diuretics, such as furosemide.

==Acute pancreatitis==
{{Main|Acute pancreatitis}}

==Chronic pancreatitis==
{{Main|Chronic pancreatitis}}

=Cystic lesions - overview=
===General===
*True cystic lesions are uncommon.
**A true cystic lesion: ''must'' have an epithelial lining.
***Only 10% of cystic lesions are true cystic lesions, i.e. 90% of cystic lesions are really [[Pancreatic pseudocyst|pseudocysts]].
*It is hard to differentiate pseudocysts & cysts.

===Cystic tumours - clinical===
General:
*Usually diagnosed by imaging (CT/MRI, ERCP, Endoscopic ultrasound).
**50% incidental finding.
*Vague symptoms
*Abdominal mass.
*Weight loss.
*Jaundice.
*Usually favourable prognosis - mostly benign.

===Most important cystic lesions===
*Serous.
*Mucinous.
**Ovarian-like stroma.
*Solid pseudopapillay tumours.
*Intraductal papillary mucinous tumour (IPMT).
**No ovarian-like stroma.

Mnemonic ''SIMS'': Serous, IPMT, Mucinous, Solid pseudopapillary tumour.

====Useful stains====
*PAS-D.

====Mucinous vs. IMPT====
IMPT:
*No ovarian-like stroma.
*Usually has total pancreatectomy.

===Cystic tumours of the pancreas===
Khalifa's table of cystic tumours:
{| class="wikitable sortable"
!Tumour
!Usual sex
!Age (years)
!Usual site
!Typical size (cm)
![[Gross pathology]]
|-
|[[serous microcystic adenoma|Serous microcystic adenoma]]
|female
|66
|body & tail
|11
|[http://www.joplink.net/prev/200905/25_fig06.jpg (joplink.net]<ref>URL: [http://www.joplink.net/prev/200905/25.html http://www.joplink.net/prev/200905/25.html]. Accessed on: 15 February 2012.</ref>, [http://oac.med.jhmi.edu/cpc/images/cpc5/33.jpg (jhmi.edu)]<ref name=jhmi>URL: [http://oac.med.jhmi.edu/cpc/cases/cpc5/cpc5_answer.html http://oac.med.jhmi.edu/cpc/cases/cpc5/cpc5_answer.html]. Accessed on: 15 February 2012.</ref>
|-
|[[IPMN|Intraductal papillary mucinous tumour (IPMT)]]
|male
|62
|head
|4
|[http://oac.med.jhmi.edu/cpc/images/cpc5/28.jpg (jhmi.edu)]<ref name=jhmi>URL: [http://oac.med.jhmi.edu/cpc/cases/cpc5/cpc5_answer.html http://oac.med.jhmi.edu/cpc/cases/cpc5/cpc5_answer.html]. Accessed on: 15 February 2012.</ref>
|-
|Mucinous tumour
|female
|49
|body & tail
|10
|[http://radiology.rsna.org/content/251/1/77/F8.expansion.html (rsna.org)]
|-
|[[solid pseudopapillary tumour|Solid pseudopapillary tumour]]
|female
|35
|any
|7.5
|[http://www.ajronline.org/content/195/4/947/F4.expansion.html (ajronline.org)], [http://www.flickr.com/photos/35441329@N05/5249538296/ (flickr.com/humpath)]
|}

=Cystic lesions=
==Serous tumours - overview==
===General===
*Cell of origin: intralobular duct cells (ductular cells).
*Glycogen rich - but do not produce mucin.

====Subclassication====
*[[Serous microcystic adenoma]] ([[AKA]] serous cystadenoma<ref name=Ref_Sternberg4_1630>{{Ref Sternberg4|1630}}</ref>).
** Many small cysts.
*Serous oligocystic adenoma.
** Large cysts.
*Serous cystadenocarcinoma - very rare.<ref name=pmid22009426>{{Cite journal | last1 = Bano | first1 = S. | last2 = Upreti | first2 = L. | last3 = Puri | first3 = SK. | last4 = Chaudhary | first4 = V. | last5 = Sakuja | first5 = P. | title = Imaging of pancreatic serous cystadenocarcinoma. | journal = Jpn J Radiol | volume = 29 | issue = 10 | pages = 730-4 | month = Dec | year = 2011 | doi = 10.1007/s11604-011-0617-3 | PMID = 22009426 }}</ref>

Note:
*If one mucin +ve cell, tumour = a mucinous tumour.

==Serous cystadenoma of the pancreas==
*[[AKA]] ''serous microcystic adenoma'',<ref name=Ref_Sternberg4_1630>{{Ref Sternberg4|1630}}</ref> [[AKA]] ''pancreatic serous cystadenoma''.
{{Main|Serous cystadenoma of the pancreas}}

==Mucinous cystic neoplasms of the pancreas==
*Gastro-entero-pancreatic cell differentiation with hypercellular ovarian-type stroma.
**Stroma --> cellular.
*2-2.5% of all exocrine pancreatic tumours.
*Almost exclusively in women.
*Mean age - 49 years.
*>80% in body and tail.
*Average size ~10 cm.

Note:
*Looks different than serous tumour.

===Subclassification===
*Mucinous cystadenoma.
*Borderline mucinous cystic tumour.
*Mucinous cystadenocarcinoma.

===Borderline vs. Carcinoma===
*Few mitoses in borderline.

===Radiology===
*Mucinous tumours: multilocular.
*Generally larger than serous.
*Often partially solid and cystic.
*Often calcified.
**Calcification rare in serous.
*Usually tail & body.

===Microscopic===
====Mucinous cystadenoma====
Features:<ref name=Ref_GLP489>{{Ref GLP|489}}</ref>
*Simple tall columnar epithelium with large mucin vacuole on apical aspect.
*"Ovarian-type stroma" under epithelium.
**Ovarin-type stroma: high density of small (non-wavy) spindle cells with eosinophilic cytoplasm.

Notes:
*Appearance similar to ''mucinous cystadenoma'' in the [[ovarian tumours|ovary]].
*Mucin stains +ve (intracytoplasmic).

=====Images=====
<gallery>
Image:Benign_pancreatic_mucinous_cystic_neoplasm_-_very_low_mag.jpg | Benign mucinous cystic neoplasm - very low mag. (WC)
Image:Benign_pancreatic_mucinous_cystic_neoplasm_-_low_mag.jpg | Benign mucinous cystic neoplasm - low mag.(WC)
Image:Benign_pancreatic_mucinous_cystic_neoplasm_-_intermed_mag.jpg | Benign mucinous cystic neoplasm - intermed. mag. (WC)
Image:Benign_pancreatic_mucinous_cystic_neoplasm_-_high_mag.jpg | Benign mucinous cystic neoplasm - showing stroma - high mag. (WC)
</gallery>
www:
*[http://radiology.uchc.edu/eAtlas/Images/GYN/5705b.gif Mucinous cystadenoma - ovary (uchc.edu)].
[[File:4 477025809 sl 1.png|Mucinous cystic neoplasm of pancreas]]
[[File:4 477025809 sl 2.png|Mucinous cystic neoplasm of pancreas]]
[[File:4 477025809 sl 3.png|Mucinous cystic neoplasm of pancreas]]
[[File:4 477025809 sl 4.png|Mucinous cystic neoplasm of pancreas]]
[[File:4 477025809 sl 5.png|Mucinous cystic neoplasm of pancreas]]
[[File:4 477025809 sl 6.png|Mucinous cystic neoplasm of pancreas]]
[[File:4 477025809 sl 7.png|Mucinous cystic neoplasm of pancreas]] 
Benign mucinous cystic neoplasm of pancreas in a 62 year old woman. A. CT scan showed a peripherally calcified spheroidal mass at the tail of the pancreas. Cytology only showed debris and inflammatory cells, but CEA of the fluid was 2875.2 ng/mL. B. Almost all sections of the cyst showed acellular debris topping a fibrous, often calcified wall, consistent with a pseudocyst. C. Extensive sampling, undertaken because of the high CEA, revealed rare sections with a lining. D. Lining nuclei are bland, with even chromatin. Shape and size variation, as well as darkening when shrunken, are all explicable by degeneration. E. Within distal pancreas, a focus of changes of chronic pancreatitis is seen upper left, while a pancreatic duct in lower right shows an intraductal proliferation. F. Tumor cells show mucinous vacuoles, with better preserved nuclei. Nuclear appearances remain bland. G. Cellular ovarian stroma appeared beneath epithelium of a separate focus of the cystic neoplasm.

====Borderline mucinous cystic tumour====
Features:
*May have finger like projections.
*Pseudostratification of epithelium.

Notes:
* Surgery does not change based on diagnosis on frozen section.
** Only question is "Is the margin clear?".
* Borderline tumours are rare.

====Carcinoma====
*Cells floating in mucin.

====Mucinous tumour versus pseudocyst====
{| class="wikitable sortable"
! Finding
! Mucinous tumour
! Pseudocyst
|-
|Amylase & lipase || low || high
|-
|Viscosity || high || low
|-
|[[CEA]], CA125 || high || low
|}

Prognosis:
*Benign looking tumours have the potential to transform into carcinoma.
*No report of assoc. pseudomyxoma peritonei.
**US boards question -- it is an exception ... others one cause it.
*Prognosis of m. cystadenocarcinoma is slightly better than that of ductal adenocarcinoma.

==Intraductal papillary mucinous tumour==
*Abbreviated ''IPMT''.
*[[AKA]] ''intraductal papillary mucinous neoplasm'', abbreviated ''IPMN''.
{{Main|Intraductal papillary mucinous tumour}}

==Solid pseudopapillary tumour==
*[[AKA]] ''solid pseudopapillary neoplasm'', abbreviation ''SPN''.
*[[AKA]] ''solid and papillary epithelial neoplasm'', abbreviated ''SPEN''.<ref>URL: [http://brighamrad.harvard.edu/Cases/bwh/hcache/360/full.html http://brighamrad.harvard.edu/Cases/bwh/hcache/360/full.html]. Accessed on: 31 October 2011.</ref>
{{Main|Solid pseudopapillary tumour}}

=Pre-malignant lesions=
==Pancreatic intraepithelial neoplasia==
*Abbreviated ''PanIN''.
{{Main|Pancreatic intraepithelial neoplasia}}

=Solid tumours=
==Invasive ductal carcinoma of the pancreas==
*[[AKA]] ''ductal adenocarcinoma''.
*[[AKA]] ''pancreatic ductal adenocarcinoma''.
*[[AKA]] ''pancreatic adenocarcinoma''.
{{Main|Invasive ductal carcinoma of the pancreas}}

==Pancreatic neuroendocrine tumour==
*Abbreviated ''PanNET''.<ref name=pmid22198808/>
*[[AKA]] ''pancreatic islet cell tumour''<ref name=pmid22198808>{{Cite journal | last1 = Burns | first1 = WR. | last2 = Edil | first2 = BH. | title = Neuroendocrine Pancreatic Tumors: Guidelines for Management and Update. | journal = Curr Treat Options Oncol | volume = | issue = | pages = | month = Dec | year = 2011 | doi = 10.1007/s11864-011-0172-2 | PMID = 22198808 }}</ref> - considered to be an outdated term.
*[[AKA]] ''islet cell tumour'' - considered to be an outdated term.
{{Main|Neuroendocrine tumour of the pancreas}}

==Acinar cell carcinoma of the pancreas==
:'''Not''' to be confused with ''[[acinic cell carcinoma]]''.
*[[AKA]] ''acinar cell carcinoma''.
*[[AKA]] ''pancreatic acinar cell carcinoma''.<ref name=pmid>{{Cite journal | last1 = Thomas | first1 = PC. | last2 = Nash | first2 = GF. | last3 = Aldridge | first3 = MC. | title = Pancreatic acinar cell carcinoma presenting as acute pancreatitis. | journal = HPB (Oxford) | volume = 5 | issue = 2 | pages = 111-3 | month = | year = 2003 | doi = 10.1080/13651820310001153 | PMID = 18332967 }}</ref>
{{Main|Acinar cell carcinoma of the pancreas}}

==Pancreatoblastoma==
{{Main|Pancreatoblastoma}}

=See also=
*[[Duodenum]].
*[[Gallbladder]].
*[[Gastrointestinal pathology]].
*[[Von Hippel-Lindau syndrome]].
*[[IgG4-related systemic disease]].

=References=
{{reflist|2}}

==Further reading==
{{Cite journal | last1 = Klimstra | first1 = DS. | last2 = Pitman | first2 = MB. | last3 = Hruban | first3 = RH. | title = An algorithmic approach to the diagnosis of pancreatic neoplasms. | journal = Arch Pathol Lab Med | volume = 133 | issue = 3 | pages = 454-64 | month = Mar | year = 2009 | doi = 10.1043/1543-2165-133.3.454 | PMID = 19260750 }}

=External links=
*[http://pancreaticcancer2000.com/page1.htm Pancreatic cancer - PanINs - pancreaticcancer2000.com].

[[Category:Gastrointestinal pathology]]

Pancreas

2017-02-03T16:20:53Z

Mitchell: /* Images */ added a case

[[Image:Gray 1100 Pancreatic duct.png|thumb|right|250px|A drawing of the pancreas. (WC/Gray's Anatomy)]]
The '''pancreas''' hangs-out in the upper abdomen. It occasionally is afflicited by cancers, the most common of which is very fatal.

Pancreatic cytopathology is dealt with in the ''[[gastrointestinal cytopathology]]'' article.

A general introduction to gastrointestinal pathology is in the ''[[gastrointestinal pathology]]'' article.

=Introduction=
==Normal anatomy==
Divided into three portions: head, body & tail:<ref>URL: [http://www.cap.org/apps/docs/committees/cancer/cancer_protocols/2011/PancreasEndo_11protocol.pdf http://www.cap.org/apps/docs/committees/cancer/cancer_protocols/2011/PancreasEndo_11protocol.pdf]. Accessed on: 29 March 2012.</ref>
*Head:
**Includes unicate process.
**Extends to the left edge of the superior mesenteric vein (SMV) - by definition.
***All of the SMV is with the head.
*Body:
**Right edge of the superior mesenteric vein to the left edge of aorta - by definition.
***All of the aorta is with the body.
*Tail:
**Remainder of pancreas.

==Pancreatic surgeries==
Common pancreatic surgeries include:
*Whipple procedure ([[AKA]] pancreaticoduodenal resection) - includes [[duodenum]] and usually the distal [[stomach]] (antrum).
*Distal pancreatectomy.
**Removal of tail +/- body.
**Specimen usually comes with the [[spleen]].
**Typically done form [[islet cell tumour]]s.
*Total pancreatectomy.
**Specimen usually comes with the spleen.

===Whipple procedure===
*[[AKA]] ''pancreaticoduodenectomy''.

Indications:
*Head of pancreas lesions, duodenal lesions.

[[Margins]]:<ref>URL: [http://www.cap.org/apps/docs/committees/cancer/cancer_protocols/2011/SmallbowelNET_11protocol.pdf http://www.cap.org/apps/docs/committees/cancer/cancer_protocols/2011/SmallbowelNET_11protocol.pdf]. Accessed on: 29 March 2012.</ref>
#Proximal mucosal margin (stomach or duodenum).
#Distal mucosal margin (duodenum or jejunum).
#Bile duct margin.
#Pancreatic retroperitoneal (uncinate process) margin.
#*At SB done ''on edge'' (not ''en face'').
#Pancreatic neck transection margin ([[AKA]] distal pancreatic resection margin);<ref name=pmid20485150>{{Cite journal | last1 = Jamieson | first1 = NB. | last2 = Foulis | first2 = AK. | last3 = Oien | first3 = KA. | last4 = Going | first4 = JJ. | last5 = Glen | first5 = P. | last6 = Dickson | first6 = EJ. | last7 = Imrie | first7 = CW. | last8 = McKay | first8 = CJ. | last9 = Carter | first9 = R. | title = Positive mobilization margins alone do not influence survival following pancreatico-duodenectomy for pancreatic ductal adenocarcinoma. | journal = Ann Surg | volume = 251 | issue = 6 | pages = 1003-10 | month = Jun | year = 2010 | doi = 10.1097/SLA.0b013e3181d77369 | PMID = 20485150 }}</ref> usu. ''en face'' and ''in toto''.<ref>URL: [http://www.cap.org/apps/docs/committees/cancer/cancer_protocols/2011/PancreasEndo_11protocol.pdf http://www.cap.org/apps/docs/committees/cancer/cancer_protocols/2011/PancreasEndo_11protocol.pdf]. Accessed on: 6 April 2012.</ref>
#Sometimes superior mesenteric vein (SMV).
#Rarely superior mesenteric artery (SMA) margin.

[[Opening]]:
#Open the proximal (stomach) and distal (small bowel) stappled margins.
#Open the duodenum along it length on the anterior aspect.
#Open the stomach along the greater curvature.
#Join the cuts that open the stomach and duodenum.

==General classification of pancreatic tumours==
*Metstatses.
**Most common = renal cell carcinoma.
*Primary.
**Endocrine.
***Usually small as hormonally active.
**Exocrine.

===Pancreas neoplasms in a table===
{| class="wikitable sortable"
!| Type
!| Key feature
!| Subtypes
!| Image
!| IHC
!| Detailed microscopic
!| Usual location
!| Other
!| DDx
|-
| Serous tumours
| cuboidal cells, clear cytoplasm
| cystadenoma, borderline t., cystadenocarcinoma
| [http://commons.wikimedia.org/wiki/File:Pancreatic_serous_cystadenoma_%281%29.jpg], [http://commons.wikimedia.org/wiki/File:Pancreatic_serous_cystadenoma_%282%29.jpg (WC)], [http://commons.wikimedia.org/wiki/File:Pancreatic_serous_cystadenoma_-_intermed_mag.jpg (WC)]
| IHC?
| cuboidal cells, clear cytoplasm, central nucleus
| body or tail
| cystadenoma may be assoc. with [[von Hippel-Lindau syndrome]]
| [[clear cell renal cell carcinoma|clear cell RCC]], oligomucinous mucinous tumours
|-
| [[Intraductal papillary mucinous tumour]] (IPMT)
| mucin, no ovarian-like stroma
| clear cell variant
| [http://wjso.com/content/8/1/25/figure/F1 (wjso.com)], [http://path.upmc.edu/cases/case451/images/fig01.jpg (upmc.edu)]
| IHC?
| papillae, tall columnar mucin-producing cells
| head
| -
| mucious neoplasms (other pancreatic, duodenal), intra-ampullary papillary-tubular neoplasm (see [[ampullary carcinoma]])
|-
| Mucinous tumour
| mucin, ovarian-like stroma
| cystadenoma, borderline t., cystadenocarcinoma
| [http://commons.wikimedia.org/w/index.php?title=File:Benign_pancreatic_mucinous_cystic_neoplasm_-_intermed_mag.jpg (WC)], [http://commons.wikimedia.org/w/index.php?title=File:Benign_pancreatic_mucinous_cystic_neoplasm_-_high_mag.jpg (WC)]
| IHC?
| tall columnar mucin-producing cells, ovarian-like stroma
| body or tail
| -
| [[IPMT]], metastatic mucinous tumours
|-
| [[Solid pseudopapillary tumour|Solid pseudopapillary tumour]]
| eosinophilic intracytoplasmic globules
| clear cell variant (cytoplasm clear)
| [http://commons.wikimedia.org/w/index.php?title=File:Solid_pseudopapillary_tumour_-_intermed_mag.jpg (WC)], [http://jcp.bmj.com/content/61/11/1153/F1.large.jpg (bmj.com)]
| beta-catenin +ve, E-cadherin +ve, synaptophysin +ve, chromogranin -ve
| sheets of cells, focally loosely cohesive, eosinophilic cytoplasm, uniform nuclei with grooves
| none (head, body or tail)
| usu. younger women
| [[pancreatic ductal adenocarcinoma|ductal adenocarcinoma]], [[neuroendocrine tumour]]s
|-
| [[Invasive ductal carcinoma of the pancreas|Ductal adenocarcinoma]]
| irregular shaped glands, cytologic atypia
| mucinous, spindle cell, mixed ductal-endocrine
| [http://commons.wikimedia.org/wiki/File:Pancreas_adenocarcinoma_%284%29_Case_01.jpg (WC)], [http://commons.wikimedia.org/wiki/File:Pancreas_adenocarcinoma_%282%29_Case_01.jpg (WC)]
| IHC?
| glands, sheets, single cells, nuc. atypia, +/-mitoses, +/-[[necrosis]]
| head
| arises from the precursor ''PanIN''
| ampullary carcinoma, [[chronic pancreatitis]]
|-
| [[Pancreatoblastoma]]
| squamoid nests, whorling
| -
| [http://www.nature.com/modpathol/journal/v20/n1s/fig_tab/3800686f16.html#figure-title (nature.com)]
| [[CK7]] (acinar comp.), CK8, CK18, [[CK19]]
| squamoid nests of cells, whorling, nested growth, +/-keratinization
| none
| usu. paediatric population
| [[acinar cell carcinoma of the pancreas|acinar cell carcinoma]]
|-
| [[Acinar cell carcinoma of the pancreas|Acinar cell carcinoma]]
| acinar arch.
| -
| [http://commons.wikimedia.org/wiki/File:Acinar_cell_carcinoma_of_the_pancreas_-_very_high_mag.jpg (WC)], [http://www.histopathology-india.net/acinar%20cell%20ca.JPG (histopathology-india.net)]
| trypsin, lipase
| nests or [[trabeculae]], nucleolus, mod. basophilic granular cytoplasm
| head (slight predilection)
| -
| pancreatoblastoma
|-
| Undifferentiated carcinoma with osteoclast-like [[giant cell]]s
| giant cells
| -
| Image?
| IHC?
| giant cells, usu. with AIS or inv. ductal adenocarcinoma
| head
| -
| anaplastic carcinoma
|-
| [[Chronic pancreatitis]]
| fibrosis, loss of acinar tissue, preservation of lobular arch.
| -
| [http://www.pathology.vcu.edu/education/gi/lab1.b.html]
| IHC?
| loss of acinar tissue with preservation of islets, fibrosis
| ?
| not a neoplasm, included here as it is in the (clinical) DDx
| [[pancreatic ductal adenocarcinoma|ductal adenocarcinoma]]
|}

===WHO classification===
Benign epithelial:
*[[Pancreatic serous cystadenoma|Serous cystadenoma]].
*[[Pancreatic mucinous cystadenoma|Mucinous cystadenoma]].
*[[Intraductal papillary mucinous neoplasm|Intraductal papillary mucinous adenoma]].
*[[Mature teratoma]].

Borderline epithelial:
*Mucinous cystic neoplasm with moderate dysplasia.
*[[Intraductal papillary mucinous neoplasm|Intraductal papillary mucinous neoplasm with moderate dysplasia]].
*[[Solid pseudopapillary neoplasm]]

Malignant epithelial:
*[[Pancreatic ductal adenocarcinoma|Ductal adenocarcinoma]].
**Mucinous noncystic carcinoma.
**[[Signet ring cell carcinoma]].
**[[Adenosquamous carcinoma]].
**Undifferentiated carcinoma.
**Undifferentiated carcinoma with osteoclast-like giant cells.
**Mixed ductal-endocrine carcinoma.
*[[Pancreatic serous cystadenocarcinoma|Serous cystadenocarcinoma]].
*[[Pancreatic mucinous cystadenocarcinoma|Mucinous cystadenocarcinoma]].
**Invasive.
**Noninvasive.
*[[Intraductal papillary mucinous neoplasm|Intraductal papillary mucinous carcinoma]].
**Invasive.
**Noninvasive.
*[[Acinar cell carcinoma of the pancreas|Acinar cell carcinoma]].
*[[Pancreatoblastoma]].
*[[Solid pseudopapillary neoplasm|Solid pseudopapillary carcinoma]].

Soft tissue tumours:
*See ''[[soft tissue lesions]]''.

=Ectopic pancreatic tissue=
It comes in two flavours:<ref>URL: [http://test.pathologyportal.org/newindex.htm?92nd/specgasth2.htm http://test.pathologyportal.org/newindex.htm?92nd/specgasth2.htm]. Accessed on: 14 March 2011.</ref>
*Pancreatic ectopia.
*Pancreatic (acinar) metaplasia.

==Pancreatic acinar metaplasia==
*Abbreviated ''PAM''.
*[[AKA]] ''pancreatic metaplasia''.<ref name=pmid8724024>{{Cite journal | last1 = Stachura | first1 = J. | last2 = Konturek | first2 = JW. | last3 = Urbanczyk | first3 = K. | last4 = Bogdal | first4 = J. | last5 = Mach | first5 = T. | last6 = Domschke | first6 = W. | title = Endoscopic and histological appearance of pancreatic metaplasia in the human gastric mucosa: a preliminary report on a recently recognized new type of gastric mucosal metaplasia. | journal = Eur J Gastroenterol Hepatol | volume = 8 | issue = 3 | pages = 239-43 | month = Mar | year = 1996 | doi = | PMID = 8724024 }}</ref>

===General===
*Common in the GI tract.
*Found in ~ 17-19% of [[stomach|gastro]][[esophagus|esophageal]] junction biopsies.<ref name=pmid23989798/><ref name=pmid20012917>{{cite journal |author=Johansson J, Håkansson HO, Mellblom L, ''et al.'' |title=Pancreatic acinar metaplasia in the distal oesophagus and the gastric cardia: prevalence, predictors and relation to GORD |journal=J. Gastroenterol. |volume=45 |issue=3 |pages=291–9 |year=2010 |month=March |pmid=20012917 |doi=10.1007/s00535-009-0161-4 |url=}}</ref>
*Associated with intestinal metaplasis.<ref name=pmid23989798>{{Cite journal | last1 = Schneider | first1 = NI. | last2 = Plieschnegger | first2 = W. | last3 = Geppert | first3 = M. | last4 = Wigginghaus | first4 = B. | last5 = Höss | first5 = GM. | last6 = Eherer | first6 = A. | last7 = Wolf | first7 = EM. | last8 = Rehak | first8 = P. | last9 = Vieth | first9 = M. | title = Pancreatic acinar cells-a normal finding at the gastroesophageal junction? Data from a prospective Central European multicenter study. | journal = Virchows Arch | volume = | issue = | pages = | month = Aug | year = 2013 | doi = 10.1007/s00428-013-1471-8 | PMID = 23989798 }}</ref>
**Not associated with changes of [[GERD]], or [[Helicobacter gastritis]].<ref name=pmid23989798/>

===Gross===
*May be a single lesion or a cluster of lesions.<ref name=pmid8724024/>

Note:
*''Not'' associated with the endoscopic diagnosis of esophagitis or [[Barrett's esophagus]].<ref name=pmid23989798/>

===Microscopic===
Features:
*Pancreatic acini - only.
**Intensely eosinophilic cytoplasm.

Negatives:
*No pancreatic ducts.
*No islets of Langerhans (pancreatic islets).

====Images====
<gallery>
Image:Pancreatic_acinar_metaplasia_-_high_mag.jpg | PAM - high mag. (WC/Nephron)
Image:Pancreatic_acinar_metaplasia_-_low_mag.jpg | PAM - low mag. (WC/Nephron)
</gallery>
===IHC===
Features:<ref>{{Cite journal | last1 = Doglioni | first1 = C. | last2 = Laurino | first2 = L. | last3 = Dei Tos | first3 = AP. | last4 = De Boni | first4 = M. | last5 = Franzin | first5 = G. | last6 = Braidotti | first6 = P. | last7 = Viale | first7 = G. | title = Pancreatic (acinar) metaplasia of the gastric mucosa. Histology, ultrastructure, immunocytochemistry, and clinicopathologic correlations of 101 cases. | journal = Am J Surg Pathol | volume = 17 | issue = 11 | pages = 1134-43 | month = Nov | year = 1993 | doi = | PMID = 8214258 }}</ref>
*Trypase +ve.
*Lipase +ve.

===Sign out===
It can be debated whether it is worth reporting.
<pre>
ESOPHAGUS (DISTAL), BIOPSY:
- COLUMNAR EPITHELIUM WITH MODERATE CHRONIC, FOCALLY ACTIVE, INFLAMMATION, AND
PANCREATIC ACINAR METAPLASIA.
- REACTIVE SQUAMOUS EPITHELIUM.
- NEGATIVE FOR INTESTINAL METAPLASIA.
- NEGATIVE FOR DYSPLASIA AND NEGATIVE FOR MALIGNANCY.
</pre>

==Pancreatic ectopia==
===General===
*May be confused with something pathologic.

===Microscopic===
Features:
*Consists of pancreatic acini ''and'' pancreatic ducts.
*+/-Islets of Langerhans.

=Inflammatory=
==Pancreatitis==
===Classification===
*[[Acute pancreatitis]].
*[[Chronic pancreatitis]].

===Etiology===
Mnemonic ''I GET SMASHED'':
*Idiopathic.
*[[Gallstones]] ~45%.
*Ethanol ~35%.
*Tumours (pancreas, ampulla).
*Scorpion bites, snake bites.
*Microbial - mumps (paramyxovirus), [[Epstein-Barr virus]] (EBV), [[cytomegalovirus]] (CMV), mycoplasma.
*Autoimmune - [[Crohn's disease]], [[polyarteritis nodosa]] (PAN), [[systemic lupus erythematosus]] (SLE).
*Surgery/trauma, e.g. ERCP, motor vehicle collision.
*Hypercalcemia, hyperlipidemia/hypertriglyceridemia, [[hypothermia]].
*Emboli, e.g. post-[[CABG]].
*Drugs - ''SAND'' = steroids & sulfonamides, azathioprine, [[NSAID]]s, diuretics, such as furosemide.

==Acute pancreatitis==
{{Main|Acute pancreatitis}}

==Chronic pancreatitis==
{{Main|Chronic pancreatitis}}

=Cystic lesions - overview=
===General===
*True cystic lesions are uncommon.
**A true cystic lesion: ''must'' have an epithelial lining.
***Only 10% of cystic lesions are true cystic lesions, i.e. 90% of cystic lesions are really [[Pancreatic pseudocyst|pseudocysts]].
*It is hard to differentiate pseudocysts & cysts.

===Cystic tumours - clinical===
General:
*Usually diagnosed by imaging (CT/MRI, ERCP, Endoscopic ultrasound).
**50% incidental finding.
*Vague symptoms
*Abdominal mass.
*Weight loss.
*Jaundice.
*Usually favourable prognosis - mostly benign.

===Most important cystic lesions===
*Serous.
*Mucinous.
**Ovarian-like stroma.
*Solid pseudopapillay tumours.
*Intraductal papillary mucinous tumour (IPMT).
**No ovarian-like stroma.

Mnemonic ''SIMS'': Serous, IPMT, Mucinous, Solid pseudopapillary tumour.

====Useful stains====
*PAS-D.

====Mucinous vs. IMPT====
IMPT:
*No ovarian-like stroma.
*Usually has total pancreatectomy.

===Cystic tumours of the pancreas===
Khalifa's table of cystic tumours:
{| class="wikitable sortable"
!Tumour
!Usual sex
!Age (years)
!Usual site
!Typical size (cm)
![[Gross pathology]]
|-
|[[serous microcystic adenoma|Serous microcystic adenoma]]
|female
|66
|body & tail
|11
|[http://www.joplink.net/prev/200905/25_fig06.jpg (joplink.net]<ref>URL: [http://www.joplink.net/prev/200905/25.html http://www.joplink.net/prev/200905/25.html]. Accessed on: 15 February 2012.</ref>, [http://oac.med.jhmi.edu/cpc/images/cpc5/33.jpg (jhmi.edu)]<ref name=jhmi>URL: [http://oac.med.jhmi.edu/cpc/cases/cpc5/cpc5_answer.html http://oac.med.jhmi.edu/cpc/cases/cpc5/cpc5_answer.html]. Accessed on: 15 February 2012.</ref>
|-
|[[IPMN|Intraductal papillary mucinous tumour (IPMT)]]
|male
|62
|head
|4
|[http://oac.med.jhmi.edu/cpc/images/cpc5/28.jpg (jhmi.edu)]<ref name=jhmi>URL: [http://oac.med.jhmi.edu/cpc/cases/cpc5/cpc5_answer.html http://oac.med.jhmi.edu/cpc/cases/cpc5/cpc5_answer.html]. Accessed on: 15 February 2012.</ref>
|-
|Mucinous tumour
|female
|49
|body & tail
|10
|[http://radiology.rsna.org/content/251/1/77/F8.expansion.html (rsna.org)]
|-
|[[solid pseudopapillary tumour|Solid pseudopapillary tumour]]
|female
|35
|any
|7.5
|[http://www.ajronline.org/content/195/4/947/F4.expansion.html (ajronline.org)], [http://www.flickr.com/photos/35441329@N05/5249538296/ (flickr.com/humpath)]
|}

=Cystic lesions=
==Serous tumours - overview==
===General===
*Cell of origin: intralobular duct cells (ductular cells).
*Glycogen rich - but do not produce mucin.

====Subclassication====
*[[Serous microcystic adenoma]] ([[AKA]] serous cystadenoma<ref name=Ref_Sternberg4_1630>{{Ref Sternberg4|1630}}</ref>).
** Many small cysts.
*Serous oligocystic adenoma.
** Large cysts.
*Serous cystadenocarcinoma - very rare.<ref name=pmid22009426>{{Cite journal | last1 = Bano | first1 = S. | last2 = Upreti | first2 = L. | last3 = Puri | first3 = SK. | last4 = Chaudhary | first4 = V. | last5 = Sakuja | first5 = P. | title = Imaging of pancreatic serous cystadenocarcinoma. | journal = Jpn J Radiol | volume = 29 | issue = 10 | pages = 730-4 | month = Dec | year = 2011 | doi = 10.1007/s11604-011-0617-3 | PMID = 22009426 }}</ref>

Note:
*If one mucin +ve cell, tumour = a mucinous tumour.

==Serous cystadenoma of the pancreas==
*[[AKA]] ''serous microcystic adenoma'',<ref name=Ref_Sternberg4_1630>{{Ref Sternberg4|1630}}</ref> [[AKA]] ''pancreatic serous cystadenoma''.
{{Main|Serous cystadenoma of the pancreas}}

==Mucinous cystic neoplasms of the pancreas==
*Gastro-entero-pancreatic cell differentiation with hypercellular ovarian-type stroma.
**Stroma --> cellular.
*2-2.5% of all exocrine pancreatic tumours.
*Almost exclusively in women.
*Mean age - 49 years.
*>80% in body and tail.
*Average size ~10 cm.

Note:
*Looks different than serous tumour.

===Subclassification===
*Mucinous cystadenoma.
*Borderline mucinous cystic tumour.
*Mucinous cystadenocarcinoma.

===Borderline vs. Carcinoma===
*Few mitoses in borderline.

===Radiology===
*Mucinous tumours: multilocular.
*Generally larger than serous.
*Often partially solid and cystic.
*Often calcified.
**Calcification rare in serous.
*Usually tail & body.

===Microscopic===
====Mucinous cystadenoma====
Features:<ref name=Ref_GLP489>{{Ref GLP|489}}</ref>
*Simple tall columnar epithelium with large mucin vacuole on apical aspect.
*"Ovarian-type stroma" under epithelium.
**Ovarin-type stroma: high density of small (non-wavy) spindle cells with eosinophilic cytoplasm.

Notes:
*Appearance similar to ''mucinous cystadenoma'' in the [[ovarian tumours|ovary]].
*Mucin stains +ve (intracytoplasmic).

=====Images=====
<gallery>
Image:Benign_pancreatic_mucinous_cystic_neoplasm_-_very_low_mag.jpg | Benign mucinous cystic neoplasm - very low mag. (WC)
Image:Benign_pancreatic_mucinous_cystic_neoplasm_-_low_mag.jpg | Benign mucinous cystic neoplasm - low mag.(WC)
Image:Benign_pancreatic_mucinous_cystic_neoplasm_-_intermed_mag.jpg | Benign mucinous cystic neoplasm - intermed. mag. (WC)
Image:Benign_pancreatic_mucinous_cystic_neoplasm_-_high_mag.jpg | Benign mucinous cystic neoplasm - showing stroma - high mag. (WC)
</gallery>
www:
*[http://radiology.uchc.edu/eAtlas/Images/GYN/5705b.gif Mucinous cystadenoma - ovary (uchc.edu)].
[[File:4 477025809 sl 1.png|Mucinous cystic neoplasm of pancreas]]
[[File:4 477025809 sl 2.png|Mucinous cystic neoplasm of pancreas]]
[[File:4 477025809 sl 3.png|Mucinous cystic neoplasm of pancreas]]
[[File:4 477025809 sl 4.png|Mucinous cystic neoplasm of pancreas]]
[[File:4 477025809 sl 5.png|Mucinous cystic neoplasm of pancreas]]
[[File:4 477025809 sl 6.png|Mucinous cystic neoplasm of pancreas]] 
Benign mucinous cystic neoplasm of pancreas in a 62 year old woman. A. CT scan showed a peripherally calcified spheroidal mass at the tail of the pancreas. Cytology only showed debris and inflammatory cells, but CEA of the fluid was 2875.2 ng/mL. B. Almost all sections of the cyst showed acellular debris topping a fibrous, often calcified wall, consistent with a pseudocyst. C. Extensive sampling, undertaken because of the high CEA, revealed rare sections with a lining. D. Lining nuclei are bland, with even chromatin. Shape and size variation, as well as darkening when shrunken, are all explicable by degeneration. E. Within distal pancreas, a focus of changes of chronic pancreatitis is seen upper left, while a pancreatic duct in lower right shows an intraductal proliferation. F. Tumor cells show mucinous vacuoles, with better preserved nuclei. Nuclear appearances remain bland. Ovarian type stroma was not seen.

====Borderline mucinous cystic tumour====
Features:
*May have finger like projections.
*Pseudostratification of epithelium.

Notes:
* Surgery does not change based on diagnosis on frozen section.
** Only question is "Is the margin clear?".
* Borderline tumours are rare.

====Carcinoma====
*Cells floating in mucin.

====Mucinous tumour versus pseudocyst====
{| class="wikitable sortable"
! Finding
! Mucinous tumour
! Pseudocyst
|-
|Amylase & lipase || low || high
|-
|Viscosity || high || low
|-
|[[CEA]], CA125 || high || low
|}

Prognosis:
*Benign looking tumours have the potential to transform into carcinoma.
*No report of assoc. pseudomyxoma peritonei.
**US boards question -- it is an exception ... others one cause it.
*Prognosis of m. cystadenocarcinoma is slightly better than that of ductal adenocarcinoma.

==Intraductal papillary mucinous tumour==
*Abbreviated ''IPMT''.
*[[AKA]] ''intraductal papillary mucinous neoplasm'', abbreviated ''IPMN''.
{{Main|Intraductal papillary mucinous tumour}}

==Solid pseudopapillary tumour==
*[[AKA]] ''solid pseudopapillary neoplasm'', abbreviation ''SPN''.
*[[AKA]] ''solid and papillary epithelial neoplasm'', abbreviated ''SPEN''.<ref>URL: [http://brighamrad.harvard.edu/Cases/bwh/hcache/360/full.html http://brighamrad.harvard.edu/Cases/bwh/hcache/360/full.html]. Accessed on: 31 October 2011.</ref>
{{Main|Solid pseudopapillary tumour}}

=Pre-malignant lesions=
==Pancreatic intraepithelial neoplasia==
*Abbreviated ''PanIN''.
{{Main|Pancreatic intraepithelial neoplasia}}

=Solid tumours=
==Invasive ductal carcinoma of the pancreas==
*[[AKA]] ''ductal adenocarcinoma''.
*[[AKA]] ''pancreatic ductal adenocarcinoma''.
*[[AKA]] ''pancreatic adenocarcinoma''.
{{Main|Invasive ductal carcinoma of the pancreas}}

==Pancreatic neuroendocrine tumour==
*Abbreviated ''PanNET''.<ref name=pmid22198808/>
*[[AKA]] ''pancreatic islet cell tumour''<ref name=pmid22198808>{{Cite journal | last1 = Burns | first1 = WR. | last2 = Edil | first2 = BH. | title = Neuroendocrine Pancreatic Tumors: Guidelines for Management and Update. | journal = Curr Treat Options Oncol | volume = | issue = | pages = | month = Dec | year = 2011 | doi = 10.1007/s11864-011-0172-2 | PMID = 22198808 }}</ref> - considered to be an outdated term.
*[[AKA]] ''islet cell tumour'' - considered to be an outdated term.
{{Main|Neuroendocrine tumour of the pancreas}}

==Acinar cell carcinoma of the pancreas==
:'''Not''' to be confused with ''[[acinic cell carcinoma]]''.
*[[AKA]] ''acinar cell carcinoma''.
*[[AKA]] ''pancreatic acinar cell carcinoma''.<ref name=pmid>{{Cite journal | last1 = Thomas | first1 = PC. | last2 = Nash | first2 = GF. | last3 = Aldridge | first3 = MC. | title = Pancreatic acinar cell carcinoma presenting as acute pancreatitis. | journal = HPB (Oxford) | volume = 5 | issue = 2 | pages = 111-3 | month = | year = 2003 | doi = 10.1080/13651820310001153 | PMID = 18332967 }}</ref>
{{Main|Acinar cell carcinoma of the pancreas}}

==Pancreatoblastoma==
{{Main|Pancreatoblastoma}}

=See also=
*[[Duodenum]].
*[[Gallbladder]].
*[[Gastrointestinal pathology]].
*[[Von Hippel-Lindau syndrome]].
*[[IgG4-related systemic disease]].

=References=
{{reflist|2}}

==Further reading==
{{Cite journal | last1 = Klimstra | first1 = DS. | last2 = Pitman | first2 = MB. | last3 = Hruban | first3 = RH. | title = An algorithmic approach to the diagnosis of pancreatic neoplasms. | journal = Arch Pathol Lab Med | volume = 133 | issue = 3 | pages = 454-64 | month = Mar | year = 2009 | doi = 10.1043/1543-2165-133.3.454 | PMID = 19260750 }}

=External links=
*[http://pancreaticcancer2000.com/page1.htm Pancreatic cancer - PanINs - pancreaticcancer2000.com].

[[Category:Gastrointestinal pathology]]

Adult granulosa cell tumour

2017-02-01T16:52:41Z

Mitchell: /* Images */ added a case

'''Adult granulosa cell tumour''' is an [[ovarian tumour]]. It is also known as '''granulosa cell tumour'''. It should '''not''' be confused with the ''[[granular cell tumour]]''.

Ideally, it should be called ''adult granulosa cell tumour'' to avoid confusion with ''[[juvenile granulosa cell tumour]]''.

==General==
*May secrete estrogen.
**May present with endometrial pathology, e.g. [[endometrial hyperplasia]] ''or'' endometrioid [[endometrial carcinoma]].
**Occasionally secrete antrogens lead to virilization.<ref name=pmid19062005>{{Cite journal | last1 = Patel | first1 = SS. | last2 = Carrick | first2 = KS. | last3 = Carr | first3 = BR. | title = Virilization persists in a woman with an androgen-secreting granulosa cell tumor. | journal = Fertil Steril | volume = 91 | issue = 3 | pages = 933.e13-5 | month = Mar | year = 2009 | doi = 10.1016/j.fertnstert.2008.10.038 | PMID = 19062005 }}</ref>

Note:
*Normal granulosa cells convert androgen from the theca cells to estrogen and/or progesterone.<ref name=pmid15541573>{{Cite journal | last1 = Havelock | first1 = JC. | last2 = Rainey | first2 = WE. | last3 = Carr | first3 = BR. | title = Ovarian granulosa cell lines. | journal = Mol Cell Endocrinol | volume = 228 | issue = 1-2 | pages = 67-78 | month = Dec | year = 2004 | doi = 10.1016/j.mce.2004.04.018 | PMID = 15541573 }}</ref>

==Gross==
*Classically solid.

==Microscopic==
Features:
* Classic appearance includes gland-like structures filled with acidophilic material (Call-Exner bodies).
* Small cuboidal to polygonal cell in sheets ''or'' strands ''or'' cords.
* Nuclear grooves.

Note:
*There is a "10% rule" -- if less than 10% of a SCST is granulosa cells... it isn't granulosa cell tumour.
*Juvenile variant of GCT has more nuclear pleomorphism.

DDx:<ref>{{Cite journal | last1 = Kommoss | first1 = S. | last2 = Anglesio | first2 = MS. | last3 = Mackenzie | first3 = R. | last4 = Yang | first4 = W. | last5 = Senz | first5 = J. | last6 = Ho | first6 = J. | last7 = Bell | first7 = L. | last8 = Lee | first8 = S. | last9 = Lorette | first9 = J. | title = FOXL2 molecular testing in ovarian neoplasms: diagnostic approach and procedural guidelines. | journal = Mod Pathol | volume = 26 | issue = 6 | pages = 860-7 | month = Jun | year = 2013 | doi = 10.1038/modpathol.2012.226 | PMID = 23348906 }}</ref>
* [[Urothelial cell carcinoma]] (UCC).
** UCC usually has extensive necrosis.
* [[Brenner tumour]].
* [[Sertoli cell tumour]].
* [[Sertoli-Leydig cell tumour]].
* [[Endometrial stromal sarcoma]].

===Images===
<gallery>
Image:Granulosa_cell_tumour1.jpg | Granulosa cell tumour - low mag. (WC)
Image:Granulosa_cell_tumour2.jpg | Granulosa cell tumour - high mag. (WC)
</gallery>
[[File:5ov41630891386282 sl 1.png|Granulosa cell tumor.]]
[[File:5ov41630891386282 sl 2.png|Granulosa cell tumor.]]
[[File:5ov41630891386282 sl 3.png|Granulosa cell tumor.]]
[[File:5ov41630891386282 sl 4.png|Granulosa cell tumor.]]
[[File:5ov41630891386282 sl 5.png|Granulosa cell tumor.]]
 
Adult granulosa cell tumor of left ovary of 92 year old Mexican American woman. CT scan. 18 x 12 x 20 cm multi-loculated multi-septated cystic mass fills the entire urinary pelvis and extending up to the lower abdomen. A. A diffuse pattern appears at low power. B. Pale, round to ovoid nuclei lack mitoses, have little discernible cytoplasm, and are haphazardly arranged. Nuclear grooves, two with arrows, are readily identified. Nucleoli are small. Necrosis was not seen. C. Occasional tubules, indistinguishable from those seen in well-differentiated Sertoli cell tumors, are not considered reason to doubt a diagnosis of granulosa cell tumor if they account for less than 10% of the tumor; these were the sole such tubules in this specimen. D. Call-Exner bodies often bear degenerating nuclei.

==IHC==
* Inhibin positive.<ref name=Ref_PBoD1102>{{Ref PBoD|1102}}</ref>
** Inhibin negative in ''[[Brenner tumour]]''.
*Calretinin +ve.

==Molecular==
:Currently not used for diagnosis.
*FOXL2 point mutation<ref name=pmid22240241 >{{Cite journal | last1 = Jamieson | first1 = S. | last2 = Fuller | first2 = PJ. | title = Molecular pathogenesis of granulosa cell tumors of the ovary. | journal = Endocr Rev | volume = 33 | issue = 1 | pages = 109-44 | month = Feb | year = 2012 | doi = 10.1210/er.2011-0014 | PMID = 22240241 }}</ref> seen in 86 of 89 tumours.<ref name=pmid19516027>{{Cite journal | last1 = Shah | first1 = SP. | last2 = Köbel | first2 = M. | last3 = Senz | first3 = J. | last4 = Morin | first4 = RD. | last5 = Clarke | first5 = BA. | last6 = Wiegand | first6 = KC. | last7 = Leung | first7 = G. | last8 = Zayed | first8 = A. | last9 = Mehl | first9 = E. | title = Mutation of FOXL2 in granulosa-cell tumors of the ovary. | journal = N Engl J Med | volume = 360 | issue = 26 | pages = 2719-29 | month = Jun | year = 2009 | doi = 10.1056/NEJMoa0902542 | PMID = 19516027 }}</ref>

==See also==
*[[Ovarian tumours]].

==References==
{{Reflist|2}}

[[Category:Ovarian tumours]]
[[Category:Diagnosis]]

Liver neoplasms

2017-01-31T23:15:23Z

Mitchell: /* Hematopoietic tumors */ added a case

[[Image:Secondary tumor deposits in the liver from a primary cancer of the pancreas.jpg|thumb|right|300px|Liver metastases at [[gross pathology|gross]].]]
This article examines '''liver neoplasms''' and '''pre-malignant lesions of the liver'''. In North America, most malignant liver lesions are [[liver metastasis|metastases]].

This article focuses on primary malignancies of the liver, neoplastic liver lesions, and biliary malignancies.
It only briefly discusses metastatic lesions. An introduction to ''liver pathology'' is in the ''[[liver]]'' article. Medical liver disease is dealt with in the ''[[medical liver disease]]'' article.

=Overview=
===Dysplasic lesions of the liver===
Types:<ref>STC. S.30-37, 19 Jan 2009.</ref>
*"Large cell dysplasia" (AKA ''large cell change'') - not considered a precursor for HCC, not considered a dysplasia.<ref name=pmid16982109>{{Cite journal | last1 = Park | first1 = YN. | last2 = Roncalli | first2 = M. | title = Large liver cell dysplasia: a controversial entity. | journal = J Hepatol | volume = 45 | issue = 5 | pages = 734-43 | month = Nov | year = 2006 | doi = 10.1016/j.jhep.2006.08.002 | PMID = 16982109 }}</ref>
*[[Small liver cell dysplasia]] ([[AKA]] small cell dysplasia).
*Low grade dysplasia.
*High grade dysplasia.

===Neoplastic lesions===
*[[Hepatic adenoma]].

===Malignant lesions of the liver===
*[[Hepatocellular carcinoma]] (HCC) - most common malignant liver primary in adults.
*[[Hepatoblastoma]] - malignant liver primary in children.
*Intrahepatic [[cholangiocarcinoma]] (ICC).<ref name=pmid19212669>{{Cite journal | last1 = Shirakawa | first1 = H. | last2 = Kuronuma | first2 = T. | last3 = Nishimura | first3 = Y. | last4 = Hasebe | first4 = T. | last5 = Nakano | first5 = M. | last6 = Gotohda | first6 = N. | last7 = Takahashi | first7 = S. | last8 = Nakagohri | first8 = T. | last9 = Konishi | first9 = M. | title = Glypican-3 is a useful diagnostic marker for a component of hepatocellular carcinoma in human liver cancer. | journal = Int J Oncol | volume = 34 | issue = 3 | pages = 649-56 | month = Mar | year = 2009 | doi = | PMID = 19212669 | url = http://www.spandidos-publications.com/serveFile/ijo_34_3_649_PDF.pdf?type=article&article_id=ijo_34_3_649&item=PDF}}</ref>
*Combined hepatocellular carcinoma and intrahepatic cholangiocarcinoma (CHC).

===Lesions that arise in a non-cirrhotic liver===
Hepatocellular:
*[[Hepatic adenoma]].
*[[Fibrolamellar hepatocellular carcinoma]].
*[[Focal nodular hyperplasia]].

Other:
*[[Metastasis]].
*[[Cholangiocarcinoma]].
*[[Liver hemangioma]].

===Tabular comparison===
====Precursors====
Features of HCC & its precursors - generated from DCHH<ref name=Ref_DCHH170-1>{{Ref DCHH|170-1}}</ref> and STC:
{| class="wikitable"
| '''Features''' || '''SLCD''' || '''Low-grade dysplasia''' || '''High-grade dysplasia''' || '''HCC'''
|-
| Plate thickness || <3 cells || <=2 cells || <=3 cells, usu. >2 cells || '''>3 cells'''
|-
| Reticulin (stain) || intact chicken wire || intact chicken wire || intact chicken wire || '''damaged chicken wire'''
|-
| Nuclear changes || nuc. enlargement, hyperchromasia || +/- atypia (???) || marked atypia || +/- incr. NCR, +/-irreg. nuc. contour
|-
| Cytoplasmic change || hyperchromasia, decr. as cell size preserved || none (???) || +/- basophilia || variable (lighter vs. hyperchromasia)
|-
| Portal tracts || ? || loss of portal tracts || loss of portal tracts || loss of portal tracts
|-
| Management || follow ??? || follow || ablate || ablate/surgery
|-
|}
Abbreviations:
*SLCD = small liver cell dysplasia.

Notes:
*Large cell dysplasia:
**Cell size ~ 2x normal, [[NC ratio]] ~ normal.
*SLCD:
**Cell size ~ 1/2x normal, NC ratio - increased.

====Hepatic tumours====
Benign:
{| class="wikitable sortable"
! Entity
! Gross
! Microscopic
! IHC/stains
! Other
! Images
|-
| [[Hepatic hemangioma]]
| similar to normal liver parenchyma, red (hemorrhagic), well-circumscribed
| spaces lined by benign endothelial cells
| CD31+ (???)
| -
| [http://radiographics.rsna.org/content/24/6/1719/F8.expansion.html gross (rsna.org)]
|-
| [[Focal nodular hyperplasia]]
| central scar, large vessels, usu. well-circumscribed
| large arteries, unpaired arteries, bile duct proliferation
|
| usu. diagnosed by imaging
| [http://radiographics.rsna.org/content/24/1/3/F1.expansion.html gross (rsna.org)]
|-
| [[Hepatocellular adenoma]]
| subcapsular, well-circumscribed
| loss of portal tracts, nuclear glycogenation
| reticulin - liver plate thickness <= 3
| background not cirrhotic, assoc. [[OCP]]
| [http://www.mda-sy.com/up//uploads/images/mda-sy-d768fd265c.jpg gross (mda-sy.com)<ref>URL: [http://www.mda-sy.com/vb/showthread.php?p=5083&langid=1 http://www.mda-sy.com/vb/showthread.php?p=5083&langid=1]. Accessed on: 16 February 2012.</ref>]
|}

Malignant:
{| class="wikitable sortable"
! Entity
! Gross
! Microscopic
! IHC/stains
! Other
! Images
|-
| [[Liver metastasis]]
| multiple, white lesions
| variable, usu. tubular (glandular) with pseudostratified hyperchromatic nuclei
| CK7-, [[CK20]]+ (colorectal), HepPar-1-, [[CK19]]-
| [[colorectal carcinoma]] most common
| [[Image:Secondary_tumor_deposits_in_the_liver_from_a_primary_cancer_of_the_pancreas.jpg | thumb| center| 150px| Metastases. (WC)]]
|-
| [[Hepatocellular carcinoma]]
| poorly circumscribed, +/-necrosis, +/-hemorrhage
| loss of portal tracts, unpaired arteries, +/-nuclear atypia
| reticulin - liver plate thickness > 3
| background often cirrhotic
| [[Image:Hepatocellular_carcinoma_1.jpg |thumb|center|150px| HCC. (WC/Uthman)]]
|-
| [[Cholangiocarcinoma]]
| cauliflower-like outline, white, classically solitary, no cirrhosis
| tubular architecture and mild [[nuclear atypia]] (adenocarcinoma), [[desmoplastic stroma]]
| CK7+, CK19+
| background usu. not cirrhotic
| [[Image:Cholangiocarcinoma.png |thumb|center|150px| Cholangiocarcinoma. (WC)]]
|}

=Dysplasia of the liver=
==Small liver cell dysplasia==
*Abbreviated ''SLCD''.
*[[AKA]] ''small cell dysplasia''.
===General===
*Considered a precursor to [[HCC]].
**Frequently found in livers with HCC - when compared to livers without HCC.<ref name=pmid9401407>{{Cite journal | last1 = Szczepański | first1 = W. | title = Liver cell dysplasia in liver cirrhosis and hepatocellular carcinoma. | journal = Pol J Pathol | volume = 48 | issue = 3 | pages = 147-57 | month = | year = 1997 | doi = | PMID = 9401407 }}</ref>

===Microscopic===
Features:<ref>STC S.32, 19 Jan 2009.</ref>
*Cells similar in size to normal hepatocytes.
**Name derived from the fact that there is also an entity that was called ''large cell dysplasia'' (AKA ''large liver cell dysplasia'',<ref name=pmid9401407>{{Cite journal | last1 = Szczepański | first1 = W. | title = Liver cell dysplasia in liver cirrhosis and hepatocellular carcinoma. | journal = Pol J Pathol | volume = 48 | issue = 3 | pages = 147-57 | month = | year = 1997 | doi = | PMID = 9401407 }}</ref> and ''large cell change'').
*Increased [[NC ratio]] - "more blue".
*Mild nuclear and cytoplasmic hyperchromatism.

Notes:
*Normal hepatic architecture (main differentiator from HCC).
*Remember "... [[Basics|blue is bad]]".

Micrograph:
*[http://www.medscape.com/viewarticle/515219_3 Low resolution micrograph of SCD (medscape.com)].

==Low-grade hepatocellular dysplasia==
*Generally referred to as ''low-grade dysplasia'' as the context is usually clear.
===Microscopic===
*Uniform cells - "noticeably different from normal".<ref>STC - 19 Jan 2009. (???)</ref>
**Changes in nuclear size, irregular nuclear contour and/or changes in cytoplasm staining.
*Loss of portal tracts.
*Irregular margin.

Notes:
*DCHH describes LGD as: "normal hepatocytes in plates <nowiki>[of normal thickness]</nowiki>".<ref name=Ref_DCHH170-1>{{Ref DCHH|170-1}}</ref>

DDx:
*[[Nodular regenerative hyperplasia]] - lacks: compressed rim of cells, central portal tract.<ref name=Ref_DCHH170-1>{{Ref DCHH|170-1}}</ref>

==High-grade hepatocellular dysplasia==
*Generally referred to as ''high-grade dysplasia'' as the context is usually clear.
===General===
*"Bader" version of ''[[Low-grade hepatocellular dysplasia|low-grade dyplasia]]''.

===Microscopic===
Features - in addition to those of low grade dysplasia:<ref name=Ref_DCHH170-1>{{Ref DCHH|170-1}}</ref>
*Liver plate >2 cells thick.
*Significant nuclear atypia.
*Basophilic cytoplasm.

DDx:
*[[Low-grade hepatocellular dysplasia]].
*[[Hepatocellular carcinoma]].

Image:
*[http://radiographics.rsna.org/content/22/5/1023.figures-only Series of liver micrographs including high grade dysplasia (radiographics.rsna.org)].

=Benign hepatic neoplasms=
==Bile duct hamartoma==
A. [[File:1 BDH 1 680x512px.tif|Trichrome shows fibrous spaces with dilated ducts (20X).]]
B. [[File:2 BDH 1 680x512px.tif|Bizarre, ramifying tubules with dilatations (100X).]]
 
C. [[File:3 BDH 1 680x512px.tif|Bland epithelial linings (400X).]]
D. [[File:4 BDH 1 680x512px.tif|Surrounding tract with tortuous bile ducts & inflammation, likely secondary to hamartomas (200X).]]

Bile duct hamartomas. A. Trichrome shows fibrous spaces with dilated ducts. B. Bizarre, ramifying tubules with dilatations. C. Bland epithelial linings. D. Surrounding tract with tortuous bile ducts & inflammation, likely secondary to hamartomas.

==Bile duct adenoma==
:''Should '''not''' be confused with [[bile duct hamartoma]].''
{{Main|Bile duct adenoma}}

==Hepatic adenoma==
*[[AKA]] ''hepatocellular adenoma'', abbreviated ''HCA''.
{{Main|Hepatic adenoma}}

==Hepatobiliary mucinous cystadenoma==
*[[AKA]] ''biliary cystadenoma''.
===General===
*Benign neoplasm.
**May transform into a malignancy.<ref name=pmid20698207>{{Cite journal | last1 = Yu | first1 = J. | last2 = Wang | first2 = Y. | last3 = Yu | first3 = X. | last4 = Liang | first4 = P. | title = Hepatobiliary mucinous cystadenoma and cystadenocarcinoma: report of six cases and review of the literature. | journal = Hepatogastroenterology | volume = 57 | issue = 99-100 | pages = 451-5 | month = | year = | doi = | PMID = 20698207 }}</ref>

===Microscopic===
Features:
*Cystic spaces lined by a mucinous epithelium (simple columnar epithelium with a clear cytoplasm).
*Surrounding dense ovarian like stroma.

DDX:
[[Biliary Intraductal Papillary Neoplasm]]
*no surrounding ovarian stroma
*Intraductal - connects with the biliary tree lumen.

Note:
*Similar to [[pancreatic mucinous cystadenoma]].

==Cavernous hemangioma==

A. [[File:1 CAV 1 680x512px.tif|Fibrous foci with increased spaces, hepatocyte focus with nonspecific fibrotic bridge (40X).]]
B. [[File:2 CAV 1 680x512px.tif|Cavernous hemangioma with flat, non-atypical endothelium (200X).]]
 
C. [[File:3 CAV 1 680x512px.tif|Tortuous bile ducts/ductules, not to be considered generalized in presence of mass (200X).]]
D. [[File:4 CAV 1 680x512px.tif|Tortuous bile ductsductules, not to be considered generalized in presence of mass (200X).]]

Cavernous hemangioma. A. Fibrous foci with increased spaces, hepatocyte focus with nonspecific fibrotic bridge. B. Cavernous hemangioma with flat, non-atypical endothelium. C. Tortuous bile ductules, not to be considered generalized in presence of mass. D. Tortuous bile ducts, not to be considered generalized in presence of mass.

=Malignant hepatic neoplasms=
In North America, the most common malignant liver tumour is [[liver metastasis|metastases]].

==Hepatoblastoma==
===General===
*Most common liver cancer in children.<ref name=Ref_PBoD923>{{Ref PBoD|923}}</ref><ref name=emed_hepatoblastoma>URL: [http://emedicine.medscape.com/article/986802-overview http://emedicine.medscape.com/article/986802-overview]. Accessed on: 29 November 2009.</ref>
**Rare in adolescents and adults.
**Age of diagnosis usu. ~1 year old; most less than 3 years old.
*Surgical biopsy; core needle biopsy ''not'' done as as lesion is vascular.

Associations:
*[[Beckwith-Wiedemann syndrome]].<ref name=pmid9544889>{{cite journal |author=DeBaun MR, Tucker MA |title=Risk of cancer during the first four years of life in children from The Beckwith-Wiedemann Syndrome Registry |journal=J. Pediatr. |volume=132 |issue=3 Pt 1 |pages=398–400 |year=1998 |month=March |pmid=9544889 |doi= |url=}}</ref>
*[[Familial adenomatous polyposis]].

Clinical:
*Usually present with hepatomegaly.
*High AFP.<ref>URL: [http://emedicine.medscape.com/article/986802-diagnosis http://emedicine.medscape.com/article/986802-diagnosis]. Accessed on: 11 February 2011.</ref>

===Microscopic===
Features:
*[[Small round cell tumour]].
*Fetal hepatocytes ~ 1:3 NC ratio, eosinophilic cytoplasm.
*+/-Mesenchymal component
**Immature fibrous tissue, osteoid or cartilage.

DDx:
*[[Small round cell tumours]].
**[[Neuroblastoma]].
*[[Teratoma]].
*[[Hepatocellular carcinoma]] - separated based on histomorphology alone.

====Images====
<gallery>
Image:Hepatoblastoma_-_2_-_very_high_mag.jpg | Hepatoblastoma - very high mag. (WC/Nephron)
Image:Hepatoblastoma_-_high_mag.jpg | Hepatoblastoma - high mag. (WC/Nephron)
</gallery>

====Subtypes====
*Six histologic subtypes - that are subdivided into two groups:<ref>URL: [http://emedicine.medscape.com/article/986802-diagnosis http://emedicine.medscape.com/article/986802-diagnosis]. Accessed on: 11 February 2011.</ref>
** Epithelial type:
**# Fetal pattern.
**# Embryonal and fetal pattern.
**# Macrotrabecular pattern.
**#* May mimic [[hepatocellular carcinoma]] histologically.<ref>URL: [http://www.cap.org/apps/cap.portal?_nfpb=true&cntvwrPtlt_actionOverride=%2Fportlets%2FcontentViewer%2Fshow&_windowLabel=cntvwrPtlt&cntvwrPtlt{actionForm.contentReference}=cap_foundation%2FcaseOfMonth%2FMar10%2Fmar_2010_cotm_diagnosis.html&_state=maximized&_pageLabel=cntvwr#null http://www.cap.org/apps/cap.portal?_nfpb=true&cntvwrPtlt_actionOverride=%2Fportlets%2FcontentViewer%2Fshow&_windowLabel=cntvwrPtlt&cntvwrPtlt{actionForm.contentReference}=cap_foundation%2FcaseOfMonth%2FMar10%2Fmar_2010_cotm_diagnosis.html&_state=maximized&_pageLabel=cntvwr#null]. Accessed on: 11 February 2011.</ref>
**# Small cell undifferentiated pattern.
**#* Poor prognosis.
** Mixed epithelial and mesenchymal type:
**# With teratoid features.
**# Without teratoid features.

===IHC===
*Alpha-fetoprotein +ve.
*Hepatocyte specific antigen +ve esp. in fetal component.<ref name=pmid16647953>{{Cite journal | last1 = Halász | first1 = J. | last2 = Holczbauer | first2 = A. | last3 = Páska | first3 = C. | last4 = Kovács | first4 = M. | last5 = Benyó | first5 = G. | last6 = Verebély | first6 = T. | last7 = Schaff | first7 = Z. | last8 = Kiss | first8 = A. | title = Claudin-1 and claudin-2 differentiate fetal and embryonal components in human hepatoblastoma. | journal = Hum Pathol | volume = 37 | issue = 5 | pages = 555-61 | month = May | year = 2006 | doi = 10.1016/j.humpath.2005.12.015 | PMID = 16647953 }}</ref>
*Beta-catenin +ve (cytoplasmic and nuclear).<ref name=pmid16647953/>

==Hepatocellular carcinoma==
*Abbreviated ''HCC''.
{{Main|Hepatocellular carcinoma}}

==Biliary Intraductal Papillary Neoplasm<ref>{{Cite journal | Masayuki Ohtsuka, Hiroaki Shimizu, Atsushi Kato, et al., “Intraductal Papillary Neoplasms of the Bile Duct,” International Journal of Hepatology, vol. 2014, Article ID 459091, 10 pages, 2014. doi:10.1155/2014/459091}}</ref>==

===General===
*Rare
*Highest incidence in Far Eastern countries
*Association with hepatolithiasis and clonorchiasis
*Between 50 and 70 years of age
*Slight male predominance
*Intermittent abdominal pain
*Acute cholangitis
*Jaundice

*Biliary counterpart of [[pancreatic intraductal papillary mucinous neoplasm]]
*Biliary counterpart of [[intracholecystic papillary neoplasm]] (gall bladder)
*Construct consumes some cases of biliary cystadenoma/cystadenocarcinoma, biliary papilloma/papillomatosis, intraductal growth type of cholangiocarcinoma and papillary carcinoma of the extrahepatic bile duct.

===Radiology===
*Bile duct dilatation
*Intraductal masses

===Gross===
*Singular, or occasionally multiple, polypoid masses extending into the lumen of a dilated bile duct
*Or multilocular well-defined cystic mass containing mucinous fluid
*Granular or papillary mucosa
*Communication with bile duct may be difficult to confirm

===Microscopic===
*Papillary or villous growth within the lumen of an intra or extrahepatic bile duct
*Papillary fronds with fine vascular cores
*Epithelium types
**Pancreatobiliary
**Intestinal - marked mucin secretion
**Gastric
**Oncocytic types
*Dysplasia
**High or low grade
**Marked variation in histologic grade between different regions of individual tumors

*Common association with invasive cholangiocarcinoma
**Tubular adenocarcinoma
**Mucinous (colloid) carcinoma (often in association with the intestinal type).

====DDX====
*[[Biliary Mucinous Cystic Neoplasm]]
***Epithelium is surrounded by a distinct ovarian-like stroma.

====Photos====
<gallery>
Image:BileDuct IntraductalPapillaryNeoplasm LP CTR.jpg|Bile Ducts - Intraductal Papillary Neoplasm - Low power (SKB)
Image:BileDuct IntraductalPapillaryNeoplasm MP CTR.jpg|Bile Ducts - Intraductal Papillary Neoplasm - Medium power (SKB)
Image:BileDuct IntraductalPapillaryNeoplasm HP CTR.jpg|Bile Ducts - Intraductal Papillary Neoplasm - High power (SKB)
Image:BileDucts IntraductalPapillaryNeoplasm NonMucinousType LP PA.jpg|Bile Ducts - Intraductal Papillary Neoplasm - Low power (SKB)
Image:BileDucts IntraductalPapillaryNeoplasm OncocyticType HP PA.jpg|Bile Ducts - Intraductal Papillary Neoplasm - High power (SKB)
Image:BileDucts IntraductalPapillaryNeoplasm NonMucinousType HP2 PA.jpg|Bile Ducts - Intraductal Papillary Neoplasm - High power (SKB)
</gallery>

A. [[File:1 papillary cbd aca 1 680x512px.tif| Intraductal papillary neoplasm of common bile duct with associated invasive carcinoma.]]
B. [[File:2 papillary cbd aca 1 680x512px.tif| Intraductal papillary neoplasm of common bile duct with associated invasive carcinoma.]]
 
C. [[File:3 papillary cbd aca 1 680x512px.tif| Intraductal papillary neoplasm of common bile duct with associated invasive carcinoma.]]
D. [[File:4 papillary cbd aca 1 680x512px.tif| Intraductal papillary neoplasm of common bile duct with associated invasive carcinoma.]]
 
E. [[File:5 papillary cbd aca 1 680x512px.tif| Intraductal papillary neoplasm of common bile duct with associated invasive carcinoma.]]
F. [[File:6 papillary cbd aca 1 680x512px.tif| Intraductal papillary neoplasm of common bile duct with associated invasive carcinoma.]]

Intraductal papillary neoplasm of common bile duct with associated invasive carcinoma. A. The papillary tumor comprises mostly variably dilated acini. B. Tumor also shows areas of micropapillae. C. Some areas within the non-invasive tumor showed necrosis, with the black pyknotic nuclei amid red debris. D. Definite invasion was established low power by glands headed in perpendicular directions. E. Embedded in fibroblastic response are non-acinar walls and isolated epithelial groups. F. Also embedded in fibroblastic response are flat glands with nuclei showing loss of polarity (lack of respect for lateral intercellular borders shown by variable orientation to base of gland).

Notes -
*Reflect on the known marked variation in histologic grade between different regions of individual tumors when rendering an opinion on a small biopsy specimen.
*Consider the possibility of an invasive component and submit tissue generously.

See also:
PubCan [http://www.pubcan.org/printicdotopo.php?id=5755]

==Cholangiocarcinoma==
*[[AKA]] ''bile duct carcinoma''.<ref>URL: [http://www.cancer.org/cancer/bileductcancer/detailedguide/bile-duct-cancer-what-is-bile-duct-cancer http://www.cancer.org/cancer/bileductcancer/detailedguide/bile-duct-cancer-what-is-bile-duct-cancer]. Access on: 23 May 2013.</ref>
{{Main|Cholangiocarcinoma}}

==Hepatic angiosarcoma==
{{Main|Angiosarcoma}}
*[[AKA]] ''angiosarcoma of the liver''.
===General===
*Liver angiosarcomas are associated with vinyl chloride exposure.<ref name=Ref_PCPBoD8_212>{{Ref PCPBoD8|212}}</ref>

===Microscopic===
Features:
*Atypical endothelial cells - may be subtle.

==Hepatic metastasis==
{{Main|Liver metastasis}}
*[[AKA]] ''liver metastases''.
*[[AKA]] ''metastatic liver disease''.
==Hematopoietic tumors==
A [[File:1 MM 1 Covenant 680x512px.tif|One liver core was normal (Row 1 Left 40X).]]
 
B [[File:2 MM 1 Covenant 680x512px.tif|A triad with a proliferated bile ductule, otherwise normal (Row 1 Right 400X).]]
 
C [[File:3 MM 1 Covenant 680x512px.tif|The other core showed a mass of tumor mashed against normal liver (Row 2 Left 40X).]]
 
D [[File:4 MM 1 Covenant 680x512px.tif|Tumor cells showed round to ovoid nuclei without pattern and with grey cytoplasm that proved to be CD138 positive (Row 2 Right 400X).]]
 
Plasmacytoma appearing as a tumor mass. A. One liver core was normal. B. A triad with a proliferated bile ductule, otherwise normal. C. The other core showed a mass of tumor mashed against normal liver. D. Tumor cells showed round to ovoid nuclei without pattern and with grey cytoplasm that proved to be CD138 positive.

A. [[File:1 B cell lym liver 1 680x512px.tif|Apparent inflamed fibrous tract with lobular inflammatory collections in adjacent liver (Row 1 Left 40X).]]
 
B. [[File:2 B cell lym liver 1 680x512px.tif|Apparent inflamed fibrous band between two relatively hepatocyte regions (Row 1 Right 40X).]]
 
C. [[File:3 B cell lym liver 1 680x512px.tif|Apparent piecemeal necrosis with bile ductular proliferation (Row 2 Left 200X).]]
 
D. [[File:4 B cell lym liver 1 680x512px.tif|Apparent portal inflammation with unaffected interlobular bile duct (Row 2 Right 200X).]]
 
E. [[File:5 B cell lym liver 1 680x512px.tif|Apparent lobular infiltrate with small masse.]]
 
F. [[File:6 B cell lym liver 1 680x512px.tif|Proof is at high power. All cells are similar to macrophages but are too closely crowded to be macrophages. The monomorphism (one type of cell) should inspire immunohistochemical stains, which showed the patient had a B cell lymphoma.]]
 
B cell lymphoma mimicking hepatitis with fibrosis. A. Apparent inflamed fibrous tract with lobular inflammatory collections in adjacent liver. B. Apparent inflamed fibrous band between two relatively hepatocyte regions. C. Apparent piecemeal necrosis with bile ductular proliferation. D. Apparent portal inflammation with unaffected interlobular bile duct. E. Apparent lobular inflammation with collections a bit too large for usual lobular inflammation. F. Proof is at high power. All cells are similar to macrophages but are too closely crowded to be macrophages. The monomorphism (one type of cell) should inspire immunohistochemical stains, which showed the patient had a B cell lymphoma.

[[File:5 02965636298621 sl 1.png|Malignant B cell lymphoma, NOS, in a 63 year old man’s liver]]
[[File:5 02965636298621 sl 2.png|Malignant B cell lymphoma, NOS, in a 63 year old man’s liver]]
[[File:5 02965636298621 sl 3.png|Malignant B cell lymphoma, NOS, in a 63 year old man’s liver]]
[[File:5 02965636298621 sl 4.png|Malignant B cell lymphoma, NOS, in a 63 year old man’s liver]]
[[File:5 02965636298621 sl 31.png|Malignant B cell lymphoma, NOS, in a 63 year old man’s liver]]
[[File:5 02965636298621 sl 6.png|Malignant B cell lymphoma, NOS, in a 63 year old man’s liver]]
 
Malignant B cell lymphoma, NOS, in a 63 year old man’s liver. No other specimens were available for further classification. A. Tumor expands a triad and occupies parenchymal regions. B. Bounding a bile duct, modestly sized round to reniform lymphoid cells, many without nucleoli, accompany small round lymphocytes. Some of the larger cells have clefts (arrows). C. CD3 stain shows many of the lymphoid cells are intercalated reactive T cells. D. Ki67 shows less than half the tumor cells, mostly the larger ones, are in proliferative phase, arguing against the notion of a high grade B cell lymphoma. E. CD79A establishes B cell phenotype (CD20 was also positive). F. That the tumor cells are BCL2 positive evinces B cell neoplasia. The cells were CD10, BCL6, and cyclin D1 negative, militating against mantle cell lymphoma and CLL, with no follicular origin identified.

[[File:4 89735893919405 sl 1.png| High grade B cell lymphoma involving liver]]
[[File:4 89735893919405 sl 2.png| High grade B cell lymphoma involving liver]]
[[File:4 89735893919405 sl 3.png| High grade B cell lymphoma involving liver]]
[[File:4 89735893919405 sl 4.png| High grade B cell lymphoma involving liver]]
[[File:4 89735893919405 sl 5.png| High grade B cell lymphoma involving liver]] 
High grade B cell lymphoma involving liver in a 77 year old woman. A. A band of cancer abuts fibrotic liver with steatosis. B. Cancer cells show primitive, round to ovoid, variably sized, dark nucleoli and an aberrant mitoses. Cytoplasm is scant. C. Cancer cells are CD79a positive. D. Most cancer cell nuclei were positive for Ki-67, overall about 80%. E. A minority of cancer cells are CD10 positive.

=See also=
*[[Pancreas]].
*[[Gastrointestinal pathology]].
*[[Liver pathology]].

=References=
{{reflist|2}}

[[Category:Gastrointestinal pathology]]
[[Category:Liver pathology]]

Chronic cholecystitis

2017-01-31T22:06:03Z

Mitchell: /* Images */ added a case

{{ Infobox diagnosis
| Name = {{PAGENAME}}
| Image = Chronic cholecystitis and cholesterolosis -- low mag.jpg
| Width =
| Caption = Chronic cholecystitis with cholesterolosis. [[H&E stain]].
| Micro = entrapped epithelial crypts, fibrosis/muscular hypertrophy of gallbladder wall, +/-foamy macrophages
| Subtypes =
| LMDDx = [[acute cholecystitis]], [[gallbladder adenocarcinoma]], [[gallbladder adenomyoma]], [[intestinal metaplasia of the gallbladder]]
| Stains =
| IHC =
| EM =
| Molecular =
| IF =
| Gross = +/-strawberry-like appearance, yellow stones, fibrotic wall
| Grossing =
| Site = [[gallbladder]]
| Assdx = [[cholelithiasis]], [[gallbladder cholesterolosis]], [[obesity]]
| Syndromes =
| Clinicalhx = biliary colic, usu. fertile fat females forty years or less
| Signs =
| Symptoms = constant right upper quadrant pain after a meal (biliary colic)
| Prevalence = very common
| Bloodwork =
| Rads =
| Endoscopy =
| Prognosis = good, benign
| Other =
| ClinDDx =
}}
'''Chronic cholecystitis''', abbreviated '''CC''', is a very common pathology of the [[gallbladder]] and increasing in prevalence with the expanding waist lines.

==General==
===Epidemiology===
*Female, [[obese|fat]], fertile, family history, forty (though now getting younger... as people get fatter).

===Etiology===
*Cholelithiasis.
*Thick bile (acalculous cholecystitis).

===Clinical (classic)===
*Constant right upper quadrant pain after a fatty meal (biliary colic).
*Positive Murphy's sign (physical exam, with ultrasound).

==Gross==
*+/-[[Cholelithiasis]] - strongly associated pathology.
*+/-Strawberry-like appearance - common (due to [[gallbladder cholesterolosis]]).
**Small ridges (microvillus architecture) + yellow.
***Normal gallbladder mucosa = smooth, green.
*+/-Congestion/erythema.
*+/-Wall thickening - typically ~ 6-7 mm.<ref name=pmid21879282>{{Cite journal | last1 = Kim | first1 = HJ. | last2 = Park | first2 = JH. | last3 = Park | first3 = DI. | last4 = Cho | first4 = YK. | last5 = Sohn | first5 = CI. | last6 = Jeon | first6 = WK. | last7 = Kim | first7 = BI. | last8 = Choi | first8 = SH. | title = Clinical usefulness of endoscopic ultrasonography in the differential diagnosis of gallbladder wall thickening. | journal = Dig Dis Sci | volume = 57 | issue = 2 | pages = 508-15 | month = Feb | year = 2012 | doi = 10.1007/s10620-011-1870-0 | PMID = 21879282 }}</ref>

Note:
*Wall thickening (due to congestion/edema) is the important gross finding in ''[[acute cholecystitis]]''.
*Wall thickenss greater than 10 mm should raise the suspicion of malignancy.<ref name=pmid21879282/>

==Microscopic==
Features:<ref name=Ref_GLP439>{{Ref GLP|439}}</ref>
*Thickening of the gallbladder wall - due to fibrosis/muscular hypertrophy - '''key feature'''.
*Chronic inflammatory cells - usu. "minimal".
**Lymphocytes - most common.
*Rokitansky-Aschoff sinuses - common.<ref>URL: [http://www.whonamedit.com/synd.cfm/983.html http://www.whonamedit.com/synd.cfm/983.html]. Accessed on: 29 October 2011.</ref>
**Entrapped epithelial crypts -- pockets of epithelium in the wall of the gallbladder.
*+/-Foamy macrophages in the lamina propria ([[cholesterolosis of the gallbladder]]).

DDx:
*[[Gallbladder cholesterolosis]] and chronic cholecystitis.
*[[Gallbladder adenomyoma]].
*[[Acute cholecystitis]] - more inflammation, lack Rokitansky-Aschoff sinuses, +/-mucosal erosions.
*Cholecystectomy for [[gallstone pancreatitis]] - intraepithelial [[neutrophil]] clusters common, history essential.
*[[Intestinal metaplasia of the gallbladder]] - goblet cells present, may be focal.
*[[Gallbladder adenocarcinoma]].

