Libre Pathology - User contributions [en]

Tissue fixation

2025-10-12T19:48:51Z

Mark: my contribution from ganfyd.org (now inactive), slightly modified

'''Tissue fixation''', usually just '''fixation''', is an important part of tissue preparation for histologic examination. It is typically done with formalin.

==Implications==
Pathologist have a great lifestyle 'cause tissue takes long to fix; the penetration of tissue by formalin is 1 mm/hour.<ref>Gross rounds. 14 August 2009.</ref>

==Ratio==
The dictum is:<ref>URL: [http://www.cap.org/apps/docs/committees/cancer/cancer_protocols/2011/UvealMelanom_11protocol.pdf http://www.cap.org/apps/docs/committees/cancer/cancer_protocols/2011/UvealMelanom_11protocol.pdf]. Accessed on: 27 March 2012.</ref>
*''The volume of fixative should be 10x the volume of specimen.''

==Tissue fixation==
A list of fixatives:<ref name=pmid18251585>{{Cite journal | last1 = Hunt | first1 = JL. | title = Molecular pathology in anatomic pathology practice: a review of basic principles. | journal = Arch Pathol Lab Med | volume = 132 | issue = 2 | pages = 248-60 | month = Feb | year = 2008 | doi = 10.1043/1543-2165(2008)132[248:MPIAPP]2.0.CO;2 | PMID = 18251585 | url = http://www.archivesofpathology.org/doi/pdf/10.1043/1543-2165%282008%29132%5B248%3AMPIAPP%5D2.0.CO%3B2 }}
</ref>
{| class="wikitable sortable" style="margin-left:auto;margin-right:auto"
! Fixative
! Comment
|-
| Formalin, neutral buffered
| standard fixative
|-
| Formalin, unbuffered
| ???
|-
| Glutaraldehyde<ref name=pmid8787969>{{Cite journal | last1 = Prentø | first1 = P. | title = Glutaraldehyde for electron microscopy: a practical investigation of commercial glutaraldehydes and glutaraldehyde-storage conditions. | journal = Histochem J | volume = 27 | issue = 11 | pages = 906-13 | month = Nov | year = 1995 | doi = | PMID = 8787969 }}</ref>
| [[electron microscopy]]
|-
| Ethanol
| [[cytopathology]]
|-
| Carnoy
| ???
|-
| Bouin
| toxic ???
|-
| B5
| used for [[lymphoma]], superior morphology - but toxic, not good for IHC & DNA analysis<ref>{{Cite journal | last1 = Bonds | first1 = LA. | last2 = Barnes | first2 = P. | last3 = Foucar | first3 = K. | last4 = Sever | first4 = CE. | title = Acetic acid-zinc-formalin: a safe alternative to B-5 fixative. | journal = Am J Clin Pathol | volume = 124 | issue = 2 | pages = 205-11 | month = Aug | year = 2005 | doi = 10.1309/29DA-CY9K-BHNW-4BG6 | PMID = 16040290 }}</ref>
|-
| IBF fixative
| used bone marrow and lymphatic tissue;<ref>URL: [http://www.leicabiosystems.com/specimen-preparation/consumables/reagents-solutions/fixatives/details/product/ibf-tissue-fixative-1/ http://www.leicabiosystems.com/specimen-preparation/consumables/reagents-solutions/fixatives/details/product/ibf-tissue-fixative-1/]. Accessed on: 26 September 2014.</ref> gives better nuclear detail in prostate biopsies compared to formalin<ref name=pmid16390230>{{Cite journal | last1 = Trpkov | first1 = K. | last2 = Renault | first2 = P. | last3 = Yilmaz | first3 = A. | last4 = Ali-Ridha | first4 = N. | title = IBF as a formalin substitute fixative in prostate biopsy pathology. | journal = Arch Pathol Lab Med | volume = 130 | issue = 1 | pages = 13-4 | month = Jan | year = 2006 | doi = 10.1043/1543-2165(2006)130[13b:IAAFSF]2.0.CO;2 | PMID = 16390230 |URL = http://www.archivesofpathology.org/doi/full/10.1043/1543-2165(2006)130%5B13b%3AIAAFSF%5D2.0.CO%3B2 }}</ref>
|}

=Tissue fixation=
==Formalin==
*May be written (incorrectly) as "formulin".
*Formaldehyde + methanol.

Formaldehyde is often supplied as a 37% w/v solution. To prevent polymerisation of formaldehyde, methanol is added. The resulting solution is often referred to as formalin. This can be further diluted and buffered to produce 10% formalin (equivalent to 4% formaldehyde). This concentration is often used as a fixative and preservative for histological specimens. It gives tissues a firmer texture, making subsequent cut-up easier and also stops autolysis and necrosis of the tissue by inactivating micro-organisms and proteolytic enzymes. Poorly fixed tissue stains unreliably and certain features may be lost. Mitotic figures, for instance, are easily lost in poorly fixed tissue. Formalin is also used to preserve prosected and dissected cadavers. As a rule of thumb, fixation occurs at about 1 mm per hour, but the reality is more complex as fixation lags behind diffusion and fixation also changes the tissue properties, slowing diffusion.<ref name="pmid22483550">{{cite journal |vauthors=Buesa RJ, Peshkov MV |title=How much formalin is enough to fix tissues? |journal=Ann Diagn Pathol |volume=16 |issue=3 |pages=202–9 |date=June 2012 |pmid=22483550 |doi=10.1016/j.anndiagpath.2011.12.003 |url=}}</ref>

Formalin cross-links sections of the peptide chains of proteins as well as nucleic acids. The effect on the former alters epitopes, which means that antibodies designed for fresh tissue may not work with fixed tissue. The cross-linking process can be partially reversed with various methods of antigen retrieval. The effect on nucleic acids is to reduce DNA quality.

=Fixing marking dye=
To fix marking dye:
*Formal-acetic alcohol (FAA):<ref>URL: [http://www.brunelmicroscopes.co.uk/acatalog/Solvents___Reagents.html http://www.brunelmicroscopes.co.uk/acatalog/Solvents___Reagents.html]. Accessed on: 5 January 2011.</ref>
*Bouin's solution.

==Formal-acetic-alcohol==
General:
*Different recipes exist.

One recipe:<ref>URL: [https://fscimage.fishersci.com/msds/45357.htm https://fscimage.fishersci.com/msds/45357.htm]. Accessed on: 5 January 2011.</ref>
*Ethanol.
*Acetic acid.
*Formaldehyde.
*Methanol.

=See also=
*[[Basics]].
*[[Histology artifacts]].
*[[Formalin-fixed paraffin-embedded]].

=References=
{{Reflist|2}}

=External links=
*[http://www.wisegeek.com/what-is-formalin.htm What is formalin (wisegeek.com)].
*[http://en.wikipedia.org/wiki/Fixation_%28histology%29 Fixation (WP)].
*[http://www-bioc.rice.edu/bios576/histology/histology.htm General overview of histology (rice.edu)].

[[Category:Basics]]

Vas deferens

2025-09-27T20:29:07Z

Mark: added plural

[[Image:Normal_Vas_Deferens%2C_Human_%283952564123%29.jpg|thumb|right|Vas deferens. (WC/Ed Uthman)]]
The '''vas deferens''' (plural: vasa deferentia) are often seen as part of a [[prostate gland|prostatectomy]] specimen.<ref>URL: [http://www.upmccancercenters.com/cancer/prostate/radprostretropubic.html http://www.upmccancercenters.com/cancer/prostate/radprostretropubic.html]. Accessed on: 26 September 2011.</ref> They are the component of the [[spermatic cord]] that carries the sperm.

They often arrive alone -- removed for family planning ([[vasectomy]]), where the job of the pathologist is to confirm a full transverse section.

==Normal vas deferens==
:''Vasectomy'' redirects here.
===General===
*Seen in the context of ''vasectomy''.

Note:
*Vasectomy is associated with [[testicle|testicular changes]] - increased seminiferous tubule wall thickness and decreased number of Sertoli cells.<ref name=pmid4058505>{{Cite journal | last1 = Jarow | first1 = JP. | last2 = Budin | first2 = RE. | last3 = Dym | first3 = M. | last4 = Zirkin | first4 = BR. | last5 = Noren | first5 = S. | last6 = Marshall | first6 = FF. | title = Quantitative pathologic changes in the human testis after vasectomy. A controlled study. | journal = N Engl J Med | volume = 313 | issue = 20 | pages = 1252-6 | month = Nov | year = 1985 | doi = 10.1056/NEJM198511143132003 | PMID = 4058505 }}</ref>

===Gross===
*Cylindrical piece of tissue.

Note:
*Surface should be inked.
===Microscopic===
Features:<ref name=pmid19926581/>
*Tubular structure - three muscle layers.
**Inner longitudinal (thin).
**Middle circular (thick).
**Outer longitudinal (thick).
*Epithelium
**Apical cells = columnar, ciliated.
**Basal cells = cuboidal.

Note:
*Muscle layers - like in bowel.
*A complete loop of epithelium should be visualized in the plane of section.

DDx:
*Missed vas deferens.
**Intermediate size blood vessels +/- denudation.
**Ureter.
*Incomplete vasectomy - only partial lumen.

===IHC===
Features:<ref name=pmid19926581>{{Cite journal | last1 = Sasaki | first1 = K. | last2 = Bastacky | first2 = SI. | last3 = Zynger | first3 = DL. | last4 = Parwani | first4 = AV. | title = Use of immunohistochemical markers to confirm the presence of vas deferens in vasectomy specimens. | journal = Am J Clin Pathol | volume = 132 | issue = 6 | pages = 893-8 | month = Dec | year = 2009 | doi = 10.1309/AJCPQZX4WS8UPKGG | PMID = 19926581 }}
</ref>
*CD10 +ve (marker of Wolffian differentiation).
*Pankeratin +ve.
*PAX-8 +ve (100%).<ref name=pmid32633248>{{cite journal |authors=Ortiz-Rey JA, Domínguez-de Dios J, Pérez-Schoch M, San Miguel-Fraile P, Gómez-de María C |title=[New immunohistochemistry markers to determine presence of vas deferens in vasectomy specimen.] |language=Spanish; Castilian |journal=Arch Esp Urol |volume=73 |issue=6 |pages=534–540 |date=July 2020 |pmid=32633248 |doi= |url=}}</ref>
*GATA-3 +ve.<ref name=pmid33012491>{{cite journal |authors=Ortiz-Rey JA, Domínguez-de Dios J, Pérez-Schoch M, San Miguel-Fraile P, Gómez-de María C |title=[E-Cadherine and GATA-3 are useful in the confirmation of the vas deferens in vasectomy specimens] |language=Spanish; Castilian |journal=Rev Esp Patol |volume=53 |issue=4 |pages=218–225 |date=2020 |pmid=33012491 |doi=10.1016/j.patol.2020.02.005 |url=}}</ref>
*ERG -ve.<ref name=pmid32633248/>
*CD34 -ve.<ref name=pmid32633248/>

===Sign out===
====Right then left====
<pre>
A. VAS DEFERENS, RIGHT, VASECTOMY:
- VAS DEFERENS WITHIN NORMAL LIMITS, LOOP OF EPITHELIUM AND MUSCLE LAYERS PRESENT.

B. VAS DEFERENS, LEFT, VASECTOMY:
- VAS DEFERENS WITHIN NORMAL LIMITS, LOOP OF EPITHELIUM AND MUSCLE LAYERS PRESENT.
</pre>

====Left then right====
<pre>
A. Vas Deferens, Left, Vasectomy:
- Vas deferens within normal limits, loop of epithelium and muscle layers present.

B. Vas Deferens, Right, Vasectomy:
- Vas deferens within normal limits, loop of epithelium and muscle layers present.
</pre>

<pre>
A. VAS DEFERENS, LEFT, VASECTOMY:
- VAS DEFERENS WITHIN NORMAL LIMITS, LOOP OF EPITHELIUM AND MUSCLE LAYERS PRESENT.

B. VAS DEFERENS, RIGHT, VASECTOMY:
- VAS DEFERENS WITHIN NORMAL LIMITS, LOOP OF EPITHELIUM AND MUSCLE LAYERS PRESENT.
</pre>

====Single container====
<pre>
VAS DEFERENS, RIGHT AND LEFT, VASECTOMY:
- VAS DEFERENS WITHIN NORMAL LIMITS, LOOPS OF EPITHELIUM AND MUSCLE LAYERS PRESENT.
</pre>

=====Alternate=====
<pre>
VAS DEFERENS, RIGHT AND LEFT, VASECTOMY:
- VAS DEFERENS WITHIN NORMAL LIMITS, LOOPS OF EPITHELIUM AND MUSCLE LAYERS PRESENT
ON BOTH SLIDE A1-1 AND SLIDE A2-1.
</pre>

=====One container is empty=====
<pre>
A. VAS DEFERENS ("LEFT"), VASECTOMY:
- VAS DEFERENS WITHIN NORMAL LIMITS, LOOPS OF EPITHELIUM AND MUSCLE LAYERS PRESENT
ON BOTH SLIDE A1-1 AND SLIDE A2-1.
- SEE COMMENT.

B. VAS DEFERENS ("RIGHT"), VASECTOMY:
- NO TISSUE IDENTIFIED, SEE COMMENT.

COMMENT:
Both specimens (left vas deferens and right vas deferens) may have been placed in
container A. See 'gross' section of report. Clinical correlation is essential.
</pre>

====Incomplete loop====
<pre>
A. VAS DEFERENS, RIGHT, VASECTOMY:
- VAS DEFERENS WITHOUT SIGNIFICANT PATHOLOGY - INCOMPLETE LOOP OF EPITHELIUM, SEE COMMENT.

B. VAS DEFERENS, LEFT, VASECTOMY:
- VAS DEFERENS WITHIN NORMAL LIMITS, LOOP OF EPITHELIUM AND MUSCLE LAYERS PRESENT.

COMMENT:
Clinical correlation is suggested.
</pre>

====Oblique cut====
<pre>
A. VAS DEFERENS, RIGHT, VASECTOMY:
- VAS DEFERENS WITHOUT SIGNIFICANT PATHOLOGY - OBLIQUE SECTION WITH COMPRESSED
LOOP OF EPITHELIUM, SEE COMMENT.

B. VAS DEFERENS, LEFT, VASECTOMY:
- VAS DEFERENS WITHIN NORMAL LIMITS, LOOP OF EPITHELIUM AND MUSCLE LAYERS PRESENT.

COMMENT:
Clinical correlation is suggested.
</pre>
Notes:
*The word ''loop'' is preferred over the words ''cross section'' as:
*#The words ''cross section'' imply the cut is perpendicular to the axis.
*#It is possible that a section with a loop of epithelium is the result of a non-transecting cut that generates an ovoid defect in the wall of the vas deferens.

====No definite epithelium====
<pre>
A. VAS DEFERENS, LEFT, VASECTOMY:
- VAS DEFERENS WITHIN NORMAL LIMITS, LOOP OF EPITHELIUM AND MUSCLE LAYERS PRESENT.

B. VAS DEFERENS, RIGHT, VASECTOMY:
- COMPATIBLE WITH VAS DEFERENS, WITHOUT COMPLETE LOOP OF EPITHELIUM, SEE COMMENT.

COMMENT - PART B:
Definite vas deferens epithelium is not identified; however, the muscle layering seen is
compatible with a vas deferens. Levels were cut (x4).

Clinical correlation is suggested.
</pre>

====No vas deferens identified====
<pre>
A. CONNECTIVE TISSUE, RIGHT, "VASECTOMY":
- NO VAS DEFERENS IDENTIFIED.
- BENIGN FIBROMUSCULAR TISSUE WITH INTERMEDIATE BLOOD VESSELS.

B. CONNECTIVE TISSUE, LEFT, "VASECTOMY":
- NO VAS DEFERENS IDENTIFIED.
- BENIGN FIBROMUSCULAR TISSUE WITH INTERMEDIATE BLOOD VESSELS.

COMMENT:
Levels were cut (x3). Clinical correlation is suggested.
</pre>

==Vasitis nodosa==
{{Main|Vasitis nodosa}}

==Bilateral absence of the vas deferens==
*Seen in [[cystic fibrosis]].

==See also==
*[[Ditzels]].
*[[Genitourinary pathology]].
*[[Prostate gland]].
*[[Testis]].
*[[Male infertility]].
*[[Epididymis]].

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

[[Category:Genitourinary pathology]]

P63

2024-07-18T22:03:21Z

Mark: rare P63 +ve prostate cancers

{{ Infobox immunostain
| Name = {{PAGENAME}}
| Image = High_grade_squamous_intraepithelial_lesion_-_2_-_p63_--_intermed_mag.jpg
| Width =
| Caption = p63 staining in squamous epithelium with dysplasia.
| Abbrev =
| Synonyms =
| Similar = [[p40]] (more [[specificity|specific]] for squamous cell carcinoma)
| Clones =
| Use = breast pathology (invasion vs. in situ), prostate pathology (HGPIN vs. cancer), lung (adenocarcinoma vs. squamous)
| Subspecial =
| Pattern = nuclear staining
| Positive = [[squamous cell carcinoma]], [[urothelial carcinoma]]
| Negative = [[prostate carcinoma]], most [[lung adenocarcinoma]], breast carcinoma
| Other =
}}
'''p63''' is a commonly used [[immunostain]]. p63, like most other "p" stains, is a nuclear stain.

==Pattern==
*Nuclear staining.
*Stains basal cells in a normal squamous epithelium.
**Superficial cells are typically negative.
**In dysplasia, the staining is seen more superficially,<ref name=pmid19700941>{{Cite journal | last1 = Houghton | first1 = O. | last2 = McCluggage | first2 = WG. | title = The expression and diagnostic utility of p63 in the female genital tract. | journal = Adv Anat Pathol | volume = 16 | issue = 5 | pages = 316-21 | month = Sep | year = 2009 | doi = 10.1097/PAP.0b013e3181b507c6 | PMID = 19700941 }}</ref> as one might expect as most squamous carcinomas are positive for p63.

Note:
*Cytoplasmic staining suggestive of muscle differentiation - seen in [[rhabdomyosarcoma]].<ref name=pmid21623385>{{Cite journal | last1 = Martin | first1 = SE. | last2 = Temm | first2 = CJ. | last3 = Goheen | first3 = MP. | last4 = Ulbright | first4 = TM. | last5 = Hattab | first5 = EM. | title = Cytoplasmic p63 immunohistochemistry is a useful marker for muscle differentiation: an immunohistochemical and immunoelectron microscopic study. | journal = Mod Pathol | volume = 24 | issue = 10 | pages = 1320-6 | month = Oct | year = 2011 | doi = 10.1038/modpathol.2011.89 | PMID = 21623385 }}</ref>

==Staining==
===Positive - common use===
*Marker of [[squamous cell carcinoma]].
*[[Urothelial carcinoma]].<ref name=pmid15976812>{{Cite journal | last1 = Lewis | first1 = JS. | last2 = Ritter | first2 = JH. | last3 = El-Mofty | first3 = S. | title = Alternative epithelial markers in sarcomatoid carcinomas of the head and neck, lung, and bladder-p63, MOC-31, and TTF-1. | journal = Mod Pathol | volume = 18 | issue = 11 | pages = 1471-81 | month = Nov | year = 2005 | doi = 10.1038/modpathol.3800451 | PMID = 15976812 | URL = http://www.nature.com/modpathol/journal/v18/n11/full/3800451a.html}}</ref>
*[[Small cell carcinoma of the lung]] ~80% of cases.<ref name=pmid15551738>{{Cite journal | last1 = Au | first1 = NH. | last2 = Gown | first2 = AM. | last3 = Cheang | first3 = M. | last4 = Huntsman | first4 = D. | last5 = Yorida | first5 = E. | last6 = Elliott | first6 = WM. | last7 = Flint | first7 = J. | last8 = English | first8 = J. | last9 = Gilks | first9 = CB. | title = P63 expression in lung carcinoma: a tissue microarray study of 408 cases. | journal = Appl Immunohistochem Mol Morphol | volume = 12 | issue = 3 | pages = 240-7 | month = Sep | year = 2004 | doi = 10.1097/00129039-200409000-00010 | PMID = 15551738 }}</ref>

===Invasive versus in situ===
Thresholding (invasive vs. pre-invasive):
*Prostate basal cell marker.
*Breast myoepithelial cell marker.

===Negative===
[[Image:Poorly differentiated carcinoma -- p63 - intermed mag.jpg|thumb|right|200px|Negative p63 staining in a poorly differentiated [[carcinoma]].]]
*[[Malignant mesothelioma]].<ref name=pmid18064689>{{Cite journal | last1 = Pu | first1 = RT. | last2 = Pang | first2 = Y. | last3 = Michael | first3 = CW. | title = Utility of WT-1, p63, MOC31, mesothelin, and cytokeratin (K903 and CK5/6) immunostains in differentiating adenocarcinoma, squamous cell carcinoma, and malignant mesothelioma in effusions. | journal = Diagn Cytopathol | volume = 36 | issue = 1 | pages = 20-5 | month = Jan | year = 2008 | doi = 10.1002/dc.20747 | PMID = 18064689 }}</ref>
*[[Breast carcinoma]].
*[[Prostatic carcinoma]] (rare cases can be P63 positive<ref name=pmid23991727>{{cite journal |vauthors=Wu A, Kunju LP |title=Prostate cancer with aberrant diffuse p63 expression: report of a case and review of the literature and morphologic mimics |journal=Arch Pathol Lab Med |volume=137 |issue=9 |pages=1179–84 |date=September 2013 |pmid=23991727 |doi=10.5858/arpa.2013-0254-CR |url=}}</ref>).

==Non-classic tumours==
*Di Como ''et al''<ref name=pmid11839669>{{Cite journal | last1 = Di Como | first1 = CJ. | last2 = Urist | first2 = MJ. | last3 = Babayan | first3 = I. | last4 = Drobnjak | first4 = M. | last5 = Hedvat | first5 = CV. | last6 = Teruya-Feldstein | first6 = J. | last7 = Pohar | first7 = K. | last8 = Hoos | first8 = A. | last9 = Cordon-Cardo | first9 = C. | title = p63 expression profiles in human normal and tumor tissues. | journal = Clin Cancer Res | volume = 8 | issue = 2 | pages = 494-501 | month = Feb | year = 2002 | doi = | PMID = 11839669 }}</ref> looked at a large cross-section of tumours.
*Jo and Fletcher<ref name=pmid22031315>{{Cite journal | last1 = Jo | first1 = VY. | last2 = Fletcher | first2 = CD. | title = p63 immunohistochemical staining is limited in soft tissue tumors. | journal = Am J Clin Pathol | volume = 136 | issue = 5 | pages = 762-6 | month = Nov | year = 2011 | doi = 10.1309/AJCPXNUC7JZSKWEU | PMID = 22031315 }}</ref> did a paper on [[soft tissue lesions]] and p63.

==See also==
*[[Immunostaining]].
*[[Stains]].

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

[[Category:Immunohistochemistry]]

SOX11

2023-10-01T20:27:41Z

Mark: other references

'''SOX11''' [[immunostain]].

==Positive==
*Lymphomas:
**[[Mantle cell lymphoma]]<ref name=pmid17934069>{{cite journal |vauthors=Ek S, Dictor M, Jerkeman M, Jirström K, Borrebaeck CA |title=Nuclear expression of the non B-cell lineage Sox11 transcription factor identifies mantle cell lymphoma |journal=Blood |volume=111 |issue=2 |pages=800–5 |date=January 2008 |pmid=17934069 |doi=10.1182/blood-2007-06-093401 |url=}}</ref> (prognostic significance initially described in <ref name=pmid18729857>{{cite journal |vauthors=Wang X, Asplund AC, Porwit A, Flygare J, Smith CI, Christensson B, Sander B |title=The subcellular Sox11 distribution pattern identifies subsets of mantle cell lymphoma: correlation to overall survival |journal=Br J Haematol |volume=143 |issue=2 |pages=248–52 |date=October 2008 |pmid=18729857 |doi=10.1111/j.1365-2141.2008.07329.x |url=}}</ref> not borne out by subsequent studies)
**[[Burkitt's lymphoma]]<ref name=pmid19880779>{{cite journal |vauthors=Dictor M, Ek S, Sundberg M, Warenholt J, György C, Sernbo S, Gustavsson E, Abu-Alsoud W, Wadström T, Borrebaeck C |title=Strong lymphoid nuclear expression of SOX11 transcription factor defines lymphoblastic neoplasms, mantle cell lymphoma and Burkitt's lymphoma |journal=Haematologica |volume=94 |issue=11 |pages=1563–8 |date=November 2009 |pmid=19880779 |pmc=2770967 |doi=10.3324/haematol.2009.008474 |url=}}</ref>
**[[Lymphoblastic lymphoma]]<ref name=pmid19880779></ref>
*[[Merkel cell carcinoma]]<ref name=pmid36745184>{{cite journal |vauthors=Cho WC, Vanderbeck K, Nagarajan P, Milton DR, Gill P, Wang WL, Curry JL, Torres-Cabala CA, Ivan D, Prieto VG, Aung PP |title=SOX11 Is an Effective Discriminatory Marker, When Used in Conjunction With CK20 and TTF1, for Merkel Cell Carcinoma: Comparative Analysis of SOX11, CK20, PAX5, and TTF1 Expression in Merkel Cell Carcinoma and Pulmonary Small Cell Carcinoma |journal=Arch Pathol Lab Med |volume=147 |issue=7 |pages=758–766 |date=July 2023 |pmid=36745184 |doi=10.5858/arpa.2022-0238-OA |ur=}}</ref>

==References==
{{Reflist|1}}

[[Category:Immunohistochemistry]]

SOX11

2023-10-01T20:20:02Z

Mark: Starter

'''SOX11''' [[immunostain]].

==Positive==
*[[Mantle cell lymphoma]]
*[[Merkel cell carcinoma]]<ref name=pmid36745184>{{cite journal |vauthors=Cho WC, Vanderbeck K, Nagarajan P, Milton DR, Gill P, Wang WL, Curry JL, Torres-Cabala CA, Ivan D, Prieto VG, Aung PP |title=SOX11 Is an Effective Discriminatory Marker, When Used in Conjunction With CK20 and TTF1, for Merkel Cell Carcinoma: Comparative Analysis of SOX11, CK20, PAX5, and TTF1 Expression in Merkel Cell Carcinoma and Pulmonary Small Cell Carcinoma |journal=Arch Pathol Lab Med |volume=147 |issue=7 |pages=758–766 |date=July 2023 |pmid=36745184 |doi=10.5858/arpa.2022-0238-OA |ur=}}

==References==
{{Reflist|1}}

[[Category:Immunohistochemistry]]

Anaplastic large cell lymphoma

2023-09-29T19:00:25Z

Mark: additional features

{{ Infobox diagnosis
| Name = {{PAGENAME}}
| Image = Anaplastic_large_cell_lymphoma_-_cropped_-_very_high_mag.jpg
| Width =
| Caption = Anaplastic large cell lymphoma. [[H&E stain]].
| Synonyms =
| Micro = large cells with eosinophilic cytoplasm, Hallmark cells ("horseshoe-shaped or donut-shaped nucleus + eosinophilic paranuclear region")
| Subtypes =
| LMDDx = [[Hodgkin's lymphoma]], poorly differentiated [[carcinoma]]
| Stains =
| IHC = CD30 +ve, ALK-1 -ve/+ve, CD45 +ve, CD4 +ve, CD3 -ve/+ve, CD7 -ve/+ve, EMA +ve
| EM =
| Molecular = t(2,5)(p23;q35)
| IF =
| Gross =
| Grossing =
| Site = [[skin]], [[lymph node]], other
| Assdx =
| Syndromes =
| Clinicalhx =
| Signs =
| Symptoms =
| Prevalence = uncommon
| Bloodwork =
| Rads =
| Endoscopy =
| Prognosis = good to poor, dependent on ALK status and site
| Other =
| ClinDDx =
| Tx =
}}
'''Anaplastic large cell lymphoma''', abbreviated '''ALCL''', is an uncommon large cell [[lymphoma]].

==General==
*May look a lot like a carcinoma.
**Often subcapsular in LNs.
*Usually T-cell derived.
*May be isolated to the [[skin]] - good prognosis.

Subtypes:
* Systemic ALCL.
* Cutaneous ALCL -- ALK -ve.

ALK IHC - systemic form:
* +ve = good prognosis (generally a disease of children, teenagers and young adults)
* -ve = bad prognosis

==Microscopic==
Features:
*Large cells with eosinophilic cytoplasm.
*Usually appear cohesive.
*May be subcapsular in a [[lymph node]] and mimic a carcinoma.
*''Hallmark cells'' = "horseshoe-shaped or [[donut cell|donut-shaped nucleus]] + eosinophilic paranuclear region"<ref name=pmid17941004>{{Cite journal | last1 = Rapkiewicz | first1 = A. | last2 = Wen | first2 = H. | last3 = Sen | first3 = F. | last4 = Das | first4 = K. | title = Cytomorphologic examination of anaplastic large cell lymphoma by fine-needle aspiration cytology. | journal = Cancer | volume = 111 | issue = 6 | pages = 499-507 | month = Dec | year = 2007 | doi = 10.1002/cncr.23120 | PMID = 17941004 | url=http://onlinelibrary.wiley.com/doi/10.1002/cncr.23120/full}}</ref><ref name=pmid12419758>{{Cite journal | last1 = Ponzoni | first1 = M. | last2 = Terreni | first2 = MR. | last3 = Ciceri | first3 = F. | last4 = Ferreri | first4 = AJ. | last5 = Gerevini | first5 = S. | last6 = Anzalone | first6 = N. | last7 = Valle | first7 = M. | last8 = Pizzolito | first8 = S. | last9 = Arrigoni | first9 = G. | title = Primary brain CD30+ ALK1+ anaplastic large cell lymphoma ('ALKoma'): the first case with a combination of 'not common' variants. | journal = Ann Oncol | volume = 13 | issue = 11 | pages = 1827-32 | month = Nov | year = 2002 | doi = | PMID = 12419758 }}</ref> - '''key feature'''.
**The donut-shaped version is also known as a "wreath cell"<ref>{{Cite journal | last1 = Amin | first1 = HM. | last2 = Lai | first2 = R. | title = Pathobiology of ALK+ anaplastic large-cell lymphoma. | journal = Blood | volume = 110 | issue = 7 | pages = 2259-67 | month = Oct | year = 2007 | doi = 10.1182/blood-2007-04-060715 | PMID = 17519389 | url=http://bloodjournal.hematologylibrary.org/content/110/7/2259.full.html}}</ref> - large (multi-nucleated) cells with (morphologically) one toroidal-shaped nucleus.
*ALK+ ALCL includes variants without the classical hallmark cells, e.g. small cell variant and lymphohistiocytic variant

DDx:
*[[Hodgkin's lymphoma]]
*Anaplastic variants of other haematolymphoid malignancies, e.g. DLBCL or myeloma
*Carcinoma
*Melanoma

===Images===
<gallery>
Image: Anaplastic large cell lymphoma - high mag.jpg | ALCL - high mag. (WC)
Image:Anaplastic_large_cell_lymphoma_-_very_high_mag.jpg | ALCL - very high mag. (WC)
Image:Anaplastic_large_cell_lymphoma_-_cropped_-_very_high_mag.jpg | ALCL - cropped - very high mag. (WC)
</gallery>
www:
*[http://path.upmc.edu/cases/case363.html ALCL - several images (upmc.edu)].
*[http://path.upmc.edu/cases/case557.html Small cell variant of ALCL - several images (upmc.edu)].

==IHC==
Features:
*CD30 +ve (usually strong and diffuse)
*ALK-1 -ve/+ve; strongly supports ALCL Dx if +ve.
*CD45 +ve.
*CD4 +ve.
*CD3 -ve/+ve.
*CD7 -ve/+ve.
*EMA +ve.
*Cytotoxic markers (e.g. TIA, perforin)

==Molecular==
*In ALK+ ALCL, there is commonly an ALK1 rearrangement.
**This may be ALK::NPM1, i.e. t(2,5)(p23;q35)<ref name=pmid8547653>{{cite journal |author=Lamant L, Meggetto F, al Saati T, ''et al.'' |title=High incidence of the t(2;5)(p23;q35) translocation in anaplastic large cell lymphoma and its lack of detection in Hodgkin's disease. Comparison of cytogenetic analysis, reverse transcriptase-polymerase chain reaction, and P-80 immunostaining |journal=Blood |volume=87 |issue=1 |pages=284–91 |year=1996 |month=January |pmid=8547653 |doi= |url=}}</ref> - combined nuclear and cytoplasmic ALK staining is a surrogate for this translocation.
*Other non-NPM1 partners may occur. A ALK1 break-apart probe will detect these.

==See also==
*[[Lymphoma]].
*[[Diffuse large B-cell lymphoma]].

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

[[Category:Lymphoma]]
[[Category:Diagnosis]]

Medullary colorectal carcinoma

2023-06-01T21:15:04Z

Mark: add gallery

{{ Infobox diagnosis
| Name = {{PAGENAME}}
| Image = Photomicrograph_of_colorectal_medullary_carcinoma_x20a.jpg
| Width =
| Caption = Micrograph of a medullary colorectal carcinoma. [[H&E stain]].
| Synonyms =
| Micro = Sheet-like architecture of malignant cells with vesicular nuclei, prominent nucleoli, and abundant eosinophilic cytoplasm. Admixed inflammatory cells (lymphocytes and neutrophils) are common.
| Subtypes =
| LMDDx = Poorly differentiated adenocarcinoma, melanoma, poorly differentiated neuroendocrine tumours, high grade lymphoma
| Stains =
| IHC = May lose CK20 and CDX2. Frequent loss of MLH1/PMS2. SATB2 +ve, BRAF VE1 +ve, calretinin +ve
| EM =
| Molecular =
| IF =
| Gross =
| Grossing =
| Staging =
| Site = Colorectum, most commonly right side of colon
| Assdx =
| Syndromes =
| Clinicalhx =
| Signs =
| Symptoms =
| Prevalence = 1-3% of all colorectal carcinomas
| Bloodwork =
| Rads =
| Endoscopy =
| Prognosis = Some papers suggest better prognosis than conventional adenocarcinoma
| Other =
| ClinDDx =
| Tx =
}}
'''Medullary colorectal carcinoma''' is a rare type of [[colorectal carcinoma]]. Precise incidence difficult to determine as there no strict criteria for diagnosis, especially if the tumour also contains conventional adenocarcinoma. Cases may not be recognised and diagnosed as poorly differentiated adenocarcinona instead.<ref name=pmid33247957>{{cite journal |vauthors=Scott N, West NP, Cairns A, Rotimi O |title=Is medullary carcinoma of the colon underdiagnosed? An audit of poorly differentiated colorectal carcinomas in a large national health service teaching hospital |journal=Histopathology |volume=78 |issue=7 |pages=963–969 |date=June 2021 |pmid=33247957 |doi=10.1111/his.14310 |url=}}</ref>

==General==
*Rare subtype of colorectal carcinoma. In these papers: 1.1%<ref name=pmid33247957/>, 2.8%<ref name=pmid25572685>{{cite journal |vauthors=Knox RD, Luey N, Sioson L, Kedziora A, Clarkson A, Watson N, Toon CW, Cussigh C, Pincott S, Pillinger S, Salama Y, Evans J, Percy J, Schnitzler M, Engel A, Gill AJ |title=Medullary colorectal carcinoma revisited: a clinical and pathological study of 102 cases |journal=Ann Surg Oncol |volume=22 |issue=9 |pages=2988–96 |date=September 2015 |pmid=25572685 |doi=10.1245/s10434-014-4355-5 |url=}}</ref>, and 3.6%<ref name=pmid10561306>{{cite journal |vauthors=Lanza G, Gafà R, Matteuzzi M, Santini A |title=Medullary-type poorly differentiated adenocarcinoma of the large bowel: a distinct clinicopathologic entity characterized by microsatellite instability and improved survival |journal=J Clin Oncol |volume=17 |issue=8 |pages=2429–38 |date=August 1999 |pmid=10561306 |doi=10.1200/JCO.1999.17.8.2429 |url=}}</ref>
*Typically has [[MSI|microsatellite instability]].<ref name=pmid24815832 >{{cite journal |authors=Cunningham J, Kantekure K, Saif MW |title=Medullary carcinoma of the colon: a case series and review of the literature |journal=In Vivo |volume=28 |issue=3 |pages=311–4 |date=2014 |pmid=24815832 |doi= |url=}}</ref>
*Prognostic significance dependent on study.
**A small series suggests the prognosis of medullary carcinoma with MSI is worse that conventional colorectal carcinoma without MSI.<ref>{{cite journal |authors=Gómez-Álvarez MA, Lino-Silva LS, Salcedo-Hernández RA, Padilla-Rosciano A, Ruiz-García EB, López-Basave HN, Calderillo-Ruiz G, Aguilar-Romero JM, Domínguez-Rodríguez JA, Herrera-Gómez Á, Meneses-García A |title=Medullary colonic carcinoma with microsatellite instability has lower survival compared with conventional colonic adenocarcinoma with microsatellite instability |journal=Prz Gastroenterol |volume=12 |issue=3 |pages=208–214 |date=2017 |pmid=29123583 |pmc=5672702 |doi=10.5114/pg.2016.64740 |url=}}</ref>
**A series with 102 cases suggests a better prognosis when compared on the basis of other pathological characteristics.<ref name=pmid25572685/>

==Gross==
*Well-circumscribed.

==Microscopic==
Features:
*Poorly differentiated carcinoma:
**Noninfiltrative border.
**Solid pattern/nests.
**No gland formation.
**Lymphocytic infiltrate.

DDx:
*Other (poorly differentiated) [[colorectal carcinoma]]s.
**Colorectal cancer with loss of [[SMARCB1]] expression.<ref name=pmid32083567/>
*Carcinomas with neuroendocrine differentiation.
*[[Lymphoepithelioma-like carcinoma]] of the colon.<ref>{{cite journal |authors=Delaney D, Chetty R |title=Lymphoepithelioma-like carcinoma of the colon |journal=Int J Clin Exp Pathol |volume=5 |issue=1 |pages=105–9 |date=2012 |pmid=22295155 |pmc=3267494 |doi= |url=}}</ref>

==IHC==
Features:<ref name=pmid24815832/>
*CDX2 +ve (though can be lost)
*Beta-catenin +ve.
*MLH1/PMS2 loss of staining.
*Calretinin (67%-73%)<ref>{{cite journal |authors=Winn B, Tavares R, Fanion J, Noble L, Gao J, Sabo E, Resnick MB |title=Differentiating the undifferentiated: immunohistochemical profile of medullary carcinoma of the colon with an emphasis on intestinal differentiation |journal=Hum. Pathol. |volume=40 |issue=3 |pages=398–404 |date=March 2009 |pmid=18992917 |pmc=2657293 |doi=10.1016/j.humpath.2008.08.014 |url=}}</ref><ref>{{cite journal |authors=Lin F, Shi J, Zhu S, Chen Z, Li A, Chen T, Wang HL, Liu H |title=Cadherin-17 and SATB2 are sensitive and specific immunomarkers for medullary carcinoma of the large intestine |journal=Arch. Pathol. Lab. Med. |volume=138 |issue=8 |pages=1015–26 |date=August 2014 |pmid=24437456 |doi=10.5858/arpa.2013-0452-OA |url=}}</ref>

Notes:
*CDX2, beta-catenin, MLH1 useful for differentiating from poorly differentiated colorectal carcinoma.
*SMARCB1 loss - reported in one case.<ref name=pmid32083567>{{cite journal |authors=Melloul S, Mosnier JF, Masliah-Planchon J, Lepage C, Le Malicot K, Gornet JM, Edeline J, Dansette D, Texereau P, Delattre O, Laurent Puig P, Taieb J, Emile JF |title=Loss of SMARCB1 expression in colon carcinoma |journal=Cancer Biomark |volume=27 |issue=3 |pages=399–406 |date=2020 |pmid=32083567 |doi=10.3233/CBM-190287 |url=}}</ref>

===Images===
<gallery>
Image:Photomicrograph of colorectal medullary carcinoma x20a.jpg | Note numerous interspersed inflammatory cells (WC)
Image:Photomicrograph of colorectal medullary carcinoma x20d.jpg | Note numerous interspersed inflammatory cells (WC)
</gallery>

<gallery>
Image: Photomicrograph of medullary carcinoma at anorectum x4a.jpg | Medullary carcinoma - low mag. (WC)
Image: Photomicrograph of medullary carcinoma at anorectum x20a.jpg | Medullary carcinoma - medium/high mag. (WC)
Image: Photomicrograph of medullary carcinoma CK7 immunohistochemistry x20.png | CK7 negative (WC)
Image: Photomicrograph of medullary carcinoma CK20 immunohistochemistry x20.png | CK20 negative (WC)
Image: Photomicrograph of medullary carcinoma CDX2 immunohistochemistry x20.png | CDX2 variably positive (WC)
Image: Photomicrograph of medullary carcinoma SATB2 immunohistochemistry x20.png | SATB2 positive (WC)
Image: Photomicrograph of medullary carcinoma MLH1 immunohistochemistry x20.png | Loss of MLH1 expression (WC)
Image: Photomicrograph of medullary carcinoma PMS2 immunohistochemistry x20.png | Loss of PMS2 expression (WC)
Image: Photomicrograph of medullary carcinoma BRAF-VE1 immunohistochemistry x20.png | BRAF VE1 positive (WC)
</gallery>

==See also==
*[[Colorectal adenocarcinoma]].