===Images===
<gallery>
Image: Chronic cholecystitis and cholesterolosis -- intermed mag.jpg | CC - intermed. mag. (WC)
Image:Gallbladder_cholesterolosis_micro.jpg | Cholesterolosis. (WC)
</gallery>
[[File:Reactive change in cholecystitis A sl 1.png| Extensive Rokitansky-Aschoff sinuses in a 64 year ood woman]]
[[File:Reactive change in cholecystitis A sl 2.png| Extensive Rokitansky-Aschoff sinuses in a 64 year ood woman]]
[[File:Reactive change in cholecystitis A sl 3.png| Extensive Rokitansky-Aschoff sinuses in a 64 year ood woman]]
[[File:Reactive change in cholecystitis A sl 4.png| Extensive Rokitansky-Aschoff sinuses in a 64 year ood woman]] 
Extensive Rokitansky-Aschoff sinuses in a 64 year ood woman. A. Extending from a benign, chronically inflamed plicae are Rikitansky-Aschoff sinuses. Note their travel in between muscle bundles can be recognized as continuity to the surface. B. In between the gall stone at lower left and the lymphoid aggregate at upper right lies the gallbladder wall. Note the longitudinal extensions of the Rokitansky-Aschoff sinuses, as well as the ballooning outside the wall at lower right. C. The mucosa shows extensive reactive branching. Note again the predominant extension between muscle bundles, recognizable by the stroma about the sinuses, some of which are branched, pushing the muscle wall aside. There is no desmoplasia, but some gallbladder adenocarcinomas show little recognizable desmoplasia. D. The focus on the right is difficult to identify as lying between muscle bundles. The triple parallel tubules argue against neoplasia. The lack of cancerous nuclear change is important as well.

[[File:5gb41630891386282 sl 1.png| Chronic cholecystitis with reactive changes.]]
[[File:5gb41630891386282 sl 2.png| Chronic cholecystitis with reactive changes.]]
[[File:5gb41630891386282 sl 3.png| Chronic cholecystitis with reactive changes.]]
[[File:5gb41630891386282 sl 4.png| Chronic cholecystitis with reactive changes.]] 
Chronic cholecystitis with reactive epithelial atypia in a 92 year old. A. Lymphoid follicles are associated with chronically inflamed plicae. B. Neutrophils lie within cytoplasm of epithelium. Nuclei show variability in size and, to a lesser degree, shape. Some cells are multinucleated. Polarity is generally, but not always, preserved, with most nuclei at the base of the cell, with the longer nuclear dimension, when the nucleus is not round, being perpendicular to the luminal surface. C. Monoclonal CEA stains neutrophils, but not epithelial cells. D. CD10 stains the luminal surfaces of epithelial cells, a finding that militates against dysplasia.

==Sign out==
<pre>
Gallbladder, Cholecystectomy:
- Cholelithiasis.
- Chronic cholecystitis, mild.
- One benign lymph node.
</pre>

====Block letters====
<pre>
GALLBLADDER, CHOLECYSTECTOMY:
- CHRONIC CHOLECYSTITIS.
- CHOLELITHIASIS.
</pre>

===Without stones===
<pre>
GALLBLADDER, CHOLECYSTECTOMY:
- CHRONIC CHOLECYSTITIS.
- NO GALLSTONES IDENTIFIED.
</pre>

===Liver present===
<pre>
GALLBLADDER, CHOLECYSTECTOMY:
- CHRONIC CHOLECYSTITIS.
- CHOLELITHIASIS.
- SMALL AMOUNT OF LIVER WITHOUT APPARENT PATHOLOGY.
</pre>

<pre>
GALLBLADDER, CHOLECYSTECTOMY:
- CHRONIC CHOLECYSTITIS WITH MILD CHOLESTEROLOSIS.
- CHOLELITHIASIS.
- SMALL AMOUNT OF LIVER WITH CAUTERY/CRUSH ARTIFACT.
</pre>

===Micro===
The sections shows gallbladder wall with Rokitansky-Aschoff sinuses and a moderate mixed
inflammatory infiltrate predominantly consisting of lymphocytes. No nuclear atypia is seen.

====Post-cholecystostomy tube====
The sections shows gallbladder wall with edema, a moderate mixed inflammatory infiltrate
(predominantly consisting of lymphocytes and plasma cells), and mucosal erosions. Reactive
fibroblasts and hemosiderin-laden macrophages are present. No significant nuclear changes
are seen. One benign lymph node is present.

==See also==
*[[Acute cholecystitis]].
*[[Gallbladder]].

==References==
{{Reflist|2}}

[[Category:Gallbladder]]
[[Category:Diagnosis]]

Peripheral nerve sheath tumours

2017-01-26T16:59:35Z

Mitchell: /* Microscopic */

'''Peripheral nerve sheath tumours''', abbreviated '''PNSTs''', are common in [[neuropathology]] and occasionally show-up elsewhere. A very common PNST is the [[schwannoma]].

=Classification=
A classification:<ref name=pmid17893219>{{cite journal |author=Wippold FJ, Lubner M, Perrin RJ, Lämmle M, Perry A |title=Neuropathology for the neuroradiologist: Antoni A and Antoni B tissue patterns |journal=AJNR Am J Neuroradiol |volume=28 |issue=9 |pages=1633–8 |year=2007 |month=October |pmid=17893219 |doi=10.3174/ajnr.A0682 |url=http://www.ajnr.org/cgi/reprint/28/9/1633}}</ref>
*Benign:
**[[Schwannoma]].
**[[Neurofibroma]].
**[[Perineurioma]].
**[[Traumatic neuroma]].
*Malignant:
**[[Malignant peripheral nerve sheath tumour]] (MPNST).

=Specific diagnoses=
==Schwannoma==
{{Main|Schwannoma}}

==Perineurioma==
===General===
*Benign tumour derived from perineurial cells (intraneural or soft tissue).
**ICD-O 9571/0
** WHO grade I
*Rarely malignant soft tissue perineurioma.

Variant:
*Reticular perineurioma.<ref name=pmid11257623>{{Cite journal | last1 = Graadt van Roggen | first1 = JF. | last2 = McMenamin | first2 = ME. | last3 = Belchis | first3 = DA. | last4 = Nielsen | first4 = GP. | last5 = Rosenberg | first5 = AE. | last6 = Fletcher | first6 = CD. | title = Reticular perineurioma: a distinctive variant of soft tissue perineurioma. | journal = Am J Surg Pathol | volume = 25 | issue = 4 | pages = 485-93 | month = Apr | year = 2001 | doi = | PMID = 11257623 }}</ref>

===Macroscopy===
*Intraneural perineurioma: segmental tubular enlargement of the nerve.
*Soft tissue perineurioma: Well circumscribed, but not encapsulated.

===Microscopic===
Features:<ref name=Ref_Sternberg5_424>{{Ref Sternberg5|424}}</ref>
*Perineural epithelioid cells.
**Abundant pale, fluffy appearing cytoplasm.

Note:
*May be intraneural.<ref name=Ref_Sternberg5_424>{{Ref Sternberg5|424}}</ref>
**Typical pseudo-onion bulbs.
**Long considered hypertrophic neuropathy.
**Rare (less than 1% of all nerve sheath tumours).

DDx:
*[[Neuroma]].
*[[Neurofibroma]].
*[[Schwannoma]].
**S100 +ve, EMA -ve.<ref name=Ref_Sternberg5_424>{{Ref Sternberg5|424}}</ref>
*[[Liposarcoma]] - reticular perineurioma.

Images:
*[http://www.conganat.org/seap/reuniones/almagro2000/scruz/tnerviog5.htm Perineurioma (conganat.org)].

<gallery>
File:Perineurioma,_HE_stain.jpg | Pseudo-onion bulbs in a intraneural perioneurioma (WC/jensflorian)
</gallery>

===IHC===
Features:<ref name=pmid15958848>{{Cite journal | last1 = Hornick | first1 = JL. | last2 = Fletcher | first2 = CD. | title = Soft tissue perineurioma: clinicopathologic analysis of 81 cases including those with atypical histologic features. | journal = Am J Surg Pathol | volume = 29 | issue = 7 | pages = 845-58 | month = Jul | year = 2005 | doi = | PMID = 15958848 }}</ref><ref name=pmid1497116>{{Cite journal | last1 = Tsang | first1 = WY. | last2 = Chan | first2 = JK. | last3 = Chow | first3 = LT. | last4 = Tse | first4 = CC. | title = Perineurioma: an uncommon soft tissue neoplasm distinct from localized hypertrophic neuropathy and neurofibroma. | journal = Am J Surg Pathol | volume = 16 | issue = 8 | pages = 756-63 | month = Aug | year = 1992 | doi = | PMID = 1497116 }}</ref>
*S100 -ve.
*EMA +ve.
*CD34 ~65% +ve.<ref name=pmid15958848/>

==Traumatic neuroma==
===General===
*Consequence of trauma - diagnosis requires history of trauma.
**May mimic a cancer recurrence at the site of a surgery.<ref name=pmid22330690/>

===Microscopic===
Features:<ref name=Ref_DCHH317>{{Ref DCHH|317}}</ref><ref name=pmid22330690/>
*+/-Nerve - that was injured.
*Grouping of disordered nerve fibre bundles in fibrous tissue (collagen) - '''key feature'''.
*+/-Myxoid change.
*+/-Axonal swellings (ovoid pink/purple blobs).

DDx:
*[[Morton neuroma]] (foot).

Images:
*[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3296625/figure/F2/ Traumatic neuroma (nih.gov)].<ref name=pmid22330690>{{Cite journal | last1 = Li | first1 = Q. | last2 = Gao | first2 = EL. | last3 = Yang | first3 = YL. | last4 = Hu | first4 = HY. | last5 = Hu | first5 = XQ. | title = Traumatic neuroma in a patient with breast cancer after mastectomy: a case report and review of the literature. | journal = World J Surg Oncol | volume = 10 | issue = | pages = 35 | month = | year = 2012 | doi = 10.1186/1477-7819-10-35 | PMID = 22330690 }}</ref>
*[http://path.upmc.edu/cases/case502.html Traumatic neuroma - several images (upmc.edu)].
*[http://www.sarcomaimages.com/index.php?v=Neuroma,-Traumatic Traumatic neuroma (sarcomaimages.com)].
*[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2627419/figure/F1/ Traumatic neuroma (nih.gov)].<ref name=pmid17554193>{{Cite journal | last1 = Kwon | first1 = JH. | last2 = Ryu | first2 = SW. | last3 = Kang | first3 = YN. | title = Traumatic neuroma around the celiac trunk after gastrectomy mimicking a nodal metastasis: a case report. | journal = Korean J Radiol | volume = 8 | issue = 3 | pages = 242-5 | month = | year = | doi = | PMID = 17554193 | PMC = 2627419 }}</ref>
*[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2835865/figure/F3/ Neuroma (nih.gov)].<ref name=pmid20224738>{{Cite journal | last1 = Kitcat | first1 = M. | last2 = Hunter | first2 = JE. | last3 = Malata | first3 = CM. | title = Sciatic neuroma presenting forty years after above-knee amputation. | journal = Open Orthop J | volume = 3 | issue = | pages = 125-7 | month = | year = 2009 | doi = 10.2174/1874325000903010125 | PMID = 20224738 }}</ref>

===Sign out===
<pre>
SOFT TISSUE LESION, RIGHT WRIST, EXCISION:
- TRAUMATIC NEUROMA.
- BENIGN FIBROADIPOSE TISSUE.
</pre>

====Micro====
The sections show disordered nerve fibre bundles in fibrous tissue.

==Palisaded encapsulated neuroma==
*Abbreviated ''PEN''.
*[[AKA]] ''palisaded and encapsulated neuroma''.
*[[AKA]] ''solitary circumscribed neuroma''.

===General===
*Flesh-colour [[papule]] - classically on the face.<ref name=Ref_Derm536>{{Ref Derm|536}}</ref>
*Isolated finding - not associated with a systemic disease or malignancy.<ref name=pmid18718196>{{Cite journal | last1 = Newman | first1 = MD. | last2 = Milgraum | first2 = S. | title = Palisaded encapsulated neuroma (PEN): an often misdiagnosed neural tumor. | journal = Dermatol Online J | volume = 14 | issue = 7 | pages = 12 | month = | year = 2008 | doi = | PMID = 18718196 }}</ref>
*Superficial skin papule.<ref>S. Sade. 8 September 2011.</ref>
*It is considered hyperplastic rather than neoplastic. <ref>Rosai & Ackermann, Surgical Pathology, 10th ed. p183</ref>

===Microscopic===
Features:<ref name=Ref_Derm536>{{Ref Derm|536}}</ref>
*Encapsulated dermal spindle cell lesion.
**Fasciular arrangement.
**Neural-type spindle cells:
**#Not vacuolated.
**#Nuclei have pointy ends.
**#Sometimes epitheloid appearance.
*Intralesional clefts.
**Useful to differentiate from schwannoma.

DDx:
*[[Schwannoma]]:<ref name=Ref_Derm536>{{Ref Derm|536}}</ref>
**No intralesional clefts.
**More variability in the cellularity.
**May be deep.

Other considerations:
*[[Leiomyoma]] - cytoplasm not vacuolated, nuclei more elliptical.

Images:
*[http://dermatology.cdlib.org/147/case_presentation/pen/2.jpg PEN (cdlib.org)].<ref name=pmid18718196>{{Cite journal | last1 = Newman | first1 = MD. | last2 = Milgraum | first2 = S. | title = Palisaded encapsulated neuroma (PEN): an often misdiagnosed neural tumor. | journal = Dermatol Online J | volume = 14 | issue = 7 | pages = 12 | month = | year = 2008 | doi = | PMID = 18718196 }}</ref>

<gallery>
File:Palisaded_and_Encapsulated_Neuroma_(3952635881).jpg | Palisaded and encapsulated neuroma (Ed Uthman)
File:Palisaded_and_Encapsulated_Neuroma,_S-100_Immunostain_(3953412396).jpg| PEN, S-100 staining (Ed Uthman)

</gallery>
[[File:569 dp sl 1.png| Palisading/encapcuslated neuroma]]
[[File:569 dp sl 2.png| Palisading/encapcuslated neuroma]] 
Palisading/encapsulated (Reed’s) neuroma. A. A dermal nodule shows an attenuated capsule (black arrows) about a fasciculated spindle cell lesion with artefactual clefts (green arrows). B. The bland spindled nuclei, amid clear cytoplasm with thin eosinophilic wisps, are often wavy (black arrows), with pointed ends (green arrows); leiomyomas have blunt ended nuclei and more eosinophilic cytoplasm. These benign neoplasms, unlike neurofibromas, lack an association with neurofibromatosis.

===IHC===
Features:<ref name=pmid18718196/>
*S100 +ve.
*EMA +ve (capsule of lesion).

==Neurofibroma==
{{Main|Neurofibroma}}
Includes discussion of ''plexiform neurofibroma''.

==Neurothekeoma==
*[[AKA]] ''myxoma of the nerve sheath'', [[AKA]] ''nerve sheath myxoma''.
*There is growing evidence that neurothekomas and dermal nerve sheath myxomas are distinct entities.<ref>{{Cite journal | last1 = Sheth | first1 = S. | last2 = Li | first2 = X. | last3 = Binder | first3 = S. | last4 = Dry | first4 = SM. | title = Differential gene expression profiles of neurothekeomas and nerve sheath myxomas by microarray analysis. | journal = Mod Pathol | volume = 24 | issue = 3 | pages = 343-54 | month = Mar | year = 2011 | doi = 10.1038/modpathol.2010.203 | PMID = 21297585 }}</ref>

===General===
*Rare.
*Female > male.

===Microscopic===
Features:<ref name=pmid17325474>{{cite journal |author=Hornick JL, Fletcher CD |title=Cellular neurothekeoma: detailed characterization in a series of 133 cases |journal=Am. J. Surg. Pathol. |volume=31 |issue=3 |pages=329–40 |year=2007 |month=March |pmid=17325474 |doi=10.1097/01.pas.0000213360.03133.89 |url=}}</ref>
*Superficial dermal lesion:
**Usu. lobulated or micronodular architecture - '''key feature'''.
***+/-Focal sheeting.
**Spindle/epithelioid morphology with pale eosinophilic cytoplasm - '''key feature'''.
**+/-Inflammation around lesion.
**+/-Surrounded by collagen.

Notes:
*No atypia.
*Mitoses rare/none.
*Often poorly circumscribed.

Subtypes:<ref name=pmid10555009>{{cite journal |author=Wang AR, May D, Bourne P, Scott G |title=PGP9.5: a marker for cellular neurothekeoma |journal=Am. J. Surg. Pathol. |volume=23 |issue=11 |pages=1401–7 |year=1999 |month=November |pmid=10555009 |doi= |url=}}</ref>
*Cellular.
*[[Myxoid]].
*Intermediate.

DDx:
*[[Dermatofibroma]].
*[[Angiomatoid fibrous histiocytoma]] -- have cystic blood filled spaces, inflammation.<ref>URL: [http://surgpathcriteria.stanford.edu/softfib/angiomatoid_fibrous_histiocytoma/ http://surgpathcriteria.stanford.edu/softfib/angiomatoid_fibrous_histiocytoma/]. Accessed on: 11 May 2011.</ref>

Images:
*[http://en.wikipedia.org/wiki/File:Neurothekeoma2.JPG Neurothekeoma (WP)].
*[http://path.upmc.edu/cases/case586.html Neurothekeoma - several images (upmc.edu)].
*[http://www.dermpedia.org/files/images/Image2_49.jpg Nerve sheath myxoma (dermpedia)]]

===IHC===
Features:<ref name=pmid17325474/>
*NKI/C3 ([[AKA]] NKI-C3) +ve.
*NSE +/-ve.

Others:<ref name=pmid17592278>{{cite journal |author=Fetsch JF, Laskin WB, Hallman JR, Lupton GP, Miettinen M |title=Neurothekeoma: an analysis of 178 tumors with detailed immunohistochemical data and long-term patient follow-up information |journal=Am. J. Surg. Pathol. |volume=31 |issue=7 |pages=1103–14 |year=2007 |month=July |pmid=17592278 |doi=10.1097/PAS.0b013e31802d96af |url=}}</ref>
*Vimentin +ve.
*CD10 +ve.
*Microphthalmia transcription factor +ve.
*PGP9.5 +ve.

Exclusionary:
*S100 -ve.
**Exclude other peripheral nerve sheath tumours. (???)
**Myxoid variant +ve. {{fact}}

==Malignant peripheral nerve sheath tumour==
{{Main|Malignant peripheral nerve sheath tumour}}

==Malignant triton tumour==
*Abbreviated ''MTT''.
*[[AKA]] ''malignant peripheral nerve sheath tumor with rhabdomyosarcomatous differentiation''.<ref name=pmid17149968>{{Cite journal | last1 = Stasik | first1 = CJ. | last2 = Tawfik | first2 = O. | title = Malignant peripheral nerve sheath tumor with rhabdomyosarcomatous differentiation (malignant triton tumor). | journal = Arch Pathol Lab Med | volume = 130 | issue = 12 | pages = 1878-81 | month = Dec | year = 2006 | doi = 10.1043/1543-2165(2006)130[1878:MPNSTW]2.0.CO;2 | PMID = 17149968 }}</ref>

===General===
*Rare.
*Considered to be a variant of ''[[MPNST]]''.
*Prognosis worse that conventional MPNST.<ref name=pmid17149968/>
**Five year survival ~14%.<ref name=pmid22253011>{{Cite journal | last1 = McConnell | first1 = YJ. | last2 = Giacomantonio | first2 = CA. | title = Malignant triton tumors-complete surgical resection and adjuvant radiotherapy associated with improved survival. | journal = J Surg Oncol | volume = | issue = | pages = | month = Jan | year = 2012 | doi = 10.1002/jso.23042 | PMID = 22253011 }}</ref>
*Diagnosis may require clinical information, i.e. individual has a history of [[neurofibromatosis type 1]] (NF1).

Note:
*A handful of ''benign triton tumours'' are reported; these are considered ''neuromuscular [[hamartoma]]s''.<ref name=pmid15814954>{{Cite journal | last1 = Castro | first1 = DE. | last2 = Raghuram | first2 = K. | last3 = Phillips | first3 = CD. | title = Benign triton tumor of the trigeminal nerve. | journal = AJNR Am J Neuroradiol | volume = 26 | issue = 4 | pages = 967-9 | month = Apr | year = 2005 | doi = | PMID = 15814954 }}
</ref>
===Microscopic===
Features - Woodruff criteria - all three required:<ref name=pmid17149968/>
# (a) Tumour arise from a peripheral nerve ''or'' (b) individual has [[NF1]] ''or'' (c) lesion a metastasis arising in the context of (a) or (b).
# Schwann cell tumour characteristics.
# Rhabdomyoblasts.
#* Eccentric nucleus.
#* Moderate amount of eosinophilic cytoplasm.
#* +/-Cross-striations.

DDx:
*[[Malignant peripheral nerve sheath tumour]].
*[[Adult fibrosarcoma]].
*[[Synovial sarcoma]].
*[[Rhabdomyosarcoma]].
*[[Carcinosarcoma]].

===IHC===
Features:
*S100 +ve/-ve -- usu. focal if positive.<ref name=pmid17149968/>
*Leu-7 +ve/-ve.
*Myelin basic protein +ve/-ve.

Rhabdomyoblastic differentiation:<ref name=pmid17149968/>
*Desmin.
*Actin.
*Myogenin.

===EM===
*+/-Sarcomeres.<ref name=pmid17149968/>

==Morton neuroma==
:[[AKA]] ''plantar interdigital neuroma''.<ref name=pmid22995258>{{Cite journal | last1 = Makki | first1 = D. | last2 = Haddad | first2 = BZ. | last3 = Mahmood | first3 = Z. | last4 = Shahid | first4 = MS. | last5 = Pathak | first5 = S. | last6 = Garnham | first6 = I. | title = Efficacy of corticosteroid injection versus size of plantar interdigital neuroma. | journal = Foot Ankle Int | volume = 33 | issue = 9 | pages = 722-6 | month = Sep | year = 2012 | doi = DOI: 10.3113/FAI.2012.0722 | PMID = 22995258 }}</ref>
{{Main|Morton neuroma}}

=See also=
*[[Neuropathology]].
*[[Gastrointestinal pathology]].

=References=
{{Reflist|2}}

[[Category:Neuropathology]]
[[Category:Peripheral nerve sheath tumours]]

Medical liver disease

2017-01-23T15:52:43Z

Mitchell: /* Images */

[[Image:Ground glass hepatocytes high mag cropped 2.jpg|thumb|right|[[Micrograph]] showing ground glass hepatocytes, as seen in chronic [[hepatitis B]]. [[H&E stain]].]]
This article deals with '''medical [[liver]] disease'''. An introduction to the liver and approach is found in the ''[[liver]]'' article.

Every differential in liver pathology has "drugs"<ref>{{Ref PCPBoD8|448}}</ref> -- if it isn't clearly malignancy.

Liver neoplasms are dealt with in the ''[[liver neoplasms]]'' article.

Medical liver biopsies are often non-specific, as the liver has the same appearance for many mechanisms of injury, especially when the injury is marked. The clinical history, serology and imaging are essential for proper interpretations in this domain of pathology.

=Review of liver blood work=
===Inflammation activity===
*ALT.
*AST.

===Cholestatic markers===
*ALP.
*GGT - used to assess whether the ALP is an "honest" value, elevated in cirrhosis.

===Cirrhosis/decompensation===
*PLT - low is suggestive of dysfunction.
*INR - high is bad, unless anticoagulated.

===Other===
*Bilirubin.
**Direct (AKA conjugated).
**Indirect (AKA unconjugated).

A short DDx of elevated:<ref>{{Ref PCPBoD8|441}}</ref>
*Indirect:
**[[Gilbert syndrome]].
**Crigler-Najjar syndrome type 1.
**Crigler-Najjar syndrome type 2.
*Direct:
**Rotor syndrome.
**Dubin-Johnson syndomre.

===Viral hepatitis===
*HBV DNA.
*HCV RNA.
*HBs Ag, HBs Ab, HBe Ag, HBe Ab.
*HCV Ab.

Others:
*[[Epstein-Barr virus]] (EBV).
*[[Cytomegalovirus]] (CMV) - especially in the immune incompetent.

====Hepatitis B====
Meaning & utility of the various [[Hepatitis B]] tests:<ref>URL: [http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/hepatology/hepatitis-B/ http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/hepatology/hepatitis-B/]. Accessed on: 16 May 2011.</ref><ref name=lto_hepb>URL: [http://www.labtestsonline.org/understanding/analytes/hepatitis_b/test.html http://www.labtestsonline.org/understanding/analytes/hepatitis_b/test.html]. Accessed on: 16 May 2011.</ref>
{| class="wikitable sortable" border="1"
! Test name
! Location
! Positive test
! Negative test
! Usual question
|-
| HBs Ag||Surface||Virus active||No active infection||Active infection?
|-
| HBs Ab||Surface||Exposed OR vaccinated||No exposure OR no vaccine OR loss of Ab||Immunization status?
|-
| HBe Ag||Virus core||Infect. w/ viral replication||No active infection||Active infect. w/ viral replication?
|-
| HBe Ab||Virus core||Exposed to virus||Infect. w/o antibody response OR not exposed||Immune response to infection?
|-
| HBV DNA||-||Active||Not active/no exposure||Viral load/how active?
|-
| HBc Ab||Virus core||Virus active/previous exposure||No exposure||Early active infection?
|}
Notes:
*''HBc Ab'' may test for acute (IgM) or chronic infection - dependent on specific antibody test; it is often used to look for early infection.<ref name=lto_hepb>URL: [http://www.labtestsonline.org/understanding/analytes/hepatitis_b/test.html http://www.labtestsonline.org/understanding/analytes/hepatitis_b/test.html]. Accessed on: 16 May 2011.</ref>
*''Carriers of hepatitis B'': HBs Ag +ve, HBs Ab -ve, HBc Ag -ve, HBc Ab +ve, HBe Ag -ve, HBe Ab +ve.<ref>URL: [http://labtestsonline.org/understanding/analytes/hepatitis-b/tab/test http://labtestsonline.org/understanding/analytes/hepatitis-b/tab/test]. Accessed on: 3 May 2012.</ref>

===Markers for rare liver diseases===
*Ceruloplasm - low think ''[[Wilson's disease]]''; typical value for Wilson's ~ 0.12 g/L.
**<0.20 g/L is a criteria for Wilson's disease.<ref name=pmid18556333>Diagnostic accuracy of serum ceruloplasmin in Wilson disease: determination of sensitivity and specificity by ROC curve analysis among ATP7B-genotyped subjects. Mak CM, Lam CW, Tam S. Clin Chem. 2008 Aug;54(8):1356-62. Epub 2008 Jun 12. PMID 18556333. URL: [http://www.clinchem.org/cgi/reprint/54/8/1356.pdf http://www.clinchem.org/cgi/reprint/54/8/1356.pdf]. Accessed on: 28 September 2009.</ref>
*Alpha-1 antitrypsin - if low think ''deficiency''.

===Hemosiderosis===
*Ferritin - high.
*Iron saturation - high.

Causes:
*Hemochromatosis.
*Hemolysis, chronic.
*Cirrhosis.

=Medical imaging=
Blood flow:<ref>URL: [http://insidesurgery.com/2010/12/hepatopedal-hepatofugal-flow/ http://insidesurgery.com/2010/12/hepatopedal-hepatofugal-flow/]. Accessed on: 2 December 2011.</ref>
*Hepatopedal flow = normal portal vein flow.
*Hepatofugal flow = reversed portal vein flow.

==Interventional measurements==
Wedged to free hepatic venous pressure:<ref name=pmid1864548>{{Cite journal | last1 = Bion | first1 = E. | last2 = Brenard | first2 = R. | last3 = Pariente | first3 = EA. | last4 = Lebrec | first4 = D. | last5 = Degott | first5 = C. | last6 = Maitre | first6 = F. | last7 = Benhamou | first7 = JP. | title = Sinusoidal portal hypertension in hepatic amyloidosis. | journal = Gut | volume = 32 | issue = 2 | pages = 227-30 | month = Feb | year = 1991 | doi = | PMID = 1864548 | PMC = 1378815 | URL = http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1378815/?tool=pubmed }}</ref>
*Normal = 1-4 mmHg.
**Elevated in [[portal hypertension]].

=Liver biopsy=
==Medical liver biopsy adequacy==
Liver biopsy specimens should be:<ref>{{Ref MacSween|418}}</ref>
*2.0 cm in length and contain 11-15 portal tracts,
*The core should be deeper than 1.0 cm from the liver capsule; specimens close to the capsule may lead to over grading of fibrosis.

==Reporting==
{{Main|Pathology reports}}
<pre>
Specimen, procedure:
- Diagnosis.
</pre>
The diagnosis usually contains grading and staging information, e.g. ''activity 2 /4, Laennec fibrosis stage 1 /4''.

In the context of medical liver disease:
*Grade = inflammation/activity.
*Stage = severity of fibrosis/architectural changes.

Notes:
*The term "acute" is infrequently used in liver pathology.
*In the liver: neutrophils ''is not'' acute -- unlike most elsewhere in the body.<ref>OA. September 2009.</ref>

===A microscopic checklist===
<pre>
Size of biopsy: Adequate
Fragmentation: Absent
Fibrosis: Stage 2-3/4, mostly stage 2
Fibrous septa: Present
Septa with curved contours: Present – focally only
Large droplet steatosis (% of hepatocytes): Present, moderate 60%
Ballooning of hepatocytes: Present, rare
Mallory-Denk bodies: Present, rare
Portal inflammation: Present
Interface activity: Minimal (0-1/4)
Lobular necroinflammation: Minimal
Ducts: Present in normal numbers
Duct injury: Absent
Ductular reaction: Absent
Cholestasis: Absent
Terminal hepatic venules: Present
Iron stain: Absent
Ground glass cells with routine stains: Absent
PASD for alpha-1 antitrypsin droplets: Negative
</pre>

=Viral hepatitis=
These are common. The diagnoses are based on serology. The serology is covered in the ''[[Liver_pathology#Viral_hepatitis|viral hepatitis]]'' section in the ''[[liver pathology]]'' article.

Typically classified as:<ref name=pmid8048409>{{Cite journal | title = Terminology of chronic hepatitis, hepatic allograft rejection, and nodular lesions of the liver: summary of recommendations developed by an international working party, supported by the World Congresses of Gastroenterology, Los Angeles, 1994. | journal = Am J Gastroenterol | volume = 89 | issue = 8 Suppl | pages = S177-81 | month = Aug | year = 1994 | doi = | PMID = 8048409 }}</ref><ref>URL: [http://familydoctor.org/familydoctor/en/diseases-conditions/hepatitis-b.html http://familydoctor.org/familydoctor/en/diseases-conditions/hepatitis-b.html]. Accessed on: 2 May 2012.</ref>
#Acute < 6 months duration.
#Chronic > 6 months duration.

==Hepatitis A==
*Infection is self-limited, i.e. not persistent.
**May present as ''[[fulminant hepatic necrosis]]''.
*Usually asymptomatic in children.<ref name=pmid20068336>{{cite journal |author=Jeong SH, Lee HS |title=Hepatitis A: clinical manifestations and management |journal=Intervirology |volume=53 |issue=1 |pages=15–9 |year=2010 |pmid=20068336 |doi=10.1159/000252779 |url=}}</ref>
*Serology is diagnostic.

==Hepatitis B==
:''Hepatitis B virus'', abbreviated ''HBV'', redirects here.
{{Main|Hepatitis B}}

==Hepatitis C==
{{Main|Hepatitis C}}

=Other infections=
*Hydatid disease (Hydatid cyst).
*Ascaris.
*Fasciola

==Hydatid disease==
*[[AKA]] ''hydatid cyst''.
===General===
*Etiology: ''[[Echinococcus]]''.

===Microscopic===
Features:
*Laminated wall +/- calcification.<ref name=Ref_PBPoD8_448>{{Ref PCPBoD8|448}}</ref>
*Organisms -- see ''[[Echinococcus]]''.

====Images====
<gallery>
Image:Liver_cyst_wall_-_intermed_mag.jpg | Liver cyst wall - intermed. mag. (WC)
Image:Liver_cyst_wall_-_high_mag.jpg | Liver cyst wall - high mag. (WC)
Image: Laminated liver cyst wall - intermed mag.jpg | Characteristic laminated portion - intermed. mag. (WC)
Image: Laminated liver cyst wall - high mag.jpg | Characteristic laminated portion - high mag. (WC)
</gallery>
[[www]]:
*[http://pathmicro.med.sc.edu/parasitology/hydatid-hist1.jpg Hydatid cyst (med.sc.edu)].
*[http://www.atlas.or.kr/atlas/include/viewImg.html?uid=645 Hydatid cyst (atlas.or.kr)].
*[http://casereports.bmj.com/content/2009/bcr.04.2009.1798.full Hydatid cyst (casereports.bmj.com)].

==Abscess==
A. [[File:1 ABS 1 680x512px.tif|A process replaces most of the liver parenchyma (20X).]]
 
B. [[File:2 ABS 1 680x512px.tif|Fibrinopurulent exudate apposes granulation tissue (200X).]]
 
C. [[File:3 ABS 1 680x512px.tif|Neutrophils lie in widened sinusoids (200X)..]]
 
D. [[File:4 ABS 1 680x512px.tif|Trichrome shows collagenization of spaces of Disse. Scarring about an abscess or other mass lesion should not be interpreted as reflective of the liver in general (200X).]]
 
Abscess. A. A process replaces most of the liver parenchyma. B. Fibrinopurulent exudate apposes granulation tissue. C. Neutrophils lie in widened sinusoids. D. Trichrome shows collagenization of spaces of Disse. Scarring about an abscess or other mass lesion should not be interpreted as reflective of the liver in general (LR 200X).

==Coccidiomycosis==
A. [[File:Coccidiomycosis - 1 - 40X 680x512px shot.tif|500x500px Granulomas at low power]]
 
B. [[File:Coccidiomycosis - 1 - 200X 680x513px shot.tif|500x500px Granulomas with centrally crowded cells & lady slipper macrophage nuclei]]
 
C. [[File:Coccidiomycosis - 1 - 400X 1369x1024px shot.tif|500x500px Center of previous granuloma showing pyknotic macrophage nuclei]]
 
D. [[File:Coccidiomycosis - 1 - GMS 400X 1369x1024px shot.tif|500x500px Four Coccidiomycotic spherules]]
 
Coccidiomycosis. A. Note the granulomas in otherwise undisturbed liver (UL). B. Granuloma with centrally crowded cells & lady slipper macrophage nuclei. C. Center of granuloma with pyknotic macrophage nuclei, "necrotizing". D. Organisms on GMS stain.

=Metabolic and toxic=
==Alcoholic liver disease==
===General===
*Acute and/or chronic liver changes due to excessive [[alcohol]] use - includes:
**''[[Alcoholic steatohepatitis]]'' (ASH), [[AKA]] ''alcoholic hepatitis''.<ref>URL: [http://emedicine.medscape.com/article/170539-overview http://emedicine.medscape.com/article/170539-overview]. Accessed on: 3 May 2012.</ref>
***Alcoholic hepatitis can be with minimal steatosis.<ref>STC. 6 December 2010.</ref>
**[[Steatosis]] - classically macrovescicular and centrilobular.
**Alcoholic [[cirrhosis]].

====Classic lab findings in EtOH abusers====
*AST & ALT elevated with AST:ALT=2:1.
*GGT elevated.
*MCV increased.

===Gross pathology/radiologic findings===
*Classically micronodular pattern.
**May be macronodular.

===Microscopic===
See:
*''[[Steatohepatitis]]'' section and ''[[ballooning degeneration]]'' section.

Features:
*Often zone III damage.
*Cholestatsis common, i.e. yellow staining.
**NASH (non-alcoholic steatohepatitis) usu. does not have cholestasis.<ref>STC. 6 December 2010.</ref>
*Fibrosis starts at central veins.
*Neutrophils (often helpful) -- few other things have PMNs. (???)
**Neutrophils cluster around cells with Mallory hyaline.

====Images====
{|
[[File:1 etoh 3 680x512px.tif| Alcoholic hepatitis with Metavir stage IV fibrosis (advanced fibrosis/cirrhosis).]]
[[File:2 etoh 3 680x512px.tif| Alcoholic hepatitis with Metavir stage IV fibrosis (advanced fibrosis/cirrhosis).]]
 
[[File:3 etoh 3 680x512px.tif| Alcoholic hepatitis with Metavir stage IV fibrosis (advanced fibrosis/cirrhosis).]]
[[File:4 etoh 3 680x512px.tif| Alcoholic hepatitis with Metavir stage IV fibrosis (advanced fibrosis/cirrhosis).]]
 
[[File:5 etoh 3 680x512px.tif| Alcoholic hepatitis with Metavir stage IV fibrosis (advanced fibrosis/cirrhosis).]]
[[File:6 etoh 3 680x512px.tif| Alcoholic hepatitis with Metavir stage IV fibrosis (advanced fibrosis/cirrhosis).]]
|}
Alcoholic hepatitis with Metavir stage IV fibrosis (advanced fibrosis/cirrhosis).
Trichrome shows relatively non-inflamed fibrous bands, as well as [between green dots] nodules. The lack of regeneration throughout might have precluded a diagnosis of cirrhosis, but stage IV fibrosis under the Metavir system is justified (Row 1 Left 20X). Reticulin shows regenerative nodules [left] with mostly two or more nuclei between black lines juxtaposed to non-regenerative hepatocytes on the right, without piecemeal necrosis. (Row 1 Right 100X). Regenerative nodules show occasional neutrophils [red arrow] and cytoplasmic tufts of ballooned cells, sometimes possibly Mallory hyalin [green arrows] (Row 2 Left 200X). Triads (note vein [green arrow], artery [yellow arrow], and interlobular bile duct [blue arrow]) generally showed little or no interface hepatitis, even when expanded by fibrosis and inflamed (Row 2 Right 200X). Occasional foci of spotty necrosis were seen (Row 3 Left 200X). This edge of an inflamed triads shows neutrophils about proliferated bile ducts [red arrows], as well as Mallory-Denk bodies [blue arrows] (Row 4 Left 400X).
{|
[[File:1 etoh 4 680x512px.tif| Cirrhosis in an alcoholic.]]
[[File:2 etoh 4 680x512px.tif| Cirrhosis in an alcoholic.]]
 
[[File:3 etoh 4 680x512px.tif| Cirrhosis in an alcoholic.]]
[[File:4 etoh 4 680x512px.tif| Cirrhosis in an alcoholic.]]
 
[[File:5 etoh 4 680x512px.tif| Cirrhosis in an alcoholic.]]
[[File:6 etoh 4 680x512px.tif| Cirrhosis in an alcoholic.]]
|}
Definite cirrhosis in an alcoholic. Hepatocyte free bands parse tissue, with occasional definite islands [arrows] (Row 1 Left 40X). Trichrome establishes blue fibrosis about isles [arrows] (Row 1 Right 40X). Reticulin stain shows nodules with regeneration, wherein a large proportion of them are at least two nuclei thick [arrows] (Row 2 Left 200X). Bile duct proliferation can be difficult, sometimes mimicking cholangiocarcinoma. Follow the double headed arrows to see how the ductules can be seen to proliferate from a single sources, with all ducts being complete, without necrotic epithelial cells. (Row 2 Right 400X). PAS with distase can help, as cholangiocarcinoma generally lacks the red rim of proliferating bile ductules [arrows]; again note the connections that can be made between the ductule openings by the blue double headed arrows. The cyan double headed arrows show general parallelism, consistent with uniform directionality induced by extrinsic force, not a neoplastic spread (Row 3 Left 400X). Trichrome shows the most difficult focus. Double headed arrows display the connectivity seen before of the proliferated bile ductules. Note that numerous pairs of adjacent perpendicular glands without a head to foot appearance are not seen that would indicate the disorderly spread of cholangiocarcinoma (Row 3 Right 400X).

{|
[[File:1 ALC 2 680x512px.tif|Expanded, inflamed triads with increased bile duct/vascular openings. Mild steatosis (40X).]]
[[File:2 ALC 2 680x512px.tif|Trichrome stain shows periportal fibrosis [red arrowheads] (200X).]]
 
[[File:3 ALC 2 680x512px.tif|PAS with diastase stain shows proliferated bile ductules [blue arrowheads] in stroma with mixed inflammatory infiltrate (400X)]]
[[File:4 ALC 2 680x512px.tif|Neutrophils about ballooned hepatocyte (satellitosis) [yellow arrowheads]. Councilman bodies [green arrowheads] (400X).]]
|}
Alcoholic hepatitis without cirrhosis. No history of viral disease. AMA negative. Expanded, inflamed triads with increased bile duct/vascular openings. Mild steatosis (UL 40X). Trichrome stain shows periportal fibrosis [red arrowheads] (UR 200X). PAS with diastase stain shows proliferated bile ductules [blue arrowheads] in stroma with mixed inflammatory infiltrate (LL 400X) Neutrophils about ballooned hepatocyte (satellitosis) [yellow arrowheads]. Councilman bodies [green arrowheads] (LR 400X).

Notes:
*If portal inflammatory infiltrates more than mild, r/o other causes i.e. [[viral hepatitis]].
*Mallory bodies once thought to be characteristic; now considered non-specific and generally poorly understood.<ref>{{cite journal |author=Jensen K, Gluud C |title=The Mallory body: theories on development and pathological significance (Part 2 of a literature survey) |journal=Hepatology |volume=20 |issue=5 |pages=1330-42 |year=1994 |month=November |pmid=7927269 |doi= |url=}}</ref>
*Some consider ''alcoholic liver disease'' a clinical diagnosis, i.e. as a pathologist one does not diagnose it.<ref>MG. September 2009.</ref>

==Non-alcoholic fatty liver disease==
*Abbreviated ''NAFLD''.
*Fatty liver that is not due to alcohol; includes obesity-related fatty liver, metabolic disease/diabetes-related fatty liver.

===NASH===
*Non-alcoholic steatohepatitis - see ''steatohepatitis'' section.
*Histologically indistinguishable from ASH.
*NASH is a ''clinical diagnosis'' based on exclusion of alcohol.

==Steatohepatitis==
{{Main|Steatohepatitis}}

=Autoimmune=
==Autoimmune hepatitis==
*Abbreviated ''AIH''.
{{Main|Autoimmune hepatitis}}

==Primary biliary cirrhosis==
*Abbreviated PBC.
{{Main|Primary biliary cirrhosis}}

==Autoimmune hepatitis with obstruction - combined changes==
{|
[[File:1 AIH OBS 1.tif|Low power shows inflammation; portal triads, lobules, central veins cannot be distinguished (40X).]]
[[File:2 AIH OBS 1.tif|Trichrome shows central venous sclerosis (red arrowhead), periportal fibrosis (green arrowhead), & space of Disse collagenization (yellow arrowhead); juxtaposition of central vein & portal tract indicates collapse, no definite bridging was seen (100X)]]
 
[[File:3 AIH OBS 1.tif|Central vein is inflamed with a rare plasma cell (cyan arrowhead) (400X).]]
[[File:4 AIH OBS 1.tif|Interface hepatitis with plasma cells (yellow arrows) and ballooned hepatocytes (red arrows). Lobule is disorganized (400X).]]
 
[[File:5 AIH OBS 1.tif|Proliferating bile ductules (blue arrows) with occasional neutrophils (fucsia arrows), indicative of obstruction, but not acute cholangitis, which requires inflamed bile duct itself, best diagnosed with associated blood vessel (400X).]]
[[File:6 AIH OBS 1.tif|Rare distorted rosettes with greenish brown strands of bile (left arrow) or bile plugs (right arrow) (400X).]]
|}
Patient with SLE and obstructive jaundice that resolved with apparent passage of stone. Low power shows inflammation; portal triads, lobules, central veins cannot be distinguished (left row 1 40X). Trichrome shows central venous sclerosis (red arrowhead), periportal fibrosis (green arrowhead), & space of Disse collagenization (yellow arrowhead); juxtaposition of central vein & portal tract indicates collapse, no definite bridging was seen (right row 1 100X). Central vein is inflamed with a rare plasma cell (cyan arrowhead) (left row 2 400X). Interface hepatitis with plasma cells (yellow arrows) and ballooned hepatocytes (red arrows). Lobule is disorganized (right row 2 400X). Proliferating bile ductules (blue arrows) with occasional neutrophils (fucsia arrows), indicative of obstruction, but not acute cholangitis, which requires inflamed bile duct itself, best diagnosed with associated blood vessel (left row 3 400X). Rare distorted rosettes with greenish brown strands of bile (left arrow) or bile plugs (right arrow) (right row 3 400X).

==Autoimmune hepatitis-primary biliary cirrhosis overlap syndrome==
*Abbreviation ''AIH-PBC OS''.
===General===
Epidemiology:
*Rare.

Serology:<ref name=pmid19491855>{{Cite journal | last1 = Muratori | first1 = P. | last2 = Granito | first2 = A. | last3 = Pappas | first3 = G. | last4 = Pendino | first4 = GM. | last5 = Quarneti | first5 = C. | last6 = Cicola | first6 = R. | last7 = Menichella | first7 = R. | last8 = Ferri | first8 = S. | last9 = Cassani | first9 = F. | title = The serological profile of the autoimmune hepatitis/primary biliary cirrhosis overlap syndrome. | journal = Am J Gastroenterol | volume = 104 | issue = 6 | pages = 1420-5 | month = Jun | year = 2009 | doi = 10.1038/ajg.2009.126 | PMID = 19491855 }}</ref>
*AMA +ve.
*Anti-dsDNA +ve.

===Microscopic===
:See: ''[[autoimmune hepatitis]]'' and ''[[primary biliary cirrhosis]]''.
{|
[[File:1 AIH PBC 1 680x512px.tif|Expanded portal tracts with fuzzy edges (40X).]]
[[File:2 AIH PBC 1 680x512px.tif|Interface hepatitis with plasma cells (400X).]]
 
[[File:3 AIH PBC 1 680x512px.tif|Loose granuloma (400X).]]
[[File:4 AIH PBC 1 680x512px.tif|Damaged bile duct (400X).]]
|}

AIH/PBC overlap. AMA & ANA positive with Alkaline phosphatase > 2 upper limit of normal & one ALT > 5 times upper limit of normal. Expanded portal tracts with fuzzy edges (UL 40X). IInterface hepatitis with plasma cells (UR 400X). Loose granuloma (LL 400X). Damaged bile duct (LR 400X).

==Primary sclerosing cholangitis==
*Abbreviated ''PSC''.
{{Main|Primary sclerosing cholangitis}}

=Hereditary=
==Caroli disease==
===General===
*Genetic disease.
**Frequently associated with [[autosomal recessive polycystic kidney disease]] (ARPKD).<ref name=omim263200>{{OMIM|263200}}</ref>
**May be seen in isolation.<ref name=omim600643>{{OMIM|600643}}</ref>

Clinical:<ref name=pmid17461493>{{Cite journal | last1 = Yonem | first1 = O. | last2 = Bayraktar | first2 = Y. | title = Clinical characteristics of Caroli's syndrome. | journal = World J Gastroenterol | volume = 13 | issue = 13 | pages = 1934-7 | month = Apr | year = 2007 | doi = | PMID = 17461493 }}</ref>
*Recurrent [[cholangitis]].
*Recurrent [[cholelithiasis]].
*[[Cholangiocarcinoma]]<ref name=pmid17461492>{{Cite journal | last1 = Yonem | first1 = O. | last2 = Bayraktar | first2 = Y. | title = Clinical characteristics of Caroli's disease. | journal = World J Gastroenterol | volume = 13 | issue = 13 | pages = 1930-3 | month = Apr | year = 2007 | doi = | PMID = 17461492 }}</ref> - seen in ~7% of cases.<ref name=pmid15347876>{{Cite journal | last1 = Karim | first1 = AS. | title = Caroli's disease. | journal = Indian Pediatr | volume = 41 | issue = 8 | pages = 848-50 | month = Aug | year = 2004 | doi = | PMID = 15347876 }}</ref>

Note:
*''Caroli syndrome'' = Caroli disease + congenital hepatic fibrosis.<ref name=pmid15888616>{{Cite journal | last1 = Brancatelli | first1 = G. | last2 = Federle | first2 = MP. | last3 = Vilgrain | first3 = V. | last4 = Vullierme | first4 = MP. | last5 = Marin | first5 = D. | last6 = Lagalla | first6 = R. | title = Fibropolycystic liver disease: CT and MR imaging findings. | journal = Radiographics | volume = 25 | issue = 3 | pages = 659-70 | month = | year = | doi = 10.1148/rg.253045114 | PMID = 15888616 | URL = http://radiographics.rsna.org/content/25/3/659.long }}</ref>

===Gross===
*Dilated bile ducts.<ref name=omim263200/>

===Microscopic===
Features:<ref name=pmid17461493/>
*Dilated bile ducts.
*Periductal fibrosis. (???)
*+/-Fibrosis.

Image:
*[http://www.meddean.luc.edu/lumen/MedEd/orfpath/11-3-10.jpg Caroli disease (meddean.luc.edu)].<ref>URL: [http://www.meddean.luc.edu/lumen/MedEd/orfpath/develop.htm http://www.meddean.luc.edu/lumen/MedEd/orfpath/develop.htm]. Accessed on: 1 December 2011.</ref>

==Hereditary hemochromatosis==
:''For secondary causes see [[secondary hemochromatosis]]''.
{{Main|Hereditary hemochromatosis}}

==Wilson disease==
{{Main|Wilson's disease}}

==Alpha-1 antitrypsin deficiency==
*[[AKA]] ''alpha1-antiprotease inhibitor deficiency''.
{{Main|Alpha-1 antitrypsin deficiency }}

=Other=
==Budd-Chiari syndrome==
*[[AKA]] ''hepatic vein obstruction''.
===General===
*Hepatic outflow obstruction.

Clinical triad:<ref name=pmid21573256>{{Cite journal | last1 = Fox | first1 = MA. | last2 = Fox | first2 = JA. | last3 = Davies | first3 = MH. | title = Budd-Chiari syndrome--a review of the diagnosis and management. | journal = Acute Med | volume = 10 | issue = 1 | pages = 5-9 | month = | year = 2011 | doi = | PMID = 21573256 }}</ref>
*Ascites.
*Abdominal pain.
*Hepatomegaly.

Etiology:
*~50% have a [[myeloproliferative disease]].<ref name=pmid18814079>{{Cite journal | last1 = Plessier | first1 = A. | last2 = Valla | first2 = DC. | title = Budd-Chiari syndrome. | journal = Semin Liver Dis | volume = 28 | issue = 3 | pages = 259-69 | month = Aug | year = 2008 | doi = 10.1055/s-0028-1085094 | PMID = 18814079 }}</ref>
*May be due to mass effect from a tumour.

Clinical DDx:
*[[Hepatic veno-occlusive disease]].

===Microscopic===
Features:<ref name=pmid17569137>{{Cite journal | last1 = Aydinli | first1 = M. | last2 = Bayraktar | first2 = Y. | title = Budd-Chiari syndrome: etiology, pathogenesis and diagnosis. | journal = World J Gastroenterol | volume = 13 | issue = 19 | pages = 2693-6 | month = May | year = 2007 | doi = | PMID = 17569137 | url=http://www.wjgnet.com/1007-9327/full/v13/i19/2693.htm }}</ref>
*Sinusoidal dilation in zone III (congestion).
*+/-Hepatocyte drop-out.
*+/-Centrilobular fibrosis.

DDx congestion:
*Congestive heart failure ([[congestive hepatopathy]]).
*Constrictive pericarditis.

==Vanishing bile duct syndrome==
*[[AKA]] ''bile duct loss'', [[AKA]] ''ductopenia''.<ref name=pmid11521176/>
===General===
*Fatal.

DDx:<ref name=pmid18242505/>
*[[Primary biliary cirrhosis]].
*[[Primary sclerosing cholangitis]].
*[[GVHD]].<ref name=pmid7994249>{{Cite journal | last1 = Yeh | first1 = KH. | last2 = Hsieh | first2 = HC. | last3 = Tang | first3 = JL. | last4 = Lin | first4 = MT. | last5 = Yang | first5 = CH. | last6 = Chen | first6 = YC. | title = Severe isolated acute hepatic graft-versus-host disease with vanishing bile duct syndrome. | journal = Bone Marrow Transplant | volume = 14 | issue = 2 | pages = 319-21 | month = Aug | year = 1994 | doi = | PMID = 7994249 }}</ref>
*[[Drug-induced liver disease|Drugs]].<ref name=pmid11352118>{{Cite journal | last1 = Chitturi | first1 = S. | last2 = Farrell | first2 = GC. | title = Drug-induced cholestasis. | journal = Semin Gastrointest Dis | volume = 12 | issue = 2 | pages = 113-24 | month = Apr | year = 2001 | doi = | PMID = 11352118 }}</ref>
*Chronic rejection.<ref name=pmid11521176>{{Cite journal | last1 = Inomata | first1 = Y. | last2 = Tanaka | first2 = K. | title = Pathogenesis and treatment of bile duct loss after liver transplantation. | journal = J Hepatobiliary Pancreat Surg | volume = 8 | issue = 4 | pages = 316-22 | month = | year = 2001 | doi = 10.1007/s0053410080316 | PMID = 11521176 }}</ref>

===Microscopic===
Features:<ref name=pmid18242505>{{Cite journal | last1 = Reau | first1 = NS. | last2 = Jensen | first2 = DM. | title = Vanishing bile duct syndrome. | journal = Clin Liver Dis | volume = 12 | issue = 1 | pages = 203-17, x | month = Feb | year = 2008 | doi = 10.1016/j.cld.2007.11.007 | PMID = 18242505 }}</ref>
*Loss of intrahepatitic bile ducts - '''key feature'''.
*Cholestasis.

Note:
*May occur without fibrosis and inflammation; thus, can be easy to miss.

===IHC===
*[[CK7]] -ve.
**Marks bile ducts.

==Extrahepatic biliary obstruction==
{|
[[File:1 OBS 3 680x512px.tif|Sinusoidal dilatation, circular spaces of hepatocytes, small portal triads(40X).]]
[[File:2 OBS 3 680x512px.tif|Bile in hepatocytes about central vein & in plugs in canaliculi [yellow arrowhead] (400X).]]
 
[[File:3 OBS 3 680x512px.tif|Trichrome shows fibrosis about central vein (400X).]]
[[File:4 OBS 3 680x512px.tif|PAS with diastase shows portal triads with mild edema and chronic inflammation, without tortuous bile duct (400X).]]
|}
Early extrahepatic biliary obstruction, demonstrated radiographically, transient, with rise in bilirubin, alkaline phosphatase, and transaminases. Pure canalicular cholestasis near terminal hepatic venules also seen in acute hepatitis, drug reactions, benign recurrent cholestasis, pregnancy, sepsis, & lymphomas. Sinusoidal dilatation, circular spaces of hepatocytes, small portal triads(UL 40X). Bile in hepatocytes about central vein & in plugs in canaliculi [yellow arrowhead] (UR 400X). Trichrome shows fibrosis about central vein (LL 400X). PAS with diastase shows portal triads with mild edema and chronic inflammation, without tortuous bile duct (LR 400X).

{|
[[File:1 OBS 2 680x512px.tif|Expanded inflamed portal triads, swollen hepatocytes (40X)]]
[[File:2 OBS 2 680x512px.tif|Edematous stroma, proliferating ductules [yellow arrowheads], PAS-D macrophages [red arrowhead] (PAS with diastasse, 200X)]]
 
[[File:3 OBS 2 680x512px.tif|Disordered, often swollen hepatocytes,some with feathery degeneration (net like spaces in cytoplasm [blue arrowhead], rare Councilman body [green arrowhead] (400X)]]
[[File:4 OBS 2 1360x1024px.tif|Bile in hepatocytes [cyan arrrowhead] & in canaliculi [purple arrowheads]. Empty acinar spaces bounded by hepatocytes [orange arrowhead] (400X, higher pixel),]]
|}
Changes of extrahepatic biliary obstruction, months duration. Expanded inflamed portal triads, swollen hepatocytes (UL 40X). Edematous stroma, proliferating ductules [yellow arrowheads], PAS-D macrophages [red arrowhead] (UR PAS with diastasse, 200X). Disordered, often swollen hepatocytes,some with feathery degeneration (net like spaces in cytoplasm) [blue arrowhead], rare Councilman body [green arrowhead] (LL 400X). Bile in hepatocytes [cyan arrrowhead] & in canaliculi [purple arrowheads]. Empty acinar spaces bounded by hepatocytes [orange arrowhead] (LR 400X).
{|
[[File:1 Bd obs 4 680x512px.tif|Expanded, light colored portal triads (arrows)(20X).]]
[[File:2 Bd obs 4 680x512px.tif|Proliferating bile ductules (cyan arrows) with neutrophils (yellow arrows), not specific for acute cholangitis, of assistance with large bile duct obstruction (400X)..]]
 
[[File:3 Bd obs 4 680x512px.tif|Uninflamed interlobular duct (yellow arrow) with, accompanying blood vessel (red arrow) (400X)]]
[[File:4 Bd obs 4 680x512px.tif|Bile infarct with pyknotic nuclei (arrows)(400X).]]
 
[[File:5 Bd obs 4 680x512px.tif|Bile (arrow) in interlobular bile duct with disordered nuclei (400X).]]
[[File:6 Bd obs 4 680x512px.tif|Bile plugs in cannaliculi (red arrows), feathery degeneration producing foamy macrophage like hepatocytes (yellow arrows)(400X).]]
|}
Large bile duct obstruction. Expanded, light colored portal triads (arrows)(Row 1 Left 20X). Proliferating bile ductules (cyan arrows) with neutrophils (yellow arrows), not specific for acute cholangitis, of assistance with large bile duct obstruction (Row 1 Right 400X). Uninflamed interlobular duct (yellow arrow) with, accompanying blood vessel (red arrow) (Row 2 Left 400X). Bile infarct with pyknotic nuclei (arrows)(Row 2 Right 400X). Bile (arrow) in interlobular bile duct with disordered nuclei (Row 3 Left 400X). Bile plugs in cannaliculi (red arrows), feathery degeneration producing foamy macrophage-like hepatocytes (yellow arrows)(Row 3 Right 400X).

==Congestive hepatopathy==
===General===
*Liver failure due to (right) heart failure.
*AKA ''cardiac cirrhosis'' - a term used by clinicians.
**Generally, it does not satisfy pathologic criteria for cirrhosis.<ref>URL: [http://emedicine.medscape.com/article/151792-overview http://emedicine.medscape.com/article/151792-overview]. Accessed on: 17 June 2010.</ref>

===Gross===
*"Nutmeg" liver - yellow spotted appearance.

===Microscopic===
Features:<ref>URL: [http://emedicine.medscape.com/article/151792-diagnosis http://emedicine.medscape.com/article/151792-diagnosis]. Accessed on: 17 June 2010.</ref>
*Zone III atrophy.
*Portal venule (central vein) distension.
*Perisinusoidal fibrosis - progresses to centrilobular fibrosis and then diffuse fibrosis.
*Dilation of sinusoids in ''all'' zone III areas - '''key feature'''.<ref>Suggested by OA. September 2009.</ref>

DDx:
*[[Hemangioma of the liver]] - should be focal lesion.

====Images====
<gallery>
Image:Congestive_hepatopathy_high_mag.jpg | Mild congestive hepatopathy. (WC)
</gallery>
{|
[[File:1 CEN NEC 1 680x512px.tif|PAS without diastase shows ovoids of necrosis {40X).]]
[[File:2 CEN NEC 1 680x512px.tif|Necrosis with central vein [yellow arrowhead], inflammatory cells, residual Councilman body [green arrowhead], and hepatocyte with mitotic figure [red arrowhead] (400X).]]
 
[[File:3 CEN NEC 1 680x512px.tif|Trichrome highlights fibrosis about central vein [yellow arrowhead] & shows beginning scar formation [green arrowheads]. Note residual atrophic hepatocytes [blue arrowheads] (400X).]]
[[File:4 CEN NEC 1 680x512px.tif|Portal triads are largely unaffected (400X).]]
|}
Centrilobular necrosis (seen in circulatory failure and with toxins/drugs). PAS without diastase shows ovoids of necrosis {UL 40X). Necrosis with central vein [yellow arrowhead], inflammatory cells, residual Councilman body [green arrowhead], and hepatocyte with mitotic figure [red arrowhead] (UR 400X). Trichrome highlights fibrosis about central vein [yellow arrowhead] & shows beginning scar formation [green arrowheads]. Note residual atrophic hepatocytes [blue arrowheads] (LL 400X). Portal triads are largely unaffected (LR 400X)

{|
[[File:1 CHF 1 680x512px.tif|Dilated and undilated sinusoidal regions (40X).]]
[[File:2 CHF 1 680x512px.tif|Thrombi in sinusoids; glycogenated nuclei likely reflect patient’s diabetes mellitus (400X).]]
 
[[File:3 CHF 1 680x512px.tif|Dilated portal vein (400X).]]
[[File:4 CHF 1 680x512px.tif|Reticulin shows collapse (thick black lines) as well as a dilated portal vein (200X).]]
 
[[File:5 CHF 1 680x512px.tif|Trichrome shows space of Disse collagenization (pericellular fibrosis) (200X).]]
[[File:6 CHF 1 680x512px.tif|Trichrome shows periportal fibrosis; no bridging was seen (200X).]]
|}
Patient with congestive heart failure and stage I fibrosis. Dilated and undilated sinusoidal regions (left row 1 40X). Thrombi in sinusoids; glycogenated nuclei likely reflect patient’s diabetes mellitus (right row 1 400X). Dilated portal vein (left row 2 400X). Reticulin shows black lines of bridging, too thick for collapse (right row 2 200X). Trichrome shows space of Disse collagenization (pericellular fibrosis) (left row 3 200X). Trichrome shows bridge beginning off to right; when it is more than a mere spike, it is a bridge (right row 3 200X).

==Drug-induced liver disease==
*[[AKA]] ''drug-induced liver toxicity''.
{{Main|Drug-induced liver disease}}

==Focal nodular hyperplasia==
*Abbreviated ''FNH''.
{{Main|Focal nodular hyperplasia}}

==Nodular regenerative hyperplasia==
===General===
*Associated with renal transplants, [[bone marrow transplant]]s and [[vasculitides]].<ref name=Ref_PBoD922>{{Ref PBoD|922}}</ref>
*Can lead to [[portal hypertension]] and many of the associated complications.<ref name=pmid22554152>{{Cite journal | last1 = Bissonnette | first1 = J. | last2 = Généreux | first2 = A. | last3 = Côté | first3 = J. | last4 = Nguyen | first4 = B. | last5 = Perreault | first5 = P. | last6 = Bouchard | first6 = L. | last7 = Pomier-Layrargues | first7 = G. | title = Hepatic hemodynamics in 24 patients with nodular regenerative hyperplasia and symptomatic portal hypertension. | journal = J Gastroenterol Hepatol | volume = 27 | issue = 8 | pages = 1336-40 | month = Aug | year = 2012 | doi = 10.1111/j.1440-1746.2012.07168.x | PMID = 22554152 }}
</ref>

====Etiology====
*Arterial hypervascularity secondary to loss of hepatic vein radicles (loss of central venule in hepatic lobule).<ref name=Ref_PBoD922>{{Ref PBoD|922}}</ref>

ASIDE: radicle = ramulus - smallest branch or vessel or nerve.<ref name=Dorlands2>Dorland's Medical Dictionary. 30th Ed.</ref>

===Gross===
*Diffuse nodularity - whole liver.

===Microscopic===
Features:<ref name=Ref_PBoD922>{{Ref PBoD|922}}</ref>
*"Plump" hepatocytes surrounded by atrophic ones.
*No fibrosis.

==Sinuosoidal obstruction syndrome==
*May be referred to as ''Hepatic veno-occlusive disease''.<ref name=pmid11928077>{{Cite journal | last1 = DeLeve | first1 = LD. | last2 = Shulman | first2 = HM. | last3 = McDonald | first3 = GB. | title = Toxic injury to hepatic sinusoids: sinusoidal obstruction syndrome (veno-occlusive disease). | journal = Semin Liver Dis | volume = 22 | issue = 1 | pages = 27-42 | month = Feb | year = 2002 | doi = 10.1055/s-2002-23204 | PMID = 11928077 }}.</ref>
===General===
*Term for obstruction due to toxicity from a chemotherapeutic agent.<ref name=pmid16393276>{{Cite journal | last1 = Helmy | first1 = A. | title = Review article: updates in the pathogenesis and therapy of hepatic sinusoidal obstruction syndrome. | journal = Aliment Pharmacol Ther | volume = 23 | issue = 1 | pages = 11-25 | month = Jan | year = 2006 | doi = 10.1111/j.1365-2036.2006.02742.x | PMID = 16393276 }}</ref><ref name=pmid17569137>{{Cite journal | last1 = Aydinli | first1 = M. | last2 = Bayraktar | first2 = Y. | title = Budd-Chiari syndrome: etiology, pathogenesis and diagnosis. | journal = World J Gastroenterol | volume = 13 | issue = 19 | pages = 2693-6 | month = May | year = 2007 | doi = | PMID = 17569137 | url=http://www.wjgnet.com/1007-9327/full/v13/i19/2693.htm }}</ref>

Clinical DDx:
*[[Budd-Chiari syndrome]].

===Microscopic===
Features:<ref name=pmid17569137>{{Cite journal | last1 = Aydinli | first1 = M. | last2 = Bayraktar | first2 = Y. | title = Budd-Chiari syndrome: etiology, pathogenesis and diagnosis. | journal = World J Gastroenterol | volume = 13 | issue = 19 | pages = 2693-6 | month = May | year = 2007 | doi = | PMID = 17569137 | url=http://www.wjgnet.com/1007-9327/full/v13/i19/2693.htm }}</ref>
*Subendothelial swelling in hepatic venules.

Negatives:
*No thrombosis.

==Ascending Cholangitis (Acute Cholangitis)==
===General===
*Term for infection of bile ducts, usually due to obstruction

Clinical DDx:

===Microscopic===
====Images====

A. [[File:1 asc chol 1 680x512px.tif|Rounded, clear (edematous) portal tracts (arrows) separated by hepatocytes with dilated sinusoids (Row 1 Left 40X).]]
 
B. [[File:2 asc chol 1 680x512px.tif|Neutrophils about hepatocytes (arrows) have spilled into the lobule from a portal tract (Row 1 Right 200X).]]
 
C. [[File:3 asc chol 1 680x512px.tif|Proliferated bile ductules (arrows) bearing neutrophils within epithelium and lumens are features of obstruction that should prompt a search for interlobular ducts with acute inflammation (Row 2 Left 400X).]]
 
D. [[File:4 asc chol 1 680x512px.tif|The epithelium of the ducts can be severely degenerated. Neutrophils (cyan arrows) invade epithelium of an interlobular duct that are recognizable mainly as a circle of rounded nuclei; the associated arteriole (red arrow) should be identified to ensure an interlobular duct is being evaluated. Note the proliferated bile ductules (blue arrows) (Row 2 Right 400X).]]
 
E. [[File:5 asc chol 1 680x512px.tif|A PAS without diastase stain colors the arteriole (blue arrow), as well as the rim of the interlobular duct within which lies a neutrophil (cyan arrow) (Row 2 Right 400X). .]]
 
F. [[File:6 asc chol 1 680x512px.tif|A PAS with diastase stain colors the arteriole (red arrow), as well as the rim of the interlobular duct within which lies a neutrophil (cyan arrow) (Row 1 Right 400X)]]
 
Acute cholangitis in a patient with multiple bile duct procedures. After the biopsy, removal of bile duct stones released pus. A. Rounded, clear (edematous) portal tracts (arrows) separated by hepatocytes with dilated sinusoids. B. Neutrophils about hepatocytes (arrows) have spilled into the lobule from a portal tract. C, Proliferated bile ductules (arrows) bearing neutrophils within epithelium and lumens are features of obstruction that should prompt a search for interlobular ducts with acute inflammation. D. The epithelium of the ducts can be severely degenerated. Neutrophils (cyan arrows) invade epithelium of an interlobular duct that are recognizable mainly as a circle of rounded nuclei; the associated arteriole (red arrow) should be identified to ensure an interlobular duct is being evaluated. Note the proliferated bile ductules (blue arrows). E. A PAS without diastase stain colors the arteriole (blue arrow), as well as the rim of the interlobular duct within which lies a neutrophil (cyan arrow). F. A PAS with diastase stain colors the arteriole (red arrow), as well as the rim of the interlobular duct within which lies a neutrophil (cyan arrow).

A.[[File:1 Sep Acu Cho 1 680x512px.tif|Low power shows variably sized inflamed portal tracts (40X)]]
 
B. [[File:2 Sep Acu Cho 1 680x512px.tif|Trichrome shows dilated sinusoids and space of Disse collagenization (200X)]]
 
C. [[File:3 Sep Acu Cho 1 680x512px.tif|Inflammatory focus with macrophages and neutrophils (400X).]]
 
D. [[File:4 Sep Acu Cho 1 680x512px.tif|PAS with diastase shows proliferated bile ductules at edge of triad with neutrophils, which should not be used to make a definite diagnosis of acute cholangitis (400X).]]
 
E. [[File:5 Sep Acu Cho 1 680x512px.tif|PAS without diastase showing acutely inflamed bile duct, with accompanying blood vessel of similar size, diagnostic of acute cholangitis (400X).]]
 
F. [[File:6 Sep Acu Cho 1 680x512px.tif|PAS with diastase showing neutrophil in bille duct lumen, diagnostic of acute cholangitis (400X).]]
 
Patient with sepsis and acute cholangitis. A. Low power shows variably sized inflamed portal tracts. B. Trichrome shows dilated sinusoids and space of Disse collagenization. C. Inflammatory focus with macrophages and neutrophils. D. PAS with diastase shows proliferated bile ductules at edge of triad with neutrophils, which should not be used to make a definite diagnosis of acute cholangitis. E. PAS without diastase showing acutely inflamed bile duct, with accompanying blood vessel of similar size, diagnostic of acute cholangitis. F. PAS with diastase showing neutrophil in bille duct lumen, diagnostic of acute cholangitis.

==Polycystic kidney disease and the liver==
{{Main|Cystic kidney disease}}
===General===
Complications of PKD in the liver:<ref>{{Ref MacSween|174-5}}</ref>
#Infected cyst.
#Cholangiocarcinoma.
#Cholestasis/obstruction due to duct compression.<ref>URL: [http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=9184868 http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=9184868]. Accessed on: 23 September 2009.</ref>

Cysts:
*Cysts in the liver, like the kidney, are thought to enlarge with age.

===Microscopic===
Features:<ref>{{Ref MacSween|176}}</ref>
*''Von Meyenburg complexes'' ([[bile duct hamartoma]]):
**Cluster of dilated ducts with "altered" bile.
**Surrounded by collagenous stroma.
**Separate from the portal areas.<ref>Meyenburg complex. Stedman's Medical Dictionary. 27th Ed.</reF>

Images:
*[http://commons.wikimedia.org/wiki/File:Von_Meyenburg_complex_low_mag.jpg Von Meyenburg complex - bile duct hamartoma (WC)].
*[http://commons.wikimedia.org/wiki/File:Bile_duct_hamartoma_intermed_mag.jpg Bile duct hamartoma (WC)].

Notes:
*Appearance on ultrasound<ref name=pmid17287178>Bile duct hamartomas--the von Meyenburg complex. Salles VJ, Marotta A, Netto JM, Speranzini MB, Martins MR. Hepatobiliary Pancreat Dis Int. 2007 Feb;6(1):108-9. PMID 17287178.</ref> and CT (hypodense)<ref name=pmid19294869>[The von Meyenburg complex] Schwab SA, Bautz W, Uder M, Kuefner MA. Rontgenpraxis. 2008;56(6):241-4. German. PMID 19294869.</ref> - similar to metastases.

==Peliosis hepatis==
===General===
*Associated with:
**Infections.
**Malignancy.
**Other stuff.
*Rarely biopsied.

===Microscopic===
Features:
*Cyst lined by endothelium.
**Usu. incomplete.
*Blood.
{|
[[File:1 PEL 1 680x512px.tif|Hemorrhage at left end, dilated sinusoids elsewhere (20X).]]
[[File:2 PEL 1 680x512px.tif|Ramifying dilated sinusoidal spaces (100X).]]
 
[[File:3 PEL 1 680x512px.tif|PAS with diastase shows flat lining (400X).]]
[[File:4 PEL 1 680x512px.tif|Necrotic hepatocytes in cords, presumably due to pressure (400X).]]
|}
Peliosis hepatis. Hemorrhage at left end, dilated sinusoids elsewhere (UL 20X). Ramifying dilated sinusoidal spaces (UR 100X). PAS with diastase shows flat lining (LL 400X). Necrotic hepatocytes in cords, presumably due to pressure (LR 400X).

==Total parenteral nutrition==
*Abbreviated ''TPN''.

===General===
*Indication: short gut syndrome, others.

===Microscopic===
Variable - may range from: steatosis, steatohepatitis, cholestasis, fibrosis and cirrhosis.<ref name=pmid16766237>{{cite journal |author=Guglielmi FW, Boggio-Bertinet D, Federico A, ''et al.'' |title=Total parenteral nutrition-related gastroenterological complications |journal=Dig Liver Dis |volume=38 |issue=9 |pages=623–42 |year=2006 |month=September |pmid=16766237 |doi=10.1016/j.dld.2006.04.002 |url=}}</ref>

Features (classic):<ref>{{Cite journal | last1 = Li | first1 = SJ. | last2 = Nussbaum | first2 = MS. | last3 = McFadden | first3 = DW. | last4 = Gapen | first4 = CL. | last5 = Dayal | first5 = R. | last6 = Fischer | first6 = JE. | title = Addition of glucagon to total parenteral nutrition (TPN) prevents hepatic steatosis in rats. | journal = Surgery | volume = 104 | issue = 2 | pages = 350-7 | month = Aug | year = 1988 | doi = | PMID = 3135627 }}</ref><ref>{{Cite journal | last1 = Stanko | first1 = RT. | last2 = Nathan | first2 = G. | last3 = Mendelow | first3 = H. | last4 = Adibi | first4 = SA. | title = Development of hepatic cholestasis and fibrosis in patients with massive loss of intestine supported by prolonged parenteral nutrition. | journal = Gastroenterology | volume = 92 | issue = 1 | pages = 197-202 | month = Jan | year = 1987 | doi = | PMID = 3096806 }}
</ref>
*[[Steatosis]] (periportal) - early.
*Cholestasis - late.

==Giant cell hepatitis==
*[[AKA]] ''neonatal giant cell hepatitis''.

:See: ''[[Giant cell hepatitis]]''.

==Hepatic amyloidosis==
{{Main|Amyloidosis}}
*[[AKA]] ''liver amyloidosis''.
*[[AKA]] ''amyloidosis of the liver''.
===General===
*Diffuse abundant amyloid within the space of Disse is associated with [[portal hypertension]].<ref name=pmid1864548>{{Cite journal | last1 = Bion | first1 = E. | last2 = Brenard | first2 = R. | last3 = Pariente | first3 = EA. | last4 = Lebrec | first4 = D. | last5 = Degott | first5 = C. | last6 = Maitre | first6 = F. | last7 = Benhamou | first7 = JP. | title = Sinusoidal portal hypertension in hepatic amyloidosis. | journal = Gut | volume = 32 | issue = 2 | pages = 227-30 | month = Feb | year = 1991 | doi = | PMID = 1864548 | PMC = 1378815 | URL = http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1378815/?tool=pubmed }}</ref>

===Microscopic===
Features:
*Amorphous extracellular pink stuff on H&E - see ''[[amyloid]]'' article.

DDx:
*[[Fibrolamellar hepatocellular carcinoma]].

====Images====
<gallery>
Image:Hepatic_amyloidosis_-_low_mag.jpg | Amyloidosis of the liver - low mag. (WC)
Image:Hepatic_amyloidosis_-_intermed_mag.jpg | Amyloidosis of the liver - intermed. mag. (WC)
Image:Hepatic_amyloidosis_-_high_mag.jpg | Amyloidosis of the liver - high mag. (WC)
Image:Hepatic_amyloidosis_-_very_high_mag.jpg | Amyloidosis of the liver - very high mag. (WC)
</gallery>
{|
[[File:1 AMY 1 680x512px.tif|Amorphous material replaces hepatic parenchyma [4X]]]
[[File:2 AMY 1 680x512px.tif|Material barely stains blue on trichrome [10X]]]
 
[[File:3 AMY 1 680x512px.tif|Material stains red on unpolarized Congo Red [40X]]]
[[File:4 AMY 1 680x512px.tif|Material stains apple green on polarized Congo Red [40X]]]
|}
Amyloidosis. Amorphous material replaces hepatic parenchyma [UL 4X]. Material barely stains blue on trichrome [UR 10X] Material stains red on unpolarized Congo Red [LL 40X] Material stains apple green on polarized Congo Red [LR 40X]

===Stains===
*[[Congo red]] +ve.

==Fulminant hepatic necrosis==
===General===
Etiology:
*Viral, i.e. [[Hepatitis A]], [[Hepatitis B]]; [[Hepatitis C]] - extremely rare.
*Trauma.
*Shock.

===Microscopic===
{|
[[File:1 Necrosis 2 680x512px.tif| Submassive hepatic necrosis.]]
[[File:2 Necrosis 2 680x512px.tif| Submassive hepatic necrosis.]]
 
[[File:3 Necrosis 2 680x512px.tif| Submassive hepatic necrosis.]]
[[File:4 Necrosis 2 680x512px.tif| Submassive hepatic necrosis.]]
 
[[File:5 Necrosis 2 680x512px.tif| Submassive hepatic necrosis.]]
[[File:6 Necrosis 2 680x512px.tif| Submassive hepatic necrosis.]]
|}
Submassive hepatic necrosis. Patient had transaminases in the thousands that rapidly dropped to normal. Pink preserved parenchyma strews empty necrotic spaces (Row 1 Left 20X). Focus of necrosis with no apparent hepatocytes macrophages abuts apparently normal liver (Row 1 Right 200X). Iron stain shows the macrophages bear hemosiderin (Row 2 Left 200X). Reticulin stain highlights the recently dead liver cells (Row 2 Right 200X). Reticulin stain shows a necrotic bridge forming; the multiple small black circles preclude diagnosis of a fibrous bridge (Row 3 Left 200X). Trichrome shows the necrotic bridge (“collapse”) lacks much collagen deposition, as would be expected for bridging fibrosis (Row 3 Right 200X).

Features:
*Hepatocyte [[necrosis]].
*Bile duct proliferation.

DDx:
*[[Cholangiocarcinoma]].
*[[Angiosarcoma]].

==Secondary hemochromatosis==
:''For the hereditary one see [[hereditary hemochromatosis]]''.
===General===
*Iron overload secondary to blood transfusions for hereditary or acquired anemia.<ref name=pmid19727383/>
**Primary hemochromatosis due to a defect in iron processing - called ''[[hereditary hemochromatosis]]''.
*Imaging considered the best test, as iron deposition is patchy.<ref name=pmid19727383/>

Selected hereditary causes:<ref name=pmid19727383>{{Cite journal | last1 = Gattermann | first1 = N. | title = The treatment of secondary hemochromatosis. | journal = Dtsch Arztebl Int | volume = 106 | issue = 30 | pages = 499-504, I | month = Jul | year = 2009 | doi = 10.3238/arztebl.2009.0499 | PMID = 19727383 | PMC = 2735704 | URL = http://www.ncbi.nlm.nih.gov.myaccess.library.utoronto.ca/pmc/articles/PMC2735704/?tool=pubmed}}</ref>
*Thalassemia.
*[[Sickle cell anemia]].
*Hereditary sideroblastic anemia.

Selected acquired causes:<ref name=pmid19727383/>
*[[Myelodysplastic syndromes]]
*Myelofibrosis
*Aplastic anemia, intractable.

===Microscopic===
:See ''[[hereditary hemochromatosis]]''.