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

[[Category:Diagnosis]]
[[Category:Gastrointestinal pathology]]

Medullary colorectal carcinoma

2023-06-01T20:39:41Z

Mark: add infobox

{{ Infobox diagnosis
| Name = {{PAGENAME}}
| Image = Photomicrograph_of_colorectal_medullary_carcinoma_x20a.jpg
| Width =
| Caption = Micrograph of a medullary colorectal carcinoma. [[H&E stain]].
| Synonyms =
| Micro = Sheet-like architecture of malignant cells with vesicular nuclei, prominent nucleoli, and abundant eosinophilic cytoplasm. Admixed inflammatory cells (lymphocytes and neutrophils) are common.
| Subtypes =
| LMDDx = Poorly differentiated adenocarcinoma, melanoma, poorly differentiated neuroendocrine tumours, high grade lymphoma
| Stains =
| IHC = May lose CK20 and CDX2. Frequent loss of MLH1/PMS2. SATB2 +ve, BRAF VE1 +ve, calretinin +ve
| EM =
| Molecular =
| IF =
| Gross =
| Grossing =
| Staging =
| Site = Colorectum, most commonly right side of colon
| Assdx =
| Syndromes =
| Clinicalhx =
| Signs =
| Symptoms =
| Prevalence = 1-3% of all colorectal carcinomas
| Bloodwork =
| Rads =
| Endoscopy =
| Prognosis = Some papers suggest better prognosis than conventional adenocarcinoma
| Other =
| ClinDDx =
| Tx =
}}
'''Medullary colorectal carcinoma''' is a rare type of [[colorectal carcinoma]]. Precise incidence difficult to determine as there no strict criteria for diagnosis, especially if the tumour also contains conventional adenocarcinoma. Cases may not be recognised and diagnosed as poorly differentiated adenocarcinona instead.<ref name=pmid33247957>{{cite journal |vauthors=Scott N, West NP, Cairns A, Rotimi O |title=Is medullary carcinoma of the colon underdiagnosed? An audit of poorly differentiated colorectal carcinomas in a large national health service teaching hospital |journal=Histopathology |volume=78 |issue=7 |pages=963–969 |date=June 2021 |pmid=33247957 |doi=10.1111/his.14310 |url=}}</ref>

==General==
*Rare subtype of colorectal carcinoma. In these papers: 1.1%<ref name=pmid33247957/>, 2.8%<ref name=pmid25572685>{{cite journal |vauthors=Knox RD, Luey N, Sioson L, Kedziora A, Clarkson A, Watson N, Toon CW, Cussigh C, Pincott S, Pillinger S, Salama Y, Evans J, Percy J, Schnitzler M, Engel A, Gill AJ |title=Medullary colorectal carcinoma revisited: a clinical and pathological study of 102 cases |journal=Ann Surg Oncol |volume=22 |issue=9 |pages=2988–96 |date=September 2015 |pmid=25572685 |doi=10.1245/s10434-014-4355-5 |url=}}</ref>, and 3.6%<ref name=pmid10561306>{{cite journal |vauthors=Lanza G, Gafà R, Matteuzzi M, Santini A |title=Medullary-type poorly differentiated adenocarcinoma of the large bowel: a distinct clinicopathologic entity characterized by microsatellite instability and improved survival |journal=J Clin Oncol |volume=17 |issue=8 |pages=2429–38 |date=August 1999 |pmid=10561306 |doi=10.1200/JCO.1999.17.8.2429 |url=}}</ref>
*Typically has [[MSI|microsatellite instability]].<ref name=pmid24815832 >{{cite journal |authors=Cunningham J, Kantekure K, Saif MW |title=Medullary carcinoma of the colon: a case series and review of the literature |journal=In Vivo |volume=28 |issue=3 |pages=311–4 |date=2014 |pmid=24815832 |doi= |url=}}</ref>
*Prognostic significance dependent on study.
**A small series suggests the prognosis of medullary carcinoma with MSI is worse that conventional colorectal carcinoma without MSI.<ref>{{cite journal |authors=Gómez-Álvarez MA, Lino-Silva LS, Salcedo-Hernández RA, Padilla-Rosciano A, Ruiz-García EB, López-Basave HN, Calderillo-Ruiz G, Aguilar-Romero JM, Domínguez-Rodríguez JA, Herrera-Gómez Á, Meneses-García A |title=Medullary colonic carcinoma with microsatellite instability has lower survival compared with conventional colonic adenocarcinoma with microsatellite instability |journal=Prz Gastroenterol |volume=12 |issue=3 |pages=208–214 |date=2017 |pmid=29123583 |pmc=5672702 |doi=10.5114/pg.2016.64740 |url=}}</ref>
**A series with 102 cases suggests a better prognosis when compared on the basis of other pathological characteristics.<ref name=pmid25572685/>

==Gross==
*Well-circumscribed.

==Microscopic==
Features:
*Poorly differentiated carcinoma:
**Noninfiltrative border.
**Solid pattern/nests.
**No gland formation.
**Lymphocytic infiltrate.

DDx:
*Other (poorly differentiated) [[colorectal carcinoma]]s.
**Colorectal cancer with loss of [[SMARCB1]] expression.<ref name=pmid32083567/>
*Carcinomas with neuroendocrine differentiation.
*[[Lymphoepithelioma-like carcinoma]] of the colon.<ref>{{cite journal |authors=Delaney D, Chetty R |title=Lymphoepithelioma-like carcinoma of the colon |journal=Int J Clin Exp Pathol |volume=5 |issue=1 |pages=105–9 |date=2012 |pmid=22295155 |pmc=3267494 |doi= |url=}}</ref>

==IHC==
Features:<ref name=pmid24815832/>
*CDX2 +ve (though can be lost)
*Beta-catenin +ve.
*MLH1/PMS2 loss of staining.
*Calretinin (67%-73%)<ref>{{cite journal |authors=Winn B, Tavares R, Fanion J, Noble L, Gao J, Sabo E, Resnick MB |title=Differentiating the undifferentiated: immunohistochemical profile of medullary carcinoma of the colon with an emphasis on intestinal differentiation |journal=Hum. Pathol. |volume=40 |issue=3 |pages=398–404 |date=March 2009 |pmid=18992917 |pmc=2657293 |doi=10.1016/j.humpath.2008.08.014 |url=}}</ref><ref>{{cite journal |authors=Lin F, Shi J, Zhu S, Chen Z, Li A, Chen T, Wang HL, Liu H |title=Cadherin-17 and SATB2 are sensitive and specific immunomarkers for medullary carcinoma of the large intestine |journal=Arch. Pathol. Lab. Med. |volume=138 |issue=8 |pages=1015–26 |date=August 2014 |pmid=24437456 |doi=10.5858/arpa.2013-0452-OA |url=}}</ref>

Notes:
*CDX2, beta-catenin, MLH1 useful for differentiating from poorly differentiated colorectal carcinoma.
*SMARCB1 loss - reported in one case.<ref name=pmid32083567>{{cite journal |authors=Melloul S, Mosnier JF, Masliah-Planchon J, Lepage C, Le Malicot K, Gornet JM, Edeline J, Dansette D, Texereau P, Delattre O, Laurent Puig P, Taieb J, Emile JF |title=Loss of SMARCB1 expression in colon carcinoma |journal=Cancer Biomark |volume=27 |issue=3 |pages=399–406 |date=2020 |pmid=32083567 |doi=10.3233/CBM-190287 |url=}}</ref>

==See also==
*[[Colorectal adenocarcinoma]].

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

[[Category:Diagnosis]]
[[Category:Gastrointestinal pathology]]

Medullary colorectal carcinoma

2023-06-01T20:11:24Z

Mark: correcting mistake in PubMed ID

'''Medullary colorectal carcinoma''' is a rare type of [[colorectal carcinoma]]. Precise incidence difficult to determine as there no strict criteria for diagnosis, especially if the tumour also contains conventional adenocarcinoma. Cases may not be recognised and diagnosed as poorly differentiated adenocarcinona instead.<ref name=pmid33247957>{{cite journal |vauthors=Scott N, West NP, Cairns A, Rotimi O |title=Is medullary carcinoma of the colon underdiagnosed? An audit of poorly differentiated colorectal carcinomas in a large national health service teaching hospital |journal=Histopathology |volume=78 |issue=7 |pages=963–969 |date=June 2021 |pmid=33247957 |doi=10.1111/his.14310 |url=}}</ref>

==General==
*Rare subtype of colorectal carcinoma. In these papers: 1.1%<ref name=pmid33247957/>, 2.8%<ref name=pmid25572685>{{cite journal |vauthors=Knox RD, Luey N, Sioson L, Kedziora A, Clarkson A, Watson N, Toon CW, Cussigh C, Pincott S, Pillinger S, Salama Y, Evans J, Percy J, Schnitzler M, Engel A, Gill AJ |title=Medullary colorectal carcinoma revisited: a clinical and pathological study of 102 cases |journal=Ann Surg Oncol |volume=22 |issue=9 |pages=2988–96 |date=September 2015 |pmid=25572685 |doi=10.1245/s10434-014-4355-5 |url=}}</ref>, and 3.6%<ref name=pmid10561306>{{cite journal |vauthors=Lanza G, Gafà R, Matteuzzi M, Santini A |title=Medullary-type poorly differentiated adenocarcinoma of the large bowel: a distinct clinicopathologic entity characterized by microsatellite instability and improved survival |journal=J Clin Oncol |volume=17 |issue=8 |pages=2429–38 |date=August 1999 |pmid=10561306 |doi=10.1200/JCO.1999.17.8.2429 |url=}}</ref>
*Typically has [[MSI|microsatellite instability]].<ref name=pmid24815832 >{{cite journal |authors=Cunningham J, Kantekure K, Saif MW |title=Medullary carcinoma of the colon: a case series and review of the literature |journal=In Vivo |volume=28 |issue=3 |pages=311–4 |date=2014 |pmid=24815832 |doi= |url=}}</ref>
*Prognostic significance dependent on study.
**A small series suggests the prognosis of medullary carcinoma with MSI is worse that conventional colorectal carcinoma without MSI.<ref>{{cite journal |authors=Gómez-Álvarez MA, Lino-Silva LS, Salcedo-Hernández RA, Padilla-Rosciano A, Ruiz-García EB, López-Basave HN, Calderillo-Ruiz G, Aguilar-Romero JM, Domínguez-Rodríguez JA, Herrera-Gómez Á, Meneses-García A |title=Medullary colonic carcinoma with microsatellite instability has lower survival compared with conventional colonic adenocarcinoma with microsatellite instability |journal=Prz Gastroenterol |volume=12 |issue=3 |pages=208–214 |date=2017 |pmid=29123583 |pmc=5672702 |doi=10.5114/pg.2016.64740 |url=}}</ref>
**A series with 102 cases suggests a better prognosis when compared on the basis of other pathological characteristics.<ref name=pmid25572685>{{cite journal |authors=Knox RD, Luey N, Sioson L, Kedziora A, Clarkson A, Watson N, Toon CW, Cussigh C, Pincott S, Pillinger S, Salama Y, Evans J, Percy J, Schnitzler M, Engel A, Gill AJ |title=Medullary colorectal carcinoma revisited: a clinical and pathological study of 102 cases |journal=Ann. Surg. Oncol. |volume=22 |issue=9 |pages=2988–96 |date=September 2015 |pmid=25572685 |doi=10.1245/s10434-014-4355-5 |url=}}</ref>

==Gross==
*Well-circumscribed.

==Microscopic==
Features:
*Poorly differentiated carcinoma:
**Noninfiltrative border.
**Solid pattern/nests.
**No gland formation.
**Lymphocytic infiltrate.

DDx:
*Other (poorly differentiated) [[colorectal carcinoma]]s.
**Colorectal cancer with loss of [[SMARCB1]] expression.<ref name=pmid32083567/>
*Carcinomas with neuroendocrine differentiation.
*[[Lymphoepithelioma-like carcinoma]] of the colon.<ref>{{cite journal |authors=Delaney D, Chetty R |title=Lymphoepithelioma-like carcinoma of the colon |journal=Int J Clin Exp Pathol |volume=5 |issue=1 |pages=105–9 |date=2012 |pmid=22295155 |pmc=3267494 |doi= |url=}}</ref>

==IHC==
Features:<ref name=pmid24815832/>
*CDX2 +ve (though can be lost)
*Beta-catenin +ve.
*MLH1/PMS2 loss of staining.
*Calretinin (67%-73%)<ref>{{cite journal |authors=Winn B, Tavares R, Fanion J, Noble L, Gao J, Sabo E, Resnick MB |title=Differentiating the undifferentiated: immunohistochemical profile of medullary carcinoma of the colon with an emphasis on intestinal differentiation |journal=Hum. Pathol. |volume=40 |issue=3 |pages=398–404 |date=March 2009 |pmid=18992917 |pmc=2657293 |doi=10.1016/j.humpath.2008.08.014 |url=}}</ref><ref>{{cite journal |authors=Lin F, Shi J, Zhu S, Chen Z, Li A, Chen T, Wang HL, Liu H |title=Cadherin-17 and SATB2 are sensitive and specific immunomarkers for medullary carcinoma of the large intestine |journal=Arch. Pathol. Lab. Med. |volume=138 |issue=8 |pages=1015–26 |date=August 2014 |pmid=24437456 |doi=10.5858/arpa.2013-0452-OA |url=}}</ref>

Notes:
*CDX2, beta-catenin, MLH1 useful for differentiating from poorly differentiated colorectal carcinoma.
*SMARCB1 loss - reported in one case.<ref name=pmid32083567>{{cite journal |authors=Melloul S, Mosnier JF, Masliah-Planchon J, Lepage C, Le Malicot K, Gornet JM, Edeline J, Dansette D, Texereau P, Delattre O, Laurent Puig P, Taieb J, Emile JF |title=Loss of SMARCB1 expression in colon carcinoma |journal=Cancer Biomark |volume=27 |issue=3 |pages=399–406 |date=2020 |pmid=32083567 |doi=10.3233/CBM-190287 |url=}}</ref>

==See also==
*[[Colorectal adenocarcinoma]].

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

[[Category:Diagnosis]]
[[Category:Gastrointestinal pathology]]

Medullary colorectal carcinoma

2023-06-01T20:10:14Z

Mark: references for proportion of all colorectal cancers

'''Medullary colorectal carcinoma''' is a rare type of [[colorectal carcinoma]]. Precise incidence difficult to determine as there no strict criteria for diagnosis, especially if the tumour also contains conventional adenocarcinoma. Cases may not be recognised and diagnosed as poorly differentiated adenocarcinona instead.<ref name=pmid25572685>{{cite journal |vauthors=Scott N, West NP, Cairns A, Rotimi O |title=Is medullary carcinoma of the colon underdiagnosed? An audit of poorly differentiated colorectal carcinomas in a large national health service teaching hospital |journal=Histopathology |volume=78 |issue=7 |pages=963–969 |date=June 2021 |pmid=33247957 |doi=10.1111/his.14310 |url=}}</ref>

==General==
*Rare subtype of colorectal carcinoma. In these papers: 1.1%<ref name=pmid25572685/>, 2.8%<ref name=pmid25572685>{{cite journal |vauthors=Knox RD, Luey N, Sioson L, Kedziora A, Clarkson A, Watson N, Toon CW, Cussigh C, Pincott S, Pillinger S, Salama Y, Evans J, Percy J, Schnitzler M, Engel A, Gill AJ |title=Medullary colorectal carcinoma revisited: a clinical and pathological study of 102 cases |journal=Ann Surg Oncol |volume=22 |issue=9 |pages=2988–96 |date=September 2015 |pmid=25572685 |doi=10.1245/s10434-014-4355-5 |url=}}</ref>, and 3.6%<ref name=pmid10561306>{{cite journal |vauthors=Lanza G, Gafà R, Matteuzzi M, Santini A |title=Medullary-type poorly differentiated adenocarcinoma of the large bowel: a distinct clinicopathologic entity characterized by microsatellite instability and improved survival |journal=J Clin Oncol |volume=17 |issue=8 |pages=2429–38 |date=August 1999 |pmid=10561306 |doi=10.1200/JCO.1999.17.8.2429 |url=}}</ref>
*Typically has [[MSI|microsatellite instability]].<ref name=pmid24815832 >{{cite journal |authors=Cunningham J, Kantekure K, Saif MW |title=Medullary carcinoma of the colon: a case series and review of the literature |journal=In Vivo |volume=28 |issue=3 |pages=311–4 |date=2014 |pmid=24815832 |doi= |url=}}</ref>
*Prognostic significance dependent on study.
**A small series suggests the prognosis of medullary carcinoma with MSI is worse that conventional colorectal carcinoma without MSI.<ref>{{cite journal |authors=Gómez-Álvarez MA, Lino-Silva LS, Salcedo-Hernández RA, Padilla-Rosciano A, Ruiz-García EB, López-Basave HN, Calderillo-Ruiz G, Aguilar-Romero JM, Domínguez-Rodríguez JA, Herrera-Gómez Á, Meneses-García A |title=Medullary colonic carcinoma with microsatellite instability has lower survival compared with conventional colonic adenocarcinoma with microsatellite instability |journal=Prz Gastroenterol |volume=12 |issue=3 |pages=208–214 |date=2017 |pmid=29123583 |pmc=5672702 |doi=10.5114/pg.2016.64740 |url=}}</ref>
**A series with 102 cases suggests a better prognosis when compared on the basis of other pathological characteristics.<ref name=pmid25572685>{{cite journal |authors=Knox RD, Luey N, Sioson L, Kedziora A, Clarkson A, Watson N, Toon CW, Cussigh C, Pincott S, Pillinger S, Salama Y, Evans J, Percy J, Schnitzler M, Engel A, Gill AJ |title=Medullary colorectal carcinoma revisited: a clinical and pathological study of 102 cases |journal=Ann. Surg. Oncol. |volume=22 |issue=9 |pages=2988–96 |date=September 2015 |pmid=25572685 |doi=10.1245/s10434-014-4355-5 |url=}}</ref>

==Gross==
*Well-circumscribed.

==Microscopic==
Features:
*Poorly differentiated carcinoma:
**Noninfiltrative border.
**Solid pattern/nests.
**No gland formation.
**Lymphocytic infiltrate.

DDx:
*Other (poorly differentiated) [[colorectal carcinoma]]s.
**Colorectal cancer with loss of [[SMARCB1]] expression.<ref name=pmid32083567/>
*Carcinomas with neuroendocrine differentiation.
*[[Lymphoepithelioma-like carcinoma]] of the colon.<ref>{{cite journal |authors=Delaney D, Chetty R |title=Lymphoepithelioma-like carcinoma of the colon |journal=Int J Clin Exp Pathol |volume=5 |issue=1 |pages=105–9 |date=2012 |pmid=22295155 |pmc=3267494 |doi= |url=}}</ref>

==IHC==
Features:<ref name=pmid24815832/>
*CDX2 +ve (though can be lost)
*Beta-catenin +ve.
*MLH1/PMS2 loss of staining.
*Calretinin (67%-73%)<ref>{{cite journal |authors=Winn B, Tavares R, Fanion J, Noble L, Gao J, Sabo E, Resnick MB |title=Differentiating the undifferentiated: immunohistochemical profile of medullary carcinoma of the colon with an emphasis on intestinal differentiation |journal=Hum. Pathol. |volume=40 |issue=3 |pages=398–404 |date=March 2009 |pmid=18992917 |pmc=2657293 |doi=10.1016/j.humpath.2008.08.014 |url=}}</ref><ref>{{cite journal |authors=Lin F, Shi J, Zhu S, Chen Z, Li A, Chen T, Wang HL, Liu H |title=Cadherin-17 and SATB2 are sensitive and specific immunomarkers for medullary carcinoma of the large intestine |journal=Arch. Pathol. Lab. Med. |volume=138 |issue=8 |pages=1015–26 |date=August 2014 |pmid=24437456 |doi=10.5858/arpa.2013-0452-OA |url=}}</ref>

Notes:
*CDX2, beta-catenin, MLH1 useful for differentiating from poorly differentiated colorectal carcinoma.
*SMARCB1 loss - reported in one case.<ref name=pmid32083567>{{cite journal |authors=Melloul S, Mosnier JF, Masliah-Planchon J, Lepage C, Le Malicot K, Gornet JM, Edeline J, Dansette D, Texereau P, Delattre O, Laurent Puig P, Taieb J, Emile JF |title=Loss of SMARCB1 expression in colon carcinoma |journal=Cancer Biomark |volume=27 |issue=3 |pages=399–406 |date=2020 |pmid=32083567 |doi=10.3233/CBM-190287 |url=}}</ref>

==See also==
*[[Colorectal adenocarcinoma]].

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

[[Category:Diagnosis]]
[[Category:Gastrointestinal pathology]]

Granulocytic sarcoma

2023-01-10T22:09:04Z

Mark: cases can occasionally precede full blown AML

{{ Infobox diagnosis
| Name = {{PAGENAME}}
| Image = Chloroma_-_very_high_mag.jpg
| Width =
| Caption = Chloroma. [[H&E stain]].
| Synonyms = extramedullary leukemia, myeloid sarcoma and chloroma, myeloblastoma, chloromyeloma, chloromyelosarcoma, granulocytic leukosarcoma, myelosarcoma
| Micro = atypical small blue cells ~2x resting lymphocyte, infiltrative
| Subtypes =
| LMDDx = [[small round cell tumours]]
| Stains =
| IHC = CD117 +ve, CD43 +ve, CD34 +ve/-ve
| EM =
| Molecular =
| IF =
| Gross =
| Grossing =
| Site = [[soft tissue lesion]]
| Assdx =
| Syndromes =
| Clinicalhx =
| Signs =
| Symptoms =
| Prevalence = rare
| Bloodwork =
| Rads =
| Endoscopy =
| Prognosis =
| Other =
| ClinDDx = other [[soft tissue lesions]]
| Tx = see ''[[acute myeloid leukemia]]''
}}
'''Granulocytic sarcoma''' is an uncommon [[malignant]] [[soft tissue lesion]] that really represents a hematologic malignancy; it is a soft tissue manifestation of [[acute myeloid leukemia]]. It is ''not'' a [[sarcoma]]. In a small number of cases, granulocytic sarcoma may precede systemic disease and may show a aleukaemic picture, i.e. there may not be significant numbers of blasts circulating in the blood.

Numerous other terms refer to this including '''extramedullary leukemia''',<ref name=pmid21795742>{{Cite journal | last1 = Bakst | first1 = RL. | last2 = Tallman | first2 = MS. | last3 = Douer | first3 = D. | last4 = Yahalom | first4 = J. | title = How I treat extramedullary acute myeloid leukemia. | journal = Blood | volume = 118 | issue = 14 | pages = 3785-93 | month = Oct | year = 2011 | doi = 10.1182/blood-2011-04-347229 | PMID = 21795742 }}</ref> '''myeloid sarcoma''' and '''chloroma'''.

Less common terms include:<ref name=pmid21556238>{{Cite journal | last1 = Eom | first1 = KS. | last2 = Kim | first2 = TY. | title = Intraparenchymal myeloid sarcoma and subsequent spinal myeloid sarcoma for acute myeloblastic leukemia. | journal = J Korean Neurosurg Soc | volume = 49 | issue = 3 | pages = 171-4 | month = Mar | year = 2011 | doi = 10.3340/jkns.2011.49.3.171 | PMID = 21556238 | PMC = 3085814 | url = http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3085814/ }}</ref> '''myeloblastoma''', '''chloromyeloma''', '''chloromyelosarcoma''', '''granulocytic leukosarcoma''', and '''myelosarcoma'''.

==General==
*Soft tissue manifestation of [[acute myeloid leukemia]].<ref name=pmid21556238/>
*WBC elevated, low or normal range.<ref name=pmid25678833>{{Cite journal | last1 = Arthur | first1 = C. | last2 = Cermak | first2 = J. | last3 = Delaunay | first3 = J. | last4 = Mayer | first4 = J. | last5 = Mazur | first5 = G. | last6 = Thomas | first6 = X. | last7 = Wierzbowska | first7 = A. | last8 = Jones | first8 = MM. | last9 = Berrak | first9 = E. | title = Post hoc analysis of the relationship between baseline white blood cell count and survival outcome in a randomized Phase III trial of decitabine in older patients with newly diagnosed acute myeloid leukemia. | journal = J Blood Med | volume = 6 | issue = | pages = 25-9 | month = | year = 2015 | doi = 10.2147/JBM.S64067 | PMID = 25678833 }}</ref>

==Microscopic==
Features:
*Cluster of atypical small blue cells in [[soft tissue lesions|soft tissue]] with scant cytoplasm.

DDx:
*[[Small cell carcinoma]]
*Large cell lymphomas ([[DLBCL]], [[ALCL]]).
*Other [[small round cell tumour]]s.

===Images===
<gallery>
Image:Chloroma - intermed mag.jpg | Chloroma - intermed. mag. (WC)
Image:Chloroma_-_high_mag.jpg | Chloroma - high mag. (WC)
Image:Chloroma_-_very_high_mag.jpg | Chloroma - very high mag. (WC)
Image:Myeloid sarcoma within a lymph node x40 magnification.jpg | Myeloid sarcoma within a lymph node (WC)
</gallery>
www:
*[http://path.upmc.edu/cases/case306/micro.html Granulocytic sarcoma - several crappy images (upmc.edu)].
*[http://path.upmc.edu/cases/case379.html Myeloid sarcoma - several images (upmc.edu)].

==IHC==
Features:<ref name=pmid24969631>{{Cite journal | last1 = Seifert | first1 = RP. | last2 = Bulkeley | first2 = W. | last3 = Zhang | first3 = L. | last4 = Menes | first4 = M. | last5 = Bui | first5 = MM. | title = A practical approach to diagnose soft tissue myeloid sarcoma preceding or coinciding with acute myeloid leukemia. | journal = Ann Diagn Pathol | volume = 18 | issue = 4 | pages = 253-60 | month = Aug | year = 2014 | doi = 10.1016/j.anndiagpath.2014.06.001 | PMID = 24969631 }}</ref>
Markers of immaturity:
*CD34 +ve/-ve (5 of 9 cases).
*CD117 +ve (9 of 9 cases).
*TdT
Myeloid markers:
*CD43 +ve (7 of 7 cases) - sensitive, but not specific
*Myeloperoxidase +ve (8 of 10 cases).
*CD11c (myelomonocytic marker)
*CD13 (granulopoietic marker)
*CD33 (granulopoietic marker, specific but less sensitive)

CD34, CD117 and myeloperoxidase are more commonly positive in cases showing granulopoietic differentiation, but can be negative in cases with a myelomonocytic or monocytic differentiation, where CD68, CD163 and lysozyme may be helpful.<ref name=pmid23530613>{{cite journal |vauthors=Zhou J, Bell D, Medeiros LJ |title=Myeloid sarcoma of the head and neck region |journal=Arch Pathol Lab Med |volume=137 |issue=11 |pages=1560–8 |date=November 2013 |pmid=23530613 |doi=10.5858/arpa.2012-0537-OA |url=}}</ref>

==Sign out==
*It is prudent to mention ''acute myeloid leukemia'' somewhere in the report to ensure the appropriate referral is made.

==See also==
*[[Soft tissue lesions]].
*[[Intravascular lymphoma]].

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

[[Category:Diagnosis]]
[[Category:Soft tissue lesions]]

User talk:Mark

2023-01-10T22:03:47Z

Mark: new citation generator link

== PubMed references ==

Thanks for the edits!

In [https://librepathology.org/w/index.php?title=GATA3&diff=48535&oldid=46435 this edit] you noted that you "...have yet to work out how to convert pmid numbers to wikimedia references". This is described in some detail in the ''[[Libre_Pathology:References|References]]'' article.

The short version is:
# Open: http://librepathology.org/cite-gen/
# Copy & paste the PMID into the input box
# Click ''Generate''
# Copy output into the page you are editing

I hope the above helps! [[User:Michael|Michael]] ([[User talk:Michael|talk]]) 09:41, 7 February 2018 (EST)

Reminder for me of new link: https://citation-template-filling.toolforge.org/cgi-bin/index.cgi

== The Silver Microscope ==

[[Image: Nachet collection - German microscope with silver mounts - Wellcome M0000219.jpg|thumb|150px|The Silver Microscope]]
Thank you for your contributions! [[Special:ContributionScores|You've surpassed >30 edits]]. Here is a small token of appreciation: [[Libre Pathology:Silver microscope|The Silver Microscope]]. [[User:Michael|Michael]] ([[User talk:Michael|talk]]) 11:23, 20 June 2018 (EDT)

Granulocytic sarcoma

2023-01-10T22:00:07Z

Mark: add another image; other IHC markers

{{ Infobox diagnosis
| Name = {{PAGENAME}}
| Image = Chloroma_-_very_high_mag.jpg
| Width =
| Caption = Chloroma. [[H&E stain]].
| Synonyms = extramedullary leukemia, myeloid sarcoma and chloroma, myeloblastoma, chloromyeloma, chloromyelosarcoma, granulocytic leukosarcoma, myelosarcoma
| Micro = atypical small blue cells ~2x resting lymphocyte, infiltrative
| Subtypes =
| LMDDx = [[small round cell tumours]]
| Stains =
| IHC = CD117 +ve, CD43 +ve, CD34 +ve/-ve
| EM =
| Molecular =
| IF =
| Gross =
| Grossing =
| Site = [[soft tissue lesion]]
| Assdx =
| Syndromes =
| Clinicalhx =
| Signs =
| Symptoms =
| Prevalence = rare
| Bloodwork =
| Rads =
| Endoscopy =
| Prognosis =
| Other =
| ClinDDx = other [[soft tissue lesions]]
| Tx = see ''[[acute myeloid leukemia]]''
}}
'''Granulocytic sarcoma''' is an uncommon [[malignant]] [[soft tissue lesion]] that really represents a hematologic malignancy; it is a soft tissue manifestation of [[acute myeloid leukemia]]. It is ''not'' a [[sarcoma]].

Numerous other terms refer to this including '''extramedullary leukemia''',<ref name=pmid21795742>{{Cite journal | last1 = Bakst | first1 = RL. | last2 = Tallman | first2 = MS. | last3 = Douer | first3 = D. | last4 = Yahalom | first4 = J. | title = How I treat extramedullary acute myeloid leukemia. | journal = Blood | volume = 118 | issue = 14 | pages = 3785-93 | month = Oct | year = 2011 | doi = 10.1182/blood-2011-04-347229 | PMID = 21795742 }}</ref> '''myeloid sarcoma''' and '''chloroma'''.

Less common terms include:<ref name=pmid21556238>{{Cite journal | last1 = Eom | first1 = KS. | last2 = Kim | first2 = TY. | title = Intraparenchymal myeloid sarcoma and subsequent spinal myeloid sarcoma for acute myeloblastic leukemia. | journal = J Korean Neurosurg Soc | volume = 49 | issue = 3 | pages = 171-4 | month = Mar | year = 2011 | doi = 10.3340/jkns.2011.49.3.171 | PMID = 21556238 | PMC = 3085814 | url = http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3085814/ }}</ref> '''myeloblastoma''', '''chloromyeloma''', '''chloromyelosarcoma''', '''granulocytic leukosarcoma''', and '''myelosarcoma'''.

==General==
*Soft tissue manifestation of [[acute myeloid leukemia]].<ref name=pmid21556238/>
*WBC elevated, low or normal range.<ref name=pmid25678833>{{Cite journal | last1 = Arthur | first1 = C. | last2 = Cermak | first2 = J. | last3 = Delaunay | first3 = J. | last4 = Mayer | first4 = J. | last5 = Mazur | first5 = G. | last6 = Thomas | first6 = X. | last7 = Wierzbowska | first7 = A. | last8 = Jones | first8 = MM. | last9 = Berrak | first9 = E. | title = Post hoc analysis of the relationship between baseline white blood cell count and survival outcome in a randomized Phase III trial of decitabine in older patients with newly diagnosed acute myeloid leukemia. | journal = J Blood Med | volume = 6 | issue = | pages = 25-9 | month = | year = 2015 | doi = 10.2147/JBM.S64067 | PMID = 25678833 }}</ref>

==Microscopic==
Features:
*Cluster of atypical small blue cells in [[soft tissue lesions|soft tissue]] with scant cytoplasm.

DDx:
*[[Small cell carcinoma]]
*Large cell lymphomas ([[DLBCL]], [[ALCL]]).
*Other [[small round cell tumour]]s.

===Images===
<gallery>
Image:Chloroma - intermed mag.jpg | Chloroma - intermed. mag. (WC)
Image:Chloroma_-_high_mag.jpg | Chloroma - high mag. (WC)
Image:Chloroma_-_very_high_mag.jpg | Chloroma - very high mag. (WC)
Image:Myeloid sarcoma within a lymph node x40 magnification.jpg | Myeloid sarcoma within a lymph node (WC)
</gallery>
www:
*[http://path.upmc.edu/cases/case306/micro.html Granulocytic sarcoma - several crappy images (upmc.edu)].
*[http://path.upmc.edu/cases/case379.html Myeloid sarcoma - several images (upmc.edu)].

==IHC==
Features:<ref name=pmid24969631>{{Cite journal | last1 = Seifert | first1 = RP. | last2 = Bulkeley | first2 = W. | last3 = Zhang | first3 = L. | last4 = Menes | first4 = M. | last5 = Bui | first5 = MM. | title = A practical approach to diagnose soft tissue myeloid sarcoma preceding or coinciding with acute myeloid leukemia. | journal = Ann Diagn Pathol | volume = 18 | issue = 4 | pages = 253-60 | month = Aug | year = 2014 | doi = 10.1016/j.anndiagpath.2014.06.001 | PMID = 24969631 }}</ref>
Markers of immaturity:
*CD34 +ve/-ve (5 of 9 cases).
*CD117 +ve (9 of 9 cases).
*TdT
Myeloid markers:
*CD43 +ve (7 of 7 cases) - sensitive, but not specific
*Myeloperoxidase +ve (8 of 10 cases).
*CD11c (myelomonocytic marker)
*CD13 (granulopoietic marker)
*CD33 (granulopoietic marker, specific but less sensitive)

CD34, CD117 and myeloperoxidase are more commonly positive in cases showing granulopoietic differentiation, but can be negative in cases with a myelomonocytic or monocytic differentiation, where CD68, CD163 and lysozyme may be helpful.<ref name=pmid23530613>{{cite journal |vauthors=Zhou J, Bell D, Medeiros LJ |title=Myeloid sarcoma of the head and neck region |journal=Arch Pathol Lab Med |volume=137 |issue=11 |pages=1560–8 |date=November 2013 |pmid=23530613 |doi=10.5858/arpa.2012-0537-OA |url=}}</ref>

==Sign out==
*It is prudent to mention ''acute myeloid leukemia'' somewhere in the report to ensure the appropriate referral is made.

==See also==
*[[Soft tissue lesions]].
*[[Intravascular lymphoma]].

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

[[Category:Diagnosis]]
[[Category:Soft tissue lesions]]

Merkel cell carcinoma

2023-01-10T21:32:37Z

Mark: many ALK1 +ve

{{ Infobox diagnosis
| Name = {{PAGENAME}}
| Image = Merkel_cell_carcinoma_-_high_mag.jpg
| Width =
| Caption = Merkel cell carcinoma. [[H&E stain]].
| Micro = neuroendocrine nuclear features (round nucleus, small nucleoli/no nucleolus, stippled chromatin), usually scant cytoplasm, usually small (~3x resting lymphocyte), often in sheets
| Subtypes =
| LMDDx = [[small cell carcinoma]], cutaneous [[Ewing sarcoma]], [[Burkitt lymphoma]], other [[small round blue cell tumours]]
| Stains =
| IHC = Merkel cell polyomavirus +ve, CK20 +ve (perinuclear dot-like), CD56 +ve, TTF-1 -ve, CK7 -ve, NF +ve
| EM =
| Molecular =
| IF =
| Gross =
| Grossing =
| Site = [[skin]]
| Assdx =
| Syndromes =
| Clinicalhx = +/-immunosuppressed/immunoincompetent
| Signs =
| Symptoms =
| Prevalence = rare
| Bloodwork =
| Rads =
| Endoscopy =
| Prognosis = poor
| Other =
| ClinDDx =
}}
{{ Infobox external links
| Name = {{PAGENAME}}
| EHVSC =
| EHVSC_mult =
| pathprotocols =
| wikipedia = merkel cell carcinoma
| pathoutlines =
}}
'''Merkel cell carcinoma''', abbreviated '''MCC''', is an uncommon aggressive form of skin cancer.

==General==
Features:<ref name=pmid20418670>{{Cite journal | last1 = Calder | first1 = KB. | last2 = Smoller | first2 = BR. | title = New insights into merkel cell carcinoma. | journal = Adv Anat Pathol | volume = 17 | issue = 3 | pages = 155-61 | month = May | year = 2010 | doi = 10.1097/PAP.0b013e3181d97836 | PMID = 20418670 }}</ref>
*Rare.
*Aggressive course/poor prognosis.
*Neuroendocrine-like.<ref name=pmid19395876>{{Cite journal | last1 = Pulitzer | first1 = MP. | last2 = Amin | first2 = BD. | last3 = Busam | first3 = KJ. | title = Merkel cell carcinoma: review. | journal = Adv Anat Pathol | volume = 16 | issue = 3 | pages = 135-44 | month = May | year = 2009 | doi = 10.1097/PAP.0b013e3181a12f5a | PMID = 19395876 }}
</ref>

Etiology:
*Most caused by ''Merkel cell [[polyomavirus]]''.<ref name=pmid18202256>{{Cite journal | last1 = Feng | first1 = H. | last2 = Shuda | first2 = M. | last3 = Chang | first3 = Y. | last4 = Moore | first4 = PS. | title = Clonal integration of a polyomavirus in human Merkel cell carcinoma. | journal = Science | volume = 319 | issue = 5866 | pages = 1096-100 | month = Feb | year = 2008 | doi = 10.1126/science.1152586 | PMID = 18202256 }}</ref><ref name=pmid20418670/>
*Immunocompromised/immunosuppressed (e.g. organ transplant recipients).

==Microscopic==
Features:<ref name=Ref_WMSP491>{{Ref WMSP|491}}</ref>
*Neuroendocrine nuclear features - round nucleus, small nucleoli/no nucleolus, stippled chromatin - '''key feature'''.
*Typically medium size cells ~3x resting lymphocyte.
**May be small or large.
*Architecture: nests, sheets or trabeculae.
*Scant cytoplasm.
*Abundant mitoses. †
*+/-Nuclear moulding.
**Nuclei of adjacent cells conform to one another.
*+/-Tumour infiltrating lymphocytes. ‡

Notes:
*† >10 mitoses/HPF = poor prognosis - definition suffers from [[HPFitis]].<ref name=capp_mcc>URL: [http://www.cap.org/apps/docs/committees/cancer/cancer_protocols /2011/SkinMerkelCell_11protocol.pdf http://www.cap.org/apps/docs/committees/cancer/cancer_protocols/2011/SkinMerkelCell_11protocol.pdf]. Accessed on: 28 March 2012.</ref>
*‡ May be associated with a worse prognosis.<ref name=capp_mcc/>
*Merkel cell carcinoma [[lymph node metastases]] is difficult to diagnose with routine stains; use of IHC stains are advised.<ref name=capp_mcc/>
*Arise from the epidermis - very rarely in situ.<ref name=pmid15606676>{{Cite journal | last1 = Ferringer | first1 = T. | last2 = Rogers | first2 = HC. | last3 = Metcalf | first3 = JS. | title = Merkel cell carcinoma in situ. | journal = J Cutan Pathol | volume = 32 | issue = 2 | pages = 162-5 | month = Feb | year = 2005 | doi = 10.1111/j.0303-6987.2005.00270.x | PMID = 15606676 }}</ref>

DDx:
*[[Basal cell carcinoma]] - no stippled chromatin, less mitoses active.
*Cutaneous [[Ewing sarcoma]] - sorted-out with immunostains.
*[[Lymphoma]].
**[[Burkitt lymphoma]].
*Metastatic [[small cell carcinoma]].
*Other [[small round cell tumours]].

===Images===
<gallery>
Image:Merkel_cell_carcinoma_-_intermed_mag.jpg | MCC - intermed. mag. (WC/Nephron)
Image:Merkel_cell_carcinoma_-_high_mag.jpg | MCC - high mag. (WC/Nephron)
Image:Merkel_cell_carcinoma_-_very_high_mag.jpg | MCC - very high mag. (WC/Nephron)
Image:Merkelcellcarcinoma_Tag.jpg | Merkel cell carcinoma - nested pattern (WC)
</gallery>
www:
*[http://www.bccancer.bc.ca/HPI/CE/cytotechnology/cytosleuthquiz/nongyne/ng12hist.htm MCC (bccancer.bc.ca)].
*[http://www.joplink.net/prev/200403/07.html MCC (joplink.net)].
*[http://www.ispub.com/ispub/ijd/volume_5_number_2_8/concurrent_merkel_cell_carcinoma_and_bowen_s_disease_of_the_thigh/bowen-fig3.jpg Merkel cell carcinoma (ispub.com)].
*[http://path.upmc.edu/cases/case398.html Merkel cell carcinoma - several images (upmc.edu)].

==IHC==
Features:
*CK7 -ve.
*CK20 +ve (perinuclear dot-like).<ref name=pmid11533085>{{Cite journal | last1 = Leech | first1 = SN. | last2 = Kolar | first2 = AJ. | last3 = Barrett | first3 = PD. | last4 = Sinclair | first4 = SA. | last5 = Leonard | first5 = N. | title = Merkel cell carcinoma can be distinguished from metastatic small cell carcinoma using antibodies to cytokeratin 20 and thyroid transcription factor 1. | journal = J Clin Pathol | volume = 54 | issue = 9 | pages = 727-9 | month = Sep | year = 2001 | doi = | PMID = 11533085 | URL = http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1731517/ }}</ref>
*CAM5.2 +ve (dot-like pattern).
*CD56 +ve.
*AE1/AE3 +ve.
*Merkel cell polyomavirus +ve ~85% of cases.<ref name=pmid21870327>{{Cite journal | last1 = Jung | first1 = HS. | last2 = Choi | first2 = YL. | last3 = Choi | first3 = JS. | last4 = Roh | first4 = JH. | last5 = Pyon | first5 = JK. | last6 = Woo | first6 = KJ. | last7 = Lee | first7 = EH. | last8 = Jang | first8 = KT. | last9 = Han | first9 = J. | title = Detection of Merkel cell polyomavirus in Merkel cell carcinomas and small cell carcinomas by PCR and immunohistochemistry. | journal = Histol Histopathol | volume = 26 | issue = 10 | pages = 1231-41 | month = Oct | year = 2011 | doi = | PMID = 21870327 }}</ref>
*NF +ve (12 of 13 cases).<ref name=pmid16625069>{{cite journal |authors=Bobos M, Hytiroglou P, Kostopoulos I, Karkavelas G, Papadimitriou CS |title=Immunohistochemical distinction between merkel cell carcinoma and small cell carcinoma of the lung |journal=Am J Dermatopathol |volume=28 |issue=2 |pages=99–104 |date=April 2006 |pmid=16625069 |doi=10.1097/01.dad.0000183701.67366.c7 |url=}}</ref>
**Useful to differentiate from [[small cell carcinoma of lung]].

Others:
*TTF-1 -ve.
*NSE +ve.<ref name=pmid15606676/>
*PAX5 +ve.<ref name=pmid25040178>{{Cite journal | last1 = Jankowski | first1 = M. | last2 = Kopinski | first2 = P. | last3 = Schwartz | first3 = R. | last4 = Czajkowski | first4 = R. | title = Merkel cell carcinoma: is this a true carcinoma? | journal = Exp Dermatol | volume = 23 | issue = 11 | pages = 792-4 | month = Nov | year = 2014 | doi = 10.1111/exd.12490 | PMID = 25040178 }}</ref>
*ALK1<ref name=pmid23574788>{{cite journal |vauthors=Filtenborg-Barnkob BE, Bzorek M |title=Expression of anaplastic lymphoma kinase in Merkel cell carcinomas |journal=Hum Pathol |volume=44 |issue=8 |pages=1656–64 |date=August 2013 |pmid=23574788 |doi=10.1016/j.humpath.2012.11.021 |url=}}</ref>

==EM==
*''[[Neurosecretory granules]]'' ([[AKA]] dense-core granules).<ref name=pmid9062165>{{Cite journal | last1 = Gil-Moreno | first1 = A. | last2 = Garcia-Jiménez | first2 = A. | last3 = González-Bosquet | first3 = J. | last4 = Esteller | first4 = M. | last5 = Castellví-Vives | first5 = J. | last6 = Martínez Palones | first6 = JM. | last7 = Xercavins | first7 = J. | title = Merkel cell carcinoma of the vulva. | journal = Gynecol Oncol | volume = 64 | issue = 3 | pages = 526-32 | month = Mar | year = 1997 | doi = | PMID = 9062165 }}</ref>

==See also==
*[[Dermatologic neoplasms]].
*[[Small cell carcinoma]].
*[[Dermatopathology]].
*[[Viruses and cancer]].

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

[[Category:Diagnosis]]
[[Category:Dermatopathology]]

Sclerotic metastasis

2023-01-06T22:19:45Z

Mark: other sclerotic bone lesions

'''Sclerotic metastasis''' refers the imaging appearance of [[metastatic disease]]. Sclerotic metastases are less common than [[lytic metastases]].

The classic sclerotic metastases are:<ref>URL: [http://www.svuhradiology.ie/case-study/lytic-bone-metastasis/ http://www.svuhradiology.ie/case-study/lytic-bone-metastasis/]. Accessed on: 2023 January 3.</ref>
*Breast cancer.
*Prostate cancer.

Sclerotic bone lesions which are not strictly metastases can also be seen in:
*[[Systemic mastocytosis]]
*Certain forms of [[myeloma]] (e.g. so-called "osteosclerotic" myeloma in [[POEMS syndrome]])

==See also==
*[[Lytic metastasis]].