==Hepatic sarcoidosis==
{{Main|Hepatic sarcoidosis}}
==Overlapping Disorders==

[[File:1 Mixed Disorder 1 680x512px.tif|Changes of steatohepatitis and interface hepatitis, with granuloma. Patient with diabetes was ANA, AMA, HCV, HBV negative, without drugs known to produce granulomas or interface hepatitis. This may be a case of AMA negative primary biliary cirrhosis, but studies to determine that with certainty were not performed.]]
[[File:2 Mixed Disorder 1 680x512px.tif|Changes of steatohepatitis and interface hepatitis, with granuloma. Patient with diabetes was ANA, AMA, HCV, HBV negative, without drugs known to produce granulomas or interface hepatitis. This may be a case of AMA negative primary biliary cirrhosis, but studies to determine that with certainty were not performed.]]
[[File:3 Mixed Disorder 1 680x512px.tif|Changes of steatohepatitis and interface hepatitis, with granuloma. Patient with diabetes was ANA, AMA, HCV, HBV negative, without drugs known to produce granulomas or interface hepatitis. This may be a case of AMA negative primary biliary cirrhosis, but studies to determine that with certainty were not performed.]]
[[File:4 Mixed Disorder 1 680x512px.tif|Changes of steatohepatitis and interface hepatitis, with granuloma. Patient with diabetes was ANA, AMA, HCV, HBV negative, without drugs known to produce granulomas or interface hepatitis. This may be a case of AMA negative primary biliary cirrhosis, but studies to determine that with certainty were not performed.]]
[[File:5 Mixed Disorder 1 680x512px.tif|Changes of steatohepatitis and interface hepatitis, with granuloma. Patient with diabetes was ANA, AMA, HCV, HBV negative, without drugs known to produce granulomas or interface hepatitis. This may be a case of AMA negative primary biliary cirrhosis, but studies to determine that with certainty were not performed.]]
[[File:6 Mixed Disorder 1 680x512px.tif|Changes of steatohepatitis and interface hepatitis, with granuloma. Patient with diabetes was ANA, AMA, HCV, HBV negative, without drugs known to produce granulomas or interface hepatitis. This may be a case of AMA negative primary biliary cirrhosis, but studies to determine that with certainty were not performed.]] 
Changes of steatohepatitis and interface hepatitis, with granuloma. Patient with diabetes was ANA, AMA, HCV, HBV negative, without drugs known to produce granulomas or interface hepatitis. This may be a case of AMA negative primary biliary cirrhosis, but studies to determine that with certainty were not performed. A. Low power shows hepatocytes afflicted by steatosis and an inflamed portal tract. B. In a region of fatty change lie cytoplasmic tufts of ballooning degeneration (green arrows) and a lipogranuloma (black arrow). C. At the portal-hepatocyte junction lies interface hepatitis (black arrows), as well as extension of inflammation into the lobule (green arrows). D. Red hepatocytes bounded by inflammation denote piecemeal necrosis [PAS without diastase]. E. Giant cells intermixed with lymphocytes prove a portal granuloma [PAS without diastase]. F. A blue fibrous bridge extends from a triad [Trichrome].

[[File:4 95599552608917 sl 1.png|Acute obstructive changes and changes of recurrent acute injury]]
[[File:4 95599552608917 sl 2.png|Acute obstructive changes and changes of recurrent acute injury]]
[[File:4 95599552608917 sl 3.png|Acute obstructive changes and changes of recurrent acute injury]]
[[File:4 95599552608917 sl 4.png|Acute obstructive changes and changes of recurrent acute injury]]
[[File:4 95599552608917 sl 5.png|Acute obstructive changes and changes of recurrent acute injury]]
[[File:4 95599552608917 sl 6.png|Acute obstructive changes and changes of recurrent acute injury]]
[[File:4 95599552608917 sl 7.png|Acute obstructive changes and changes of recurrent acute injury]] 
Acute obstructive changes and changes of recurrent injury in 46 yo man with Clostridium perfringens positive blood culture, an ERCP that showed duodenal compression by the pancreas with resultant bile duct dilatation. The patient had had and continued to have multiple bouts of acute pancreatitis. At the time of biopsy, decreased platelet count/hemoglobin/albumin, elevated lipase/amylase/PT/PTT, normal alkaline phosphatase, bilirubin, AST/ALT, AMA, hepatitis virus serology, ANA. A. Fragment biopsy shows inflamed triads and bridges. B. Trichrome shows bridges without nodules, evidence of prior injury; the patient subsequently developed multiple episodes of pancreatitis. C. Reticulin shows piecemeal necrosis, with black lines bounding individual hepatocytes at interface (arrows). D. Collapse is shown by closly approximated thick black lines; one cannot call portal-central collapse without seeing a central vein. Note on this and the other reticulin image that regeneration, two cell thick cords, is not prominent. E. PAS D of two portal triads, far nearer than normal, both expanded. Note increased number of ducts/ductules (red arrows), neutrophils, and PAS-D macrophages. F. PAS D shows collapse extending from a triad to a portion of a lobule with steatosis. No feathery degeneration or bile duct plugs were seen. Neither were foci of spotty necrosis or abscess seen. G. Other triads, again edematous, showed more of a chronic inflammatory response, with occasional plasma cells (black arrows). Also present are neutrophils (red arrows). The bile duct (grey arrow) near the artery (brown arrow) shows mildly disturbed nuclei. Note early proliferated bile ductules (cyan arrows).

[[File:6 17281676469188 sl 1.png| Hepatitis B virus with steatohepatitis]]
[[File:6 17281676469188 sl 2.png| Hepatitis B virus with steatohepatitis]]
[[File:6 17281676469188 sl 3.png| Hepatitis B virus with steatohepatitis]]
[[File:6 17281676469188 sl 4.png| Hepatitis B virus with steatohepatitis]]
[[File:6 17281676469188 sl 5.png| Hepatitis B virus with steatohepatitis]]
[[File:6 17281676469188 sl 6.png| Hepatitis B virus with steatohepatitis]] 
Hepatitis B virus with steatohepatitis in a 36 year old man with hepatitis B surface antigen and hepatitis Be antigen positivity, Hepatitis be QTPC of 1750 cop/mL, an occasionally mildly elevated (42) ALT, and normal glucose, alkaline phosphatase, bilirubin, and other transaminases. He had a history of alcohol abuse, which became controlled. A. Triads show scant inflammation without definite interface hepatitis. About one-fourth of the lobule, not pan-acinar, is afflicted by steatosis. B. Occasional tufts are seen (arrow), indicating focal ballooning sufficient for a diagnosis of steatohepatitis. C. Glycogenated nuclei (black arrows) and hepatocytes with feathery degeneration (red arrows) are seen. D. Very rare foci of spotty necrosis were seen. E. Apart from this triad and the one in the trichrome stain in F, which had moderate inflammation comprising lymphocytes and macrophages, all triads were small, most without any inflammation at all. Neither collapse nor piecemeal necrosis were seen on reticulin stain. F. Trichrome stain showed only portal fibrosis. The interhepatocyte fibrosis required for brunt fibrosis stage I was not seen. Hence, one would grade this as follows: A) Chronic hepatitis (history of hepatitis B), Metavir activity index 1, Piecemeal necrosis 0, Lobular necrosis 1, Metavir fibrosis stage 1, B) Steatohepaitits, Brunt necroinflammatory grade 1, Brunt fibrosis stage 0.

=See also=
*[[Pancreas]].
*[[Gastrointestinal pathology]].
*[[Liver neoplasms]].
*[[Liver]].

=References=
{{reflist|2}}

[[Category:Gastrointestinal pathology]]
[[Category:Liver pathology]]
[[Category:Medical liver disease]]

Medical liver disease

2017-01-23T15:52:30Z

Mitchell: /* Images */

[[Image:Ground glass hepatocytes high mag cropped 2.jpg|thumb|right|[[Micrograph]] showing ground glass hepatocytes, as seen in chronic [[hepatitis B]]. [[H&E stain]].]]
This article deals with '''medical [[liver]] disease'''. An introduction to the liver and approach is found in the ''[[liver]]'' article.

Every differential in liver pathology has "drugs"<ref>{{Ref PCPBoD8|448}}</ref> -- if it isn't clearly malignancy.

Liver neoplasms are dealt with in the ''[[liver neoplasms]]'' article.

Medical liver biopsies are often non-specific, as the liver has the same appearance for many mechanisms of injury, especially when the injury is marked. The clinical history, serology and imaging are essential for proper interpretations in this domain of pathology.

=Review of liver blood work=
===Inflammation activity===
*ALT.
*AST.

===Cholestatic markers===
*ALP.
*GGT - used to assess whether the ALP is an "honest" value, elevated in cirrhosis.

===Cirrhosis/decompensation===
*PLT - low is suggestive of dysfunction.
*INR - high is bad, unless anticoagulated.

===Other===
*Bilirubin.
**Direct (AKA conjugated).
**Indirect (AKA unconjugated).

A short DDx of elevated:<ref>{{Ref PCPBoD8|441}}</ref>
*Indirect:
**[[Gilbert syndrome]].
**Crigler-Najjar syndrome type 1.
**Crigler-Najjar syndrome type 2.
*Direct:
**Rotor syndrome.
**Dubin-Johnson syndomre.

===Viral hepatitis===
*HBV DNA.
*HCV RNA.
*HBs Ag, HBs Ab, HBe Ag, HBe Ab.
*HCV Ab.

Others:
*[[Epstein-Barr virus]] (EBV).
*[[Cytomegalovirus]] (CMV) - especially in the immune incompetent.

====Hepatitis B====
Meaning & utility of the various [[Hepatitis B]] tests:<ref>URL: [http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/hepatology/hepatitis-B/ http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/hepatology/hepatitis-B/]. Accessed on: 16 May 2011.</ref><ref name=lto_hepb>URL: [http://www.labtestsonline.org/understanding/analytes/hepatitis_b/test.html http://www.labtestsonline.org/understanding/analytes/hepatitis_b/test.html]. Accessed on: 16 May 2011.</ref>
{| class="wikitable sortable" border="1"
! Test name
! Location
! Positive test
! Negative test
! Usual question
|-
| HBs Ag||Surface||Virus active||No active infection||Active infection?
|-
| HBs Ab||Surface||Exposed OR vaccinated||No exposure OR no vaccine OR loss of Ab||Immunization status?
|-
| HBe Ag||Virus core||Infect. w/ viral replication||No active infection||Active infect. w/ viral replication?
|-
| HBe Ab||Virus core||Exposed to virus||Infect. w/o antibody response OR not exposed||Immune response to infection?
|-
| HBV DNA||-||Active||Not active/no exposure||Viral load/how active?
|-
| HBc Ab||Virus core||Virus active/previous exposure||No exposure||Early active infection?
|}
Notes:
*''HBc Ab'' may test for acute (IgM) or chronic infection - dependent on specific antibody test; it is often used to look for early infection.<ref name=lto_hepb>URL: [http://www.labtestsonline.org/understanding/analytes/hepatitis_b/test.html http://www.labtestsonline.org/understanding/analytes/hepatitis_b/test.html]. Accessed on: 16 May 2011.</ref>
*''Carriers of hepatitis B'': HBs Ag +ve, HBs Ab -ve, HBc Ag -ve, HBc Ab +ve, HBe Ag -ve, HBe Ab +ve.<ref>URL: [http://labtestsonline.org/understanding/analytes/hepatitis-b/tab/test http://labtestsonline.org/understanding/analytes/hepatitis-b/tab/test]. Accessed on: 3 May 2012.</ref>

===Markers for rare liver diseases===
*Ceruloplasm - low think ''[[Wilson's disease]]''; typical value for Wilson's ~ 0.12 g/L.
**<0.20 g/L is a criteria for Wilson's disease.<ref name=pmid18556333>Diagnostic accuracy of serum ceruloplasmin in Wilson disease: determination of sensitivity and specificity by ROC curve analysis among ATP7B-genotyped subjects. Mak CM, Lam CW, Tam S. Clin Chem. 2008 Aug;54(8):1356-62. Epub 2008 Jun 12. PMID 18556333. URL: [http://www.clinchem.org/cgi/reprint/54/8/1356.pdf http://www.clinchem.org/cgi/reprint/54/8/1356.pdf]. Accessed on: 28 September 2009.</ref>
*Alpha-1 antitrypsin - if low think ''deficiency''.

===Hemosiderosis===
*Ferritin - high.
*Iron saturation - high.

Causes:
*Hemochromatosis.
*Hemolysis, chronic.
*Cirrhosis.

=Medical imaging=
Blood flow:<ref>URL: [http://insidesurgery.com/2010/12/hepatopedal-hepatofugal-flow/ http://insidesurgery.com/2010/12/hepatopedal-hepatofugal-flow/]. Accessed on: 2 December 2011.</ref>
*Hepatopedal flow = normal portal vein flow.
*Hepatofugal flow = reversed portal vein flow.

==Interventional measurements==
Wedged to free hepatic venous pressure:<ref name=pmid1864548>{{Cite journal | last1 = Bion | first1 = E. | last2 = Brenard | first2 = R. | last3 = Pariente | first3 = EA. | last4 = Lebrec | first4 = D. | last5 = Degott | first5 = C. | last6 = Maitre | first6 = F. | last7 = Benhamou | first7 = JP. | title = Sinusoidal portal hypertension in hepatic amyloidosis. | journal = Gut | volume = 32 | issue = 2 | pages = 227-30 | month = Feb | year = 1991 | doi = | PMID = 1864548 | PMC = 1378815 | URL = http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1378815/?tool=pubmed }}</ref>
*Normal = 1-4 mmHg.
**Elevated in [[portal hypertension]].

=Liver biopsy=
==Medical liver biopsy adequacy==
Liver biopsy specimens should be:<ref>{{Ref MacSween|418}}</ref>
*2.0 cm in length and contain 11-15 portal tracts,
*The core should be deeper than 1.0 cm from the liver capsule; specimens close to the capsule may lead to over grading of fibrosis.

==Reporting==
{{Main|Pathology reports}}
<pre>
Specimen, procedure:
- Diagnosis.
</pre>
The diagnosis usually contains grading and staging information, e.g. ''activity 2 /4, Laennec fibrosis stage 1 /4''.

In the context of medical liver disease:
*Grade = inflammation/activity.
*Stage = severity of fibrosis/architectural changes.

Notes:
*The term "acute" is infrequently used in liver pathology.
*In the liver: neutrophils ''is not'' acute -- unlike most elsewhere in the body.<ref>OA. September 2009.</ref>

===A microscopic checklist===
<pre>
Size of biopsy: Adequate
Fragmentation: Absent
Fibrosis: Stage 2-3/4, mostly stage 2
Fibrous septa: Present
Septa with curved contours: Present – focally only
Large droplet steatosis (% of hepatocytes): Present, moderate 60%
Ballooning of hepatocytes: Present, rare
Mallory-Denk bodies: Present, rare
Portal inflammation: Present
Interface activity: Minimal (0-1/4)
Lobular necroinflammation: Minimal
Ducts: Present in normal numbers
Duct injury: Absent
Ductular reaction: Absent
Cholestasis: Absent
Terminal hepatic venules: Present
Iron stain: Absent
Ground glass cells with routine stains: Absent
PASD for alpha-1 antitrypsin droplets: Negative
</pre>

=Viral hepatitis=
These are common. The diagnoses are based on serology. The serology is covered in the ''[[Liver_pathology#Viral_hepatitis|viral hepatitis]]'' section in the ''[[liver pathology]]'' article.

Typically classified as:<ref name=pmid8048409>{{Cite journal | title = Terminology of chronic hepatitis, hepatic allograft rejection, and nodular lesions of the liver: summary of recommendations developed by an international working party, supported by the World Congresses of Gastroenterology, Los Angeles, 1994. | journal = Am J Gastroenterol | volume = 89 | issue = 8 Suppl | pages = S177-81 | month = Aug | year = 1994 | doi = | PMID = 8048409 }}</ref><ref>URL: [http://familydoctor.org/familydoctor/en/diseases-conditions/hepatitis-b.html http://familydoctor.org/familydoctor/en/diseases-conditions/hepatitis-b.html]. Accessed on: 2 May 2012.</ref>
#Acute < 6 months duration.
#Chronic > 6 months duration.

==Hepatitis A==
*Infection is self-limited, i.e. not persistent.
**May present as ''[[fulminant hepatic necrosis]]''.
*Usually asymptomatic in children.<ref name=pmid20068336>{{cite journal |author=Jeong SH, Lee HS |title=Hepatitis A: clinical manifestations and management |journal=Intervirology |volume=53 |issue=1 |pages=15–9 |year=2010 |pmid=20068336 |doi=10.1159/000252779 |url=}}</ref>
*Serology is diagnostic.

==Hepatitis B==
:''Hepatitis B virus'', abbreviated ''HBV'', redirects here.
{{Main|Hepatitis B}}

==Hepatitis C==
{{Main|Hepatitis C}}

=Other infections=
*Hydatid disease (Hydatid cyst).
*Ascaris.
*Fasciola

==Hydatid disease==
*[[AKA]] ''hydatid cyst''.
===General===
*Etiology: ''[[Echinococcus]]''.

===Microscopic===
Features:
*Laminated wall +/- calcification.<ref name=Ref_PBPoD8_448>{{Ref PCPBoD8|448}}</ref>
*Organisms -- see ''[[Echinococcus]]''.

====Images====
<gallery>
Image:Liver_cyst_wall_-_intermed_mag.jpg | Liver cyst wall - intermed. mag. (WC)
Image:Liver_cyst_wall_-_high_mag.jpg | Liver cyst wall - high mag. (WC)
Image: Laminated liver cyst wall - intermed mag.jpg | Characteristic laminated portion - intermed. mag. (WC)
Image: Laminated liver cyst wall - high mag.jpg | Characteristic laminated portion - high mag. (WC)
</gallery>
[[www]]:
*[http://pathmicro.med.sc.edu/parasitology/hydatid-hist1.jpg Hydatid cyst (med.sc.edu)].
*[http://www.atlas.or.kr/atlas/include/viewImg.html?uid=645 Hydatid cyst (atlas.or.kr)].
*[http://casereports.bmj.com/content/2009/bcr.04.2009.1798.full Hydatid cyst (casereports.bmj.com)].

==Abscess==
A. [[File:1 ABS 1 680x512px.tif|A process replaces most of the liver parenchyma (20X).]]
 
B. [[File:2 ABS 1 680x512px.tif|Fibrinopurulent exudate apposes granulation tissue (200X).]]
 
C. [[File:3 ABS 1 680x512px.tif|Neutrophils lie in widened sinusoids (200X)..]]
 
D. [[File:4 ABS 1 680x512px.tif|Trichrome shows collagenization of spaces of Disse. Scarring about an abscess or other mass lesion should not be interpreted as reflective of the liver in general (200X).]]
 
Abscess. A. A process replaces most of the liver parenchyma. B. Fibrinopurulent exudate apposes granulation tissue. C. Neutrophils lie in widened sinusoids. D. Trichrome shows collagenization of spaces of Disse. Scarring about an abscess or other mass lesion should not be interpreted as reflective of the liver in general (LR 200X).

==Coccidiomycosis==
A. [[File:Coccidiomycosis - 1 - 40X 680x512px shot.tif|500x500px Granulomas at low power]]
 
B. [[File:Coccidiomycosis - 1 - 200X 680x513px shot.tif|500x500px Granulomas with centrally crowded cells & lady slipper macrophage nuclei]]
 
C. [[File:Coccidiomycosis - 1 - 400X 1369x1024px shot.tif|500x500px Center of previous granuloma showing pyknotic macrophage nuclei]]
 
D. [[File:Coccidiomycosis - 1 - GMS 400X 1369x1024px shot.tif|500x500px Four Coccidiomycotic spherules]]
 
Coccidiomycosis. A. Note the granulomas in otherwise undisturbed liver (UL). B. Granuloma with centrally crowded cells & lady slipper macrophage nuclei. C. Center of granuloma with pyknotic macrophage nuclei, "necrotizing". D. Organisms on GMS stain.

=Metabolic and toxic=
==Alcoholic liver disease==
===General===
*Acute and/or chronic liver changes due to excessive [[alcohol]] use - includes:
**''[[Alcoholic steatohepatitis]]'' (ASH), [[AKA]] ''alcoholic hepatitis''.<ref>URL: [http://emedicine.medscape.com/article/170539-overview http://emedicine.medscape.com/article/170539-overview]. Accessed on: 3 May 2012.</ref>
***Alcoholic hepatitis can be with minimal steatosis.<ref>STC. 6 December 2010.</ref>
**[[Steatosis]] - classically macrovescicular and centrilobular.
**Alcoholic [[cirrhosis]].

====Classic lab findings in EtOH abusers====
*AST & ALT elevated with AST:ALT=2:1.
*GGT elevated.
*MCV increased.

===Gross pathology/radiologic findings===
*Classically micronodular pattern.
**May be macronodular.

===Microscopic===
See:
*''[[Steatohepatitis]]'' section and ''[[ballooning degeneration]]'' section.

Features:
*Often zone III damage.
*Cholestatsis common, i.e. yellow staining.
**NASH (non-alcoholic steatohepatitis) usu. does not have cholestasis.<ref>STC. 6 December 2010.</ref>
*Fibrosis starts at central veins.
*Neutrophils (often helpful) -- few other things have PMNs. (???)
**Neutrophils cluster around cells with Mallory hyaline.

====Images====
A. [[File:1 etoh 3 680x512px.tif| Alcoholic hepatitis with Metavir stage IV fibrosis (advanced fibrosis/cirrhosis).]]
 
B. [[File:2 etoh 3 680x512px.tif| Alcoholic hepatitis with Metavir stage IV fibrosis (advanced fibrosis/cirrhosis).]]
 
C. [[File:3 etoh 3 680x512px.tif| Alcoholic hepatitis with Metavir stage IV fibrosis (advanced fibrosis/cirrhosis).]]
 
D. [[File:4 etoh 3 680x512px.tif| Alcoholic hepatitis with Metavir stage IV fibrosis (advanced fibrosis/cirrhosis).]]
 
E. [[File:5 etoh 3 680x512px.tif| Alcoholic hepatitis with Metavir stage IV fibrosis (advanced fibrosis/cirrhosis).]]
 
F. [[File:6 etoh 3 680x512px.tif| Alcoholic hepatitis with Metavir stage IV fibrosis (advanced fibrosis/cirrhosis).]]
 
Alcoholic hepatitis with Metavir stage IV fibrosis (advanced fibrosis/cirrhosis). A. Trichrome shows relatively non-inflamed fibrous bands, as well as [between green dots] nodules. The lack of regeneration throughout might have precluded a diagnosis of cirrhosis, but stage IV fibrosis under the Metavir system is justified. B. Reticulin shows regenerative nodules [left] with mostly two or more nuclei between black lines juxtaposed to non-regenerative hepatocytes on the right, without piecemeal necrosis. C. Regenerative nodules show occasional neutrophils [red arrow] and cytoplasmic tufts of ballooned cells, sometimes possibly Mallory hyalin [green arrows]. D. Triads (note vein [green arrow], artery [yellow arrow], and interlobular bile duct [blue arrow]) generally showed little or no interface hepatitis, even when expanded by fibrosis and inflamed. E. Occasional foci of spotty necrosis were seen. F. This edge of an inflamed triads shows neutrophils about proliferated bile ducts [red arrows], as well as Mallory-Denk bodies [blue arrows].

A. [[File:1 etoh 4 680x512px.tif| Cirrhosis in an alcoholic.]]
 
B. [[File:2 etoh 4 680x512px.tif| Cirrhosis in an alcoholic.]]
 
C. [[File:3 etoh 4 680x512px.tif| Cirrhosis in an alcoholic.]]
 
D. [[File:4 etoh 4 680x512px.tif| Cirrhosis in an alcoholic.]]
 
E. [[File:5 etoh 4 680x512px.tif| Cirrhosis in an alcoholic.]]
 
F. [[File:6 etoh 4 680x512px.tif| Cirrhosis in an alcoholic.]]

Definite cirrhosis in an alcoholic. A. Hepatocyte free bands parse tissue, with occasional definite islands [arrows]. B. Trichrome establishes blue fibrosis about isles [arrows]. C. Reticulin stain shows nodules with regeneration, wherein a large proportion of them are at least two nuclei thick [arrows]. D. Bile duct proliferation can be difficult, sometimes mimicking cholangiocarcinoma. Follow the double headed arrows to see how the ductules can be seen to proliferate from a single sources, with all ducts being complete, without necrotic epithelial cells. E. PAS with distase can help, as cholangiocarcinoma generally lacks the red rim of proliferating bile ductules [arrows]; again note the connections that can be made between the ductule openings by the blue double headed arrows. The cyan double headed arrows show general parallelism, consistent with uniform directionality induced by extrinsic force, not a neoplastic spread. F. Trichrome shows the most difficult focus. Double headed arrows display the connectivity seen before of the proliferated bile ductules. Note that numerous pairs of adjacent perpendicular glands without a head to foot appearance are not seen that would indicate the disorderly spread of cholangiocarcinoma.

{|
[[File:1 ALC 2 680x512px.tif|Expanded, inflamed triads with increased bile duct/vascular openings. Mild steatosis (40X).]]
[[File:2 ALC 2 680x512px.tif|Trichrome stain shows periportal fibrosis [red arrowheads] (200X).]]
 
[[File:3 ALC 2 680x512px.tif|PAS with diastase stain shows proliferated bile ductules [blue arrowheads] in stroma with mixed inflammatory infiltrate (400X)]]
[[File:4 ALC 2 680x512px.tif|Neutrophils about ballooned hepatocyte (satellitosis) [yellow arrowheads]. Councilman bodies [green arrowheads] (400X).]]
|}
Alcoholic hepatitis without cirrhosis. No history of viral disease. AMA negative. Expanded, inflamed triads with increased bile duct/vascular openings. Mild steatosis (UL 40X). Trichrome stain shows periportal fibrosis [red arrowheads] (UR 200X). PAS with diastase stain shows proliferated bile ductules [blue arrowheads] in stroma with mixed inflammatory infiltrate (LL 400X) Neutrophils about ballooned hepatocyte (satellitosis) [yellow arrowheads]. Councilman bodies [green arrowheads] (LR 400X).

Notes:
*If portal inflammatory infiltrates more than mild, r/o other causes i.e. [[viral hepatitis]].
*Mallory bodies once thought to be characteristic; now considered non-specific and generally poorly understood.<ref>{{cite journal |author=Jensen K, Gluud C |title=The Mallory body: theories on development and pathological significance (Part 2 of a literature survey) |journal=Hepatology |volume=20 |issue=5 |pages=1330-42 |year=1994 |month=November |pmid=7927269 |doi= |url=}}</ref>
*Some consider ''alcoholic liver disease'' a clinical diagnosis, i.e. as a pathologist one does not diagnose it.<ref>MG. September 2009.</ref>

==Non-alcoholic fatty liver disease==
*Abbreviated ''NAFLD''.
*Fatty liver that is not due to alcohol; includes obesity-related fatty liver, metabolic disease/diabetes-related fatty liver.

===NASH===
*Non-alcoholic steatohepatitis - see ''steatohepatitis'' section.
*Histologically indistinguishable from ASH.
*NASH is a ''clinical diagnosis'' based on exclusion of alcohol.

==Steatohepatitis==
{{Main|Steatohepatitis}}

=Autoimmune=
==Autoimmune hepatitis==
*Abbreviated ''AIH''.
{{Main|Autoimmune hepatitis}}

==Primary biliary cirrhosis==
*Abbreviated PBC.
{{Main|Primary biliary cirrhosis}}

==Autoimmune hepatitis with obstruction - combined changes==
{|
[[File:1 AIH OBS 1.tif|Low power shows inflammation; portal triads, lobules, central veins cannot be distinguished (40X).]]
[[File:2 AIH OBS 1.tif|Trichrome shows central venous sclerosis (red arrowhead), periportal fibrosis (green arrowhead), & space of Disse collagenization (yellow arrowhead); juxtaposition of central vein & portal tract indicates collapse, no definite bridging was seen (100X)]]
 
[[File:3 AIH OBS 1.tif|Central vein is inflamed with a rare plasma cell (cyan arrowhead) (400X).]]
[[File:4 AIH OBS 1.tif|Interface hepatitis with plasma cells (yellow arrows) and ballooned hepatocytes (red arrows). Lobule is disorganized (400X).]]
 
[[File:5 AIH OBS 1.tif|Proliferating bile ductules (blue arrows) with occasional neutrophils (fucsia arrows), indicative of obstruction, but not acute cholangitis, which requires inflamed bile duct itself, best diagnosed with associated blood vessel (400X).]]
[[File:6 AIH OBS 1.tif|Rare distorted rosettes with greenish brown strands of bile (left arrow) or bile plugs (right arrow) (400X).]]
|}
Patient with SLE and obstructive jaundice that resolved with apparent passage of stone. Low power shows inflammation; portal triads, lobules, central veins cannot be distinguished (left row 1 40X). Trichrome shows central venous sclerosis (red arrowhead), periportal fibrosis (green arrowhead), & space of Disse collagenization (yellow arrowhead); juxtaposition of central vein & portal tract indicates collapse, no definite bridging was seen (right row 1 100X). Central vein is inflamed with a rare plasma cell (cyan arrowhead) (left row 2 400X). Interface hepatitis with plasma cells (yellow arrows) and ballooned hepatocytes (red arrows). Lobule is disorganized (right row 2 400X). Proliferating bile ductules (blue arrows) with occasional neutrophils (fucsia arrows), indicative of obstruction, but not acute cholangitis, which requires inflamed bile duct itself, best diagnosed with associated blood vessel (left row 3 400X). Rare distorted rosettes with greenish brown strands of bile (left arrow) or bile plugs (right arrow) (right row 3 400X).

==Autoimmune hepatitis-primary biliary cirrhosis overlap syndrome==
*Abbreviation ''AIH-PBC OS''.
===General===
Epidemiology:
*Rare.

Serology:<ref name=pmid19491855>{{Cite journal | last1 = Muratori | first1 = P. | last2 = Granito | first2 = A. | last3 = Pappas | first3 = G. | last4 = Pendino | first4 = GM. | last5 = Quarneti | first5 = C. | last6 = Cicola | first6 = R. | last7 = Menichella | first7 = R. | last8 = Ferri | first8 = S. | last9 = Cassani | first9 = F. | title = The serological profile of the autoimmune hepatitis/primary biliary cirrhosis overlap syndrome. | journal = Am J Gastroenterol | volume = 104 | issue = 6 | pages = 1420-5 | month = Jun | year = 2009 | doi = 10.1038/ajg.2009.126 | PMID = 19491855 }}</ref>
*AMA +ve.
*Anti-dsDNA +ve.

===Microscopic===
:See: ''[[autoimmune hepatitis]]'' and ''[[primary biliary cirrhosis]]''.
{|
[[File:1 AIH PBC 1 680x512px.tif|Expanded portal tracts with fuzzy edges (40X).]]
[[File:2 AIH PBC 1 680x512px.tif|Interface hepatitis with plasma cells (400X).]]
 
[[File:3 AIH PBC 1 680x512px.tif|Loose granuloma (400X).]]
[[File:4 AIH PBC 1 680x512px.tif|Damaged bile duct (400X).]]
|}

AIH/PBC overlap. AMA & ANA positive with Alkaline phosphatase > 2 upper limit of normal & one ALT > 5 times upper limit of normal. Expanded portal tracts with fuzzy edges (UL 40X). IInterface hepatitis with plasma cells (UR 400X). Loose granuloma (LL 400X). Damaged bile duct (LR 400X).

==Primary sclerosing cholangitis==
*Abbreviated ''PSC''.
{{Main|Primary sclerosing cholangitis}}

=Hereditary=
==Caroli disease==
===General===
*Genetic disease.
**Frequently associated with [[autosomal recessive polycystic kidney disease]] (ARPKD).<ref name=omim263200>{{OMIM|263200}}</ref>
**May be seen in isolation.<ref name=omim600643>{{OMIM|600643}}</ref>

Clinical:<ref name=pmid17461493>{{Cite journal | last1 = Yonem | first1 = O. | last2 = Bayraktar | first2 = Y. | title = Clinical characteristics of Caroli's syndrome. | journal = World J Gastroenterol | volume = 13 | issue = 13 | pages = 1934-7 | month = Apr | year = 2007 | doi = | PMID = 17461493 }}</ref>
*Recurrent [[cholangitis]].
*Recurrent [[cholelithiasis]].
*[[Cholangiocarcinoma]]<ref name=pmid17461492>{{Cite journal | last1 = Yonem | first1 = O. | last2 = Bayraktar | first2 = Y. | title = Clinical characteristics of Caroli's disease. | journal = World J Gastroenterol | volume = 13 | issue = 13 | pages = 1930-3 | month = Apr | year = 2007 | doi = | PMID = 17461492 }}</ref> - seen in ~7% of cases.<ref name=pmid15347876>{{Cite journal | last1 = Karim | first1 = AS. | title = Caroli's disease. | journal = Indian Pediatr | volume = 41 | issue = 8 | pages = 848-50 | month = Aug | year = 2004 | doi = | PMID = 15347876 }}</ref>

Note:
*''Caroli syndrome'' = Caroli disease + congenital hepatic fibrosis.<ref name=pmid15888616>{{Cite journal | last1 = Brancatelli | first1 = G. | last2 = Federle | first2 = MP. | last3 = Vilgrain | first3 = V. | last4 = Vullierme | first4 = MP. | last5 = Marin | first5 = D. | last6 = Lagalla | first6 = R. | title = Fibropolycystic liver disease: CT and MR imaging findings. | journal = Radiographics | volume = 25 | issue = 3 | pages = 659-70 | month = | year = | doi = 10.1148/rg.253045114 | PMID = 15888616 | URL = http://radiographics.rsna.org/content/25/3/659.long }}</ref>

===Gross===
*Dilated bile ducts.<ref name=omim263200/>

===Microscopic===
Features:<ref name=pmid17461493/>
*Dilated bile ducts.
*Periductal fibrosis. (???)
*+/-Fibrosis.

Image:
*[http://www.meddean.luc.edu/lumen/MedEd/orfpath/11-3-10.jpg Caroli disease (meddean.luc.edu)].<ref>URL: [http://www.meddean.luc.edu/lumen/MedEd/orfpath/develop.htm http://www.meddean.luc.edu/lumen/MedEd/orfpath/develop.htm]. Accessed on: 1 December 2011.</ref>

==Hereditary hemochromatosis==
:''For secondary causes see [[secondary hemochromatosis]]''.
{{Main|Hereditary hemochromatosis}}

==Wilson disease==
{{Main|Wilson's disease}}

==Alpha-1 antitrypsin deficiency==
*[[AKA]] ''alpha1-antiprotease inhibitor deficiency''.
{{Main|Alpha-1 antitrypsin deficiency }}

=Other=
==Budd-Chiari syndrome==
*[[AKA]] ''hepatic vein obstruction''.
===General===
*Hepatic outflow obstruction.

Clinical triad:<ref name=pmid21573256>{{Cite journal | last1 = Fox | first1 = MA. | last2 = Fox | first2 = JA. | last3 = Davies | first3 = MH. | title = Budd-Chiari syndrome--a review of the diagnosis and management. | journal = Acute Med | volume = 10 | issue = 1 | pages = 5-9 | month = | year = 2011 | doi = | PMID = 21573256 }}</ref>
*Ascites.
*Abdominal pain.
*Hepatomegaly.

Etiology:
*~50% have a [[myeloproliferative disease]].<ref name=pmid18814079>{{Cite journal | last1 = Plessier | first1 = A. | last2 = Valla | first2 = DC. | title = Budd-Chiari syndrome. | journal = Semin Liver Dis | volume = 28 | issue = 3 | pages = 259-69 | month = Aug | year = 2008 | doi = 10.1055/s-0028-1085094 | PMID = 18814079 }}</ref>
*May be due to mass effect from a tumour.

Clinical DDx:
*[[Hepatic veno-occlusive disease]].

===Microscopic===
Features:<ref name=pmid17569137>{{Cite journal | last1 = Aydinli | first1 = M. | last2 = Bayraktar | first2 = Y. | title = Budd-Chiari syndrome: etiology, pathogenesis and diagnosis. | journal = World J Gastroenterol | volume = 13 | issue = 19 | pages = 2693-6 | month = May | year = 2007 | doi = | PMID = 17569137 | url=http://www.wjgnet.com/1007-9327/full/v13/i19/2693.htm }}</ref>
*Sinusoidal dilation in zone III (congestion).
*+/-Hepatocyte drop-out.
*+/-Centrilobular fibrosis.

DDx congestion:
*Congestive heart failure ([[congestive hepatopathy]]).
*Constrictive pericarditis.

==Vanishing bile duct syndrome==
*[[AKA]] ''bile duct loss'', [[AKA]] ''ductopenia''.<ref name=pmid11521176/>
===General===
*Fatal.

DDx:<ref name=pmid18242505/>
*[[Primary biliary cirrhosis]].
*[[Primary sclerosing cholangitis]].
*[[GVHD]].<ref name=pmid7994249>{{Cite journal | last1 = Yeh | first1 = KH. | last2 = Hsieh | first2 = HC. | last3 = Tang | first3 = JL. | last4 = Lin | first4 = MT. | last5 = Yang | first5 = CH. | last6 = Chen | first6 = YC. | title = Severe isolated acute hepatic graft-versus-host disease with vanishing bile duct syndrome. | journal = Bone Marrow Transplant | volume = 14 | issue = 2 | pages = 319-21 | month = Aug | year = 1994 | doi = | PMID = 7994249 }}</ref>
*[[Drug-induced liver disease|Drugs]].<ref name=pmid11352118>{{Cite journal | last1 = Chitturi | first1 = S. | last2 = Farrell | first2 = GC. | title = Drug-induced cholestasis. | journal = Semin Gastrointest Dis | volume = 12 | issue = 2 | pages = 113-24 | month = Apr | year = 2001 | doi = | PMID = 11352118 }}</ref>
*Chronic rejection.<ref name=pmid11521176>{{Cite journal | last1 = Inomata | first1 = Y. | last2 = Tanaka | first2 = K. | title = Pathogenesis and treatment of bile duct loss after liver transplantation. | journal = J Hepatobiliary Pancreat Surg | volume = 8 | issue = 4 | pages = 316-22 | month = | year = 2001 | doi = 10.1007/s0053410080316 | PMID = 11521176 }}</ref>

===Microscopic===
Features:<ref name=pmid18242505>{{Cite journal | last1 = Reau | first1 = NS. | last2 = Jensen | first2 = DM. | title = Vanishing bile duct syndrome. | journal = Clin Liver Dis | volume = 12 | issue = 1 | pages = 203-17, x | month = Feb | year = 2008 | doi = 10.1016/j.cld.2007.11.007 | PMID = 18242505 }}</ref>
*Loss of intrahepatitic bile ducts - '''key feature'''.
*Cholestasis.

Note:
*May occur without fibrosis and inflammation; thus, can be easy to miss.

===IHC===
*[[CK7]] -ve.
**Marks bile ducts.

==Extrahepatic biliary obstruction==
{|
[[File:1 OBS 3 680x512px.tif|Sinusoidal dilatation, circular spaces of hepatocytes, small portal triads(40X).]]
[[File:2 OBS 3 680x512px.tif|Bile in hepatocytes about central vein & in plugs in canaliculi [yellow arrowhead] (400X).]]
 
[[File:3 OBS 3 680x512px.tif|Trichrome shows fibrosis about central vein (400X).]]
[[File:4 OBS 3 680x512px.tif|PAS with diastase shows portal triads with mild edema and chronic inflammation, without tortuous bile duct (400X).]]
|}
Early extrahepatic biliary obstruction, demonstrated radiographically, transient, with rise in bilirubin, alkaline phosphatase, and transaminases. Pure canalicular cholestasis near terminal hepatic venules also seen in acute hepatitis, drug reactions, benign recurrent cholestasis, pregnancy, sepsis, & lymphomas. Sinusoidal dilatation, circular spaces of hepatocytes, small portal triads(UL 40X). Bile in hepatocytes about central vein & in plugs in canaliculi [yellow arrowhead] (UR 400X). Trichrome shows fibrosis about central vein (LL 400X). PAS with diastase shows portal triads with mild edema and chronic inflammation, without tortuous bile duct (LR 400X).

{|
[[File:1 OBS 2 680x512px.tif|Expanded inflamed portal triads, swollen hepatocytes (40X)]]
[[File:2 OBS 2 680x512px.tif|Edematous stroma, proliferating ductules [yellow arrowheads], PAS-D macrophages [red arrowhead] (PAS with diastasse, 200X)]]
 
[[File:3 OBS 2 680x512px.tif|Disordered, often swollen hepatocytes,some with feathery degeneration (net like spaces in cytoplasm [blue arrowhead], rare Councilman body [green arrowhead] (400X)]]
[[File:4 OBS 2 1360x1024px.tif|Bile in hepatocytes [cyan arrrowhead] & in canaliculi [purple arrowheads]. Empty acinar spaces bounded by hepatocytes [orange arrowhead] (400X, higher pixel),]]
|}
Changes of extrahepatic biliary obstruction, months duration. Expanded inflamed portal triads, swollen hepatocytes (UL 40X). Edematous stroma, proliferating ductules [yellow arrowheads], PAS-D macrophages [red arrowhead] (UR PAS with diastasse, 200X). Disordered, often swollen hepatocytes,some with feathery degeneration (net like spaces in cytoplasm) [blue arrowhead], rare Councilman body [green arrowhead] (LL 400X). Bile in hepatocytes [cyan arrrowhead] & in canaliculi [purple arrowheads]. Empty acinar spaces bounded by hepatocytes [orange arrowhead] (LR 400X).
{|
[[File:1 Bd obs 4 680x512px.tif|Expanded, light colored portal triads (arrows)(20X).]]
[[File:2 Bd obs 4 680x512px.tif|Proliferating bile ductules (cyan arrows) with neutrophils (yellow arrows), not specific for acute cholangitis, of assistance with large bile duct obstruction (400X)..]]
 
[[File:3 Bd obs 4 680x512px.tif|Uninflamed interlobular duct (yellow arrow) with, accompanying blood vessel (red arrow) (400X)]]
[[File:4 Bd obs 4 680x512px.tif|Bile infarct with pyknotic nuclei (arrows)(400X).]]
 
[[File:5 Bd obs 4 680x512px.tif|Bile (arrow) in interlobular bile duct with disordered nuclei (400X).]]
[[File:6 Bd obs 4 680x512px.tif|Bile plugs in cannaliculi (red arrows), feathery degeneration producing foamy macrophage like hepatocytes (yellow arrows)(400X).]]
|}
Large bile duct obstruction. Expanded, light colored portal triads (arrows)(Row 1 Left 20X). Proliferating bile ductules (cyan arrows) with neutrophils (yellow arrows), not specific for acute cholangitis, of assistance with large bile duct obstruction (Row 1 Right 400X). Uninflamed interlobular duct (yellow arrow) with, accompanying blood vessel (red arrow) (Row 2 Left 400X). Bile infarct with pyknotic nuclei (arrows)(Row 2 Right 400X). Bile (arrow) in interlobular bile duct with disordered nuclei (Row 3 Left 400X). Bile plugs in cannaliculi (red arrows), feathery degeneration producing foamy macrophage-like hepatocytes (yellow arrows)(Row 3 Right 400X).

==Congestive hepatopathy==
===General===
*Liver failure due to (right) heart failure.
*AKA ''cardiac cirrhosis'' - a term used by clinicians.
**Generally, it does not satisfy pathologic criteria for cirrhosis.<ref>URL: [http://emedicine.medscape.com/article/151792-overview http://emedicine.medscape.com/article/151792-overview]. Accessed on: 17 June 2010.</ref>

===Gross===
*"Nutmeg" liver - yellow spotted appearance.

===Microscopic===
Features:<ref>URL: [http://emedicine.medscape.com/article/151792-diagnosis http://emedicine.medscape.com/article/151792-diagnosis]. Accessed on: 17 June 2010.</ref>
*Zone III atrophy.
*Portal venule (central vein) distension.
*Perisinusoidal fibrosis - progresses to centrilobular fibrosis and then diffuse fibrosis.
*Dilation of sinusoids in ''all'' zone III areas - '''key feature'''.<ref>Suggested by OA. September 2009.</ref>

DDx:
*[[Hemangioma of the liver]] - should be focal lesion.

====Images====
<gallery>
Image:Congestive_hepatopathy_high_mag.jpg | Mild congestive hepatopathy. (WC)
</gallery>
{|
[[File:1 CEN NEC 1 680x512px.tif|PAS without diastase shows ovoids of necrosis {40X).]]
[[File:2 CEN NEC 1 680x512px.tif|Necrosis with central vein [yellow arrowhead], inflammatory cells, residual Councilman body [green arrowhead], and hepatocyte with mitotic figure [red arrowhead] (400X).]]
 
[[File:3 CEN NEC 1 680x512px.tif|Trichrome highlights fibrosis about central vein [yellow arrowhead] & shows beginning scar formation [green arrowheads]. Note residual atrophic hepatocytes [blue arrowheads] (400X).]]
[[File:4 CEN NEC 1 680x512px.tif|Portal triads are largely unaffected (400X).]]
|}
Centrilobular necrosis (seen in circulatory failure and with toxins/drugs). PAS without diastase shows ovoids of necrosis {UL 40X). Necrosis with central vein [yellow arrowhead], inflammatory cells, residual Councilman body [green arrowhead], and hepatocyte with mitotic figure [red arrowhead] (UR 400X). Trichrome highlights fibrosis about central vein [yellow arrowhead] & shows beginning scar formation [green arrowheads]. Note residual atrophic hepatocytes [blue arrowheads] (LL 400X). Portal triads are largely unaffected (LR 400X)

{|
[[File:1 CHF 1 680x512px.tif|Dilated and undilated sinusoidal regions (40X).]]
[[File:2 CHF 1 680x512px.tif|Thrombi in sinusoids; glycogenated nuclei likely reflect patient’s diabetes mellitus (400X).]]
 
[[File:3 CHF 1 680x512px.tif|Dilated portal vein (400X).]]
[[File:4 CHF 1 680x512px.tif|Reticulin shows collapse (thick black lines) as well as a dilated portal vein (200X).]]
 
[[File:5 CHF 1 680x512px.tif|Trichrome shows space of Disse collagenization (pericellular fibrosis) (200X).]]
[[File:6 CHF 1 680x512px.tif|Trichrome shows periportal fibrosis; no bridging was seen (200X).]]
|}
Patient with congestive heart failure and stage I fibrosis. Dilated and undilated sinusoidal regions (left row 1 40X). Thrombi in sinusoids; glycogenated nuclei likely reflect patient’s diabetes mellitus (right row 1 400X). Dilated portal vein (left row 2 400X). Reticulin shows black lines of bridging, too thick for collapse (right row 2 200X). Trichrome shows space of Disse collagenization (pericellular fibrosis) (left row 3 200X). Trichrome shows bridge beginning off to right; when it is more than a mere spike, it is a bridge (right row 3 200X).

==Drug-induced liver disease==
*[[AKA]] ''drug-induced liver toxicity''.
{{Main|Drug-induced liver disease}}

==Focal nodular hyperplasia==
*Abbreviated ''FNH''.
{{Main|Focal nodular hyperplasia}}

==Nodular regenerative hyperplasia==
===General===
*Associated with renal transplants, [[bone marrow transplant]]s and [[vasculitides]].<ref name=Ref_PBoD922>{{Ref PBoD|922}}</ref>
*Can lead to [[portal hypertension]] and many of the associated complications.<ref name=pmid22554152>{{Cite journal | last1 = Bissonnette | first1 = J. | last2 = Généreux | first2 = A. | last3 = Côté | first3 = J. | last4 = Nguyen | first4 = B. | last5 = Perreault | first5 = P. | last6 = Bouchard | first6 = L. | last7 = Pomier-Layrargues | first7 = G. | title = Hepatic hemodynamics in 24 patients with nodular regenerative hyperplasia and symptomatic portal hypertension. | journal = J Gastroenterol Hepatol | volume = 27 | issue = 8 | pages = 1336-40 | month = Aug | year = 2012 | doi = 10.1111/j.1440-1746.2012.07168.x | PMID = 22554152 }}
</ref>

====Etiology====
*Arterial hypervascularity secondary to loss of hepatic vein radicles (loss of central venule in hepatic lobule).<ref name=Ref_PBoD922>{{Ref PBoD|922}}</ref>

ASIDE: radicle = ramulus - smallest branch or vessel or nerve.<ref name=Dorlands2>Dorland's Medical Dictionary. 30th Ed.</ref>

===Gross===
*Diffuse nodularity - whole liver.

===Microscopic===
Features:<ref name=Ref_PBoD922>{{Ref PBoD|922}}</ref>
*"Plump" hepatocytes surrounded by atrophic ones.
*No fibrosis.

==Sinuosoidal obstruction syndrome==
*May be referred to as ''Hepatic veno-occlusive disease''.<ref name=pmid11928077>{{Cite journal | last1 = DeLeve | first1 = LD. | last2 = Shulman | first2 = HM. | last3 = McDonald | first3 = GB. | title = Toxic injury to hepatic sinusoids: sinusoidal obstruction syndrome (veno-occlusive disease). | journal = Semin Liver Dis | volume = 22 | issue = 1 | pages = 27-42 | month = Feb | year = 2002 | doi = 10.1055/s-2002-23204 | PMID = 11928077 }}.</ref>
===General===
*Term for obstruction due to toxicity from a chemotherapeutic agent.<ref name=pmid16393276>{{Cite journal | last1 = Helmy | first1 = A. | title = Review article: updates in the pathogenesis and therapy of hepatic sinusoidal obstruction syndrome. | journal = Aliment Pharmacol Ther | volume = 23 | issue = 1 | pages = 11-25 | month = Jan | year = 2006 | doi = 10.1111/j.1365-2036.2006.02742.x | PMID = 16393276 }}</ref><ref name=pmid17569137>{{Cite journal | last1 = Aydinli | first1 = M. | last2 = Bayraktar | first2 = Y. | title = Budd-Chiari syndrome: etiology, pathogenesis and diagnosis. | journal = World J Gastroenterol | volume = 13 | issue = 19 | pages = 2693-6 | month = May | year = 2007 | doi = | PMID = 17569137 | url=http://www.wjgnet.com/1007-9327/full/v13/i19/2693.htm }}</ref>

Clinical DDx:
*[[Budd-Chiari syndrome]].

===Microscopic===
Features:<ref name=pmid17569137>{{Cite journal | last1 = Aydinli | first1 = M. | last2 = Bayraktar | first2 = Y. | title = Budd-Chiari syndrome: etiology, pathogenesis and diagnosis. | journal = World J Gastroenterol | volume = 13 | issue = 19 | pages = 2693-6 | month = May | year = 2007 | doi = | PMID = 17569137 | url=http://www.wjgnet.com/1007-9327/full/v13/i19/2693.htm }}</ref>
*Subendothelial swelling in hepatic venules.

Negatives:
*No thrombosis.

==Ascending Cholangitis (Acute Cholangitis)==
===General===
*Term for infection of bile ducts, usually due to obstruction

Clinical DDx:

===Microscopic===
====Images====

A. [[File:1 asc chol 1 680x512px.tif|Rounded, clear (edematous) portal tracts (arrows) separated by hepatocytes with dilated sinusoids (Row 1 Left 40X).]]
 
B. [[File:2 asc chol 1 680x512px.tif|Neutrophils about hepatocytes (arrows) have spilled into the lobule from a portal tract (Row 1 Right 200X).]]
 
C. [[File:3 asc chol 1 680x512px.tif|Proliferated bile ductules (arrows) bearing neutrophils within epithelium and lumens are features of obstruction that should prompt a search for interlobular ducts with acute inflammation (Row 2 Left 400X).]]
 
D. [[File:4 asc chol 1 680x512px.tif|The epithelium of the ducts can be severely degenerated. Neutrophils (cyan arrows) invade epithelium of an interlobular duct that are recognizable mainly as a circle of rounded nuclei; the associated arteriole (red arrow) should be identified to ensure an interlobular duct is being evaluated. Note the proliferated bile ductules (blue arrows) (Row 2 Right 400X).]]
 
E. [[File:5 asc chol 1 680x512px.tif|A PAS without diastase stain colors the arteriole (blue arrow), as well as the rim of the interlobular duct within which lies a neutrophil (cyan arrow) (Row 2 Right 400X). .]]
 
F. [[File:6 asc chol 1 680x512px.tif|A PAS with diastase stain colors the arteriole (red arrow), as well as the rim of the interlobular duct within which lies a neutrophil (cyan arrow) (Row 1 Right 400X)]]
 
Acute cholangitis in a patient with multiple bile duct procedures. After the biopsy, removal of bile duct stones released pus. A. Rounded, clear (edematous) portal tracts (arrows) separated by hepatocytes with dilated sinusoids. B. Neutrophils about hepatocytes (arrows) have spilled into the lobule from a portal tract. C, Proliferated bile ductules (arrows) bearing neutrophils within epithelium and lumens are features of obstruction that should prompt a search for interlobular ducts with acute inflammation. D. The epithelium of the ducts can be severely degenerated. Neutrophils (cyan arrows) invade epithelium of an interlobular duct that are recognizable mainly as a circle of rounded nuclei; the associated arteriole (red arrow) should be identified to ensure an interlobular duct is being evaluated. Note the proliferated bile ductules (blue arrows). E. A PAS without diastase stain colors the arteriole (blue arrow), as well as the rim of the interlobular duct within which lies a neutrophil (cyan arrow). F. A PAS with diastase stain colors the arteriole (red arrow), as well as the rim of the interlobular duct within which lies a neutrophil (cyan arrow).

A.[[File:1 Sep Acu Cho 1 680x512px.tif|Low power shows variably sized inflamed portal tracts (40X)]]
 
B. [[File:2 Sep Acu Cho 1 680x512px.tif|Trichrome shows dilated sinusoids and space of Disse collagenization (200X)]]
 
C. [[File:3 Sep Acu Cho 1 680x512px.tif|Inflammatory focus with macrophages and neutrophils (400X).]]
 
D. [[File:4 Sep Acu Cho 1 680x512px.tif|PAS with diastase shows proliferated bile ductules at edge of triad with neutrophils, which should not be used to make a definite diagnosis of acute cholangitis (400X).]]
 
E. [[File:5 Sep Acu Cho 1 680x512px.tif|PAS without diastase showing acutely inflamed bile duct, with accompanying blood vessel of similar size, diagnostic of acute cholangitis (400X).]]
 
F. [[File:6 Sep Acu Cho 1 680x512px.tif|PAS with diastase showing neutrophil in bille duct lumen, diagnostic of acute cholangitis (400X).]]
 
Patient with sepsis and acute cholangitis. A. Low power shows variably sized inflamed portal tracts. B. Trichrome shows dilated sinusoids and space of Disse collagenization. C. Inflammatory focus with macrophages and neutrophils. D. PAS with diastase shows proliferated bile ductules at edge of triad with neutrophils, which should not be used to make a definite diagnosis of acute cholangitis. E. PAS without diastase showing acutely inflamed bile duct, with accompanying blood vessel of similar size, diagnostic of acute cholangitis. F. PAS with diastase showing neutrophil in bille duct lumen, diagnostic of acute cholangitis.

==Polycystic kidney disease and the liver==
{{Main|Cystic kidney disease}}
===General===
Complications of PKD in the liver:<ref>{{Ref MacSween|174-5}}</ref>
#Infected cyst.
#Cholangiocarcinoma.
#Cholestasis/obstruction due to duct compression.<ref>URL: [http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=9184868 http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=9184868]. Accessed on: 23 September 2009.</ref>

Cysts:
*Cysts in the liver, like the kidney, are thought to enlarge with age.

===Microscopic===
Features:<ref>{{Ref MacSween|176}}</ref>
*''Von Meyenburg complexes'' ([[bile duct hamartoma]]):
**Cluster of dilated ducts with "altered" bile.
**Surrounded by collagenous stroma.
**Separate from the portal areas.<ref>Meyenburg complex. Stedman's Medical Dictionary. 27th Ed.</reF>

Images:
*[http://commons.wikimedia.org/wiki/File:Von_Meyenburg_complex_low_mag.jpg Von Meyenburg complex - bile duct hamartoma (WC)].
*[http://commons.wikimedia.org/wiki/File:Bile_duct_hamartoma_intermed_mag.jpg Bile duct hamartoma (WC)].

Notes:
*Appearance on ultrasound<ref name=pmid17287178>Bile duct hamartomas--the von Meyenburg complex. Salles VJ, Marotta A, Netto JM, Speranzini MB, Martins MR. Hepatobiliary Pancreat Dis Int. 2007 Feb;6(1):108-9. PMID 17287178.</ref> and CT (hypodense)<ref name=pmid19294869>[The von Meyenburg complex] Schwab SA, Bautz W, Uder M, Kuefner MA. Rontgenpraxis. 2008;56(6):241-4. German. PMID 19294869.</ref> - similar to metastases.

==Peliosis hepatis==
===General===
*Associated with:
**Infections.
**Malignancy.
**Other stuff.
*Rarely biopsied.

===Microscopic===
Features:
*Cyst lined by endothelium.
**Usu. incomplete.
*Blood.
{|
[[File:1 PEL 1 680x512px.tif|Hemorrhage at left end, dilated sinusoids elsewhere (20X).]]
[[File:2 PEL 1 680x512px.tif|Ramifying dilated sinusoidal spaces (100X).]]
 
[[File:3 PEL 1 680x512px.tif|PAS with diastase shows flat lining (400X).]]
[[File:4 PEL 1 680x512px.tif|Necrotic hepatocytes in cords, presumably due to pressure (400X).]]
|}
Peliosis hepatis. Hemorrhage at left end, dilated sinusoids elsewhere (UL 20X). Ramifying dilated sinusoidal spaces (UR 100X). PAS with diastase shows flat lining (LL 400X). Necrotic hepatocytes in cords, presumably due to pressure (LR 400X).

==Total parenteral nutrition==
*Abbreviated ''TPN''.

===General===
*Indication: short gut syndrome, others.

===Microscopic===
Variable - may range from: steatosis, steatohepatitis, cholestasis, fibrosis and cirrhosis.<ref name=pmid16766237>{{cite journal |author=Guglielmi FW, Boggio-Bertinet D, Federico A, ''et al.'' |title=Total parenteral nutrition-related gastroenterological complications |journal=Dig Liver Dis |volume=38 |issue=9 |pages=623–42 |year=2006 |month=September |pmid=16766237 |doi=10.1016/j.dld.2006.04.002 |url=}}</ref>

Features (classic):<ref>{{Cite journal | last1 = Li | first1 = SJ. | last2 = Nussbaum | first2 = MS. | last3 = McFadden | first3 = DW. | last4 = Gapen | first4 = CL. | last5 = Dayal | first5 = R. | last6 = Fischer | first6 = JE. | title = Addition of glucagon to total parenteral nutrition (TPN) prevents hepatic steatosis in rats. | journal = Surgery | volume = 104 | issue = 2 | pages = 350-7 | month = Aug | year = 1988 | doi = | PMID = 3135627 }}</ref><ref>{{Cite journal | last1 = Stanko | first1 = RT. | last2 = Nathan | first2 = G. | last3 = Mendelow | first3 = H. | last4 = Adibi | first4 = SA. | title = Development of hepatic cholestasis and fibrosis in patients with massive loss of intestine supported by prolonged parenteral nutrition. | journal = Gastroenterology | volume = 92 | issue = 1 | pages = 197-202 | month = Jan | year = 1987 | doi = | PMID = 3096806 }}
</ref>
*[[Steatosis]] (periportal) - early.
*Cholestasis - late.

==Giant cell hepatitis==
*[[AKA]] ''neonatal giant cell hepatitis''.

:See: ''[[Giant cell hepatitis]]''.

==Hepatic amyloidosis==
{{Main|Amyloidosis}}
*[[AKA]] ''liver amyloidosis''.
*[[AKA]] ''amyloidosis of the liver''.
===General===
*Diffuse abundant amyloid within the space of Disse is associated with [[portal hypertension]].<ref name=pmid1864548>{{Cite journal | last1 = Bion | first1 = E. | last2 = Brenard | first2 = R. | last3 = Pariente | first3 = EA. | last4 = Lebrec | first4 = D. | last5 = Degott | first5 = C. | last6 = Maitre | first6 = F. | last7 = Benhamou | first7 = JP. | title = Sinusoidal portal hypertension in hepatic amyloidosis. | journal = Gut | volume = 32 | issue = 2 | pages = 227-30 | month = Feb | year = 1991 | doi = | PMID = 1864548 | PMC = 1378815 | URL = http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1378815/?tool=pubmed }}</ref>

===Microscopic===
Features:
*Amorphous extracellular pink stuff on H&E - see ''[[amyloid]]'' article.

DDx:
*[[Fibrolamellar hepatocellular carcinoma]].

====Images====
<gallery>
Image:Hepatic_amyloidosis_-_low_mag.jpg | Amyloidosis of the liver - low mag. (WC)
Image:Hepatic_amyloidosis_-_intermed_mag.jpg | Amyloidosis of the liver - intermed. mag. (WC)
Image:Hepatic_amyloidosis_-_high_mag.jpg | Amyloidosis of the liver - high mag. (WC)
Image:Hepatic_amyloidosis_-_very_high_mag.jpg | Amyloidosis of the liver - very high mag. (WC)
</gallery>
{|
[[File:1 AMY 1 680x512px.tif|Amorphous material replaces hepatic parenchyma [4X]]]
[[File:2 AMY 1 680x512px.tif|Material barely stains blue on trichrome [10X]]]
 
[[File:3 AMY 1 680x512px.tif|Material stains red on unpolarized Congo Red [40X]]]
[[File:4 AMY 1 680x512px.tif|Material stains apple green on polarized Congo Red [40X]]]
|}
Amyloidosis. Amorphous material replaces hepatic parenchyma [UL 4X]. Material barely stains blue on trichrome [UR 10X] Material stains red on unpolarized Congo Red [LL 40X] Material stains apple green on polarized Congo Red [LR 40X]

===Stains===
*[[Congo red]] +ve.

==Fulminant hepatic necrosis==
===General===
Etiology:
*Viral, i.e. [[Hepatitis A]], [[Hepatitis B]]; [[Hepatitis C]] - extremely rare.
*Trauma.
*Shock.

===Microscopic===
{|
[[File:1 Necrosis 2 680x512px.tif| Submassive hepatic necrosis.]]
[[File:2 Necrosis 2 680x512px.tif| Submassive hepatic necrosis.]]
 
[[File:3 Necrosis 2 680x512px.tif| Submassive hepatic necrosis.]]
[[File:4 Necrosis 2 680x512px.tif| Submassive hepatic necrosis.]]
 
[[File:5 Necrosis 2 680x512px.tif| Submassive hepatic necrosis.]]
[[File:6 Necrosis 2 680x512px.tif| Submassive hepatic necrosis.]]
|}
Submassive hepatic necrosis. Patient had transaminases in the thousands that rapidly dropped to normal. Pink preserved parenchyma strews empty necrotic spaces (Row 1 Left 20X). Focus of necrosis with no apparent hepatocytes macrophages abuts apparently normal liver (Row 1 Right 200X). Iron stain shows the macrophages bear hemosiderin (Row 2 Left 200X). Reticulin stain highlights the recently dead liver cells (Row 2 Right 200X). Reticulin stain shows a necrotic bridge forming; the multiple small black circles preclude diagnosis of a fibrous bridge (Row 3 Left 200X). Trichrome shows the necrotic bridge (“collapse”) lacks much collagen deposition, as would be expected for bridging fibrosis (Row 3 Right 200X).

Features:
*Hepatocyte [[necrosis]].
*Bile duct proliferation.

DDx:
*[[Cholangiocarcinoma]].
*[[Angiosarcoma]].

==Secondary hemochromatosis==
:''For the hereditary one see [[hereditary hemochromatosis]]''.
===General===
*Iron overload secondary to blood transfusions for hereditary or acquired anemia.<ref name=pmid19727383/>
**Primary hemochromatosis due to a defect in iron processing - called ''[[hereditary hemochromatosis]]''.
*Imaging considered the best test, as iron deposition is patchy.<ref name=pmid19727383/>

Selected hereditary causes:<ref name=pmid19727383>{{Cite journal | last1 = Gattermann | first1 = N. | title = The treatment of secondary hemochromatosis. | journal = Dtsch Arztebl Int | volume = 106 | issue = 30 | pages = 499-504, I | month = Jul | year = 2009 | doi = 10.3238/arztebl.2009.0499 | PMID = 19727383 | PMC = 2735704 | URL = http://www.ncbi.nlm.nih.gov.myaccess.library.utoronto.ca/pmc/articles/PMC2735704/?tool=pubmed}}</ref>
*Thalassemia.
*[[Sickle cell anemia]].
*Hereditary sideroblastic anemia.

Selected acquired causes:<ref name=pmid19727383/>
*[[Myelodysplastic syndromes]]
*Myelofibrosis
*Aplastic anemia, intractable.

===Microscopic===
:See ''[[hereditary hemochromatosis]]''.

==Hepatic sarcoidosis==
{{Main|Hepatic sarcoidosis}}
==Overlapping Disorders==

[[File:1 Mixed Disorder 1 680x512px.tif|Changes of steatohepatitis and interface hepatitis, with granuloma. Patient with diabetes was ANA, AMA, HCV, HBV negative, without drugs known to produce granulomas or interface hepatitis. This may be a case of AMA negative primary biliary cirrhosis, but studies to determine that with certainty were not performed.]]
[[File:2 Mixed Disorder 1 680x512px.tif|Changes of steatohepatitis and interface hepatitis, with granuloma. Patient with diabetes was ANA, AMA, HCV, HBV negative, without drugs known to produce granulomas or interface hepatitis. This may be a case of AMA negative primary biliary cirrhosis, but studies to determine that with certainty were not performed.]]
[[File:3 Mixed Disorder 1 680x512px.tif|Changes of steatohepatitis and interface hepatitis, with granuloma. Patient with diabetes was ANA, AMA, HCV, HBV negative, without drugs known to produce granulomas or interface hepatitis. This may be a case of AMA negative primary biliary cirrhosis, but studies to determine that with certainty were not performed.]]
[[File:4 Mixed Disorder 1 680x512px.tif|Changes of steatohepatitis and interface hepatitis, with granuloma. Patient with diabetes was ANA, AMA, HCV, HBV negative, without drugs known to produce granulomas or interface hepatitis. This may be a case of AMA negative primary biliary cirrhosis, but studies to determine that with certainty were not performed.]]
[[File:5 Mixed Disorder 1 680x512px.tif|Changes of steatohepatitis and interface hepatitis, with granuloma. Patient with diabetes was ANA, AMA, HCV, HBV negative, without drugs known to produce granulomas or interface hepatitis. This may be a case of AMA negative primary biliary cirrhosis, but studies to determine that with certainty were not performed.]]
[[File:6 Mixed Disorder 1 680x512px.tif|Changes of steatohepatitis and interface hepatitis, with granuloma. Patient with diabetes was ANA, AMA, HCV, HBV negative, without drugs known to produce granulomas or interface hepatitis. This may be a case of AMA negative primary biliary cirrhosis, but studies to determine that with certainty were not performed.]] 
Changes of steatohepatitis and interface hepatitis, with granuloma. Patient with diabetes was ANA, AMA, HCV, HBV negative, without drugs known to produce granulomas or interface hepatitis. This may be a case of AMA negative primary biliary cirrhosis, but studies to determine that with certainty were not performed. A. Low power shows hepatocytes afflicted by steatosis and an inflamed portal tract. B. In a region of fatty change lie cytoplasmic tufts of ballooning degeneration (green arrows) and a lipogranuloma (black arrow). C. At the portal-hepatocyte junction lies interface hepatitis (black arrows), as well as extension of inflammation into the lobule (green arrows). D. Red hepatocytes bounded by inflammation denote piecemeal necrosis [PAS without diastase]. E. Giant cells intermixed with lymphocytes prove a portal granuloma [PAS without diastase]. F. A blue fibrous bridge extends from a triad [Trichrome].

[[File:4 95599552608917 sl 1.png|Acute obstructive changes and changes of recurrent acute injury]]
[[File:4 95599552608917 sl 2.png|Acute obstructive changes and changes of recurrent acute injury]]
[[File:4 95599552608917 sl 3.png|Acute obstructive changes and changes of recurrent acute injury]]
[[File:4 95599552608917 sl 4.png|Acute obstructive changes and changes of recurrent acute injury]]
[[File:4 95599552608917 sl 5.png|Acute obstructive changes and changes of recurrent acute injury]]
[[File:4 95599552608917 sl 6.png|Acute obstructive changes and changes of recurrent acute injury]]
[[File:4 95599552608917 sl 7.png|Acute obstructive changes and changes of recurrent acute injury]] 
Acute obstructive changes and changes of recurrent injury in 46 yo man with Clostridium perfringens positive blood culture, an ERCP that showed duodenal compression by the pancreas with resultant bile duct dilatation. The patient had had and continued to have multiple bouts of acute pancreatitis. At the time of biopsy, decreased platelet count/hemoglobin/albumin, elevated lipase/amylase/PT/PTT, normal alkaline phosphatase, bilirubin, AST/ALT, AMA, hepatitis virus serology, ANA. A. Fragment biopsy shows inflamed triads and bridges. B. Trichrome shows bridges without nodules, evidence of prior injury; the patient subsequently developed multiple episodes of pancreatitis. C. Reticulin shows piecemeal necrosis, with black lines bounding individual hepatocytes at interface (arrows). D. Collapse is shown by closly approximated thick black lines; one cannot call portal-central collapse without seeing a central vein. Note on this and the other reticulin image that regeneration, two cell thick cords, is not prominent. E. PAS D of two portal triads, far nearer than normal, both expanded. Note increased number of ducts/ductules (red arrows), neutrophils, and PAS-D macrophages. F. PAS D shows collapse extending from a triad to a portion of a lobule with steatosis. No feathery degeneration or bile duct plugs were seen. Neither were foci of spotty necrosis or abscess seen. G. Other triads, again edematous, showed more of a chronic inflammatory response, with occasional plasma cells (black arrows). Also present are neutrophils (red arrows). The bile duct (grey arrow) near the artery (brown arrow) shows mildly disturbed nuclei. Note early proliferated bile ductules (cyan arrows).

[[File:6 17281676469188 sl 1.png| Hepatitis B virus with steatohepatitis]]
[[File:6 17281676469188 sl 2.png| Hepatitis B virus with steatohepatitis]]
[[File:6 17281676469188 sl 3.png| Hepatitis B virus with steatohepatitis]]
[[File:6 17281676469188 sl 4.png| Hepatitis B virus with steatohepatitis]]
[[File:6 17281676469188 sl 5.png| Hepatitis B virus with steatohepatitis]]
[[File:6 17281676469188 sl 6.png| Hepatitis B virus with steatohepatitis]] 
Hepatitis B virus with steatohepatitis in a 36 year old man with hepatitis B surface antigen and hepatitis Be antigen positivity, Hepatitis be QTPC of 1750 cop/mL, an occasionally mildly elevated (42) ALT, and normal glucose, alkaline phosphatase, bilirubin, and other transaminases. He had a history of alcohol abuse, which became controlled. A. Triads show scant inflammation without definite interface hepatitis. About one-fourth of the lobule, not pan-acinar, is afflicted by steatosis. B. Occasional tufts are seen (arrow), indicating focal ballooning sufficient for a diagnosis of steatohepatitis. C. Glycogenated nuclei (black arrows) and hepatocytes with feathery degeneration (red arrows) are seen. D. Very rare foci of spotty necrosis were seen. E. Apart from this triad and the one in the trichrome stain in F, which had moderate inflammation comprising lymphocytes and macrophages, all triads were small, most without any inflammation at all. Neither collapse nor piecemeal necrosis were seen on reticulin stain. F. Trichrome stain showed only portal fibrosis. The interhepatocyte fibrosis required for brunt fibrosis stage I was not seen. Hence, one would grade this as follows: A) Chronic hepatitis (history of hepatitis B), Metavir activity index 1, Piecemeal necrosis 0, Lobular necrosis 1, Metavir fibrosis stage 1, B) Steatohepaitits, Brunt necroinflammatory grade 1, Brunt fibrosis stage 0.

=See also=
*[[Pancreas]].
*[[Gastrointestinal pathology]].
*[[Liver neoplasms]].
*[[Liver]].

=References=
{{reflist|2}}

[[Category:Gastrointestinal pathology]]
[[Category:Liver pathology]]
[[Category:Medical liver disease]]

Medical liver disease

2017-01-23T15:45:45Z

Mitchell: /* Coccidiomycosis */

[[Image:Ground glass hepatocytes high mag cropped 2.jpg|thumb|right|[[Micrograph]] showing ground glass hepatocytes, as seen in chronic [[hepatitis B]]. [[H&E stain]].]]
This article deals with '''medical [[liver]] disease'''. An introduction to the liver and approach is found in the ''[[liver]]'' article.

Every differential in liver pathology has "drugs"<ref>{{Ref PCPBoD8|448}}</ref> -- if it isn't clearly malignancy.

Liver neoplasms are dealt with in the ''[[liver neoplasms]]'' article.

Medical liver biopsies are often non-specific, as the liver has the same appearance for many mechanisms of injury, especially when the injury is marked. The clinical history, serology and imaging are essential for proper interpretations in this domain of pathology.

=Review of liver blood work=
===Inflammation activity===
*ALT.
*AST.

===Cholestatic markers===
*ALP.
*GGT - used to assess whether the ALP is an "honest" value, elevated in cirrhosis.

===Cirrhosis/decompensation===
*PLT - low is suggestive of dysfunction.
*INR - high is bad, unless anticoagulated.

===Other===
*Bilirubin.
**Direct (AKA conjugated).
**Indirect (AKA unconjugated).

A short DDx of elevated:<ref>{{Ref PCPBoD8|441}}</ref>
*Indirect:
**[[Gilbert syndrome]].
**Crigler-Najjar syndrome type 1.
**Crigler-Najjar syndrome type 2.
*Direct:
**Rotor syndrome.
**Dubin-Johnson syndomre.

===Viral hepatitis===
*HBV DNA.
*HCV RNA.
*HBs Ag, HBs Ab, HBe Ag, HBe Ab.
*HCV Ab.

Others:
*[[Epstein-Barr virus]] (EBV).
*[[Cytomegalovirus]] (CMV) - especially in the immune incompetent.

====Hepatitis B====
Meaning & utility of the various [[Hepatitis B]] tests:<ref>URL: [http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/hepatology/hepatitis-B/ http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/hepatology/hepatitis-B/]. Accessed on: 16 May 2011.</ref><ref name=lto_hepb>URL: [http://www.labtestsonline.org/understanding/analytes/hepatitis_b/test.html http://www.labtestsonline.org/understanding/analytes/hepatitis_b/test.html]. Accessed on: 16 May 2011.</ref>
{| class="wikitable sortable" border="1"
! Test name
! Location
! Positive test
! Negative test
! Usual question
|-
| HBs Ag||Surface||Virus active||No active infection||Active infection?
|-
| HBs Ab||Surface||Exposed OR vaccinated||No exposure OR no vaccine OR loss of Ab||Immunization status?
|-
| HBe Ag||Virus core||Infect. w/ viral replication||No active infection||Active infect. w/ viral replication?
|-
| HBe Ab||Virus core||Exposed to virus||Infect. w/o antibody response OR not exposed||Immune response to infection?
|-
| HBV DNA||-||Active||Not active/no exposure||Viral load/how active?
|-
| HBc Ab||Virus core||Virus active/previous exposure||No exposure||Early active infection?
|}
Notes:
*''HBc Ab'' may test for acute (IgM) or chronic infection - dependent on specific antibody test; it is often used to look for early infection.<ref name=lto_hepb>URL: [http://www.labtestsonline.org/understanding/analytes/hepatitis_b/test.html http://www.labtestsonline.org/understanding/analytes/hepatitis_b/test.html]. Accessed on: 16 May 2011.</ref>
*''Carriers of hepatitis B'': HBs Ag +ve, HBs Ab -ve, HBc Ag -ve, HBc Ab +ve, HBe Ag -ve, HBe Ab +ve.<ref>URL: [http://labtestsonline.org/understanding/analytes/hepatitis-b/tab/test http://labtestsonline.org/understanding/analytes/hepatitis-b/tab/test]. Accessed on: 3 May 2012.</ref>

===Markers for rare liver diseases===
*Ceruloplasm - low think ''[[Wilson's disease]]''; typical value for Wilson's ~ 0.12 g/L.
**<0.20 g/L is a criteria for Wilson's disease.<ref name=pmid18556333>Diagnostic accuracy of serum ceruloplasmin in Wilson disease: determination of sensitivity and specificity by ROC curve analysis among ATP7B-genotyped subjects. Mak CM, Lam CW, Tam S. Clin Chem. 2008 Aug;54(8):1356-62. Epub 2008 Jun 12. PMID 18556333. URL: [http://www.clinchem.org/cgi/reprint/54/8/1356.pdf http://www.clinchem.org/cgi/reprint/54/8/1356.pdf]. Accessed on: 28 September 2009.</ref>
*Alpha-1 antitrypsin - if low think ''deficiency''.

===Hemosiderosis===
*Ferritin - high.
*Iron saturation - high.

Causes:
*Hemochromatosis.
*Hemolysis, chronic.
*Cirrhosis.

=Medical imaging=
Blood flow:<ref>URL: [http://insidesurgery.com/2010/12/hepatopedal-hepatofugal-flow/ http://insidesurgery.com/2010/12/hepatopedal-hepatofugal-flow/]. Accessed on: 2 December 2011.</ref>
*Hepatopedal flow = normal portal vein flow.
*Hepatofugal flow = reversed portal vein flow.

==Interventional measurements==
Wedged to free hepatic venous pressure:<ref name=pmid1864548>{{Cite journal | last1 = Bion | first1 = E. | last2 = Brenard | first2 = R. | last3 = Pariente | first3 = EA. | last4 = Lebrec | first4 = D. | last5 = Degott | first5 = C. | last6 = Maitre | first6 = F. | last7 = Benhamou | first7 = JP. | title = Sinusoidal portal hypertension in hepatic amyloidosis. | journal = Gut | volume = 32 | issue = 2 | pages = 227-30 | month = Feb | year = 1991 | doi = | PMID = 1864548 | PMC = 1378815 | URL = http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1378815/?tool=pubmed }}</ref>
*Normal = 1-4 mmHg.
**Elevated in [[portal hypertension]].

=Liver biopsy=
==Medical liver biopsy adequacy==
Liver biopsy specimens should be:<ref>{{Ref MacSween|418}}</ref>
*2.0 cm in length and contain 11-15 portal tracts,
*The core should be deeper than 1.0 cm from the liver capsule; specimens close to the capsule may lead to over grading of fibrosis.

==Reporting==
{{Main|Pathology reports}}
<pre>
Specimen, procedure:
- Diagnosis.
</pre>
The diagnosis usually contains grading and staging information, e.g. ''activity 2 /4, Laennec fibrosis stage 1 /4''.

In the context of medical liver disease:
*Grade = inflammation/activity.
*Stage = severity of fibrosis/architectural changes.

Notes:
*The term "acute" is infrequently used in liver pathology.
*In the liver: neutrophils ''is not'' acute -- unlike most elsewhere in the body.<ref>OA. September 2009.</ref>

===A microscopic checklist===
<pre>
Size of biopsy: Adequate
Fragmentation: Absent
Fibrosis: Stage 2-3/4, mostly stage 2
Fibrous septa: Present
Septa with curved contours: Present – focally only
Large droplet steatosis (% of hepatocytes): Present, moderate 60%
Ballooning of hepatocytes: Present, rare
Mallory-Denk bodies: Present, rare
Portal inflammation: Present
Interface activity: Minimal (0-1/4)
Lobular necroinflammation: Minimal
Ducts: Present in normal numbers
Duct injury: Absent
Ductular reaction: Absent
Cholestasis: Absent
Terminal hepatic venules: Present
Iron stain: Absent
Ground glass cells with routine stains: Absent
PASD for alpha-1 antitrypsin droplets: Negative
</pre>

=Viral hepatitis=
These are common. The diagnoses are based on serology. The serology is covered in the ''[[Liver_pathology#Viral_hepatitis|viral hepatitis]]'' section in the ''[[liver pathology]]'' article.

Typically classified as:<ref name=pmid8048409>{{Cite journal | title = Terminology of chronic hepatitis, hepatic allograft rejection, and nodular lesions of the liver: summary of recommendations developed by an international working party, supported by the World Congresses of Gastroenterology, Los Angeles, 1994. | journal = Am J Gastroenterol | volume = 89 | issue = 8 Suppl | pages = S177-81 | month = Aug | year = 1994 | doi = | PMID = 8048409 }}</ref><ref>URL: [http://familydoctor.org/familydoctor/en/diseases-conditions/hepatitis-b.html http://familydoctor.org/familydoctor/en/diseases-conditions/hepatitis-b.html]. Accessed on: 2 May 2012.</ref>
#Acute < 6 months duration.
#Chronic > 6 months duration.

==Hepatitis A==
*Infection is self-limited, i.e. not persistent.
**May present as ''[[fulminant hepatic necrosis]]''.
*Usually asymptomatic in children.<ref name=pmid20068336>{{cite journal |author=Jeong SH, Lee HS |title=Hepatitis A: clinical manifestations and management |journal=Intervirology |volume=53 |issue=1 |pages=15–9 |year=2010 |pmid=20068336 |doi=10.1159/000252779 |url=}}</ref>
*Serology is diagnostic.

==Hepatitis B==
:''Hepatitis B virus'', abbreviated ''HBV'', redirects here.
{{Main|Hepatitis B}}

==Hepatitis C==
{{Main|Hepatitis C}}

=Other infections=
*Hydatid disease (Hydatid cyst).
*Ascaris.
*Fasciola

==Hydatid disease==
*[[AKA]] ''hydatid cyst''.
===General===
*Etiology: ''[[Echinococcus]]''.