==References==
{{Reflist|1}}

[[Category:Clinical]]

Tumour deposit

2021-08-08T21:00:05Z

Mark: tnm8

A '''tumour deposit''' is a microscopic or macroscopic tumour nodule in the lymphatic drainage bed of the (primary) tumour. The term is applied in [[colorectal adenocarcinoma]] and has also been described in [[gastric cancer]].<ref name=pmid23184289>{{Cite journal | last1 = Lee | first1 = HS. | last2 = Lee | first2 = HE. | last3 = Yang | first3 = HK. | last4 = Kim | first4 = WH. | title = Perigastric tumor deposits in primary gastric cancer: implications for patient prognosis and staging. | journal = Ann Surg Oncol | volume = 20 | issue = 5 | pages = 1604-13 | month = May | year = 2013 | doi = 10.1245/s10434-012-2692-9 | PMID = 23184289 }}</ref>

It is also known as '''discoutinuous extramural extension''' and '''peritumoural deposit'''.

Conceptually, tumour deposits are like the ''[[in-transit metastases]]'' of [[malignant melanoma]]<ref name=pmid19136930>{{Cite journal | last1 = Puppa | first1 = G. | last2 = Ueno | first2 = H. | last3 = Kayahara | first3 = M. | last4 = Capelli | first4 = P. | last5 = Canzonieri | first5 = V. | last6 = Colombari | first6 = R. | last7 = Maisonneuve | first7 = P. | last8 = Pelosi | first8 = G. | title = Tumor deposits are encountered in advanced colorectal cancer and other adenocarcinomas: an expanded classification with implications for colorectal cancer staging system including a unifying concept of in-transit metastases. | journal = Mod Pathol | volume = 22 | issue = 3 | pages = 410-5 | month = Mar | year = 2009 | doi = 10.1038/modpathol.2008.198 | PMID = 19136930 }}</ref> and [[dermatopathology]]; however, it is important to note that on a practical level the specific (morphologic/clinical) definitions of ''tumour deposit'' and ''in-transit metastasis'' are different.

==General==
Significance:
*Poor prognosticator.
**Can be understood as a type of invasive front/border, e.g. ''well-circumscribed border'' versus ''infiltrative border''.<ref name=pmid24112678/>

==Definition==
Definition - TNM/AJCC 8th edition for colorectal cancer:
"Tumor deposits are defined as discrete tumor nodules within the lymph drainage area of the primary carcinoma without identifiable lymph node tissue or identifiable vascular or neural structure. The shape, contour, and size of the deposit are not considered in these designations."

Definition - TNM/AJCC 7th edition for colorectal cancer:<ref name=pmid21555695/>
*Microscopic or macroscopic nodule in the lymphatic drainage bed of the tumour.
**No standardized distance (from tumour) criteria are defined.<ref name=pmid24112678>{{Cite journal | last1 = Ueno | first1 = H. | last2 = Hashiguchi | first2 = Y. | last3 = Shimazaki | first3 = H. | last4 = Shinto | first4 = E. | last5 = Kajiwara | first5 = Y. | last6 = Nakanishi | first6 = K. | last7 = Kato | first7 = K. | last8 = Maekawa | first8 = K. | last9 = Nakamura | first9 = T. | title = Peritumoral deposits as an adverse prognostic indicator of colorectal cancer. | journal = Am J Surg | volume = | issue = | pages = | month = Oct | year = 2013 | doi = 10.1016/j.amjsurg.2013.04.009 | PMID = 24112678 }}</ref>
*No findings suggestive of it being a lymph node replaced by tumour:
*#No significant lymphoid tissue.
*#Irregular contour.
*#*Round nodules of tumour are considered lymph nodes that are replaced by tumour.

Notes:
*The definition of ''tumour deposit'' has changed significantly between the TMN/AJCC fifth, sixth, seventh editions.<ref name=pmid21555695/>
*Lesions that are ''not'' in the drainage bed of the tumour are [[Colorectal_cancer_staging#Metastasis_stage|metastatic disease]], pM1b.

===Ueno criteria===
Ueno ''et al.'' propose that a tumour deposit is either:<ref name=pmid24112678/>
#>=2 mm from the tumour front.
#>=2 mm (radially) from the deepest aspect of the muscularis propria, if the tumour is not present in the plane of section.

==Staging==
Staging implications in [[colorectal cancer]]:
*Tumour deposits are '''not''' counted as (positive) lymph nodes<ref name=pmid21555695>{{Cite journal | last1 = Nagtegaal | first1 = ID. | last2 = Tot | first2 = T. | last3 = Jayne | first3 = DG. | last4 = McShane | first4 = P. | last5 = Nihlberg | first5 = A. | last6 = Marshall | first6 = HC. | last7 = Påhlman | first7 = L. | last8 = Brown | first8 = JM. | last9 = Guillou | first9 = PJ. | title = Lymph nodes, tumor deposits, and TNM: are we getting better? | journal = J Clin Oncol | volume = 29 | issue = 18 | pages = 2487-92 | month = Jun | year = 2011 | doi = 10.1200/JCO.2011.34.6429 | PMID = 21555695 }}</ref> and in the context of positive lymph nodes do not change the [[Colorectal_cancer_staging#Nodal_stage|N stage]].
**If no positive lymph nodes are present, the N stage is pN1c.
*The T stage is ''not'' affected by tumour deposits.<ref name=pmid21555695/>

==See also==
*[[Colorectal carcinoma]].
*[[Metastasis]].

==References==
{{Reflist|1}}

[[Category:Gastrointestinal pathology]]

Pseudolipomatosis coli

2021-08-02T20:40:05Z

Mark: starter

Clear spaces within the large bowel due to air tracking into the mucosa from endoscopic insufflation.

[[Pneumatosis intestinalis cystoides]] tends to be deeper and may be associated with chronic changes such as foreign body giant cells.

Pseudolipomatosis

2021-08-02T19:58:17Z

Mark: redirect

#REDIRECT[[Pseudolipomatosis coli]]

CD56

2021-03-26T22:39:06Z

Mark: myeloma

'''CD56''' is a commonly available [[immunostain]] that is seen in a number of tumours. It is a sensitive [[neuroendocrine marker|marker of neuroendocrine differentiation]].

==Positive==
===Carcinomas===
*[[Neuroendocrine carcinoma]].
*[[Small cell carcinoma]].
*[[Merkel cell carcinoma]].<ref name=pmid12727026>{{Cite journal | last1 = Kurokawa | first1 = M. | last2 = Nabeshima | first2 = K. | last3 = Akiyama | first3 = Y. | last4 = Maeda | first4 = S. | last5 = Nishida | first5 = T. | last6 = Nakayama | first6 = F. | last7 = Amano | first7 = M. | last8 = Ogata | first8 = K. | last9 = Setoyama | first9 = M. | title = CD56: a useful marker for diagnosing Merkel cell carcinoma. | journal = J Dermatol Sci | volume = 31 | issue = 3 | pages = 219-24 | month = May | year = 2003 | doi = | PMID = 12727026 }}</ref>

===Lymphoid===
*[[Acute myeloid leukemia]].<ref name=nordiqc>URL: [http://www.nordiqc.org/Epitopes/CD56/CD56.htm http://www.nordiqc.org/Epitopes/CD56/CD56.htm]. Accessed on: September 13, 2014.</ref>
*[[Chronic myeloid leukemia]].<ref name=nordiqc/>
*[[Extranodal NK/T-cell lymphoma, nasal type]].
*[[Hepatosplenic T-cell lymphoma]].
*[[Plasma cell myeloma]]

===Others===
*[[Rhabdomyosarcoma]].<ref name=pmid18487991>{{Cite journal | last1 = Bahrami | first1 = A. | last2 = Gown | first2 = AM. | last3 = Baird | first3 = GS. | last4 = Hicks | first4 = MJ. | last5 = Folpe | first5 = AL. | title = Aberrant expression of epithelial and neuroendocrine markers in alveolar rhabdomyosarcoma: a potentially serious diagnostic pitfall. | journal = Mod Pathol | volume = 21 | issue = 7 | pages = 795-806 | month = Jul | year = 2008 | doi = 10.1038/modpathol.2008.86 | PMID = 18487991 }}</ref>
*[[Solid pseudopapillary tumour‎]].
*[[Follicular dendritic cell sarcoma]].

==Occasionally positive==
*[[Renal cell carcinoma]] ~18% of cases.<ref name=pmid20462442>{{cite journal |authors=Ronkainen H, Soini Y, Vaarala MH, Kauppila S, Hirvikoski P |title=Evaluation of neuroendocrine markers in renal cell carcinoma |journal=Diagn Pathol |volume=5 |issue= |pages=28 |date=May 2010 |pmid=20462442 |pmc=2876076 |doi=10.1186/1746-1596-5-28 |url=}}</ref>

==See also==
*[[Immunohistochemistry]].

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

[[Category:Immunohistochemistry]]

POEMS syndrome

2021-03-26T22:34:25Z

Mark: typically osteosclerotic

'''POEMS syndrome''' is a constellation of findings, best thought of as a paraneoplastic syndrome due to clonal plasma cells:<ref name=pmid18477219>{{cite journal |author=Yuri T, Yamazaki F, Takasu K, Shikata N, Tsubura A |title=Glomeruloid hemangioma |journal=Pathol. Int. |volume=58 |issue=6 |pages=390–5 |year=2008 |month=June |pmid=18477219 |doi=10.1111/j.1440-1827.2008.02241.x |url=}}</ref>
*Polyneuropathy.
*Organomegaly.
*Endocrinopathy.
*M-protein.
*Skin changes.

==Diagnostic criteria==
Requires both mandatory criteria and at least one each from major and minor criteria:<ref name=pmid31012139>{{cite journal |authors=Dispenzieri A |title=POEMS Syndrome: 2019 Update on diagnosis, risk-stratification, and management |journal=Am. J. Hematol. |volume=94 |issue=7 |pages=812–827 |date=July 2019 |pmid=31012139 |doi=10.1002/ajh.25495 |url=}}</ref>

''Mandatory:''
# Polyneuropathy (typically demyelinating).
# Monoclonal plasma cell proliferation (usually lambda).
''Major:''
# [[Castleman disease]]
# Sclerotic bone lesions.
# Vascular endothelial growth factor elevation.
''Minor:''
# Organomegaly (splenomegaly, hepatomegaly or lymphadenopathy).
# Extravascular volume overload.
# Endocrinopathy.
# Skin changes.
# Papilloedema.
# Thrombocytosis/polycythemia.

==Pathology==
*The [[pathologist]] may come across an undiagnosed case in the form of a ''[[glomeruloid hemangioma]]''; however, glomeruloid [[hemangioma]]s are not always associated with the POEMS syndrome.<ref name=pmid19077091>{{cite journal |author=González-Guerra E, Haro MR, Fariña MC, Martín L, Manzarbeitia L, Requena L |title=Glomeruloid haemangioma is not always associated with POEMS syndrome |journal=Clin. Exp. Dermatol. |volume=34 |issue=7 |pages=800–3 |year=2009 |month=October |pmid=19077091 |doi=10.1111/j.1365-2230.2008.02997.x |url=}}</ref>
*POEMS syndrome typically cause osteosclerotic bone deposits (so-called osteosclerotic myeloma), in contrast to the lytic lesions seen in more conventional [[plasma cell myeloma]].{{fact}}

==See also==
*[[POEM]] - a treatment for [[achalasia]].

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

[[Category:Syndromes]]

Gastrointestinal stromal tumour

2020-11-15T17:28:39Z

Mark: mutations

{{ Infobox diagnosis
| Name = {{PAGENAME}}
| Image = Gastrointestinal_stromal_tumour_-_very_low_mag.jpg
| Width =
| Caption = Gastrointestinal stromal tumour. [[H&E stain]].
| Micro = spindle ''or'' epithelioid ''or'' mixed morphology, usu. centred on the muscularis propria
| Subtypes =
| LMDDx = [[schwannoma]], [[leiomyoma]], [[leiomyosarcoma]], [[neurofibroma]], [[desmoid-type fibromatosis]]
| Stains =
| IHC = CD117 +ve, [[DOG1]] +ve, CD34 +ve, S-100 -ve
| EM =
| Molecular = mutation in KIT gene ''or'' PDGFRA gene
| IF =
| Gross =
| Grossing =
| Staging = [[gastrointestinal stromal tumour staging]]
| Site = [[stomach]], [[small intestine]], other sites
| Assdx =
| Syndromes = [[Neurofibromatosis type 1]], [[Carney triad]], [[Carney-Stratakis syndrome]]
| Clinicalhx =
| Signs =
| Symptoms =
| Prevalence =
| Bloodwork =
| Rads =
| Endoscopy =
| Prognosis = good to poor - dependent on size, site & mitotic rate
| Other =
| ClinDDx =
}}
The '''gastrointestinal stromal tumour''', abbreviated '''GIST''', is an uncommon tumour of the [[gastrointestinal tract pathology|gastrointestinal tract]].

==General==
===Definition===
*Tumour resulting from a mutation in the KIT gene ''or'' PDGFRA (Platelet-derived growth factor receptor, alpha polypeptide) gene.<ref name=pmid17090188/>
*Cases wild-type for KIT or PDFGRA may harbour defects in the [[succinate dehydrogenase]] complex, NF-1, BRAF, or extremely rarely KRAS.

===Epidemiology===
*Arise from ''Interstitial cells of Cajal''.<ref name=pmid17090188>{{cite journal |author=Miettinen M, Lasota J |title=Gastrointestinal stromal tumors: review on morphology, molecular pathology, prognosis, and differential diagnosis |journal=Arch. Pathol. Lab. Med. |volume=130 |issue=10 |pages=1466–78 |year=2006 |month=October |pmid=17090188 |doi= |url=http://journals.allenpress.com/jrnlserv/?request=get-abstract&issn=0003-9985&volume=130&page=1466}}</ref>

May be familial/syndromic:<ref name=pmid20848108>{{cite journal |author=Agaimy A, Hartmann A |title=[Hereditary and non-hereditary syndromic gastointestinal stromal tumours] |language=German |journal=Pathologe |volume=31 |issue=6 |pages=430–7 |year=2010 |month=October |pmid=20848108 |doi=10.1007/s00292-010-1354-6 |url=}}</ref>
*[[Neurofibromatosis|Neurofibromatosis 1]] (von Recklinghausen's disease).
*[[Carney triad]].
*[[Carney-Stratakis syndrome]] - GISTs and [[paraganglioma]] - due to mutation in the genes for [[succinate dehydrogenase]].<ref name=pmid22997454>{{Cite journal | last1 = Blay | first1 = JY. | last2 = Blomqvist | first2 = C. | last3 = Bonvalot | first3 = S. | last4 = Boukovinas | first4 = I. | last5 = Casali | first5 = PG. | last6 = De Alava | first6 = E. | last7 = Dei Tos | first7 = AP. | last8 = Dirksen | first8 = U. | last9 = Duffaud | first9 = F. | title = Gastrointestinal stromal tumors: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. | journal = Ann Oncol | volume = 23 Suppl 7 | issue = | pages = vii49-55 | month = Oct | year = 2012 | doi = 10.1093/annonc/mds252 | PMID = 22997454 | url = http://annonc.oxfordjournals.org/content/23/suppl_7/vii49.full }}</ref>

===Treatment===
*[[Imatinib]] (Gleevec) - drug was developed for [[chronic myelogenous leukemia]].
**There are other similar drugs, e.g. ''[[nilotinib]]'' and ''[[dasatinib]]''.

===Factors predictive of malignant behaviour===
Features suggesting a bad prognosis:<ref name=pmid17090188/>
*Large size.
**Often benign if small size.
*High mitotic rate (for area 5mm2).
*Site - small intestine GISTs worse than stomach GISTs.

Small intestine bad prognosis:<ref name=pmid17090188/>
* >5 mitoses/5 mm2 ''or'' size >10 cm.

Stomach bad prognosis:<ref name=pmid17090188/>
* >5 mitoses/5 mm2 ''and'' size >5 cm.

===Location===
Most common locations in order:<ref name=pmid17090188/>
*60% in stomach.
*35% in small intestine.
*5% elsewhere.

Notes:
*Small intestinal GISTs have a worse prognosis than gastric ones.<ref name=pmid17090188/>
*GISTs almost never metastasize to the [[lymph node]]s (except for SDH-B deficient epithelioid GISTs)
**Most common [[metastasis]] locations: [[liver]], abdominal soft tissue.

==Microscopic==
Features:
*Classically, spindle cell morphology ~ 50% of tumours.<ref name=pmid15613856>{{Cite journal | last1 = Miettinen | first1 = M. | last2 = Sobin | first2 = LH. | last3 = Lasota | first3 = J. | title = Gastrointestinal stromal tumors of the stomach: a clinicopathologic, immunohistochemical, and molecular genetic study of 1765 cases with long-term follow-up. | journal = Am J Surg Pathol | volume = 29 | issue = 1 | pages = 52-68 | month = Jan | year = 2005 | doi = | PMID = 15613856 }}</ref>
** May be epithelioid (round) ~40% of tumours.
** Mixed epithelioid and spindle cell tumours ~10% tumours.
*+/-Cytoplasmic inclusions<ref name=pmid7757951>{{cite journal |author=Pasquinelli G, Severi B, Martinelli GN, Santini D, Gelli MC, Tison V |title=Gastro-intestinal stromal tumors: an ultrastructural reinterpretation of the clear cell component |journal=J. Submicrosc. Cytol. Pathol. |volume=27 |issue=2 |pages=251–7 |year=1995 |month=April |pmid=7757951 |doi= |url=}}</ref> - perinuclear.<ref>{{Cite journal | last1 = Boşoteanu | first1 = M. | last2 = Boşoteanu | first2 = C. | last3 = Deacu | first3 = M. | last4 = Aşchie | first4 = M. | title = Differential diagnosis of a gastric stromal tumor: case report and literature review. | journal = Rom J Morphol Embryol | volume = 52 | issue = 4 | pages = 1361-8 | month = | year = 2011 | doi = | PMID = 22203947 }}</ref>
*Classically splits the layers of the ''muscularis propria'' - as this is where the ''interstitial cells of Cajal'' are located.<ref name=pmid16402273>{{cite journal |author=Agaimy A, Wünsch PH |title=Gastrointestinal stromal tumours: a regular origin in the muscularis propria, but an extremely diverse gross presentation. A review of 200 cases to critically re-evaluate the concept of so-called extra-gastrointestinal stromal tumours |journal=Langenbecks Arch Surg |volume=391 |issue=4 |pages=322–9 |year=2006 |month=August |pmid=16402273 |doi=10.1007/s00423-005-0005-5 |url=}}</ref>
*+/-Skenoid fibres - extracellular collagen bundles<ref name=pmid15798063/> ~ 2-5 x 60 micrometers - uncommon finding.
**Not seen in gastric GISTs.<ref name=pmid12692202/>
**High [[specificity]] for GIST.

===DDx===
*[[Leiomyosarcoma]].
*[[Leiomyoma]] - esp. in the [[esophagus]].
*Neural tumours.
**[[Neurofibroma]].
**[[Schwannoma]] (GFAP +ve).
***GFAP uniformly neg. in GISTs.<ref name=pmid17090188/>
*[[Desmoid-type fibromatosis]].
*[[Epstein-Barr virus-associated smooth muscle tumour]] - very uncommon, in immunoincompetent individuals.<ref name=pmid16330945>{{Cite journal | last1 = Deyrup | first1 = AT. | last2 = Lee | first2 = VK. | last3 = Hill | first3 = CE. | last4 = Cheuk | first4 = W. | last5 = Toh | first5 = HC. | last6 = Kesavan | first6 = S. | last7 = Chan | first7 = EW. | last8 = Weiss | first8 = SW. | title = Epstein-Barr virus-associated smooth muscle tumors are distinctive mesenchymal tumors reflecting multiple infection events: a clinicopathologic and molecular analysis of 29 tumors from 19 patients. | journal = Am J Surg Pathol | volume = 30 | issue = 1 | pages = 75-82 | month = Jan | year = 2006 | doi = | PMID = 16330945 }}</ref>

===Images===
*www:
**[http://radiographics.rsna.org/content/25/2/455/F67.expansion.html GIST (radiographics.rsna.org)].<ref name=pmid15798063>{{Cite journal | last1 = Levy | first1 = AD. | last2 = Patel | first2 = N. | last3 = Dow | first3 = N. | last4 = Abbott | first4 = RM. | last5 = Miettinen | first5 = M. | last6 = Sobin | first6 = LH. | title = From the archives of the AFIP: abdominal neoplasms in patients with neurofibromatosis type 1: radiologic-pathologic correlation. | journal = Radiographics | volume = 25 | issue = 2 | pages = 455-80 | month = | year = | doi = 10.1148/rg.252045176 | PMID = 15798063 |URL = http://radiographics.rsnajnls.org/cgi/pmidlookup?view=long&pmid=15798063}}</ref>
**[http://radiographics.rsna.org/content/25/2/455/F68.expansion.html GIST with skenoid fibres (radiographics.rsna.org)].<ref name=pmid15798063/>
**[http://www.nature.com/modpathol/journal/v16/n4/fig_tab/3880774f6.html GIST with skenoid fibres (nature.com)].<ref name=pmid12692202>{{Cite journal | last1 = Greenson | first1 = JK. | title = Gastrointestinal stromal tumors and other mesenchymal lesions of the gut. | journal = Mod Pathol | volume = 16 | issue = 4 | pages = 366-75 | month = Apr | year = 2003 | doi = 10.1097/01.MP.0000062860.60390.C7 | PMID = 12692202 | URL = http://www.nature.com/modpathol/journal/v16/n4/full/3880774a.html}}</ref>

<gallery>
Image:Gastric_GIST_%282%29.jpg | GIST - low mag. (WC/KGH)
Image:Gastric_GIST_%281%29.jpg | GIST - high mag. (WC/KGH)
</gallery>
<gallery>
Image:Gastrointestinal_stromal_tumour_-_very_low_mag.jpg | Intestinal spindle cell GIST - very low mag. (WC/Nephron)
Image:Gastrointestinal_stromal_tumour_-_low_mag.jpg | Intestinal spindle cell GIST - low mag. (WC/Nephron)
Image:Gastrointestinal_stromal_tumour_-_intermed_mag.jpg | Intestinal spindle cell GIST - intermed. mag. (WC/Nephron)
Image:Gastrointestinal_stromal_tumour_-_high_mag.jpg | Intestinal spindle cell GIST - high mag. (WC/Nephron)
Image:Gastrointestinal_stromal_tumour_-_very_high_mag.jpg | Intestinal spindle cell GIST - very high mag. (WC/Nephron)
Image:Gastrointestinal_stromal_tumour_-_superf_-_intermed_mag.jpg | Epithelioid GIST - intermed. mag. (WC/Nephron)
</gallery>

==IHC==
*CD117 +ve in 95%.<ref name=pmid17090188/>
**[[Mast cell]]s are the internal positive control.
*[[DOG1]] +ve.<ref name=pmid19011564>{{Cite journal | last1 = Liegl | first1 = B. | last2 = Hornick | first2 = JL. | last3 = Corless | first3 = CL. | last4 = Fletcher | first4 = CD. | title = Monoclonal antibody DOG1.1 shows higher sensitivity than KIT in the diagnosis of gastrointestinal stromal tumors, including unusual subtypes. | journal = Am J Surg Pathol | volume = 33 | issue = 3 | pages = 437-46 | month = Mar | year = 2009 | doi = 10.1097/PAS.0b013e318186b158 | PMID = 19011564 }}</ref>

Others:
*CD34 +ve in 70%.<ref name=pmid17090188/>
*Desmin +ve in 5%.<ref name=pmid17090188/>
*WT1 +ve -- cytoplasmic (28/28 cases<ref name=pmid18528287>{{Cite journal | last1 = Bing | first1 = Z. | last2 = Pasha | first2 = TL. | last3 = Acs | first3 = G. | last4 = Zhang | first4 = PJ. | title = Cytoplasmic overexpression of WT-1 in gastrointestinal stromal tumor and other soft tissue tumors. | journal = Appl Immunohistochem Mol Morphol | volume = 16 | issue = 4 | pages = 316-21 | month = Jul | year = 2008 | doi = 10.1097/PAI.0b013e31815c2e02 | PMID = 18528287 }}</ref>).
===IHC work-up panel===
*S-100 (neural tumours, rarely +ve in GISTs<ref name=pmid17090188/>).
*CD34, CD117 (GIST).
*Desmin (muscle tumours).

==Molecular tests==
:See ''[[Molecular_pathology_tests#Other]]''.
*Sequence Kit gene, PDGFRA gene.
**Kit gene sequencing is being done more frequently as of late-- if a mutation is found it suggest the drug ''[[imatinib]]'' will be effective.
**Exon 11 mutation associated with malignant behaviour.<ref name=pmid9916918>{{Cite journal | last1 = Lasota | first1 = J. | last2 = Jasinski | first2 = M. | last3 = Sarlomo-Rikala | first3 = M. | last4 = Miettinen | first4 = M. | title = Mutations in exon 11 of c-Kit occur preferentially in malignant versus benign gastrointestinal stromal tumors and do not occur in leiomyomas or leiomyosarcomas. | journal = Am J Pathol | volume = 154 | issue = 1 | pages = 53-60 | month = Jan | year = 1999 | doi = 10.1016/S0002-9440(10)65250-9 | PMID = 9916918 }}</ref>
**Secondary mutations of c-kit lead to imatinib resistance,<ref name=pmid26779618>{{Cite journal | last1 = Wada | first1 = N. | last2 = Kurokawa | first2 = Y. | last3 = Takahashi | first3 = T. | last4 = Hamakawa | first4 = T. | last5 = Hirota | first5 = S. | last6 = Naka | first6 = T. | last7 = Miyazaki | first7 = Y. | last8 = Makino | first8 = T. | last9 = Yamasaki | first9 = M. | title = Detecting Secondary C-KIT Mutations in the Peripheral Blood of Patients with Imatinib-Resistant Gastrointestinal Stromal Tumor. | journal = Oncology | volume = 90 | issue = 2 | pages = 112-7 | month = | year = 2016 | doi = 10.1159/000442948 | PMID = 26779618 }}</ref> and resistance to other similar inhibitors.

==Gastrointestinal stromal tumour staging==
{{Main|Gastrointestinal stromal tumour staging}}
GIST has its own staging.

==Sign out==
<pre>
STOMACH (MASS), LESSER CURVE, WEDGE RESECTION:
- GASTROINTESTINAL STROMAL TUMOUR (GIST).
-- MARGINS NEGATIVE FOR GIST.

COMMENT:
The tumour stains as follows:
POSITIVE: CD117, CD34.
NEGATIVE: Desmin, S-100.
</pre>

<pre>
SMALL BOWEL (ILEUM), RESECTION:
- GASTROINTESTINAL STROMAL TUMOUR (GIST), LOW-GRADE, NO RISK OF
PROGRESSIVE DISEASE.
-- MARGINS NEGATIVE FOR GIST.
-- PLEASE SEE TUMOUR SUMMARY.
- THREE BENIGN LYMPH NODES.

COMMENT:
The tumour stains as follows:
POSITIVE: CD117, CD34.
NEGATIVE: Desmin, S-100.
PROLIFERATION (Ki-67): <1%.
</pre>

====Incidental GIST====
<pre>
Partial Stomach, Sleeve Gastrectomy:
- Stomach wall with incidental GASTROINTESTINAL STROMAL TUMOUR (GIST), 2 mm in maximal dimension.
-- Margin clear.
- Gastric mucosa within normal limits.

Comment:
The tumour stains as follows:
POSITIVE: DOG1, CD117, CD34.
NEGATIVE: desmin, S-100.
PROLIFERATION (Ki-67): <2%.
</pre>

===Staging===
*The stage is primarily determined by the tumour size and mitotic grade.
**In the stomach, the mitotic grade determines whether a given tumour is Stage I or Stage III.<ref>{{Cite journal | last1 = Coccolini | first1 = F. | last2 = Catena | first2 = F. | last3 = Ansaloni | first3 = L. | last4 = Pinna | first4 = AD. | title = Gastrointestinal stromal tumor and mitosis, pay attention. | journal = World J Gastroenterol | volume = 18 | issue = 6 | pages = 587-8 | month = Feb | year = 2012 | doi = 10.3748/wjg.v18.i6.587 | PMID = 22363128 }}</ref>

===Micro===
The sections show a spindle cell lesion that is well-circumscribed and without significant
nuclear pleomorphism. No lymphocytic cuff is surrounding the lesion. The lesion is focally
seen at the inked soft tissue margin. Three mitoses are seen in 5 mm*mm.

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

==References==
{{reflist|2}}

[[Category:Gastrointestinal pathology]]
[[Category:Diagnosis]]

BRAF V600E mutation

2020-11-15T11:17:43Z

Mark: more detail about endosalpingiosis

[[Image:BRAF_V600E_mutant_melanoma.jpg|thumb|300px|right|BRAF V600E positivity in [[malignant melanoma]]. VE1 immunostain.]]
The '''BRAF V600E mutation''', also '''BRAF V600E''', is a common recurrent mutation in the BRAF gene that is seen in many types of tumours and [[cancer]].<ref name=pmid21638088/>

A more general discussion about ''BRAF'' is in ''[[BRAF mutation]]''.

==General==
The ''BRAF gene'', formally known as ''v-RAF murine sarcoma viral oncogene homolog B1'', is a serine threonine kinase.<ref>{{OMIM|164757}}</ref>

The mutation can be demonstrated with [[Molecular pathology tests|molecular testing]] ([[ARMS]]). Also, a mutation specific [[immunostain]] (''VE1'') is available.<ref name=pmid21638088>{{Cite journal | last1 = Capper | first1 = D. | last2 = Preusser | first2 = M. | last3 = Habel | first3 = A. | last4 = Sahm | first4 = F. | last5 = Ackermann | first5 = U. | last6 = Schindler | first6 = G. | last7 = Pusch | first7 = S. | last8 = Mechtersheimer | first8 = G. | last9 = Zentgraf | first9 = H. | title = Assessment of BRAF V600E mutation status by immunohistochemistry with a mutation-specific monoclonal antibody. | journal = Acta Neuropathol | volume = 122 | issue = 1 | pages = 11-9 | month = Jul | year = 2011 | doi = 10.1007/s00401-011-0841-z | PMID = 21638088 }}</ref>

==Positive==
===Commonly mutated===
*[[Malignant melanoma]] (55%).<ref name=pmid22012135>{{Cite journal | last1 = Capper | first1 = D. | last2 = Berghoff | first2 = AS. | last3 = Magerle | first3 = M. | last4 = Ilhan | first4 = A. | last5 = Wöhrer | first5 = A. | last6 = Hackl | first6 = M. | last7 = Pichler | first7 = J. | last8 = Pusch | first8 = S. | last9 = Meyer | first9 = J. | title = Immunohistochemical testing of BRAF V600E status in 1,120 tumor tissue samples of patients with brain metastases. | journal = Acta Neuropathol | volume = 123 | issue = 2 | pages = 223-33 | month = Feb | year = 2012 | doi = 10.1007/s00401-011-0887-y | PMID = 22012135 }}</ref>
*[[Papillary thyroid carcinoma]] (79%).<ref>{{Cite journal | last1 = Ilie | first1 = MI. | last2 = Lassalle | first2 = S. | last3 = Long-Mira | first3 = E. | last4 = Bonnetaud | first4 = C. | last5 = Bordone | first5 = O. | last6 = Lespinet | first6 = V. | last7 = Lamy | first7 = A. | last8 = Sabourin | first8 = JC. | last9 = Haudebourg | first9 = J. | title = Diagnostic value of immunohistochemistry for the detection of the BRAF(V600E) mutation in papillary thyroid carcinoma: comparative analysis with three DNA-based assays. | journal = Thyroid | volume = 24 | issue = 5 | pages = 858-66 | month = May | year = 2014 | doi = 10.1089/thy.2013.0302 | PMID = 24417277 }}</ref>
*[[Ganglioglioma]] (58%).<ref>{{Cite journal | last1 = Koelsche | first1 = C. | last2 = Wöhrer | first2 = A. | last3 = Jeibmann | first3 = A. | last4 = Schittenhelm | first4 = J. | last5 = Schindler | first5 = G. | last6 = Preusser | first6 = M. | last7 = Lasitschka | first7 = F. | last8 = von Deimling | first8 = A. | last9 = Capper | first9 = D. | title = Mutant BRAF V600E protein in ganglioglioma is predominantly expressed by neuronal tumor cells. | journal = Acta Neuropathol | volume = 125 | issue = 6 | pages = 891-900 | month = Jun | year = 2013 | doi = 10.1007/s00401-013-1100-2 | PMID = 23435618 }}</ref>
*[[Pleomorphic xanthoastrocytoma]] (78%).<ref>{{Cite journal | last1 = Koelsche | first1 = C. | last2 = Sahm | first2 = F. | last3 = Wöhrer | first3 = A. | last4 = Jeibmann | first4 = A. | last5 = Schittenhelm | first5 = J. | last6 = Kohlhof | first6 = P. | last7 = Preusser | first7 = M. | last8 = Romeike | first8 = B. | last9 = Dohmen-Scheufler | first9 = H. | title = BRAF-mutated pleomorphic xanthoastrocytoma is associated with temporal location, reticulin fiber deposition and CD34 expression. | journal = Brain Pathol | volume = 24 | issue = 3 | pages = 221-9 | month = Apr | year = 2014 | doi = 10.1111/bpa.12111 | PMID = 24345274 }}</ref>
*[[Hairy cell leukemia]] (>90%)
*Histiocytic disorders: [[Langerhans cell histiocytosis]] and [[Erdheim-Chester disease]]
*Metanephric adenoma <ref name=pmid22727996>{{Cite journal | last1 = Choueiri | first1 = TK. | last2 = Cheville | first2 = J. | last3 = Palescandolo | first3 = E. | last4 = Fay | first4 = AP. | last5 = Kantoff | first5 = PW. | last6 = Atkins | first6 = MB. | last7 = McKenney | first7 = JK. | last8 = Brown | first8 = V. | last9 = Lampron | first9 = ME. | title = BRAF mutations in metanephric adenoma of the kidney. | journal = Eur Urol | volume = 62 | issue = 5 | pages = 917-22 | month = Nov | year = 2012 | doi = 10.1016/j.eururo.2012.05.051 | PMID = 22727996 }}</ref><ref name=pmid25602792>{{Cite journal | last1 = Udager | first1 = AM. | last2 = Pan | first2 = J. | last3 = Magers | first3 = MJ. | last4 = Palapattu | first4 = GS. | last5 = Morgan | first5 = TM. | last6 = Montgomery | first6 = JS. | last7 = Weizer | first7 = AZ. | last8 = Hafez | first8 = KS. | last9 = Miller | first9 = DC. | title = Molecular and immunohistochemical characterization reveals novel BRAF mutations in metanephric adenoma. | journal = Am J Surg Pathol | volume = 39 | issue = 4 | pages = 549-57 | month = Apr | year = 2015 | doi = 10.1097/PAS.0000000000000377 | PMID = 25602792 }}</ref>

===Less commonly mutated===
*[[Colorectal cancer]] (5.5%).<ref name=pmid22012135>{{Cite journal | last1 = Capper | first1 = D. | last2 = Berghoff | first2 = AS. | last3 = Magerle | first3 = M. | last4 = Ilhan | first4 = A. | last5 = Wöhrer | first5 = A. | last6 = Hackl | first6 = M. | last7 = Pichler | first7 = J. | last8 = Pusch | first8 = S. | last9 = Meyer | first9 = J. | title = Immunohistochemical testing of BRAF V600E status in 1,120 tumor tissue samples of patients with brain metastases. | journal = Acta Neuropathol | volume = 123 | issue = 2 | pages = 223-33 | month = Feb | year = 2012 | doi = 10.1007/s00401-011-0887-y | PMID = 22012135 }}</ref>
*[[Ovarian cancer]] (7%).<ref name=pmid22012135>{{Cite journal | last1 = Capper | first1 = D. | last2 = Berghoff | first2 = AS. | last3 = Magerle | first3 = M. | last4 = Ilhan | first4 = A. | last5 = Wöhrer | first5 = A. | last6 = Hackl | first6 = M. | last7 = Pichler | first7 = J. | last8 = Pusch | first8 = S. | last9 = Meyer | first9 = J. | title = Immunohistochemical testing of BRAF V600E status in 1,120 tumor tissue samples of patients with brain metastases. | journal = Acta Neuropathol | volume = 123 | issue = 2 | pages = 223-33 | month = Feb | year = 2012 | doi = 10.1007/s00401-011-0887-y | PMID = 22012135 }}</ref>
*[[Lung adenocarcinoma]] (5%).<ref name=pmid23131393>{{Cite journal | last1 = Ilie | first1 = M. | last2 = Long | first2 = E. | last3 = Hofman | first3 = V. | last4 = Dadone | first4 = B. | last5 = Marquette | first5 = CH. | last6 = Mouroux | first6 = J. | last7 = Vignaud | first7 = JM. | last8 = Begueret | first8 = H. | last9 = Merlio | first9 = JP. | title = Diagnostic value of immunohistochemistry for the detection of the BRAFV600E mutation in primary lung adenocarcinoma Caucasian patients. | journal = Ann Oncol | volume = 24 | issue = 3 | pages = 742-8 | month = Mar | year = 2013 | doi = 10.1093/annonc/mds534 | PMID = 23131393 }}</ref>
*Endosalpingiosis, especially those with synchronous or metachronous low grade serous neoplasms (up to 8/21).<ref>{{cite journal |vauthors=Chui MH, Shih IM |title=Oncogenic BRAF and KRAS mutations in endosalpingiosis |journal=J Pathol |volume=250 |issue=2 |pages=148–158 |date=February 2020 |pmid=31576556 |doi=10.1002/path.5353 |url=}}</ref>

==See also==
*[[Immunohistochemistry]].
*[[Molecular pathology tests]].
*[[KRAS mutation]].
*[[Cancer Hotspot Panel v2]].
*[[BRAF mutation]].

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

[[Category:Immunohistochemistry]]

BRAF V600E mutation

2020-11-15T10:13:07Z

Mark: endosalpingiosis

[[Image:BRAF_V600E_mutant_melanoma.jpg|thumb|300px|right|BRAF V600E positivity in [[malignant melanoma]]. VE1 immunostain.]]
The '''BRAF V600E mutation''', also '''BRAF V600E''', is a common recurrent mutation in the BRAF gene that is seen in many types of tumours and [[cancer]].<ref name=pmid21638088/>

A more general discussion about ''BRAF'' is in ''[[BRAF mutation]]''.

==General==
The ''BRAF gene'', formally known as ''v-RAF murine sarcoma viral oncogene homolog B1'', is a serine threonine kinase.<ref>{{OMIM|164757}}</ref>

The mutation can be demonstrated with [[Molecular pathology tests|molecular testing]] ([[ARMS]]). Also, a mutation specific [[immunostain]] (''VE1'') is available.<ref name=pmid21638088>{{Cite journal | last1 = Capper | first1 = D. | last2 = Preusser | first2 = M. | last3 = Habel | first3 = A. | last4 = Sahm | first4 = F. | last5 = Ackermann | first5 = U. | last6 = Schindler | first6 = G. | last7 = Pusch | first7 = S. | last8 = Mechtersheimer | first8 = G. | last9 = Zentgraf | first9 = H. | title = Assessment of BRAF V600E mutation status by immunohistochemistry with a mutation-specific monoclonal antibody. | journal = Acta Neuropathol | volume = 122 | issue = 1 | pages = 11-9 | month = Jul | year = 2011 | doi = 10.1007/s00401-011-0841-z | PMID = 21638088 }}</ref>

==Positive==
===Commonly mutated===
*[[Malignant melanoma]] (55%).<ref name=pmid22012135>{{Cite journal | last1 = Capper | first1 = D. | last2 = Berghoff | first2 = AS. | last3 = Magerle | first3 = M. | last4 = Ilhan | first4 = A. | last5 = Wöhrer | first5 = A. | last6 = Hackl | first6 = M. | last7 = Pichler | first7 = J. | last8 = Pusch | first8 = S. | last9 = Meyer | first9 = J. | title = Immunohistochemical testing of BRAF V600E status in 1,120 tumor tissue samples of patients with brain metastases. | journal = Acta Neuropathol | volume = 123 | issue = 2 | pages = 223-33 | month = Feb | year = 2012 | doi = 10.1007/s00401-011-0887-y | PMID = 22012135 }}</ref>
*[[Papillary thyroid carcinoma]] (79%).<ref>{{Cite journal | last1 = Ilie | first1 = MI. | last2 = Lassalle | first2 = S. | last3 = Long-Mira | first3 = E. | last4 = Bonnetaud | first4 = C. | last5 = Bordone | first5 = O. | last6 = Lespinet | first6 = V. | last7 = Lamy | first7 = A. | last8 = Sabourin | first8 = JC. | last9 = Haudebourg | first9 = J. | title = Diagnostic value of immunohistochemistry for the detection of the BRAF(V600E) mutation in papillary thyroid carcinoma: comparative analysis with three DNA-based assays. | journal = Thyroid | volume = 24 | issue = 5 | pages = 858-66 | month = May | year = 2014 | doi = 10.1089/thy.2013.0302 | PMID = 24417277 }}</ref>
*[[Ganglioglioma]] (58%).<ref>{{Cite journal | last1 = Koelsche | first1 = C. | last2 = Wöhrer | first2 = A. | last3 = Jeibmann | first3 = A. | last4 = Schittenhelm | first4 = J. | last5 = Schindler | first5 = G. | last6 = Preusser | first6 = M. | last7 = Lasitschka | first7 = F. | last8 = von Deimling | first8 = A. | last9 = Capper | first9 = D. | title = Mutant BRAF V600E protein in ganglioglioma is predominantly expressed by neuronal tumor cells. | journal = Acta Neuropathol | volume = 125 | issue = 6 | pages = 891-900 | month = Jun | year = 2013 | doi = 10.1007/s00401-013-1100-2 | PMID = 23435618 }}</ref>
*[[Pleomorphic xanthoastrocytoma]] (78%).<ref>{{Cite journal | last1 = Koelsche | first1 = C. | last2 = Sahm | first2 = F. | last3 = Wöhrer | first3 = A. | last4 = Jeibmann | first4 = A. | last5 = Schittenhelm | first5 = J. | last6 = Kohlhof | first6 = P. | last7 = Preusser | first7 = M. | last8 = Romeike | first8 = B. | last9 = Dohmen-Scheufler | first9 = H. | title = BRAF-mutated pleomorphic xanthoastrocytoma is associated with temporal location, reticulin fiber deposition and CD34 expression. | journal = Brain Pathol | volume = 24 | issue = 3 | pages = 221-9 | month = Apr | year = 2014 | doi = 10.1111/bpa.12111 | PMID = 24345274 }}</ref>
*[[Hairy cell leukemia]] (>90%)
*Histiocytic disorders: [[Langerhans cell histiocytosis]] and [[Erdheim-Chester disease]]
*Metanephric adenoma <ref name=pmid22727996>{{Cite journal | last1 = Choueiri | first1 = TK. | last2 = Cheville | first2 = J. | last3 = Palescandolo | first3 = E. | last4 = Fay | first4 = AP. | last5 = Kantoff | first5 = PW. | last6 = Atkins | first6 = MB. | last7 = McKenney | first7 = JK. | last8 = Brown | first8 = V. | last9 = Lampron | first9 = ME. | title = BRAF mutations in metanephric adenoma of the kidney. | journal = Eur Urol | volume = 62 | issue = 5 | pages = 917-22 | month = Nov | year = 2012 | doi = 10.1016/j.eururo.2012.05.051 | PMID = 22727996 }}</ref><ref name=pmid25602792>{{Cite journal | last1 = Udager | first1 = AM. | last2 = Pan | first2 = J. | last3 = Magers | first3 = MJ. | last4 = Palapattu | first4 = GS. | last5 = Morgan | first5 = TM. | last6 = Montgomery | first6 = JS. | last7 = Weizer | first7 = AZ. | last8 = Hafez | first8 = KS. | last9 = Miller | first9 = DC. | title = Molecular and immunohistochemical characterization reveals novel BRAF mutations in metanephric adenoma. | journal = Am J Surg Pathol | volume = 39 | issue = 4 | pages = 549-57 | month = Apr | year = 2015 | doi = 10.1097/PAS.0000000000000377 | PMID = 25602792 }}</ref>