===Microscopic===
Features:
*Laminated wall +/- calcification.<ref name=Ref_PBPoD8_448>{{Ref PCPBoD8|448}}</ref>
*Organisms -- see ''[[Echinococcus]]''.

====Images====
<gallery>
Image:Liver_cyst_wall_-_intermed_mag.jpg | Liver cyst wall - intermed. mag. (WC)
Image:Liver_cyst_wall_-_high_mag.jpg | Liver cyst wall - high mag. (WC)
Image: Laminated liver cyst wall - intermed mag.jpg | Characteristic laminated portion - intermed. mag. (WC)
Image: Laminated liver cyst wall - high mag.jpg | Characteristic laminated portion - high mag. (WC)
</gallery>
[[www]]:
*[http://pathmicro.med.sc.edu/parasitology/hydatid-hist1.jpg Hydatid cyst (med.sc.edu)].
*[http://www.atlas.or.kr/atlas/include/viewImg.html?uid=645 Hydatid cyst (atlas.or.kr)].
*[http://casereports.bmj.com/content/2009/bcr.04.2009.1798.full Hydatid cyst (casereports.bmj.com)].

==Abscess==
A. [[File:1 ABS 1 680x512px.tif|A process replaces most of the liver parenchyma (20X).]]
 
B. [[File:2 ABS 1 680x512px.tif|Fibrinopurulent exudate apposes granulation tissue (200X).]]
 
C. [[File:3 ABS 1 680x512px.tif|Neutrophils lie in widened sinusoids (200X)..]]
 
D. [[File:4 ABS 1 680x512px.tif|Trichrome shows collagenization of spaces of Disse. Scarring about an abscess or other mass lesion should not be interpreted as reflective of the liver in general (200X).]]
 
Abscess. A. A process replaces most of the liver parenchyma. B. Fibrinopurulent exudate apposes granulation tissue. C. Neutrophils lie in widened sinusoids. D. Trichrome shows collagenization of spaces of Disse. Scarring about an abscess or other mass lesion should not be interpreted as reflective of the liver in general (LR 200X).

==Coccidiomycosis==
A. [[File:Coccidiomycosis - 1 - 40X 680x512px shot.tif|500x500px Granulomas at low power]]
 
B. [[File:Coccidiomycosis - 1 - 200X 680x513px shot.tif|500x500px Granulomas with centrally crowded cells & lady slipper macrophage nuclei]]
 
C. [[File:Coccidiomycosis - 1 - 400X 1369x1024px shot.tif|500x500px Center of previous granuloma showing pyknotic macrophage nuclei]]
 
D. [[File:Coccidiomycosis - 1 - GMS 400X 1369x1024px shot.tif|500x500px Four Coccidiomycotic spherules]]
 
Coccidiomycosis. A. Note the granulomas in otherwise undisturbed liver (UL). B. Granuloma with centrally crowded cells & lady slipper macrophage nuclei. C. Center of granuloma with pyknotic macrophage nuclei, "necrotizing". D. Organisms on GMS stain.

=Metabolic and toxic=
==Alcoholic liver disease==
===General===
*Acute and/or chronic liver changes due to excessive [[alcohol]] use - includes:
**''[[Alcoholic steatohepatitis]]'' (ASH), [[AKA]] ''alcoholic hepatitis''.<ref>URL: [http://emedicine.medscape.com/article/170539-overview http://emedicine.medscape.com/article/170539-overview]. Accessed on: 3 May 2012.</ref>
***Alcoholic hepatitis can be with minimal steatosis.<ref>STC. 6 December 2010.</ref>
**[[Steatosis]] - classically macrovescicular and centrilobular.
**Alcoholic [[cirrhosis]].

====Classic lab findings in EtOH abusers====
*AST & ALT elevated with AST:ALT=2:1.
*GGT elevated.
*MCV increased.

===Gross pathology/radiologic findings===
*Classically micronodular pattern.
**May be macronodular.

===Microscopic===
See:
*''[[Steatohepatitis]]'' section and ''[[ballooning degeneration]]'' section.

Features:
*Often zone III damage.
*Cholestatsis common, i.e. yellow staining.
**NASH (non-alcoholic steatohepatitis) usu. does not have cholestasis.<ref>STC. 6 December 2010.</ref>
*Fibrosis starts at central veins.
*Neutrophils (often helpful) -- few other things have PMNs. (???)
**Neutrophils cluster around cells with Mallory hyaline.

====Images====
{|
[[File:1 etoh 3 680x512px.tif| Alcoholic hepatitis with Metavir stage IV fibrosis (advanced fibrosis/cirrhosis).]]
[[File:2 etoh 3 680x512px.tif| Alcoholic hepatitis with Metavir stage IV fibrosis (advanced fibrosis/cirrhosis).]]
 
[[File:3 etoh 3 680x512px.tif| Alcoholic hepatitis with Metavir stage IV fibrosis (advanced fibrosis/cirrhosis).]]
[[File:4 etoh 3 680x512px.tif| Alcoholic hepatitis with Metavir stage IV fibrosis (advanced fibrosis/cirrhosis).]]
 
[[File:5 etoh 3 680x512px.tif| Alcoholic hepatitis with Metavir stage IV fibrosis (advanced fibrosis/cirrhosis).]]
[[File:6 etoh 3 680x512px.tif| Alcoholic hepatitis with Metavir stage IV fibrosis (advanced fibrosis/cirrhosis).]]
|}
Alcoholic hepatitis with Metavir stage IV fibrosis (advanced fibrosis/cirrhosis).
Trichrome shows relatively non-inflamed fibrous bands, as well as [between green dots] nodules. The lack of regeneration throughout might have precluded a diagnosis of cirrhosis, but stage IV fibrosis under the Metavir system is justified (Row 1 Left 20X). Reticulin shows regenerative nodules [left] with mostly two or more nuclei between black lines juxtaposed to non-regenerative hepatocytes on the right, without piecemeal necrosis. (Row 1 Right 100X). Regenerative nodules show occasional neutrophils [red arrow] and cytoplasmic tufts of ballooned cells, sometimes possibly Mallory hyalin [green arrows] (Row 2 Left 200X). Triads (note vein [green arrow], artery [yellow arrow], and interlobular bile duct [blue arrow]) generally showed little or no interface hepatitis, even when expanded by fibrosis and inflamed (Row 2 Right 200X). Occasional foci of spotty necrosis were seen (Row 3 Left 200X). This edge of an inflamed triads shows neutrophils about proliferated bile ducts [red arrows], as well as Mallory-Denk bodies [blue arrows] (Row 4 Left 400X).
{|
[[File:1 etoh 4 680x512px.tif| Cirrhosis in an alcoholic.]]
[[File:2 etoh 4 680x512px.tif| Cirrhosis in an alcoholic.]]
 
[[File:3 etoh 4 680x512px.tif| Cirrhosis in an alcoholic.]]
[[File:4 etoh 4 680x512px.tif| Cirrhosis in an alcoholic.]]
 
[[File:5 etoh 4 680x512px.tif| Cirrhosis in an alcoholic.]]
[[File:6 etoh 4 680x512px.tif| Cirrhosis in an alcoholic.]]
|}
Definite cirrhosis in an alcoholic. Hepatocyte free bands parse tissue, with occasional definite islands [arrows] (Row 1 Left 40X). Trichrome establishes blue fibrosis about isles [arrows] (Row 1 Right 40X). Reticulin stain shows nodules with regeneration, wherein a large proportion of them are at least two nuclei thick [arrows] (Row 2 Left 200X). Bile duct proliferation can be difficult, sometimes mimicking cholangiocarcinoma. Follow the double headed arrows to see how the ductules can be seen to proliferate from a single sources, with all ducts being complete, without necrotic epithelial cells. (Row 2 Right 400X). PAS with distase can help, as cholangiocarcinoma generally lacks the red rim of proliferating bile ductules [arrows]; again note the connections that can be made between the ductule openings by the blue double headed arrows. The cyan double headed arrows show general parallelism, consistent with uniform directionality induced by extrinsic force, not a neoplastic spread (Row 3 Left 400X). Trichrome shows the most difficult focus. Double headed arrows display the connectivity seen before of the proliferated bile ductules. Note that numerous pairs of adjacent perpendicular glands without a head to foot appearance are not seen that would indicate the disorderly spread of cholangiocarcinoma (Row 3 Right 400X).

{|
[[File:1 ALC 2 680x512px.tif|Expanded, inflamed triads with increased bile duct/vascular openings. Mild steatosis (40X).]]
[[File:2 ALC 2 680x512px.tif|Trichrome stain shows periportal fibrosis [red arrowheads] (200X).]]
 
[[File:3 ALC 2 680x512px.tif|PAS with diastase stain shows proliferated bile ductules [blue arrowheads] in stroma with mixed inflammatory infiltrate (400X)]]
[[File:4 ALC 2 680x512px.tif|Neutrophils about ballooned hepatocyte (satellitosis) [yellow arrowheads]. Councilman bodies [green arrowheads] (400X).]]
|}
Alcoholic hepatitis without cirrhosis. No history of viral disease. AMA negative. Expanded, inflamed triads with increased bile duct/vascular openings. Mild steatosis (UL 40X). Trichrome stain shows periportal fibrosis [red arrowheads] (UR 200X). PAS with diastase stain shows proliferated bile ductules [blue arrowheads] in stroma with mixed inflammatory infiltrate (LL 400X) Neutrophils about ballooned hepatocyte (satellitosis) [yellow arrowheads]. Councilman bodies [green arrowheads] (LR 400X).

Notes:
*If portal inflammatory infiltrates more than mild, r/o other causes i.e. [[viral hepatitis]].
*Mallory bodies once thought to be characteristic; now considered non-specific and generally poorly understood.<ref>{{cite journal |author=Jensen K, Gluud C |title=The Mallory body: theories on development and pathological significance (Part 2 of a literature survey) |journal=Hepatology |volume=20 |issue=5 |pages=1330-42 |year=1994 |month=November |pmid=7927269 |doi= |url=}}</ref>
*Some consider ''alcoholic liver disease'' a clinical diagnosis, i.e. as a pathologist one does not diagnose it.<ref>MG. September 2009.</ref>

==Non-alcoholic fatty liver disease==
*Abbreviated ''NAFLD''.
*Fatty liver that is not due to alcohol; includes obesity-related fatty liver, metabolic disease/diabetes-related fatty liver.

===NASH===
*Non-alcoholic steatohepatitis - see ''steatohepatitis'' section.
*Histologically indistinguishable from ASH.
*NASH is a ''clinical diagnosis'' based on exclusion of alcohol.

==Steatohepatitis==
{{Main|Steatohepatitis}}

=Autoimmune=
==Autoimmune hepatitis==
*Abbreviated ''AIH''.
{{Main|Autoimmune hepatitis}}

==Primary biliary cirrhosis==
*Abbreviated PBC.
{{Main|Primary biliary cirrhosis}}

==Autoimmune hepatitis with obstruction - combined changes==
{|
[[File:1 AIH OBS 1.tif|Low power shows inflammation; portal triads, lobules, central veins cannot be distinguished (40X).]]
[[File:2 AIH OBS 1.tif|Trichrome shows central venous sclerosis (red arrowhead), periportal fibrosis (green arrowhead), & space of Disse collagenization (yellow arrowhead); juxtaposition of central vein & portal tract indicates collapse, no definite bridging was seen (100X)]]
 
[[File:3 AIH OBS 1.tif|Central vein is inflamed with a rare plasma cell (cyan arrowhead) (400X).]]
[[File:4 AIH OBS 1.tif|Interface hepatitis with plasma cells (yellow arrows) and ballooned hepatocytes (red arrows). Lobule is disorganized (400X).]]
 
[[File:5 AIH OBS 1.tif|Proliferating bile ductules (blue arrows) with occasional neutrophils (fucsia arrows), indicative of obstruction, but not acute cholangitis, which requires inflamed bile duct itself, best diagnosed with associated blood vessel (400X).]]
[[File:6 AIH OBS 1.tif|Rare distorted rosettes with greenish brown strands of bile (left arrow) or bile plugs (right arrow) (400X).]]
|}
Patient with SLE and obstructive jaundice that resolved with apparent passage of stone. Low power shows inflammation; portal triads, lobules, central veins cannot be distinguished (left row 1 40X). Trichrome shows central venous sclerosis (red arrowhead), periportal fibrosis (green arrowhead), & space of Disse collagenization (yellow arrowhead); juxtaposition of central vein & portal tract indicates collapse, no definite bridging was seen (right row 1 100X). Central vein is inflamed with a rare plasma cell (cyan arrowhead) (left row 2 400X). Interface hepatitis with plasma cells (yellow arrows) and ballooned hepatocytes (red arrows). Lobule is disorganized (right row 2 400X). Proliferating bile ductules (blue arrows) with occasional neutrophils (fucsia arrows), indicative of obstruction, but not acute cholangitis, which requires inflamed bile duct itself, best diagnosed with associated blood vessel (left row 3 400X). Rare distorted rosettes with greenish brown strands of bile (left arrow) or bile plugs (right arrow) (right row 3 400X).

==Autoimmune hepatitis-primary biliary cirrhosis overlap syndrome==
*Abbreviation ''AIH-PBC OS''.
===General===
Epidemiology:
*Rare.

Serology:<ref name=pmid19491855>{{Cite journal | last1 = Muratori | first1 = P. | last2 = Granito | first2 = A. | last3 = Pappas | first3 = G. | last4 = Pendino | first4 = GM. | last5 = Quarneti | first5 = C. | last6 = Cicola | first6 = R. | last7 = Menichella | first7 = R. | last8 = Ferri | first8 = S. | last9 = Cassani | first9 = F. | title = The serological profile of the autoimmune hepatitis/primary biliary cirrhosis overlap syndrome. | journal = Am J Gastroenterol | volume = 104 | issue = 6 | pages = 1420-5 | month = Jun | year = 2009 | doi = 10.1038/ajg.2009.126 | PMID = 19491855 }}</ref>
*AMA +ve.
*Anti-dsDNA +ve.

===Microscopic===
:See: ''[[autoimmune hepatitis]]'' and ''[[primary biliary cirrhosis]]''.
{|
[[File:1 AIH PBC 1 680x512px.tif|Expanded portal tracts with fuzzy edges (40X).]]
[[File:2 AIH PBC 1 680x512px.tif|Interface hepatitis with plasma cells (400X).]]
 
[[File:3 AIH PBC 1 680x512px.tif|Loose granuloma (400X).]]
[[File:4 AIH PBC 1 680x512px.tif|Damaged bile duct (400X).]]
|}

AIH/PBC overlap. AMA & ANA positive with Alkaline phosphatase > 2 upper limit of normal & one ALT > 5 times upper limit of normal. Expanded portal tracts with fuzzy edges (UL 40X). IInterface hepatitis with plasma cells (UR 400X). Loose granuloma (LL 400X). Damaged bile duct (LR 400X).

==Primary sclerosing cholangitis==
*Abbreviated ''PSC''.
{{Main|Primary sclerosing cholangitis}}

=Hereditary=
==Caroli disease==
===General===
*Genetic disease.
**Frequently associated with [[autosomal recessive polycystic kidney disease]] (ARPKD).<ref name=omim263200>{{OMIM|263200}}</ref>
**May be seen in isolation.<ref name=omim600643>{{OMIM|600643}}</ref>

Clinical:<ref name=pmid17461493>{{Cite journal | last1 = Yonem | first1 = O. | last2 = Bayraktar | first2 = Y. | title = Clinical characteristics of Caroli's syndrome. | journal = World J Gastroenterol | volume = 13 | issue = 13 | pages = 1934-7 | month = Apr | year = 2007 | doi = | PMID = 17461493 }}</ref>
*Recurrent [[cholangitis]].
*Recurrent [[cholelithiasis]].
*[[Cholangiocarcinoma]]<ref name=pmid17461492>{{Cite journal | last1 = Yonem | first1 = O. | last2 = Bayraktar | first2 = Y. | title = Clinical characteristics of Caroli's disease. | journal = World J Gastroenterol | volume = 13 | issue = 13 | pages = 1930-3 | month = Apr | year = 2007 | doi = | PMID = 17461492 }}</ref> - seen in ~7% of cases.<ref name=pmid15347876>{{Cite journal | last1 = Karim | first1 = AS. | title = Caroli's disease. | journal = Indian Pediatr | volume = 41 | issue = 8 | pages = 848-50 | month = Aug | year = 2004 | doi = | PMID = 15347876 }}</ref>

Note:
*''Caroli syndrome'' = Caroli disease + congenital hepatic fibrosis.<ref name=pmid15888616>{{Cite journal | last1 = Brancatelli | first1 = G. | last2 = Federle | first2 = MP. | last3 = Vilgrain | first3 = V. | last4 = Vullierme | first4 = MP. | last5 = Marin | first5 = D. | last6 = Lagalla | first6 = R. | title = Fibropolycystic liver disease: CT and MR imaging findings. | journal = Radiographics | volume = 25 | issue = 3 | pages = 659-70 | month = | year = | doi = 10.1148/rg.253045114 | PMID = 15888616 | URL = http://radiographics.rsna.org/content/25/3/659.long }}</ref>

===Gross===
*Dilated bile ducts.<ref name=omim263200/>

===Microscopic===
Features:<ref name=pmid17461493/>
*Dilated bile ducts.
*Periductal fibrosis. (???)
*+/-Fibrosis.

Image:
*[http://www.meddean.luc.edu/lumen/MedEd/orfpath/11-3-10.jpg Caroli disease (meddean.luc.edu)].<ref>URL: [http://www.meddean.luc.edu/lumen/MedEd/orfpath/develop.htm http://www.meddean.luc.edu/lumen/MedEd/orfpath/develop.htm]. Accessed on: 1 December 2011.</ref>

==Hereditary hemochromatosis==
:''For secondary causes see [[secondary hemochromatosis]]''.
{{Main|Hereditary hemochromatosis}}

==Wilson disease==
{{Main|Wilson's disease}}

==Alpha-1 antitrypsin deficiency==
*[[AKA]] ''alpha1-antiprotease inhibitor deficiency''.
{{Main|Alpha-1 antitrypsin deficiency }}

=Other=
==Budd-Chiari syndrome==
*[[AKA]] ''hepatic vein obstruction''.
===General===
*Hepatic outflow obstruction.

Clinical triad:<ref name=pmid21573256>{{Cite journal | last1 = Fox | first1 = MA. | last2 = Fox | first2 = JA. | last3 = Davies | first3 = MH. | title = Budd-Chiari syndrome--a review of the diagnosis and management. | journal = Acute Med | volume = 10 | issue = 1 | pages = 5-9 | month = | year = 2011 | doi = | PMID = 21573256 }}</ref>
*Ascites.
*Abdominal pain.
*Hepatomegaly.

Etiology:
*~50% have a [[myeloproliferative disease]].<ref name=pmid18814079>{{Cite journal | last1 = Plessier | first1 = A. | last2 = Valla | first2 = DC. | title = Budd-Chiari syndrome. | journal = Semin Liver Dis | volume = 28 | issue = 3 | pages = 259-69 | month = Aug | year = 2008 | doi = 10.1055/s-0028-1085094 | PMID = 18814079 }}</ref>
*May be due to mass effect from a tumour.

Clinical DDx:
*[[Hepatic veno-occlusive disease]].

===Microscopic===
Features:<ref name=pmid17569137>{{Cite journal | last1 = Aydinli | first1 = M. | last2 = Bayraktar | first2 = Y. | title = Budd-Chiari syndrome: etiology, pathogenesis and diagnosis. | journal = World J Gastroenterol | volume = 13 | issue = 19 | pages = 2693-6 | month = May | year = 2007 | doi = | PMID = 17569137 | url=http://www.wjgnet.com/1007-9327/full/v13/i19/2693.htm }}</ref>
*Sinusoidal dilation in zone III (congestion).
*+/-Hepatocyte drop-out.
*+/-Centrilobular fibrosis.

DDx congestion:
*Congestive heart failure ([[congestive hepatopathy]]).
*Constrictive pericarditis.

==Vanishing bile duct syndrome==
*[[AKA]] ''bile duct loss'', [[AKA]] ''ductopenia''.<ref name=pmid11521176/>
===General===
*Fatal.

DDx:<ref name=pmid18242505/>
*[[Primary biliary cirrhosis]].
*[[Primary sclerosing cholangitis]].
*[[GVHD]].<ref name=pmid7994249>{{Cite journal | last1 = Yeh | first1 = KH. | last2 = Hsieh | first2 = HC. | last3 = Tang | first3 = JL. | last4 = Lin | first4 = MT. | last5 = Yang | first5 = CH. | last6 = Chen | first6 = YC. | title = Severe isolated acute hepatic graft-versus-host disease with vanishing bile duct syndrome. | journal = Bone Marrow Transplant | volume = 14 | issue = 2 | pages = 319-21 | month = Aug | year = 1994 | doi = | PMID = 7994249 }}</ref>
*[[Drug-induced liver disease|Drugs]].<ref name=pmid11352118>{{Cite journal | last1 = Chitturi | first1 = S. | last2 = Farrell | first2 = GC. | title = Drug-induced cholestasis. | journal = Semin Gastrointest Dis | volume = 12 | issue = 2 | pages = 113-24 | month = Apr | year = 2001 | doi = | PMID = 11352118 }}</ref>
*Chronic rejection.<ref name=pmid11521176>{{Cite journal | last1 = Inomata | first1 = Y. | last2 = Tanaka | first2 = K. | title = Pathogenesis and treatment of bile duct loss after liver transplantation. | journal = J Hepatobiliary Pancreat Surg | volume = 8 | issue = 4 | pages = 316-22 | month = | year = 2001 | doi = 10.1007/s0053410080316 | PMID = 11521176 }}</ref>

===Microscopic===
Features:<ref name=pmid18242505>{{Cite journal | last1 = Reau | first1 = NS. | last2 = Jensen | first2 = DM. | title = Vanishing bile duct syndrome. | journal = Clin Liver Dis | volume = 12 | issue = 1 | pages = 203-17, x | month = Feb | year = 2008 | doi = 10.1016/j.cld.2007.11.007 | PMID = 18242505 }}</ref>
*Loss of intrahepatitic bile ducts - '''key feature'''.
*Cholestasis.

Note:
*May occur without fibrosis and inflammation; thus, can be easy to miss.

===IHC===
*[[CK7]] -ve.
**Marks bile ducts.

==Extrahepatic biliary obstruction==
{|
[[File:1 OBS 3 680x512px.tif|Sinusoidal dilatation, circular spaces of hepatocytes, small portal triads(40X).]]
[[File:2 OBS 3 680x512px.tif|Bile in hepatocytes about central vein & in plugs in canaliculi [yellow arrowhead] (400X).]]
 
[[File:3 OBS 3 680x512px.tif|Trichrome shows fibrosis about central vein (400X).]]
[[File:4 OBS 3 680x512px.tif|PAS with diastase shows portal triads with mild edema and chronic inflammation, without tortuous bile duct (400X).]]
|}
Early extrahepatic biliary obstruction, demonstrated radiographically, transient, with rise in bilirubin, alkaline phosphatase, and transaminases. Pure canalicular cholestasis near terminal hepatic venules also seen in acute hepatitis, drug reactions, benign recurrent cholestasis, pregnancy, sepsis, & lymphomas. Sinusoidal dilatation, circular spaces of hepatocytes, small portal triads(UL 40X). Bile in hepatocytes about central vein & in plugs in canaliculi [yellow arrowhead] (UR 400X). Trichrome shows fibrosis about central vein (LL 400X). PAS with diastase shows portal triads with mild edema and chronic inflammation, without tortuous bile duct (LR 400X).

{|
[[File:1 OBS 2 680x512px.tif|Expanded inflamed portal triads, swollen hepatocytes (40X)]]
[[File:2 OBS 2 680x512px.tif|Edematous stroma, proliferating ductules [yellow arrowheads], PAS-D macrophages [red arrowhead] (PAS with diastasse, 200X)]]
 
[[File:3 OBS 2 680x512px.tif|Disordered, often swollen hepatocytes,some with feathery degeneration (net like spaces in cytoplasm [blue arrowhead], rare Councilman body [green arrowhead] (400X)]]
[[File:4 OBS 2 1360x1024px.tif|Bile in hepatocytes [cyan arrrowhead] & in canaliculi [purple arrowheads]. Empty acinar spaces bounded by hepatocytes [orange arrowhead] (400X, higher pixel),]]
|}
Changes of extrahepatic biliary obstruction, months duration. Expanded inflamed portal triads, swollen hepatocytes (UL 40X). Edematous stroma, proliferating ductules [yellow arrowheads], PAS-D macrophages [red arrowhead] (UR PAS with diastasse, 200X). Disordered, often swollen hepatocytes,some with feathery degeneration (net like spaces in cytoplasm) [blue arrowhead], rare Councilman body [green arrowhead] (LL 400X). Bile in hepatocytes [cyan arrrowhead] & in canaliculi [purple arrowheads]. Empty acinar spaces bounded by hepatocytes [orange arrowhead] (LR 400X).
{|
[[File:1 Bd obs 4 680x512px.tif|Expanded, light colored portal triads (arrows)(20X).]]
[[File:2 Bd obs 4 680x512px.tif|Proliferating bile ductules (cyan arrows) with neutrophils (yellow arrows), not specific for acute cholangitis, of assistance with large bile duct obstruction (400X)..]]
 
[[File:3 Bd obs 4 680x512px.tif|Uninflamed interlobular duct (yellow arrow) with, accompanying blood vessel (red arrow) (400X)]]
[[File:4 Bd obs 4 680x512px.tif|Bile infarct with pyknotic nuclei (arrows)(400X).]]
 
[[File:5 Bd obs 4 680x512px.tif|Bile (arrow) in interlobular bile duct with disordered nuclei (400X).]]
[[File:6 Bd obs 4 680x512px.tif|Bile plugs in cannaliculi (red arrows), feathery degeneration producing foamy macrophage like hepatocytes (yellow arrows)(400X).]]
|}
Large bile duct obstruction. Expanded, light colored portal triads (arrows)(Row 1 Left 20X). Proliferating bile ductules (cyan arrows) with neutrophils (yellow arrows), not specific for acute cholangitis, of assistance with large bile duct obstruction (Row 1 Right 400X). Uninflamed interlobular duct (yellow arrow) with, accompanying blood vessel (red arrow) (Row 2 Left 400X). Bile infarct with pyknotic nuclei (arrows)(Row 2 Right 400X). Bile (arrow) in interlobular bile duct with disordered nuclei (Row 3 Left 400X). Bile plugs in cannaliculi (red arrows), feathery degeneration producing foamy macrophage-like hepatocytes (yellow arrows)(Row 3 Right 400X).

==Congestive hepatopathy==
===General===
*Liver failure due to (right) heart failure.
*AKA ''cardiac cirrhosis'' - a term used by clinicians.
**Generally, it does not satisfy pathologic criteria for cirrhosis.<ref>URL: [http://emedicine.medscape.com/article/151792-overview http://emedicine.medscape.com/article/151792-overview]. Accessed on: 17 June 2010.</ref>

===Gross===
*"Nutmeg" liver - yellow spotted appearance.

===Microscopic===
Features:<ref>URL: [http://emedicine.medscape.com/article/151792-diagnosis http://emedicine.medscape.com/article/151792-diagnosis]. Accessed on: 17 June 2010.</ref>
*Zone III atrophy.
*Portal venule (central vein) distension.
*Perisinusoidal fibrosis - progresses to centrilobular fibrosis and then diffuse fibrosis.
*Dilation of sinusoids in ''all'' zone III areas - '''key feature'''.<ref>Suggested by OA. September 2009.</ref>

DDx:
*[[Hemangioma of the liver]] - should be focal lesion.

====Images====
<gallery>
Image:Congestive_hepatopathy_high_mag.jpg | Mild congestive hepatopathy. (WC)
</gallery>
{|
[[File:1 CEN NEC 1 680x512px.tif|PAS without diastase shows ovoids of necrosis {40X).]]
[[File:2 CEN NEC 1 680x512px.tif|Necrosis with central vein [yellow arrowhead], inflammatory cells, residual Councilman body [green arrowhead], and hepatocyte with mitotic figure [red arrowhead] (400X).]]
 
[[File:3 CEN NEC 1 680x512px.tif|Trichrome highlights fibrosis about central vein [yellow arrowhead] & shows beginning scar formation [green arrowheads]. Note residual atrophic hepatocytes [blue arrowheads] (400X).]]
[[File:4 CEN NEC 1 680x512px.tif|Portal triads are largely unaffected (400X).]]
|}
Centrilobular necrosis (seen in circulatory failure and with toxins/drugs). PAS without diastase shows ovoids of necrosis {UL 40X). Necrosis with central vein [yellow arrowhead], inflammatory cells, residual Councilman body [green arrowhead], and hepatocyte with mitotic figure [red arrowhead] (UR 400X). Trichrome highlights fibrosis about central vein [yellow arrowhead] & shows beginning scar formation [green arrowheads]. Note residual atrophic hepatocytes [blue arrowheads] (LL 400X). Portal triads are largely unaffected (LR 400X)

{|
[[File:1 CHF 1 680x512px.tif|Dilated and undilated sinusoidal regions (40X).]]
[[File:2 CHF 1 680x512px.tif|Thrombi in sinusoids; glycogenated nuclei likely reflect patient’s diabetes mellitus (400X).]]
 
[[File:3 CHF 1 680x512px.tif|Dilated portal vein (400X).]]
[[File:4 CHF 1 680x512px.tif|Reticulin shows collapse (thick black lines) as well as a dilated portal vein (200X).]]
 
[[File:5 CHF 1 680x512px.tif|Trichrome shows space of Disse collagenization (pericellular fibrosis) (200X).]]
[[File:6 CHF 1 680x512px.tif|Trichrome shows periportal fibrosis; no bridging was seen (200X).]]
|}
Patient with congestive heart failure and stage I fibrosis. Dilated and undilated sinusoidal regions (left row 1 40X). Thrombi in sinusoids; glycogenated nuclei likely reflect patient’s diabetes mellitus (right row 1 400X). Dilated portal vein (left row 2 400X). Reticulin shows black lines of bridging, too thick for collapse (right row 2 200X). Trichrome shows space of Disse collagenization (pericellular fibrosis) (left row 3 200X). Trichrome shows bridge beginning off to right; when it is more than a mere spike, it is a bridge (right row 3 200X).

==Drug-induced liver disease==
*[[AKA]] ''drug-induced liver toxicity''.
{{Main|Drug-induced liver disease}}

==Focal nodular hyperplasia==
*Abbreviated ''FNH''.
{{Main|Focal nodular hyperplasia}}

==Nodular regenerative hyperplasia==
===General===
*Associated with renal transplants, [[bone marrow transplant]]s and [[vasculitides]].<ref name=Ref_PBoD922>{{Ref PBoD|922}}</ref>
*Can lead to [[portal hypertension]] and many of the associated complications.<ref name=pmid22554152>{{Cite journal | last1 = Bissonnette | first1 = J. | last2 = Généreux | first2 = A. | last3 = Côté | first3 = J. | last4 = Nguyen | first4 = B. | last5 = Perreault | first5 = P. | last6 = Bouchard | first6 = L. | last7 = Pomier-Layrargues | first7 = G. | title = Hepatic hemodynamics in 24 patients with nodular regenerative hyperplasia and symptomatic portal hypertension. | journal = J Gastroenterol Hepatol | volume = 27 | issue = 8 | pages = 1336-40 | month = Aug | year = 2012 | doi = 10.1111/j.1440-1746.2012.07168.x | PMID = 22554152 }}
</ref>

====Etiology====
*Arterial hypervascularity secondary to loss of hepatic vein radicles (loss of central venule in hepatic lobule).<ref name=Ref_PBoD922>{{Ref PBoD|922}}</ref>

ASIDE: radicle = ramulus - smallest branch or vessel or nerve.<ref name=Dorlands2>Dorland's Medical Dictionary. 30th Ed.</ref>

===Gross===
*Diffuse nodularity - whole liver.

===Microscopic===
Features:<ref name=Ref_PBoD922>{{Ref PBoD|922}}</ref>
*"Plump" hepatocytes surrounded by atrophic ones.
*No fibrosis.

==Sinuosoidal obstruction syndrome==
*May be referred to as ''Hepatic veno-occlusive disease''.<ref name=pmid11928077>{{Cite journal | last1 = DeLeve | first1 = LD. | last2 = Shulman | first2 = HM. | last3 = McDonald | first3 = GB. | title = Toxic injury to hepatic sinusoids: sinusoidal obstruction syndrome (veno-occlusive disease). | journal = Semin Liver Dis | volume = 22 | issue = 1 | pages = 27-42 | month = Feb | year = 2002 | doi = 10.1055/s-2002-23204 | PMID = 11928077 }}.</ref>
===General===
*Term for obstruction due to toxicity from a chemotherapeutic agent.<ref name=pmid16393276>{{Cite journal | last1 = Helmy | first1 = A. | title = Review article: updates in the pathogenesis and therapy of hepatic sinusoidal obstruction syndrome. | journal = Aliment Pharmacol Ther | volume = 23 | issue = 1 | pages = 11-25 | month = Jan | year = 2006 | doi = 10.1111/j.1365-2036.2006.02742.x | PMID = 16393276 }}</ref><ref name=pmid17569137>{{Cite journal | last1 = Aydinli | first1 = M. | last2 = Bayraktar | first2 = Y. | title = Budd-Chiari syndrome: etiology, pathogenesis and diagnosis. | journal = World J Gastroenterol | volume = 13 | issue = 19 | pages = 2693-6 | month = May | year = 2007 | doi = | PMID = 17569137 | url=http://www.wjgnet.com/1007-9327/full/v13/i19/2693.htm }}</ref>

Clinical DDx:
*[[Budd-Chiari syndrome]].

===Microscopic===
Features:<ref name=pmid17569137>{{Cite journal | last1 = Aydinli | first1 = M. | last2 = Bayraktar | first2 = Y. | title = Budd-Chiari syndrome: etiology, pathogenesis and diagnosis. | journal = World J Gastroenterol | volume = 13 | issue = 19 | pages = 2693-6 | month = May | year = 2007 | doi = | PMID = 17569137 | url=http://www.wjgnet.com/1007-9327/full/v13/i19/2693.htm }}</ref>
*Subendothelial swelling in hepatic venules.

Negatives:
*No thrombosis.

==Ascending Cholangitis (Acute Cholangitis)==
===General===
*Term for infection of bile ducts, usually due to obstruction

Clinical DDx:

===Microscopic===
====Images====

A. [[File:1 asc chol 1 680x512px.tif|Rounded, clear (edematous) portal tracts (arrows) separated by hepatocytes with dilated sinusoids (Row 1 Left 40X).]]
 
B. [[File:2 asc chol 1 680x512px.tif|Neutrophils about hepatocytes (arrows) have spilled into the lobule from a portal tract (Row 1 Right 200X).]]
 
C. [[File:3 asc chol 1 680x512px.tif|Proliferated bile ductules (arrows) bearing neutrophils within epithelium and lumens are features of obstruction that should prompt a search for interlobular ducts with acute inflammation (Row 2 Left 400X).]]
 
D. [[File:4 asc chol 1 680x512px.tif|The epithelium of the ducts can be severely degenerated. Neutrophils (cyan arrows) invade epithelium of an interlobular duct that are recognizable mainly as a circle of rounded nuclei; the associated arteriole (red arrow) should be identified to ensure an interlobular duct is being evaluated. Note the proliferated bile ductules (blue arrows) (Row 2 Right 400X).]]
 
E. [[File:5 asc chol 1 680x512px.tif|A PAS without diastase stain colors the arteriole (blue arrow), as well as the rim of the interlobular duct within which lies a neutrophil (cyan arrow) (Row 2 Right 400X). .]]
 
F. [[File:6 asc chol 1 680x512px.tif|A PAS with diastase stain colors the arteriole (red arrow), as well as the rim of the interlobular duct within which lies a neutrophil (cyan arrow) (Row 1 Right 400X)]]
 
Acute cholangitis in a patient with multiple bile duct procedures. After the biopsy, removal of bile duct stones released pus. A. Rounded, clear (edematous) portal tracts (arrows) separated by hepatocytes with dilated sinusoids. B. Neutrophils about hepatocytes (arrows) have spilled into the lobule from a portal tract. C, Proliferated bile ductules (arrows) bearing neutrophils within epithelium and lumens are features of obstruction that should prompt a search for interlobular ducts with acute inflammation. D. The epithelium of the ducts can be severely degenerated. Neutrophils (cyan arrows) invade epithelium of an interlobular duct that are recognizable mainly as a circle of rounded nuclei; the associated arteriole (red arrow) should be identified to ensure an interlobular duct is being evaluated. Note the proliferated bile ductules (blue arrows). E. A PAS without diastase stain colors the arteriole (blue arrow), as well as the rim of the interlobular duct within which lies a neutrophil (cyan arrow). F. A PAS with diastase stain colors the arteriole (red arrow), as well as the rim of the interlobular duct within which lies a neutrophil (cyan arrow).

A.[[File:1 Sep Acu Cho 1 680x512px.tif|Low power shows variably sized inflamed portal tracts (40X)]]
 
B. [[File:2 Sep Acu Cho 1 680x512px.tif|Trichrome shows dilated sinusoids and space of Disse collagenization (200X)]]
 
C. [[File:3 Sep Acu Cho 1 680x512px.tif|Inflammatory focus with macrophages and neutrophils (400X).]]
 
D. [[File:4 Sep Acu Cho 1 680x512px.tif|PAS with diastase shows proliferated bile ductules at edge of triad with neutrophils, which should not be used to make a definite diagnosis of acute cholangitis (400X).]]
 
E. [[File:5 Sep Acu Cho 1 680x512px.tif|PAS without diastase showing acutely inflamed bile duct, with accompanying blood vessel of similar size, diagnostic of acute cholangitis (400X).]]
 
F. [[File:6 Sep Acu Cho 1 680x512px.tif|PAS with diastase showing neutrophil in bille duct lumen, diagnostic of acute cholangitis (400X).]]
 
Patient with sepsis and acute cholangitis. A. Low power shows variably sized inflamed portal tracts. B. Trichrome shows dilated sinusoids and space of Disse collagenization. C. Inflammatory focus with macrophages and neutrophils. D. PAS with diastase shows proliferated bile ductules at edge of triad with neutrophils, which should not be used to make a definite diagnosis of acute cholangitis. E. PAS without diastase showing acutely inflamed bile duct, with accompanying blood vessel of similar size, diagnostic of acute cholangitis. F. PAS with diastase showing neutrophil in bille duct lumen, diagnostic of acute cholangitis.

==Polycystic kidney disease and the liver==
{{Main|Cystic kidney disease}}
===General===
Complications of PKD in the liver:<ref>{{Ref MacSween|174-5}}</ref>
#Infected cyst.
#Cholangiocarcinoma.
#Cholestasis/obstruction due to duct compression.<ref>URL: [http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=9184868 http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=9184868]. Accessed on: 23 September 2009.</ref>

Cysts:
*Cysts in the liver, like the kidney, are thought to enlarge with age.

===Microscopic===
Features:<ref>{{Ref MacSween|176}}</ref>
*''Von Meyenburg complexes'' ([[bile duct hamartoma]]):
**Cluster of dilated ducts with "altered" bile.
**Surrounded by collagenous stroma.
**Separate from the portal areas.<ref>Meyenburg complex. Stedman's Medical Dictionary. 27th Ed.</reF>

Images:
*[http://commons.wikimedia.org/wiki/File:Von_Meyenburg_complex_low_mag.jpg Von Meyenburg complex - bile duct hamartoma (WC)].
*[http://commons.wikimedia.org/wiki/File:Bile_duct_hamartoma_intermed_mag.jpg Bile duct hamartoma (WC)].

Notes:
*Appearance on ultrasound<ref name=pmid17287178>Bile duct hamartomas--the von Meyenburg complex. Salles VJ, Marotta A, Netto JM, Speranzini MB, Martins MR. Hepatobiliary Pancreat Dis Int. 2007 Feb;6(1):108-9. PMID 17287178.</ref> and CT (hypodense)<ref name=pmid19294869>[The von Meyenburg complex] Schwab SA, Bautz W, Uder M, Kuefner MA. Rontgenpraxis. 2008;56(6):241-4. German. PMID 19294869.</ref> - similar to metastases.

==Peliosis hepatis==
===General===
*Associated with:
**Infections.
**Malignancy.
**Other stuff.
*Rarely biopsied.

===Microscopic===
Features:
*Cyst lined by endothelium.
**Usu. incomplete.
*Blood.
{|
[[File:1 PEL 1 680x512px.tif|Hemorrhage at left end, dilated sinusoids elsewhere (20X).]]
[[File:2 PEL 1 680x512px.tif|Ramifying dilated sinusoidal spaces (100X).]]
 
[[File:3 PEL 1 680x512px.tif|PAS with diastase shows flat lining (400X).]]
[[File:4 PEL 1 680x512px.tif|Necrotic hepatocytes in cords, presumably due to pressure (400X).]]
|}
Peliosis hepatis. Hemorrhage at left end, dilated sinusoids elsewhere (UL 20X). Ramifying dilated sinusoidal spaces (UR 100X). PAS with diastase shows flat lining (LL 400X). Necrotic hepatocytes in cords, presumably due to pressure (LR 400X).

==Total parenteral nutrition==
*Abbreviated ''TPN''.

===General===
*Indication: short gut syndrome, others.

===Microscopic===
Variable - may range from: steatosis, steatohepatitis, cholestasis, fibrosis and cirrhosis.<ref name=pmid16766237>{{cite journal |author=Guglielmi FW, Boggio-Bertinet D, Federico A, ''et al.'' |title=Total parenteral nutrition-related gastroenterological complications |journal=Dig Liver Dis |volume=38 |issue=9 |pages=623–42 |year=2006 |month=September |pmid=16766237 |doi=10.1016/j.dld.2006.04.002 |url=}}</ref>

Features (classic):<ref>{{Cite journal | last1 = Li | first1 = SJ. | last2 = Nussbaum | first2 = MS. | last3 = McFadden | first3 = DW. | last4 = Gapen | first4 = CL. | last5 = Dayal | first5 = R. | last6 = Fischer | first6 = JE. | title = Addition of glucagon to total parenteral nutrition (TPN) prevents hepatic steatosis in rats. | journal = Surgery | volume = 104 | issue = 2 | pages = 350-7 | month = Aug | year = 1988 | doi = | PMID = 3135627 }}</ref><ref>{{Cite journal | last1 = Stanko | first1 = RT. | last2 = Nathan | first2 = G. | last3 = Mendelow | first3 = H. | last4 = Adibi | first4 = SA. | title = Development of hepatic cholestasis and fibrosis in patients with massive loss of intestine supported by prolonged parenteral nutrition. | journal = Gastroenterology | volume = 92 | issue = 1 | pages = 197-202 | month = Jan | year = 1987 | doi = | PMID = 3096806 }}
</ref>
*[[Steatosis]] (periportal) - early.
*Cholestasis - late.

==Giant cell hepatitis==
*[[AKA]] ''neonatal giant cell hepatitis''.

:See: ''[[Giant cell hepatitis]]''.

==Hepatic amyloidosis==
{{Main|Amyloidosis}}
*[[AKA]] ''liver amyloidosis''.
*[[AKA]] ''amyloidosis of the liver''.
===General===
*Diffuse abundant amyloid within the space of Disse is associated with [[portal hypertension]].<ref name=pmid1864548>{{Cite journal | last1 = Bion | first1 = E. | last2 = Brenard | first2 = R. | last3 = Pariente | first3 = EA. | last4 = Lebrec | first4 = D. | last5 = Degott | first5 = C. | last6 = Maitre | first6 = F. | last7 = Benhamou | first7 = JP. | title = Sinusoidal portal hypertension in hepatic amyloidosis. | journal = Gut | volume = 32 | issue = 2 | pages = 227-30 | month = Feb | year = 1991 | doi = | PMID = 1864548 | PMC = 1378815 | URL = http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1378815/?tool=pubmed }}</ref>

===Microscopic===
Features:
*Amorphous extracellular pink stuff on H&E - see ''[[amyloid]]'' article.

DDx:
*[[Fibrolamellar hepatocellular carcinoma]].

====Images====
<gallery>
Image:Hepatic_amyloidosis_-_low_mag.jpg | Amyloidosis of the liver - low mag. (WC)
Image:Hepatic_amyloidosis_-_intermed_mag.jpg | Amyloidosis of the liver - intermed. mag. (WC)
Image:Hepatic_amyloidosis_-_high_mag.jpg | Amyloidosis of the liver - high mag. (WC)
Image:Hepatic_amyloidosis_-_very_high_mag.jpg | Amyloidosis of the liver - very high mag. (WC)
</gallery>
{|
[[File:1 AMY 1 680x512px.tif|Amorphous material replaces hepatic parenchyma [4X]]]
[[File:2 AMY 1 680x512px.tif|Material barely stains blue on trichrome [10X]]]
 
[[File:3 AMY 1 680x512px.tif|Material stains red on unpolarized Congo Red [40X]]]
[[File:4 AMY 1 680x512px.tif|Material stains apple green on polarized Congo Red [40X]]]
|}
Amyloidosis. Amorphous material replaces hepatic parenchyma [UL 4X]. Material barely stains blue on trichrome [UR 10X] Material stains red on unpolarized Congo Red [LL 40X] Material stains apple green on polarized Congo Red [LR 40X]

===Stains===
*[[Congo red]] +ve.

==Fulminant hepatic necrosis==
===General===
Etiology:
*Viral, i.e. [[Hepatitis A]], [[Hepatitis B]]; [[Hepatitis C]] - extremely rare.
*Trauma.
*Shock.

===Microscopic===
{|
[[File:1 Necrosis 2 680x512px.tif| Submassive hepatic necrosis.]]
[[File:2 Necrosis 2 680x512px.tif| Submassive hepatic necrosis.]]
 
[[File:3 Necrosis 2 680x512px.tif| Submassive hepatic necrosis.]]
[[File:4 Necrosis 2 680x512px.tif| Submassive hepatic necrosis.]]
 
[[File:5 Necrosis 2 680x512px.tif| Submassive hepatic necrosis.]]
[[File:6 Necrosis 2 680x512px.tif| Submassive hepatic necrosis.]]
|}
Submassive hepatic necrosis. Patient had transaminases in the thousands that rapidly dropped to normal. Pink preserved parenchyma strews empty necrotic spaces (Row 1 Left 20X). Focus of necrosis with no apparent hepatocytes macrophages abuts apparently normal liver (Row 1 Right 200X). Iron stain shows the macrophages bear hemosiderin (Row 2 Left 200X). Reticulin stain highlights the recently dead liver cells (Row 2 Right 200X). Reticulin stain shows a necrotic bridge forming; the multiple small black circles preclude diagnosis of a fibrous bridge (Row 3 Left 200X). Trichrome shows the necrotic bridge (“collapse”) lacks much collagen deposition, as would be expected for bridging fibrosis (Row 3 Right 200X).

Features:
*Hepatocyte [[necrosis]].
*Bile duct proliferation.

DDx:
*[[Cholangiocarcinoma]].
*[[Angiosarcoma]].

==Secondary hemochromatosis==
:''For the hereditary one see [[hereditary hemochromatosis]]''.
===General===
*Iron overload secondary to blood transfusions for hereditary or acquired anemia.<ref name=pmid19727383/>
**Primary hemochromatosis due to a defect in iron processing - called ''[[hereditary hemochromatosis]]''.
*Imaging considered the best test, as iron deposition is patchy.<ref name=pmid19727383/>

Selected hereditary causes:<ref name=pmid19727383>{{Cite journal | last1 = Gattermann | first1 = N. | title = The treatment of secondary hemochromatosis. | journal = Dtsch Arztebl Int | volume = 106 | issue = 30 | pages = 499-504, I | month = Jul | year = 2009 | doi = 10.3238/arztebl.2009.0499 | PMID = 19727383 | PMC = 2735704 | URL = http://www.ncbi.nlm.nih.gov.myaccess.library.utoronto.ca/pmc/articles/PMC2735704/?tool=pubmed}}</ref>
*Thalassemia.
*[[Sickle cell anemia]].
*Hereditary sideroblastic anemia.

Selected acquired causes:<ref name=pmid19727383/>
*[[Myelodysplastic syndromes]]
*Myelofibrosis
*Aplastic anemia, intractable.

===Microscopic===
:See ''[[hereditary hemochromatosis]]''.

==Hepatic sarcoidosis==
{{Main|Hepatic sarcoidosis}}
==Overlapping Disorders==

[[File:1 Mixed Disorder 1 680x512px.tif|Changes of steatohepatitis and interface hepatitis, with granuloma. Patient with diabetes was ANA, AMA, HCV, HBV negative, without drugs known to produce granulomas or interface hepatitis. This may be a case of AMA negative primary biliary cirrhosis, but studies to determine that with certainty were not performed.]]
[[File:2 Mixed Disorder 1 680x512px.tif|Changes of steatohepatitis and interface hepatitis, with granuloma. Patient with diabetes was ANA, AMA, HCV, HBV negative, without drugs known to produce granulomas or interface hepatitis. This may be a case of AMA negative primary biliary cirrhosis, but studies to determine that with certainty were not performed.]]
[[File:3 Mixed Disorder 1 680x512px.tif|Changes of steatohepatitis and interface hepatitis, with granuloma. Patient with diabetes was ANA, AMA, HCV, HBV negative, without drugs known to produce granulomas or interface hepatitis. This may be a case of AMA negative primary biliary cirrhosis, but studies to determine that with certainty were not performed.]]
[[File:4 Mixed Disorder 1 680x512px.tif|Changes of steatohepatitis and interface hepatitis, with granuloma. Patient with diabetes was ANA, AMA, HCV, HBV negative, without drugs known to produce granulomas or interface hepatitis. This may be a case of AMA negative primary biliary cirrhosis, but studies to determine that with certainty were not performed.]]
[[File:5 Mixed Disorder 1 680x512px.tif|Changes of steatohepatitis and interface hepatitis, with granuloma. Patient with diabetes was ANA, AMA, HCV, HBV negative, without drugs known to produce granulomas or interface hepatitis. This may be a case of AMA negative primary biliary cirrhosis, but studies to determine that with certainty were not performed.]]
[[File:6 Mixed Disorder 1 680x512px.tif|Changes of steatohepatitis and interface hepatitis, with granuloma. Patient with diabetes was ANA, AMA, HCV, HBV negative, without drugs known to produce granulomas or interface hepatitis. This may be a case of AMA negative primary biliary cirrhosis, but studies to determine that with certainty were not performed.]] 
Changes of steatohepatitis and interface hepatitis, with granuloma. Patient with diabetes was ANA, AMA, HCV, HBV negative, without drugs known to produce granulomas or interface hepatitis. This may be a case of AMA negative primary biliary cirrhosis, but studies to determine that with certainty were not performed. A. Low power shows hepatocytes afflicted by steatosis and an inflamed portal tract. B. In a region of fatty change lie cytoplasmic tufts of ballooning degeneration (green arrows) and a lipogranuloma (black arrow). C. At the portal-hepatocyte junction lies interface hepatitis (black arrows), as well as extension of inflammation into the lobule (green arrows). D. Red hepatocytes bounded by inflammation denote piecemeal necrosis [PAS without diastase]. E. Giant cells intermixed with lymphocytes prove a portal granuloma [PAS without diastase]. F. A blue fibrous bridge extends from a triad [Trichrome].

[[File:4 95599552608917 sl 1.png|Acute obstructive changes and changes of recurrent acute injury]]
[[File:4 95599552608917 sl 2.png|Acute obstructive changes and changes of recurrent acute injury]]
[[File:4 95599552608917 sl 3.png|Acute obstructive changes and changes of recurrent acute injury]]
[[File:4 95599552608917 sl 4.png|Acute obstructive changes and changes of recurrent acute injury]]
[[File:4 95599552608917 sl 5.png|Acute obstructive changes and changes of recurrent acute injury]]
[[File:4 95599552608917 sl 6.png|Acute obstructive changes and changes of recurrent acute injury]]
[[File:4 95599552608917 sl 7.png|Acute obstructive changes and changes of recurrent acute injury]] 
Acute obstructive changes and changes of recurrent injury in 46 yo man with Clostridium perfringens positive blood culture, an ERCP that showed duodenal compression by the pancreas with resultant bile duct dilatation. The patient had had and continued to have multiple bouts of acute pancreatitis. At the time of biopsy, decreased platelet count/hemoglobin/albumin, elevated lipase/amylase/PT/PTT, normal alkaline phosphatase, bilirubin, AST/ALT, AMA, hepatitis virus serology, ANA. A. Fragment biopsy shows inflamed triads and bridges. B. Trichrome shows bridges without nodules, evidence of prior injury; the patient subsequently developed multiple episodes of pancreatitis. C. Reticulin shows piecemeal necrosis, with black lines bounding individual hepatocytes at interface (arrows). D. Collapse is shown by closly approximated thick black lines; one cannot call portal-central collapse without seeing a central vein. Note on this and the other reticulin image that regeneration, two cell thick cords, is not prominent. E. PAS D of two portal triads, far nearer than normal, both expanded. Note increased number of ducts/ductules (red arrows), neutrophils, and PAS-D macrophages. F. PAS D shows collapse extending from a triad to a portion of a lobule with steatosis. No feathery degeneration or bile duct plugs were seen. Neither were foci of spotty necrosis or abscess seen. G. Other triads, again edematous, showed more of a chronic inflammatory response, with occasional plasma cells (black arrows). Also present are neutrophils (red arrows). The bile duct (grey arrow) near the artery (brown arrow) shows mildly disturbed nuclei. Note early proliferated bile ductules (cyan arrows).

[[File:6 17281676469188 sl 1.png| Hepatitis B virus with steatohepatitis]]
[[File:6 17281676469188 sl 2.png| Hepatitis B virus with steatohepatitis]]
[[File:6 17281676469188 sl 3.png| Hepatitis B virus with steatohepatitis]]
[[File:6 17281676469188 sl 4.png| Hepatitis B virus with steatohepatitis]]
[[File:6 17281676469188 sl 5.png| Hepatitis B virus with steatohepatitis]]
[[File:6 17281676469188 sl 6.png| Hepatitis B virus with steatohepatitis]] 
Hepatitis B virus with steatohepatitis in a 36 year old man with hepatitis B surface antigen and hepatitis Be antigen positivity, Hepatitis be QTPC of 1750 cop/mL, an occasionally mildly elevated (42) ALT, and normal glucose, alkaline phosphatase, bilirubin, and other transaminases. He had a history of alcohol abuse, which became controlled. A. Triads show scant inflammation without definite interface hepatitis. About one-fourth of the lobule, not pan-acinar, is afflicted by steatosis. B. Occasional tufts are seen (arrow), indicating focal ballooning sufficient for a diagnosis of steatohepatitis. C. Glycogenated nuclei (black arrows) and hepatocytes with feathery degeneration (red arrows) are seen. D. Very rare foci of spotty necrosis were seen. E. Apart from this triad and the one in the trichrome stain in F, which had moderate inflammation comprising lymphocytes and macrophages, all triads were small, most without any inflammation at all. Neither collapse nor piecemeal necrosis were seen on reticulin stain. F. Trichrome stain showed only portal fibrosis. The interhepatocyte fibrosis required for brunt fibrosis stage I was not seen. Hence, one would grade this as follows: A) Chronic hepatitis (history of hepatitis B), Metavir activity index 1, Piecemeal necrosis 0, Lobular necrosis 1, Metavir fibrosis stage 1, B) Steatohepaitits, Brunt necroinflammatory grade 1, Brunt fibrosis stage 0.

=See also=
*[[Pancreas]].
*[[Gastrointestinal pathology]].
*[[Liver neoplasms]].
*[[Liver]].

=References=
{{reflist|2}}

[[Category:Gastrointestinal pathology]]
[[Category:Liver pathology]]
[[Category:Medical liver disease]]

Medical liver disease

2017-01-23T15:43:20Z

Mitchell: /* Abscess */

[[Image:Ground glass hepatocytes high mag cropped 2.jpg|thumb|right|[[Micrograph]] showing ground glass hepatocytes, as seen in chronic [[hepatitis B]]. [[H&E stain]].]]
This article deals with '''medical [[liver]] disease'''. An introduction to the liver and approach is found in the ''[[liver]]'' article.

Every differential in liver pathology has "drugs"<ref>{{Ref PCPBoD8|448}}</ref> -- if it isn't clearly malignancy.

Liver neoplasms are dealt with in the ''[[liver neoplasms]]'' article.

Medical liver biopsies are often non-specific, as the liver has the same appearance for many mechanisms of injury, especially when the injury is marked. The clinical history, serology and imaging are essential for proper interpretations in this domain of pathology.

=Review of liver blood work=
===Inflammation activity===
*ALT.
*AST.

===Cholestatic markers===
*ALP.
*GGT - used to assess whether the ALP is an "honest" value, elevated in cirrhosis.

===Cirrhosis/decompensation===
*PLT - low is suggestive of dysfunction.
*INR - high is bad, unless anticoagulated.

===Other===
*Bilirubin.
**Direct (AKA conjugated).
**Indirect (AKA unconjugated).

A short DDx of elevated:<ref>{{Ref PCPBoD8|441}}</ref>
*Indirect:
**[[Gilbert syndrome]].
**Crigler-Najjar syndrome type 1.
**Crigler-Najjar syndrome type 2.
*Direct:
**Rotor syndrome.
**Dubin-Johnson syndomre.

===Viral hepatitis===
*HBV DNA.
*HCV RNA.
*HBs Ag, HBs Ab, HBe Ag, HBe Ab.
*HCV Ab.

Others:
*[[Epstein-Barr virus]] (EBV).
*[[Cytomegalovirus]] (CMV) - especially in the immune incompetent.

====Hepatitis B====
Meaning & utility of the various [[Hepatitis B]] tests:<ref>URL: [http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/hepatology/hepatitis-B/ http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/hepatology/hepatitis-B/]. Accessed on: 16 May 2011.</ref><ref name=lto_hepb>URL: [http://www.labtestsonline.org/understanding/analytes/hepatitis_b/test.html http://www.labtestsonline.org/understanding/analytes/hepatitis_b/test.html]. Accessed on: 16 May 2011.</ref>
{| class="wikitable sortable" border="1"
! Test name
! Location
! Positive test
! Negative test
! Usual question
|-
| HBs Ag||Surface||Virus active||No active infection||Active infection?
|-
| HBs Ab||Surface||Exposed OR vaccinated||No exposure OR no vaccine OR loss of Ab||Immunization status?
|-
| HBe Ag||Virus core||Infect. w/ viral replication||No active infection||Active infect. w/ viral replication?
|-
| HBe Ab||Virus core||Exposed to virus||Infect. w/o antibody response OR not exposed||Immune response to infection?
|-
| HBV DNA||-||Active||Not active/no exposure||Viral load/how active?
|-
| HBc Ab||Virus core||Virus active/previous exposure||No exposure||Early active infection?
|}
Notes:
*''HBc Ab'' may test for acute (IgM) or chronic infection - dependent on specific antibody test; it is often used to look for early infection.<ref name=lto_hepb>URL: [http://www.labtestsonline.org/understanding/analytes/hepatitis_b/test.html http://www.labtestsonline.org/understanding/analytes/hepatitis_b/test.html]. Accessed on: 16 May 2011.</ref>
*''Carriers of hepatitis B'': HBs Ag +ve, HBs Ab -ve, HBc Ag -ve, HBc Ab +ve, HBe Ag -ve, HBe Ab +ve.<ref>URL: [http://labtestsonline.org/understanding/analytes/hepatitis-b/tab/test http://labtestsonline.org/understanding/analytes/hepatitis-b/tab/test]. Accessed on: 3 May 2012.</ref>

===Markers for rare liver diseases===
*Ceruloplasm - low think ''[[Wilson's disease]]''; typical value for Wilson's ~ 0.12 g/L.
**<0.20 g/L is a criteria for Wilson's disease.<ref name=pmid18556333>Diagnostic accuracy of serum ceruloplasmin in Wilson disease: determination of sensitivity and specificity by ROC curve analysis among ATP7B-genotyped subjects. Mak CM, Lam CW, Tam S. Clin Chem. 2008 Aug;54(8):1356-62. Epub 2008 Jun 12. PMID 18556333. URL: [http://www.clinchem.org/cgi/reprint/54/8/1356.pdf http://www.clinchem.org/cgi/reprint/54/8/1356.pdf]. Accessed on: 28 September 2009.</ref>
*Alpha-1 antitrypsin - if low think ''deficiency''.

===Hemosiderosis===
*Ferritin - high.
*Iron saturation - high.

Causes:
*Hemochromatosis.
*Hemolysis, chronic.
*Cirrhosis.

=Medical imaging=
Blood flow:<ref>URL: [http://insidesurgery.com/2010/12/hepatopedal-hepatofugal-flow/ http://insidesurgery.com/2010/12/hepatopedal-hepatofugal-flow/]. Accessed on: 2 December 2011.</ref>
*Hepatopedal flow = normal portal vein flow.
*Hepatofugal flow = reversed portal vein flow.

==Interventional measurements==
Wedged to free hepatic venous pressure:<ref name=pmid1864548>{{Cite journal | last1 = Bion | first1 = E. | last2 = Brenard | first2 = R. | last3 = Pariente | first3 = EA. | last4 = Lebrec | first4 = D. | last5 = Degott | first5 = C. | last6 = Maitre | first6 = F. | last7 = Benhamou | first7 = JP. | title = Sinusoidal portal hypertension in hepatic amyloidosis. | journal = Gut | volume = 32 | issue = 2 | pages = 227-30 | month = Feb | year = 1991 | doi = | PMID = 1864548 | PMC = 1378815 | URL = http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1378815/?tool=pubmed }}</ref>
*Normal = 1-4 mmHg.
**Elevated in [[portal hypertension]].

=Liver biopsy=
==Medical liver biopsy adequacy==
Liver biopsy specimens should be:<ref>{{Ref MacSween|418}}</ref>
*2.0 cm in length and contain 11-15 portal tracts,
*The core should be deeper than 1.0 cm from the liver capsule; specimens close to the capsule may lead to over grading of fibrosis.

==Reporting==
{{Main|Pathology reports}}
<pre>
Specimen, procedure:
- Diagnosis.
</pre>
The diagnosis usually contains grading and staging information, e.g. ''activity 2 /4, Laennec fibrosis stage 1 /4''.

In the context of medical liver disease:
*Grade = inflammation/activity.
*Stage = severity of fibrosis/architectural changes.

Notes:
*The term "acute" is infrequently used in liver pathology.
*In the liver: neutrophils ''is not'' acute -- unlike most elsewhere in the body.<ref>OA. September 2009.</ref>

===A microscopic checklist===
<pre>
Size of biopsy: Adequate
Fragmentation: Absent
Fibrosis: Stage 2-3/4, mostly stage 2
Fibrous septa: Present
Septa with curved contours: Present – focally only
Large droplet steatosis (% of hepatocytes): Present, moderate 60%
Ballooning of hepatocytes: Present, rare
Mallory-Denk bodies: Present, rare
Portal inflammation: Present
Interface activity: Minimal (0-1/4)
Lobular necroinflammation: Minimal
Ducts: Present in normal numbers
Duct injury: Absent
Ductular reaction: Absent
Cholestasis: Absent
Terminal hepatic venules: Present
Iron stain: Absent
Ground glass cells with routine stains: Absent
PASD for alpha-1 antitrypsin droplets: Negative
</pre>

=Viral hepatitis=
These are common. The diagnoses are based on serology. The serology is covered in the ''[[Liver_pathology#Viral_hepatitis|viral hepatitis]]'' section in the ''[[liver pathology]]'' article.

Typically classified as:<ref name=pmid8048409>{{Cite journal | title = Terminology of chronic hepatitis, hepatic allograft rejection, and nodular lesions of the liver: summary of recommendations developed by an international working party, supported by the World Congresses of Gastroenterology, Los Angeles, 1994. | journal = Am J Gastroenterol | volume = 89 | issue = 8 Suppl | pages = S177-81 | month = Aug | year = 1994 | doi = | PMID = 8048409 }}</ref><ref>URL: [http://familydoctor.org/familydoctor/en/diseases-conditions/hepatitis-b.html http://familydoctor.org/familydoctor/en/diseases-conditions/hepatitis-b.html]. Accessed on: 2 May 2012.</ref>
#Acute < 6 months duration.
#Chronic > 6 months duration.

==Hepatitis A==
*Infection is self-limited, i.e. not persistent.
**May present as ''[[fulminant hepatic necrosis]]''.
*Usually asymptomatic in children.<ref name=pmid20068336>{{cite journal |author=Jeong SH, Lee HS |title=Hepatitis A: clinical manifestations and management |journal=Intervirology |volume=53 |issue=1 |pages=15–9 |year=2010 |pmid=20068336 |doi=10.1159/000252779 |url=}}</ref>
*Serology is diagnostic.

==Hepatitis B==
:''Hepatitis B virus'', abbreviated ''HBV'', redirects here.
{{Main|Hepatitis B}}

==Hepatitis C==
{{Main|Hepatitis C}}

=Other infections=
*Hydatid disease (Hydatid cyst).
*Ascaris.
*Fasciola

==Hydatid disease==
*[[AKA]] ''hydatid cyst''.
===General===
*Etiology: ''[[Echinococcus]]''.

===Microscopic===
Features:
*Laminated wall +/- calcification.<ref name=Ref_PBPoD8_448>{{Ref PCPBoD8|448}}</ref>
*Organisms -- see ''[[Echinococcus]]''.

====Images====
<gallery>
Image:Liver_cyst_wall_-_intermed_mag.jpg | Liver cyst wall - intermed. mag. (WC)
Image:Liver_cyst_wall_-_high_mag.jpg | Liver cyst wall - high mag. (WC)
Image: Laminated liver cyst wall - intermed mag.jpg | Characteristic laminated portion - intermed. mag. (WC)
Image: Laminated liver cyst wall - high mag.jpg | Characteristic laminated portion - high mag. (WC)
</gallery>
[[www]]:
*[http://pathmicro.med.sc.edu/parasitology/hydatid-hist1.jpg Hydatid cyst (med.sc.edu)].
*[http://www.atlas.or.kr/atlas/include/viewImg.html?uid=645 Hydatid cyst (atlas.or.kr)].
*[http://casereports.bmj.com/content/2009/bcr.04.2009.1798.full Hydatid cyst (casereports.bmj.com)].

==Abscess==
A. [[File:1 ABS 1 680x512px.tif|A process replaces most of the liver parenchyma (20X).]]
 
B. [[File:2 ABS 1 680x512px.tif|Fibrinopurulent exudate apposes granulation tissue (200X).]]
 
C. [[File:3 ABS 1 680x512px.tif|Neutrophils lie in widened sinusoids (200X)..]]
 
D. [[File:4 ABS 1 680x512px.tif|Trichrome shows collagenization of spaces of Disse. Scarring about an abscess or other mass lesion should not be interpreted as reflective of the liver in general (200X).]]
 
Abscess. A. A process replaces most of the liver parenchyma. B. Fibrinopurulent exudate apposes granulation tissue. C. Neutrophils lie in widened sinusoids. D. Trichrome shows collagenization of spaces of Disse. Scarring about an abscess or other mass lesion should not be interpreted as reflective of the liver in general (LR 200X).

==Coccidiomycosis==
Coccidiomycosis
Table show [[GRAN-COC]]
{|
[[File:Coccidiomycosis - 1 - 40X 680x512px shot.tif|500x500px Granulomas at low power]]
[[File:Coccidiomycosis - 1 - 200X 680x513px shot.tif|500x500px Granulomas with centrally crowded cells & lady slipper macrophage nuclei]]
 
[[File:Coccidiomycosis - 1 - 400X 1369x1024px shot.tif|500x500px Center of previous granuloma showing pyknotic macrophage nuclei]]
[[File:Coccidiomycosis - 1 - GMS 400X 1369x1024px shot.tif|500x500px Four Coccidiomycotic spherules]]
|}
Note the granulomas in otherwise undisturbed liver (UL), the larger prior granuloma with centrally crowded cells & lady slipper macrophage nuclei (UR), the center of the granuloma with pyknotic macrophage nuclei "necrotizing" (LL), and the organisms on GMS stain (LR).

=Metabolic and toxic=
==Alcoholic liver disease==
===General===
*Acute and/or chronic liver changes due to excessive [[alcohol]] use - includes:
**''[[Alcoholic steatohepatitis]]'' (ASH), [[AKA]] ''alcoholic hepatitis''.<ref>URL: [http://emedicine.medscape.com/article/170539-overview http://emedicine.medscape.com/article/170539-overview]. Accessed on: 3 May 2012.</ref>
***Alcoholic hepatitis can be with minimal steatosis.<ref>STC. 6 December 2010.</ref>
**[[Steatosis]] - classically macrovescicular and centrilobular.
**Alcoholic [[cirrhosis]].

====Classic lab findings in EtOH abusers====
*AST & ALT elevated with AST:ALT=2:1.
*GGT elevated.
*MCV increased.

===Gross pathology/radiologic findings===
*Classically micronodular pattern.
**May be macronodular.

===Microscopic===
See:
*''[[Steatohepatitis]]'' section and ''[[ballooning degeneration]]'' section.

Features:
*Often zone III damage.
*Cholestatsis common, i.e. yellow staining.
**NASH (non-alcoholic steatohepatitis) usu. does not have cholestasis.<ref>STC. 6 December 2010.</ref>
*Fibrosis starts at central veins.
*Neutrophils (often helpful) -- few other things have PMNs. (???)
**Neutrophils cluster around cells with Mallory hyaline.

====Images====
{|
[[File:1 etoh 3 680x512px.tif| Alcoholic hepatitis with Metavir stage IV fibrosis (advanced fibrosis/cirrhosis).]]
[[File:2 etoh 3 680x512px.tif| Alcoholic hepatitis with Metavir stage IV fibrosis (advanced fibrosis/cirrhosis).]]
 
[[File:3 etoh 3 680x512px.tif| Alcoholic hepatitis with Metavir stage IV fibrosis (advanced fibrosis/cirrhosis).]]
[[File:4 etoh 3 680x512px.tif| Alcoholic hepatitis with Metavir stage IV fibrosis (advanced fibrosis/cirrhosis).]]
 
[[File:5 etoh 3 680x512px.tif| Alcoholic hepatitis with Metavir stage IV fibrosis (advanced fibrosis/cirrhosis).]]
[[File:6 etoh 3 680x512px.tif| Alcoholic hepatitis with Metavir stage IV fibrosis (advanced fibrosis/cirrhosis).]]
|}
Alcoholic hepatitis with Metavir stage IV fibrosis (advanced fibrosis/cirrhosis).
Trichrome shows relatively non-inflamed fibrous bands, as well as [between green dots] nodules. The lack of regeneration throughout might have precluded a diagnosis of cirrhosis, but stage IV fibrosis under the Metavir system is justified (Row 1 Left 20X). Reticulin shows regenerative nodules [left] with mostly two or more nuclei between black lines juxtaposed to non-regenerative hepatocytes on the right, without piecemeal necrosis. (Row 1 Right 100X). Regenerative nodules show occasional neutrophils [red arrow] and cytoplasmic tufts of ballooned cells, sometimes possibly Mallory hyalin [green arrows] (Row 2 Left 200X). Triads (note vein [green arrow], artery [yellow arrow], and interlobular bile duct [blue arrow]) generally showed little or no interface hepatitis, even when expanded by fibrosis and inflamed (Row 2 Right 200X). Occasional foci of spotty necrosis were seen (Row 3 Left 200X). This edge of an inflamed triads shows neutrophils about proliferated bile ducts [red arrows], as well as Mallory-Denk bodies [blue arrows] (Row 4 Left 400X).
{|
[[File:1 etoh 4 680x512px.tif| Cirrhosis in an alcoholic.]]
[[File:2 etoh 4 680x512px.tif| Cirrhosis in an alcoholic.]]
 
[[File:3 etoh 4 680x512px.tif| Cirrhosis in an alcoholic.]]
[[File:4 etoh 4 680x512px.tif| Cirrhosis in an alcoholic.]]
 
[[File:5 etoh 4 680x512px.tif| Cirrhosis in an alcoholic.]]
[[File:6 etoh 4 680x512px.tif| Cirrhosis in an alcoholic.]]
|}
Definite cirrhosis in an alcoholic. Hepatocyte free bands parse tissue, with occasional definite islands [arrows] (Row 1 Left 40X). Trichrome establishes blue fibrosis about isles [arrows] (Row 1 Right 40X). Reticulin stain shows nodules with regeneration, wherein a large proportion of them are at least two nuclei thick [arrows] (Row 2 Left 200X). Bile duct proliferation can be difficult, sometimes mimicking cholangiocarcinoma. Follow the double headed arrows to see how the ductules can be seen to proliferate from a single sources, with all ducts being complete, without necrotic epithelial cells. (Row 2 Right 400X). PAS with distase can help, as cholangiocarcinoma generally lacks the red rim of proliferating bile ductules [arrows]; again note the connections that can be made between the ductule openings by the blue double headed arrows. The cyan double headed arrows show general parallelism, consistent with uniform directionality induced by extrinsic force, not a neoplastic spread (Row 3 Left 400X). Trichrome shows the most difficult focus. Double headed arrows display the connectivity seen before of the proliferated bile ductules. Note that numerous pairs of adjacent perpendicular glands without a head to foot appearance are not seen that would indicate the disorderly spread of cholangiocarcinoma (Row 3 Right 400X).

{|
[[File:1 ALC 2 680x512px.tif|Expanded, inflamed triads with increased bile duct/vascular openings. Mild steatosis (40X).]]
[[File:2 ALC 2 680x512px.tif|Trichrome stain shows periportal fibrosis [red arrowheads] (200X).]]
 
[[File:3 ALC 2 680x512px.tif|PAS with diastase stain shows proliferated bile ductules [blue arrowheads] in stroma with mixed inflammatory infiltrate (400X)]]
[[File:4 ALC 2 680x512px.tif|Neutrophils about ballooned hepatocyte (satellitosis) [yellow arrowheads]. Councilman bodies [green arrowheads] (400X).]]
|}
Alcoholic hepatitis without cirrhosis. No history of viral disease. AMA negative. Expanded, inflamed triads with increased bile duct/vascular openings. Mild steatosis (UL 40X). Trichrome stain shows periportal fibrosis [red arrowheads] (UR 200X). PAS with diastase stain shows proliferated bile ductules [blue arrowheads] in stroma with mixed inflammatory infiltrate (LL 400X) Neutrophils about ballooned hepatocyte (satellitosis) [yellow arrowheads]. Councilman bodies [green arrowheads] (LR 400X).

Notes:
*If portal inflammatory infiltrates more than mild, r/o other causes i.e. [[viral hepatitis]].
*Mallory bodies once thought to be characteristic; now considered non-specific and generally poorly understood.<ref>{{cite journal |author=Jensen K, Gluud C |title=The Mallory body: theories on development and pathological significance (Part 2 of a literature survey) |journal=Hepatology |volume=20 |issue=5 |pages=1330-42 |year=1994 |month=November |pmid=7927269 |doi= |url=}}</ref>
*Some consider ''alcoholic liver disease'' a clinical diagnosis, i.e. as a pathologist one does not diagnose it.<ref>MG. September 2009.</ref>

==Non-alcoholic fatty liver disease==
*Abbreviated ''NAFLD''.
*Fatty liver that is not due to alcohol; includes obesity-related fatty liver, metabolic disease/diabetes-related fatty liver.

===NASH===
*Non-alcoholic steatohepatitis - see ''steatohepatitis'' section.
*Histologically indistinguishable from ASH.
*NASH is a ''clinical diagnosis'' based on exclusion of alcohol.

==Steatohepatitis==
{{Main|Steatohepatitis}}

=Autoimmune=
==Autoimmune hepatitis==
*Abbreviated ''AIH''.
{{Main|Autoimmune hepatitis}}

==Primary biliary cirrhosis==
*Abbreviated PBC.
{{Main|Primary biliary cirrhosis}}

==Autoimmune hepatitis with obstruction - combined changes==
{|
[[File:1 AIH OBS 1.tif|Low power shows inflammation; portal triads, lobules, central veins cannot be distinguished (40X).]]
[[File:2 AIH OBS 1.tif|Trichrome shows central venous sclerosis (red arrowhead), periportal fibrosis (green arrowhead), & space of Disse collagenization (yellow arrowhead); juxtaposition of central vein & portal tract indicates collapse, no definite bridging was seen (100X)]]
 
[[File:3 AIH OBS 1.tif|Central vein is inflamed with a rare plasma cell (cyan arrowhead) (400X).]]
[[File:4 AIH OBS 1.tif|Interface hepatitis with plasma cells (yellow arrows) and ballooned hepatocytes (red arrows). Lobule is disorganized (400X).]]
 
[[File:5 AIH OBS 1.tif|Proliferating bile ductules (blue arrows) with occasional neutrophils (fucsia arrows), indicative of obstruction, but not acute cholangitis, which requires inflamed bile duct itself, best diagnosed with associated blood vessel (400X).]]
[[File:6 AIH OBS 1.tif|Rare distorted rosettes with greenish brown strands of bile (left arrow) or bile plugs (right arrow) (400X).]]
|}
Patient with SLE and obstructive jaundice that resolved with apparent passage of stone. Low power shows inflammation; portal triads, lobules, central veins cannot be distinguished (left row 1 40X). Trichrome shows central venous sclerosis (red arrowhead), periportal fibrosis (green arrowhead), & space of Disse collagenization (yellow arrowhead); juxtaposition of central vein & portal tract indicates collapse, no definite bridging was seen (right row 1 100X). Central vein is inflamed with a rare plasma cell (cyan arrowhead) (left row 2 400X). Interface hepatitis with plasma cells (yellow arrows) and ballooned hepatocytes (red arrows). Lobule is disorganized (right row 2 400X). Proliferating bile ductules (blue arrows) with occasional neutrophils (fucsia arrows), indicative of obstruction, but not acute cholangitis, which requires inflamed bile duct itself, best diagnosed with associated blood vessel (left row 3 400X). Rare distorted rosettes with greenish brown strands of bile (left arrow) or bile plugs (right arrow) (right row 3 400X).

==Autoimmune hepatitis-primary biliary cirrhosis overlap syndrome==
*Abbreviation ''AIH-PBC OS''.
===General===
Epidemiology:
*Rare.

Serology:<ref name=pmid19491855>{{Cite journal | last1 = Muratori | first1 = P. | last2 = Granito | first2 = A. | last3 = Pappas | first3 = G. | last4 = Pendino | first4 = GM. | last5 = Quarneti | first5 = C. | last6 = Cicola | first6 = R. | last7 = Menichella | first7 = R. | last8 = Ferri | first8 = S. | last9 = Cassani | first9 = F. | title = The serological profile of the autoimmune hepatitis/primary biliary cirrhosis overlap syndrome. | journal = Am J Gastroenterol | volume = 104 | issue = 6 | pages = 1420-5 | month = Jun | year = 2009 | doi = 10.1038/ajg.2009.126 | PMID = 19491855 }}</ref>
*AMA +ve.
*Anti-dsDNA +ve.

===Microscopic===
:See: ''[[autoimmune hepatitis]]'' and ''[[primary biliary cirrhosis]]''.
{|
[[File:1 AIH PBC 1 680x512px.tif|Expanded portal tracts with fuzzy edges (40X).]]
[[File:2 AIH PBC 1 680x512px.tif|Interface hepatitis with plasma cells (400X).]]
 
[[File:3 AIH PBC 1 680x512px.tif|Loose granuloma (400X).]]
[[File:4 AIH PBC 1 680x512px.tif|Damaged bile duct (400X).]]
|}

AIH/PBC overlap. AMA & ANA positive with Alkaline phosphatase > 2 upper limit of normal & one ALT > 5 times upper limit of normal. Expanded portal tracts with fuzzy edges (UL 40X). IInterface hepatitis with plasma cells (UR 400X). Loose granuloma (LL 400X). Damaged bile duct (LR 400X).