===Less commonly mutated===
*[[Colorectal cancer]] (5.5%).<ref name=pmid22012135>{{Cite journal | last1 = Capper | first1 = D. | last2 = Berghoff | first2 = AS. | last3 = Magerle | first3 = M. | last4 = Ilhan | first4 = A. | last5 = Wöhrer | first5 = A. | last6 = Hackl | first6 = M. | last7 = Pichler | first7 = J. | last8 = Pusch | first8 = S. | last9 = Meyer | first9 = J. | title = Immunohistochemical testing of BRAF V600E status in 1,120 tumor tissue samples of patients with brain metastases. | journal = Acta Neuropathol | volume = 123 | issue = 2 | pages = 223-33 | month = Feb | year = 2012 | doi = 10.1007/s00401-011-0887-y | PMID = 22012135 }}</ref>
*[[Ovarian cancer]] (7%).<ref name=pmid22012135>{{Cite journal | last1 = Capper | first1 = D. | last2 = Berghoff | first2 = AS. | last3 = Magerle | first3 = M. | last4 = Ilhan | first4 = A. | last5 = Wöhrer | first5 = A. | last6 = Hackl | first6 = M. | last7 = Pichler | first7 = J. | last8 = Pusch | first8 = S. | last9 = Meyer | first9 = J. | title = Immunohistochemical testing of BRAF V600E status in 1,120 tumor tissue samples of patients with brain metastases. | journal = Acta Neuropathol | volume = 123 | issue = 2 | pages = 223-33 | month = Feb | year = 2012 | doi = 10.1007/s00401-011-0887-y | PMID = 22012135 }}</ref>
*[[Lung adenocarcinoma]] (5%).<ref name=pmid23131393>{{Cite journal | last1 = Ilie | first1 = M. | last2 = Long | first2 = E. | last3 = Hofman | first3 = V. | last4 = Dadone | first4 = B. | last5 = Marquette | first5 = CH. | last6 = Mouroux | first6 = J. | last7 = Vignaud | first7 = JM. | last8 = Begueret | first8 = H. | last9 = Merlio | first9 = JP. | title = Diagnostic value of immunohistochemistry for the detection of the BRAFV600E mutation in primary lung adenocarcinoma Caucasian patients. | journal = Ann Oncol | volume = 24 | issue = 3 | pages = 742-8 | month = Mar | year = 2013 | doi = 10.1093/annonc/mds534 | PMID = 23131393 }}</ref>
*Endosalpingiosis<ref>{{cite journal |vauthors=Chui MH, Shih IM |title=Oncogenic BRAF and KRAS mutations in endosalpingiosis |journal=J Pathol |volume=250 |issue=2 |pages=148–158 |date=February 2020 |pmid=31576556 |doi=10.1002/path.5353 |url=}}</ref>

==See also==
*[[Immunohistochemistry]].
*[[Molecular pathology tests]].
*[[KRAS mutation]].
*[[Cancer Hotspot Panel v2]].
*[[BRAF mutation]].

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

[[Category:Immunohistochemistry]]

Paired box gene 5

2020-11-14T12:57:54Z

Mark: update image

{{ Infobox immunostain
| Name = {{PAGENAME}}
| Image = PAX5_immunohistochemistry_in_relapsed_classical_Hodgkin's_lymphoma.jpg
| Width =
| Caption = PAX5 staining in a classical Hodgkin's lymphoma
| Abbrev = PAX5
| Synonyms =
| Similar =
| Clones =
| Use = B-cell marker, weakly positive in classical Hodgkin's lymphoma
| Subspecial = [[hematopathology]]
| Pattern = nuclear stain
| Positive = B-cell lymphoma, [[classical Hodgkin's lymphoma]]
| Negative =
| Other =
}}
'''Paired box gene 5''', commonly known by the abbreviation '''PAX5''', is a [[immunostain]] used in [[hematopathology]].

==Tumours with positive staining==
*B-cell lymphomas
*[[Hodgkin lymphoma]]
**typically weak in classical Hodgkin's lymphoma
**strong in nodular lymphocyte-predominant Hodgkin's lymphoma

==Negative staining==
*Plasmablastic neoplasms

==See also==
*[[Immunostains]].

==References==
{{Reflist|1}}

[[Category:Immunohistochemistry]]

Paired box gene 5

2020-11-14T12:15:05Z

Mark: starter

{{ Infobox immunostain
| Name = {{PAGENAME}}
| Image = Poorly differentiated carcinoma -- PAX8 - intermed mag.jpg
| Width =
| Caption = PAX5 staining in a classical Hodgkin's lymphoma
| Abbrev = PAX5
| Synonyms =
| Similar =
| Clones =
| Use = B-cell marker, weakly positive in classical Hodgkin's lymphoma
| Subspecial = [[hematopathology]]
| Pattern = nuclear stain
| Positive = B-cell lymphoma, [[classical Hodgkin's lymphoma]]
| Negative =
| Other =
}}
'''Paired box gene 5''', commonly known by the abbreviation '''PAX5''', is a [[immunostain]] used in [[hematopathology]].

==Tumours with positive staining==
*B-cell lymphomas
*[[Hodgkin lymphoma]]
**typically weak in classical Hodgkin's lymphoma
**strong in nodular lymphocyte-predominant Hodgkin's lymphoma

==Negative staining==
*Plasmablastic neoplasms

==See also==
*[[Immunostains]].

==References==
{{Reflist|1}}

[[Category:Immunohistochemistry]]

PAX5

2020-11-14T12:10:23Z

Mark: redirect

#REDIRECT[[Paired box gene 5]]

Paired box gene 8

2020-11-14T12:09:30Z

Mark: wikify PAX5

{{ Infobox immunostain
| Name = {{PAGENAME}}
| Image = Poorly differentiated carcinoma -- PAX8 - intermed mag.jpg
| Width =
| Caption = PAX8 staining in a poorly differentiated [[carcinoma]].
| Abbrev = PAX8
| Synonyms =
| Similar =
| Clones =
| Use = RCC versus other, gynecologic tract malignancy versus other
| Subspecial = [[gynecologic pathology]], [[genitourinary pathology]]
| Pattern = nuclear stain
| Positive = [[renal cell carcinoma]]s, [[renal oncocytoma]], thyroid tumours, [[serous carcinoma]], [[endometrial carcinoma]]s
| Negative =
| Other =
}}
'''Paired box gene 8''', commonly known by the abbreviation '''PAX8''', is a commonly used [[immunostain]] in [[gynecologic pathology]] and [[genitourinary pathology]].

==Tumours with positive staining==
*Thyroid tumours ~ 90%.<ref name=pmid21552115>{{Cite journal | last1 = Laury | first1 = AR. | last2 = Perets | first2 = R. | last3 = Piao | first3 = H. | last4 = Krane | first4 = JF. | last5 = Barletta | first5 = JA. | last6 = French | first6 = C. | last7 = Chirieac | first7 = LR. | last8 = Lis | first8 = R. | last9 = Loda | first9 = M. | title = A comprehensive analysis of PAX8 expression in human epithelial tumors. | journal = Am J Surg Pathol | volume = 35 | issue = 6 | pages = 816-26 | month = Jun | year = 2011 | doi = 10.1097/PAS.0b013e318216c112 | PMID = 21552115 }}</ref>
*[[Renal cell carcinoma]]s ~ 90%.<ref name=pmid21552115/>
*[[Renal oncocytoma]]s ~ 80%.<ref name=pmid21552115/>
*High-grade [[ovarian serous carcinoma]]s ~ 99%.<ref name=pmid21552115/>
*Nonserous epithelial [[ovarian tumours|ovarian neoplasms]] ~ 70%.<ref name=pmid21552115/>
*[[Endometrial carcinoma]]s ~ 98%.<ref name=pmid21552115/>
*[[Pancreatic neuroendocrine tumour]] ~ 74%.<ref name=pmid20890270>{{Cite journal | last1 = Sangoi | first1 = AR. | last2 = Ohgami | first2 = RS. | last3 = Pai | first3 = RK. | last4 = Beck | first4 = AH. | last5 = McKenney | first5 = JK. | last6 = Pai | first6 = RK. | title = PAX8 expression reliably distinguishes pancreatic well-differentiated neuroendocrine tumors from ileal and pulmonary well-differentiated neuroendocrine tumors and pancreatic acinar cell carcinoma. | journal = Mod Pathol | volume = 24 | issue = 3 | pages = 412-24 | month = Mar | year = 2011 | doi = 10.1038/modpathol.2010.176 | PMID = 20890270 }}</ref>
**Can help differentiate from lung NETs.
*Epithelial component of thymic tumors 77-100% depending on sub-type<ref name=pmid21552115/><ref name=pmid21836478>{{cite journal |vauthors=Weissferdt A, Moran CA |title=Pax8 expression in thymic epithelial neoplasms: an immunohistochemical analysis |journal=Am. J. Surg. Pathol. |volume=35 |issue=9 |pages=1305–10 |date=September 2011 |pmid=21836478 |doi=10.1097/PAS.0b013e3182260735 |url=}}</ref>

===May be positive===
*Peritoneal [[malignant mesothelioma]] (5 +ve of 27<ref name=pmid28877056>{{cite journal |vauthors=Chapel DB, Husain AN, Krausz T, McGregor SM |title=PAX8 Expression in a Subset of Malignant Peritoneal Mesotheliomas and Benign Mesothelium has Diagnostic Implications in the Differential Diagnosis of Ovarian Serous Carcinoma |journal=Am. J. Surg. Pathol. |volume=41 |issue=12 |pages=1675–1682 |date=December 2017 |pmid=28877056 |doi=10.1097/PAS.0000000000000935 |url=}}</ref>).

==Negative staining==
[[Image:Lymphoma - lung - PAX8 -- intermed mag.jpg|thumb|right|300px|Negative PAX8 staining in a lymphoma.]]
*[[Urothelial carcinoma]] - can be positive (3 positive/18 bladder tumours<ref name=pmid21552115/>).
*[[Lymphoma]] (beware false positive staining due to polyclonal PAX8 antibodies cross-reacting with [[PAX5]])<ref name=pmid22037256>{{cite journal |vauthors=Moretti L, Medeiros LJ, Kunkalla K, Williams MD, Singh RR, Vega F |title=N-terminal PAX8 polyclonal antibody shows cross-reactivity with N-terminal region of PAX5 and is responsible for reports of PAX8 positivity in malignant lymphomas |journal=Mod. Pathol. |volume=25 |issue=2 |pages=231–6 |date=February 2012 |pmid=22037256 |doi=10.1038/modpathol.2011.162 |url=}}</ref>
*[[Malignant melanoma]].<ref name=pmid21285870>{{Cite journal | last1 = Tacha | first1 = D. | last2 = Zhou | first2 = D. | last3 = Cheng | first3 = L. | title = Expression of PAX8 in normal and neoplastic tissues: a comprehensive immunohistochemical study. | journal = Appl Immunohistochem Mol Morphol | volume = 19 | issue = 4 | pages = 293-9 | month = Jul | year = 2011 | doi = 10.1097/PAI.0b013e3182025f66 | PMID = 21285870 }}</ref>

==See also==
*[[Immunostains]].

==References==
{{Reflist|1}}

[[Category:Immunohistochemistry]]

Enteropathy-associated T-cell lymphoma

2020-08-09T12:49:06Z

Mark: epidermiotropic -> epitheliotropic

{{ Infobox diagnosis
| Name = {{PAGENAME}}
| Image = Enteropathy-associated_T_cell_lymphoma_-_low_mag.jpg
| Width =
| Caption = Enteropathy-associated T cell lymphoma. [[H&E stain]].
| Synonyms = enteropathy-type T-cell lymphoma
| Micro = large or medium-sized lymphoid cells in the mucosa and submucosa
| Subtypes = Historical: pleomorphic anaplastic (type I), monomorphic (type II)
| LMDDx = other lymphomas
| Stains =
| IHC = CD3 +ve, CD5 -ve, CD8 -ve/+ve, CD56 -ve/+ve, CD30 +ve
| EM =
| Molecular =
| IF =
| Gross =
| Grossing =
| Site = [[duodenum]]
| Assdx = [[celiac disease]]
| Syndromes =
| Clinicalhx = history of celiac disease
| Signs =
| Symptoms =
| Prevalence = uncommon
| Bloodwork =
| Rads =
| Endoscopy =
| Prognosis = poor
| Other =
| ClinDDx = dependent on presentation - other causes of [[SBO]], e.g. [[duodenal adenocarcinoma]]
| Tx =
}}
'''Enteropathy-associated T-cell lymphoma''', abbreviated '''EATL''', is an uncommon type of [[lymphoma]] associated with [[celiac disease]].

It is also known as '''enteropathy-type T-cell lymphoma''', abbreviated '''ETTL'''.

==General==
*T cell lymphoma classically due to [[celiac sprue]].
*Historically subdivided into type I and type II.<ref name=pmid21566094>{{cite journal |author=Delabie J, et al |title=Enteropathy-associated T-cell lymphoma: clinical and histological findings from the International Peripheral T-Cell Lymphoma Project|journal=Blood |volume=118|issue=148|pages= 148|year=2011|month=July}}</ref>
**''Pleomorphic anaplastic'' (type I) associated with celiac sprue.<ref name=pmid17511112/> - this is now referred to as EATL since the 2017 revision of the WHO blue book 4th edition.
**''Monomorphic'' (type II) not associated with celiac sprue - this is separate entity known as [[monomorphic epitheliotropic intestinal T-cell lymphoma]] (MEITL); it is no longer referred to as EATL as it is not associated with an enteropathy.
*Poor prognosis.<ref name=pmid23313469>{{Cite journal | last1 = Malamut | first1 = G. | last2 = Chandesris | first2 = O. | last3 = Verkarre | first3 = V. | last4 = Meresse | first4 = B. | last5 = Callens | first5 = C. | last6 = Macintyre | first6 = E. | last7 = Bouhnik | first7 = Y. | last8 = Gornet | first8 = JM. | last9 = Allez | first9 = M. | title = Enteropathy associated T cell lymphoma in celiac disease: a large retrospective study. | journal = Dig Liver Dis | volume = 45 | issue = 5 | pages = 377-84 | month = May | year = 2013 | doi = 10.1016/j.dld.2012.12.001 | PMID = 23313469 }}</ref>
**Five-year survival as low as 20%.<ref name=pmid24876396>{{Cite journal | last1 = Pun | first1 = AH. | last2 = Kasmeridis | first2 = H. | last3 = Rieger | first3 = N. | last4 = Loganathan | first4 = A. | title = Enteropathy associated T-cell lymphoma presenting with multiple episodes of small bowel haemorrhage and perforation. | journal = J Surg Case Rep | volume = 2014 | issue = 3 | pages = | month = | year = 2014 | doi = 10.1093/jscr/rju013 | PMID = 24876396 }}</ref>

Presentations - may include:
*[[Small bowel obstruction]] (SBO) or perforation.<ref name=pmid23555174>{{Cite journal | last1 = Kim | first1 = JB. | last2 = Kim | first2 = SH. | last3 = Cho | first3 = YK. | last4 = Ahn | first4 = SB. | last5 = Jo | first5 = YJ. | last6 = Park | first6 = YS. | last7 = Lee | first7 = JH. | last8 = Kim | first8 = DH. | last9 = Lee | first9 = H. | title = A case of colon perforation due to enteropathy-associated T-cell lymphoma. | journal = World J Gastroenterol | volume = 19 | issue = 11 | pages = 1841-4 | month = Mar | year = 2013 | doi = 10.3748/wjg.v19.i11.1841 | PMID = 23555174 }}</ref>
*GI hemorrhage.<ref name=pmid24876396/>

Treatment:
*Chemotherapy.<ref>{{Cite journal | last1 = Cairoli | first1 = A. | last2 = Ketterer | first2 = N. | last3 = Barelli | first3 = S. | last4 = Duchosal | first4 = MA. | title = High-dose therapy and autologous hematopoietic stem cell transplant in T-cell lymphoma: a single center experience. | journal = Leuk Lymphoma | volume = 55 | issue = 8 | pages = 1827-31 | month = Aug | year = 2014 | doi = 10.3109/10428194.2013.852666 | PMID = 24138331 }}</ref>
*Autologous stem cell transplantation.<ref name=pmid23361910>{{Cite journal | last1 = Jantunen | first1 = E. | last2 = Boumendil | first2 = A. | last3 = Finel | first3 = H. | last4 = Luan | first4 = JJ. | last5 = Johnson | first5 = P. | last6 = Rambaldi | first6 = A. | last7 = Haynes | first7 = A. | last8 = Duchosal | first8 = MA. | last9 = Bethge | first9 = W. | title = Autologous stem cell transplantation for enteropathy-associated T-cell lymphoma: a retrospective study by the EBMT. | journal = Blood | volume = 121 | issue = 13 | pages = 2529-32 | month = Mar | year = 2013 | doi = 10.1182/blood-2012-11-466839 | PMID = 23361910 }}</ref>

==Gross==
Features:<ref name=pmid24959225>{{Cite journal | last1 = Jiao | first1 = G. | last2 = Zheng | first2 = Z. | last3 = Jiang | first3 = K. | last4 = Zhang | first4 = J. | last5 = Wang | first5 = B. | title = Enteropathy-associated T-cell lymphoma presenting with gastrointestinal tract symptoms: A report of two cases and review of diagnostic challenges and clinicopathological correlation. | journal = Oncol Lett | volume = 8 | issue = 1 | pages = 91-94 | month = Jul | year = 2014 | doi = 10.3892/ol.2014.2105 | PMID = 24959225 }}</ref>
*Typically manifest as ulcers, fissures or plaques. †

Notes:
*† B-cell lymphomas are typically raised nodules.<ref name=pmid24959225/>

==Microscopic==
Features:<ref name=pmid21323966>{{Cite journal | last1 = Takeshita | first1 = M. | last2 = Nakamura | first2 = S. | last3 = Kikuma | first3 = K. | last4 = Nakayama | first4 = Y. | last5 = Nimura | first5 = S. | last6 = Yao | first6 = T. | last7 = Urabe | first7 = S. | last8 = Ogawara | first8 = S. | last9 = Yonemasu | first9 = H. | title = Pathological and immunohistological findings and genetic aberrations of intestinal enteropathy-associated T cell lymphoma in Japan. | journal = Histopathology | volume = 58 | issue = 3 | pages = 395-407 | month = Feb | year = 2011 | doi = 10.1111/j.1365-2559.2011.03768.x | PMID = 21323966 }}</ref>
*Abundant large ''or'' medium-sized lymphoid cells in the mucosa and submucosa.
**Large-sized cells ~ 2x RBC diameter = type 1.
**Medium sized cells ~ 1.5x RBC diameter = type 2.
*Intestinal epithelium usually preserved.

DDx:
*Other types of lymphoma.
**[[DLBCL]].
**[[Anaplastic large cell lymphoma]].<ref name=pmid24325295>{{Cite journal | last1 = Kim | first1 = do H. | last2 = Lee | first2 = D. | last3 = Kim | first3 = JW. | last4 = Huh | first4 = J. | last5 = Park | first5 = SH. | last6 = Ha | first6 = HK. | last7 = Suh | first7 = C. | last8 = Yoon | first8 = SM. | last9 = Kim | first9 = KJ. | title = Endoscopic and clinical analysis of primary T-cell lymphoma of the gastrointestinal tract according to pathological subtype. | journal = J Gastroenterol Hepatol | volume = 29 | issue = 5 | pages = 934-43 | month = May | year = 2014 | doi = 10.1111/jgh.12471 | PMID = 24325295 }}</ref>

===Image===
<gallery>
Image:Enteropathy-associated_T_cell_lymphoma_-_low_mag.jpg | EATL. (WC)
</gallery>

==IHC==
Features - type 1:<ref name=pmid21323966/><ref name=pmid17511112>{{cite journal |vauthors=Zettl A, deLeeuw R, Haralambieva E, Mueller-Hermelink HK |title=Enteropathy-type T-cell lymphoma |journal=Am. J. Clin. Pathol. |volume=127 |issue=5 |pages=701–6 |date=May 2007 |pmid=17511112 |doi=10.1309/nw2bk1dxb0eqg55h |url=}}</ref>
*[[CD56]] -ve.

Features - type 2:<ref name=pmid21323966/><ref name=pmid21921780>{{Cite journal | last1 = Chan | first1 = JK. | last2 = Chan | first2 = AC. | last3 = Cheuk | first3 = W. | last4 = Wan | first4 = SK. | last5 = Lee | first5 = WK. | last6 = Lui | first6 = YH. | last7 = Chan | first7 = WK. | title = Type II enteropathy-associated T-cell lymphoma: a distinct aggressive lymphoma with frequent γδ T-cell receptor expression. | journal = Am J Surg Pathol | volume = 35 | issue = 10 | pages = 1557-69 | month = Oct | year = 2011 | doi = 10.1097/PAS.0b013e318222dfcd | PMID = 21921780 }}</ref>
*CD3 +ve.
*CD5 -ve.
*CD8 -ve/+ve.
*CD56 +ve.
*CD30 +ve.

==See also==
*[[Lymphoma]].
*[[Celiac disease]].