==Primary sclerosing cholangitis==
*Abbreviated ''PSC''.
{{Main|Primary sclerosing cholangitis}}

=Hereditary=
==Caroli disease==
===General===
*Genetic disease.
**Frequently associated with [[autosomal recessive polycystic kidney disease]] (ARPKD).<ref name=omim263200>{{OMIM|263200}}</ref>
**May be seen in isolation.<ref name=omim600643>{{OMIM|600643}}</ref>

Clinical:<ref name=pmid17461493>{{Cite journal | last1 = Yonem | first1 = O. | last2 = Bayraktar | first2 = Y. | title = Clinical characteristics of Caroli's syndrome. | journal = World J Gastroenterol | volume = 13 | issue = 13 | pages = 1934-7 | month = Apr | year = 2007 | doi = | PMID = 17461493 }}</ref>
*Recurrent [[cholangitis]].
*Recurrent [[cholelithiasis]].
*[[Cholangiocarcinoma]]<ref name=pmid17461492>{{Cite journal | last1 = Yonem | first1 = O. | last2 = Bayraktar | first2 = Y. | title = Clinical characteristics of Caroli's disease. | journal = World J Gastroenterol | volume = 13 | issue = 13 | pages = 1930-3 | month = Apr | year = 2007 | doi = | PMID = 17461492 }}</ref> - seen in ~7% of cases.<ref name=pmid15347876>{{Cite journal | last1 = Karim | first1 = AS. | title = Caroli's disease. | journal = Indian Pediatr | volume = 41 | issue = 8 | pages = 848-50 | month = Aug | year = 2004 | doi = | PMID = 15347876 }}</ref>

Note:
*''Caroli syndrome'' = Caroli disease + congenital hepatic fibrosis.<ref name=pmid15888616>{{Cite journal | last1 = Brancatelli | first1 = G. | last2 = Federle | first2 = MP. | last3 = Vilgrain | first3 = V. | last4 = Vullierme | first4 = MP. | last5 = Marin | first5 = D. | last6 = Lagalla | first6 = R. | title = Fibropolycystic liver disease: CT and MR imaging findings. | journal = Radiographics | volume = 25 | issue = 3 | pages = 659-70 | month = | year = | doi = 10.1148/rg.253045114 | PMID = 15888616 | URL = http://radiographics.rsna.org/content/25/3/659.long }}</ref>

===Gross===
*Dilated bile ducts.<ref name=omim263200/>

===Microscopic===
Features:<ref name=pmid17461493/>
*Dilated bile ducts.
*Periductal fibrosis. (???)
*+/-Fibrosis.

Image:
*[http://www.meddean.luc.edu/lumen/MedEd/orfpath/11-3-10.jpg Caroli disease (meddean.luc.edu)].<ref>URL: [http://www.meddean.luc.edu/lumen/MedEd/orfpath/develop.htm http://www.meddean.luc.edu/lumen/MedEd/orfpath/develop.htm]. Accessed on: 1 December 2011.</ref>

==Hereditary hemochromatosis==
:''For secondary causes see [[secondary hemochromatosis]]''.
{{Main|Hereditary hemochromatosis}}

==Wilson disease==
{{Main|Wilson's disease}}

==Alpha-1 antitrypsin deficiency==
*[[AKA]] ''alpha1-antiprotease inhibitor deficiency''.
{{Main|Alpha-1 antitrypsin deficiency }}

=Other=
==Budd-Chiari syndrome==
*[[AKA]] ''hepatic vein obstruction''.
===General===
*Hepatic outflow obstruction.

Clinical triad:<ref name=pmid21573256>{{Cite journal | last1 = Fox | first1 = MA. | last2 = Fox | first2 = JA. | last3 = Davies | first3 = MH. | title = Budd-Chiari syndrome--a review of the diagnosis and management. | journal = Acute Med | volume = 10 | issue = 1 | pages = 5-9 | month = | year = 2011 | doi = | PMID = 21573256 }}</ref>
*Ascites.
*Abdominal pain.
*Hepatomegaly.

Etiology:
*~50% have a [[myeloproliferative disease]].<ref name=pmid18814079>{{Cite journal | last1 = Plessier | first1 = A. | last2 = Valla | first2 = DC. | title = Budd-Chiari syndrome. | journal = Semin Liver Dis | volume = 28 | issue = 3 | pages = 259-69 | month = Aug | year = 2008 | doi = 10.1055/s-0028-1085094 | PMID = 18814079 }}</ref>
*May be due to mass effect from a tumour.

Clinical DDx:
*[[Hepatic veno-occlusive disease]].

===Microscopic===
Features:<ref name=pmid17569137>{{Cite journal | last1 = Aydinli | first1 = M. | last2 = Bayraktar | first2 = Y. | title = Budd-Chiari syndrome: etiology, pathogenesis and diagnosis. | journal = World J Gastroenterol | volume = 13 | issue = 19 | pages = 2693-6 | month = May | year = 2007 | doi = | PMID = 17569137 | url=http://www.wjgnet.com/1007-9327/full/v13/i19/2693.htm }}</ref>
*Sinusoidal dilation in zone III (congestion).
*+/-Hepatocyte drop-out.
*+/-Centrilobular fibrosis.

DDx congestion:
*Congestive heart failure ([[congestive hepatopathy]]).
*Constrictive pericarditis.

==Vanishing bile duct syndrome==
*[[AKA]] ''bile duct loss'', [[AKA]] ''ductopenia''.<ref name=pmid11521176/>
===General===
*Fatal.

DDx:<ref name=pmid18242505/>
*[[Primary biliary cirrhosis]].
*[[Primary sclerosing cholangitis]].
*[[GVHD]].<ref name=pmid7994249>{{Cite journal | last1 = Yeh | first1 = KH. | last2 = Hsieh | first2 = HC. | last3 = Tang | first3 = JL. | last4 = Lin | first4 = MT. | last5 = Yang | first5 = CH. | last6 = Chen | first6 = YC. | title = Severe isolated acute hepatic graft-versus-host disease with vanishing bile duct syndrome. | journal = Bone Marrow Transplant | volume = 14 | issue = 2 | pages = 319-21 | month = Aug | year = 1994 | doi = | PMID = 7994249 }}</ref>
*[[Drug-induced liver disease|Drugs]].<ref name=pmid11352118>{{Cite journal | last1 = Chitturi | first1 = S. | last2 = Farrell | first2 = GC. | title = Drug-induced cholestasis. | journal = Semin Gastrointest Dis | volume = 12 | issue = 2 | pages = 113-24 | month = Apr | year = 2001 | doi = | PMID = 11352118 }}</ref>
*Chronic rejection.<ref name=pmid11521176>{{Cite journal | last1 = Inomata | first1 = Y. | last2 = Tanaka | first2 = K. | title = Pathogenesis and treatment of bile duct loss after liver transplantation. | journal = J Hepatobiliary Pancreat Surg | volume = 8 | issue = 4 | pages = 316-22 | month = | year = 2001 | doi = 10.1007/s0053410080316 | PMID = 11521176 }}</ref>

===Microscopic===
Features:<ref name=pmid18242505>{{Cite journal | last1 = Reau | first1 = NS. | last2 = Jensen | first2 = DM. | title = Vanishing bile duct syndrome. | journal = Clin Liver Dis | volume = 12 | issue = 1 | pages = 203-17, x | month = Feb | year = 2008 | doi = 10.1016/j.cld.2007.11.007 | PMID = 18242505 }}</ref>
*Loss of intrahepatitic bile ducts - '''key feature'''.
*Cholestasis.

Note:
*May occur without fibrosis and inflammation; thus, can be easy to miss.

===IHC===
*[[CK7]] -ve.
**Marks bile ducts.

==Extrahepatic biliary obstruction==
{|
[[File:1 OBS 3 680x512px.tif|Sinusoidal dilatation, circular spaces of hepatocytes, small portal triads(40X).]]
[[File:2 OBS 3 680x512px.tif|Bile in hepatocytes about central vein & in plugs in canaliculi [yellow arrowhead] (400X).]]
 
[[File:3 OBS 3 680x512px.tif|Trichrome shows fibrosis about central vein (400X).]]
[[File:4 OBS 3 680x512px.tif|PAS with diastase shows portal triads with mild edema and chronic inflammation, without tortuous bile duct (400X).]]
|}
Early extrahepatic biliary obstruction, demonstrated radiographically, transient, with rise in bilirubin, alkaline phosphatase, and transaminases. Pure canalicular cholestasis near terminal hepatic venules also seen in acute hepatitis, drug reactions, benign recurrent cholestasis, pregnancy, sepsis, & lymphomas. Sinusoidal dilatation, circular spaces of hepatocytes, small portal triads(UL 40X). Bile in hepatocytes about central vein & in plugs in canaliculi [yellow arrowhead] (UR 400X). Trichrome shows fibrosis about central vein (LL 400X). PAS with diastase shows portal triads with mild edema and chronic inflammation, without tortuous bile duct (LR 400X).

{|
[[File:1 OBS 2 680x512px.tif|Expanded inflamed portal triads, swollen hepatocytes (40X)]]
[[File:2 OBS 2 680x512px.tif|Edematous stroma, proliferating ductules [yellow arrowheads], PAS-D macrophages [red arrowhead] (PAS with diastasse, 200X)]]
 
[[File:3 OBS 2 680x512px.tif|Disordered, often swollen hepatocytes,some with feathery degeneration (net like spaces in cytoplasm [blue arrowhead], rare Councilman body [green arrowhead] (400X)]]
[[File:4 OBS 2 1360x1024px.tif|Bile in hepatocytes [cyan arrrowhead] & in canaliculi [purple arrowheads]. Empty acinar spaces bounded by hepatocytes [orange arrowhead] (400X, higher pixel),]]
|}
Changes of extrahepatic biliary obstruction, months duration. Expanded inflamed portal triads, swollen hepatocytes (UL 40X). Edematous stroma, proliferating ductules [yellow arrowheads], PAS-D macrophages [red arrowhead] (UR PAS with diastasse, 200X). Disordered, often swollen hepatocytes,some with feathery degeneration (net like spaces in cytoplasm) [blue arrowhead], rare Councilman body [green arrowhead] (LL 400X). Bile in hepatocytes [cyan arrrowhead] & in canaliculi [purple arrowheads]. Empty acinar spaces bounded by hepatocytes [orange arrowhead] (LR 400X).
{|
[[File:1 Bd obs 4 680x512px.tif|Expanded, light colored portal triads (arrows)(20X).]]
[[File:2 Bd obs 4 680x512px.tif|Proliferating bile ductules (cyan arrows) with neutrophils (yellow arrows), not specific for acute cholangitis, of assistance with large bile duct obstruction (400X)..]]
 
[[File:3 Bd obs 4 680x512px.tif|Uninflamed interlobular duct (yellow arrow) with, accompanying blood vessel (red arrow) (400X)]]
[[File:4 Bd obs 4 680x512px.tif|Bile infarct with pyknotic nuclei (arrows)(400X).]]
 
[[File:5 Bd obs 4 680x512px.tif|Bile (arrow) in interlobular bile duct with disordered nuclei (400X).]]
[[File:6 Bd obs 4 680x512px.tif|Bile plugs in cannaliculi (red arrows), feathery degeneration producing foamy macrophage like hepatocytes (yellow arrows)(400X).]]
|}
Large bile duct obstruction. Expanded, light colored portal triads (arrows)(Row 1 Left 20X). Proliferating bile ductules (cyan arrows) with neutrophils (yellow arrows), not specific for acute cholangitis, of assistance with large bile duct obstruction (Row 1 Right 400X). Uninflamed interlobular duct (yellow arrow) with, accompanying blood vessel (red arrow) (Row 2 Left 400X). Bile infarct with pyknotic nuclei (arrows)(Row 2 Right 400X). Bile (arrow) in interlobular bile duct with disordered nuclei (Row 3 Left 400X). Bile plugs in cannaliculi (red arrows), feathery degeneration producing foamy macrophage-like hepatocytes (yellow arrows)(Row 3 Right 400X).

==Congestive hepatopathy==
===General===
*Liver failure due to (right) heart failure.
*AKA ''cardiac cirrhosis'' - a term used by clinicians.
**Generally, it does not satisfy pathologic criteria for cirrhosis.<ref>URL: [http://emedicine.medscape.com/article/151792-overview http://emedicine.medscape.com/article/151792-overview]. Accessed on: 17 June 2010.</ref>

===Gross===
*"Nutmeg" liver - yellow spotted appearance.

===Microscopic===
Features:<ref>URL: [http://emedicine.medscape.com/article/151792-diagnosis http://emedicine.medscape.com/article/151792-diagnosis]. Accessed on: 17 June 2010.</ref>
*Zone III atrophy.
*Portal venule (central vein) distension.
*Perisinusoidal fibrosis - progresses to centrilobular fibrosis and then diffuse fibrosis.
*Dilation of sinusoids in ''all'' zone III areas - '''key feature'''.<ref>Suggested by OA. September 2009.</ref>

DDx:
*[[Hemangioma of the liver]] - should be focal lesion.

====Images====
<gallery>
Image:Congestive_hepatopathy_high_mag.jpg | Mild congestive hepatopathy. (WC)
</gallery>
{|
[[File:1 CEN NEC 1 680x512px.tif|PAS without diastase shows ovoids of necrosis {40X).]]
[[File:2 CEN NEC 1 680x512px.tif|Necrosis with central vein [yellow arrowhead], inflammatory cells, residual Councilman body [green arrowhead], and hepatocyte with mitotic figure [red arrowhead] (400X).]]
 
[[File:3 CEN NEC 1 680x512px.tif|Trichrome highlights fibrosis about central vein [yellow arrowhead] & shows beginning scar formation [green arrowheads]. Note residual atrophic hepatocytes [blue arrowheads] (400X).]]
[[File:4 CEN NEC 1 680x512px.tif|Portal triads are largely unaffected (400X).]]
|}
Centrilobular necrosis (seen in circulatory failure and with toxins/drugs). PAS without diastase shows ovoids of necrosis {UL 40X). Necrosis with central vein [yellow arrowhead], inflammatory cells, residual Councilman body [green arrowhead], and hepatocyte with mitotic figure [red arrowhead] (UR 400X). Trichrome highlights fibrosis about central vein [yellow arrowhead] & shows beginning scar formation [green arrowheads]. Note residual atrophic hepatocytes [blue arrowheads] (LL 400X). Portal triads are largely unaffected (LR 400X)

{|
[[File:1 CHF 1 680x512px.tif|Dilated and undilated sinusoidal regions (40X).]]
[[File:2 CHF 1 680x512px.tif|Thrombi in sinusoids; glycogenated nuclei likely reflect patient’s diabetes mellitus (400X).]]
 
[[File:3 CHF 1 680x512px.tif|Dilated portal vein (400X).]]
[[File:4 CHF 1 680x512px.tif|Reticulin shows collapse (thick black lines) as well as a dilated portal vein (200X).]]
 
[[File:5 CHF 1 680x512px.tif|Trichrome shows space of Disse collagenization (pericellular fibrosis) (200X).]]
[[File:6 CHF 1 680x512px.tif|Trichrome shows periportal fibrosis; no bridging was seen (200X).]]
|}
Patient with congestive heart failure and stage I fibrosis. Dilated and undilated sinusoidal regions (left row 1 40X). Thrombi in sinusoids; glycogenated nuclei likely reflect patient’s diabetes mellitus (right row 1 400X). Dilated portal vein (left row 2 400X). Reticulin shows black lines of bridging, too thick for collapse (right row 2 200X). Trichrome shows space of Disse collagenization (pericellular fibrosis) (left row 3 200X). Trichrome shows bridge beginning off to right; when it is more than a mere spike, it is a bridge (right row 3 200X).

==Drug-induced liver disease==
*[[AKA]] ''drug-induced liver toxicity''.
{{Main|Drug-induced liver disease}}

==Focal nodular hyperplasia==
*Abbreviated ''FNH''.
{{Main|Focal nodular hyperplasia}}

==Nodular regenerative hyperplasia==
===General===
*Associated with renal transplants, [[bone marrow transplant]]s and [[vasculitides]].<ref name=Ref_PBoD922>{{Ref PBoD|922}}</ref>
*Can lead to [[portal hypertension]] and many of the associated complications.<ref name=pmid22554152>{{Cite journal | last1 = Bissonnette | first1 = J. | last2 = Généreux | first2 = A. | last3 = Côté | first3 = J. | last4 = Nguyen | first4 = B. | last5 = Perreault | first5 = P. | last6 = Bouchard | first6 = L. | last7 = Pomier-Layrargues | first7 = G. | title = Hepatic hemodynamics in 24 patients with nodular regenerative hyperplasia and symptomatic portal hypertension. | journal = J Gastroenterol Hepatol | volume = 27 | issue = 8 | pages = 1336-40 | month = Aug | year = 2012 | doi = 10.1111/j.1440-1746.2012.07168.x | PMID = 22554152 }}
</ref>

====Etiology====
*Arterial hypervascularity secondary to loss of hepatic vein radicles (loss of central venule in hepatic lobule).<ref name=Ref_PBoD922>{{Ref PBoD|922}}</ref>

ASIDE: radicle = ramulus - smallest branch or vessel or nerve.<ref name=Dorlands2>Dorland's Medical Dictionary. 30th Ed.</ref>

===Gross===
*Diffuse nodularity - whole liver.

===Microscopic===
Features:<ref name=Ref_PBoD922>{{Ref PBoD|922}}</ref>
*"Plump" hepatocytes surrounded by atrophic ones.
*No fibrosis.

==Sinuosoidal obstruction syndrome==
*May be referred to as ''Hepatic veno-occlusive disease''.<ref name=pmid11928077>{{Cite journal | last1 = DeLeve | first1 = LD. | last2 = Shulman | first2 = HM. | last3 = McDonald | first3 = GB. | title = Toxic injury to hepatic sinusoids: sinusoidal obstruction syndrome (veno-occlusive disease). | journal = Semin Liver Dis | volume = 22 | issue = 1 | pages = 27-42 | month = Feb | year = 2002 | doi = 10.1055/s-2002-23204 | PMID = 11928077 }}.</ref>
===General===
*Term for obstruction due to toxicity from a chemotherapeutic agent.<ref name=pmid16393276>{{Cite journal | last1 = Helmy | first1 = A. | title = Review article: updates in the pathogenesis and therapy of hepatic sinusoidal obstruction syndrome. | journal = Aliment Pharmacol Ther | volume = 23 | issue = 1 | pages = 11-25 | month = Jan | year = 2006 | doi = 10.1111/j.1365-2036.2006.02742.x | PMID = 16393276 }}</ref><ref name=pmid17569137>{{Cite journal | last1 = Aydinli | first1 = M. | last2 = Bayraktar | first2 = Y. | title = Budd-Chiari syndrome: etiology, pathogenesis and diagnosis. | journal = World J Gastroenterol | volume = 13 | issue = 19 | pages = 2693-6 | month = May | year = 2007 | doi = | PMID = 17569137 | url=http://www.wjgnet.com/1007-9327/full/v13/i19/2693.htm }}</ref>

Clinical DDx:
*[[Budd-Chiari syndrome]].

===Microscopic===
Features:<ref name=pmid17569137>{{Cite journal | last1 = Aydinli | first1 = M. | last2 = Bayraktar | first2 = Y. | title = Budd-Chiari syndrome: etiology, pathogenesis and diagnosis. | journal = World J Gastroenterol | volume = 13 | issue = 19 | pages = 2693-6 | month = May | year = 2007 | doi = | PMID = 17569137 | url=http://www.wjgnet.com/1007-9327/full/v13/i19/2693.htm }}</ref>
*Subendothelial swelling in hepatic venules.

Negatives:
*No thrombosis.

==Ascending Cholangitis (Acute Cholangitis)==
===General===
*Term for infection of bile ducts, usually due to obstruction

Clinical DDx:

===Microscopic===
====Images====

A. [[File:1 asc chol 1 680x512px.tif|Rounded, clear (edematous) portal tracts (arrows) separated by hepatocytes with dilated sinusoids (Row 1 Left 40X).]]
 
B. [[File:2 asc chol 1 680x512px.tif|Neutrophils about hepatocytes (arrows) have spilled into the lobule from a portal tract (Row 1 Right 200X).]]
 
C. [[File:3 asc chol 1 680x512px.tif|Proliferated bile ductules (arrows) bearing neutrophils within epithelium and lumens are features of obstruction that should prompt a search for interlobular ducts with acute inflammation (Row 2 Left 400X).]]
 
D. [[File:4 asc chol 1 680x512px.tif|The epithelium of the ducts can be severely degenerated. Neutrophils (cyan arrows) invade epithelium of an interlobular duct that are recognizable mainly as a circle of rounded nuclei; the associated arteriole (red arrow) should be identified to ensure an interlobular duct is being evaluated. Note the proliferated bile ductules (blue arrows) (Row 2 Right 400X).]]
 
E. [[File:5 asc chol 1 680x512px.tif|A PAS without diastase stain colors the arteriole (blue arrow), as well as the rim of the interlobular duct within which lies a neutrophil (cyan arrow) (Row 2 Right 400X). .]]
 
F. [[File:6 asc chol 1 680x512px.tif|A PAS with diastase stain colors the arteriole (red arrow), as well as the rim of the interlobular duct within which lies a neutrophil (cyan arrow) (Row 1 Right 400X)]]
 
Acute cholangitis in a patient with multiple bile duct procedures. After the biopsy, removal of bile duct stones released pus. A. Rounded, clear (edematous) portal tracts (arrows) separated by hepatocytes with dilated sinusoids. B. Neutrophils about hepatocytes (arrows) have spilled into the lobule from a portal tract. C, Proliferated bile ductules (arrows) bearing neutrophils within epithelium and lumens are features of obstruction that should prompt a search for interlobular ducts with acute inflammation. D. The epithelium of the ducts can be severely degenerated. Neutrophils (cyan arrows) invade epithelium of an interlobular duct that are recognizable mainly as a circle of rounded nuclei; the associated arteriole (red arrow) should be identified to ensure an interlobular duct is being evaluated. Note the proliferated bile ductules (blue arrows). E. A PAS without diastase stain colors the arteriole (blue arrow), as well as the rim of the interlobular duct within which lies a neutrophil (cyan arrow). F. A PAS with diastase stain colors the arteriole (red arrow), as well as the rim of the interlobular duct within which lies a neutrophil (cyan arrow).

A.[[File:1 Sep Acu Cho 1 680x512px.tif|Low power shows variably sized inflamed portal tracts (40X)]]
 
B. [[File:2 Sep Acu Cho 1 680x512px.tif|Trichrome shows dilated sinusoids and space of Disse collagenization (200X)]]
 
C. [[File:3 Sep Acu Cho 1 680x512px.tif|Inflammatory focus with macrophages and neutrophils (400X).]]
 
D. [[File:4 Sep Acu Cho 1 680x512px.tif|PAS with diastase shows proliferated bile ductules at edge of triad with neutrophils, which should not be used to make a definite diagnosis of acute cholangitis (400X).]]
 
E. [[File:5 Sep Acu Cho 1 680x512px.tif|PAS without diastase showing acutely inflamed bile duct, with accompanying blood vessel of similar size, diagnostic of acute cholangitis (400X).]]
 
F. [[File:6 Sep Acu Cho 1 680x512px.tif|PAS with diastase showing neutrophil in bille duct lumen, diagnostic of acute cholangitis (400X).]]
 
Patient with sepsis and acute cholangitis. A. Low power shows variably sized inflamed portal tracts. B. Trichrome shows dilated sinusoids and space of Disse collagenization. C. Inflammatory focus with macrophages and neutrophils. D. PAS with diastase shows proliferated bile ductules at edge of triad with neutrophils, which should not be used to make a definite diagnosis of acute cholangitis. E. PAS without diastase showing acutely inflamed bile duct, with accompanying blood vessel of similar size, diagnostic of acute cholangitis. F. PAS with diastase showing neutrophil in bille duct lumen, diagnostic of acute cholangitis.

==Polycystic kidney disease and the liver==
{{Main|Cystic kidney disease}}
===General===
Complications of PKD in the liver:<ref>{{Ref MacSween|174-5}}</ref>
#Infected cyst.
#Cholangiocarcinoma.
#Cholestasis/obstruction due to duct compression.<ref>URL: [http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=9184868 http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=9184868]. Accessed on: 23 September 2009.</ref>

Cysts:
*Cysts in the liver, like the kidney, are thought to enlarge with age.

===Microscopic===
Features:<ref>{{Ref MacSween|176}}</ref>
*''Von Meyenburg complexes'' ([[bile duct hamartoma]]):
**Cluster of dilated ducts with "altered" bile.
**Surrounded by collagenous stroma.
**Separate from the portal areas.<ref>Meyenburg complex. Stedman's Medical Dictionary. 27th Ed.</reF>

Images:
*[http://commons.wikimedia.org/wiki/File:Von_Meyenburg_complex_low_mag.jpg Von Meyenburg complex - bile duct hamartoma (WC)].
*[http://commons.wikimedia.org/wiki/File:Bile_duct_hamartoma_intermed_mag.jpg Bile duct hamartoma (WC)].

Notes:
*Appearance on ultrasound<ref name=pmid17287178>Bile duct hamartomas--the von Meyenburg complex. Salles VJ, Marotta A, Netto JM, Speranzini MB, Martins MR. Hepatobiliary Pancreat Dis Int. 2007 Feb;6(1):108-9. PMID 17287178.</ref> and CT (hypodense)<ref name=pmid19294869>[The von Meyenburg complex] Schwab SA, Bautz W, Uder M, Kuefner MA. Rontgenpraxis. 2008;56(6):241-4. German. PMID 19294869.</ref> - similar to metastases.

==Peliosis hepatis==
===General===
*Associated with:
**Infections.
**Malignancy.
**Other stuff.
*Rarely biopsied.

===Microscopic===
Features:
*Cyst lined by endothelium.
**Usu. incomplete.
*Blood.
{|
[[File:1 PEL 1 680x512px.tif|Hemorrhage at left end, dilated sinusoids elsewhere (20X).]]
[[File:2 PEL 1 680x512px.tif|Ramifying dilated sinusoidal spaces (100X).]]
 
[[File:3 PEL 1 680x512px.tif|PAS with diastase shows flat lining (400X).]]
[[File:4 PEL 1 680x512px.tif|Necrotic hepatocytes in cords, presumably due to pressure (400X).]]
|}
Peliosis hepatis. Hemorrhage at left end, dilated sinusoids elsewhere (UL 20X). Ramifying dilated sinusoidal spaces (UR 100X). PAS with diastase shows flat lining (LL 400X). Necrotic hepatocytes in cords, presumably due to pressure (LR 400X).

==Total parenteral nutrition==
*Abbreviated ''TPN''.

===General===
*Indication: short gut syndrome, others.

===Microscopic===
Variable - may range from: steatosis, steatohepatitis, cholestasis, fibrosis and cirrhosis.<ref name=pmid16766237>{{cite journal |author=Guglielmi FW, Boggio-Bertinet D, Federico A, ''et al.'' |title=Total parenteral nutrition-related gastroenterological complications |journal=Dig Liver Dis |volume=38 |issue=9 |pages=623–42 |year=2006 |month=September |pmid=16766237 |doi=10.1016/j.dld.2006.04.002 |url=}}</ref>

Features (classic):<ref>{{Cite journal | last1 = Li | first1 = SJ. | last2 = Nussbaum | first2 = MS. | last3 = McFadden | first3 = DW. | last4 = Gapen | first4 = CL. | last5 = Dayal | first5 = R. | last6 = Fischer | first6 = JE. | title = Addition of glucagon to total parenteral nutrition (TPN) prevents hepatic steatosis in rats. | journal = Surgery | volume = 104 | issue = 2 | pages = 350-7 | month = Aug | year = 1988 | doi = | PMID = 3135627 }}</ref><ref>{{Cite journal | last1 = Stanko | first1 = RT. | last2 = Nathan | first2 = G. | last3 = Mendelow | first3 = H. | last4 = Adibi | first4 = SA. | title = Development of hepatic cholestasis and fibrosis in patients with massive loss of intestine supported by prolonged parenteral nutrition. | journal = Gastroenterology | volume = 92 | issue = 1 | pages = 197-202 | month = Jan | year = 1987 | doi = | PMID = 3096806 }}
</ref>
*[[Steatosis]] (periportal) - early.
*Cholestasis - late.

==Giant cell hepatitis==
*[[AKA]] ''neonatal giant cell hepatitis''.

:See: ''[[Giant cell hepatitis]]''.

==Hepatic amyloidosis==
{{Main|Amyloidosis}}
*[[AKA]] ''liver amyloidosis''.
*[[AKA]] ''amyloidosis of the liver''.
===General===
*Diffuse abundant amyloid within the space of Disse is associated with [[portal hypertension]].<ref name=pmid1864548>{{Cite journal | last1 = Bion | first1 = E. | last2 = Brenard | first2 = R. | last3 = Pariente | first3 = EA. | last4 = Lebrec | first4 = D. | last5 = Degott | first5 = C. | last6 = Maitre | first6 = F. | last7 = Benhamou | first7 = JP. | title = Sinusoidal portal hypertension in hepatic amyloidosis. | journal = Gut | volume = 32 | issue = 2 | pages = 227-30 | month = Feb | year = 1991 | doi = | PMID = 1864548 | PMC = 1378815 | URL = http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1378815/?tool=pubmed }}</ref>

===Microscopic===
Features:
*Amorphous extracellular pink stuff on H&E - see ''[[amyloid]]'' article.

DDx:
*[[Fibrolamellar hepatocellular carcinoma]].

====Images====
<gallery>
Image:Hepatic_amyloidosis_-_low_mag.jpg | Amyloidosis of the liver - low mag. (WC)
Image:Hepatic_amyloidosis_-_intermed_mag.jpg | Amyloidosis of the liver - intermed. mag. (WC)
Image:Hepatic_amyloidosis_-_high_mag.jpg | Amyloidosis of the liver - high mag. (WC)
Image:Hepatic_amyloidosis_-_very_high_mag.jpg | Amyloidosis of the liver - very high mag. (WC)
</gallery>
{|
[[File:1 AMY 1 680x512px.tif|Amorphous material replaces hepatic parenchyma [4X]]]
[[File:2 AMY 1 680x512px.tif|Material barely stains blue on trichrome [10X]]]
 
[[File:3 AMY 1 680x512px.tif|Material stains red on unpolarized Congo Red [40X]]]
[[File:4 AMY 1 680x512px.tif|Material stains apple green on polarized Congo Red [40X]]]
|}
Amyloidosis. Amorphous material replaces hepatic parenchyma [UL 4X]. Material barely stains blue on trichrome [UR 10X] Material stains red on unpolarized Congo Red [LL 40X] Material stains apple green on polarized Congo Red [LR 40X]

===Stains===
*[[Congo red]] +ve.

==Fulminant hepatic necrosis==
===General===
Etiology:
*Viral, i.e. [[Hepatitis A]], [[Hepatitis B]]; [[Hepatitis C]] - extremely rare.
*Trauma.
*Shock.

===Microscopic===
{|
[[File:1 Necrosis 2 680x512px.tif| Submassive hepatic necrosis.]]
[[File:2 Necrosis 2 680x512px.tif| Submassive hepatic necrosis.]]
 
[[File:3 Necrosis 2 680x512px.tif| Submassive hepatic necrosis.]]
[[File:4 Necrosis 2 680x512px.tif| Submassive hepatic necrosis.]]
 
[[File:5 Necrosis 2 680x512px.tif| Submassive hepatic necrosis.]]
[[File:6 Necrosis 2 680x512px.tif| Submassive hepatic necrosis.]]
|}
Submassive hepatic necrosis. Patient had transaminases in the thousands that rapidly dropped to normal. Pink preserved parenchyma strews empty necrotic spaces (Row 1 Left 20X). Focus of necrosis with no apparent hepatocytes macrophages abuts apparently normal liver (Row 1 Right 200X). Iron stain shows the macrophages bear hemosiderin (Row 2 Left 200X). Reticulin stain highlights the recently dead liver cells (Row 2 Right 200X). Reticulin stain shows a necrotic bridge forming; the multiple small black circles preclude diagnosis of a fibrous bridge (Row 3 Left 200X). Trichrome shows the necrotic bridge (“collapse”) lacks much collagen deposition, as would be expected for bridging fibrosis (Row 3 Right 200X).

Features:
*Hepatocyte [[necrosis]].
*Bile duct proliferation.

DDx:
*[[Cholangiocarcinoma]].
*[[Angiosarcoma]].

==Secondary hemochromatosis==
:''For the hereditary one see [[hereditary hemochromatosis]]''.
===General===
*Iron overload secondary to blood transfusions for hereditary or acquired anemia.<ref name=pmid19727383/>
**Primary hemochromatosis due to a defect in iron processing - called ''[[hereditary hemochromatosis]]''.
*Imaging considered the best test, as iron deposition is patchy.<ref name=pmid19727383/>

Selected hereditary causes:<ref name=pmid19727383>{{Cite journal | last1 = Gattermann | first1 = N. | title = The treatment of secondary hemochromatosis. | journal = Dtsch Arztebl Int | volume = 106 | issue = 30 | pages = 499-504, I | month = Jul | year = 2009 | doi = 10.3238/arztebl.2009.0499 | PMID = 19727383 | PMC = 2735704 | URL = http://www.ncbi.nlm.nih.gov.myaccess.library.utoronto.ca/pmc/articles/PMC2735704/?tool=pubmed}}</ref>
*Thalassemia.
*[[Sickle cell anemia]].
*Hereditary sideroblastic anemia.

Selected acquired causes:<ref name=pmid19727383/>
*[[Myelodysplastic syndromes]]
*Myelofibrosis
*Aplastic anemia, intractable.

===Microscopic===
:See ''[[hereditary hemochromatosis]]''.

==Hepatic sarcoidosis==
{{Main|Hepatic sarcoidosis}}
==Overlapping Disorders==

[[File:1 Mixed Disorder 1 680x512px.tif|Changes of steatohepatitis and interface hepatitis, with granuloma. Patient with diabetes was ANA, AMA, HCV, HBV negative, without drugs known to produce granulomas or interface hepatitis. This may be a case of AMA negative primary biliary cirrhosis, but studies to determine that with certainty were not performed.]]
[[File:2 Mixed Disorder 1 680x512px.tif|Changes of steatohepatitis and interface hepatitis, with granuloma. Patient with diabetes was ANA, AMA, HCV, HBV negative, without drugs known to produce granulomas or interface hepatitis. This may be a case of AMA negative primary biliary cirrhosis, but studies to determine that with certainty were not performed.]]
[[File:3 Mixed Disorder 1 680x512px.tif|Changes of steatohepatitis and interface hepatitis, with granuloma. Patient with diabetes was ANA, AMA, HCV, HBV negative, without drugs known to produce granulomas or interface hepatitis. This may be a case of AMA negative primary biliary cirrhosis, but studies to determine that with certainty were not performed.]]
[[File:4 Mixed Disorder 1 680x512px.tif|Changes of steatohepatitis and interface hepatitis, with granuloma. Patient with diabetes was ANA, AMA, HCV, HBV negative, without drugs known to produce granulomas or interface hepatitis. This may be a case of AMA negative primary biliary cirrhosis, but studies to determine that with certainty were not performed.]]
[[File:5 Mixed Disorder 1 680x512px.tif|Changes of steatohepatitis and interface hepatitis, with granuloma. Patient with diabetes was ANA, AMA, HCV, HBV negative, without drugs known to produce granulomas or interface hepatitis. This may be a case of AMA negative primary biliary cirrhosis, but studies to determine that with certainty were not performed.]]
[[File:6 Mixed Disorder 1 680x512px.tif|Changes of steatohepatitis and interface hepatitis, with granuloma. Patient with diabetes was ANA, AMA, HCV, HBV negative, without drugs known to produce granulomas or interface hepatitis. This may be a case of AMA negative primary biliary cirrhosis, but studies to determine that with certainty were not performed.]] 
Changes of steatohepatitis and interface hepatitis, with granuloma. Patient with diabetes was ANA, AMA, HCV, HBV negative, without drugs known to produce granulomas or interface hepatitis. This may be a case of AMA negative primary biliary cirrhosis, but studies to determine that with certainty were not performed. A. Low power shows hepatocytes afflicted by steatosis and an inflamed portal tract. B. In a region of fatty change lie cytoplasmic tufts of ballooning degeneration (green arrows) and a lipogranuloma (black arrow). C. At the portal-hepatocyte junction lies interface hepatitis (black arrows), as well as extension of inflammation into the lobule (green arrows). D. Red hepatocytes bounded by inflammation denote piecemeal necrosis [PAS without diastase]. E. Giant cells intermixed with lymphocytes prove a portal granuloma [PAS without diastase]. F. A blue fibrous bridge extends from a triad [Trichrome].

[[File:4 95599552608917 sl 1.png|Acute obstructive changes and changes of recurrent acute injury]]
[[File:4 95599552608917 sl 2.png|Acute obstructive changes and changes of recurrent acute injury]]
[[File:4 95599552608917 sl 3.png|Acute obstructive changes and changes of recurrent acute injury]]
[[File:4 95599552608917 sl 4.png|Acute obstructive changes and changes of recurrent acute injury]]
[[File:4 95599552608917 sl 5.png|Acute obstructive changes and changes of recurrent acute injury]]
[[File:4 95599552608917 sl 6.png|Acute obstructive changes and changes of recurrent acute injury]]
[[File:4 95599552608917 sl 7.png|Acute obstructive changes and changes of recurrent acute injury]] 
Acute obstructive changes and changes of recurrent injury in 46 yo man with Clostridium perfringens positive blood culture, an ERCP that showed duodenal compression by the pancreas with resultant bile duct dilatation. The patient had had and continued to have multiple bouts of acute pancreatitis. At the time of biopsy, decreased platelet count/hemoglobin/albumin, elevated lipase/amylase/PT/PTT, normal alkaline phosphatase, bilirubin, AST/ALT, AMA, hepatitis virus serology, ANA. A. Fragment biopsy shows inflamed triads and bridges. B. Trichrome shows bridges without nodules, evidence of prior injury; the patient subsequently developed multiple episodes of pancreatitis. C. Reticulin shows piecemeal necrosis, with black lines bounding individual hepatocytes at interface (arrows). D. Collapse is shown by closly approximated thick black lines; one cannot call portal-central collapse without seeing a central vein. Note on this and the other reticulin image that regeneration, two cell thick cords, is not prominent. E. PAS D of two portal triads, far nearer than normal, both expanded. Note increased number of ducts/ductules (red arrows), neutrophils, and PAS-D macrophages. F. PAS D shows collapse extending from a triad to a portion of a lobule with steatosis. No feathery degeneration or bile duct plugs were seen. Neither were foci of spotty necrosis or abscess seen. G. Other triads, again edematous, showed more of a chronic inflammatory response, with occasional plasma cells (black arrows). Also present are neutrophils (red arrows). The bile duct (grey arrow) near the artery (brown arrow) shows mildly disturbed nuclei. Note early proliferated bile ductules (cyan arrows).

[[File:6 17281676469188 sl 1.png| Hepatitis B virus with steatohepatitis]]
[[File:6 17281676469188 sl 2.png| Hepatitis B virus with steatohepatitis]]
[[File:6 17281676469188 sl 3.png| Hepatitis B virus with steatohepatitis]]
[[File:6 17281676469188 sl 4.png| Hepatitis B virus with steatohepatitis]]
[[File:6 17281676469188 sl 5.png| Hepatitis B virus with steatohepatitis]]
[[File:6 17281676469188 sl 6.png| Hepatitis B virus with steatohepatitis]] 
Hepatitis B virus with steatohepatitis in a 36 year old man with hepatitis B surface antigen and hepatitis Be antigen positivity, Hepatitis be QTPC of 1750 cop/mL, an occasionally mildly elevated (42) ALT, and normal glucose, alkaline phosphatase, bilirubin, and other transaminases. He had a history of alcohol abuse, which became controlled. A. Triads show scant inflammation without definite interface hepatitis. About one-fourth of the lobule, not pan-acinar, is afflicted by steatosis. B. Occasional tufts are seen (arrow), indicating focal ballooning sufficient for a diagnosis of steatohepatitis. C. Glycogenated nuclei (black arrows) and hepatocytes with feathery degeneration (red arrows) are seen. D. Very rare foci of spotty necrosis were seen. E. Apart from this triad and the one in the trichrome stain in F, which had moderate inflammation comprising lymphocytes and macrophages, all triads were small, most without any inflammation at all. Neither collapse nor piecemeal necrosis were seen on reticulin stain. F. Trichrome stain showed only portal fibrosis. The interhepatocyte fibrosis required for brunt fibrosis stage I was not seen. Hence, one would grade this as follows: A) Chronic hepatitis (history of hepatitis B), Metavir activity index 1, Piecemeal necrosis 0, Lobular necrosis 1, Metavir fibrosis stage 1, B) Steatohepaitits, Brunt necroinflammatory grade 1, Brunt fibrosis stage 0.

=See also=
*[[Pancreas]].
*[[Gastrointestinal pathology]].
*[[Liver neoplasms]].
*[[Liver]].

=References=
{{reflist|2}}

[[Category:Gastrointestinal pathology]]
[[Category:Liver pathology]]
[[Category:Medical liver disease]]

Medical liver disease

2017-01-23T15:41:37Z

Mitchell: /* Images */

[[Image:Ground glass hepatocytes high mag cropped 2.jpg|thumb|right|[[Micrograph]] showing ground glass hepatocytes, as seen in chronic [[hepatitis B]]. [[H&E stain]].]]
This article deals with '''medical [[liver]] disease'''. An introduction to the liver and approach is found in the ''[[liver]]'' article.

Every differential in liver pathology has "drugs"<ref>{{Ref PCPBoD8|448}}</ref> -- if it isn't clearly malignancy.

Liver neoplasms are dealt with in the ''[[liver neoplasms]]'' article.

Medical liver biopsies are often non-specific, as the liver has the same appearance for many mechanisms of injury, especially when the injury is marked. The clinical history, serology and imaging are essential for proper interpretations in this domain of pathology.

=Review of liver blood work=
===Inflammation activity===
*ALT.
*AST.

===Cholestatic markers===
*ALP.
*GGT - used to assess whether the ALP is an "honest" value, elevated in cirrhosis.

===Cirrhosis/decompensation===
*PLT - low is suggestive of dysfunction.
*INR - high is bad, unless anticoagulated.

===Other===
*Bilirubin.
**Direct (AKA conjugated).
**Indirect (AKA unconjugated).

A short DDx of elevated:<ref>{{Ref PCPBoD8|441}}</ref>
*Indirect:
**[[Gilbert syndrome]].
**Crigler-Najjar syndrome type 1.
**Crigler-Najjar syndrome type 2.
*Direct:
**Rotor syndrome.
**Dubin-Johnson syndomre.

===Viral hepatitis===
*HBV DNA.
*HCV RNA.
*HBs Ag, HBs Ab, HBe Ag, HBe Ab.
*HCV Ab.

Others:
*[[Epstein-Barr virus]] (EBV).
*[[Cytomegalovirus]] (CMV) - especially in the immune incompetent.

====Hepatitis B====
Meaning & utility of the various [[Hepatitis B]] tests:<ref>URL: [http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/hepatology/hepatitis-B/ http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/hepatology/hepatitis-B/]. Accessed on: 16 May 2011.</ref><ref name=lto_hepb>URL: [http://www.labtestsonline.org/understanding/analytes/hepatitis_b/test.html http://www.labtestsonline.org/understanding/analytes/hepatitis_b/test.html]. Accessed on: 16 May 2011.</ref>
{| class="wikitable sortable" border="1"
! Test name
! Location
! Positive test
! Negative test
! Usual question
|-
| HBs Ag||Surface||Virus active||No active infection||Active infection?
|-
| HBs Ab||Surface||Exposed OR vaccinated||No exposure OR no vaccine OR loss of Ab||Immunization status?
|-
| HBe Ag||Virus core||Infect. w/ viral replication||No active infection||Active infect. w/ viral replication?
|-
| HBe Ab||Virus core||Exposed to virus||Infect. w/o antibody response OR not exposed||Immune response to infection?
|-
| HBV DNA||-||Active||Not active/no exposure||Viral load/how active?
|-
| HBc Ab||Virus core||Virus active/previous exposure||No exposure||Early active infection?
|}
Notes:
*''HBc Ab'' may test for acute (IgM) or chronic infection - dependent on specific antibody test; it is often used to look for early infection.<ref name=lto_hepb>URL: [http://www.labtestsonline.org/understanding/analytes/hepatitis_b/test.html http://www.labtestsonline.org/understanding/analytes/hepatitis_b/test.html]. Accessed on: 16 May 2011.</ref>
*''Carriers of hepatitis B'': HBs Ag +ve, HBs Ab -ve, HBc Ag -ve, HBc Ab +ve, HBe Ag -ve, HBe Ab +ve.<ref>URL: [http://labtestsonline.org/understanding/analytes/hepatitis-b/tab/test http://labtestsonline.org/understanding/analytes/hepatitis-b/tab/test]. Accessed on: 3 May 2012.</ref>

===Markers for rare liver diseases===
*Ceruloplasm - low think ''[[Wilson's disease]]''; typical value for Wilson's ~ 0.12 g/L.
**<0.20 g/L is a criteria for Wilson's disease.<ref name=pmid18556333>Diagnostic accuracy of serum ceruloplasmin in Wilson disease: determination of sensitivity and specificity by ROC curve analysis among ATP7B-genotyped subjects. Mak CM, Lam CW, Tam S. Clin Chem. 2008 Aug;54(8):1356-62. Epub 2008 Jun 12. PMID 18556333. URL: [http://www.clinchem.org/cgi/reprint/54/8/1356.pdf http://www.clinchem.org/cgi/reprint/54/8/1356.pdf]. Accessed on: 28 September 2009.</ref>
*Alpha-1 antitrypsin - if low think ''deficiency''.

===Hemosiderosis===
*Ferritin - high.
*Iron saturation - high.

Causes:
*Hemochromatosis.
*Hemolysis, chronic.
*Cirrhosis.

=Medical imaging=
Blood flow:<ref>URL: [http://insidesurgery.com/2010/12/hepatopedal-hepatofugal-flow/ http://insidesurgery.com/2010/12/hepatopedal-hepatofugal-flow/]. Accessed on: 2 December 2011.</ref>
*Hepatopedal flow = normal portal vein flow.
*Hepatofugal flow = reversed portal vein flow.

==Interventional measurements==
Wedged to free hepatic venous pressure:<ref name=pmid1864548>{{Cite journal | last1 = Bion | first1 = E. | last2 = Brenard | first2 = R. | last3 = Pariente | first3 = EA. | last4 = Lebrec | first4 = D. | last5 = Degott | first5 = C. | last6 = Maitre | first6 = F. | last7 = Benhamou | first7 = JP. | title = Sinusoidal portal hypertension in hepatic amyloidosis. | journal = Gut | volume = 32 | issue = 2 | pages = 227-30 | month = Feb | year = 1991 | doi = | PMID = 1864548 | PMC = 1378815 | URL = http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1378815/?tool=pubmed }}</ref>
*Normal = 1-4 mmHg.
**Elevated in [[portal hypertension]].

=Liver biopsy=
==Medical liver biopsy adequacy==
Liver biopsy specimens should be:<ref>{{Ref MacSween|418}}</ref>
*2.0 cm in length and contain 11-15 portal tracts,
*The core should be deeper than 1.0 cm from the liver capsule; specimens close to the capsule may lead to over grading of fibrosis.

==Reporting==
{{Main|Pathology reports}}
<pre>
Specimen, procedure:
- Diagnosis.
</pre>
The diagnosis usually contains grading and staging information, e.g. ''activity 2 /4, Laennec fibrosis stage 1 /4''.

In the context of medical liver disease:
*Grade = inflammation/activity.
*Stage = severity of fibrosis/architectural changes.

Notes:
*The term "acute" is infrequently used in liver pathology.
*In the liver: neutrophils ''is not'' acute -- unlike most elsewhere in the body.<ref>OA. September 2009.</ref>

===A microscopic checklist===
<pre>
Size of biopsy: Adequate
Fragmentation: Absent
Fibrosis: Stage 2-3/4, mostly stage 2
Fibrous septa: Present
Septa with curved contours: Present – focally only
Large droplet steatosis (% of hepatocytes): Present, moderate 60%
Ballooning of hepatocytes: Present, rare
Mallory-Denk bodies: Present, rare
Portal inflammation: Present
Interface activity: Minimal (0-1/4)
Lobular necroinflammation: Minimal
Ducts: Present in normal numbers
Duct injury: Absent
Ductular reaction: Absent
Cholestasis: Absent
Terminal hepatic venules: Present
Iron stain: Absent
Ground glass cells with routine stains: Absent
PASD for alpha-1 antitrypsin droplets: Negative
</pre>

=Viral hepatitis=
These are common. The diagnoses are based on serology. The serology is covered in the ''[[Liver_pathology#Viral_hepatitis|viral hepatitis]]'' section in the ''[[liver pathology]]'' article.

Typically classified as:<ref name=pmid8048409>{{Cite journal | title = Terminology of chronic hepatitis, hepatic allograft rejection, and nodular lesions of the liver: summary of recommendations developed by an international working party, supported by the World Congresses of Gastroenterology, Los Angeles, 1994. | journal = Am J Gastroenterol | volume = 89 | issue = 8 Suppl | pages = S177-81 | month = Aug | year = 1994 | doi = | PMID = 8048409 }}</ref><ref>URL: [http://familydoctor.org/familydoctor/en/diseases-conditions/hepatitis-b.html http://familydoctor.org/familydoctor/en/diseases-conditions/hepatitis-b.html]. Accessed on: 2 May 2012.</ref>
#Acute < 6 months duration.
#Chronic > 6 months duration.

==Hepatitis A==
*Infection is self-limited, i.e. not persistent.
**May present as ''[[fulminant hepatic necrosis]]''.
*Usually asymptomatic in children.<ref name=pmid20068336>{{cite journal |author=Jeong SH, Lee HS |title=Hepatitis A: clinical manifestations and management |journal=Intervirology |volume=53 |issue=1 |pages=15–9 |year=2010 |pmid=20068336 |doi=10.1159/000252779 |url=}}</ref>
*Serology is diagnostic.

==Hepatitis B==
:''Hepatitis B virus'', abbreviated ''HBV'', redirects here.
{{Main|Hepatitis B}}

==Hepatitis C==
{{Main|Hepatitis C}}

=Other infections=
*Hydatid disease (Hydatid cyst).
*Ascaris.
*Fasciola

==Hydatid disease==
*[[AKA]] ''hydatid cyst''.
===General===
*Etiology: ''[[Echinococcus]]''.

===Microscopic===
Features:
*Laminated wall +/- calcification.<ref name=Ref_PBPoD8_448>{{Ref PCPBoD8|448}}</ref>
*Organisms -- see ''[[Echinococcus]]''.

====Images====
<gallery>
Image:Liver_cyst_wall_-_intermed_mag.jpg | Liver cyst wall - intermed. mag. (WC)
Image:Liver_cyst_wall_-_high_mag.jpg | Liver cyst wall - high mag. (WC)
Image: Laminated liver cyst wall - intermed mag.jpg | Characteristic laminated portion - intermed. mag. (WC)
Image: Laminated liver cyst wall - high mag.jpg | Characteristic laminated portion - high mag. (WC)
</gallery>
[[www]]:
*[http://pathmicro.med.sc.edu/parasitology/hydatid-hist1.jpg Hydatid cyst (med.sc.edu)].
*[http://www.atlas.or.kr/atlas/include/viewImg.html?uid=645 Hydatid cyst (atlas.or.kr)].
*[http://casereports.bmj.com/content/2009/bcr.04.2009.1798.full Hydatid cyst (casereports.bmj.com)].

==Abscess==
{|
[[File:1 ABS 1 680x512px.tif|A process replaces most of the liver parenchyma (20X).]]
[[File:2 ABS 1 680x512px.tif|Fibrinopurulent exudate apposes granulation tissue (200X).]]
 
[[File:3 ABS 1 680x512px.tif|Neutrophils lie in widened sinusoids (200X)..]]
[[File:4 ABS 1 680x512px.tif|Trichrome shows collagenization of spaces of Disse. Scarring about an abscess or other mass lesion should not be interpreted as reflective of the liver in general (200X).]]
|}
Abscess. A process replaces most of the liver parenchyma (UL 20X). Fibrinopurulent exudate apposes granulation tissue (UR 200X). Neutrophils lie in widened sinusoids (LL 200X).Trichrome shows collagenization of spaces of Disse. Scarring about an abscess or other mass lesion should not be interpreted as reflective of the liver in general (LR 200X).

==Coccidiomycosis==
Coccidiomycosis
Table show [[GRAN-COC]]
{|
[[File:Coccidiomycosis - 1 - 40X 680x512px shot.tif|500x500px Granulomas at low power]]
[[File:Coccidiomycosis - 1 - 200X 680x513px shot.tif|500x500px Granulomas with centrally crowded cells & lady slipper macrophage nuclei]]
 
[[File:Coccidiomycosis - 1 - 400X 1369x1024px shot.tif|500x500px Center of previous granuloma showing pyknotic macrophage nuclei]]
[[File:Coccidiomycosis - 1 - GMS 400X 1369x1024px shot.tif|500x500px Four Coccidiomycotic spherules]]
|}
Note the granulomas in otherwise undisturbed liver (UL), the larger prior granuloma with centrally crowded cells & lady slipper macrophage nuclei (UR), the center of the granuloma with pyknotic macrophage nuclei "necrotizing" (LL), and the organisms on GMS stain (LR).

=Metabolic and toxic=
==Alcoholic liver disease==
===General===
*Acute and/or chronic liver changes due to excessive [[alcohol]] use - includes:
**''[[Alcoholic steatohepatitis]]'' (ASH), [[AKA]] ''alcoholic hepatitis''.<ref>URL: [http://emedicine.medscape.com/article/170539-overview http://emedicine.medscape.com/article/170539-overview]. Accessed on: 3 May 2012.</ref>
***Alcoholic hepatitis can be with minimal steatosis.<ref>STC. 6 December 2010.</ref>
**[[Steatosis]] - classically macrovescicular and centrilobular.
**Alcoholic [[cirrhosis]].

====Classic lab findings in EtOH abusers====
*AST & ALT elevated with AST:ALT=2:1.
*GGT elevated.
*MCV increased.

===Gross pathology/radiologic findings===
*Classically micronodular pattern.
**May be macronodular.

===Microscopic===
See:
*''[[Steatohepatitis]]'' section and ''[[ballooning degeneration]]'' section.

Features:
*Often zone III damage.
*Cholestatsis common, i.e. yellow staining.
**NASH (non-alcoholic steatohepatitis) usu. does not have cholestasis.<ref>STC. 6 December 2010.</ref>
*Fibrosis starts at central veins.
*Neutrophils (often helpful) -- few other things have PMNs. (???)
**Neutrophils cluster around cells with Mallory hyaline.

====Images====
{|
[[File:1 etoh 3 680x512px.tif| Alcoholic hepatitis with Metavir stage IV fibrosis (advanced fibrosis/cirrhosis).]]
[[File:2 etoh 3 680x512px.tif| Alcoholic hepatitis with Metavir stage IV fibrosis (advanced fibrosis/cirrhosis).]]
 
[[File:3 etoh 3 680x512px.tif| Alcoholic hepatitis with Metavir stage IV fibrosis (advanced fibrosis/cirrhosis).]]
[[File:4 etoh 3 680x512px.tif| Alcoholic hepatitis with Metavir stage IV fibrosis (advanced fibrosis/cirrhosis).]]
 
[[File:5 etoh 3 680x512px.tif| Alcoholic hepatitis with Metavir stage IV fibrosis (advanced fibrosis/cirrhosis).]]
[[File:6 etoh 3 680x512px.tif| Alcoholic hepatitis with Metavir stage IV fibrosis (advanced fibrosis/cirrhosis).]]
|}
Alcoholic hepatitis with Metavir stage IV fibrosis (advanced fibrosis/cirrhosis).
Trichrome shows relatively non-inflamed fibrous bands, as well as [between green dots] nodules. The lack of regeneration throughout might have precluded a diagnosis of cirrhosis, but stage IV fibrosis under the Metavir system is justified (Row 1 Left 20X). Reticulin shows regenerative nodules [left] with mostly two or more nuclei between black lines juxtaposed to non-regenerative hepatocytes on the right, without piecemeal necrosis. (Row 1 Right 100X). Regenerative nodules show occasional neutrophils [red arrow] and cytoplasmic tufts of ballooned cells, sometimes possibly Mallory hyalin [green arrows] (Row 2 Left 200X). Triads (note vein [green arrow], artery [yellow arrow], and interlobular bile duct [blue arrow]) generally showed little or no interface hepatitis, even when expanded by fibrosis and inflamed (Row 2 Right 200X). Occasional foci of spotty necrosis were seen (Row 3 Left 200X). This edge of an inflamed triads shows neutrophils about proliferated bile ducts [red arrows], as well as Mallory-Denk bodies [blue arrows] (Row 4 Left 400X).
{|
[[File:1 etoh 4 680x512px.tif| Cirrhosis in an alcoholic.]]
[[File:2 etoh 4 680x512px.tif| Cirrhosis in an alcoholic.]]
 
[[File:3 etoh 4 680x512px.tif| Cirrhosis in an alcoholic.]]
[[File:4 etoh 4 680x512px.tif| Cirrhosis in an alcoholic.]]
 
[[File:5 etoh 4 680x512px.tif| Cirrhosis in an alcoholic.]]
[[File:6 etoh 4 680x512px.tif| Cirrhosis in an alcoholic.]]
|}
Definite cirrhosis in an alcoholic. Hepatocyte free bands parse tissue, with occasional definite islands [arrows] (Row 1 Left 40X). Trichrome establishes blue fibrosis about isles [arrows] (Row 1 Right 40X). Reticulin stain shows nodules with regeneration, wherein a large proportion of them are at least two nuclei thick [arrows] (Row 2 Left 200X). Bile duct proliferation can be difficult, sometimes mimicking cholangiocarcinoma. Follow the double headed arrows to see how the ductules can be seen to proliferate from a single sources, with all ducts being complete, without necrotic epithelial cells. (Row 2 Right 400X). PAS with distase can help, as cholangiocarcinoma generally lacks the red rim of proliferating bile ductules [arrows]; again note the connections that can be made between the ductule openings by the blue double headed arrows. The cyan double headed arrows show general parallelism, consistent with uniform directionality induced by extrinsic force, not a neoplastic spread (Row 3 Left 400X). Trichrome shows the most difficult focus. Double headed arrows display the connectivity seen before of the proliferated bile ductules. Note that numerous pairs of adjacent perpendicular glands without a head to foot appearance are not seen that would indicate the disorderly spread of cholangiocarcinoma (Row 3 Right 400X).

{|
[[File:1 ALC 2 680x512px.tif|Expanded, inflamed triads with increased bile duct/vascular openings. Mild steatosis (40X).]]
[[File:2 ALC 2 680x512px.tif|Trichrome stain shows periportal fibrosis [red arrowheads] (200X).]]
 
[[File:3 ALC 2 680x512px.tif|PAS with diastase stain shows proliferated bile ductules [blue arrowheads] in stroma with mixed inflammatory infiltrate (400X)]]
[[File:4 ALC 2 680x512px.tif|Neutrophils about ballooned hepatocyte (satellitosis) [yellow arrowheads]. Councilman bodies [green arrowheads] (400X).]]
|}
Alcoholic hepatitis without cirrhosis. No history of viral disease. AMA negative. Expanded, inflamed triads with increased bile duct/vascular openings. Mild steatosis (UL 40X). Trichrome stain shows periportal fibrosis [red arrowheads] (UR 200X). PAS with diastase stain shows proliferated bile ductules [blue arrowheads] in stroma with mixed inflammatory infiltrate (LL 400X) Neutrophils about ballooned hepatocyte (satellitosis) [yellow arrowheads]. Councilman bodies [green arrowheads] (LR 400X).

Notes:
*If portal inflammatory infiltrates more than mild, r/o other causes i.e. [[viral hepatitis]].
*Mallory bodies once thought to be characteristic; now considered non-specific and generally poorly understood.<ref>{{cite journal |author=Jensen K, Gluud C |title=The Mallory body: theories on development and pathological significance (Part 2 of a literature survey) |journal=Hepatology |volume=20 |issue=5 |pages=1330-42 |year=1994 |month=November |pmid=7927269 |doi= |url=}}</ref>
*Some consider ''alcoholic liver disease'' a clinical diagnosis, i.e. as a pathologist one does not diagnose it.<ref>MG. September 2009.</ref>

==Non-alcoholic fatty liver disease==
*Abbreviated ''NAFLD''.
*Fatty liver that is not due to alcohol; includes obesity-related fatty liver, metabolic disease/diabetes-related fatty liver.

===NASH===
*Non-alcoholic steatohepatitis - see ''steatohepatitis'' section.
*Histologically indistinguishable from ASH.
*NASH is a ''clinical diagnosis'' based on exclusion of alcohol.

==Steatohepatitis==
{{Main|Steatohepatitis}}

=Autoimmune=
==Autoimmune hepatitis==
*Abbreviated ''AIH''.
{{Main|Autoimmune hepatitis}}

==Primary biliary cirrhosis==
*Abbreviated PBC.
{{Main|Primary biliary cirrhosis}}

==Autoimmune hepatitis with obstruction - combined changes==
{|
[[File:1 AIH OBS 1.tif|Low power shows inflammation; portal triads, lobules, central veins cannot be distinguished (40X).]]
[[File:2 AIH OBS 1.tif|Trichrome shows central venous sclerosis (red arrowhead), periportal fibrosis (green arrowhead), & space of Disse collagenization (yellow arrowhead); juxtaposition of central vein & portal tract indicates collapse, no definite bridging was seen (100X)]]
 
[[File:3 AIH OBS 1.tif|Central vein is inflamed with a rare plasma cell (cyan arrowhead) (400X).]]
[[File:4 AIH OBS 1.tif|Interface hepatitis with plasma cells (yellow arrows) and ballooned hepatocytes (red arrows). Lobule is disorganized (400X).]]
 
[[File:5 AIH OBS 1.tif|Proliferating bile ductules (blue arrows) with occasional neutrophils (fucsia arrows), indicative of obstruction, but not acute cholangitis, which requires inflamed bile duct itself, best diagnosed with associated blood vessel (400X).]]
[[File:6 AIH OBS 1.tif|Rare distorted rosettes with greenish brown strands of bile (left arrow) or bile plugs (right arrow) (400X).]]
|}
Patient with SLE and obstructive jaundice that resolved with apparent passage of stone. Low power shows inflammation; portal triads, lobules, central veins cannot be distinguished (left row 1 40X). Trichrome shows central venous sclerosis (red arrowhead), periportal fibrosis (green arrowhead), & space of Disse collagenization (yellow arrowhead); juxtaposition of central vein & portal tract indicates collapse, no definite bridging was seen (right row 1 100X). Central vein is inflamed with a rare plasma cell (cyan arrowhead) (left row 2 400X). Interface hepatitis with plasma cells (yellow arrows) and ballooned hepatocytes (red arrows). Lobule is disorganized (right row 2 400X). Proliferating bile ductules (blue arrows) with occasional neutrophils (fucsia arrows), indicative of obstruction, but not acute cholangitis, which requires inflamed bile duct itself, best diagnosed with associated blood vessel (left row 3 400X). Rare distorted rosettes with greenish brown strands of bile (left arrow) or bile plugs (right arrow) (right row 3 400X).

==Autoimmune hepatitis-primary biliary cirrhosis overlap syndrome==
*Abbreviation ''AIH-PBC OS''.
===General===
Epidemiology:
*Rare.

Serology:<ref name=pmid19491855>{{Cite journal | last1 = Muratori | first1 = P. | last2 = Granito | first2 = A. | last3 = Pappas | first3 = G. | last4 = Pendino | first4 = GM. | last5 = Quarneti | first5 = C. | last6 = Cicola | first6 = R. | last7 = Menichella | first7 = R. | last8 = Ferri | first8 = S. | last9 = Cassani | first9 = F. | title = The serological profile of the autoimmune hepatitis/primary biliary cirrhosis overlap syndrome. | journal = Am J Gastroenterol | volume = 104 | issue = 6 | pages = 1420-5 | month = Jun | year = 2009 | doi = 10.1038/ajg.2009.126 | PMID = 19491855 }}</ref>
*AMA +ve.
*Anti-dsDNA +ve.

===Microscopic===
:See: ''[[autoimmune hepatitis]]'' and ''[[primary biliary cirrhosis]]''.
{|
[[File:1 AIH PBC 1 680x512px.tif|Expanded portal tracts with fuzzy edges (40X).]]
[[File:2 AIH PBC 1 680x512px.tif|Interface hepatitis with plasma cells (400X).]]
 
[[File:3 AIH PBC 1 680x512px.tif|Loose granuloma (400X).]]
[[File:4 AIH PBC 1 680x512px.tif|Damaged bile duct (400X).]]
|}

AIH/PBC overlap. AMA & ANA positive with Alkaline phosphatase > 2 upper limit of normal & one ALT > 5 times upper limit of normal. Expanded portal tracts with fuzzy edges (UL 40X). IInterface hepatitis with plasma cells (UR 400X). Loose granuloma (LL 400X). Damaged bile duct (LR 400X).

==Primary sclerosing cholangitis==
*Abbreviated ''PSC''.
{{Main|Primary sclerosing cholangitis}}

=Hereditary=
==Caroli disease==
===General===
*Genetic disease.
**Frequently associated with [[autosomal recessive polycystic kidney disease]] (ARPKD).<ref name=omim263200>{{OMIM|263200}}</ref>
**May be seen in isolation.<ref name=omim600643>{{OMIM|600643}}</ref>

Clinical:<ref name=pmid17461493>{{Cite journal | last1 = Yonem | first1 = O. | last2 = Bayraktar | first2 = Y. | title = Clinical characteristics of Caroli's syndrome. | journal = World J Gastroenterol | volume = 13 | issue = 13 | pages = 1934-7 | month = Apr | year = 2007 | doi = | PMID = 17461493 }}</ref>
*Recurrent [[cholangitis]].
*Recurrent [[cholelithiasis]].
*[[Cholangiocarcinoma]]<ref name=pmid17461492>{{Cite journal | last1 = Yonem | first1 = O. | last2 = Bayraktar | first2 = Y. | title = Clinical characteristics of Caroli's disease. | journal = World J Gastroenterol | volume = 13 | issue = 13 | pages = 1930-3 | month = Apr | year = 2007 | doi = | PMID = 17461492 }}</ref> - seen in ~7% of cases.<ref name=pmid15347876>{{Cite journal | last1 = Karim | first1 = AS. | title = Caroli's disease. | journal = Indian Pediatr | volume = 41 | issue = 8 | pages = 848-50 | month = Aug | year = 2004 | doi = | PMID = 15347876 }}</ref>

Note:
*''Caroli syndrome'' = Caroli disease + congenital hepatic fibrosis.<ref name=pmid15888616>{{Cite journal | last1 = Brancatelli | first1 = G. | last2 = Federle | first2 = MP. | last3 = Vilgrain | first3 = V. | last4 = Vullierme | first4 = MP. | last5 = Marin | first5 = D. | last6 = Lagalla | first6 = R. | title = Fibropolycystic liver disease: CT and MR imaging findings. | journal = Radiographics | volume = 25 | issue = 3 | pages = 659-70 | month = | year = | doi = 10.1148/rg.253045114 | PMID = 15888616 | URL = http://radiographics.rsna.org/content/25/3/659.long }}</ref>

===Gross===
*Dilated bile ducts.<ref name=omim263200/>

===Microscopic===
Features:<ref name=pmid17461493/>
*Dilated bile ducts.
*Periductal fibrosis. (???)
*+/-Fibrosis.

Image:
*[http://www.meddean.luc.edu/lumen/MedEd/orfpath/11-3-10.jpg Caroli disease (meddean.luc.edu)].<ref>URL: [http://www.meddean.luc.edu/lumen/MedEd/orfpath/develop.htm http://www.meddean.luc.edu/lumen/MedEd/orfpath/develop.htm]. Accessed on: 1 December 2011.</ref>

==Hereditary hemochromatosis==
:''For secondary causes see [[secondary hemochromatosis]]''.
{{Main|Hereditary hemochromatosis}}

==Wilson disease==
{{Main|Wilson's disease}}

==Alpha-1 antitrypsin deficiency==
*[[AKA]] ''alpha1-antiprotease inhibitor deficiency''.
{{Main|Alpha-1 antitrypsin deficiency }}

=Other=
==Budd-Chiari syndrome==
*[[AKA]] ''hepatic vein obstruction''.
===General===
*Hepatic outflow obstruction.

Clinical triad:<ref name=pmid21573256>{{Cite journal | last1 = Fox | first1 = MA. | last2 = Fox | first2 = JA. | last3 = Davies | first3 = MH. | title = Budd-Chiari syndrome--a review of the diagnosis and management. | journal = Acute Med | volume = 10 | issue = 1 | pages = 5-9 | month = | year = 2011 | doi = | PMID = 21573256 }}</ref>
*Ascites.
*Abdominal pain.
*Hepatomegaly.

Etiology:
*~50% have a [[myeloproliferative disease]].<ref name=pmid18814079>{{Cite journal | last1 = Plessier | first1 = A. | last2 = Valla | first2 = DC. | title = Budd-Chiari syndrome. | journal = Semin Liver Dis | volume = 28 | issue = 3 | pages = 259-69 | month = Aug | year = 2008 | doi = 10.1055/s-0028-1085094 | PMID = 18814079 }}</ref>
*May be due to mass effect from a tumour.

Clinical DDx:
*[[Hepatic veno-occlusive disease]].

===Microscopic===
Features:<ref name=pmid17569137>{{Cite journal | last1 = Aydinli | first1 = M. | last2 = Bayraktar | first2 = Y. | title = Budd-Chiari syndrome: etiology, pathogenesis and diagnosis. | journal = World J Gastroenterol | volume = 13 | issue = 19 | pages = 2693-6 | month = May | year = 2007 | doi = | PMID = 17569137 | url=http://www.wjgnet.com/1007-9327/full/v13/i19/2693.htm }}</ref>
*Sinusoidal dilation in zone III (congestion).
*+/-Hepatocyte drop-out.
*+/-Centrilobular fibrosis.

DDx congestion:
*Congestive heart failure ([[congestive hepatopathy]]).
*Constrictive pericarditis.

==Vanishing bile duct syndrome==
*[[AKA]] ''bile duct loss'', [[AKA]] ''ductopenia''.<ref name=pmid11521176/>
===General===
*Fatal.

DDx:<ref name=pmid18242505/>
*[[Primary biliary cirrhosis]].
*[[Primary sclerosing cholangitis]].
*[[GVHD]].<ref name=pmid7994249>{{Cite journal | last1 = Yeh | first1 = KH. | last2 = Hsieh | first2 = HC. | last3 = Tang | first3 = JL. | last4 = Lin | first4 = MT. | last5 = Yang | first5 = CH. | last6 = Chen | first6 = YC. | title = Severe isolated acute hepatic graft-versus-host disease with vanishing bile duct syndrome. | journal = Bone Marrow Transplant | volume = 14 | issue = 2 | pages = 319-21 | month = Aug | year = 1994 | doi = | PMID = 7994249 }}</ref>
*[[Drug-induced liver disease|Drugs]].<ref name=pmid11352118>{{Cite journal | last1 = Chitturi | first1 = S. | last2 = Farrell | first2 = GC. | title = Drug-induced cholestasis. | journal = Semin Gastrointest Dis | volume = 12 | issue = 2 | pages = 113-24 | month = Apr | year = 2001 | doi = | PMID = 11352118 }}</ref>
*Chronic rejection.<ref name=pmid11521176>{{Cite journal | last1 = Inomata | first1 = Y. | last2 = Tanaka | first2 = K. | title = Pathogenesis and treatment of bile duct loss after liver transplantation. | journal = J Hepatobiliary Pancreat Surg | volume = 8 | issue = 4 | pages = 316-22 | month = | year = 2001 | doi = 10.1007/s0053410080316 | PMID = 11521176 }}</ref>

===Microscopic===
Features:<ref name=pmid18242505>{{Cite journal | last1 = Reau | first1 = NS. | last2 = Jensen | first2 = DM. | title = Vanishing bile duct syndrome. | journal = Clin Liver Dis | volume = 12 | issue = 1 | pages = 203-17, x | month = Feb | year = 2008 | doi = 10.1016/j.cld.2007.11.007 | PMID = 18242505 }}</ref>
*Loss of intrahepatitic bile ducts - '''key feature'''.
*Cholestasis.

Note:
*May occur without fibrosis and inflammation; thus, can be easy to miss.

===IHC===
*[[CK7]] -ve.
**Marks bile ducts.

==Extrahepatic biliary obstruction==
{|
[[File:1 OBS 3 680x512px.tif|Sinusoidal dilatation, circular spaces of hepatocytes, small portal triads(40X).]]
[[File:2 OBS 3 680x512px.tif|Bile in hepatocytes about central vein & in plugs in canaliculi [yellow arrowhead] (400X).]]
 
[[File:3 OBS 3 680x512px.tif|Trichrome shows fibrosis about central vein (400X).]]
[[File:4 OBS 3 680x512px.tif|PAS with diastase shows portal triads with mild edema and chronic inflammation, without tortuous bile duct (400X).]]
|}
Early extrahepatic biliary obstruction, demonstrated radiographically, transient, with rise in bilirubin, alkaline phosphatase, and transaminases. Pure canalicular cholestasis near terminal hepatic venules also seen in acute hepatitis, drug reactions, benign recurrent cholestasis, pregnancy, sepsis, & lymphomas. Sinusoidal dilatation, circular spaces of hepatocytes, small portal triads(UL 40X). Bile in hepatocytes about central vein & in plugs in canaliculi [yellow arrowhead] (UR 400X). Trichrome shows fibrosis about central vein (LL 400X). PAS with diastase shows portal triads with mild edema and chronic inflammation, without tortuous bile duct (LR 400X).

{|
[[File:1 OBS 2 680x512px.tif|Expanded inflamed portal triads, swollen hepatocytes (40X)]]
[[File:2 OBS 2 680x512px.tif|Edematous stroma, proliferating ductules [yellow arrowheads], PAS-D macrophages [red arrowhead] (PAS with diastasse, 200X)]]
 
[[File:3 OBS 2 680x512px.tif|Disordered, often swollen hepatocytes,some with feathery degeneration (net like spaces in cytoplasm [blue arrowhead], rare Councilman body [green arrowhead] (400X)]]
[[File:4 OBS 2 1360x1024px.tif|Bile in hepatocytes [cyan arrrowhead] & in canaliculi [purple arrowheads]. Empty acinar spaces bounded by hepatocytes [orange arrowhead] (400X, higher pixel),]]
|}
Changes of extrahepatic biliary obstruction, months duration. Expanded inflamed portal triads, swollen hepatocytes (UL 40X). Edematous stroma, proliferating ductules [yellow arrowheads], PAS-D macrophages [red arrowhead] (UR PAS with diastasse, 200X). Disordered, often swollen hepatocytes,some with feathery degeneration (net like spaces in cytoplasm) [blue arrowhead], rare Councilman body [green arrowhead] (LL 400X). Bile in hepatocytes [cyan arrrowhead] & in canaliculi [purple arrowheads]. Empty acinar spaces bounded by hepatocytes [orange arrowhead] (LR 400X).
{|
[[File:1 Bd obs 4 680x512px.tif|Expanded, light colored portal triads (arrows)(20X).]]
[[File:2 Bd obs 4 680x512px.tif|Proliferating bile ductules (cyan arrows) with neutrophils (yellow arrows), not specific for acute cholangitis, of assistance with large bile duct obstruction (400X)..]]
 
[[File:3 Bd obs 4 680x512px.tif|Uninflamed interlobular duct (yellow arrow) with, accompanying blood vessel (red arrow) (400X)]]
[[File:4 Bd obs 4 680x512px.tif|Bile infarct with pyknotic nuclei (arrows)(400X).]]
 
[[File:5 Bd obs 4 680x512px.tif|Bile (arrow) in interlobular bile duct with disordered nuclei (400X).]]
[[File:6 Bd obs 4 680x512px.tif|Bile plugs in cannaliculi (red arrows), feathery degeneration producing foamy macrophage like hepatocytes (yellow arrows)(400X).]]
|}
Large bile duct obstruction. Expanded, light colored portal triads (arrows)(Row 1 Left 20X). Proliferating bile ductules (cyan arrows) with neutrophils (yellow arrows), not specific for acute cholangitis, of assistance with large bile duct obstruction (Row 1 Right 400X). Uninflamed interlobular duct (yellow arrow) with, accompanying blood vessel (red arrow) (Row 2 Left 400X). Bile infarct with pyknotic nuclei (arrows)(Row 2 Right 400X). Bile (arrow) in interlobular bile duct with disordered nuclei (Row 3 Left 400X). Bile plugs in cannaliculi (red arrows), feathery degeneration producing foamy macrophage-like hepatocytes (yellow arrows)(Row 3 Right 400X).

==Congestive hepatopathy==
===General===
*Liver failure due to (right) heart failure.
*AKA ''cardiac cirrhosis'' - a term used by clinicians.
**Generally, it does not satisfy pathologic criteria for cirrhosis.<ref>URL: [http://emedicine.medscape.com/article/151792-overview http://emedicine.medscape.com/article/151792-overview]. Accessed on: 17 June 2010.</ref>

===Gross===
*"Nutmeg" liver - yellow spotted appearance.

===Microscopic===
Features:<ref>URL: [http://emedicine.medscape.com/article/151792-diagnosis http://emedicine.medscape.com/article/151792-diagnosis]. Accessed on: 17 June 2010.</ref>
*Zone III atrophy.
*Portal venule (central vein) distension.
*Perisinusoidal fibrosis - progresses to centrilobular fibrosis and then diffuse fibrosis.
*Dilation of sinusoids in ''all'' zone III areas - '''key feature'''.<ref>Suggested by OA. September 2009.</ref>

DDx:
*[[Hemangioma of the liver]] - should be focal lesion.

====Images====
<gallery>
Image:Congestive_hepatopathy_high_mag.jpg | Mild congestive hepatopathy. (WC)
</gallery>
{|
[[File:1 CEN NEC 1 680x512px.tif|PAS without diastase shows ovoids of necrosis {40X).]]
[[File:2 CEN NEC 1 680x512px.tif|Necrosis with central vein [yellow arrowhead], inflammatory cells, residual Councilman body [green arrowhead], and hepatocyte with mitotic figure [red arrowhead] (400X).]]
 
[[File:3 CEN NEC 1 680x512px.tif|Trichrome highlights fibrosis about central vein [yellow arrowhead] & shows beginning scar formation [green arrowheads]. Note residual atrophic hepatocytes [blue arrowheads] (400X).]]
[[File:4 CEN NEC 1 680x512px.tif|Portal triads are largely unaffected (400X).]]
|}
Centrilobular necrosis (seen in circulatory failure and with toxins/drugs). PAS without diastase shows ovoids of necrosis {UL 40X). Necrosis with central vein [yellow arrowhead], inflammatory cells, residual Councilman body [green arrowhead], and hepatocyte with mitotic figure [red arrowhead] (UR 400X). Trichrome highlights fibrosis about central vein [yellow arrowhead] & shows beginning scar formation [green arrowheads]. Note residual atrophic hepatocytes [blue arrowheads] (LL 400X). Portal triads are largely unaffected (LR 400X)

{|
[[File:1 CHF 1 680x512px.tif|Dilated and undilated sinusoidal regions (40X).]]
[[File:2 CHF 1 680x512px.tif|Thrombi in sinusoids; glycogenated nuclei likely reflect patient’s diabetes mellitus (400X).]]
 
[[File:3 CHF 1 680x512px.tif|Dilated portal vein (400X).]]
[[File:4 CHF 1 680x512px.tif|Reticulin shows collapse (thick black lines) as well as a dilated portal vein (200X).]]
 
[[File:5 CHF 1 680x512px.tif|Trichrome shows space of Disse collagenization (pericellular fibrosis) (200X).]]
[[File:6 CHF 1 680x512px.tif|Trichrome shows periportal fibrosis; no bridging was seen (200X).]]
|}
Patient with congestive heart failure and stage I fibrosis. Dilated and undilated sinusoidal regions (left row 1 40X). Thrombi in sinusoids; glycogenated nuclei likely reflect patient’s diabetes mellitus (right row 1 400X). Dilated portal vein (left row 2 400X). Reticulin shows black lines of bridging, too thick for collapse (right row 2 200X). Trichrome shows space of Disse collagenization (pericellular fibrosis) (left row 3 200X). Trichrome shows bridge beginning off to right; when it is more than a mere spike, it is a bridge (right row 3 200X).

==Drug-induced liver disease==
*[[AKA]] ''drug-induced liver toxicity''.
{{Main|Drug-induced liver disease}}

==Focal nodular hyperplasia==
*Abbreviated ''FNH''.
{{Main|Focal nodular hyperplasia}}

==Nodular regenerative hyperplasia==
===General===
*Associated with renal transplants, [[bone marrow transplant]]s and [[vasculitides]].<ref name=Ref_PBoD922>{{Ref PBoD|922}}</ref>
*Can lead to [[portal hypertension]] and many of the associated complications.<ref name=pmid22554152>{{Cite journal | last1 = Bissonnette | first1 = J. | last2 = Généreux | first2 = A. | last3 = Côté | first3 = J. | last4 = Nguyen | first4 = B. | last5 = Perreault | first5 = P. | last6 = Bouchard | first6 = L. | last7 = Pomier-Layrargues | first7 = G. | title = Hepatic hemodynamics in 24 patients with nodular regenerative hyperplasia and symptomatic portal hypertension. | journal = J Gastroenterol Hepatol | volume = 27 | issue = 8 | pages = 1336-40 | month = Aug | year = 2012 | doi = 10.1111/j.1440-1746.2012.07168.x | PMID = 22554152 }}
</ref>

====Etiology====
*Arterial hypervascularity secondary to loss of hepatic vein radicles (loss of central venule in hepatic lobule).<ref name=Ref_PBoD922>{{Ref PBoD|922}}</ref>

ASIDE: radicle = ramulus - smallest branch or vessel or nerve.<ref name=Dorlands2>Dorland's Medical Dictionary. 30th Ed.</ref>

===Gross===
*Diffuse nodularity - whole liver.

===Microscopic===
Features:<ref name=Ref_PBoD922>{{Ref PBoD|922}}</ref>
*"Plump" hepatocytes surrounded by atrophic ones.
*No fibrosis.

==Sinuosoidal obstruction syndrome==
*May be referred to as ''Hepatic veno-occlusive disease''.<ref name=pmid11928077>{{Cite journal | last1 = DeLeve | first1 = LD. | last2 = Shulman | first2 = HM. | last3 = McDonald | first3 = GB. | title = Toxic injury to hepatic sinusoids: sinusoidal obstruction syndrome (veno-occlusive disease). | journal = Semin Liver Dis | volume = 22 | issue = 1 | pages = 27-42 | month = Feb | year = 2002 | doi = 10.1055/s-2002-23204 | PMID = 11928077 }}.</ref>
===General===
*Term for obstruction due to toxicity from a chemotherapeutic agent.<ref name=pmid16393276>{{Cite journal | last1 = Helmy | first1 = A. | title = Review article: updates in the pathogenesis and therapy of hepatic sinusoidal obstruction syndrome. | journal = Aliment Pharmacol Ther | volume = 23 | issue = 1 | pages = 11-25 | month = Jan | year = 2006 | doi = 10.1111/j.1365-2036.2006.02742.x | PMID = 16393276 }}</ref><ref name=pmid17569137>{{Cite journal | last1 = Aydinli | first1 = M. | last2 = Bayraktar | first2 = Y. | title = Budd-Chiari syndrome: etiology, pathogenesis and diagnosis. | journal = World J Gastroenterol | volume = 13 | issue = 19 | pages = 2693-6 | month = May | year = 2007 | doi = | PMID = 17569137 | url=http://www.wjgnet.com/1007-9327/full/v13/i19/2693.htm }}</ref>

Clinical DDx:
*[[Budd-Chiari syndrome]].

===Microscopic===
Features:<ref name=pmid17569137>{{Cite journal | last1 = Aydinli | first1 = M. | last2 = Bayraktar | first2 = Y. | title = Budd-Chiari syndrome: etiology, pathogenesis and diagnosis. | journal = World J Gastroenterol | volume = 13 | issue = 19 | pages = 2693-6 | month = May | year = 2007 | doi = | PMID = 17569137 | url=http://www.wjgnet.com/1007-9327/full/v13/i19/2693.htm }}</ref>
*Subendothelial swelling in hepatic venules.

Negatives:
*No thrombosis.

==Ascending Cholangitis (Acute Cholangitis)==
===General===
*Term for infection of bile ducts, usually due to obstruction

Clinical DDx:

===Microscopic===
====Images====

A. [[File:1 asc chol 1 680x512px.tif|Rounded, clear (edematous) portal tracts (arrows) separated by hepatocytes with dilated sinusoids (Row 1 Left 40X).]]
 
B. [[File:2 asc chol 1 680x512px.tif|Neutrophils about hepatocytes (arrows) have spilled into the lobule from a portal tract (Row 1 Right 200X).]]
 
C. [[File:3 asc chol 1 680x512px.tif|Proliferated bile ductules (arrows) bearing neutrophils within epithelium and lumens are features of obstruction that should prompt a search for interlobular ducts with acute inflammation (Row 2 Left 400X).]]
 
D. [[File:4 asc chol 1 680x512px.tif|The epithelium of the ducts can be severely degenerated. Neutrophils (cyan arrows) invade epithelium of an interlobular duct that are recognizable mainly as a circle of rounded nuclei; the associated arteriole (red arrow) should be identified to ensure an interlobular duct is being evaluated. Note the proliferated bile ductules (blue arrows) (Row 2 Right 400X).]]
 
E. [[File:5 asc chol 1 680x512px.tif|A PAS without diastase stain colors the arteriole (blue arrow), as well as the rim of the interlobular duct within which lies a neutrophil (cyan arrow) (Row 2 Right 400X). .]]
 
F. [[File:6 asc chol 1 680x512px.tif|A PAS with diastase stain colors the arteriole (red arrow), as well as the rim of the interlobular duct within which lies a neutrophil (cyan arrow) (Row 1 Right 400X)]]
 
Acute cholangitis in a patient with multiple bile duct procedures. After the biopsy, removal of bile duct stones released pus. A. Rounded, clear (edematous) portal tracts (arrows) separated by hepatocytes with dilated sinusoids. B. Neutrophils about hepatocytes (arrows) have spilled into the lobule from a portal tract. C, Proliferated bile ductules (arrows) bearing neutrophils within epithelium and lumens are features of obstruction that should prompt a search for interlobular ducts with acute inflammation. D. The epithelium of the ducts can be severely degenerated. Neutrophils (cyan arrows) invade epithelium of an interlobular duct that are recognizable mainly as a circle of rounded nuclei; the associated arteriole (red arrow) should be identified to ensure an interlobular duct is being evaluated. Note the proliferated bile ductules (blue arrows). E. A PAS without diastase stain colors the arteriole (blue arrow), as well as the rim of the interlobular duct within which lies a neutrophil (cyan arrow). F. A PAS with diastase stain colors the arteriole (red arrow), as well as the rim of the interlobular duct within which lies a neutrophil (cyan arrow).

A.[[File:1 Sep Acu Cho 1 680x512px.tif|Low power shows variably sized inflamed portal tracts (40X)]]
 
B. [[File:2 Sep Acu Cho 1 680x512px.tif|Trichrome shows dilated sinusoids and space of Disse collagenization (200X)]]
 
C. [[File:3 Sep Acu Cho 1 680x512px.tif|Inflammatory focus with macrophages and neutrophils (400X).]]
 
D. [[File:4 Sep Acu Cho 1 680x512px.tif|PAS with diastase shows proliferated bile ductules at edge of triad with neutrophils, which should not be used to make a definite diagnosis of acute cholangitis (400X).]]
 
E. [[File:5 Sep Acu Cho 1 680x512px.tif|PAS without diastase showing acutely inflamed bile duct, with accompanying blood vessel of similar size, diagnostic of acute cholangitis (400X).]]
 
F. [[File:6 Sep Acu Cho 1 680x512px.tif|PAS with diastase showing neutrophil in bille duct lumen, diagnostic of acute cholangitis (400X).]]
 
Patient with sepsis and acute cholangitis. A. Low power shows variably sized inflamed portal tracts. B. Trichrome shows dilated sinusoids and space of Disse collagenization. C. Inflammatory focus with macrophages and neutrophils. D. PAS with diastase shows proliferated bile ductules at edge of triad with neutrophils, which should not be used to make a definite diagnosis of acute cholangitis. E. PAS without diastase showing acutely inflamed bile duct, with accompanying blood vessel of similar size, diagnostic of acute cholangitis. F. PAS with diastase showing neutrophil in bille duct lumen, diagnostic of acute cholangitis.

==Polycystic kidney disease and the liver==
{{Main|Cystic kidney disease}}
===General===
Complications of PKD in the liver:<ref>{{Ref MacSween|174-5}}</ref>
#Infected cyst.
#Cholangiocarcinoma.
#Cholestasis/obstruction due to duct compression.<ref>URL: [http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=9184868 http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=9184868]. Accessed on: 23 September 2009.</ref>

Cysts:
*Cysts in the liver, like the kidney, are thought to enlarge with age.

===Microscopic===
Features:<ref>{{Ref MacSween|176}}</ref>
*''Von Meyenburg complexes'' ([[bile duct hamartoma]]):
**Cluster of dilated ducts with "altered" bile.
**Surrounded by collagenous stroma.
**Separate from the portal areas.<ref>Meyenburg complex. Stedman's Medical Dictionary. 27th Ed.</reF>

Images:
*[http://commons.wikimedia.org/wiki/File:Von_Meyenburg_complex_low_mag.jpg Von Meyenburg complex - bile duct hamartoma (WC)].
*[http://commons.wikimedia.org/wiki/File:Bile_duct_hamartoma_intermed_mag.jpg Bile duct hamartoma (WC)].

Notes:
*Appearance on ultrasound<ref name=pmid17287178>Bile duct hamartomas--the von Meyenburg complex. Salles VJ, Marotta A, Netto JM, Speranzini MB, Martins MR. Hepatobiliary Pancreat Dis Int. 2007 Feb;6(1):108-9. PMID 17287178.</ref> and CT (hypodense)<ref name=pmid19294869>[The von Meyenburg complex] Schwab SA, Bautz W, Uder M, Kuefner MA. Rontgenpraxis. 2008;56(6):241-4. German. PMID 19294869.</ref> - similar to metastases.

==Peliosis hepatis==
===General===
*Associated with:
**Infections.
**Malignancy.
**Other stuff.
*Rarely biopsied.

===Microscopic===
Features:
*Cyst lined by endothelium.
**Usu. incomplete.
*Blood.
{|
[[File:1 PEL 1 680x512px.tif|Hemorrhage at left end, dilated sinusoids elsewhere (20X).]]
[[File:2 PEL 1 680x512px.tif|Ramifying dilated sinusoidal spaces (100X).]]
 
[[File:3 PEL 1 680x512px.tif|PAS with diastase shows flat lining (400X).]]
[[File:4 PEL 1 680x512px.tif|Necrotic hepatocytes in cords, presumably due to pressure (400X).]]
|}
Peliosis hepatis. Hemorrhage at left end, dilated sinusoids elsewhere (UL 20X). Ramifying dilated sinusoidal spaces (UR 100X). PAS with diastase shows flat lining (LL 400X). Necrotic hepatocytes in cords, presumably due to pressure (LR 400X).

==Total parenteral nutrition==
*Abbreviated ''TPN''.

===General===
*Indication: short gut syndrome, others.

===Microscopic===
Variable - may range from: steatosis, steatohepatitis, cholestasis, fibrosis and cirrhosis.<ref name=pmid16766237>{{cite journal |author=Guglielmi FW, Boggio-Bertinet D, Federico A, ''et al.'' |title=Total parenteral nutrition-related gastroenterological complications |journal=Dig Liver Dis |volume=38 |issue=9 |pages=623–42 |year=2006 |month=September |pmid=16766237 |doi=10.1016/j.dld.2006.04.002 |url=}}</ref>

Features (classic):<ref>{{Cite journal | last1 = Li | first1 = SJ. | last2 = Nussbaum | first2 = MS. | last3 = McFadden | first3 = DW. | last4 = Gapen | first4 = CL. | last5 = Dayal | first5 = R. | last6 = Fischer | first6 = JE. | title = Addition of glucagon to total parenteral nutrition (TPN) prevents hepatic steatosis in rats. | journal = Surgery | volume = 104 | issue = 2 | pages = 350-7 | month = Aug | year = 1988 | doi = | PMID = 3135627 }}</ref><ref>{{Cite journal | last1 = Stanko | first1 = RT. | last2 = Nathan | first2 = G. | last3 = Mendelow | first3 = H. | last4 = Adibi | first4 = SA. | title = Development of hepatic cholestasis and fibrosis in patients with massive loss of intestine supported by prolonged parenteral nutrition. | journal = Gastroenterology | volume = 92 | issue = 1 | pages = 197-202 | month = Jan | year = 1987 | doi = | PMID = 3096806 }}
</ref>
*[[Steatosis]] (periportal) - early.
*Cholestasis - late.

==Giant cell hepatitis==
*[[AKA]] ''neonatal giant cell hepatitis''.

:See: ''[[Giant cell hepatitis]]''.

==Hepatic amyloidosis==
{{Main|Amyloidosis}}
*[[AKA]] ''liver amyloidosis''.
*[[AKA]] ''amyloidosis of the liver''.
===General===
*Diffuse abundant amyloid within the space of Disse is associated with [[portal hypertension]].<ref name=pmid1864548>{{Cite journal | last1 = Bion | first1 = E. | last2 = Brenard | first2 = R. | last3 = Pariente | first3 = EA. | last4 = Lebrec | first4 = D. | last5 = Degott | first5 = C. | last6 = Maitre | first6 = F. | last7 = Benhamou | first7 = JP. | title = Sinusoidal portal hypertension in hepatic amyloidosis. | journal = Gut | volume = 32 | issue = 2 | pages = 227-30 | month = Feb | year = 1991 | doi = | PMID = 1864548 | PMC = 1378815 | URL = http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1378815/?tool=pubmed }}</ref>

===Microscopic===
Features:
*Amorphous extracellular pink stuff on H&E - see ''[[amyloid]]'' article.

DDx:
*[[Fibrolamellar hepatocellular carcinoma]].

====Images====
<gallery>
Image:Hepatic_amyloidosis_-_low_mag.jpg | Amyloidosis of the liver - low mag. (WC)
Image:Hepatic_amyloidosis_-_intermed_mag.jpg | Amyloidosis of the liver - intermed. mag. (WC)
Image:Hepatic_amyloidosis_-_high_mag.jpg | Amyloidosis of the liver - high mag. (WC)
Image:Hepatic_amyloidosis_-_very_high_mag.jpg | Amyloidosis of the liver - very high mag. (WC)
</gallery>
{|
[[File:1 AMY 1 680x512px.tif|Amorphous material replaces hepatic parenchyma [4X]]]
[[File:2 AMY 1 680x512px.tif|Material barely stains blue on trichrome [10X]]]
 
[[File:3 AMY 1 680x512px.tif|Material stains red on unpolarized Congo Red [40X]]]
[[File:4 AMY 1 680x512px.tif|Material stains apple green on polarized Congo Red [40X]]]
|}
Amyloidosis. Amorphous material replaces hepatic parenchyma [UL 4X]. Material barely stains blue on trichrome [UR 10X] Material stains red on unpolarized Congo Red [LL 40X] Material stains apple green on polarized Congo Red [LR 40X]

===Stains===
*[[Congo red]] +ve.

==Fulminant hepatic necrosis==
===General===
Etiology:
*Viral, i.e. [[Hepatitis A]], [[Hepatitis B]]; [[Hepatitis C]] - extremely rare.
*Trauma.
*Shock.

===Microscopic===
{|
[[File:1 Necrosis 2 680x512px.tif| Submassive hepatic necrosis.]]
[[File:2 Necrosis 2 680x512px.tif| Submassive hepatic necrosis.]]
 
[[File:3 Necrosis 2 680x512px.tif| Submassive hepatic necrosis.]]
[[File:4 Necrosis 2 680x512px.tif| Submassive hepatic necrosis.]]
 
[[File:5 Necrosis 2 680x512px.tif| Submassive hepatic necrosis.]]
[[File:6 Necrosis 2 680x512px.tif| Submassive hepatic necrosis.]]
|}
Submassive hepatic necrosis. Patient had transaminases in the thousands that rapidly dropped to normal. Pink preserved parenchyma strews empty necrotic spaces (Row 1 Left 20X). Focus of necrosis with no apparent hepatocytes macrophages abuts apparently normal liver (Row 1 Right 200X). Iron stain shows the macrophages bear hemosiderin (Row 2 Left 200X). Reticulin stain highlights the recently dead liver cells (Row 2 Right 200X). Reticulin stain shows a necrotic bridge forming; the multiple small black circles preclude diagnosis of a fibrous bridge (Row 3 Left 200X). Trichrome shows the necrotic bridge (“collapse”) lacks much collagen deposition, as would be expected for bridging fibrosis (Row 3 Right 200X).

Features:
*Hepatocyte [[necrosis]].
*Bile duct proliferation.

DDx:
*[[Cholangiocarcinoma]].
*[[Angiosarcoma]].

==Secondary hemochromatosis==
:''For the hereditary one see [[hereditary hemochromatosis]]''.
===General===
*Iron overload secondary to blood transfusions for hereditary or acquired anemia.<ref name=pmid19727383/>
**Primary hemochromatosis due to a defect in iron processing - called ''[[hereditary hemochromatosis]]''.
*Imaging considered the best test, as iron deposition is patchy.<ref name=pmid19727383/>

Selected hereditary causes:<ref name=pmid19727383>{{Cite journal | last1 = Gattermann | first1 = N. | title = The treatment of secondary hemochromatosis. | journal = Dtsch Arztebl Int | volume = 106 | issue = 30 | pages = 499-504, I | month = Jul | year = 2009 | doi = 10.3238/arztebl.2009.0499 | PMID = 19727383 | PMC = 2735704 | URL = http://www.ncbi.nlm.nih.gov.myaccess.library.utoronto.ca/pmc/articles/PMC2735704/?tool=pubmed}}</ref>
*Thalassemia.
*[[Sickle cell anemia]].
*Hereditary sideroblastic anemia.

Selected acquired causes:<ref name=pmid19727383/>
*[[Myelodysplastic syndromes]]
*Myelofibrosis
*Aplastic anemia, intractable.

===Microscopic===
:See ''[[hereditary hemochromatosis]]''.

==Hepatic sarcoidosis==
{{Main|Hepatic sarcoidosis}}
==Overlapping Disorders==

[[File:1 Mixed Disorder 1 680x512px.tif|Changes of steatohepatitis and interface hepatitis, with granuloma. Patient with diabetes was ANA, AMA, HCV, HBV negative, without drugs known to produce granulomas or interface hepatitis. This may be a case of AMA negative primary biliary cirrhosis, but studies to determine that with certainty were not performed.]]
[[File:2 Mixed Disorder 1 680x512px.tif|Changes of steatohepatitis and interface hepatitis, with granuloma. Patient with diabetes was ANA, AMA, HCV, HBV negative, without drugs known to produce granulomas or interface hepatitis. This may be a case of AMA negative primary biliary cirrhosis, but studies to determine that with certainty were not performed.]]
[[File:3 Mixed Disorder 1 680x512px.tif|Changes of steatohepatitis and interface hepatitis, with granuloma. Patient with diabetes was ANA, AMA, HCV, HBV negative, without drugs known to produce granulomas or interface hepatitis. This may be a case of AMA negative primary biliary cirrhosis, but studies to determine that with certainty were not performed.]]
[[File:4 Mixed Disorder 1 680x512px.tif|Changes of steatohepatitis and interface hepatitis, with granuloma. Patient with diabetes was ANA, AMA, HCV, HBV negative, without drugs known to produce granulomas or interface hepatitis. This may be a case of AMA negative primary biliary cirrhosis, but studies to determine that with certainty were not performed.]]
[[File:5 Mixed Disorder 1 680x512px.tif|Changes of steatohepatitis and interface hepatitis, with granuloma. Patient with diabetes was ANA, AMA, HCV, HBV negative, without drugs known to produce granulomas or interface hepatitis. This may be a case of AMA negative primary biliary cirrhosis, but studies to determine that with certainty were not performed.]]
[[File:6 Mixed Disorder 1 680x512px.tif|Changes of steatohepatitis and interface hepatitis, with granuloma. Patient with diabetes was ANA, AMA, HCV, HBV negative, without drugs known to produce granulomas or interface hepatitis. This may be a case of AMA negative primary biliary cirrhosis, but studies to determine that with certainty were not performed.]] 
Changes of steatohepatitis and interface hepatitis, with granuloma. Patient with diabetes was ANA, AMA, HCV, HBV negative, without drugs known to produce granulomas or interface hepatitis. This may be a case of AMA negative primary biliary cirrhosis, but studies to determine that with certainty were not performed. A. Low power shows hepatocytes afflicted by steatosis and an inflamed portal tract. B. In a region of fatty change lie cytoplasmic tufts of ballooning degeneration (green arrows) and a lipogranuloma (black arrow). C. At the portal-hepatocyte junction lies interface hepatitis (black arrows), as well as extension of inflammation into the lobule (green arrows). D. Red hepatocytes bounded by inflammation denote piecemeal necrosis [PAS without diastase]. E. Giant cells intermixed with lymphocytes prove a portal granuloma [PAS without diastase]. F. A blue fibrous bridge extends from a triad [Trichrome].

[[File:4 95599552608917 sl 1.png|Acute obstructive changes and changes of recurrent acute injury]]
[[File:4 95599552608917 sl 2.png|Acute obstructive changes and changes of recurrent acute injury]]
[[File:4 95599552608917 sl 3.png|Acute obstructive changes and changes of recurrent acute injury]]
[[File:4 95599552608917 sl 4.png|Acute obstructive changes and changes of recurrent acute injury]]
[[File:4 95599552608917 sl 5.png|Acute obstructive changes and changes of recurrent acute injury]]
[[File:4 95599552608917 sl 6.png|Acute obstructive changes and changes of recurrent acute injury]]
[[File:4 95599552608917 sl 7.png|Acute obstructive changes and changes of recurrent acute injury]] 
Acute obstructive changes and changes of recurrent injury in 46 yo man with Clostridium perfringens positive blood culture, an ERCP that showed duodenal compression by the pancreas with resultant bile duct dilatation. The patient had had and continued to have multiple bouts of acute pancreatitis. At the time of biopsy, decreased platelet count/hemoglobin/albumin, elevated lipase/amylase/PT/PTT, normal alkaline phosphatase, bilirubin, AST/ALT, AMA, hepatitis virus serology, ANA. A. Fragment biopsy shows inflamed triads and bridges. B. Trichrome shows bridges without nodules, evidence of prior injury; the patient subsequently developed multiple episodes of pancreatitis. C. Reticulin shows piecemeal necrosis, with black lines bounding individual hepatocytes at interface (arrows). D. Collapse is shown by closly approximated thick black lines; one cannot call portal-central collapse without seeing a central vein. Note on this and the other reticulin image that regeneration, two cell thick cords, is not prominent. E. PAS D of two portal triads, far nearer than normal, both expanded. Note increased number of ducts/ductules (red arrows), neutrophils, and PAS-D macrophages. F. PAS D shows collapse extending from a triad to a portion of a lobule with steatosis. No feathery degeneration or bile duct plugs were seen. Neither were foci of spotty necrosis or abscess seen. G. Other triads, again edematous, showed more of a chronic inflammatory response, with occasional plasma cells (black arrows). Also present are neutrophils (red arrows). The bile duct (grey arrow) near the artery (brown arrow) shows mildly disturbed nuclei. Note early proliferated bile ductules (cyan arrows).

[[File:6 17281676469188 sl 1.png| Hepatitis B virus with steatohepatitis]]
[[File:6 17281676469188 sl 2.png| Hepatitis B virus with steatohepatitis]]
[[File:6 17281676469188 sl 3.png| Hepatitis B virus with steatohepatitis]]
[[File:6 17281676469188 sl 4.png| Hepatitis B virus with steatohepatitis]]
[[File:6 17281676469188 sl 5.png| Hepatitis B virus with steatohepatitis]]
[[File:6 17281676469188 sl 6.png| Hepatitis B virus with steatohepatitis]] 
Hepatitis B virus with steatohepatitis in a 36 year old man with hepatitis B surface antigen and hepatitis Be antigen positivity, Hepatitis be QTPC of 1750 cop/mL, an occasionally mildly elevated (42) ALT, and normal glucose, alkaline phosphatase, bilirubin, and other transaminases. He had a history of alcohol abuse, which became controlled. A. Triads show scant inflammation without definite interface hepatitis. About one-fourth of the lobule, not pan-acinar, is afflicted by steatosis. B. Occasional tufts are seen (arrow), indicating focal ballooning sufficient for a diagnosis of steatohepatitis. C. Glycogenated nuclei (black arrows) and hepatocytes with feathery degeneration (red arrows) are seen. D. Very rare foci of spotty necrosis were seen. E. Apart from this triad and the one in the trichrome stain in F, which had moderate inflammation comprising lymphocytes and macrophages, all triads were small, most without any inflammation at all. Neither collapse nor piecemeal necrosis were seen on reticulin stain. F. Trichrome stain showed only portal fibrosis. The interhepatocyte fibrosis required for brunt fibrosis stage I was not seen. Hence, one would grade this as follows: A) Chronic hepatitis (history of hepatitis B), Metavir activity index 1, Piecemeal necrosis 0, Lobular necrosis 1, Metavir fibrosis stage 1, B) Steatohepaitits, Brunt necroinflammatory grade 1, Brunt fibrosis stage 0.

=See also=
*[[Pancreas]].
*[[Gastrointestinal pathology]].
*[[Liver neoplasms]].
*[[Liver]].

=References=
{{reflist|2}}

[[Category:Gastrointestinal pathology]]
[[Category:Liver pathology]]
[[Category:Medical liver disease]]

Medical liver disease

2017-01-23T15:33:29Z

Mitchell: /* Overlapping Disorders */ added a case

[[Image:Ground glass hepatocytes high mag cropped 2.jpg|thumb|right|[[Micrograph]] showing ground glass hepatocytes, as seen in chronic [[hepatitis B]]. [[H&E stain]].]]
This article deals with '''medical [[liver]] disease'''. An introduction to the liver and approach is found in the ''[[liver]]'' article.

Every differential in liver pathology has "drugs"<ref>{{Ref PCPBoD8|448}}</ref> -- if it isn't clearly malignancy.

Liver neoplasms are dealt with in the ''[[liver neoplasms]]'' article.

Medical liver biopsies are often non-specific, as the liver has the same appearance for many mechanisms of injury, especially when the injury is marked. The clinical history, serology and imaging are essential for proper interpretations in this domain of pathology.

=Review of liver blood work=
===Inflammation activity===
*ALT.
*AST.

===Cholestatic markers===
*ALP.
*GGT - used to assess whether the ALP is an "honest" value, elevated in cirrhosis.

===Cirrhosis/decompensation===
*PLT - low is suggestive of dysfunction.
*INR - high is bad, unless anticoagulated.

===Other===
*Bilirubin.
**Direct (AKA conjugated).
**Indirect (AKA unconjugated).

A short DDx of elevated:<ref>{{Ref PCPBoD8|441}}</ref>
*Indirect:
**[[Gilbert syndrome]].
**Crigler-Najjar syndrome type 1.
**Crigler-Najjar syndrome type 2.
*Direct:
**Rotor syndrome.
**Dubin-Johnson syndomre.

===Viral hepatitis===
*HBV DNA.
*HCV RNA.
*HBs Ag, HBs Ab, HBe Ag, HBe Ab.
*HCV Ab.

Others:
*[[Epstein-Barr virus]] (EBV).
*[[Cytomegalovirus]] (CMV) - especially in the immune incompetent.

====Hepatitis B====
Meaning & utility of the various [[Hepatitis B]] tests:<ref>URL: [http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/hepatology/hepatitis-B/ http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/hepatology/hepatitis-B/]. Accessed on: 16 May 2011.</ref><ref name=lto_hepb>URL: [http://www.labtestsonline.org/understanding/analytes/hepatitis_b/test.html http://www.labtestsonline.org/understanding/analytes/hepatitis_b/test.html]. Accessed on: 16 May 2011.</ref>
{| class="wikitable sortable" border="1"
! Test name
! Location
! Positive test
! Negative test
! Usual question
|-
| HBs Ag||Surface||Virus active||No active infection||Active infection?
|-
| HBs Ab||Surface||Exposed OR vaccinated||No exposure OR no vaccine OR loss of Ab||Immunization status?
|-
| HBe Ag||Virus core||Infect. w/ viral replication||No active infection||Active infect. w/ viral replication?
|-
| HBe Ab||Virus core||Exposed to virus||Infect. w/o antibody response OR not exposed||Immune response to infection?
|-
| HBV DNA||-||Active||Not active/no exposure||Viral load/how active?
|-
| HBc Ab||Virus core||Virus active/previous exposure||No exposure||Early active infection?
|}
Notes:
*''HBc Ab'' may test for acute (IgM) or chronic infection - dependent on specific antibody test; it is often used to look for early infection.<ref name=lto_hepb>URL: [http://www.labtestsonline.org/understanding/analytes/hepatitis_b/test.html http://www.labtestsonline.org/understanding/analytes/hepatitis_b/test.html]. Accessed on: 16 May 2011.</ref>
*''Carriers of hepatitis B'': HBs Ag +ve, HBs Ab -ve, HBc Ag -ve, HBc Ab +ve, HBe Ag -ve, HBe Ab +ve.<ref>URL: [http://labtestsonline.org/understanding/analytes/hepatitis-b/tab/test http://labtestsonline.org/understanding/analytes/hepatitis-b/tab/test]. Accessed on: 3 May 2012.</ref>

===Markers for rare liver diseases===
*Ceruloplasm - low think ''[[Wilson's disease]]''; typical value for Wilson's ~ 0.12 g/L.
**<0.20 g/L is a criteria for Wilson's disease.<ref name=pmid18556333>Diagnostic accuracy of serum ceruloplasmin in Wilson disease: determination of sensitivity and specificity by ROC curve analysis among ATP7B-genotyped subjects. Mak CM, Lam CW, Tam S. Clin Chem. 2008 Aug;54(8):1356-62. Epub 2008 Jun 12. PMID 18556333. URL: [http://www.clinchem.org/cgi/reprint/54/8/1356.pdf http://www.clinchem.org/cgi/reprint/54/8/1356.pdf]. Accessed on: 28 September 2009.</ref>
*Alpha-1 antitrypsin - if low think ''deficiency''.

===Hemosiderosis===
*Ferritin - high.
*Iron saturation - high.

Causes:
*Hemochromatosis.
*Hemolysis, chronic.
*Cirrhosis.

=Medical imaging=
Blood flow:<ref>URL: [http://insidesurgery.com/2010/12/hepatopedal-hepatofugal-flow/ http://insidesurgery.com/2010/12/hepatopedal-hepatofugal-flow/]. Accessed on: 2 December 2011.</ref>
*Hepatopedal flow = normal portal vein flow.
*Hepatofugal flow = reversed portal vein flow.

==Interventional measurements==
Wedged to free hepatic venous pressure:<ref name=pmid1864548>{{Cite journal | last1 = Bion | first1 = E. | last2 = Brenard | first2 = R. | last3 = Pariente | first3 = EA. | last4 = Lebrec | first4 = D. | last5 = Degott | first5 = C. | last6 = Maitre | first6 = F. | last7 = Benhamou | first7 = JP. | title = Sinusoidal portal hypertension in hepatic amyloidosis. | journal = Gut | volume = 32 | issue = 2 | pages = 227-30 | month = Feb | year = 1991 | doi = | PMID = 1864548 | PMC = 1378815 | URL = http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1378815/?tool=pubmed }}</ref>
*Normal = 1-4 mmHg.
**Elevated in [[portal hypertension]].

=Liver biopsy=
==Medical liver biopsy adequacy==
Liver biopsy specimens should be:<ref>{{Ref MacSween|418}}</ref>
*2.0 cm in length and contain 11-15 portal tracts,
*The core should be deeper than 1.0 cm from the liver capsule; specimens close to the capsule may lead to over grading of fibrosis.

==Reporting==
{{Main|Pathology reports}}
<pre>
Specimen, procedure:
- Diagnosis.
</pre>
The diagnosis usually contains grading and staging information, e.g. ''activity 2 /4, Laennec fibrosis stage 1 /4''.

In the context of medical liver disease:
*Grade = inflammation/activity.
*Stage = severity of fibrosis/architectural changes.

Notes:
*The term "acute" is infrequently used in liver pathology.
*In the liver: neutrophils ''is not'' acute -- unlike most elsewhere in the body.<ref>OA. September 2009.</ref>

===A microscopic checklist===
<pre>
Size of biopsy: Adequate
Fragmentation: Absent
Fibrosis: Stage 2-3/4, mostly stage 2
Fibrous septa: Present
Septa with curved contours: Present – focally only
Large droplet steatosis (% of hepatocytes): Present, moderate 60%
Ballooning of hepatocytes: Present, rare
Mallory-Denk bodies: Present, rare
Portal inflammation: Present
Interface activity: Minimal (0-1/4)
Lobular necroinflammation: Minimal
Ducts: Present in normal numbers
Duct injury: Absent
Ductular reaction: Absent
Cholestasis: Absent
Terminal hepatic venules: Present
Iron stain: Absent
Ground glass cells with routine stains: Absent
PASD for alpha-1 antitrypsin droplets: Negative
</pre>

=Viral hepatitis=
These are common. The diagnoses are based on serology. The serology is covered in the ''[[Liver_pathology#Viral_hepatitis|viral hepatitis]]'' section in the ''[[liver pathology]]'' article.

Typically classified as:<ref name=pmid8048409>{{Cite journal | title = Terminology of chronic hepatitis, hepatic allograft rejection, and nodular lesions of the liver: summary of recommendations developed by an international working party, supported by the World Congresses of Gastroenterology, Los Angeles, 1994. | journal = Am J Gastroenterol | volume = 89 | issue = 8 Suppl | pages = S177-81 | month = Aug | year = 1994 | doi = | PMID = 8048409 }}</ref><ref>URL: [http://familydoctor.org/familydoctor/en/diseases-conditions/hepatitis-b.html http://familydoctor.org/familydoctor/en/diseases-conditions/hepatitis-b.html]. Accessed on: 2 May 2012.</ref>
#Acute < 6 months duration.
#Chronic > 6 months duration.

==Hepatitis A==
*Infection is self-limited, i.e. not persistent.
**May present as ''[[fulminant hepatic necrosis]]''.
*Usually asymptomatic in children.<ref name=pmid20068336>{{cite journal |author=Jeong SH, Lee HS |title=Hepatitis A: clinical manifestations and management |journal=Intervirology |volume=53 |issue=1 |pages=15–9 |year=2010 |pmid=20068336 |doi=10.1159/000252779 |url=}}</ref>
*Serology is diagnostic.

==Hepatitis B==
:''Hepatitis B virus'', abbreviated ''HBV'', redirects here.
{{Main|Hepatitis B}}

==Hepatitis C==
{{Main|Hepatitis C}}

=Other infections=
*Hydatid disease (Hydatid cyst).
*Ascaris.
*Fasciola

==Hydatid disease==
*[[AKA]] ''hydatid cyst''.
===General===
*Etiology: ''[[Echinococcus]]''.

===Microscopic===
Features:
*Laminated wall +/- calcification.<ref name=Ref_PBPoD8_448>{{Ref PCPBoD8|448}}</ref>
*Organisms -- see ''[[Echinococcus]]''.

====Images====
<gallery>
Image:Liver_cyst_wall_-_intermed_mag.jpg | Liver cyst wall - intermed. mag. (WC)
Image:Liver_cyst_wall_-_high_mag.jpg | Liver cyst wall - high mag. (WC)
Image: Laminated liver cyst wall - intermed mag.jpg | Characteristic laminated portion - intermed. mag. (WC)
Image: Laminated liver cyst wall - high mag.jpg | Characteristic laminated portion - high mag. (WC)
</gallery>
[[www]]:
*[http://pathmicro.med.sc.edu/parasitology/hydatid-hist1.jpg Hydatid cyst (med.sc.edu)].
*[http://www.atlas.or.kr/atlas/include/viewImg.html?uid=645 Hydatid cyst (atlas.or.kr)].
*[http://casereports.bmj.com/content/2009/bcr.04.2009.1798.full Hydatid cyst (casereports.bmj.com)].

==Abscess==
{|
[[File:1 ABS 1 680x512px.tif|A process replaces most of the liver parenchyma (20X).]]
[[File:2 ABS 1 680x512px.tif|Fibrinopurulent exudate apposes granulation tissue (200X).]]
 
[[File:3 ABS 1 680x512px.tif|Neutrophils lie in widened sinusoids (200X)..]]
[[File:4 ABS 1 680x512px.tif|Trichrome shows collagenization of spaces of Disse. Scarring about an abscess or other mass lesion should not be interpreted as reflective of the liver in general (200X).]]
|}
Abscess. A process replaces most of the liver parenchyma (UL 20X). Fibrinopurulent exudate apposes granulation tissue (UR 200X). Neutrophils lie in widened sinusoids (LL 200X).Trichrome shows collagenization of spaces of Disse. Scarring about an abscess or other mass lesion should not be interpreted as reflective of the liver in general (LR 200X).

==Coccidiomycosis==
Coccidiomycosis
Table show [[GRAN-COC]]
{|
[[File:Coccidiomycosis - 1 - 40X 680x512px shot.tif|500x500px Granulomas at low power]]
[[File:Coccidiomycosis - 1 - 200X 680x513px shot.tif|500x500px Granulomas with centrally crowded cells & lady slipper macrophage nuclei]]
 
[[File:Coccidiomycosis - 1 - 400X 1369x1024px shot.tif|500x500px Center of previous granuloma showing pyknotic macrophage nuclei]]
[[File:Coccidiomycosis - 1 - GMS 400X 1369x1024px shot.tif|500x500px Four Coccidiomycotic spherules]]
|}
Note the granulomas in otherwise undisturbed liver (UL), the larger prior granuloma with centrally crowded cells & lady slipper macrophage nuclei (UR), the center of the granuloma with pyknotic macrophage nuclei "necrotizing" (LL), and the organisms on GMS stain (LR).

=Metabolic and toxic=
==Alcoholic liver disease==
===General===
*Acute and/or chronic liver changes due to excessive [[alcohol]] use - includes:
**''[[Alcoholic steatohepatitis]]'' (ASH), [[AKA]] ''alcoholic hepatitis''.<ref>URL: [http://emedicine.medscape.com/article/170539-overview http://emedicine.medscape.com/article/170539-overview]. Accessed on: 3 May 2012.</ref>
***Alcoholic hepatitis can be with minimal steatosis.<ref>STC. 6 December 2010.</ref>
**[[Steatosis]] - classically macrovescicular and centrilobular.
**Alcoholic [[cirrhosis]].

====Classic lab findings in EtOH abusers====
*AST & ALT elevated with AST:ALT=2:1.
*GGT elevated.
*MCV increased.

===Gross pathology/radiologic findings===
*Classically micronodular pattern.
**May be macronodular.

===Microscopic===
See:
*''[[Steatohepatitis]]'' section and ''[[ballooning degeneration]]'' section.

Features:
*Often zone III damage.
*Cholestatsis common, i.e. yellow staining.
**NASH (non-alcoholic steatohepatitis) usu. does not have cholestasis.<ref>STC. 6 December 2010.</ref>
*Fibrosis starts at central veins.
*Neutrophils (often helpful) -- few other things have PMNs. (???)
**Neutrophils cluster around cells with Mallory hyaline.

====Images====
{|
[[File:1 etoh 3 680x512px.tif| Alcoholic hepatitis with Metavir stage IV fibrosis (advanced fibrosis/cirrhosis).]]
[[File:2 etoh 3 680x512px.tif| Alcoholic hepatitis with Metavir stage IV fibrosis (advanced fibrosis/cirrhosis).]]
 
[[File:3 etoh 3 680x512px.tif| Alcoholic hepatitis with Metavir stage IV fibrosis (advanced fibrosis/cirrhosis).]]
[[File:4 etoh 3 680x512px.tif| Alcoholic hepatitis with Metavir stage IV fibrosis (advanced fibrosis/cirrhosis).]]
 
[[File:5 etoh 3 680x512px.tif| Alcoholic hepatitis with Metavir stage IV fibrosis (advanced fibrosis/cirrhosis).]]
[[File:6 etoh 3 680x512px.tif| Alcoholic hepatitis with Metavir stage IV fibrosis (advanced fibrosis/cirrhosis).]]
|}
Alcoholic hepatitis with Metavir stage IV fibrosis (advanced fibrosis/cirrhosis).
Trichrome shows relatively non-inflamed fibrous bands, as well as [between green dots] nodules. The lack of regeneration throughout might have precluded a diagnosis of cirrhosis, but stage IV fibrosis under the Metavir system is justified (Row 1 Left 20X). Reticulin shows regenerative nodules [left] with mostly two or more nuclei between black lines juxtaposed to non-regenerative hepatocytes on the right, without piecemeal necrosis. (Row 1 Right 100X). Regenerative nodules show occasional neutrophils [red arrow] and cytoplasmic tufts of ballooned cells, sometimes possibly Mallory hyalin [green arrows] (Row 2 Left 200X). Triads (note vein [green arrow], artery [yellow arrow], and interlobular bile duct [blue arrow]) generally showed little or no interface hepatitis, even when expanded by fibrosis and inflamed (Row 2 Right 200X). Occasional foci of spotty necrosis were seen (Row 3 Left 200X). This edge of an inflamed triads shows neutrophils about proliferated bile ducts [red arrows], as well as Mallory-Denk bodies [blue arrows] (Row 4 Left 400X).
{|
[[File:1 etoh 4 680x512px.tif| Cirrhosis in an alcoholic.]]
[[File:2 etoh 4 680x512px.tif| Cirrhosis in an alcoholic.]]
 
[[File:3 etoh 4 680x512px.tif| Cirrhosis in an alcoholic.]]
[[File:4 etoh 4 680x512px.tif| Cirrhosis in an alcoholic.]]
 
[[File:5 etoh 4 680x512px.tif| Cirrhosis in an alcoholic.]]
[[File:6 etoh 4 680x512px.tif| Cirrhosis in an alcoholic.]]
|}
Definite cirrhosis in an alcoholic. Hepatocyte free bands parse tissue, with occasional definite islands [arrows] (Row 1 Left 40X). Trichrome establishes blue fibrosis about isles [arrows] (Row 1 Right 40X). Reticulin stain shows nodules with regeneration, wherein a large proportion of them are at least two nuclei thick [arrows] (Row 2 Left 200X). Bile duct proliferation can be difficult, sometimes mimicking cholangiocarcinoma. Follow the double headed arrows to see how the ductules can be seen to proliferate from a single sources, with all ducts being complete, without necrotic epithelial cells. (Row 2 Right 400X). PAS with distase can help, as cholangiocarcinoma generally lacks the red rim of proliferating bile ductules [arrows]; again note the connections that can be made between the ductule openings by the blue double headed arrows. The cyan double headed arrows show general parallelism, consistent with uniform directionality induced by extrinsic force, not a neoplastic spread (Row 3 Left 400X). Trichrome shows the most difficult focus. Double headed arrows display the connectivity seen before of the proliferated bile ductules. Note that numerous pairs of adjacent perpendicular glands without a head to foot appearance are not seen that would indicate the disorderly spread of cholangiocarcinoma (Row 3 Right 400X).

{|
[[File:1 ALC 2 680x512px.tif|Expanded, inflamed triads with increased bile duct/vascular openings. Mild steatosis (40X).]]
[[File:2 ALC 2 680x512px.tif|Trichrome stain shows periportal fibrosis [red arrowheads] (200X).]]
 
[[File:3 ALC 2 680x512px.tif|PAS with diastase stain shows proliferated bile ductules [blue arrowheads] in stroma with mixed inflammatory infiltrate (400X)]]
[[File:4 ALC 2 680x512px.tif|Neutrophils about ballooned hepatocyte (satellitosis) [yellow arrowheads]. Councilman bodies [green arrowheads] (400X).]]
|}
Alcoholic hepatitis without cirrhosis. No history of viral disease. AMA negative. Expanded, inflamed triads with increased bile duct/vascular openings. Mild steatosis (UL 40X). Trichrome stain shows periportal fibrosis [red arrowheads] (UR 200X). PAS with diastase stain shows proliferated bile ductules [blue arrowheads] in stroma with mixed inflammatory infiltrate (LL 400X) Neutrophils about ballooned hepatocyte (satellitosis) [yellow arrowheads]. Councilman bodies [green arrowheads] (LR 400X).

Notes:
*If portal inflammatory infiltrates more than mild, r/o other causes i.e. [[viral hepatitis]].
*Mallory bodies once thought to be characteristic; now considered non-specific and generally poorly understood.<ref>{{cite journal |author=Jensen K, Gluud C |title=The Mallory body: theories on development and pathological significance (Part 2 of a literature survey) |journal=Hepatology |volume=20 |issue=5 |pages=1330-42 |year=1994 |month=November |pmid=7927269 |doi= |url=}}</ref>
*Some consider ''alcoholic liver disease'' a clinical diagnosis, i.e. as a pathologist one does not diagnose it.<ref>MG. September 2009.</ref>

==Non-alcoholic fatty liver disease==
*Abbreviated ''NAFLD''.
*Fatty liver that is not due to alcohol; includes obesity-related fatty liver, metabolic disease/diabetes-related fatty liver.

===NASH===
*Non-alcoholic steatohepatitis - see ''steatohepatitis'' section.
*Histologically indistinguishable from ASH.
*NASH is a ''clinical diagnosis'' based on exclusion of alcohol.

==Steatohepatitis==
{{Main|Steatohepatitis}}

=Autoimmune=
==Autoimmune hepatitis==
*Abbreviated ''AIH''.
{{Main|Autoimmune hepatitis}}

==Primary biliary cirrhosis==
*Abbreviated PBC.
{{Main|Primary biliary cirrhosis}}

==Autoimmune hepatitis with obstruction - combined changes==
{|
[[File:1 AIH OBS 1.tif|Low power shows inflammation; portal triads, lobules, central veins cannot be distinguished (40X).]]
[[File:2 AIH OBS 1.tif|Trichrome shows central venous sclerosis (red arrowhead), periportal fibrosis (green arrowhead), & space of Disse collagenization (yellow arrowhead); juxtaposition of central vein & portal tract indicates collapse, no definite bridging was seen (100X)]]
 
[[File:3 AIH OBS 1.tif|Central vein is inflamed with a rare plasma cell (cyan arrowhead) (400X).]]
[[File:4 AIH OBS 1.tif|Interface hepatitis with plasma cells (yellow arrows) and ballooned hepatocytes (red arrows). Lobule is disorganized (400X).]]
 
[[File:5 AIH OBS 1.tif|Proliferating bile ductules (blue arrows) with occasional neutrophils (fucsia arrows), indicative of obstruction, but not acute cholangitis, which requires inflamed bile duct itself, best diagnosed with associated blood vessel (400X).]]
[[File:6 AIH OBS 1.tif|Rare distorted rosettes with greenish brown strands of bile (left arrow) or bile plugs (right arrow) (400X).]]
|}
Patient with SLE and obstructive jaundice that resolved with apparent passage of stone. Low power shows inflammation; portal triads, lobules, central veins cannot be distinguished (left row 1 40X). Trichrome shows central venous sclerosis (red arrowhead), periportal fibrosis (green arrowhead), & space of Disse collagenization (yellow arrowhead); juxtaposition of central vein & portal tract indicates collapse, no definite bridging was seen (right row 1 100X). Central vein is inflamed with a rare plasma cell (cyan arrowhead) (left row 2 400X). Interface hepatitis with plasma cells (yellow arrows) and ballooned hepatocytes (red arrows). Lobule is disorganized (right row 2 400X). Proliferating bile ductules (blue arrows) with occasional neutrophils (fucsia arrows), indicative of obstruction, but not acute cholangitis, which requires inflamed bile duct itself, best diagnosed with associated blood vessel (left row 3 400X). Rare distorted rosettes with greenish brown strands of bile (left arrow) or bile plugs (right arrow) (right row 3 400X).

==Autoimmune hepatitis-primary biliary cirrhosis overlap syndrome==
*Abbreviation ''AIH-PBC OS''.
===General===
Epidemiology:
*Rare.

Serology:<ref name=pmid19491855>{{Cite journal | last1 = Muratori | first1 = P. | last2 = Granito | first2 = A. | last3 = Pappas | first3 = G. | last4 = Pendino | first4 = GM. | last5 = Quarneti | first5 = C. | last6 = Cicola | first6 = R. | last7 = Menichella | first7 = R. | last8 = Ferri | first8 = S. | last9 = Cassani | first9 = F. | title = The serological profile of the autoimmune hepatitis/primary biliary cirrhosis overlap syndrome. | journal = Am J Gastroenterol | volume = 104 | issue = 6 | pages = 1420-5 | month = Jun | year = 2009 | doi = 10.1038/ajg.2009.126 | PMID = 19491855 }}</ref>
*AMA +ve.
*Anti-dsDNA +ve.

===Microscopic===
:See: ''[[autoimmune hepatitis]]'' and ''[[primary biliary cirrhosis]]''.
{|
[[File:1 AIH PBC 1 680x512px.tif|Expanded portal tracts with fuzzy edges (40X).]]
[[File:2 AIH PBC 1 680x512px.tif|Interface hepatitis with plasma cells (400X).]]
 
[[File:3 AIH PBC 1 680x512px.tif|Loose granuloma (400X).]]
[[File:4 AIH PBC 1 680x512px.tif|Damaged bile duct (400X).]]
|}

AIH/PBC overlap. AMA & ANA positive with Alkaline phosphatase > 2 upper limit of normal & one ALT > 5 times upper limit of normal. Expanded portal tracts with fuzzy edges (UL 40X). IInterface hepatitis with plasma cells (UR 400X). Loose granuloma (LL 400X). Damaged bile duct (LR 400X).

==Primary sclerosing cholangitis==
*Abbreviated ''PSC''.
{{Main|Primary sclerosing cholangitis}}

=Hereditary=
==Caroli disease==
===General===
*Genetic disease.
**Frequently associated with [[autosomal recessive polycystic kidney disease]] (ARPKD).<ref name=omim263200>{{OMIM|263200}}</ref>
**May be seen in isolation.<ref name=omim600643>{{OMIM|600643}}</ref>

Clinical:<ref name=pmid17461493>{{Cite journal | last1 = Yonem | first1 = O. | last2 = Bayraktar | first2 = Y. | title = Clinical characteristics of Caroli's syndrome. | journal = World J Gastroenterol | volume = 13 | issue = 13 | pages = 1934-7 | month = Apr | year = 2007 | doi = | PMID = 17461493 }}</ref>
*Recurrent [[cholangitis]].
*Recurrent [[cholelithiasis]].
*[[Cholangiocarcinoma]]<ref name=pmid17461492>{{Cite journal | last1 = Yonem | first1 = O. | last2 = Bayraktar | first2 = Y. | title = Clinical characteristics of Caroli's disease. | journal = World J Gastroenterol | volume = 13 | issue = 13 | pages = 1930-3 | month = Apr | year = 2007 | doi = | PMID = 17461492 }}</ref> - seen in ~7% of cases.<ref name=pmid15347876>{{Cite journal | last1 = Karim | first1 = AS. | title = Caroli's disease. | journal = Indian Pediatr | volume = 41 | issue = 8 | pages = 848-50 | month = Aug | year = 2004 | doi = | PMID = 15347876 }}</ref>

Note:
*''Caroli syndrome'' = Caroli disease + congenital hepatic fibrosis.<ref name=pmid15888616>{{Cite journal | last1 = Brancatelli | first1 = G. | last2 = Federle | first2 = MP. | last3 = Vilgrain | first3 = V. | last4 = Vullierme | first4 = MP. | last5 = Marin | first5 = D. | last6 = Lagalla | first6 = R. | title = Fibropolycystic liver disease: CT and MR imaging findings. | journal = Radiographics | volume = 25 | issue = 3 | pages = 659-70 | month = | year = | doi = 10.1148/rg.253045114 | PMID = 15888616 | URL = http://radiographics.rsna.org/content/25/3/659.long }}</ref>

===Gross===
*Dilated bile ducts.<ref name=omim263200/>

===Microscopic===
Features:<ref name=pmid17461493/>
*Dilated bile ducts.
*Periductal fibrosis. (???)
*+/-Fibrosis.

Image:
*[http://www.meddean.luc.edu/lumen/MedEd/orfpath/11-3-10.jpg Caroli disease (meddean.luc.edu)].<ref>URL: [http://www.meddean.luc.edu/lumen/MedEd/orfpath/develop.htm http://www.meddean.luc.edu/lumen/MedEd/orfpath/develop.htm]. Accessed on: 1 December 2011.</ref>

==Hereditary hemochromatosis==
:''For secondary causes see [[secondary hemochromatosis]]''.
{{Main|Hereditary hemochromatosis}}

==Wilson disease==
{{Main|Wilson's disease}}

==Alpha-1 antitrypsin deficiency==
*[[AKA]] ''alpha1-antiprotease inhibitor deficiency''.
{{Main|Alpha-1 antitrypsin deficiency }}

=Other=
==Budd-Chiari syndrome==
*[[AKA]] ''hepatic vein obstruction''.
===General===
*Hepatic outflow obstruction.

Clinical triad:<ref name=pmid21573256>{{Cite journal | last1 = Fox | first1 = MA. | last2 = Fox | first2 = JA. | last3 = Davies | first3 = MH. | title = Budd-Chiari syndrome--a review of the diagnosis and management. | journal = Acute Med | volume = 10 | issue = 1 | pages = 5-9 | month = | year = 2011 | doi = | PMID = 21573256 }}</ref>
*Ascites.
*Abdominal pain.
*Hepatomegaly.

Etiology:
*~50% have a [[myeloproliferative disease]].<ref name=pmid18814079>{{Cite journal | last1 = Plessier | first1 = A. | last2 = Valla | first2 = DC. | title = Budd-Chiari syndrome. | journal = Semin Liver Dis | volume = 28 | issue = 3 | pages = 259-69 | month = Aug | year = 2008 | doi = 10.1055/s-0028-1085094 | PMID = 18814079 }}</ref>
*May be due to mass effect from a tumour.

Clinical DDx:
*[[Hepatic veno-occlusive disease]].

===Microscopic===
Features:<ref name=pmid17569137>{{Cite journal | last1 = Aydinli | first1 = M. | last2 = Bayraktar | first2 = Y. | title = Budd-Chiari syndrome: etiology, pathogenesis and diagnosis. | journal = World J Gastroenterol | volume = 13 | issue = 19 | pages = 2693-6 | month = May | year = 2007 | doi = | PMID = 17569137 | url=http://www.wjgnet.com/1007-9327/full/v13/i19/2693.htm }}</ref>
*Sinusoidal dilation in zone III (congestion).
*+/-Hepatocyte drop-out.
*+/-Centrilobular fibrosis.

DDx congestion:
*Congestive heart failure ([[congestive hepatopathy]]).
*Constrictive pericarditis.

==Vanishing bile duct syndrome==
*[[AKA]] ''bile duct loss'', [[AKA]] ''ductopenia''.<ref name=pmid11521176/>
===General===
*Fatal.

DDx:<ref name=pmid18242505/>
*[[Primary biliary cirrhosis]].
*[[Primary sclerosing cholangitis]].
*[[GVHD]].<ref name=pmid7994249>{{Cite journal | last1 = Yeh | first1 = KH. | last2 = Hsieh | first2 = HC. | last3 = Tang | first3 = JL. | last4 = Lin | first4 = MT. | last5 = Yang | first5 = CH. | last6 = Chen | first6 = YC. | title = Severe isolated acute hepatic graft-versus-host disease with vanishing bile duct syndrome. | journal = Bone Marrow Transplant | volume = 14 | issue = 2 | pages = 319-21 | month = Aug | year = 1994 | doi = | PMID = 7994249 }}</ref>
*[[Drug-induced liver disease|Drugs]].<ref name=pmid11352118>{{Cite journal | last1 = Chitturi | first1 = S. | last2 = Farrell | first2 = GC. | title = Drug-induced cholestasis. | journal = Semin Gastrointest Dis | volume = 12 | issue = 2 | pages = 113-24 | month = Apr | year = 2001 | doi = | PMID = 11352118 }}</ref>
*Chronic rejection.<ref name=pmid11521176>{{Cite journal | last1 = Inomata | first1 = Y. | last2 = Tanaka | first2 = K. | title = Pathogenesis and treatment of bile duct loss after liver transplantation. | journal = J Hepatobiliary Pancreat Surg | volume = 8 | issue = 4 | pages = 316-22 | month = | year = 2001 | doi = 10.1007/s0053410080316 | PMID = 11521176 }}</ref>

===Microscopic===
Features:<ref name=pmid18242505>{{Cite journal | last1 = Reau | first1 = NS. | last2 = Jensen | first2 = DM. | title = Vanishing bile duct syndrome. | journal = Clin Liver Dis | volume = 12 | issue = 1 | pages = 203-17, x | month = Feb | year = 2008 | doi = 10.1016/j.cld.2007.11.007 | PMID = 18242505 }}</ref>
*Loss of intrahepatitic bile ducts - '''key feature'''.
*Cholestasis.

Note:
*May occur without fibrosis and inflammation; thus, can be easy to miss.

===IHC===
*[[CK7]] -ve.
**Marks bile ducts.

==Extrahepatic biliary obstruction==
{|
[[File:1 OBS 3 680x512px.tif|Sinusoidal dilatation, circular spaces of hepatocytes, small portal triads(40X).]]
[[File:2 OBS 3 680x512px.tif|Bile in hepatocytes about central vein & in plugs in canaliculi [yellow arrowhead] (400X).]]
 
[[File:3 OBS 3 680x512px.tif|Trichrome shows fibrosis about central vein (400X).]]
[[File:4 OBS 3 680x512px.tif|PAS with diastase shows portal triads with mild edema and chronic inflammation, without tortuous bile duct (400X).]]
|}
Early extrahepatic biliary obstruction, demonstrated radiographically, transient, with rise in bilirubin, alkaline phosphatase, and transaminases. Pure canalicular cholestasis near terminal hepatic venules also seen in acute hepatitis, drug reactions, benign recurrent cholestasis, pregnancy, sepsis, & lymphomas. Sinusoidal dilatation, circular spaces of hepatocytes, small portal triads(UL 40X). Bile in hepatocytes about central vein & in plugs in canaliculi [yellow arrowhead] (UR 400X). Trichrome shows fibrosis about central vein (LL 400X). PAS with diastase shows portal triads with mild edema and chronic inflammation, without tortuous bile duct (LR 400X).

{|
[[File:1 OBS 2 680x512px.tif|Expanded inflamed portal triads, swollen hepatocytes (40X)]]
[[File:2 OBS 2 680x512px.tif|Edematous stroma, proliferating ductules [yellow arrowheads], PAS-D macrophages [red arrowhead] (PAS with diastasse, 200X)]]
 
[[File:3 OBS 2 680x512px.tif|Disordered, often swollen hepatocytes,some with feathery degeneration (net like spaces in cytoplasm [blue arrowhead], rare Councilman body [green arrowhead] (400X)]]
[[File:4 OBS 2 1360x1024px.tif|Bile in hepatocytes [cyan arrrowhead] & in canaliculi [purple arrowheads]. Empty acinar spaces bounded by hepatocytes [orange arrowhead] (400X, higher pixel),]]
|}
Changes of extrahepatic biliary obstruction, months duration. Expanded inflamed portal triads, swollen hepatocytes (UL 40X). Edematous stroma, proliferating ductules [yellow arrowheads], PAS-D macrophages [red arrowhead] (UR PAS with diastasse, 200X). Disordered, often swollen hepatocytes,some with feathery degeneration (net like spaces in cytoplasm) [blue arrowhead], rare Councilman body [green arrowhead] (LL 400X). Bile in hepatocytes [cyan arrrowhead] & in canaliculi [purple arrowheads]. Empty acinar spaces bounded by hepatocytes [orange arrowhead] (LR 400X).
{|
[[File:1 Bd obs 4 680x512px.tif|Expanded, light colored portal triads (arrows)(20X).]]
[[File:2 Bd obs 4 680x512px.tif|Proliferating bile ductules (cyan arrows) with neutrophils (yellow arrows), not specific for acute cholangitis, of assistance with large bile duct obstruction (400X)..]]
 
[[File:3 Bd obs 4 680x512px.tif|Uninflamed interlobular duct (yellow arrow) with, accompanying blood vessel (red arrow) (400X)]]
[[File:4 Bd obs 4 680x512px.tif|Bile infarct with pyknotic nuclei (arrows)(400X).]]
 
[[File:5 Bd obs 4 680x512px.tif|Bile (arrow) in interlobular bile duct with disordered nuclei (400X).]]
[[File:6 Bd obs 4 680x512px.tif|Bile plugs in cannaliculi (red arrows), feathery degeneration producing foamy macrophage like hepatocytes (yellow arrows)(400X).]]
|}
Large bile duct obstruction. Expanded, light colored portal triads (arrows)(Row 1 Left 20X). Proliferating bile ductules (cyan arrows) with neutrophils (yellow arrows), not specific for acute cholangitis, of assistance with large bile duct obstruction (Row 1 Right 400X). Uninflamed interlobular duct (yellow arrow) with, accompanying blood vessel (red arrow) (Row 2 Left 400X). Bile infarct with pyknotic nuclei (arrows)(Row 2 Right 400X). Bile (arrow) in interlobular bile duct with disordered nuclei (Row 3 Left 400X). Bile plugs in cannaliculi (red arrows), feathery degeneration producing foamy macrophage-like hepatocytes (yellow arrows)(Row 3 Right 400X).

==Congestive hepatopathy==
===General===
*Liver failure due to (right) heart failure.
*AKA ''cardiac cirrhosis'' - a term used by clinicians.
**Generally, it does not satisfy pathologic criteria for cirrhosis.<ref>URL: [http://emedicine.medscape.com/article/151792-overview http://emedicine.medscape.com/article/151792-overview]. Accessed on: 17 June 2010.</ref>

===Gross===
*"Nutmeg" liver - yellow spotted appearance.

===Microscopic===
Features:<ref>URL: [http://emedicine.medscape.com/article/151792-diagnosis http://emedicine.medscape.com/article/151792-diagnosis]. Accessed on: 17 June 2010.</ref>
*Zone III atrophy.
*Portal venule (central vein) distension.
*Perisinusoidal fibrosis - progresses to centrilobular fibrosis and then diffuse fibrosis.
*Dilation of sinusoids in ''all'' zone III areas - '''key feature'''.<ref>Suggested by OA. September 2009.</ref>

DDx:
*[[Hemangioma of the liver]] - should be focal lesion.

====Images====
<gallery>
Image:Congestive_hepatopathy_high_mag.jpg | Mild congestive hepatopathy. (WC)
</gallery>
{|
[[File:1 CEN NEC 1 680x512px.tif|PAS without diastase shows ovoids of necrosis {40X).]]
[[File:2 CEN NEC 1 680x512px.tif|Necrosis with central vein [yellow arrowhead], inflammatory cells, residual Councilman body [green arrowhead], and hepatocyte with mitotic figure [red arrowhead] (400X).]]
 
[[File:3 CEN NEC 1 680x512px.tif|Trichrome highlights fibrosis about central vein [yellow arrowhead] & shows beginning scar formation [green arrowheads]. Note residual atrophic hepatocytes [blue arrowheads] (400X).]]
[[File:4 CEN NEC 1 680x512px.tif|Portal triads are largely unaffected (400X).]]
|}
Centrilobular necrosis (seen in circulatory failure and with toxins/drugs). PAS without diastase shows ovoids of necrosis {UL 40X). Necrosis with central vein [yellow arrowhead], inflammatory cells, residual Councilman body [green arrowhead], and hepatocyte with mitotic figure [red arrowhead] (UR 400X). Trichrome highlights fibrosis about central vein [yellow arrowhead] & shows beginning scar formation [green arrowheads]. Note residual atrophic hepatocytes [blue arrowheads] (LL 400X). Portal triads are largely unaffected (LR 400X)

{|
[[File:1 CHF 1 680x512px.tif|Dilated and undilated sinusoidal regions (40X).]]
[[File:2 CHF 1 680x512px.tif|Thrombi in sinusoids; glycogenated nuclei likely reflect patient’s diabetes mellitus (400X).]]
 
[[File:3 CHF 1 680x512px.tif|Dilated portal vein (400X).]]
[[File:4 CHF 1 680x512px.tif|Reticulin shows collapse (thick black lines) as well as a dilated portal vein (200X).]]
 
[[File:5 CHF 1 680x512px.tif|Trichrome shows space of Disse collagenization (pericellular fibrosis) (200X).]]
[[File:6 CHF 1 680x512px.tif|Trichrome shows periportal fibrosis; no bridging was seen (200X).]]
|}
Patient with congestive heart failure and stage I fibrosis. Dilated and undilated sinusoidal regions (left row 1 40X). Thrombi in sinusoids; glycogenated nuclei likely reflect patient’s diabetes mellitus (right row 1 400X). Dilated portal vein (left row 2 400X). Reticulin shows black lines of bridging, too thick for collapse (right row 2 200X). Trichrome shows space of Disse collagenization (pericellular fibrosis) (left row 3 200X). Trichrome shows bridge beginning off to right; when it is more than a mere spike, it is a bridge (right row 3 200X).

==Drug-induced liver disease==
*[[AKA]] ''drug-induced liver toxicity''.
{{Main|Drug-induced liver disease}}

==Focal nodular hyperplasia==
*Abbreviated ''FNH''.
{{Main|Focal nodular hyperplasia}}

==Nodular regenerative hyperplasia==
===General===
*Associated with renal transplants, [[bone marrow transplant]]s and [[vasculitides]].<ref name=Ref_PBoD922>{{Ref PBoD|922}}</ref>
*Can lead to [[portal hypertension]] and many of the associated complications.<ref name=pmid22554152>{{Cite journal | last1 = Bissonnette | first1 = J. | last2 = Généreux | first2 = A. | last3 = Côté | first3 = J. | last4 = Nguyen | first4 = B. | last5 = Perreault | first5 = P. | last6 = Bouchard | first6 = L. | last7 = Pomier-Layrargues | first7 = G. | title = Hepatic hemodynamics in 24 patients with nodular regenerative hyperplasia and symptomatic portal hypertension. | journal = J Gastroenterol Hepatol | volume = 27 | issue = 8 | pages = 1336-40 | month = Aug | year = 2012 | doi = 10.1111/j.1440-1746.2012.07168.x | PMID = 22554152 }}
</ref>

====Etiology====
*Arterial hypervascularity secondary to loss of hepatic vein radicles (loss of central venule in hepatic lobule).<ref name=Ref_PBoD922>{{Ref PBoD|922}}</ref>

ASIDE: radicle = ramulus - smallest branch or vessel or nerve.<ref name=Dorlands2>Dorland's Medical Dictionary. 30th Ed.</ref>

===Gross===
*Diffuse nodularity - whole liver.

===Microscopic===
Features:<ref name=Ref_PBoD922>{{Ref PBoD|922}}</ref>
*"Plump" hepatocytes surrounded by atrophic ones.
*No fibrosis.

==Sinuosoidal obstruction syndrome==
*May be referred to as ''Hepatic veno-occlusive disease''.<ref name=pmid11928077>{{Cite journal | last1 = DeLeve | first1 = LD. | last2 = Shulman | first2 = HM. | last3 = McDonald | first3 = GB. | title = Toxic injury to hepatic sinusoids: sinusoidal obstruction syndrome (veno-occlusive disease). | journal = Semin Liver Dis | volume = 22 | issue = 1 | pages = 27-42 | month = Feb | year = 2002 | doi = 10.1055/s-2002-23204 | PMID = 11928077 }}.</ref>
===General===
*Term for obstruction due to toxicity from a chemotherapeutic agent.<ref name=pmid16393276>{{Cite journal | last1 = Helmy | first1 = A. | title = Review article: updates in the pathogenesis and therapy of hepatic sinusoidal obstruction syndrome. | journal = Aliment Pharmacol Ther | volume = 23 | issue = 1 | pages = 11-25 | month = Jan | year = 2006 | doi = 10.1111/j.1365-2036.2006.02742.x | PMID = 16393276 }}</ref><ref name=pmid17569137>{{Cite journal | last1 = Aydinli | first1 = M. | last2 = Bayraktar | first2 = Y. | title = Budd-Chiari syndrome: etiology, pathogenesis and diagnosis. | journal = World J Gastroenterol | volume = 13 | issue = 19 | pages = 2693-6 | month = May | year = 2007 | doi = | PMID = 17569137 | url=http://www.wjgnet.com/1007-9327/full/v13/i19/2693.htm }}</ref>

Clinical DDx:
*[[Budd-Chiari syndrome]].

===Microscopic===
Features:<ref name=pmid17569137>{{Cite journal | last1 = Aydinli | first1 = M. | last2 = Bayraktar | first2 = Y. | title = Budd-Chiari syndrome: etiology, pathogenesis and diagnosis. | journal = World J Gastroenterol | volume = 13 | issue = 19 | pages = 2693-6 | month = May | year = 2007 | doi = | PMID = 17569137 | url=http://www.wjgnet.com/1007-9327/full/v13/i19/2693.htm }}</ref>
*Subendothelial swelling in hepatic venules.

Negatives:
*No thrombosis.

==Ascending Cholangitis (Acute Cholangitis)==
===General===
*Term for infection of bile ducts, usually due to obstruction

Clinical DDx:

===Microscopic===
====Images====
{|
[[File:1 asc chol 1 680x512px.tif|Rounded, clear (edematous) portal tracts (arrows) separated by hepatocytes with dilated sinusoids (Row 1 Left 40X).]]
[[File:2 asc chol 1 680x512px.tif|Neutrophils about hepatocytes (arrows) have spilled into the lobule from a portal tract (Row 1 Right 200X).]]
 
[[File:3 asc chol 1 680x512px.tif|Proliferated bile ductules (arrows) bearing neutrophils within epithelium and lumens are features of obstruction that should prompt a search for interlobular ducts with acute inflammation (Row 2 Left 400X).]]
[[File:4 asc chol 1 680x512px.tif|The epithelium of the ducts can be severely degenerated. Neutrophils (cyan arrows) invade epithelium of an interlobular duct that are recognizable mainly as a circle of rounded nuclei; the associated arteriole (red arrow) should be identified to ensure an interlobular duct is being evaluated. Note the proliferated bile ductules (blue arrows) (Row 2 Right 400X).]]
 
[[File:5 asc chol 1 680x512px.tif|A PAS without diastase stain colors the arteriole (blue arrow), as well as the rim of the interlobular duct within which lies a neutrophil (cyan arrow) (Row 2 Right 400X). .]]
[[File:6 asc chol 1 680x512px.tif|A PAS with diastase stain colors the arteriole (red arrow), as well as the rim of the interlobular duct within which lies a neutrophil (cyan arrow) (Row 1 Right 400X)]]
|}
Acute cholangitis in a patient with multiple bile duct procedures. After the biopsy, removal of bile duct stones released pus. Rounded, clear (edematous) portal tracts (arrows) separated by hepatocytes with dilated sinusoids (Row 1 Left 40X). Neutrophils about hepatocytes (arrows) have spilled into the lobule from a portal tract (Row 1 Right 200X). Proliferated bile ductules (arrows) bearing neutrophils within epithelium and lumens are features of obstruction that should prompt a search for interlobular ducts with acute inflammation (Row 2 Left 400X). The epithelium of the ducts can be severely degenerated. Neutrophils (cyan arrows) invade epithelium of an interlobular duct that are recognizable mainly as a circle of rounded nuclei; the associated arteriole (red arrow) should be identified to ensure an interlobular duct is being evaluated. Note the proliferated bile ductules (blue arrows) (Row 2 Right 400X). A PAS without diastase stain colors the arteriole (blue arrow), as well as the rim of the interlobular duct within which lies a neutrophil (cyan arrow) (Row 3 Left 400X). A PAS with diastase stain colors the arteriole (red arrow), as well as the rim of the interlobular duct within which lies a neutrophil (cyan arrow) (Row 3 Right 400X).

{|
[[File:1 Sep Acu Cho 1 680x512px.tif|Low power shows variably sized inflamed portal tracts (40X)]]
[[File:2 Sep Acu Cho 1 680x512px.tif|Trichrome shows dilated sinusoids and space of Disse collagenization (200X)]]
 
[[File:3 Sep Acu Cho 1 680x512px.tif|Inflammatory focus with macrophages and neutrophils (400X).]]
[[File:4 Sep Acu Cho 1 680x512px.tif|PAS with diastase shows proliferated bile ductules at edge of triad with neutrophils, which should not be used to make a definite diagnosis of acute cholangitis (400X).]]
 
[[File:5 Sep Acu Cho 1 680x512px.tif|PAS without diastase showing acutely inflamed bile duct, with accompanying blood vessel of similar size, diagnostic of acute cholangitis (400X).]]
[[File:6 Sep Acu Cho 1 680x512px.tif|PAS with diastase showing neutrophil in bille duct lumen, diagnostic of acute cholangitis (400X).]]
|}
Patient with sepsis and acute cholangitis. Low power shows variably sized inflamed portal tracts (Row 1 Left 40X). Trichrome shows dilated sinusoids and space of Disse collagenization (Row 1 Right 200X). Inflammatory focus with macrophages and neutrophils (Row 2 Left 400X). PAS with diastase shows proliferated bile ductules at edge of triad with neutrophils, which should not be used to make a definite diagnosis of acute cholangitis (Row 2 Right 400X). PAS without diastase showing acutely inflamed bile duct, with accompanying blood vessel of similar size, diagnostic of acute cholangitis (Row 3 Left 400X). PAS with diastase showing neutrophil in bille duct lumen, diagnostic of acute cholangitis (Row 3 Right 400X).

==Polycystic kidney disease and the liver==
{{Main|Cystic kidney disease}}
===General===
Complications of PKD in the liver:<ref>{{Ref MacSween|174-5}}</ref>
#Infected cyst.
#Cholangiocarcinoma.
#Cholestasis/obstruction due to duct compression.<ref>URL: [http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=9184868 http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=9184868]. Accessed on: 23 September 2009.</ref>

Cysts:
*Cysts in the liver, like the kidney, are thought to enlarge with age.

===Microscopic===
Features:<ref>{{Ref MacSween|176}}</ref>
*''Von Meyenburg complexes'' ([[bile duct hamartoma]]):
**Cluster of dilated ducts with "altered" bile.
**Surrounded by collagenous stroma.
**Separate from the portal areas.<ref>Meyenburg complex. Stedman's Medical Dictionary. 27th Ed.</reF>

Images:
*[http://commons.wikimedia.org/wiki/File:Von_Meyenburg_complex_low_mag.jpg Von Meyenburg complex - bile duct hamartoma (WC)].
*[http://commons.wikimedia.org/wiki/File:Bile_duct_hamartoma_intermed_mag.jpg Bile duct hamartoma (WC)].

Notes:
*Appearance on ultrasound<ref name=pmid17287178>Bile duct hamartomas--the von Meyenburg complex. Salles VJ, Marotta A, Netto JM, Speranzini MB, Martins MR. Hepatobiliary Pancreat Dis Int. 2007 Feb;6(1):108-9. PMID 17287178.</ref> and CT (hypodense)<ref name=pmid19294869>[The von Meyenburg complex] Schwab SA, Bautz W, Uder M, Kuefner MA. Rontgenpraxis. 2008;56(6):241-4. German. PMID 19294869.</ref> - similar to metastases.

==Peliosis hepatis==
===General===
*Associated with:
**Infections.
**Malignancy.
**Other stuff.
*Rarely biopsied.

===Microscopic===
Features:
*Cyst lined by endothelium.
**Usu. incomplete.
*Blood.
{|
[[File:1 PEL 1 680x512px.tif|Hemorrhage at left end, dilated sinusoids elsewhere (20X).]]
[[File:2 PEL 1 680x512px.tif|Ramifying dilated sinusoidal spaces (100X).]]
 
[[File:3 PEL 1 680x512px.tif|PAS with diastase shows flat lining (400X).]]
[[File:4 PEL 1 680x512px.tif|Necrotic hepatocytes in cords, presumably due to pressure (400X).]]
|}
Peliosis hepatis. Hemorrhage at left end, dilated sinusoids elsewhere (UL 20X). Ramifying dilated sinusoidal spaces (UR 100X). PAS with diastase shows flat lining (LL 400X). Necrotic hepatocytes in cords, presumably due to pressure (LR 400X).

==Total parenteral nutrition==
*Abbreviated ''TPN''.

===General===
*Indication: short gut syndrome, others.

===Microscopic===
Variable - may range from: steatosis, steatohepatitis, cholestasis, fibrosis and cirrhosis.<ref name=pmid16766237>{{cite journal |author=Guglielmi FW, Boggio-Bertinet D, Federico A, ''et al.'' |title=Total parenteral nutrition-related gastroenterological complications |journal=Dig Liver Dis |volume=38 |issue=9 |pages=623–42 |year=2006 |month=September |pmid=16766237 |doi=10.1016/j.dld.2006.04.002 |url=}}</ref>

Features (classic):<ref>{{Cite journal | last1 = Li | first1 = SJ. | last2 = Nussbaum | first2 = MS. | last3 = McFadden | first3 = DW. | last4 = Gapen | first4 = CL. | last5 = Dayal | first5 = R. | last6 = Fischer | first6 = JE. | title = Addition of glucagon to total parenteral nutrition (TPN) prevents hepatic steatosis in rats. | journal = Surgery | volume = 104 | issue = 2 | pages = 350-7 | month = Aug | year = 1988 | doi = | PMID = 3135627 }}</ref><ref>{{Cite journal | last1 = Stanko | first1 = RT. | last2 = Nathan | first2 = G. | last3 = Mendelow | first3 = H. | last4 = Adibi | first4 = SA. | title = Development of hepatic cholestasis and fibrosis in patients with massive loss of intestine supported by prolonged parenteral nutrition. | journal = Gastroenterology | volume = 92 | issue = 1 | pages = 197-202 | month = Jan | year = 1987 | doi = | PMID = 3096806 }}
</ref>
*[[Steatosis]] (periportal) - early.
*Cholestasis - late.

==Giant cell hepatitis==
*[[AKA]] ''neonatal giant cell hepatitis''.

:See: ''[[Giant cell hepatitis]]''.

==Hepatic amyloidosis==
{{Main|Amyloidosis}}
*[[AKA]] ''liver amyloidosis''.
*[[AKA]] ''amyloidosis of the liver''.
===General===
*Diffuse abundant amyloid within the space of Disse is associated with [[portal hypertension]].<ref name=pmid1864548>{{Cite journal | last1 = Bion | first1 = E. | last2 = Brenard | first2 = R. | last3 = Pariente | first3 = EA. | last4 = Lebrec | first4 = D. | last5 = Degott | first5 = C. | last6 = Maitre | first6 = F. | last7 = Benhamou | first7 = JP. | title = Sinusoidal portal hypertension in hepatic amyloidosis. | journal = Gut | volume = 32 | issue = 2 | pages = 227-30 | month = Feb | year = 1991 | doi = | PMID = 1864548 | PMC = 1378815 | URL = http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1378815/?tool=pubmed }}</ref>

===Microscopic===
Features:
*Amorphous extracellular pink stuff on H&E - see ''[[amyloid]]'' article.

DDx:
*[[Fibrolamellar hepatocellular carcinoma]].

====Images====
<gallery>
Image:Hepatic_amyloidosis_-_low_mag.jpg | Amyloidosis of the liver - low mag. (WC)
Image:Hepatic_amyloidosis_-_intermed_mag.jpg | Amyloidosis of the liver - intermed. mag. (WC)
Image:Hepatic_amyloidosis_-_high_mag.jpg | Amyloidosis of the liver - high mag. (WC)
Image:Hepatic_amyloidosis_-_very_high_mag.jpg | Amyloidosis of the liver - very high mag. (WC)
</gallery>
{|
[[File:1 AMY 1 680x512px.tif|Amorphous material replaces hepatic parenchyma [4X]]]
[[File:2 AMY 1 680x512px.tif|Material barely stains blue on trichrome [10X]]]
 
[[File:3 AMY 1 680x512px.tif|Material stains red on unpolarized Congo Red [40X]]]
[[File:4 AMY 1 680x512px.tif|Material stains apple green on polarized Congo Red [40X]]]
|}
Amyloidosis. Amorphous material replaces hepatic parenchyma [UL 4X]. Material barely stains blue on trichrome [UR 10X] Material stains red on unpolarized Congo Red [LL 40X] Material stains apple green on polarized Congo Red [LR 40X]

===Stains===
*[[Congo red]] +ve.

==Fulminant hepatic necrosis==
===General===
Etiology:
*Viral, i.e. [[Hepatitis A]], [[Hepatitis B]]; [[Hepatitis C]] - extremely rare.
*Trauma.
*Shock.

===Microscopic===
{|
[[File:1 Necrosis 2 680x512px.tif| Submassive hepatic necrosis.]]
[[File:2 Necrosis 2 680x512px.tif| Submassive hepatic necrosis.]]
 
[[File:3 Necrosis 2 680x512px.tif| Submassive hepatic necrosis.]]
[[File:4 Necrosis 2 680x512px.tif| Submassive hepatic necrosis.]]
 
[[File:5 Necrosis 2 680x512px.tif| Submassive hepatic necrosis.]]
[[File:6 Necrosis 2 680x512px.tif| Submassive hepatic necrosis.]]
|}
Submassive hepatic necrosis. Patient had transaminases in the thousands that rapidly dropped to normal. Pink preserved parenchyma strews empty necrotic spaces (Row 1 Left 20X). Focus of necrosis with no apparent hepatocytes macrophages abuts apparently normal liver (Row 1 Right 200X). Iron stain shows the macrophages bear hemosiderin (Row 2 Left 200X). Reticulin stain highlights the recently dead liver cells (Row 2 Right 200X). Reticulin stain shows a necrotic bridge forming; the multiple small black circles preclude diagnosis of a fibrous bridge (Row 3 Left 200X). Trichrome shows the necrotic bridge (“collapse”) lacks much collagen deposition, as would be expected for bridging fibrosis (Row 3 Right 200X).

Features:
*Hepatocyte [[necrosis]].
*Bile duct proliferation.

DDx:
*[[Cholangiocarcinoma]].
*[[Angiosarcoma]].

==Secondary hemochromatosis==
:''For the hereditary one see [[hereditary hemochromatosis]]''.
===General===
*Iron overload secondary to blood transfusions for hereditary or acquired anemia.<ref name=pmid19727383/>
**Primary hemochromatosis due to a defect in iron processing - called ''[[hereditary hemochromatosis]]''.
*Imaging considered the best test, as iron deposition is patchy.<ref name=pmid19727383/>

Selected hereditary causes:<ref name=pmid19727383>{{Cite journal | last1 = Gattermann | first1 = N. | title = The treatment of secondary hemochromatosis. | journal = Dtsch Arztebl Int | volume = 106 | issue = 30 | pages = 499-504, I | month = Jul | year = 2009 | doi = 10.3238/arztebl.2009.0499 | PMID = 19727383 | PMC = 2735704 | URL = http://www.ncbi.nlm.nih.gov.myaccess.library.utoronto.ca/pmc/articles/PMC2735704/?tool=pubmed}}</ref>
*Thalassemia.
*[[Sickle cell anemia]].
*Hereditary sideroblastic anemia.

Selected acquired causes:<ref name=pmid19727383/>
*[[Myelodysplastic syndromes]]
*Myelofibrosis
*Aplastic anemia, intractable.

===Microscopic===
:See ''[[hereditary hemochromatosis]]''.

==Hepatic sarcoidosis==
{{Main|Hepatic sarcoidosis}}
==Overlapping Disorders==

[[File:1 Mixed Disorder 1 680x512px.tif|Changes of steatohepatitis and interface hepatitis, with granuloma. Patient with diabetes was ANA, AMA, HCV, HBV negative, without drugs known to produce granulomas or interface hepatitis. This may be a case of AMA negative primary biliary cirrhosis, but studies to determine that with certainty were not performed.]]
[[File:2 Mixed Disorder 1 680x512px.tif|Changes of steatohepatitis and interface hepatitis, with granuloma. Patient with diabetes was ANA, AMA, HCV, HBV negative, without drugs known to produce granulomas or interface hepatitis. This may be a case of AMA negative primary biliary cirrhosis, but studies to determine that with certainty were not performed.]]
[[File:3 Mixed Disorder 1 680x512px.tif|Changes of steatohepatitis and interface hepatitis, with granuloma. Patient with diabetes was ANA, AMA, HCV, HBV negative, without drugs known to produce granulomas or interface hepatitis. This may be a case of AMA negative primary biliary cirrhosis, but studies to determine that with certainty were not performed.]]
[[File:4 Mixed Disorder 1 680x512px.tif|Changes of steatohepatitis and interface hepatitis, with granuloma. Patient with diabetes was ANA, AMA, HCV, HBV negative, without drugs known to produce granulomas or interface hepatitis. This may be a case of AMA negative primary biliary cirrhosis, but studies to determine that with certainty were not performed.]]
[[File:5 Mixed Disorder 1 680x512px.tif|Changes of steatohepatitis and interface hepatitis, with granuloma. Patient with diabetes was ANA, AMA, HCV, HBV negative, without drugs known to produce granulomas or interface hepatitis. This may be a case of AMA negative primary biliary cirrhosis, but studies to determine that with certainty were not performed.]]
[[File:6 Mixed Disorder 1 680x512px.tif|Changes of steatohepatitis and interface hepatitis, with granuloma. Patient with diabetes was ANA, AMA, HCV, HBV negative, without drugs known to produce granulomas or interface hepatitis. This may be a case of AMA negative primary biliary cirrhosis, but studies to determine that with certainty were not performed.]] 
Changes of steatohepatitis and interface hepatitis, with granuloma. Patient with diabetes was ANA, AMA, HCV, HBV negative, without drugs known to produce granulomas or interface hepatitis. This may be a case of AMA negative primary biliary cirrhosis, but studies to determine that with certainty were not performed. A. Low power shows hepatocytes afflicted by steatosis and an inflamed portal tract. B. In a region of fatty change lie cytoplasmic tufts of ballooning degeneration (green arrows) and a lipogranuloma (black arrow). C. At the portal-hepatocyte junction lies interface hepatitis (black arrows), as well as extension of inflammation into the lobule (green arrows). D. Red hepatocytes bounded by inflammation denote piecemeal necrosis [PAS without diastase]. E. Giant cells intermixed with lymphocytes prove a portal granuloma [PAS without diastase]. F. A blue fibrous bridge extends from a triad [Trichrome].

[[File:4 95599552608917 sl 1.png|Acute obstructive changes and changes of recurrent acute injury]]
[[File:4 95599552608917 sl 2.png|Acute obstructive changes and changes of recurrent acute injury]]
[[File:4 95599552608917 sl 3.png|Acute obstructive changes and changes of recurrent acute injury]]
[[File:4 95599552608917 sl 4.png|Acute obstructive changes and changes of recurrent acute injury]]
[[File:4 95599552608917 sl 5.png|Acute obstructive changes and changes of recurrent acute injury]]
[[File:4 95599552608917 sl 6.png|Acute obstructive changes and changes of recurrent acute injury]]
[[File:4 95599552608917 sl 7.png|Acute obstructive changes and changes of recurrent acute injury]] 
Acute obstructive changes and changes of recurrent injury in 46 yo man with Clostridium perfringens positive blood culture, an ERCP that showed duodenal compression by the pancreas with resultant bile duct dilatation. The patient had had and continued to have multiple bouts of acute pancreatitis. At the time of biopsy, decreased platelet count/hemoglobin/albumin, elevated lipase/amylase/PT/PTT, normal alkaline phosphatase, bilirubin, AST/ALT, AMA, hepatitis virus serology, ANA. A. Fragment biopsy shows inflamed triads and bridges. B. Trichrome shows bridges without nodules, evidence of prior injury; the patient subsequently developed multiple episodes of pancreatitis. C. Reticulin shows piecemeal necrosis, with black lines bounding individual hepatocytes at interface (arrows). D. Collapse is shown by closly approximated thick black lines; one cannot call portal-central collapse without seeing a central vein. Note on this and the other reticulin image that regeneration, two cell thick cords, is not prominent. E. PAS D of two portal triads, far nearer than normal, both expanded. Note increased number of ducts/ductules (red arrows), neutrophils, and PAS-D macrophages. F. PAS D shows collapse extending from a triad to a portion of a lobule with steatosis. No feathery degeneration or bile duct plugs were seen. Neither were foci of spotty necrosis or abscess seen. G. Other triads, again edematous, showed more of a chronic inflammatory response, with occasional plasma cells (black arrows). Also present are neutrophils (red arrows). The bile duct (grey arrow) near the artery (brown arrow) shows mildly disturbed nuclei. Note early proliferated bile ductules (cyan arrows).

[[File:6 17281676469188 sl 1.png| Hepatitis B virus with steatohepatitis]]
[[File:6 17281676469188 sl 2.png| Hepatitis B virus with steatohepatitis]]
[[File:6 17281676469188 sl 3.png| Hepatitis B virus with steatohepatitis]]
[[File:6 17281676469188 sl 4.png| Hepatitis B virus with steatohepatitis]]
[[File:6 17281676469188 sl 5.png| Hepatitis B virus with steatohepatitis]]
[[File:6 17281676469188 sl 6.png| Hepatitis B virus with steatohepatitis]] 
Hepatitis B virus with steatohepatitis in a 36 year old man with hepatitis B surface antigen and hepatitis Be antigen positivity, Hepatitis be QTPC of 1750 cop/mL, an occasionally mildly elevated (42) ALT, and normal glucose, alkaline phosphatase, bilirubin, and other transaminases. He had a history of alcohol abuse, which became controlled. A. Triads show scant inflammation without definite interface hepatitis. About one-fourth of the lobule, not pan-acinar, is afflicted by steatosis. B. Occasional tufts are seen (arrow), indicating focal ballooning sufficient for a diagnosis of steatohepatitis. C. Glycogenated nuclei (black arrows) and hepatocytes with feathery degeneration (red arrows) are seen. D. Very rare foci of spotty necrosis were seen. E. Apart from this triad and the one in the trichrome stain in F, which had moderate inflammation comprising lymphocytes and macrophages, all triads were small, most without any inflammation at all. Neither collapse nor piecemeal necrosis were seen on reticulin stain. F. Trichrome stain showed only portal fibrosis. The interhepatocyte fibrosis required for brunt fibrosis stage I was not seen. Hence, one would grade this as follows: A) Chronic hepatitis (history of hepatitis B), Metavir activity index 1, Piecemeal necrosis 0, Lobular necrosis 1, Metavir fibrosis stage 1, B) Steatohepaitits, Brunt necroinflammatory grade 1, Brunt fibrosis stage 0.

=See also=
*[[Pancreas]].
*[[Gastrointestinal pathology]].
*[[Liver neoplasms]].
*[[Liver]].

=References=
{{reflist|2}}

[[Category:Gastrointestinal pathology]]
[[Category:Liver pathology]]
[[Category:Medical liver disease]]

Chronic cholecystitis

2017-01-18T20:25:46Z

Mitchell: /* Images */ added a case with extensive RA sinuses

{{ Infobox diagnosis
| Name = {{PAGENAME}}
| Image = Chronic cholecystitis and cholesterolosis -- low mag.jpg
| Width =
| Caption = Chronic cholecystitis with cholesterolosis. [[H&E stain]].
| Micro = entrapped epithelial crypts, fibrosis/muscular hypertrophy of gallbladder wall, +/-foamy macrophages
| Subtypes =
| LMDDx = [[acute cholecystitis]], [[gallbladder adenocarcinoma]], [[gallbladder adenomyoma]], [[intestinal metaplasia of the gallbladder]]
| Stains =
| IHC =
| EM =
| Molecular =
| IF =
| Gross = +/-strawberry-like appearance, yellow stones, fibrotic wall
| Grossing =
| Site = [[gallbladder]]
| Assdx = [[cholelithiasis]], [[gallbladder cholesterolosis]], [[obesity]]
| Syndromes =
| Clinicalhx = biliary colic, usu. fertile fat females forty years or less
| Signs =
| Symptoms = constant right upper quadrant pain after a meal (biliary colic)
| Prevalence = very common
| Bloodwork =
| Rads =
| Endoscopy =
| Prognosis = good, benign
| Other =
| ClinDDx =
}}
'''Chronic cholecystitis''', abbreviated '''CC''', is a very common pathology of the [[gallbladder]] and increasing in prevalence with the expanding waist lines.

==General==
===Epidemiology===
*Female, [[obese|fat]], fertile, family history, forty (though now getting younger... as people get fatter).

===Etiology===
*Cholelithiasis.
*Thick bile (acalculous cholecystitis).

===Clinical (classic)===
*Constant right upper quadrant pain after a fatty meal (biliary colic).
*Positive Murphy's sign (physical exam, with ultrasound).

==Gross==
*+/-[[Cholelithiasis]] - strongly associated pathology.
*+/-Strawberry-like appearance - common (due to [[gallbladder cholesterolosis]]).
**Small ridges (microvillus architecture) + yellow.
***Normal gallbladder mucosa = smooth, green.
*+/-Congestion/erythema.
*+/-Wall thickening - typically ~ 6-7 mm.<ref name=pmid21879282>{{Cite journal | last1 = Kim | first1 = HJ. | last2 = Park | first2 = JH. | last3 = Park | first3 = DI. | last4 = Cho | first4 = YK. | last5 = Sohn | first5 = CI. | last6 = Jeon | first6 = WK. | last7 = Kim | first7 = BI. | last8 = Choi | first8 = SH. | title = Clinical usefulness of endoscopic ultrasonography in the differential diagnosis of gallbladder wall thickening. | journal = Dig Dis Sci | volume = 57 | issue = 2 | pages = 508-15 | month = Feb | year = 2012 | doi = 10.1007/s10620-011-1870-0 | PMID = 21879282 }}</ref>

Note:
*Wall thickening (due to congestion/edema) is the important gross finding in ''[[acute cholecystitis]]''.
*Wall thickenss greater than 10 mm should raise the suspicion of malignancy.<ref name=pmid21879282/>

==Microscopic==
Features:<ref name=Ref_GLP439>{{Ref GLP|439}}</ref>
*Thickening of the gallbladder wall - due to fibrosis/muscular hypertrophy - '''key feature'''.
*Chronic inflammatory cells - usu. "minimal".
**Lymphocytes - most common.
*Rokitansky-Aschoff sinuses - common.<ref>URL: [http://www.whonamedit.com/synd.cfm/983.html http://www.whonamedit.com/synd.cfm/983.html]. Accessed on: 29 October 2011.</ref>
**Entrapped epithelial crypts -- pockets of epithelium in the wall of the gallbladder.
*+/-Foamy macrophages in the lamina propria ([[cholesterolosis of the gallbladder]]).

DDx:
*[[Gallbladder cholesterolosis]] and chronic cholecystitis.
*[[Gallbladder adenomyoma]].
*[[Acute cholecystitis]] - more inflammation, lack Rokitansky-Aschoff sinuses, +/-mucosal erosions.
*Cholecystectomy for [[gallstone pancreatitis]] - intraepithelial [[neutrophil]] clusters common, history essential.
*[[Intestinal metaplasia of the gallbladder]] - goblet cells present, may be focal.
*[[Gallbladder adenocarcinoma]].

===Images===
<gallery>
Image: Chronic cholecystitis and cholesterolosis -- intermed mag.jpg | CC - intermed. mag. (WC)
Image:Gallbladder_cholesterolosis_micro.jpg | Cholesterolosis. (WC)
</gallery>
[[File:Reactive change in cholecystitis A sl 1.png| Extensive Rokitansky-Aschoff sinuses in a 64 year ood woman]]
[[File:Reactive change in cholecystitis A sl 2.png| Extensive Rokitansky-Aschoff sinuses in a 64 year ood woman]]
[[File:Reactive change in cholecystitis A sl 3.png| Extensive Rokitansky-Aschoff sinuses in a 64 year ood woman]]
[[File:Reactive change in cholecystitis A sl 4.png| Extensive Rokitansky-Aschoff sinuses in a 64 year ood woman]] 
Extensive Rokitansky-Aschoff sinuses in a 64 year ood woman. A. Extending from a benign, chronically inflamed plicae are Rikitansky-Aschoff sinuses. Note their travel in between muscle bundles can be recognized as continuity to the surface. B. In between the gall stone at lower left and the lymphoid aggregate at upper right lies the gallbladder wall. Note the longitudinal extensions of the Rokitansky-Aschoff sinuses, as well as the ballooning outside the wall at lower right. C. The mucosa shows extensive reactive branching. Note again the predominant extension between muscle bundles, recognizable by the stroma about the sinuses, some of which are branched, pushing the muscle wall aside. There is no desmoplasia, but some gallbladder azdenocarcinomas show little recognizable desmoplasia. D. The focus on the right is difficult to identify as lying between muscle bundles. The triple parallel tubules argue against neoplasia. The lack of cancerous nuclear change is important as well.

==Sign out==
<pre>
Gallbladder, Cholecystectomy:
- Cholelithiasis.
- Chronic cholecystitis, mild.
- One benign lymph node.
</pre>

====Block letters====
<pre>
GALLBLADDER, CHOLECYSTECTOMY:
- CHRONIC CHOLECYSTITIS.
- CHOLELITHIASIS.
</pre>

===Without stones===
<pre>
GALLBLADDER, CHOLECYSTECTOMY:
- CHRONIC CHOLECYSTITIS.
- NO GALLSTONES IDENTIFIED.
</pre>

===Liver present===
<pre>
GALLBLADDER, CHOLECYSTECTOMY:
- CHRONIC CHOLECYSTITIS.
- CHOLELITHIASIS.
- SMALL AMOUNT OF LIVER WITHOUT APPARENT PATHOLOGY.
</pre>

<pre>
GALLBLADDER, CHOLECYSTECTOMY:
- CHRONIC CHOLECYSTITIS WITH MILD CHOLESTEROLOSIS.
- CHOLELITHIASIS.
- SMALL AMOUNT OF LIVER WITH CAUTERY/CRUSH ARTIFACT.
</pre>

===Micro===
The sections shows gallbladder wall with Rokitansky-Aschoff sinuses and a moderate mixed
inflammatory infiltrate predominantly consisting of lymphocytes. No nuclear atypia is seen.

====Post-cholecystostomy tube====
The sections shows gallbladder wall with edema, a moderate mixed inflammatory infiltrate
(predominantly consisting of lymphocytes and plasma cells), and mucosal erosions. Reactive
fibroblasts and hemosiderin-laden macrophages are present. No significant nuclear changes
are seen. One benign lymph node is present.

==See also==
*[[Acute cholecystitis]].
*[[Gallbladder]].

==References==
{{Reflist|2}}

[[Category:Gallbladder]]
[[Category:Diagnosis]]

Gallbladder

2017-01-18T20:09:45Z

Mitchell: /* Xanthogranulomatous cholecystitis */ *added pancreatic heterotopia

The '''gallbladder''', in pathology (and '''general surgery'''), is a growth industry... due to the worsening [[obesity]] epidemic.

=Normal=
==Anatomy==
*Body.
*Fundus.
*Neck.

Variations:
*Hartmann's pouch - invagination of the gallbladder wall at the origin of the cystic duct.

Image:
*[http://web.uni-plovdiv.bg/stu1104541018/docs/res/skandalakis'%20surgical%20anatomy%20-%202004/Chapter%2020_%20Extrahepatic%20Biliary%20Tract%20and%20Gallbladder_fichiers/loadBinaryCAS7X571.jpg Hartmann's pouch (uni-plovdiv.bg)].<ref>URL: [http://web.uni-plovdiv.bg/stu1104541018/docs/res/skandalakis'%20surgical%20anatomy%20-%202004/Chapter%2020_%20Extrahepatic%20Biliary%20Tract%20and%20Gallbladder.htm http://web.uni-plovdiv.bg/stu1104541018/docs/res/skandalakis'%20surgical%20anatomy%20-%202004/Chapter%2020_%20Extrahepatic%20Biliary%20Tract%20and%20Gallbladder.htm]. Accessed on: 13 December 2012.</ref>

==Histology==
*'''No''' muscularis mucosae.
*Small amount of lymphocytes in the lamina propria.

Note:
*As there is no ''muscularis mucosae'', the [[cancer staging]] is different; pT1a is lamina propria invasion. pT1b is muscle layer invasion.
===Image===
<gallery>
Image:Gallbladder_-_intermed_mag.jpg | Normal gallbladder - intermed. mag. (WC/Nephron)
</gallery>

=Overview=
Most common:
*Cholelithiasis with cholecystitis.

Common:
*Antral-type metaplasia.

Uncommon:
*Intestinal metaplasia.
*Gallbladder dysplasia.
*Gallbladder carcinoma.

=Common=
==Chronic cholecystitis==
{{Main|Chronic cholecystitis}}

==Acute cholecystitis==
{{Main|Acute cholecystitis}}

==Gallbladder cholesterolosis==
{{Main|Gallbladder cholesterolosis}}

==Cholelithiasis==
*[[AKA]] ''gallstones''.
{{Main|Cholelithiasis}}

=Less common pathologic diagnoses=
==Adenomyoma of the gallbladder==
*[[AKA]] ''gallbladder adenomyosis''.
*[[AKA]] ''adenomyomatosis of the gallbladder''.
*[[AKA]] ''gallbladder adenomyoma''.

===General===
*Glands in muscle.
*Analogous to what happens in the [[uterine adenomyosis|uterus]].
*Significance - may mimic malignant tumours of the gallbladder.<ref>{{Cite journal | last1 = Saul | first1 = WM. | last2 = Herrmann | first2 = PK. | title = [Adenomyoma of the gallbladder]. | journal = Dtsch Z Verdau Stoffwechselkr | volume = 48 | issue = 2 | pages = 112-6 | month = | year = 1988 | doi = | PMID = 3168899 }}</ref><ref name=pmid9350002 >{{Cite journal | last1 = Sasatomi | first1 = E. | last2 = Miyazaki | first2 = K. | last3 = Mori | first3 = M. | last4 = Satoh | first4 = T. | last5 = Nakano | first5 = S. | last6 = Tokunaga | first6 = O. | title = Polypoid adenomyoma of the gallbladder. | journal = J Gastroenterol | volume = 32 | issue = 5 | pages = 704-7 | month = Oct | year = 1997 | doi = | PMID = 9350002 }}
</ref>
*Uncommon.

===Gross===
*Cystic spaces (Rokitansky-Aschoff sinuses) - may be seen on imaging.<ref name=pmid17579153>{{Cite journal | last1 = Ching | first1 = BH. | last2 = Yeh | first2 = BM. | last3 = Westphalen | first3 = AC. | last4 = Joe | first4 = BN. | last5 = Qayyum | first5 = A. | last6 = Coakley | first6 = FV. | title = CT differentiation of adenomyomatosis and gallbladder cancer. | journal = AJR Am J Roentgenol | volume = 189 | issue = 1 | pages = 62-6 | month = Jul | year = 2007 | doi = 10.2214/AJR.06.0866 | PMID = 17579153 }}</ref><ref name=pmid16702464>{{Cite journal | last1 = Boscak | first1 = AR. | last2 = Al-Hawary | first2 = M. | last3 = Ramsburgh | first3 = SR. | title = Best cases from the AFIP: Adenomyomatosis of the gallbladder. | journal = Radiographics | volume = 26 | issue = 3 | pages = 941-6 | month = | year = | doi = 10.1148/rg.263055180 | PMID = 16702464 | URL = http://radiographics.rsna.org/content/26/3/941.long}}</ref>
*Gallbladder wall thickening.

===Microscopic===
Features:<ref name=Ref_GLP439>{{Ref GLP|439}}</ref>
*Glands in muscularis propria of the gallbladder wall - '''key feature'''.
*Significant muscular hypertrophy - '''key feature'''.
*No nuclear atypia.

DDx:
*[[Gallbladder carcinoma]].
*[[Chronic cholecystitis]] - has less muscular hypertrophy; overlaps with this diagnosis.<ref name=Ref_GLP439>{{Ref GLP|439}}</ref>
*Phrygian cap.<reF>URL: [http://radiopaedia.org/articles/phrygian_cap http://radiopaedia.org/articles/phrygian_cap]. Accessed on: 16 May 2014.</ref>

====Image====
*[http://pubs.rsna.org/na101/home/literatum/publisher/rsna/journals/content/radiographics/2006/radiographics.2006.26.issue-3/rg.263055180/production/images/medium/g06ma19c05x.jpeg Adenomyomatosis of the gallbladder (radiographics.rsna.org)].<ref name=pmid16702464/>

===Sign out===
<pre>
GALLBLADDER, CHOLECYSTECTOMY:
- CHRONIC CHOLECYSTITIS WITH MILD CHOLESTEROLOSIS AND ADENOMYOSIS (FUNDUS).
- CHOLELITHIASIS.
</pre>

==Gallbladder polyps==
===General===
*Polyps are significant as they may be adenomatous, i.e. pre-cancerous.
*These are similar to [[intestinal polyps|polyps]] found elsewhere GI tract.
===Microscopic===
:See ''[[intestinal polyps]]''.

Flat dysplasia:<ref name=Ref_DCHH172>{{Ref DCHH|172}}</ref>
*Nuclear changes.
**Increased [[NC ratio]].
**Hyperchromasia (essential).
**+/-Intestinal metaplasia --> goblet cells.

==Gallbladder diverticulosis==
===General===
*Uncommon.
*Thought to arise in the context of an outflow obstruction.<ref name=pmid4963758>{{Cite journal | last1 = Beilby | first1 = JO. | title = Diverticulosis of the gall bladder. The fundal adenoma. | journal = Br J Exp Pathol | volume = 48 | issue = 4 | pages = 455-61 | month = Aug | year = 1967 | doi = | PMID = 4963758 | PMC = 2093791 | URL = http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2093791/}}</ref>

===Microscopic===
Features:
*Mucosal pouch penetrating the muscularis propria of the gallbladder wall - '''key feature'''.

DDx:
*[[Chronic cholecystitis]].
*[[Gallbladder adenomyosis]].

===Sign out===
<pre>
GALLBLADDER, CHOLECYSTECTOMY:
- CHRONIC CHOLECYSTITIS WITH DIVERTICULOSIS.
- CHOLELITHIASIS.
</pre>

==Xanthogranulomatous cholecystitis==
*Abbreviated ''XGC''.
{{Main|Xanthogranulomatous cholecystitis}}

==Pancreatic heterotopia==
[[File:Gallbladder mass benign A sl 1.png|Pancreatic heterotopia in 35 year old women]]
[[File:Gallbladder mass benign A sl 2.png|Pancreatic heterotopia in 35 year old women]]
[[File:Gallbladder mass benign A sl 3.png|Pancreatic heterotopia in 35 year old women]]
[[File:Gallbladder mass benign A sl 4.png|Pancreatic heterotopia in 35 year old women]] 
Pancreatic heterotopia near cystic duct in 35 year old women. A. The cystic duct margin is at right; the heterotopia, at left. This cannot be a portion of the pancreas because the cystic duct margin lies proximal to the common bile duct. B. Pancreatic ducts with lobular proliferation, but without the inflammation that would usually be present were this obstruction by a gallstone. C. Nuclei of the duct and the proliferated bile ductules are bland. D. Acini are unremarkable; no pancreatic islets were seen in this case.

=Premalignant lesions=
===General===
*Metaplasia associated with carcinoma.<ref name=pmid8364865>{{cite journal |author=Duarte I, Llanos O, Domke H, Harz C, Valdivieso V |title=Metaplasia and precursor lesions of gallbladder carcinoma. Frequency, distribution, and probability of detection in routine histologic samples |journal=Cancer |volume=72 |issue=6 |pages=1878–84 |year=1993 |month=September |pmid=8364865 |doi= |url=}}</ref>

Hypothesis:<ref name=pmid15737036>{{cite journal |author=Mukhopadhyay S, Landas SK |title=Putative precursors of gallbladder dysplasia: a review of 400 routinely resected specimens |journal=Arch. Pathol. Lab. Med. |volume=129 |issue=3 |pages=386–90 |year=2005 |month=March |pmid=15737036 |doi= |url=http://www.archivesofpathology.org/doi/pdf/10.1043/1543-2165%282005%29129%3C386%3APPOGDA%3E2.0.CO%3B2 }}</ref>
*Antral type metaplasia --> intestinal metaplasia --> dysplasia --> carcinoma.

==Intestinal metaplasia of the gallbladder==
*[[AKA]] ''gallbladder [[intestinal metaplasia]]''.
{{Main|Intestinal metaplasia of the gallbladder}}

==Antral type metaplasia==
===General===
*[[AKA]] ''pyloric metaplasia'', ''pseudopyloric metaplasia'', ''mucous gland metaplasia''.<ref name=Ref_Sternberg4_1789>{{Ref Sternberg4|1789}}</ref>

===Microscopic===
Features:<ref name=Ref_Sternberg4_1789>{{Ref Sternberg4|1789}}</ref>
*Columnar cells with:
**Abundant, pale, apical mucin.
**Small basal nucleus.
*Cells often in nests -- below luminal surface.
*Cells vaguely resemble foveollar epithelium of the stomach.

Notes:
*May look similar to cells of the gallbladder neck<ref name=Ref_Sternberg4_1789>{{Ref Sternberg4|1789}}</ref> and common bile duct.<ref>Cutz, E. 3 March 2011.</ref>
**These glandular cells are not as columnar and have less well-defined cell borders.
***Cells with antral type metaplasia >2:1 (height:width), benign mucosal glands <2:1.

Images:
*[http://www.archivesofpathology.org/doi/pdf/10.1043/1543-2165%282005%29129%3C386%3APPOGDA%3E2.0.CO%3B2 Gallbladder metaplasias (archivesofpathology.org)].<ref name=pmid15737036>{{cite journal |author=Mukhopadhyay S, Landas SK |title=Putative precursors of gallbladder dysplasia: a review of 400 routinely resected specimens |journal=Arch. Pathol. Lab. Med. |volume=129 |issue=3 |pages=386–90 |year=2005 |month=March |pmid=15737036 |doi= |url=http://www.archivesofpathology.org/doi/pdf/10.1043/1543-2165%282005%29129%3C386%3APPOGDA%3E2.0.CO%3B2 }}</ref>

===Sign out===
<pre>
Gallbladder, Cholecystectomy:
- Chronic cholecystitis with antral-type metaplasia, NEGATIVE for dysplasia.
- Cholelithiasis.
</pre>

==Gallbladder adenoma==
:''Gallbladder dysplasia'' redirects here.
===General===
*Premalignant lesion.
*May be associated with [[familial adenomatous polyposis]] or [[Peutz-Jeghers syndrome]].<ref name=pmid11896229>{{Cite journal | last1 = Levy | first1 = AD. | last2 = Murakata | first2 = LA. | last3 = Abbott | first3 = RM. | last4 = Rohrmann | first4 = CA. | title = From the archives of the AFIP. Benign tumors and tumorlike lesions of the gallbladder and extrahepatic bile ducts: radiologic-pathologic correlation. Armed Forces Institute of Pathology. | journal = Radiographics | volume = 22 | issue = 2 | pages = 387-413 | month = | year = | doi = | PMID = 11896229 | url = http://radiographics.rsna.org/content/22/2/387.full }}</ref>

===Microscopic===
Features:
*Gallbladder epithelium with:
**Nuclear atypia - '''key feature'''.
***Nuclear hyperchromasia.
***Nuclear crowding (pseudostratification) ''or'' round enlarged nuclei.
**+/-Goblet cells.

Architectural subclassification:<ref name=pmid22895264>{{Cite journal | last1 = Adsay | first1 = V. | last2 = Jang | first2 = KT. | last3 = Roa | first3 = JC. | last4 = Dursun | first4 = N. | last5 = Ohike | first5 = N. | last6 = Bagci | first6 = P. | last7 = Basturk | first7 = O. | last8 = Bandyopadhyay | first8 = S. | last9 = Cheng | first9 = JD. | title = Intracholecystic papillary-tubular neoplasms (ICPN) of the gallbladder (neoplastic polyps, adenomas, and papillary neoplasms that are ≥1.0 cm): clinicopathologic and immunohistochemical analysis of 123 cases. | journal = Am J Surg Pathol | volume = 36 | issue = 9 | pages = 1279-301 | month = Sep | year = 2012 | doi = 10.1097/PAS.0b013e318262787c | PMID = 22895264 }}</ref>
*Papillary ~ 45%.
*Tubulopapillary ~ 30%.
*Tubular ~ 25%.

Notes:
*All of the gallbladder should be submitted prior to sign out to exclude non-sampled adenocarcinoma.

DDx:
*[[Gallbladder adenocarcinoma]].
*Reactive changes.

====Images====
*[http://radiographics.rsna.org/content/22/2/387/F4.expansion.html Tubular adenoma, biliary type (rsna.org)].<ref name=pmid11896229/>
*[http://www.flickr.com/photos/lunarcaustic/4986649333/ Gallbladder with high-grade dysplasia (flickr.com/lunar caustic)].

===Sign out===
<pre>
GALLBLADDER, CHOLECYSTECTOMY:
- BILIARY TYPE TUBULAR ADENOMA WITH HIGH GRADE DYSPLASIA.
- MARGINS CLEAR OF ADENOMA (NEAREST MARGIN 1.0 CM).
</pre>

==Intracholecystic Papillary Neoplasm<ref>{{Cite journal | last1 = Adsay | first1 = V. | last2 = Jang | first2 = KT. | last3 = Roa | first3 = JC. | last4 = Dursun | first4 = N. | last5 = Ohike | first5 = N. | last6 = Bagci | first6 = P. | last7 = Basturk | first7 = O. | last8 = Bandyopadhyay | first8 = S. | last9 = Cheng | first9 = JD. | title = Intracholecystic papillary-tubular neoplasms (ICPN) of the gallbladder (neoplastic polyps, adenomas, and papillary neoplasms that are ≥1.0 cm): clinicopathologic and immunohistochemical analysis of 123 cases. | journal = Am J Surg Pathol | volume = 36 | issue = 9 | pages = 1279-301 | month = Sep | year = 2012 | doi = 10.1097/PAS.0b013e318262787c | PMID = 22895264 }}
</ref>==

===General===
*Probably some overlap with 'adenoma' above
*Lesion defined as being >1cm.
*Low-grade lesions previously designated “papillary adenoma”
*High-grade lesions previously designated “noninvasive papillary carcinoma.”
*Oten arise in a background of pyloric-gland metaplasia.
*May be associated with invasive adenocarcinoma, which should be reported as intracystic papillary neoplasm with an associated invasive carcinoma and staged.

*Population
**Female (F/M=2:1)
**Mean age 61
*Presentations
**Pain
**Incidental
*No particular association with gallstones.

===Microscopic===
*Cell types
**Pancreatobiliary type
**Intestinal types with goblet, Paneth, and/or serotonin-containing cells.
*Architecture
**Papillary
**Tubulopapillary
**Tubular
*Dysplasia - high or low grade

<gallery>
Image:GallBladder IntracysticPapillaryNeoplasm WA InvasiveAdenocarcinoma LP CTR.jpg|Gall Bladder - Intracholecystic Papillary Neoplasm with Invasive Adenocarcinoma - Low power (SKB)
Image:GallBladder IntracysticPapillaryNeoplasm WA InvasiveAdenocarcinoma HP CTR.jpg|Gall Bladder - Intracholecystic Papillary Neoplasm with Invasive Adenocarcinoma - High power (SKB)
Image:GallBladder IntracysticPapillaryNeoplasm WA InvasiveAdenocarcinoma HP3 CTR.jpg|Gall Bladder - Intracholecystic Papillary Neoplasm with Invasive Adenocarcinoma - High power (SKB)
Image:GallBladder IntracysticPapillaryNeoplasm WA InvasiveAdenocarcinoma HP2 CTR.jpg|Gall Bladder - Intracholecystic Papillary Neoplasm with Invasive Adenocarcinoma - High power (SKB)
Image:GallBladder IntracysticPapillaryNeoplasm WA InvasiveAdenocarcinoma MP CTR.jpg|Gall Bladder - - Intracholecystic Papillary Neoplasm with Invasive Adenocarcinoma - Malignant gland infiltrating stroma - High power (SKB)
Image:GallBladder IntracysticPapillaryNeoplasm WA InvasiveAdenocarcinoma HP4 CTR.jpg|Gall Bladder - Intracholecystic Papillary Neoplasm with Invasive Adenocarcinoma - - Malignant gland infiltrating stroma - Very high power (SKB)
Image:Gallbladder IntracysticPapillaryNeoplasm HighGradeDysplasia LP PA.JPG|Gall Bladder - Intracholecystic Papillary Neoplasm with high grade dysplasia - Low power (SKB)
Image:Gallbladder IntracysticPapillaryNeoplasm HighGradeDysplasia MP PA.JPG|Gall Bladder - Intracholecystic Papillary Neoplasm with high grade dysplasia - Medium power (SKB)
</gallery>

Notes:
All of the gallbladder should be submitted prior to sign out to exclude invasive adenocarcinoma.

=Malignant=
==Gallbladder carcinoma==
{{Main|Gallbladder carcinoma}}

=See also=
*[[Liver]].
*[[Gastrointestinal pathology]].

=References=
{{reflist|2}}

[[Category:Gallbladder]]
[[Category:Gastrointestinal pathology]]

Alpha-1 antitrypsin deficiency

2017-01-09T21:11:36Z

Mitchell: /* Images */ added a case

{{ Infobox diagnosis
| Name = {{PAGENAME}}
| Image = Alpha-1 antitrypsin deficiency.PAS Diastase.jpg
| Width =
| Caption = Alpha-1 AT deficiency. [[PASD stain]].
| Synonyms = alpha1-antiprotease inhibitor deficiency
| Micro = +/-pink globules in zone 1 (periportal), +/-fibrosis or [[cirrhosis]]
| Subtypes =
| LMDDx =
| Stains = PASD +ve (pink globules in zone 1) - not seen in children
| IHC = A1-AT +ve globules
| EM =
| Molecular =
| IF =
| Gross =
| Grossing =
| Site = [[liver]] - see ''[[medical liver disease]]'', [[lung]] - see ''[[emphysema]]''
| Assdx =
| Syndromes =
| Clinicalhx =
| Signs =
| Symptoms =
| Prevalence = uncommon (1 in 2000-5000)
| Bloodwork =
| Rads = emphysematous changes (chest x-ray)
| Endoscopy =
| Prognosis =
| Other =
| ClinDDx =
| Tx =
}}
'''Alpha-1 antitrypsin deficiency''', abbreviated '''A1-AT''', is a relatively common genetic condition that causes lung and liver pathology.

It is also known as '''alpha1-antiprotease inhibitor deficiency'''.

This article deals with the [[medical liver disease|liver pathology]]. The lung pathology is ''panlobular emphysema'' and covered in the ''[[emphysema]]'' article.

==General==
Etiology:
*Genetic defect.
**Prevalence 1 in 2000-5000.<ref name=pmid21960536>{{Cite journal | last1 = Stoller | first1 = JK. | last2 = Aboussouan | first2 = LS. | title = A Review of Alpha-1 Antitrypsin Deficiency. | journal = Am J Respir Crit Care Med | volume = | issue = | pages = | month = Sep | year = 2011 | doi = 10.1164/rccm.201108-1428CI | PMID = 21960536 }}
</ref>

Causes:
*Lung and liver injury.
**Lung -> panlobular [[emphysema]].

==Microscopic==
Features:
*Pink globules in zone 1 (periportal).
**Globules ''not'' seen in children.
**May ''not'' be present in late stage (cirrhotic).
**Best seen on [[PASD stain]].
**Can be seen on H&E -- if one looks carefully.

Note:
*The pink globules may be seen in the context of cirrhosis; cases should be confirmed with IHC.

===Images===
<gallery>
Image:Alpha-1 antitrypsin deficiency.PAS Diastase.jpg | Alpha-1 AT deficiency - PASD. (WC/JMGardner)
</gallery>
[[File:4 37975578915035 sl 1.png|Alpha 1 anti-trypsin deficiency in 29 year old woman.]]
[[File:4 37975578915035 sl 2.png|Alpha 1 anti-trypsin deficiency in 29 year old woman.]]
[[File:4 37975578915035 sl 3.png|Alpha 1 anti-trypsin deficiency in 29 year old woman.]]
[[File:4 37975578915035 sl 4.png|Alpha 1 anti-trypsin deficiency in 29 year old woman.]] 
Alpha 1 anti-trypsin deficiency in 29 year old woman. A. At low power, there is focal steatosis and mild inflammation of portal triads. B. Foci of steatosis show rare tufts of ballooning degeneration (arrow). C. A few triads had infiltrates of macrophages and lymphocytes, none with definite interface hepatitis; note the space between the hepatocytes and the inflammatory cells. D. PAS-D showed splotches of hepatocytes with PAS-D granules. The patient was already known to have A1AT deficiency.

A. [[File:1 A1AT 1 680x512px.tif| Alpha 1 Antitrypsin deficiency with cirrhosis]] 
B. [[File:2 A1AT 1 680x512px.tif| Alpha 1 Antitrypsin deficiency with cirrhosis]] 
C. [[File:3 A1AT 1 680x512px.tif| Alpha 1 Antitrypsin deficiency with cirrhosis]] 
D. [[File:4 A1AT 1 680x512px.tif| Alpha 1 Antitrypsin deficiency with cirrhosis]] 
E. [[File:5 A1AT 1 680x512px.tif| Alpha 1 Antitrypsin deficiency with cirrhosis]] 
F. [[File:6 A1AT 1 680x512px.tif| Alpha 1 Antitrypsin deficiency with cirrhosis]] 

Alpha 1 Antitrypsin deficiency with cirrhosis. A. Dark inflamed bands bound hepatocyte nodules. B. Steatosis afflicts some hepatocyte areas, within inflamed band lie proliferated bile ductules. C. Reticulin shows regenerative (more than 2 nuclei per cord) nodules (black lines without definite directionality) amid bands. D. Trichrome shows scar. E. Hepatocytes show steatosis, foamy degeneration, and intranuclear inclusions. F. PAS-D shows A1AT cytoplasmic granules; in non-A1AT cirrhosis, these granules would neither be in so many hepatocytes nor, in general, as large.

[[File:1 A1AT 2 680x512px.tif| Alpha 1 anti-trypsin (A1AT) granules in cirrhosis, not due to A1AT deficiency; A1AT level was normal.]]
[[File:2 A1AT 2 680x512px.tif| Alpha 1 anti-trypsin (A1AT) granules in cirrhosis, not due to A1AT deficiency; A1AT level was normal.]]
[[File:3 A1AT 2 680x512px.tif| Alpha 1 anti-trypsin (A1AT) granules in cirrhosis, not due to A1AT deficiency; A1AT level was normal.]]
[[File:4 A1AT 2 680x512px.tif| Alpha 1 anti-trypsin (A1AT) granules in cirrhosis, not due to A1AT deficiency; A1AT level was normal.]]
[[File:5 A1AT 2 680x512px.tif| Alpha 1 anti-trypsin (A1AT) granules in cirrhosis, not due to A1AT deficiency; A1AT level was normal.]]
[[File:6 A1AT 2 680x512px.tif| Alpha 1 anti-trypsin (A1AT) granules in cirrhosis, not due to A1AT deficiency; A1AT level was normal.]] 

Alpha 1 anti-trypsin (A1AT) granules in cirrhosis, not due to A1AT deficiency; A1AT level was normal. A. Low power shows an inflamed foci, bands, and hepatocyte regions. B. Trichrome confirms blue fibrosis about hepatocyte isles. C. Proliferated bile ductules (black arrows) border hepatocytes with glycogenated nuclei (green arrows), consistent with the history of diabetes. D. Reticulin shows two-cell thick regenerated cords (green arrows) and circles for rosettes (black arrows). E. PAS with diastase stain shows occasional small red granules (arrows) and red dust in cytoplasm of hepatocytes near edge of regenerative nodule. E. A1AT immunostain shows occasional small brown granules (arrows) in cytoplasm of hepatocytes near edge of regenerative nodule.

www:
*[http://moon.ouhsc.edu/kfung/jty1/opaq/pathquiz/l1k001-pq01.htm Alpha-1 AT (ouhsc.edu)].
*[http://www.pathpedia.com/Education/eAtlas/Histopathology/Liver_and_bile_ducts/Alpha-1_antitrypsin_deficiency.aspx Alpha-1 AT (pathpedia.com)].

==Stains==
*PAS +ve.<ref name=pmid6189389>{{Cite journal | last1 = Qizilbash | first1 = A. | last2 = Young-Pong | first2 = O. | title = Alpha 1 antitrypsin liver disease differential diagnosis of PAS-positive, diastase-resistant globules in liver cells. | journal = Am J Clin Pathol | volume = 79 | issue = 6 | pages = 697-702 | month = Jun | year = 1983 | doi = | PMID = 6189389 }}</ref>
*PASD +ve.<ref name=pmid6189389/>

==IHC==
*A1-AT +ve globules.<Ref name=pmid3512609>{{Cite journal | last1 = Theaker | first1 = JM. | last2 = Fleming | first2 = KA. | title = Alpha-1-antitrypsin and the liver: a routine immunohistological screen. | journal = J Clin Pathol | volume = 39 | issue = 1 | pages = 58-62 | month = Jan | year = 1986 | doi = | PMID = 3512609 }}</ref>

==See also==
*[[Medical liver disease]].

==References==
{{Reflist|2}}

[[Category:Diagnosis]]
[[Category:Medical liver disease]]
[[Category:Pulmonary pathology]]

Wilson's disease

2017-01-09T19:17:20Z

Mitchell: /* Microscopic */ added a case

'''Wilson disease's''' is a rare autosomal recessive genetic disease characterized by abnormal copper transportation. Its' presentation may be atypical. In the context of [[pathology]], it is typically seen as a [[liver biopsy]].

==General==
Epidemiology:
*Rare autosomal recessive - mutation in copper-transporting adenosine triphosphatase (ATPase) gene (ATP7B).<ref name=emedicine183456>[http://emedicine.medscape.com/article/183456-overview http://emedicine.medscape.com/article/183456-overview]</ref><ref name=omim606882>{{OMIM|606882}}</ref>
**Heterozygote carrier rate approximately 1/100 persons.<ref name=emedicine183456/>
*Young individuals - usually 12-23 years old.
**May have late-onset (symptomatic when >40 years old).<ref name=pmid17433323>{{Cite journal | last1 = Ferenci | first1 = P. | last2 = Członkowska | first2 = A. | last3 = Merle | first3 = U. | last4 = Ferenc | first4 = S. | last5 = Gromadzka | first5 = G. | last6 = Yurdaydin | first6 = C. | last7 = Vogel | first7 = W. | last8 = Bruha | first8 = R. | last9 = Schmidt | first9 = HT. | title = Late-onset Wilson's disease. | journal = Gastroenterology | volume = 132 | issue = 4 | pages = 1294-8 | month = Apr | year = 2007 | doi = 10.1053/j.gastro.2007.02.057 | PMID = 17433323 }}</ref>

Clinical:
*Kayser-Fleischer rings --> on slit-lamp examination (green eyes).
*May present to psychiatry or appear to be abusing EtOH.
*Serum ceruloplasmin - lower than normal; typical value for Wilson's ~ 0.12 g/L.
**<0.20 g/L is a criteria for Wilson's disease.<ref name=pmid18556333>Diagnostic accuracy of serum ceruloplasmin in Wilson disease: determination of sensitivity and specificity by ROC curve analysis among ATP7B-genotyped subjects. Mak CM, Lam CW, Tam S. Clin Chem. 2008 Aug;54(8):1356-62. Epub 2008 Jun 12. PMID 18556333. URL: [http://www.clinchem.org/cgi/reprint/54/8/1356.pdf http://www.clinchem.org/cgi/reprint/54/8/1356.pdf]. Accessed on: 28 September 2009.</ref>

Etiology:
*Excess copper -- due to genetic defect.

==Microscopic==
Features:
*Nothing specific - known as the great mimicker of [[liver pathology]].
*[[Steatosis of the liver|Steatosis]].
*Portal fibrosis.

A. [[File:1 Wilson 1 680x512px.tif|Inflamed & relatively unaffected segments (40X).]] 
B. [[File:2 Wilson 1 680x512px.tif|Bile ductular proliferation with interface hepatitis [inflammation of periportal hepatocytes] (200X).]] 
C. [[File:3 Wilson 1 680x512px.tif|Enlarged hepatocytes, some with feathery degeneration, others with steatosis. Nuclei show nucleoli (400X).]] 
D. [[File:4 Wilson 1 680x512px.tif|Trichrome shows periportal & sinusoidal fibrosis. No bridging was seen. (100X).]] 
Wilson’s disease, pre-cirrhotic. A. Inflamed & relatively unaffected segments. B. Bile ductular proliferation with interface hepatitis [inflammation of periportal hepatocytes]. C. Enlarged hepatocytes, some with feathery degeneration, others with steatosis. Nuclei show nucleoli. D. Trichrome shows periportal & sinusoidal fibrosis.

[[File:4 38555059990939 sl 1.png|Wilson’s disease with cirrhosis]]
[[File:4 38555059990939 sl 2.png|Wilson’s disease with cirrhosis]]
[[File:4 38555059990939 sl 3.png|Wilson’s disease with cirrhosis]]
[[File:4 38555059990939 sl 4.png|Wilson’s disease with cirrhosis]]
[[File:4 38555059990939 sl 5.png|Wilson’s disease with cirrhosis]] 
Wilson’s disease with cirrhosis in a 22 year old woman. A. Nodules show steatosis without definite triads. B. Trichrome shows minute fibrous bound nodules in this case. C. Reticulin shows extensive regeneration (2-3 nuclei thick cords with lack of direction) with nodule formation. D. Bridge with extensive proliferated bile ductules and acute and chronic inflammatory cells. E. Ballooning degeneration with Mallory bodies.

==Stains==
*Copper staining positive - '''only 15% of cases'''.
**Other stains: rhodinine (red/orange granules = positive), orecin.

Notes:
*Copper staining is a non-specific finding seen in many liver diseases; it is associated with impaired bile secretion.<ref name=pmid2464523>{{cite journal |author=Miyamura H, Nakanuma Y, Kono N |title=Survey of copper granules in liver biopsy specimens from various liver abnormalities other than Wilson's disease and biliary diseases |journal=Gastroenterol. Jpn. |volume=23 |issue=6 |pages=633–8 |year=1988 |month=December |pmid=2464523 |doi= |url=}}</ref>

===Image===
*[http://openi.nlm.nih.gov/legacy/detailedresult.php?img=3375662_yjbm_85_2_249_g03&req=4 Orecin staining in Wilson's diseae (nih.gov)].

==Additional testing==
Copper quantification:
*Mass spectrometry.<ref name=pmid24731025>{{Cite journal | last1 = Hahn | first1 = SH. | title = Population screening for Wilson's disease. | journal = Ann N Y Acad Sci | volume = 1315 | issue = | pages = 64-9 | month = May | year = 2014 | doi = 10.1111/nyas.12423 | PMID = 24731025 }}</ref>
*Atomic absorption spectroscopy.
**>250 microg of copper/g of liver suggest Wilson's disease; below does not exclude it.<ref name=pmid16234011>{{Cite journal | last1 = Ferenci | first1 = P. | last2 = Steindl-Munda | first2 = P. | last3 = Vogel | first3 = W. | last4 = Jessner | first4 = W. | last5 = Gschwantler | first5 = M. | last6 = Stauber | first6 = R. | last7 = Datz | first7 = C. | last8 = Hackl | first8 = F. | last9 = Wrba | first9 = F. | title = Diagnostic value of quantitative hepatic copper determination in patients with Wilson's Disease. | journal = Clin Gastroenterol Hepatol | volume = 3 | issue = 8 | pages = 811-8 | month = Aug | year = 2005 | doi = | PMID = 16234011 }}</ref>

[[Sensitivity]]:<ref>{{Cite journal | last1 = Liggi | first1 = M. | last2 = Mais | first2 = C. | last3 = Demurtas | first3 = M. | last4 = Sorbello | first4 = O. | last5 = Demelia | first5 = E. | last6 = Civolani | first6 = A. | last7 = Demelia | first7 = L. | title = Uneven distribution of hepatic copper concentration and diagnostic value of double-sample biopsy in Wilson's disease. | journal = Scand J Gastroenterol | volume = 48 | issue = 12 | pages = 1452-8 | month = Dec | year = 2013 | doi = 10.3109/00365521.2013.845904 | PMID = 24164422 }}</ref>
*250 microg of copper/g of liver - 80-86% (value dependent on sampling).
*50 microg of copper/g of liver - 97%.

==See also==
*[[Medical liver disease]].

==References==
{{Reflist|2}}

==External links==
*[https://www.lhsc.on.ca/lab/metals/req.htm Trace metals laboratory (lhsc.on.ca)].

[[Category:Medical liver disease]]
[[Category:Diagnosis]]

Marginal zone lymphoma

2017-01-09T18:17:51Z

Mitchell: /* Images */ added a case

{{ Infobox diagnosis
| Name = {{PAGENAME}}
| Image = Marginal zone lymphoma - kidney -- intermed mag.jpg
| Width =
| Caption = Marginal zone lymphoma of the kidney. [[H&E stain]].
| Synonyms =
| Micro = small lymphoid cells +/-plasmacytoid features +/-[[lymphoepithelial lesion]]
| Subtypes =
| LMDDx = other [[small cell lymphomas]], [[DLBCL]]
| Stains =
| IHC = CD20 +ve, BCL2 +ve, CD21 +ve, CD43 +ve/-ve
| EM =
| Molecular =
| IF =
| Gross =
| Grossing =
| Site = gastrointestinal tract, [[lymph nodes]]
| Assdx =
| Syndromes =
| Clinicalhx =
| Signs =
| Symptoms =
| Prevalence = moderate
| Bloodwork =
| Rads =
| Endoscopy = +/-nodularity
| Prognosis =
| Other = CD11c +ve (flow cytometry or laser scanning cytometry)
| ClinDDx =
| Tx =
}}
'''Marginal zone lymphoma''', abbreviated '''MZL''', is a common type of lymphoma composed of [[small cell lymphomas|small cells]].

==General==
*Arise in the context chronic infections, e.g. [[Sjögren disease]] ([[salivary gland]]), [[Hashimoto thyroiditis]] ([[thyroid gland]]), [[Helicobacter pylori gastritis]] ([[stomach]]).<ref name=Ref_PCPBoD8_326>{{Ref PCPBoD8|326}}</ref>

===Classification===
*Comes in three different flavours:
*#Extranodal marginal zone lymphoma.
*#*If in ''mucosa-associated lymphoid tissue'' known as a ''MALT lymphoma'', [[AKA]] ''MALToma''. There is also a counterpart in the [[lung]] that arises from ''bronchus-associated lymphoid tissue''. These are known as ''[[BALToma]]s''.
*#Splenic marginal zone lymphoma (SMZL).
*#Nodal marginal zone lymphoma (NMZL).

==Microscopic==
Features:
*Small (lymphoid) cells that may be plasma cell-like (plasmacytoid):<ref>URL: [http://surgpathcriteria.stanford.edu/bcell/marginalnodal/printable.html http://surgpathcriteria.stanford.edu/bcell/marginalnodal/printable.html]. Accessed on: 6 March 2012.</ref>
**+/-Clockface nucleus.
**+/-Eccentric nucleus.
*+/-"[[Lymphoepithelial lesion]]" - gastric crypts invaded by a monomorphous population of lymphocytes.<ref name=pmid1452124>{{Cite journal | last1 = Papadaki | first1 = L. | last2 = Wotherspoon | first2 = AC. | last3 = Isaacson | first3 = PG. | title = The lymphoepithelial lesion of gastric low-grade B-cell lymphoma of mucosa-associated lymphoid tissue (MALT): an ultrastructural study. | journal = Histopathology | volume = 21 | issue = 5 | pages = 415-21 | month = Nov | year = 1992 | doi = | PMID = 1452124 }}</ref>
**Features:
**# Cluster of lymphocytes - three cells or more - '''key feature'''.
**#* Single lymphocytes don't count.
**# Clearing around the lymphocyte cluster.
**Not specific for MALT lymphoma, i.e. may be seen in other types of lymphoma.<ref>DB. 6 August 2010.</ref>

DDx:
*Other [[small cell lymphomas]].
*[[DLBCL]] - should be a distinctive region at low power.{{fact}}

===Images===
<gallery>
Image: Marginal zone lymphoma - kidney -- low mag.jpg | MZL - low mag. (WC)
Image: Marginal zone lymphoma - kidney -- intermed mag.jpg | MZL - intermed. mag. (WC)
Image: Marginal zone lymphoma - kidney -- high mag.jpg | MZL - high mag. (WC)
Image: Marginal zone lymphoma - kidney -- very high mag.jpg | MZL - very high mag. (WC)
Image: Marginal zone lymphoma - kidney - alt -- very high mag.jpg | MZL - very high mag. (WC)
</gallery>

[[File:5 3078322547565 sl 1.png| MALT lymphoma of stomach]]
[[File:5 3078322547565 sl 2.png| MALT lymphoma of stomach]]
[[File:5 3078322547565 sl 3.png| MALT lymphoma of stomach]]
[[File:5 3078322547565 sl 4.png| MALT lymphoma of stomach]]
[[File:5 3078322547565 sl 5.png| MALT lymphoma of stomach]] 
Extrazonal marginal zone lymphojma of mucosa-associates lymphoid tissue (MALT lymphoma) in stomach of 64 Year old man, identified in sleeve gastrectomy performed for weight loss. A. Predominantly submucosal blue masses without definite follicles. B. Small round to irregular lymphoid cells surround the most inferior pits. C. Non-neoplastic T cells are seen in abundance, sometime within pit epithelium. D. Neoplastic B cells mass and surround pits, but do not extensively invade the epithelium; lymphoepithelial lesions were not seen. E. Cancer cells expressed BCL2. Cancer cells were negative for CD5, CD10, and cyclin D1.

www:
*[http://path.upmc.edu/cases/case405.html MALT lymphoma - several images (upmc.edu)].
*[http://www.pathpedia.com/education/eatlas/histopathology/intestine_large/lymphoma_malt-type.aspx MALT lymphoma - several images (pathpedia.com)].
====Lymphoepithelial lesion====
<gallery>
Image:Gastrointestinal_lymphoepithelial_lesion_-_very_high_mag.jpg | Lymphoepithelial lesion - very high mag. (WC)
Image:Gastrointestinal_lymphoepithelial_lesion_-_intermed_mag.jpg | Lymphoepithelial lesion - intermed. mag. (WC)
</gallery>

==IHC==
Features:<ref>{{Ref Lester|95}}</ref>
*CD20 +ve.
*BCL2 +ve.
*CD21 +ve.
*CD11c +ve (flow cytometry or laser scanning cytometry - only; not available for paraffin).
*CD43 +ve/-ve.
**Typically positive in ''[[mantle cell lymphoma]].

Others:
*CD5 -ve.
*CD10 -ve.
*CD23 -ve.

==Molecular==
There are several associated with MALT lymphoma:<ref name=pmid16950858>{{cite journal |author=Bacon CM, Du MQ, Dogan A |title=Mucosa-associated lymphoid tissue (MALT) lymphoma: a practical guide for pathologists |journal=J. Clin. Pathol. |volume=60 |issue=4 |pages=361–72 |year=2007 |month=April |pmid=16950858 |pmc=2001121 |doi=10.1136/jcp.2005.031146 |url=}}</ref>
*t(11;18)(q21;q21) / API2‐MALT1<ref name=Ref_PCPBoD8_170>{{Ref PCPBoD8|170}}</ref> - most common translocation in MALT lymphoma.<ref name=pmid12406890>{{Cite journal | last1 = Streubel | first1 = B. | last2 = Lamprecht | first2 = A. | last3 = Dierlamm | first3 = J. | last4 = Cerroni | first4 = L. | last5 = Stolte | first5 = M. | last6 = Ott | first6 = G. | last7 = Raderer | first7 = M. | last8 = Chott | first8 = A. | title = T(14;18)(q32;q21) involving IGH and MALT1 is a frequent chromosomal aberration in MALT lymphoma. | journal = Blood | volume = 101 | issue = 6 | pages = 2335-9 | month = Mar | year = 2003 | doi = 10.1182/blood-2002-09-2963 | PMID = 12406890 }}
</ref>
*t(14;18)(q32;q21) / IGH‐MALT1.
**Should not be confused with t(14;18) seen in [[follicular lymphoma]] between IGH-BCL2.<ref name=pmid18359244>{{Cite journal | last1 = Vitolo | first1 = U. | last2 = Ferreri | first2 = AJ. | last3 = Montoto | first3 = S. | title = Follicular lymphomas. | journal = Crit Rev Oncol Hematol | volume = 66 | issue = 3 | pages = 248-61 | month = Jun | year = 2008 | doi = 10.1016/j.critrevonc.2008.01.014 | PMID = 18359244 }}</ref>
*t(1;14)(p22;q32) / IGH‐BCL10.

The MALT1 associated [[translocations]] can be assessed with an [[ISH]] break apart probe for MALT1.

==See also==
*[[Small cell lymphomas]].
*[[Lymphoma]].
*[[BALToma]].

==References==
{{Reflist|2}}

[[Category:Small cell lymphomas]]

Drug-induced liver disease

2017-01-03T17:37:22Z

Mitchell: /* Images */ added a case

'''Drug-induced liver disease''', also '''drug-induced liver toxicity''' and '''drug liver injury''', is relatively common.

Drug reactions in general are dealt with in ''[[drug toxicity]]''.

==General==
*Drugs can do almost anything; may include: [[granulomata]], bile duct loss, cholestasis, ischemic type injury.
*Effects can be delayed -- temporal relationship not always obvious.

==Microscopic==
Features:
*Non-specific findings.
**+/-Eosinophils<ref>{{Ref DCHH|166}}</ref> - '''significant suggestive finding'''.
**+/-Steatosis - periportal macrovesicular, microvesicular.
**+/-[[Vanishing bile duct syndrome]].
**+/-[[Granuloma]]s.

===Images===
<gallery>
Image:Drug-induced_hepatitis_low_mag.jpg | Drug-induced hepatitis - low mag. (WC)
Image:Drug-induced_hepatitis_intermed_mag.jpg | Drug-induced hepatitis - intermed. mag. (WC)
Image:Drug-induced hepatitis high mag.jpg | Drug-induced hepatitis - high mag. (WC)
</gallery>

A [[File:1 iron DILI 680x512px.tif|Hemocrhomatosis with DILI canalicular cholestasis with mild hepatocyte injury in the form of regeneration.]]
B [[File:2 iron DILI 680x512px.tif|Hemocrhomatosis with DILI canalicular cholestasis with mild hepatocyte injury in the form of regeneration.]]
 
C [[File:3 iron DILI 680x512px.tif|Hemocrhomatosis with DILI canalicular cholestasis with mild hepatocyte injury in the form of regeneration.]]
D [[File:4 iron DILI 680x512px.tif|Hemocrhomatosis with DILI canalicular cholestasis with mild hepatocyte injury in the form of regeneration.]]
 
E [[File:5 iron DILI 680x512px.tif|Hemocrhomatosis with DILI canalicular cholestasis with mild hepatocyte injury in the form of regeneration.]]
F [[File:6 iron DILI 680x512px.tif|Hemocrhomatosis with DILI canalicular cholestasis with mild hepatocyte injury in the form of regeneration.]]

Hemochromatosis with DILI canalicular cholestasis with mild hepatocyte injury in the form of regeneration. This young adult man presented with jaundice; canalicular cholestasis was explicable on the basis of one or more of the medications he had been given. Iron positivity came as a surprise. Canalicular cholestasis, accumulation of bile in canaliculi, and, at times, choangioles, is most commonly seen with steroids. When damage to hepatocytes & portal inflammation accompanies canalicular cholestasis, drugs such as chlorpromazine and erythromycin, are most often responsible. Pure ductular cholestasis has been associated with benoxaprofen or sepsis. Cholangiodestructive (e.g., with destroyed bile ducts) cholestasis has been associated with paraquat, chlorpromazye, and other drugs. Some drugs, eg, phenytoin are also noted to be associated with mixed hepatocellular/cholestatic injury. Others have bile duct proliferation with eosinophils as a response.[1]A. Present at low power are seemingly normal portal triads [black arrows], normal central veins [green arrows] and normal intervening parenchyma. B. Iron stain shows 3+ iron deposition. C. A reticulin stain shows changes of injury. Lines between portal triad [black arrow] and central vein [green arrow] lack directionality. Regeneration is seen in two-three hepatocyte cords [blue arrows] and hepatocyte rosettes [magenta arrows]; canaliculi are not highlighted by reticulin stain. D. Iron stain shows predominantly hepatocellular iron deposition [green arrows] with occasional Kupffer cell staining [black arrows]. E. Distinguishing iron from bile can be accomplished by evaluating location of pigment. In pure canalicular cholestasis with mild hepatocyte injury, unusual are macrophages with bile staining in the lobule, being as they are confined to the sinusoids; the pigment on left on H&E in a sinusoidal macrophage [green arrow], stains blue on iron stain on similar macrophage [black arrow]. F. Note the canalicular pigment on left on HE, [green arrows] ; a similar ball on the iron stain on the right lacks any stain [black arrow]. [1]H.J. Zimmerman, KG Ishak, “Hepatic injury due to drugs and toxins.” In Pathology of the Liver. RNM MacSween, et al, eds. New York: Churchill-Livingston. 2002: 638-641.

[[File:1 DILI 2 680x512px.tif| Drug induced liver injury in a young adult man]]
[[File:2 DILI 2 680x512px.tif| Drug induced liver injury in a young adult man]]
[[File:3 DILI 2 680x512px.tif| Drug induced liver injury in a young adult man]]
[[File:4 DILI 2 680x512px.tif| Drug induced liver injury in a young adult man]]
[[File:5 DILI 2 680x512px.tif| Drug induced liver injury in a young adult man]]
[[File:6 DILI 2 680x512px.tif| Drug induced liver injury in a young adult man]]

Drug induced liver injury in a young adult man. Acute onset hepatitis with albumin 3.2, ALT 1078, Alkaline phosphatase 141, direct bilirubin 6.3. A. Dark expanded triads (arrows) strew, at low power, normal hepatocyte lobules. B. A triad shows interface hepatitis (black arrows), a proliferated bile ductule (cyan arrows), and eosinophils (red arrows). C. PAS without diastase highlights interface hepatitis with intact plate, lacking piecemeal necrosis, as well as the multiple plasma cells (arrows) and a proliferated bile ductule (green arrows). D. Intense lobular inflammation, including eosinophils (red arrows) is associated with foamy cytoplasm of feathery degeneration in hepatocytes (green arrows), degenerated, small hepatocytes (cyan arrows), and a councilman body (black arrow). F. Reticulin shows regeneration, with two cell thick cords (cyan arrows) and hepatocyte rosettes (green arrows), as well as a single cell with piecemeal necrosis (black arrow). F. Trichrome shows perihepatocyte fibrosis (black arrows) and short fibrous spikes off triads (green arrows).

[[File: 4 90507225729061 sl 1.png|Focal hepatocyte necrosis and isolated granuloma, drug induced liver injury (DILI)]]
[[File: 4 90507225729061 sl 2.png|Focal hepatocyte necrosis and isolated granuloma, drug induced liver injury (DILI)]]
[[File: 4 90507225729061 sl 31.png|Focal hepatocyte necrosis and isolated granuloma, drug induced liver injury (DILI)]]
[[File: 4 90507225729061 sl 4.png|Focal hepatocyte necrosis and isolated granuloma, drug induced liver injury (DILI)]]
[[File: 4 90507225729061 sl 5.png|Focal hepatocyte necrosis and isolated granuloma, drug induced liver injury (DILI)]]

Focal hepatocyte necrosis. Drug induced liver injury (DILI) In 44 yo woman with normal bilirubin, elevated alkaline phopatase (323), slightly increased ALT (87). The patient had been taking antidepressants, which are known to have a low risk of liver injury, most commonly idiosyncratic,. A Low power shows normal triads (green arrows), in contrast to the spot of inflammation (cyan arrow).B. The spot at higher power is a granuloma not in a triad, the only such granuloma identified. C. Occasional triads show inflammation comprising mostly eosinophils. D. Occasional other foci of spotty necrosis were identified. E. Reticulin stain showed rare foci of regeneration (arrows), but no piecemeal necrosis.

[[File:5 32357864049788 sl 1.png|Drug induced liver injury, necroinflammatory with changes of chronic hepatitis]]
[[File:5 32357864049788 sl 2.png|Drug induced liver injury, necroinflammatory with changes of chronic hepatitis]]
[[File:5 32357864049788 sl 3.png|Drug induced liver injury, necroinflammatory with changes of chronic hepatitis]]
[[File:5 32357864049788 sl 4.png|Drug induced liver injury, necroinflammatory with changes of chronic hepatitis]]
[[File:5 32357864049788 sl 5.png|Drug induced liver injury, necroinflammatory with changes of chronic hepatitis]]
[[File:5 32357864049788 sl 6.png|Drug induced liver injury, necroinflammatory with changes of chronic hepatitis]] 
Drug induced liver injury, necroinflammatory with changes of chronic hepatitis, in a 71 year old man with history of piperacillin, after which an allergic reaction occurred, with alkaline phosphatase 221 IU/L, ALT 45 IU/L, normal AST/bilirubin, negative AMA/ANA/viral antibodies. ALT returned to normal rapidly, Alkaline phosphatase gradually resolved. ERCP did not show sclerosing cholangitis. A. Inflamed triads with interface hepatitis and mild steatosis are present at low power, along with a normal central vein. B. A focus of spotty necrosis (black arrow) lies near hepatocytes with ballooning degeneration (brown arrows); a normal portal triad (green arrow) is also seen. C. Most triads showed moderate to marked chronic inflammation with eosinophils (white arrows). Note bile ductular proliferation (black arrows) and ballooning degeneration (red arrows). D. Reticuliln showed only rare foci of piecemeal necrosis (arrow), without significant collapse or regenerative change. E. PAS-D shows a focus of chronic inflammation of the lobule with destruction of hepatocytes; note PAS-D macrophages. F. A single inflamed portal-portal bridge was seen, with macrophages, lymphocytes, and rare eosinophils, but not plasma cells or neutrophils.

[[File:4 40824578186586 sl 1.png|Intrahepatic, nonobstructive cholestasis in a 9 week old, premature baby boy, due presumably to TPN]]
[[File:4 40824578186586 sl 2.png|Intrahepatic, nonobstructive cholestasis in a 9 week old, premature baby boy, due presumably to TPN]]
[[File:4 40824578186586 sl 3.png|Intrahepatic, nonobstructive cholestasis in a 9 week old, premature baby boy, due presumably to TPN]]
[[File:4 40824578186586 sl 4.png|Intrahepatic, nonobstructive cholestasis in a 9 week old, premature baby boy, due presumably to TPN]]
[[File:4 40824578186586 sl 5.png|Intrahepatic, nonobstructive cholestasis in a 9 week old, premature baby boy, due presumably to TPN]]
[[File:4 40824578186586 sl 6.png|Intrahepatic, nonobstructive cholestasis in a 9 week old, premature baby boy, due presumably to TPN]]

Intrahepatic, nonobstructive cholestasis in a 9 week old, premature baby boy with 9.7 mg/dl bilirubin. Most likely due to total parenteral nutrition required for his sustenance. A. Slightly edematous triad with somewhat dilated sinusoids, without inflammatory or neoplastic aggregates at low power. B. Bile filled cholangiolar spaces (green arrows) and pseudoacini (blue arrows). C. Foci of extramedullary hematopoiesis. D. Triads did not show the edema and peripheral bile ductular proliferation normally seen with obstructive cholestasis. E. CK7 shows preservation of bile duct plates. F. Reticulin shows interruption and disorganization of liver plates, consistent with isolated cell necrosis (at this age, the inflammatory foci responding to spotty necrosis on H&E are not seen).

===Specific patterns===
Acute hepatits:
*Related to Rx - most often antibiotics.

[[Steatohepatitis]]/[[steatosis]]:<ref name=pmid16237810>{{Cite journal | last1 = Grieco | first1 = A. | last2 = Forgione | first2 = A. | last3 = Miele | first3 = L. | last4 = Vero | first4 = V. | last5 = Greco | first5 = AV. | last6 = Gasbarrini | first6 = A. | last7 = Gasbarrini | first7 = G. | title = Fatty liver and drugs. | journal = Eur Rev Med Pharmacol Sci | volume = 9 | issue = 5 | pages = 261-3 | month = | year = | doi = | PMID = 16237810 }}</ref>
*Amiodarone - cardiac arrhythmias.
*Tamoxifen - [[breast cancer]].
*Carbamazepine - seizures.

[[Cholestasis]]:
*Venlafaxine - depression.<ref name=pmid23073329>{{Cite journal | last1 = Stadlmann | first1 = S. | last2 = Portmann | first2 = S. | last3 = Tschopp | first3 = S. | last4 = Terracciano | first4 = LM. | title = Venlafaxine-induced cholestatic hepatitis: case report and review of literature. | journal = Am J Surg Pathol | volume = 36 | issue = 11 | pages = 1724-8 | month = Nov | year = 2012 | doi = 10.1097/PAS.0b013e31826af296 | PMID = 23073329 }}</ref>
*Thalidomide - [[multiple myeloma]].<ref name=pmid22789729>{{Cite journal | last1 = Vilas-Boas | first1 = F. | last2 = Gonçalves | first2 = R. | last3 = Sobrinho Simões | first3 = M. | last4 = Lopes | first4 = J. | last5 = Macedo | first5 = G. | title = Thalidomide-induced acute cholestatic hepatitis: case report and review of the literature. | journal = Gastroenterol Hepatol | volume = 35 | issue = 8 | pages = 560-6 | month = Oct | year = 2012 | doi = 10.1016/j.gastrohep.2012.05.007 | PMID = 22789729 }}</ref>

===Specific drugs===
Acetaminophen:
*Zone 3 necrosis.
**Tx: N-acetylcysteine (NAC).<ref name=pmid19621836>{{cite journal |author=Millea PJ |title=N-acetylcysteine: multiple clinical applications |journal=Am Fam Physician |volume=80 |issue=3 |pages=265–9 |year=2009 |month=August |pmid=19621836 |doi= |url=}}</ref>
***NAC is an endogenous precursor to glutathione.<ref>URL: [http://www.mskcc.org/mskcc/html/69310.cfm http://www.mskcc.org/mskcc/html/69310.cfm]. Accessed on: 19 October 2010.</ref>
**Hepatotoxicity from ''N-acetyl-p-benzoquinoneimine (NAPQI)'' due to depletion of ''glutathione''.<ref name=pmid19621836>{{cite journal |author=Millea PJ |title=N-acetylcysteine: multiple clinical applications |journal=Am Fam Physician |volume=80 |issue=3 |pages=265–9 |year=2009 |month=August |pmid=19621836 |doi= |url=}}</ref>

Methotrexate - chronic use:
*Histology:<ref>{{Ref MacSween|715}}</ref>
**Features of steatohepatitis.
***Zone III steatosis.
***Ballooning degeneration.
**Portal inflammation with mixed population (lymphocytes, macrophages, PMNs).
**Nuclear atypia (hyperchromasia, pleomorphism, vacuolation).
***Described as just nuclear size variation by some.<ref>MG. 23 September 2009.</ref>

==Sign out==
<pre>
LIVER, MEDICAL CORE BIOPSIES:
- MILD STEATOHEPATITIS AND MILD FIBROSIS (1/4).
- MILD TO MODERATE STEATOSIS.

COMMENT:
The findings are compatible with nonalcoholic steatohepatitis (NASH), alcoholic
steatohepatitis (ASH) or drug effect. The steatosis is periportal predominant; this
is not typical for NASH or ASH. Clinical correlation and review of medications
is suggested.
</pre>

==See also==
*[[Medical liver disease]].
*[[Steatohepatitis]].
*[[Cryptogenic cirrhosis]].

==References==
{{Reflist|2}}

==External links==
*[http://livertox.nih.gov Drug-liver toxicity (nih.gov)].

[[Category:Medical liver disease]]

Gallbladder carcinoma

2017-01-03T15:32:22Z

Mitchell: /* Images */ added a case

{{ Infobox diagnosis
| Name = {{PAGENAME}}
| Image = Gallbladder adenocarcinoma (2) histopathology.jpg
| Width =
| Caption = Gallbladder adenocarcinoma. [[H&E stain]].
| Micro = atypical epithelium usually gland forming, may be bland with an infiltrative growth pattern
| Subtypes =
| LMDDx = [[adenomyoma of the gallbladder]], [[metastasis|metastatic carcinoma]] (e.g. [[cholangiocarcinoma]]), [[gallbladder adenoma]]
| Stains =
| IHC = CK7 +ve, CK20 -ve, CDX2 -ve
| EM =
| Molecular =
| IF =
| Gross = lesion - usually fundus of gallbladder
| Grossing =
| Site = [[gallbladder]]
| Assdx = [[chronic cholecystitis]], [[gallstones]], [[primary sclerosing cholangitis]], [[intestinal metaplasia of the gallbladder]]
| Syndromes =
| Clinicalhx =
| Signs =
| Symptoms =
| Prevalence = uncommon
| Bloodwork =
| Rads =
| Endoscopy =
| Prognosis =
| Other =
| ClinDDx =
}}
'''Gallbladder carcinoma''' is a malignant epithelial neoplasm arising from the [[gallbladder]]. Most gallbladder carcinomas are [[adenocarcinoma]]s.

==General==
*Uncommon.

Treatment:
*Cholecystectomy +/- lymph nodes +/- partial hepatectomy.<ref name=pmid20639849>{{Cite journal | last1 = Biswas | first1 = PK. | title = Carcinoma gallbladder. | journal = Mymensingh Med J | volume = 19 | issue = 3 | pages = 477-81 | month = Jul | year = 2010 | doi = | PMID = 20639849 }}</ref>

===Epidemiology===
*Associated with [[gallstones]].
*Increased risk in [[primary sclerosing cholangitis]].
*Sex: female > male.
*Location: usually fundus, sometimes body.

Notes:
*Diffuse calcification of gallbladder wall, [[AKA]] "porcelain gallbladder" is '''not''' associated with carcinoma - based on a series of 10,741 cholecystectomies.<ref name=pmid11206901>{{cite journal |author=Towfigh S, McFadden DW, Cortina GR, ''et al'' |title=Porcelain gallbladder is not associated with gallbladder carcinoma |journal=Am Surg |volume=67 |issue=1 |pages=7?0 |year=2001 |month=January |pmid=11206901 |doi= |url=}}</ref>
**Focal mucosal calcification ''is'' associated with malignancy.<ref name=pmid11391368>{{Cite journal | last1 = Stephen | first1 = AE. | last2 = Berger | first2 = DL. | title = Carcinoma in the porcelain gallbladder: a relationship revisited. | journal = Surgery | volume = 129 | issue = 6 | pages = 699-703 | month = Jun | year = 2001 | doi = 10.1067/msy.2001.113888 | PMID = 11391368 }}</ref>
*[[Cholangiocarcinoma]] is dealt with in the ''[[liver neoplasms]]'' article.

==Gross==
*Classic: mass projecting into the lumen.
*Marked gallbladder wall thickening.
**>10 mm should be considered with suspicion.<ref name=pmid21879282>{{Cite journal | last1 = Kim | first1 = HJ. | last2 = Park | first2 = JH. | last3 = Park | first3 = DI. | last4 = Cho | first4 = YK. | last5 = Sohn | first5 = CI. | last6 = Jeon | first6 = WK. | last7 = Kim | first7 = BI. | last8 = Choi | first8 = SH. | title = Clinical usefulness of endoscopic ultrasonography in the differential diagnosis of gallbladder wall thickening. | journal = Dig Dis Sci | volume = 57 | issue = 2 | pages = 508-15 | month = Feb | year = 2012 | doi = 10.1007/s10620-011-1870-0 | PMID = 21879282 }}</ref>

Image:
*[http://www.flickr.com/photos/santoshpath/5245332515/ Papillary gallbladder adenocarcinoma (flickr.com)].
==Microscopic==
Features:
*Usually adenocarcinoma.
**Mimics appearance of [[pancreatic ductal adenocarcinoma]] -- but less cellular mucin.<ref name=Ref_DCHH174>{{Ref DCHH|174}}</ref>

Notes:
*May be very subtle, i.e. difficult to differentiate from normal glands.
**"Deep glands" that look bland shouldn't immediately be dismissed as benign.

Subtypes:
*[[Mucinous carcinoma]].<ref name=pmid23106580/>

DDx:
*[[Adenomyoma of the gallbladder]].
*[[Gallbladder adenoma]].
*[[metastasis|Metastatic carcinoma]].
**[[Cholangiocarcinoma]].
*[[Chronic cholecystitis]] with glands extending deep into the wall.

===Images===
<gallery>
Image:Gallbladder_adenocarcinoma_(1)_histopathology.jpg | GB carcinoma - low mag. (WC)
Image:Gallbladder adenocarcinoma (2) histopathology.jpg | GB carcinoma - high mag. (WC)
Image:Gallbladder adenocarcinoma (3) lymphatic invasion histopathology.jpg | GB carcinoma - LVI. (WC)
</gallery>
www:
*[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3285085/figure/F1/ Mimics of GB carcinoma (nih.gov)].<ref name=pmid22284391>{{Cite journal | last1 = Giang | first1 = TH. | last2 = Ngoc | first2 = TT. | last3 = Hassell | first3 = LA. | title = Carcinoma involving the gallbladder: a retrospective review of 23 cases - pitfalls in diagnosis of gallbladder carcinoma. | journal = Diagn Pathol | volume = 7 | issue = | pages = 10 | month = | year = 2012 | doi = 10.1186/1746-1596-7-10 | PMID = 22284391 }}</ref>
*[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3285085/figure/F2/ Dysplasia in RA sinuses (nih.gov)].
[[File:5 42027008799505 sl 1.png| Moderately differentiated adenocarcinoma of gallbladder]]
[[File:5 42027008799505 sl 2.png| Moderately differentiated adenocarcinoma of gallbladder]]
[[File:5 42027008799505 sl 3.png| Moderately differentiated adenocarcinoma of gallbladder]]
[[File:5 42027008799505 sl 4.png| Moderately differentiated adenocarcinoma of gallbladder]]
[[File:5 42027008799505 sl 5.png| Moderately differentiated adenocarcinoma of gallbladder]]
[[File:5 42027008799505 sl 6.png| Moderately differentiated adenocarcinoma of gallbladder]] 
Moderately differentiated adenocarcinoma of gallbladder in a 59 year old man. A. Tumor bounds cystic duct. B. Cystic duct at left shows high grade dysplasia. At right lie acini and nests of round and sometimes spindled cancerous nuclei. Overall most of the tumor was in tubules/acini, meaning the lesion is moderately differentiated. C. Region with Rokitansky-Aschoff sinuses showing high grade dysplasia and foci of intestinal metaplasia, with some nests likely being invasive cancer. D. Tumorous involvement of cystic duct lymph node. E. Bizarrely shaped cancerous groups. F. invasion of liver by neoplastic acini.

==IHC==
Features - conventional:<ref name=pmid23106580>{{Cite journal | last1 = Dursun | first1 = N. | last2 = Escalona | first2 = OT. | last3 = Roa | first3 = JC. | last4 = Basturk | first4 = O. | last5 = Bagci | first5 = P. | last6 = Cakir | first6 = A. | last7 = Cheng | first7 = J. | last8 = Sarmiento | first8 = J. | last9 = Losada | first9 = H. | title = Mucinous carcinomas of the gallbladder: clinicopathologic analysis of 15 cases identified in 606 carcinomas. | journal = Arch Pathol Lab Med | volume = 136 | issue = 11 | pages = 1347-58 | month = Nov | year = 2012 | doi = 10.5858/arpa.2011-0447-OA | PMID = 23106580 }}</ref>
*CK7 +ve (7 of 8 cases).
*CK20 -ve (7 of 8 cases).
*CDX2 -ve (8 of 8 cases).

==See also==
*[[Gallbladder]].
*[[Intestinal metaplasia of the gallbladder]].

==References==
{{Reflist|2}}

[[Category:Diagnosis]]
[[Category:Gallbladder]]

Colorectal adenocarcinoma

2017-01-02T18:29:43Z

Mitchell: /* Images */ added a medullary carcinoma

{{ Infobox diagnosis
| Name = {{PAGENAME}}
| Image = Colorectal adenocarcinoma - alt -- intermed mag.jpg
| Width =
| Caption = Colorectal adenocarcinoma. [[H&E stain]].
| Micro =
| Subtypes =
| LMDDx = other [[adenocarcinoma]]s (e.g. [[anal gland adenocarcinoma]], [[lung adenocarcinoma]], [[ovarian adenocarcinoma]]), [[traditional adenoma]] esp. with high-grade dysplasia, [[sessile serrated adenoma]] with dysplasia
| Stains =
| IHC = CK20 +ve, CDX2 +ve, CK7 -ve, beta-catenin (nuclear) +ve
| EM =
| Molecular =
| IF =
| Gross =
| Grossing = [[lower anterior resection for cancer grossing]], other protocols
| Staging = [[colorectal cancer staging]]
| Site = [[rectum]], [[colon]], [[cecum]], [[appendix]]
| Assdx = long standing IBD ([[Crohn's disease]], [[ulcerative colitis]]), [[traditional adenoma]] esp. with high-grade dysplasia, [[sessile serrated adenoma]] esp. with dysplasia
| Syndromes = [[familial adenomatous polyposis]], [[Lynch syndrome]], [[Peutz-Jeghers syndrome]], [[Juvenile polyposis syndrome]], [[serrated polyposis syndrome]], [[MUTYH polyposis syndrome]], [[Cowden syndrome]]
| Clinicalhx =
| Signs = +/-blood in stools, +/-abdominal mass, +/-rectal mass, +/-signs of bowel obstruction (nausea, vomiting), +/-narrow caliber stools
| Symptoms = +/-constipation
| Prevalence = common
| Bloodwork = +/-[[anemia]] (microcytic), +/-CEA elevated
| Rads = +/-"apple core" lesion (classic), +/-findings of bowel obstruction (air-fluid levels esp. with transition point)
| Endoscopy = +/-suspicious mass (exophytic or ulcerated), presence of non-lifting sign, [[Kudo pit pattern]] Type VI or Type VN
| Prognosis = good to poor
| Other = fecal occult blood test (FOBT) +ve
| ClinDDx = [[colorectal tumours]], other causes - DDx dependent on presentation
| Tx = usually surgical resection +/-chemotherapy +/-radiation
}}
'''Colorectal adenocarcinoma''' is very common, a leading cause of death due to [[cancer]], and the most common form of colon cancer.

The [[colon]] and [[rectum]] are lumped together as the mucosa in the large bowel is very similar. Thus, '''colonic adenocarcinoma''' and '''rectal adenocarcinoma''' redirect to this article.

The larger generally topic of [[colorectal tumours]] and the pathogenesis of colorectal adenocarcinoma is dealt with in the [[colorectal tumours]] article.

'''Colorectal carcinoma''', abbreviated '''CRC''', is typically considered a synonym. '''Cecal adenocarcinoma''' is also lumped into CRC.

==General==
*Very common.
*Rectum and sigmoid > proximal large bowel.

Presentation:
*[[Bright red blood per rectum]] (BRBPR).
*Constipation.
*Symptoms of bowel obstruction - nausea, vomiting.

Pathogenesis - see ''[[Colorectal_tumours#Pathogenesis_of_colorectal_carcinoma|pathogenesis of colorectal carcinoma]]''.

Clinical - serum:
*CEA elevated.<ref name=pmid24379990>{{Cite journal | last1 = Bagaria | first1 = B. | last2 = Sood | first2 = S. | last3 = Sharma | first3 = R. | last4 = Lalwani | first4 = S. | title = Comparative study of CEA and CA19-9 in esophageal, gastric and colon cancers individually and in combination (ROC curve analysis). | journal = Cancer Biol Med | volume = 10 | issue = 3 | pages = 148-57 | month = Sep | year = 2013 | doi = 10.7497/j.issn.2095-3941.2013.03.005 | PMID = 24379990 }}</ref>
*CA19-9 elevated.
*Colon cancer-specific antigen-2 (CCSA-2) elevated.<ref name=pmid24710115>{{Cite journal | last1 = Xue | first1 = G. | last2 = Wang | first2 = X. | last3 = Yang | first3 = Y. | last4 = Liu | first4 = D. | last5 = Cheng | first5 = Y. | last6 = Zhou | first6 = J. | last7 = Cao | first7 = Y. | title = Colon cancer-specific antigen-2 may be used as a detecting and prognostic marker in colorectal cancer: a preliminary observation. | journal = PLoS One | volume = 9 | issue = 4 | pages = e94252 | month = | year = 2014 | doi = 10.1371/journal.pone.0094252 | PMID = 24710115 }}</ref>
**Relatively new; ''preliminary'' in 2014.

==Gross==
Often circumferential or near circumferential:
*These are referred to as "apple core lesion" ''or'' "napkin-ring" lesion.

Mucosa:
*Granular appearance.
*Raised (exophytic) ''or'' heaped edges with ulceration.

Note:
*''Total mesorectal excisions'' should be assessed for completeness.
*The (soft tissue) radial margins, as present in TMEs and right hemicolectomies, should be inked.<ref>URL: [http://www.cancercare.on.ca/common/pages/UserFile.aspx?fileId=13954 http://www.cancercare.on.ca/common/pages/UserFile.aspx?fileId=13954]. Accessed on: 6 February 2013. </ref><ref name=pmid15790712>{{Cite journal | last1 = Bateman | first1 = AC. | last2 = Carr | first2 = NJ. | last3 = Warren | first3 = BF. | title = The retroperitoneal surface in distal caecal and proximal ascending colon carcinoma: the Cinderella surgical margin? | journal = J Clin Pathol | volume = 58 | issue = 4 | pages = 426-8 | month = Apr | year = 2005 | doi = 10.1136/jcp.2004.019802 | PMID = 15790712 }}</ref>

===Images===
<gallery>
Image:Colon_cancer.jpg | CRC - gross. (WC)
Image:Colon_cancer_2.jpg | CRC - gross. (WC)
</gallery>
<gallery>
Image:Rectum - anterior view.jpg | Rectum - anterior view. (WC)
Image:Rectum - lateral_view.jpg | Rectum - lateral view. (WC)
Image:Rectum - anterior and lateral - inked.jpg| Rectum - inked. (WC)
Image:Rectum - opened.jpg | Rectum - opened (WC)
</gallery>

==Microscopic==
Features:
*Nuclear atypia:
**Nuclear pseudostratification.
**Nuclear hyperchromasia.
**Chromatin clearing or granularity.
*+/-Necrosis.
*Architecture - important for grading:
**Glands.
**Sheets.

DDx:
*Other [[adenocarcinoma]]s (e.g. [[anal gland adenocarcinoma]], [[lung adenocarcinoma]], [[ovarian adenocarcinoma]], [[ductal adenocarcinoma of the prostate]]).
*[[Traditional adenoma]] esp. with high-grade dysplasia.
*[[Sessile serrated adenoma]] with dysplasia.

===Images===
<gallery>
Image: Colorectal adenocarcinoma -- low mag.jpg | CRC - low mag. (WC)
Image: Colorectal adenocarcinoma -- intermed mag.jpg | CRC - intermed. mag. (WC)
Image: Colorectal adenocarcinoma -- high mag.jpg | CRC - high mag. (WC)
</gallery>
<gallery>
Image: Colorectal adenocarcinoma - alt -- low mag.jpg | CRC - low mag. (WC)
Image: Colorectal adenocarcinoma - alt -- intermed mag.jpg | CRC - intermed. mag. (WC)
Image: Colorectal adenocarcinoma - alt -- high mag.jpg | CRC - high mag. (WC)
</gallery>
<gallery>
Image:Colonic_mucinous_adenocarcinoma_-_very_low_mag.jpg | [[Mucinous adenocarcinoma]] - very low mag. (WC/Nephron)
Image:Colonic_mucinous_adenocarcinoma_-_low_mag.jpg | Mucinous adenocarcinoma - low mag. (WC/Nephron)
</gallery>
<gallery>
Image:Cecal adenocarcinoma.jpg | Cecal adenocarcinoma. (WC/Nephron)
Image:Adenocarcinoma_coli.jpg | Colorectal adenocarcinoma. (WC)
Image:Crc_met_to_node1.jpg | CRC [[lymph node metastasis]]. (WC/Nephron)
</gallery>
[[File:3 13657755265018 sl 1.png|Medullary carcinoma of cecum.]]
[[File:3 13657755265018 sl 2.png|Medullary carcinoma of cecum.]]
[[File:3 13657755265018 sl 3.png|Medullary carcinoma of cecum.]]
[[File:3 13657755265018 sl 4.png|Medullary carcinoma of cecum.]] 
Medullary carcinoma of cecum of elderly woman. A. Tumor extends from the luminal surface at upper left into the muscularis propria at lower right. Note variable longitudinal spaces in the tumor. B. Tumor extends into pericolic fat. Note relative circumscription, with pushing borders. C. Tumor cells, often in seeming syncitiums, strew lymphocytes. D. In other areas, there appears to be a pattern suggesting nests and stromal trabeculums. Chromogranin/synaptophysin were negative.

www:
*[http://www.flickr.com/photos/euthman/2480926690/in/set-72057594114099781 Colorectal adenocarcinoma (flickr.com/euthman)].

===Grading===
Based on component composed of glands:
*>=50% of tumour = low-grade (''well-differentiated'' and ''moderately differentiated'').
*<50% of tumour = high-grade (''poorly-differentiated'' and ''undifferentiated'').

===Peritumoural lymphocytic response===
*[[AKA]] ''Crohn's-like lymphoid reaction''.
*[[AKA]] ''Crohn's like reaction''.<ref name=pmid19825961>{{Cite journal | last1 = Ogino | first1 = S. | last2 = Nosho | first2 = K. | last3 = Irahara | first3 = N. | last4 = Meyerhardt | first4 = JA. | last5 = Baba | first5 = Y. | last6 = Shima | first6 = K. | last7 = Glickman | first7 = JN. | last8 = Ferrone | first8 = CR. | last9 = Mino-Kenudson | first9 = M. | title = Lymphocytic reaction to colorectal cancer is associated with longer survival, independent of lymph node count, microsatellite instability, and CpG island methylator phenotype. | journal = Clin Cancer Res | volume = 15 | issue = 20 | pages = 6412-20 | month = Oct | year = 2009 | doi = 10.1158/1078-0432.CCR-09-1438 | PMID = 19825961 }}</ref>
*[[AKA]] ''Crohn-like response''.<ref>URL: [http://www.cap.org/apps/docs/committees/cancer/cancer_protocols/2012/Colon_12protocol_3200.pdf http://www.cap.org/apps/docs/committees/cancer/cancer_protocols/2012/Colon_12protocol_3200.pdf]. Accessed on: 14 September 2012.</ref>
{{Main|Peritumoural lymphocytic response}}

===Intratumoural lymphocytic response===
*[[AKA]] '' tumour-infiltrating lymphocytes'', abbreviated ''TILs''.
{{Main|Intratumoural lymphocytic response in colorectal carcinoma}}

===Tumour deposits===
*[[AKA]] ''discoutinuous extramural extension''.
*[[AKA]] ''peritumoral deposits''.
{{Main|Tumour deposit}}

===Tumour regression===
There is a three tiered regression grading system by Ryan ''et al''. for colorectal cancer that has essentially been adopted by [[CAP]]:<ref name=pmid16045774>{{Cite journal | last1 = Ryan | first1 = R. | last2 = Gibbons | first2 = D. | last3 = Hyland | first3 = JM. | last4 = Treanor | first4 = D. | last5 = White | first5 = A. | last6 = Mulcahy | first6 = HE. | last7 = O'Donoghue | first7 = DP. | last8 = Moriarty | first8 = M. | last9 = Fennelly | first9 = D. | title = Pathological response following long-course neoadjuvant chemoradiotherapy for locally advanced rectal cancer. | journal = Histopathology | volume = 47 | issue = 2 | pages = 141-6 | month = Aug | year = 2005 | doi = 10.1111/j.1365-2559.2005.02176.x | PMID = 16045774 }}</ref>
{| class="wikitable sortable"
! Grade
! Features
|-
| Grade 1
| small groups of tumour cells or single tumour cells
|-
| Grade 2
| definite tumour but more fibrosis ("cancer outgrown by fibrosis")
|-
| Grade 3
| definite tumour with no fibrosis ''or'' tumour with a lesser amount of fibrosis ("fibrosis outgrown by cancer")
|}

==IHC==
*CK7 -ve. ‡
*CK20 +ve.
*CEA +ve.
*CDX2 +ve.

Note:
* ‡ High stage colorectal cancer (CRC) may be CK7 +ve/CK20 +ve; in one series, 13% of stage 3 and 17% of stage 4 colorectal cancers were CK7 +ve/CK20 +ve.<ref name=pmid15791572>{{Cite journal | last1 = Hernandez | first1 = BY. | last2 = Frierson | first2 = HF. | last3 = Moskaluk | first3 = CA. | last4 = Li | first4 = YJ. | last5 = Clegg | first5 = L. | last6 = Cote | first6 = TR. | last7 = McCusker | first7 = ME. | last8 = Hankey | first8 = BF. | last9 = Edwards | first9 = BK. | title = CK20 and CK7 protein expression in colorectal cancer: demonstration of the utility of a population-based tissue microarray. | journal = Hum Pathol | volume = 36 | issue = 3 | pages = 275-81 | month = Mar | year = 2005 | doi = 10.1016/j.humpath.2005.01.013 | PMID = 15791572 }}</ref>

==Molecular==
*[[KRAS mutation]] analysis.
**Mutation present ~ 40% of [[CRC]].
**Mutations in codons 12 or 13 associated with failure of [[EGFR inhibitors|anti-EGFR therapy]] (e.g. ''cetuximab'', ''panitumumab'').<ref name=pmid19792050>{{Cite journal | last1 = Monzon | first1 = FA. | last2 = Ogino | first2 = S. | last3 = Hammond | first3 = ME. | last4 = Halling | first4 = KC. | last5 = Bloom | first5 = KJ. | last6 = Nikiforova | first6 = MN. | title = The role of KRAS mutation testing in the management of patients with metastatic colorectal cancer. | journal = Arch Pathol Lab Med | volume = 133 | issue = 10 | pages = 1600-6 | month = Oct | year = 2009 | doi = 10.1043/1543-2165-133.10.1600 | PMID = 19792050 }}</ref>
*BRAF mutation analysis.
**''V600E'' missense mutation found in ~10% CRC.<ref name=pmid20635392>{{cite journal |author=Tie J, Gibbs P, Lipton L, ''et al.'' |title=Optimizing targeted therapeutic development: Analysis of a colorectal cancer patient population with the BRAF(V600E) mutation |journal=Int J Cancer |volume= |issue= |pages= |year=2010 |month=July |pmid=20635392 |doi=10.1002/ijc.25555 |url=}}</ref>

Note:
*KRAS mutations and BRAF mutations are considered mutually exclusive as they occur in the same pathway.

==Sign out==
===Right hemicolectomy===
<pre>
TERMINAL ILEUM, CECUM, ASCENDING COLON AND APPENDIX, RIGHT HEMICOLECTOMY:
- INVASIVE ADENOCARCINOMA, LOW-GRADE, pT2, pN0.
-- MARGINS NEGATIVE FOR DYSPLASIA AND NEGATIVE FOR MALIGNANCY.
-- PLEASE SEE TUMOUR SUMMARY.
- SMALL BOWEL WALL WITHIN NORMAL LIMITS.
- APPENDIX WITHOUT SIGNIFICANT PATHOLOGY.
- TWELVE LYMPH NODES NEGATIVE FOR MALIGNANCY ( 0 POSITIVE / 12 ).
</pre>

====Mucinous component present====
<pre>
TERMINAL ILEUM, CECUM, ASCENDING COLON AND APPENDIX, RIGHT HEMICOLECTOMY:
- INVASIVE ADENOCARCINOMA WITH A MUCINOUS COMPONENT, LOW-GRADE, pT1, pN0.
-- MARGINS NEGATIVE FOR DYSPLASIA AND NEGATIVE FOR MALIGNANCY.
-- PLEASE SEE TUMOUR SUMMARY.
- SMALL BOWEL WALL WITHIN NORMAL LIMITS.
- APPENDIX WITHOUT SIGNIFICANT PATHOLOGY.
- FOURTEEN LYMPH NODES NEGATIVE FOR MALIGNANCY ( 0 POSITIVE / 14 ).
</pre>

===Left hemicolectomy===
<pre>
LEFT COLON, LEFT HEMICOLECTOMY:
- INVASIVE ADENOCARCINOMA, LOW-GRADE, pT1, pN0.
-- MARGINS NEGATIVE FOR DYSPLASIA AND NEGATIVE FOR MALIGNANCY.
-- TWELVE LYMPH NODES NEGATIVE FOR MALIGNANCY ( 0 POSITIVE / 12 ).
-- PLEASE SEE TUMOUR SUMMARY.
</pre>

==See also==
*[[Colon]].
*[[Colorectal tumours]].

==References==
{{Reflist|2}}

[[Category:Diagnosis]]
[[Category:Colorectal tumours]]

Pleomorphic undifferentiated sarcoma

2017-01-02T18:04:49Z

Mitchell: /* Images */ added a case

{{ Infobox diagnosis
| Name = {{PAGENAME}}
| Image = Pleomorphic_undifferentiated_sarcoma_-_very_high_mag.jpg
| Width =
| Caption = Pleomorphic undifferentiated sarcoma. [[H&E stain]].
| Synonyms = undifferentiated pleomorphic sarcoma (UPS), malignant fibrous histiocytoma (MFH)
| Micro = storiform pattern ([[AKA]] ''patternless pattern''), marked [[nuclear pleomorphism]], mitoses, necrosis (common), mix of spindle cells and epithelioid cells, deep to skin
| Subtypes =
| LMDDx = [[atypical fibroxanthoma]] (superficial), [[dedifferentiated liposarcoma]], [[leiomyosarcoma]],[[metaplastic carcinoma]], [[malignant melanoma]], [[rhabdomyosarcoma]], [[synovial sarcoma]],[[undifferentiated endometrial sarcoma]], others
| Stains =
| IHC =
| EM =
| Molecular =
| IF =
| Gross =
| Grossing =
| Site = deep [[soft tissue lesion|soft tissue]] - trunk and extremities
| Assdx =
| Syndromes =
| Clinicalhx =
| Signs =
| Symptoms =
| Prevalence = uncommon overall
| Bloodwork =
| Rads =
| Endoscopy =
| Prognosis = poor
| Other =
| ClinDDx =
| Tx = surgery if feasible
}}
'''Pleomorphic undifferentiated sarcoma''', abbreviated '''PUS''', is an undifferentiated malignant [[soft tissue lesion]].

It is also known as '''undifferentiated pleomorphic sarcoma''' (abbreviated '''UPS'''). Previously, it was known as '''malignant fibrous histiocytoma''', commonly abbreviated '''MFH'''.<ref>URL: [http://sarcomahelp.org/learning_center/mfh.html http://sarcomahelp.org/learning_center/mfh.html]. Accessed on: 8 April 2011.</ref>

==General==
*Common sarcoma.
*Usually deep tissue of the trunk and extremities.
*A diagnosis of exclusion<ref name=pmid19671033>{{cite journal |author=Matushansky I, Charytonowicz E, Mills J, Siddiqi S, Hricik T, Cordon-Cardo C |title=MFH classification: differentiating undifferentiated pleomorphic sarcoma in the 21st Century |journal=Expert Rev Anticancer Ther |volume=9 |issue=8 |pages=1135–44 |year=2009 |month=August |pmid=19671033 |pmc=3000413 |doi=10.1586/era.09.76 |url=}}</ref> / wastebasket for unclassifiable high grade sarcomas.

==Microscopic==
Features:<ref name=Ref_WMSP_613>{{Ref WMSP|613}}</ref>
*Storiform pattern ([[AKA]] ''patternless pattern'') - '''key feature'''.
*Marked [[nuclear pleomorphism]] '''key feature'''.
**Variation is nuclear size, nuclear shape and nuclear staining (esp. hyperchromasia).
*Mitoses - abundant; atypical mitoses common.
*Necrosis (common).
*Mix of spindle cells and epithelioid cells.
*Deep to skin - '''important'''.

Other findings:
*+/-Giant cells (see subclassification).
*+/-Inflammation (see subclassification).
**Neutrophils.
**Eosinophils.

Notes:
*Superficial lesions with the morphology of ''PUS'' are called by some ''[[atypical fibroxanthoma]]s'' (AFXs).

DDx:
*[[Atypical fibroxanthoma]] (AFX) - superficial skin.
*[[Dedifferentiated liposarcoma]].
*[[Leiomyosarcoma]].
*[[Metaplastic carcinoma]].
*[[Malignant melanoma]].
*[[Rhabdomyosarcoma]].
*[[Synovial sarcoma]].
*[[Undifferentiated endometrial sarcoma]] - uterus.
*Others.

===Images===
<gallery>
Image:Pleomorphic_undifferentiated_sarcoma_-_very_high_mag.jpg | PUS - high mag. (WC/Nephron)
Image:Pleomorphic_undifferentiated_sarcoma_-_intermed_mag.jpg | PUS - intermed. mag. (WC/Nephron)
</gallery>
[[File:3 13646052598462 sl 1.png|Pleomorphic sarcoma]]
[[File:3 13646052598462 sl 2.png|Pleomorphic sarcoma]]
[[File:3 13646052598462 sl 3.png|Pleomorphic sarcoma]]
[[File:3 13646052598462 sl 4.png|Pleomorphic sarcoma]] 
Pleomorphic sarcoma in thigh of late middle aged man. A. Tumor haphazardly spreads and invades and surrounds degenerated skeletal muscle fibers. B. Bizarre, sometimes multinucleated cells are seen. C. In other areas, spindle cells predominate. D. Invasion of adipose tissue by tumor should not be interpreted as proof of dedifferentiated liposarcoma; lipoblasts should be seen. Vital is remembering this is a diagnosis of exclusion, with negative keratin, CD34, CD30, S100, and CD31 stains being suggested.

===Subclassification===
Pleomorphic sarcoma (PS) is subclassified the following way:<ref name=Ref_WMSP_613-4>{{Ref WMSP|613-4}}</ref>
*PS with giant cells.
*PS with inflammation.
*PUS (not otherwise specified) - wastebasket diagnosis; if neither of the above two apply.

==IHC==
Exclusionary stains - should be negative:
*AE1/AE3.
*p63.
*Myogenin.
*S-100.
*HMB-45.

Usually negative, may be positive:<ref name=Ref_WMSP613>{{Ref WMSP|613}}</ref>
*Desmin.
*SMA.

Commonly positive:
*CD68.<ref name=Ref_WMSP613>{{Ref WMSP|613}}</ref>
*Vimentin.

==See also==
*[[Sarcoma]].

==References==
{{Reflist|2}}

[[Category:Diagnosis]]
[[Category:Soft tissue lesions]]

Juvenile granulosa cell tumour

2017-01-02T17:43:50Z

Mitchell: /* Images */ added a case

{{ Infobox diagnosis
| Name = {{PAGENAME}}
| Image = Juvenile_granulosa_cell_tumour_-_very_high_mag.jpg
| Width =
| Caption = Juvenile granulosa cell tumour. [[H&E stain]].
| Synonyms =
| Micro = microcystic spaces, cuboidal-to-polygonal cells in sheets or stands or cords, with moderate-to-marked nuclear atypia, and basophilic cytoplasm
| Subtypes =
| LMDDx = [[Brenner tumour]], [[small cell carcinoma of hypercalcemic type]]
| Stains =
| IHC = inhibin +ve, calretinin +ve
| EM =
| Molecular = trisomy 12
| IF =
| Gross = mass lesion, solid
| Grossing =
| Site = [[ovary]] - ''[[ovarian tumours]]''
| Assdx = [[endometrial hyperplasia]], [[endometrioid endometrial carcinoma]]
| Syndromes =
| Clinicalhx =
| Signs =
| Symptoms = +/-menorrhagia
| Prevalence = uncommon
| Bloodwork =
| Rads =
| Endoscopy =
| Prognosis = good to moderate (dependent on stage)
| Other =
| ClinDDx =
| Tx = surgery
}}
'''Juvenile granulosa cell tumour''' is an uncommon [[ovarian tumour]] in the ''sex cord stromal tumours'' group.

==General==
*Uncommon.<ref name=pmid23033282>{{Cite journal | last1 = Oztekin | first1 = D. | last2 = Kurt | first2 = S. | last3 = Camuzcuoglu | first3 = H. | last4 = Balsak | first4 = D. | last5 = Dicle | first5 = N. | last6 = Tinar | first6 = S. | title = Granulosa cell tumors of the ovary: review of 43 cases. | journal = J BUON | volume = 17 | issue = 3 | pages = 461-4 | month = | year = | doi = | PMID = 23033282 }}</ref>
*Reported in males.<ref>URL: [http://path.upmc.edu/cases/case631.html http://path.upmc.edu/cases/case631.html]. Accessed on: 26 January 2012.</ref>

May secrete estrogen - can present with:
*Endometrial pathology, e.g. [[endometrial hyperplasia]] ''or'' endometrioid [[endometrial carcinoma]].
*Precocious puberty.<ref name=pmid21526089>{{Cite journal | last1 = Hashemipour | first1 = M. | last2 = Moaddab | first2 = MH. | last3 = Nazem | first3 = M. | last4 = Mahzouni | first4 = P. | last5 = Salek | first5 = M. | title = Granulosa cell tumor in a six-year-old girl presented as precocious puberty. | journal = J Res Med Sci | volume = 15 | issue = 4 | pages = 240-2 | month = Jul | year = 2010 | doi = | PMID = 21526089 }}</ref>

Prognosis - granulosa cell tumours (adult and juvenile):<ref name=pmid23033282/>
*Low-stage: 97% five year survival.
*High-stage: 67% five year survival.

==Gross==
*Classically solid.

==Microscopic==
Features:
*Microcystic spaces.
*Moderate-to-marked nuclear atypia.
*Cuboidal-to-polygonal cell in sheets or stands or cords.
*Basophilic cytoplasm.

Notes:
*Juvenile variant of GCT has more nuclear pleomorphism.

DDx:
*[[Brenner tumour]].
*[[Adult granulosa cell tumour]].
*[[Small cell carcinoma of hypercalcemic type]].<ref name=pmid21993272>{{Cite journal | last1 = Bárcena | first1 = C. | last2 = Oliva | first2 = E. | title = WT1 expression in the female genital tract. | journal = Adv Anat Pathol | volume = 18 | issue = 6 | pages = 454-65 | month = Nov | year = 2011 | doi = 10.1097/PAP.0b013e318234aaed | PMID = 21993272 }}</ref>

===Images===
<gallery>
Image:Juvenile_granulosa_cell_tumour_-_intermed_mag.jpg | Juvenile granulosa cell tumour - intermed. mag. (WC)
Image:Juvenile_granulosa_cell_tumour_-_high_mag.jpg | Juvenile granulosa cell tumour - high mag. (WC)
Image:Juvenile_granulosa_cell_tumour_-_very_high_mag.jpg | Juvenile granulosa cell tumour - very high mag. (WC)
</gallery>
[[File:3 13627319654987 sl 1.png| Juvenile granulosa cell tumor]]
[[File:3 13627319654987 sl 2.png| Juvenile granulosa cell tumor]]
[[File:3 13627319654987 sl 3.png| Juvenile granulosa cell tumor]]
[[File:3 13627319654987 sl 4.png| Juvenile granulosa cell tumor]]
Juvenile granulosa cell tumor of ovary of child. A. A pink tumor shows cyst-like areas with occasional nodules at low power. B. Tumor cells haphazardly spread without longitudinal grooves, with small nucleoli, in an edematous background. C. The cysts are in fact follicles, some producing, as here, the typical basophilic fluid. D. In some regions, abundant pink cytoplasm is obvious.

==IHC==
* Inhibin positive.<ref name=Ref_PBoD1102>{{Ref PBoD|1102}}</ref>
** Inhibin negative in ''[[Brenner tumour]]''.
*Calretinin +ve.
*Ki-67 <5% (12/12 cases<ref name=pmid20349790>{{Cite journal | last1 = Kondi-Pafiti | first1 = A. | last2 = Grapsa | first2 = D. | last3 = Kairi-Vassilatou | first3 = E. | last4 = Carvounis | first4 = E. | last5 = Hasiakos | first5 = D. | last6 = Kontogianni | first6 = K. | last7 = Fotiou | first7 = S. | title = Granulosa cell tumors of the ovary: a clinicopathologic and immunohistochemical study of 21 cases. | journal = Eur J Gynaecol Oncol | volume = 31 | issue = 1 | pages = 94-8 | month = | year = 2010 | doi = | PMID = 20349790 }}</ref>).
*CD34 -ve (0 +ve/12 cases<ref name=pmid20349790/>).
*Vimentin +ve (11 +ve/12 cases<ref name=pmid20349790/>).
*CD99 +ve.<ref name=pmid17387475>{{Cite journal | last1 = Schmidt | first1 = D. | last2 = Kommoss | first2 = F. | title = [Diagnosis and differential diagnosis of granulosa cell tumor]. | journal = Pathologe | volume = 28 | issue = 3 | pages = 195-202 | month = May | year = 2007 | doi = 10.1007/s00292-007-0908-8 | PMID = 17387475 }}</ref>

==Molecular==
:''Currently '''not''' used for the diagnosis.''
*Trisomy 12.<ref name=pmid1466394>{{Cite journal | last1 = Schofield | first1 = DE. | last2 = Fletcher | first2 = JA. | title = Trisomy 12 in pediatric granulosa-stromal cell tumors. Demonstration by a modified method of fluorescence in situ hybridization on paraffin-embedded material. | journal = Am J Pathol | volume = 141 | issue = 6 | pages = 1265-9 | month = Dec | year = 1992 | doi = | PMID = 1466394 }}</ref><ref name=pmid12218213>{{Cite journal | last1 = Mayr | first1 = D. | last2 = Kaltz-Wittmer | first2 = C. | last3 = Arbogast | first3 = S. | last4 = Amann | first4 = G. | last5 = Aust | first5 = DE. | last6 = Diebold | first6 = J. | title = Characteristic pattern of genetic aberrations in ovarian granulosa cell tumors. | journal = Mod Pathol | volume = 15 | issue = 9 | pages = 951-7 | month = Sep | year = 2002 | doi = 10.1097/01.MP.0000024290.55261.14 | PMID = 12218213 }}
</ref>

==See also==
*[[Ovarian tumours]].

==References==
{{Reflist|2}}

[[Category:Ovarian tumours]]
[[Category:Diagnosis]]

Bile duct adenoma

2017-01-02T15:21:46Z

Mitchell: /* Images */ added a case

'''Bile duct adenoma''' is a benign liver lesion characterized composed of bile duct epithelium.

It is also known as a '''benign bile duct proliferation'''.<ref name=pmid24592348>{{Cite journal | last1 = Johannesen | first1 = EJ. | last2 = Wu | first2 = Z. | last3 = Holly | first3 = JS. | title = Bile duct adenoma with oncocytic features. | journal = Case Rep Pathol | volume = 2014 | issue = | pages = 282010 | month = | year = 2014 | doi = 10.1155/2014/282010 | PMID = 24592348 }}</ref>

==General==
*Benign.
*Important as it can be misdiagnosed as [[cancer]].

==Microscopic==
Features:
*Disordered bile ducts within in a fibrotic stroma.
**'''No''' (yellow) bile within, as these lesions do not have a connection to the biliary tree.
**+/-Lymphocytic cuff.<ref>URL: [http://www.surgpath4u.com/caseviewer.php?case_no=152 http://www.surgpath4u.com/caseviewer.php?case_no=152]. Accessed on: 6 March 2014.</ref>

Negatives:
*No mitotic activity.
*No necrosis.

DDx:
*[[Cholangiocarcinoma]].
*Metastatic adenocarcinoma.
**[[Pancreatic ductal adenocarcinoma]].<ref name=pmid15725808>{{Cite journal | last1 = Hornick | first1 = JL. | last2 = Lauwers | first2 = GY. | last3 = Odze | first3 = RD. | title = Immunohistochemistry can help distinguish metastatic pancreatic adenocarcinomas from bile duct adenomas and hamartomas of the liver. | journal = Am J Surg Pathol | volume = 29 | issue = 3 | pages = 381-9 | month = Mar | year = 2005 | doi = | PMID = 15725808 }}</ref>
*[[Bile duct hamartoma]] (von Meyenburg complex).

===Images===
*[http://www.ganfyd.org/index.php?title=Image:Bile_duct_adenoma_low_power.jpg Bile duct adenoma (ganfyd.org)].
*[http://www.surgpath4u.com/caseviewer.php?case_no=152 Bile duct adenoma (surgpath4u.com)].
*[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3926226/figure/fig1/ Bile duct adenoma - oncocytic - low mag. (nih.gov)].<ref name=pmid24592348/>
*[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3926226/figure/fig2/ Bile duct adenoma - oncocytic - high mag. (nih.gov)].<ref name=pmid24592348/>

[[File:5 2033397936391 sl 1.png|Bile duct adenoma]]
[[File:5 2033397936391 sl 2.png|Bile duct adenoma]]
[[File:5 2033397936391 sl 3.png|Bile duct adenoma]]
[[File:5 2033397936391 sl 4.png|Bile duct adenoma]]
[[File:5 2033397936391 sl 5.png|Bile duct adenoma]] 
Bile duct adenoma in a 67 yo man, not radiologically detected; this is important because cholangiocarcinomas are larger than bile duct adenomas. Bile duct adenomas are usually incidental findings, as in this case. These can be very difficult diagnosis; this case was evaluated by outside consultation. A. Glandular proliferation is seen. Note the curve indicated by the arrow, indicating a subcapsular location. B. The central scar, in other locations and with metastases, a finding associated with carcinoma, is in the liver a benign sign. The intense hyalin is also a benign sign, being that of a well-developed adenoma. C. Nuclear atypia in this case is modest near the region of scar, with tortuous glands. D. As the lesion progresses away from the scar, the atypia diminishes. Mitoses and outright necrosis were not identified. E. PAS-D stain shows the red rims about the glands, a benign sign, but also red cytoplasmic droplets, which is consistent with bile duct adenoma’s being known to produce mucin.

==IHC==
*CK7 +ve.
*HepPar-1 -ve.
*Ki-67 low.

Others:<ref name=pmid15725808/>
*p53 -ve.
*mCEA -ve.

==See also==
*[[Liver neoplasms]].

==References==
{{Reflist|2}}

[[Category:Liver neoplasms]]
[[Category:Diagnosis]]

Hepatitis C

2016-12-30T19:01:27Z

Mitchell: /* Images */ Added a case. Changed to better format for others. Depending on one's cell phone or computer, the images may not appear as rows. Hence, the need to letter them.

'''Hepatitis C''' is type of chronic viral hepatitis caused by the ''hepatitis C virus'' (abbreviated ''HCV'').

It is a type of [[medical liver disease]]

==General==
*Leads to [[hepatocellular carcinoma]] in the setting of [[cirrhosis]].
*Tends to be chronic; the "C" in "hepatitis C" stands for ''chronic''.
*Diagnosis is by serology.

Associated pathology:
*[[Membranoproliferative glomerulonephritis]].
*[[Membranous nephropathy]].
*[[Cryoglobulinemia]].

==Microscopic==
Features:
*Lobular inflammation - this is non-specific finding.
**Usually Grade 1, rarely Grade 2 and almost never Grade 3 or Grade 4.<ref>STC. 6 December 2010.</ref>
*Periportal steatosis in genotype 3.<ref name=pmid16614743>Yoon EJ, Hu KQ. Hepatitis C virus (HCV) infection and hepatic steatosis. Int J Med Sci. 2006;3(2):53-6. Epub 2006 Apr 1. PMID 16614743. Avialable at: [http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1415843 http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1415843]. Accessed on: September 9, 2009.</ref>
**Steatosis in hepatitis C is usually a secondary pathology, i.e. a separate pathologic process.<ref>OA. September 2009.</ref>

===Images===
[[File:5 11041788512294 sl 1.png| Acute hepatitis C]]
[[File:5 11041788512294 sl 2.png| Acute hepatitis C]]
[[File:5 11041788512294 sl 3.png| Acute hepatitis C]]
[[File:5 11041788512294 sl 4.png| Acute hepatitis C]]
[[File:5 11041788512294 sl 5.png| Acute hepatitis C]]

Acute hepatitis C presenting in a 37 year old woman with a 3 week history of jaundice, normal hepatobiliary radiologic studies, bilirubin 11.2, alkaline phosphatase 257, alanine aminotransferase 594, albumin 3, normal complete blood count, normal platelet level. No medications. A. Low power shows inflammation of triads (black arrow) with interface change, as well as disordered lobule with inflammation (red arrow). B. The triads showed intense lymphohistiocytic inflammation with interface hepatitis. Note piecemeal necrosis (black arrow) and neutrophils (red arrows). C. The hepatocytes appear haphazardly arranged with chronic inflammatory cells surrounding them in abundance. The arrow points to a Councilman body. C. Reticulin showed only isolated cell piecemeal necrosis in a minority of triads (black arrow). Regenerative cords two-three nuclei thick (green arrow) were only rarely seen. Significant collapse was not seen. D. PAS-D highlighted bile ductular proliferation (arrows). E. Feathery degeneration (foamy macrophage-like hepatocytes) was prominent in some areas. <ref name=pmid18059233>{{Cite journal | last1 = Johnson | first1 = K | last2 = Kotiesh | first2 = A | last3 = Boitnott | first3 = JK | last4 = Torbenson | first4 = M | title = Histology of symptomatic acute hepatitis C infection in immunocompetent adults. | journal = Am J Surg Pathol | volume = 31 | issue = 11| pages = 5286-96 | month = Nov | year = 2007 | doi = | PMID = 18059233 }}</ref>

A. [[File:1 HCV 9 680x512px.tif| Hepatitis C virus. Metavir Activity Index 1 (PMN 0 LN 1).]] 
B. [[File:2 HCV 9 680x512px.tif| Hepatitis C virus. Metavir Activity Index 1 (PMN 0 LN 1).]] 
C. [[File:3 HCV 9 680x512px.tif| Hepatitis C virus. Metavir Activity Index 1 (PMN 0 LN 1).]] 
D. [[File:4 HCV 9 680x512px.tif| Hepatitis C virus. Metavir Activity Index 1 (PMN 0 LN 1).]] 
E. [[File:5 HCV 9 680x512px.tif| Hepatitis C virus. Metavir Activity Index 1 (PMN 0 LN 1).]] 
F. [[File:6 HCV 9 680x512px.tif| Hepatitis C virus. Metavir Activity Index 1 (PMN 0 LN 1).]]

Hepatitis C virus. Metavir Activity Index 1 (PMN 0 LN 1). A. Preserved architecture shows small, inflamed triads [red arrows] and foci of spotty necrosis [blue arrows]. B. Trichrome shows periportal fibrosis [blue arrow] and central venous sclerosis [green arrow]. C. A higher power view of an inflamed triad with interface hepatitis, but a smooth outline, suggesting no piecemeal necrosis. D. A focus of spotty necrosis near an unafflicted triad below it. E. Reticulin shows collapse [arrows] extending from/near portal triad without piecemeal necrosis. F. Reticulin shows collapse [arrows] extending from/near central vein.

A. [[File:1 HCV 11 680x512px.tif]] 
B. [[File:2 HCV 11 680x512px.tif]] 
C. [[File:3 HCV 11 680x512px.tif]] 
D. [[File:4 HCV 11 680x512px.tif]] 
E. [[File:5 HCV 11 680x512px.tif]] 
F. [[File:6 HCV 11 680x512px.tif]]

Hepatitis C virus. Metavir activity index 1 (PMN 1 LN 1). A. Triads show inflammation with extension to portal border (interface hepatitis). B. Lymphocyte aggregates denote spotty necrosis. C. Reticulin shows focal piecemeal necrosis [arrow]. D. Trichrome shows periportal fibrous extension [arrows]. E. Trichrome shows sclerosis of central vein. F. PAS D can be useful when steatosis frustrates rosette identification; hepatocyte rosettes [arrows] have red edges.

A. [[File:1 HCV 10 680x512px.tif| HCR. Metavir Activity Index 2 (PMN 1 LN 2) Metavir fibrosis stage 3.]] 
B. [[File:2 HCV 10 680x512px.tif| HCR. Metavir Activity Index 2 (PMN 1 LN 2) Metavir fibrosis stage 3.]] 
C. [[File:3 HCV 10 680x512px.tif| HCR. Metavir Activity Index 2 (PMN 1 LN 2) Metavir fibrosis stage 3.]] 
D. [[File:4 HCV 10 680x512px.tif| HCR. Metavir Activity Index 2 (PMN 1 LN 2) Metavir fibrosis stage 3.]] 
E. [[File:5 HCV 10 680x512px.tif| HCR. Metavir Activity Index 2 (PMN 1 LN 2) Metavir fibrosis stage 3.]]
F. [[File:6 HCV 10 680x512px.tif| HCR. Metavir Activity Index 2 (PMN 1 LN 2) Metavir fibrosis stage 3.]] 

Hepatitis C Virus. Metavir Activity Index 2 (PMN 1 LN 2) Metavir fibrosis stage 3.
A. Low power showing a focus of spotty necrosis [red arrow], a triad with inflammation bounding its edge (interface necrosis) [black arrow] and a bridge [cyan arrow]. B. Reticulin showing a focus of piecemeal necrosis [arrows], where black lines bound hepatocytes & hepatocyte clusters, not a continuous region. C. Reticulin showing collapse between triads, not a bridge, given cells within strands. D. Trichrome showing collapse between triads, not a bridge, given atrophic cells precluding continuous connection between triads; the fibrosis about the triads is, on each side, a mere spike set. E. Reticulin showing a bridge, given lack of definite hepatocyte type cells within strands. F. Trichrome showing a bridge, with collagenous continuity uninterrupted by hepatocytes.

A. [[File:1 HCV 7 680x512px.tif|Hepatitis C. Metavir Activity Index 2 (PMN2, LN1), Metavir fibrosis stage 3]] 
B. [[File:2 HCV 7 680x512px.tif|Hepatitis C. Metavir Activity Index 2 (PMN2, LN1), Metavir fibrosis stage 3]] 
C. [[File:3 HCV 7 680x512px.tif|Hepatitis C. Metavir Activity Index 2 (PMN2, LN1), Metavir fibrosis stage 3]] 
D. [[File:4 HCV 7 680x512px.tif|Hepatitis C. Metavir Activity Index 2 (PMN2, LN1), Metavir fibrosis stage 3]] 
E. [[File:5 HCV 7 680x512px.tif|Hepatitis C. Metavir Activity Index 2 (PMN2, LN1), Metavir fibrosis stage 3]] 
F. [[File:6 HCV 7 680x512px.tif|Hepatitis C. Metavir Activity Index 2 (PMN2, LN1), Metavir fibrosis stage 3]] 
Hepatitis C. Metavir Activity Index 2 (PMN2, LN1), Metavir fibrosis stage 3. A.
Expanded dark triads, indicating interface hepatitis [red arrows], foci of steatosis [green arros], potential bridge [blue arrow]. B. Extending from triad are stretches of apparent necrosis [green arrows], inflammatory cells bound hepatocytes afflicted by piecemeal necrosis [yellow arrows], ballooning degeneration denoted by cytoplasmic tufts [blue arrows]. C. Reticulin shows collapse (necrosis) with thick bands [red arrows], as well as rosettes [green arrows] indicating dilated cholangioles. D. Reticulin here shows continuous piecemeal necrosis with black bounded hepatocyte islets [arrows]. E. Reticulin here shows a bridge with regeneration, wherein two or more nuclei lie between reticulin lines [arrows]. F. Trichrome demarcates one of the bridges (Row 3 Right 200X). 

[[File:HCV MAI 3 st 1.png|33.589444 101.891944]]
[[File:HCV MAI 3 st 2.png|33.589444 101.891944]]
[[File:HCV MAI 3 st 3.png|33.589444 101.891944]]
[[File:HCV MAI 3 st 4.png|33.589444 101.891944]]
[[File:HCV MAI 3 st 5.png|33.589444 101.891944]] 
Hepatitis C virus. Metavir activity index 3. Metavir fibrosis stage 1. A. Two dark expanded triads (arrows) have fuzzy edges. B. A triad shows interface hepatitis by lymphocytes and macrophages, with surrounding of hepatocytes (black arrows), piecemeal necrosis, with collections in the lobule (green arrows), spotty necrosis. The portal triad, venule and artery (blue arrows) are unaffected. The central vein’s being near the triad with a small pink line (yellow arrows) indicates significant collapse. C. Reticulin. Thick black lines between triad and central vein (blue arrows) document significant necrosis (LN 2). Two-three cell thick cords (green arrows) show regeneration. D. Reticulin. Thick black lines extending from triad, but not to a central vein, (blue arrows) are not as significant. Black lines surrounding multiple hepatocytes (green arrows) indicate moderate piecemeal necrosis (PMN 2), not severe because it does not involve most of the triad of most triads. E. Trichrome. Only fibrosis of portal triads was seen, indicating metavir fibrosis stage 1.

A. [[File:1 hcv 6 680x512px.tif|Inflamed bands cross hepatocytes with steatosis (Row 1 Left 40X).]] 
B. [[File:2 hcv 6 680x512px.tif|Trichrome shows extensive bridges (Row 1 Right 40X).]]
 
C. [[File:3 hcv 6 680x512px.tif|Trichrome also documents early nodule formation (Row 2 Left 40X).]] 
D. [[File:4 hcv 6 680x512px.tif|Reticulin shows regeneration (two nuclei per cord) in a nodule, but not throughout (Row 2 Right 200X).]]
 
E. [[File:5 hcv 6 680x512px.tif|Hematoxylin and eosin shows piecemeal necrosis as inflammatory cells surrounding hepatocytes (Row 3 Left 400X).]] 
F. [[File:6 hcv 6 680x512px.tif|Reticulin shows black lines about hepatocytes, indicating confluent piecemeal necrosis (Row 3 Right 400X).]] 
Hepatitis C with metavir stage IV fibrosis (advanced fibrosis/cirrhosis) and confluent piecemeal necrosis. A. Inflamed bands cross hepatocytes with steatosis. B. Trichrome shows extensive bridges. C. Trichrome also documents early nodule formation. D. Reticulin shows regeneration (two nuclei per cord) in a nodule, but not throughout. E. Hematoxylin and eosin shows piecemeal necrosis as inflammatory cells surrounding hepatocytes. F. Reticulin shows black lines about hepatocytes, indicating confluent piecemeal necrosis.

A. [[File:1 Hcv 12 680x512px.tif| Hepatitis C virus. Metavir activity index 3 (PMN 2, LN 2). Metavir stage 4 (cirrhosis, definite by old criteria).]] 
B. [[File:2 Hcv 12 680x512px.tif| Hepatitis C virus. Metavir activity index 3 (PMN 2, LN 2). Metavir stage 4 (cirrhosis, definite by old criteria).]] 
C. [[File:3 Hcv 12 680x512px.tif| Hepatitis C virus. Metavir activity index 3 (PMN 2, LN 2). Metavir stage 4 (cirrhosis, definite by old criteria).]] 
D. [[File:4 Hcv 12 680x512px.tif| Hepatitis C virus. Metavir activity index 3 (PMN 2, LN 2). Metavir stage 4 (cirrhosis, definite by old criteria).]] 
E. [[File:5 Hcv 12 680x512px.tif| Hepatitis C virus. Metavir activity index 3 (PMN 2, LN 2). Metavir stage 4 (cirrhosis, definite by old criteria).]] 
F. [[File:6 Hcv 12 680x512px.tif| Hepatitis C virus. Metavir activity index 3 (PMN 2, LN 2). Metavir stage 4 (cirrhosis, definite by old criteria).]] 
Hepatitis C virus. Metavir activity index 3 (PMN 2, LN 2). Metavir stage 4 (cirrhosis, definite by old criteria). A. Fragmentation raises the suspicion of cirrhosis, especially given absent triads, and an inflamed band [green arrow]; nodules [black arrow] are visible. B. Trichrome stain shows fibrosis about the nodules, whose interface will be examined in remaining images. C. Chronic inflammation shows interface hepatitis [green arrow] as well as surrounding of hepatocytes [blue arrows] for piecemeal necrosis; a necrotic hepatocyte demarcates lobular necrosis [black arrow]. D. Reticulin shows regeneration via two nucleus thick cords [green arrows], but also by rosettes [blue arrows] and, most definite, by overall lack of direction to black lines, going different ways with respect to the edge of the fibrotic, inflamed band [black arrows]; black lines surrounding hepatocytes/hepatocyte groups [black arrows] document continuous piecemeal necrosis. E. PAS without diastase stain on core biopsies can make piecemeal necrosis more obvious than on reticulin by showing stroma bounded red hepatocyte cytoplasm of cells [arrows]. F. PAS with diastase has pink lines to use to evaluate the sinusoidal structure, similar to reticulin, but not as good; note spotty necrosis [black arrow] and proliferated bile ductules [red arrows].

DDx:
*[[Hepatitis B]] (without ground glass hepatocytes).
*[[Autoimmune hepatitis]].
*[[Primary biliary cirrhosis]] without granulomas.
*[[Drug-induced liver disease|Drug reaction]].

==See also==
*[[Medical liver disease]].

==References==
{{Reflist|1}}

[[Category:Diagnosis]]
[[Category:Medical liver disease]]

Hepatitis B

2016-12-28T22:17:36Z

Mitchell: /* Image */ added a case, modified remainder to be lettered to ease use with I phone

'''Hepatitis B''' is a relatively common [[medical liver disease]] caused by the ''hepatitis B virus''.

==General==
*May lead to [[hepatocellular carcinoma]] without [[cirrhosis]].
*High prevalence.
*Diagnosis is by serology - details of serologic testing are in the ''[[Medical_liver_disease#Hepatitis_B|medical liver disease article]]''.
*A vaccination is available and done routinely in a many jurisdictions.<ref>{{Cite journal | last1 = Leuridan | first1 = E. | last2 = Van Damme | first2 = P. | title = Hepatitis B and the need for a booster dose. | journal = Clin Infect Dis | volume = 53 | issue = 1 | pages = 68-75 | month = Jul | year = 2011 | doi = 10.1093/cid/cir270 | PMID = 21653306 }}</ref>

Associated pathology:
*[[Polyarteritis nodosa]] (PAN).
*[[Membranoproliferative glomerulonephritis]].
*[[Membranous nephropathy]].

==Microscopic==
Features:
*Lobular inflammation - this is non-specific finding.
**Hepatocyte necrosis:
***Necrotic hepatocytes look a lot like neutrophils - however:
****Cytoplasm is more pink.
****Round apoptotic bodies.
*[[Ground glass hepatocytes]] - '''important'''.

DDx:
*[[Hepatitis C]].
*[[Autoimmune hepatitis]].
*[[Primary biliary cirrhosis]] without [[granulomas]].
*[[Drug-induced liver disease|Drug reaction]].

===Image===
<gallery>
Image:Ground_glass_hepatocytes_high_mag_cropped_2.jpg | GGH - high mag. (WC)
</gallery>

[[File:5 07686954470825 sl 1.png| HBV Modified HAI necroinflammatory score 5, Modified HAI fibrosis stage 2]]
[[File:5 07686954470825 sl 2.png| HBV Modified HAI necroinflammatory score 5, Modified HAI fibrosis stage 2]]
[[File:5 07686954470825 sl 3.png| HBV Modified HAI necroinflammatory score 5, Modified HAI fibrosis stage 2]]
[[File:5 07686954470825 sl 4.png| HBV Modified HAI necroinflammatory score 5, Modified HAI fibrosis stage 2]]
[[File:5 07686954470825 sl 5.png| HBV Modified HAI necroinflammatory score 5, Modified HAI fibrosis stage 2]]

42 yo woman with bepatitis B virus, modified HAI necroinflammatory grade 5, modified HAI fibrosis stage 1. (would be Metavir activity index 1, fibrosis stage 1). A Triads (red arrows) are slightly cellular, without much interface inflammation, with occasional spots suggestive of spotty necrosis (black arrows). B. Triads, this one being the most expanded, show a mild infiltrate (HAI score 1) of lymphocytes and macrophages, with only a small amount present at the interface between triad and lobule. C. A maximum of two foci of spotty necrosis (arrows) were seen in a 10X field (HAI score 2). D. Occasional foci of zone 3 collapse (thick black lines, green arrows), HAI score 1, and piecemeal necrosis (blue arrows) HAI score 1, were seen. E. Trichrome shows portal fibrosis of most triads, but no bridges, or nodules (HAI stage 2).

A. [[File:1 HBV 680x512px.tif|Portal triads, expanded, inflamed and without sharp edges. Inflammation amid hepatocytes. (40X).]]
B. [[File:2 HBV 680x512px.tif|Reticulin with bridging necrosis (100X).]]
 
C. [[File:3 HBV 680x512px.tif|Reticulin with extensive piecemeal necrosis (100X).]]
D. [[File:4 HBV 680x512px.tif|PAS without diastase with extensive piecemeal necrosis (100X).]]
 
E. [[File:5 HBV 680x512px.tif|Trichrome with bridging, no nodules or extensive bridging on slides as a whole (100X).]]
F. [[File:6HBV 680x512px.tif|Ground glass hepatocytes (400X).]]

Hepatitis B. Metavir activity index 3. Piecemeal necrosis 2. Lobular necrosis 2. Fibrosis stage 3. A. Portal triads, expanded, inflamed and without sharp edges. Inflammation amid hepatocytes. B. Reticulin with bridging necrosis. C. Reticulin with extensive piecemeal necrosis. D. PAS without diastase with extensive piecemeal necrosis. E. Trichrome with bridging, no nodules or extensive bridging on slides as a whole. F. Ground glass hepatocytes.

A. [[File:1 HBV 2 680x512px.tif| Hepatitis B virus. Metavir activity index 3 {PMN 2 LN 2]. Metavir fibrosis stage 4 (advanced fibrosis/cirrhosis).]]
B. [[File:2 HBV 2 680x512px.tif| Hepatitis B virus. Metavir activity index 3 {PMN 2 LN 2]. Metavir fibrosis stage 4 (advanced fibrosis/cirrhosis).]]
 
C. [[File:3 HBV 2 680x512px.tif| Hepatitis B virus. Metavir activity index 3 {PMN 2 LN 2]. Metavir fibrosis stage 4 (advanced fibrosis/cirrhosis).]]
D. [[File:4 HBV 2 680x512px.tif| Hepatitis B virus. Metavir activity index 3 {PMN 2 LN 2]. Metavir fibrosis stage 4 (advanced fibrosis/cirrhosis).]]
 
E. [[File:5 HBV 2 680x512px.tif| Hepatitis B virus. Metavir activity index 3 {PMN 2 LN 2]. Metavir fibrosis stage 4 (advanced fibrosis/cirrhosis).]]
F. [[File:6 HBV 2 680x512px.tif| Hepatitis B virus. Metavir activity index 3 {PMN 2 LN 2]. Metavir fibrosis stage 4 (advanced fibrosis/cirrhosis).]]

Hepatitis B virus. Metavir activity index 3 {PMN 2 LN 2]. Metavir fibrosis stage 4 (advanced fibrosis/cirrhosis). A. A fragmented specimen shows apparent nodules [black arrows]. B. Inflammatory cells extending from band suggest piecemeal necrosis [green arrows]; inflammatory foci apart from band denote spotty necrosis [blue arrows]. C. Reticulin stain shows piecemeal necrosis as black lines about hepatocyte clusters at band [blue arrows], regeneration as more than one cell thick cords [green arrows] and hepatocyte rosettes [magenta arrows]. D. On PAS without diastase, piecemeal necrosis can be seen as pink hepatocyte cytoplasmic fragments amid inflammatory cells [arrows]. E. The nodules seen at low power are confirmed to be collagen bounded, but the appreciation can be made frustrated by intense inflammation. F. Examination elsewhere shows a definite nodule pair amid fibrosis [green arrows]; note on the right the fibrous band extending from the portal triad [black arrow] with sinusoids being far more often perpendicular to the triad than they were in the regenerative nodules to the surrounding bands.

==IHC==
*Hepatitis B +ve.

==See also==
*[[Medical liver disease]].

==References==
{{Reflist|1}}

[[Category:Diagnosis]]
[[Category:Medical liver disease]]

Hepatocellular carcinoma

2016-12-28T19:34:22Z

Mitchell: /* Images */ added case

{{ Infobox diagnosis
| Name = {{PAGENAME}}
| Image = Hepatocellular_carcinoma_intermed_mag.jpg
| Width =
| Caption = Hepatocellular carcinoma.
| Micro = architectural changes - liver plate thickness >3 cells thick, +/-nuclear changes of malignancy (very common), variable architecture (pseudoglandular, trabecular, fibrolamellar, solid)
| Subtypes = sclerosing HCC, fibrolamellar HCC
| LMDDx = [[cholangiocarcinoma]], occasionally [[liver metastasis]], [[High-grade hepatocellular dysplasia|high-grade dysplasia]]
| Stains = reticulin (thickened liver plate)
| IHC = CD34 +ve sinusoids, HepPar-1 +ve (usu.), [[AFP]] +ve (usu.), CK8/18 +ve, glypican-3 +ve
| EM =
| Molecular =
| IF =
| Gross = usu. cirrhosis (micronodular or macronodular)
| Grossing =
| Site = [[liver]] - see [[liver neoplasms]]
| Assdx = causes of [[cirrhosis]], e.g. chronic [[alcoholism]], [[Hepatitis C]], [[Hepatitis B]], [[hereditary hemochromatosis]], others
| Syndromes =
| Clinicalhx =
| Signs =
| Symptoms =
| Prevalence = most common malignant primary liver tumour, less common than metastases
| Bloodwork = +/-AFP elevation
| Rads =
| Endoscopy =
| Prognosis = moderate to poor
| Other =
| ClinDDx = [[liver metastasis]], other liver tumours
}}
'''Hepatocellular carcinoma''', abbreviated '''HCC''', is the most common malignant primary liver tumour. It most often arises in the context of [[cirrhosis]].

==General==
Clinical:
*Serum AFP elevated - in approx. 50% of patients.<ref>{{Ref GLP|588}}</ref>
*Treatments: RFA (radiofrequency ablation), ethanol ablation, liver resection, liver transplant.<ref name=emed_hcc>[http://emedicine.medscape.com/article/282814-overview http://emedicine.medscape.com/article/282814-overview]</ref>
*Mean survival at time of diagnosis ~6 months.<ref name=emed_hcc/>

Epidemiology:
*Highest where prevalence of hepatitis B virus (HBV) is high.<ref name=Ref_PBoD924>{{Ref PBoD|924}}</ref>
*HCC generally arises in the setting of [[cirrhosis]].
**Cirrhosis may be regressed and therefore not appreciated.

HCCs '''without''' cirrhosis:
*Hepatitis B virus.<ref name=Ref_PBoD924>{{Ref PBoD|924}}</ref>
*Hemochromatosis.
*Fibrolamellar HCC.

Risk factors:<ref name=Ref_PBoD924>{{Ref PBoD|924}}</ref><ref name=pmid18333156>{{cite journal |author=Leong TY, Leong AS |title=Epidemiology and carcinogenesis of hepatocellular carcinoma |journal=HPB (Oxford) |volume=7 |issue=1 |pages=5–15 |year=2005 |pmid=18333156 |pmc=2023917 |doi=10.1080/13651820410024021 |url=}}</ref>
*Chronic [[alcoholism]].
*[[Hepatitis C]] virus (HCV) - chronic infection.
*[[Hepatitis B]] virus (HBV) - chronic infection.
*Aflatoxins (food contaminant - mould).<ref name=emed_hcc/>
*Hereditary tyrosinemia.
*[[Hereditary hemochromatosis]].

==Gross==
Features:<ref name=Ref_PBoD925>{{Ref PBoD|925}}</ref>
*Unifocal, multifocal or diffusely infiltrative.
**Tumours are multifocal in approx. 50% of cases;<ref name=pmid17696722>{{cite journal |author=Yusuf MA, Badar F, Meerza F, ''et al.'' |title=Survival from hepatocellular carcinoma at a cancer hospital in Pakistan |journal=Asian Pac. J. Cancer Prev. |volume=8 |issue=2 |pages=272–4 |year=2007 |pmid=17696722 |doi= |url=}}</ref><ref name=pmid11676064>{{cite journal |author=Sharieff S, Burney KA, Ahmad N, Salam A, Siddiqui T |title=Radiological features of hepatocellular carcinoma in Southern Pakistan |journal=Trop Doct |volume=31 |issue=4 |pages=224–5 |year=2001 |month=October |pmid=11676064 |doi= |url=}}</ref> some authors have suggested it is upto 75% of cases.<ref name=emed_hcc/>
*Pale in relation to surrounding liver or green (due to bile secretion).

===Images===
<gallery>
Image: Hepatocellular carcinoma 1.jpg | HCC. (WC)
Image: Hepatocellular_carcinoma_2.jpg | HCC. (WC)
</gallery>

==Microscopic==
Requirements:<ref>Adapted from STC (19 Jan 2009).</ref>
*Architectural changes.
**Liver plate more than 3 cells thick - '''key feature'''.
**Loss of reticulin scaffold - incomplete loss is considered significant.
**CD34+ staining cells, suggesting loss of epithelial cells that form the sinusoids.
**Loss of structures seen in a normal liver lobule (bile ductules, portal triad).
**Invasion of the portal tract - useful in well-diff. lesions.<ref name=pmid19177576>{{Cite journal | last1 = Kojiro | first1 = M. | last2 = Wanless | first2 = IR. | last3 = Alves | first3 = V. | last4 = Badve | first4 = S. | last5 = Balabaud | first5 = C. | last6 = Bedossa | first6 = P. | last7 = Bhathal | first7 = P. | last8 = Bioulac-Sage | first8 = P. | last9 = Brunt | first9 = EM. | title = Pathologic diagnosis of early hepatocellular carcinoma: a report of the international consensus group for hepatocellular neoplasia. | journal = Hepatology | volume = 49 | issue = 2 | pages = 658-64 | month = Feb | year = 2009 | doi = 10.1002/hep.22709 | PMID = 19177576 | url = http://onlinelibrary.wiley.com/doi/10.1002/hep.22709/pdf }}</ref>

Additional findings:<ref>Adapted from STC (19 Jan 2009).</ref>
*Nuclear changes.
**Increased NC ratio - '''key feature''' if present.
**Nuclear hyperchromasia.
**Abnormal nuclear contour.
**Mitoses.
*Cytoplasmic changes.
**Cytoplasmic hyperchromasia, clearing or lighter staining.

Varied architecture - may be:<ref>{{Ref GLP|590-1}}</ref>
*Pseudoglandular - can be confused with adenocarcinoma.
*[[Trabecular]].
*Fibrolamellar.
*Solid.

Notes:
*HCC with trabecular morphology has some resemblance to normal liver - but has extra cells.
*Fibrolamellar - better prognosis, classically in young adults.
*Stroma is usually scant.<ref>{{Ref GLP|591}}</ref>

ASIDE:
*''[[Trabecula]]'' = ''little beam''.

DDx:
*[[Cholangiocarcinoma]].
*Combined HCC-CC.<ref name=pmid21559202>{{Cite journal | last1 = Walther | first1 = Z. | last2 = Jain | first2 = D. | title = Molecular pathology of hepatic neoplasms: classification and clinical significance. | journal = Patholog Res Int | volume = 2011 | issue = | pages = 403929 | month = | year = 2011 | doi = 10.4061/2011/403929 | PMID = 21559202 | PMC = 3090128 }}</ref>
*[[High-grade hepatocellular dysplasia|High-grade dysplasia]].

===Images===
<gallery>
Image:Hepatocellular_carcinoma_low_mag.jpg | HCC - low mag. (WC)
Image:Hepatocellular_carcinoma_intermed_mag.jpg | HCC - intermed mag. (WC)
</gallery>
A
[[File:1 HCC 3 680x512px.tif| Hepatocellular carcinoma with fragments of liver afflicted by steatosis & with regenerative, benign fragments.]]
B
[[File:2 HCC 3 680x512px.tif| Hepatocellular carcinoma with fragments of liver afflicted by steatosis & with regenerative, benign fragments.]]
C
[[File:3 HCC 3 680x512px.tif| Hepatocellular carcinoma with fragments of liver afflicted by steatosis & with regenerative, benign fragments.]]
D
[[File:4 HCC 3 680x512px.tif| Hepatocellular carcinoma with fragments of liver afflicted by steatosis & with regenerative, benign fragments.]]
E
[[File:5 HCC 3 680x512px.tif| Hepatocellular carcinoma with fragments of liver afflicted by steatosis & with regenerative, benign fragments.]]
F
[[File:6 HCC 3 680x512px.tif| Hepatocellular carcinoma with fragments of liver afflicted by steatosis & with regenerative, benign fragments.]]
G
[[File:7 HCC 3 680x512px.tif| Hepatocellular carcinoma with fragments of liver afflicted by steatosis & with regenerative, benign fragments.]]
H
[[File:8 HCC 3 680x512px.tif| Hepatocellular carcinoma with fragments of liver afflicted by steatosis & with regenerative, benign fragments.]]

Hepatocellular carcinoma with fragments of liver afflicted by steatosis & with regenerative, benign fragments. A. Fragments of liver with crowded nuclei, consistent with hepatoma, as well as with steatosis [arrows]. B. Fragments of liver with crowded nuclei, consistent with hepatoma, as well as with larger amount of cytoplasm, consistent with regeneration [arrow]. C. The fatty liver below has aberrant-appearing nuclei, but not particularly crowded, in contrast to the fragment on top, which has crowded nuclei. D. Reticulin stain shows apparent expansion of nuclei between black lines on the fatty liver, but this may also be seen with simple steatosis; on the crowded liver note the lack of definite expansion. E. The regenerative focus shows abundant cytoplasm. F. Reticulin on this regenerative focus shows preservation of the low number of nuclei between black lines. G. This typical hepatocellular focus shows crowding, occasional acini, and basophilia, similar to the focus seen in row 2. Note that some cells show apparent steatosis. H. Reticulin on this hepatocellular focus shows loss of reticulin fibers, with more than six nuclei between several black lines (Row 4 Right 200X).

A
[[File:1 hcc 1 680x512px.tif|Fibrous bands dissect hepatocyte nodules, mostly hepatoma(Row 1 Left 20X).]]
B
[[File:2 hcc 1 680x512px.tif|The fibrous band on right bears proliferating bile ductules; acinar arrangement on left shows holes much larger than canaliculi (Row 1 Right 100X).]]
C
[[File:3 hcc 1 680x512px.tif|The tumor has cancerous nuclei; note the bile which makes for absolute diagnostic certainty [arrow] (Row 2 Left 400X).]]
D
[[File:4 hcc 1 680x512px.tif|Noncancerous hepatocytes on left can be compared with tumor cells on right. Note increased nuclear crowding & a subtle increment in cytoplasmic basophilia in tumor (Row 2 Right 400X).]]

Hepatocellular carcinoma with acini. A. Fibrous bands dissect hepatocyte nodules, mostly hepatoma. B. The fibrous band on right bears proliferating bile ductules; acinar arrangement on left shows holes much larger than canaliculi. C. The tumor has cancerous nuclei; note the bile which makes for absolute diagnostic certainty [arrow]. D. Noncancerous hepatocytes on left can be compared with tumor cells on right. Note increased nuclear crowding & a subtle increment in cytoplasmic basophilia in tumor.

A
[[File:1 steatohep HCC 6 680x512px.tif|Fragments of tumor at low power mimic normal hepatocyte groups without triads (Row 1 Left 20X).]]
B
[[File:2 steatohep HCC 6 680x512px.tif|Vacuoles, mostly small, occasionally become large enough to warrant “macrovesicular” [green arrows]. Note Mallory hyalin [red arrows] (Row 1 Right 400X).]]
C
[[File:3 steatohep HCC 6 680x512px.tif|Chronic inflammatory cells bound some cancer cells (Row 2 Left 400X).]]
D
[[File:4 steatohep HCC 6 680x512px.tif|Nuclear inclusions are occasionally prominent [arrows] (Row 2 Right 400X).]]

Hepatocellular carcinoma, steatohepatitic variant. A. Fragments of tumor at low power mimic normal hepatocyte groups without portal triads. B. Vacuoles, mostly small, occasionally become large enough to warrant the term “macrovesicular” [green arrows]. Note Mallory hyalin [red arrows]. D. Chronic inflammatory cells bound some cancer cells. D. Nuclear inclusions [arrows] are occasionally prominent [arrows].

[[File: HCC CL 1 sl 1.png| Hepatocellular carcinoma, clear cell variant]]
[[File: HCC CL 1 sl 2.png| Hepatocellular carcinoma, clear cell variant]]
[[File: HCC CL 1 sl 3.png| Hepatocellular carcinoma, clear cell variant]]
[[File: HCC CL 1 sl 4.png| Hepatocellular carcinoma, clear cell variant]]
[[File: HCC CL 1 sl 5.png| Hepatocellular carcinoma, clear cell variant]]

Hepatocellular carcinoma, clear cell variant. Much more difficult on biopsy than on resection is the specific identification of the clear cell variant, although it was done here. Variants are of little clinical significance apart from the fibrolamellar variant. A. Tumor fragment masses with clearing contrast with pink liver fragments. B. Tumor cell cytoplasm on the core biopsy varies, often clear, often light pink and foamy. C. PAS without diastase shows brightly positive tumor cytoplasm. D. Modestly variable, rounded nuclei show open chromatin and nucleoli. Individual pyknotic nuclei (black arrows) are insufficient as evidence of necrosis sufficient to increase grade. D. PAS with diastase shows the material is glycogen. E. At resection, the cytoplasmic clarity at low power is more impressive than on biopsy. F. The high power view of the resection specimen shows the cytoplasm is truly clear. Arrows point to Mallory bodies.

[[File:5 04760075043191 sl 1.png| Hepatocellular carcinoma arising in cirrhosis]]
[[File:5 04760075043191 sl 2.png| Hepatocellular carcinoma arising in cirrhosis]]
[[File:5 04760075043191 sl 3.png| Hepatocellular carcinoma arising in cirrhosis]]
[[File:5 04760075043191 sl 4.png| Hepatocellular carcinoma arising in cirrhosis]]
[[File:5 04760075043191 sl 5.png| Hepatocellular carcinoma arising in cirrhosis]]
[[File:5 04760075043191 sl 6.png| Hepatocellular carcinoma arising in cirrhosis]]
[[File:5 04760075043191 sl 7.png| Hepatocellular carcinoma arising in cirrhosis]]
[[File:5 04760075043191 sl 8.png| Hepatocellular carcinoma arising in cirrhosis]]

Hepatocellular carcinoma superimposed on cirrhosis in a 60 year old man. A. Dark tumor, sometimes with separate cords visible at low power (black arrow), contrasts with lightly colored regenerative nodules (green arrows) within fibrotic bands. B. Regenerative nodules are separated by a band with proliferated bile ducts, whose orientation, lacking haphazard spread, bespeaks a benign process. C. Reticulin of regenerative nodule shows two cell thick cords lacking orientation, disrupted without reason, aggregated and, at left, slighely dispersed. D. Hepatocellular carcinoma shows darker cytoplasm and more nuclei per square mm than regenerative nodules. Note the many acini, also a good sign of cancer. E. Reticulin fibers have disappeared, leaving cords with 6 or more nuclei thick in places. F. PAS D stain shows benign proliferated bile ducts, whose orientation from lower left to upper right deprives the proliferation of the haphazard nature of a cholangiocarcinoma. G. PAS-D shows the cytoplasmic digestion of glycogen in a hepatocellular carcinoma, a helpful hint at times. Note the finger like cords, the mitosis (black arrow), and the occasional acinar lumens (red arrows). H. PAS D of regenerative nodule contrasts with the image of the hepatocellular carcinoma.

===Fibrolamellar hepatocellular carcinoma===
*Abbreviated ''fibrolamellar HCC'', ''FL-HCC'', and ''FHCC''.
====General====
*Rare variant.
*Classically afflicts younger patients.
**Mean age at onset ~27 years in one study.<ref name=pmid16475212>{{Cite journal | last1 = Stipa | first1 = F. | last2 = Yoon | first2 = SS. | last3 = Liau | first3 = KH. | last4 = Fong | first4 = Y. | last5 = Jarnagin | first5 = WR. | last6 = D'Angelica | first6 = M. | last7 = Abou-Alfa | first7 = G. | last8 = Blumgart | first8 = LH. | last9 = DeMatteo | first9 = RP. | title = Outcome of patients with fibrolamellar hepatocellular carcinoma. | journal = Cancer | volume = 106 | issue = 6 | pages = 1331-8 | month = Mar | year = 2006 | doi = 10.1002/cncr.21703 | PMID = 16475212 }}</ref>
*Individuals usually do '''not''' have the classic risk factors for HCC, i.e. no [[cirrhosis]], no hepatitis.<ref name=pmid16475212/>

Clinical:
*AFP usu. not elevated.<ref name=pmid16475212/>

====Microscopic====
Features:<ref>{{Ref GLP|595-6}}</ref>
*Large polygonal tumours cells with:
**Graunular eosinophilic cytoplasm.
**Low NC ratio.<ref>STC. 6 December 2010.</ref>
*Layered dense collagen bundles.

DDx:
*[[Amyloidosis of the liver]].

Note:
*If ''conventional HCC'' is seen focally within the tumour, it is ''conventional HCC''.

=====Images=====
<gallery>
Image:Fibrolamellar_hepatocellular_carcinoma_-2-_intermed_mag.jpg | FHCC - intermed. mag. (WC)
Image:Fibrolamellar_hepatocellular_carcinoma_-2-_very_high_mag.jpg | FHCC - very high mag. (WC)
</gallery>
===Sclerosing HCC===
Features:
*Fibrosis. (???)

Notes:
*Seen in non-cirrhotic livers.

===Grading===
Edmondson-Steiner grading system:<ref name=pmid13160935>Primary carcinoma of the liver: a study of 100 cases among 48,900 necropsies. EDMONDSON HA, STEINER PE. Cancer. 1954 May;7(3):462-503. PMID 13160935.</ref><ref name=macsween5th>{{Ref MacSween|783}}</ref>
*Well-differentiated.
**Some say "it cannot be diagnosed on biopsy,"<ref>Pollet A. 28 May 2009.</ref> as it cannot be reliably differentiated from a regenerative nodule.
*Moderately differentiated.
**Round, regular nuclei, some hyperchromatism, nucleoli present, increase NC ratio.
*Poor differentiated.
**Very prominent nucleoli, pronounced nuclear irregularity.
*Undifferentiated.
**Anaplastic giant cells.

Simplified description - based on MacSween:<ref name=macsween5th/>
*Well-differentiated = cytologically near normal.
*Moderate = looks like a cancer, small nucleoli.
*Poor = bad cancer, raisin-like (irregular) nuclear membrane, large nucleoli (~1/3 of nucleus).
*Undifferentiated = death on a slide, huge cells (3-4x the size of other cells).

==IHC==
*CD34 +ve sinusoids; sinusoids in normal liver are CD34 -ve.
*HepPar-1 +ve; may be neg. in high grade tumours.
*[[AFP]] +ve; may be neg. even if the serum AFP is elevated.
*CK8/18 +ve.<ref name=pmid16680226>{{Cite journal | last1 = Stroescu | first1 = C. | last2 = Herlea | first2 = V. | last3 = Dragnea | first3 = A. | last4 = Popescu | first4 = I. | title = The diagnostic value of cytokeratins and carcinoembryonic antigen immunostaining in differentiating hepatocellular carcinomas from intrahepatic cholangiocarcinomas. | journal = J Gastrointestin Liver Dis | volume = 15 | issue = 1 | pages = 9-14 | month = Mar | year = 2006 | doi = | PMID = 16680226 }}</ref>
*Glypican-3 +ve (cytoplasmic, granular cytoplasmic or membranous).<ref name=pmid19212669>{{Cite journal | last1 = Shirakawa | first1 = H. | last2 = Kuronuma | first2 = T. | last3 = Nishimura | first3 = Y. | last4 = Hasebe | first4 = T. | last5 = Nakano | first5 = M. | last6 = Gotohda | first6 = N. | last7 = Takahashi | first7 = S. | last8 = Nakagohri | first8 = T. | last9 = Konishi | first9 = M. | title = Glypican-3 is a useful diagnostic marker for a component of hepatocellular carcinoma in human liver cancer. | journal = Int J Oncol | volume = 34 | issue = 3 | pages = 649-56 | month = Mar | year = 2009 | doi = | PMID = 19212669 | url = http://www.spandidos-publications.com/serveFile/ijo_34_3_649_PDF.pdf?type=article&article_id=ijo_34_3_649&item=PDF}}</ref>
*TTF-1 +ve cytoplasmic staining.<ref name=pmid22359993>{{Cite journal | last1 = Mishra | first1 = M. | last2 = Morgan | first2 = V. | last3 = Hamati | first3 = AK. | last4 = Al-Abbadi | first4 = M. | title = Carcinoma of unknown primary: check the liver... thanks to TTF-1. | journal = Tenn Med | volume = 105 | issue = 1 | pages = 35-6, 40 | month = Jan | year = 2012 | doi = | PMID = 22359993 }}</ref>
**Benign liver also has cytoplasmic staining.

Bile canaliculi:
*[[CD10]] +ve.<ref name=pmid15469471>{{Cite journal | last1 = Shousha | first1 = S. | last2 = Gadir | first2 = F. | last3 = Peston | first3 = D. | last4 = Bansi | first4 = D. | last5 = Thillainaygam | first5 = AV. | last6 = Murray-Lyon | first6 = IM. | title = CD10 immunostaining of bile canaliculi in liver biopsies: change of staining pattern with the development of cirrhosis. | journal = Histopathology | volume = 45 | issue = 4 | pages = 335-42 | month = Oct | year = 2004 | doi = 10.1111/j.1365-2559.2004.01927.x | PMID = 15469471 }}</ref>
*pCEA +ve.<ref>{{Cite journal | last1 = Porcell | first1 = AI. | last2 = De Young | first2 = BR. | last3 = Proca | first3 = DM. | last4 = Frankel | first4 = WL. | title = Immunohistochemical analysis of hepatocellular and adenocarcinoma in the liver: MOC31 compares favorably with other putative markers. | journal = Mod Pathol | volume = 13 | issue = 7 | pages = 773-8 | month = Jul | year = 2000 | doi = | PMID = 10912937 | URL = http://www.nature.com/modpathol/journal/v13/n7/full/3880134a.html }}</ref>

Image:
*[http://www.nature.com/modpathol/journal/v20/n1s/fig_tab/3800682f12.html#figure-title HCC - HepPar-1 (nature.com)].<ref name=pmid17486052>{{Cite journal | last1 = Goodman | first1 = ZD. | title = Neoplasms of the liver. | journal = Mod Pathol | volume = 20 Suppl 1 | issue = | pages = S49-60 | month = Feb | year = 2007 | doi = 10.1038/modpathol.3800682 | PMID = 17486052 }}</ref>

==Sign out==
===Negative core biopsy===
<pre>
LIVER CORE, BIOPSY:
- CIRRHOSIS.
- HEPATOCYTE CYTOLOGY WITHIN NORMAL LIMITS.
</pre>

==See also==
*[[Liver neoplasms]].

==References==
{{Reflist|2}}

[[Category:Diagnosis]]
[[Category:Liver neoplasms]]