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

[[Category:Diagnosis]]
[[Category:Lymphoma]]

Enteropathy-associated T-cell lymphoma

2020-08-09T12:46:28Z

Mark: former type II now classified as separate entity

{{ Infobox diagnosis
| Name = {{PAGENAME}}
| Image = Enteropathy-associated_T_cell_lymphoma_-_low_mag.jpg
| Width =
| Caption = Enteropathy-associated T cell lymphoma. [[H&E stain]].
| Synonyms = enteropathy-type T-cell lymphoma
| Micro = large or medium-sized lymphoid cells in the mucosa and submucosa
| Subtypes = Historical: pleomorphic anaplastic (type I), monomorphic (type II)
| LMDDx = other lymphomas
| Stains =
| IHC = CD3 +ve, CD5 -ve, CD8 -ve/+ve, CD56 -ve/+ve, CD30 +ve
| EM =
| Molecular =
| IF =
| Gross =
| Grossing =
| Site = [[duodenum]]
| Assdx = [[celiac disease]]
| Syndromes =
| Clinicalhx = history of celiac disease
| Signs =
| Symptoms =
| Prevalence = uncommon
| Bloodwork =
| Rads =
| Endoscopy =
| Prognosis = poor
| Other =
| ClinDDx = dependent on presentation - other causes of [[SBO]], e.g. [[duodenal adenocarcinoma]]
| Tx =
}}
'''Enteropathy-associated T-cell lymphoma''', abbreviated '''EATL''', is an uncommon type of [[lymphoma]] associated with [[celiac disease]].

It is also known as '''enteropathy-type T-cell lymphoma''', abbreviated '''ETTL'''.

==General==
*T cell lymphoma classically due to [[celiac sprue]].
*Historically subdivided into type I and type II.<ref name=pmid21566094>{{cite journal |author=Delabie J, et al |title=Enteropathy-associated T-cell lymphoma: clinical and histological findings from the International Peripheral T-Cell Lymphoma Project|journal=Blood |volume=118|issue=148|pages= 148|year=2011|month=July}}</ref>
**''Pleomorphic anaplastic'' (type I) associated with celiac sprue.<ref name=pmid17511112/> - this is now referred to as EATL since the 2017 revision of the WHO blue book 4th edition.
**''Monomorphic'' (type II) not associated with celiac sprue - this is separate entity known as [[monomorphic epidermotropic intestinal T-cell lymphoma]]; it is no longer referred to as EATL as it is not associated with an enteropathy.
*Poor prognosis.<ref name=pmid23313469>{{Cite journal | last1 = Malamut | first1 = G. | last2 = Chandesris | first2 = O. | last3 = Verkarre | first3 = V. | last4 = Meresse | first4 = B. | last5 = Callens | first5 = C. | last6 = Macintyre | first6 = E. | last7 = Bouhnik | first7 = Y. | last8 = Gornet | first8 = JM. | last9 = Allez | first9 = M. | title = Enteropathy associated T cell lymphoma in celiac disease: a large retrospective study. | journal = Dig Liver Dis | volume = 45 | issue = 5 | pages = 377-84 | month = May | year = 2013 | doi = 10.1016/j.dld.2012.12.001 | PMID = 23313469 }}</ref>
**Five-year survival as low as 20%.<ref name=pmid24876396>{{Cite journal | last1 = Pun | first1 = AH. | last2 = Kasmeridis | first2 = H. | last3 = Rieger | first3 = N. | last4 = Loganathan | first4 = A. | title = Enteropathy associated T-cell lymphoma presenting with multiple episodes of small bowel haemorrhage and perforation. | journal = J Surg Case Rep | volume = 2014 | issue = 3 | pages = | month = | year = 2014 | doi = 10.1093/jscr/rju013 | PMID = 24876396 }}</ref>

Presentations - may include:
*[[Small bowel obstruction]] (SBO) or perforation.<ref name=pmid23555174>{{Cite journal | last1 = Kim | first1 = JB. | last2 = Kim | first2 = SH. | last3 = Cho | first3 = YK. | last4 = Ahn | first4 = SB. | last5 = Jo | first5 = YJ. | last6 = Park | first6 = YS. | last7 = Lee | first7 = JH. | last8 = Kim | first8 = DH. | last9 = Lee | first9 = H. | title = A case of colon perforation due to enteropathy-associated T-cell lymphoma. | journal = World J Gastroenterol | volume = 19 | issue = 11 | pages = 1841-4 | month = Mar | year = 2013 | doi = 10.3748/wjg.v19.i11.1841 | PMID = 23555174 }}</ref>
*GI hemorrhage.<ref name=pmid24876396/>

Treatment:
*Chemotherapy.<ref>{{Cite journal | last1 = Cairoli | first1 = A. | last2 = Ketterer | first2 = N. | last3 = Barelli | first3 = S. | last4 = Duchosal | first4 = MA. | title = High-dose therapy and autologous hematopoietic stem cell transplant in T-cell lymphoma: a single center experience. | journal = Leuk Lymphoma | volume = 55 | issue = 8 | pages = 1827-31 | month = Aug | year = 2014 | doi = 10.3109/10428194.2013.852666 | PMID = 24138331 }}</ref>
*Autologous stem cell transplantation.<ref name=pmid23361910>{{Cite journal | last1 = Jantunen | first1 = E. | last2 = Boumendil | first2 = A. | last3 = Finel | first3 = H. | last4 = Luan | first4 = JJ. | last5 = Johnson | first5 = P. | last6 = Rambaldi | first6 = A. | last7 = Haynes | first7 = A. | last8 = Duchosal | first8 = MA. | last9 = Bethge | first9 = W. | title = Autologous stem cell transplantation for enteropathy-associated T-cell lymphoma: a retrospective study by the EBMT. | journal = Blood | volume = 121 | issue = 13 | pages = 2529-32 | month = Mar | year = 2013 | doi = 10.1182/blood-2012-11-466839 | PMID = 23361910 }}</ref>

==Gross==
Features:<ref name=pmid24959225>{{Cite journal | last1 = Jiao | first1 = G. | last2 = Zheng | first2 = Z. | last3 = Jiang | first3 = K. | last4 = Zhang | first4 = J. | last5 = Wang | first5 = B. | title = Enteropathy-associated T-cell lymphoma presenting with gastrointestinal tract symptoms: A report of two cases and review of diagnostic challenges and clinicopathological correlation. | journal = Oncol Lett | volume = 8 | issue = 1 | pages = 91-94 | month = Jul | year = 2014 | doi = 10.3892/ol.2014.2105 | PMID = 24959225 }}</ref>
*Typically manifest as ulcers, fissures or plaques. †

Notes:
*† B-cell lymphomas are typically raised nodules.<ref name=pmid24959225/>

==Microscopic==
Features:<ref name=pmid21323966>{{Cite journal | last1 = Takeshita | first1 = M. | last2 = Nakamura | first2 = S. | last3 = Kikuma | first3 = K. | last4 = Nakayama | first4 = Y. | last5 = Nimura | first5 = S. | last6 = Yao | first6 = T. | last7 = Urabe | first7 = S. | last8 = Ogawara | first8 = S. | last9 = Yonemasu | first9 = H. | title = Pathological and immunohistological findings and genetic aberrations of intestinal enteropathy-associated T cell lymphoma in Japan. | journal = Histopathology | volume = 58 | issue = 3 | pages = 395-407 | month = Feb | year = 2011 | doi = 10.1111/j.1365-2559.2011.03768.x | PMID = 21323966 }}</ref>
*Abundant large ''or'' medium-sized lymphoid cells in the mucosa and submucosa.
**Large-sized cells ~ 2x RBC diameter = type 1.
**Medium sized cells ~ 1.5x RBC diameter = type 2.
*Intestinal epithelium usually preserved.

DDx:
*Other types of lymphoma.
**[[DLBCL]].
**[[Anaplastic large cell lymphoma]].<ref name=pmid24325295>{{Cite journal | last1 = Kim | first1 = do H. | last2 = Lee | first2 = D. | last3 = Kim | first3 = JW. | last4 = Huh | first4 = J. | last5 = Park | first5 = SH. | last6 = Ha | first6 = HK. | last7 = Suh | first7 = C. | last8 = Yoon | first8 = SM. | last9 = Kim | first9 = KJ. | title = Endoscopic and clinical analysis of primary T-cell lymphoma of the gastrointestinal tract according to pathological subtype. | journal = J Gastroenterol Hepatol | volume = 29 | issue = 5 | pages = 934-43 | month = May | year = 2014 | doi = 10.1111/jgh.12471 | PMID = 24325295 }}</ref>

===Image===
<gallery>
Image:Enteropathy-associated_T_cell_lymphoma_-_low_mag.jpg | EATL. (WC)
</gallery>

==IHC==
Features - type 1:<ref name=pmid21323966/><ref name=pmid17511112>{{cite journal |vauthors=Zettl A, deLeeuw R, Haralambieva E, Mueller-Hermelink HK |title=Enteropathy-type T-cell lymphoma |journal=Am. J. Clin. Pathol. |volume=127 |issue=5 |pages=701–6 |date=May 2007 |pmid=17511112 |doi=10.1309/nw2bk1dxb0eqg55h |url=}}</ref>
*[[CD56]] -ve.

Features - type 2:<ref name=pmid21323966/><ref name=pmid21921780>{{Cite journal | last1 = Chan | first1 = JK. | last2 = Chan | first2 = AC. | last3 = Cheuk | first3 = W. | last4 = Wan | first4 = SK. | last5 = Lee | first5 = WK. | last6 = Lui | first6 = YH. | last7 = Chan | first7 = WK. | title = Type II enteropathy-associated T-cell lymphoma: a distinct aggressive lymphoma with frequent γδ T-cell receptor expression. | journal = Am J Surg Pathol | volume = 35 | issue = 10 | pages = 1557-69 | month = Oct | year = 2011 | doi = 10.1097/PAS.0b013e318222dfcd | PMID = 21921780 }}</ref>
*CD3 +ve.
*CD5 -ve.
*CD8 -ve/+ve.
*CD56 +ve.
*CD30 +ve.

==See also==
*[[Lymphoma]].
*[[Celiac disease]].

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

[[Category:Diagnosis]]
[[Category:Lymphoma]]

Hairy cell leukemia

2020-08-02T20:38:45Z

Mark: other IHC

[[File:Bone marrow infiltration by hairy cell leukaemia.jpg|thumb|High power magnification of a bone marrow trephine showing infiltration by hairy cell leukaemia.]]
Indolent B-cell neoplasm, abbreviated ''HCL''. Named for the appearances on peripheral blood smears. The vast majority (>95%) harbour the BRAF V600E mutation.<ref name=pmid25992240>{{Cite journal | last1 = Ahmadzadeh | first1 = A. | last2 = Shahrabi | first2 = S. | last3 = Jaseb | first3 = K. | last4 = Norozi | first4 = F. | last5 = Shahjahani | first5 = M. | last6 = Vosoughi | first6 = T. | last7 = Hajizamani | first7 = S. | last8 = Saki | first8 = N. | title = BRAF Mutation in Hairy Cell Leukemia. | journal = Oncol Rev | volume = 8 | issue = 2 | pages = 253 | month = Sep | year = 2014 | doi = 10.4081/oncol.2014.253 | PMID = 25992240 }}</ref> Mutations in other parts of the BRAF gene are described, but rare.<ref name=pmid24433452>{{Cite journal | last1 = Tschernitz | first1 = S. | last2 = Flossbach | first2 = L. | last3 = Bonengel | first3 = M. | last4 = Roth | first4 = S. | last5 = Rosenwald | first5 = A. | last6 = Geissinger | first6 = E. | title = Alternative BRAF mutations in BRAF V600E-negative hairy cell leukaemias. | journal = Br J Haematol | volume = 165 | issue = 4 | pages = 529-33 | month = May | year = 2014 | doi = 10.1111/bjh.12735 | PMID = 24433452 }}</ref>

In the bone marrow, they are associated with heavy reticulin fibrosis, commonly resulting in ''dry taps''.<ref name=pmid22499303>{{Cite journal | last1 = Galani | first1 = KS. | last2 = Subramanian | first2 = PG. | last3 = Gadage | first3 = VS. | last4 = Rahman | first4 = K. | last5 = Ashok Kumar | first5 = MS. | last6 = Shinde | first6 = S. | last7 = Mahadik | first7 = S. | last8 = Ansari | first8 = R. | last9 = Sengar | first9 = M. | title = Clinico-pathological profile of Hairy cell leukemia: critical insights gained at a tertiary care cancer hospital. | journal = Indian J Pathol Microbiol | volume = 55 | issue = 1 | pages = 61-5 | month = | year = | doi = 10.4103/0377-4929.94858 | PMID = 22499303 }}</ref>

Clinical:<ref>URL: [http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=cmed&part=A34022 http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=cmed&part=A34022]. Accessed on: 20 August 2010.</ref>
*Pancytopenia. Monocytopenia common in earlier disease.
*Splenic enlargement.
*No lymphadenopathy.
*Good prognosis (with treatment), though (likely) not curable.

==Gross==
Features:<ref name=Ref_PCPBoD8_326>{{Ref PCPBoD8|326}}</ref>
*Huge beefy red [[spleen]].
**Red as white pulp obliterated.

==Microscopic==
Features:<ref>URL: [http://emedicine.medscape.com/article/200580-diagnosis http://emedicine.medscape.com/article/200580-diagnosis]. Accessed on: 18 August 2010.</ref>
*Small cells (10-20 micrometers) with "Fried egg"-like appearance:
**Well-demarcated fuzzy cell borders,
**Clear/whispy cytoplasm and,
**Central round nucleus.
***Peri-nuclear clearing ("water-clear rim"<ref>URL: [http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=cmed&part=A34022 http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=cmed&part=A34022]. Accessed on: 20 August 2010.</ref>) -- '''key feature'''.

DDx:
*[[Hepatosplenic T-cell lymphoma]].

===Images===
<gallery>
Image:Hairy_cell_leukemia.jpg | HCL - blood film. (WC)
Image:Hairy cell leukemia - high mag.jpg | HCL - high mag. (WC)
Image:Hairy_cell_leukemia_-_very_high_mag.jpg | HCL - very high mag. (WC)
</gallery>
www:
*[http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=cmed&part=A34022&rendertype=figure&id=A34027 HCL - bone marrow (nlm.nih.gov)] from [http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=cmed&part=A34022 Holland-Frei Cancer Medicine (nlm.nih.gov)].
*[http://path.upmc.edu/cases/case240.html HCL - several images (upmc.edu)].
*[http://path.upmc.edu/cases/case691.html HCL - another case with several images (upmc.edu)].
*[http://webpathology.com/image.asp?case=380&n=3 HCL in the spleen (webpathology.com)].

==IHC==
Features:<ref>URL: [http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=cmed&part=A34022&rendertype=table&id=A34029 http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=cmed&part=A34022&rendertype=table&id=A34029]. Accessed on: 20 August 2010.</ref>
*CD20 +ve, CD11c+ve, CD25 +ve, CD103 +ve, CD123 +ve, cyclin D1 +ve, DBA44 +ve
*Annexin A1 +ve (only useful in heavy bone marrow infiltration as it is also positive in T-cells and granulopoietic cells)
*TRAP - tartrate-resistant acid phosphatase (historically histochemically, now immunohistochemically)
*[[HBME1]]<ref name=pmid24092261>{{cite journal |vauthors=Krenács L, Tóth-Lipták J, Demeter J, Piukovics K, Borbényi Z, Gogolák P, Sári E, Bagdi E |title=Monoclonal antibody HBME-1 reacts with a minor subset of B cells with villous surface and can be useful in the diagnosis of hairy cell leukemia and other indolent lymphoproliferations of villous B lymphocytes |journal=Virchows Arch. |volume=463 |issue=6 |pages=787–94 |date=December 2013 |pmid=24092261 |doi=10.1007/s00428-013-1490-5 |url=}}</ref>
*BRAF V600E mutation-specific antibody
*CD5 -ve.

Flow cytometry:
*CD19 +ve, CD11c +ve, FMC7 +ve.

==See also==
*[[Small cell lymphomas]].

==References==
{{Reflist}}

[[Category: Haematopathology]]

GATA3

2020-08-02T20:23:17Z

Mark: T-cell marker

{{ Infobox immunostain
| Name = {{PAGENAME}}
| Image = Benign urothelium - GATA3 -- high mag.jpg
| Width =
| Caption = GATA3 staining in benign [[urothelium]].
| Abbrev =
| Synonyms =
| Similar = [[thrombomodulin]]
| Clones =
| Use = bladder versus prostate, bladder versus SCC
| Subspecial = [[Genitourinary pathology]], [[Breast pathology]]
| Pattern = nuclear
| Positive = [[urothelial carcinoma]], [[invasive ductal carcinoma of the breast]], [[lobular breast carcinoma]]
| Negative = [[prostatic carcinoma]], [[squamous cell carcinoma of the lung]]
| Other =
}}
'''GATA3''' an [[immunostain]] that is increasingly used in [[genitourinary pathology]].

==Positive==
*[[Urothelial carcinoma]].<ref name=pmid22982890>{{cite journal |author=Chang A, Amin A, Gabrielson E, ''et al.'' |title=Utility of GATA3 immunohistochemistry in differentiating urothelial carcinoma from prostate adenocarcinoma and squamous cell carcinomas of the uterine cervix, anus, and lung |journal=Am. J. Surg. Pathol. |volume=36 |issue=10 |pages=1472–6 |year=2012 |month=October |pmid=22982890 |pmc=3444740 |doi=10.1097/PAS.0b013e318260cde7 |url=}}</ref>
*[[Invasive breast cancer|Breast carcinoma]] - more sensitive than [[GCDFP-15]].<ref name=pmid24145643>{{Cite journal | last1 = Miettinen | first1 = M. | last2 = McCue | first2 = PA. | last3 = Sarlomo-Rikala | first3 = M. | last4 = Rys | first4 = J. | last5 = Czapiewski | first5 = P. | last6 = Wazny | first6 = K. | last7 = Langfort | first7 = R. | last8 = Waloszczyk | first8 = P. | last9 = Biernat | first9 = W. | title = GATA3: a multispecific but potentially useful marker in surgical pathology: a systematic analysis of 2500 epithelial and nonepithelial tumors. | journal = Am J Surg Pathol | volume = 38 | issue = 1 | pages = 13-22 | month = Jan | year = 2014 | doi = 10.1097/PAS.0b013e3182a0218f | PMID = 24145643 }}</ref>
**[[Lobular breast carcinoma]].<ref name=pmid24061521>{{Cite journal | last1 = Ellis | first1 = CL. | last2 = Chang | first2 = AG. | last3 = Cimino-Mathews | first3 = A. | last4 = Argani | first4 = P. | last5 = Youssef | first5 = RF. | last6 = Kapur | first6 = P. | last7 = Montgomery | first7 = EA. | last8 = Epstein | first8 = JI. | title = GATA-3 immunohistochemistry in the differential diagnosis of adenocarcinoma of the urinary bladder. | journal = Am J Surg Pathol | volume = 37 | issue = 11 | pages = 1756-60 | month = Nov | year = 2013 | doi = 10.1097/PAS.0b013e31829cdba7 | PMID = 24061521 }}</ref>
*[[Chromophobe renal cell carcinoma]] ~50% of cases.<ref name=pmid24145643/>
*[[Trophoblastic tumours]] +ve.<ref>{{Cite journal | last1 = Mirkovic | first1 = J. | last2 = Elias | first2 = K. | last3 = Drapkin | first3 = R. | last4 = Barletta | first4 = JA. | last5 = Quade | first5 = B. | last6 = Hirsch | first6 = MS. | title = GATA3 expression in gestational trophoblastic tissues and tumours. | journal = Histopathology | volume = 67 | issue = 5 | pages = 636-44 | month = Nov | year = 2015 | doi = 10.1111/his.12681 | PMID = 25753145 }}</ref> including [[choriocarcinoma]].<ref>{{Cite journal | last1 = Osman | first1 = H. | last2 = Cheng | first2 = L. | last3 = Ulbright | first3 = TM. | last4 = Idrees | first4 = MT. | title = The utility of CDX2, GATA3, and DOG1 in the diagnosis of testicular neoplasms: an immunohistochemical study of 109 cases. | journal = Hum Pathol | volume = 48 | issue = | pages = 18-24 | month = Feb | year = 2016 | doi = 10.1016/j.humpath.2015.09.028 | PMID = 26772394 }}</ref>
*Parathyroid - [[parathyroid hyperplasia]], [[parathyroid adenoma]], [[parathyroid carcinoma]].<ref name=pmid25046229>{{Cite journal | last1 = Ordóñez | first1 = NG. | title = Value of GATA3 immunostaining in the diagnosis of parathyroid tumors. | journal = Appl Immunohistochem Mol Morphol | volume = 22 | issue = 10 | pages = 756-61 | month = | year = | doi = 10.1097/PAI.0000000000000007 | PMID = 25046229 }}</ref>
*Salivary gland tumours <ref name=pmid23604756>{{Cite journal | last1 = Schwartz | first1 = LE. | last2 = Begum | first2 = S. | last3 = Westra | first3 = WH. | last4 = Bishop | first4 = JA. | title = GATA3 immunohistochemical expression in salivary gland neoplasms. | journal = Head Neck Pathol | volume = 7 | issue = 4 | pages = 311-5 | month = Dec | year = 2013 | doi = 10.1007/s12105-013-0442-3 | PMID = 23604756 }}</ref>
*Pheochromocytoma (~70%) vs adrenocortical carcinoma (<10%<ref name=pmid2837449>{{Cite journal | last1 = Perrino | first1 = CM. | last2 = Ho | first2 = A. | last3 = Dall | first3 = CP. | last4 = Zynger | first4 = DL. | title = Utility of GATA3 in the differential diagnosis of pheochromocytoma. | journal = Histopathology | volume = 71 | issue = 3 | pages = 475-479 | month = Sep | year = 2017 | doi = 10.1111/his.13229 | PMID = 28374498 }}</ref>).
*[[Brenner tumour]]s and [[Walthard cell rest]]s.<ref name=pmid25281026>{{Cite journal | last1 = Roma | first1 = AA. | last2 = Masand | first2 = RP. | title = Ovarian Brenner tumors and Walthard nests: a histologic and immunohistochemical study. | journal = Hum Pathol | volume = 45 | issue = 12 | pages = 2417-22 | month = Dec | year = 2014 | doi = 10.1016/j.humpath.2014.08.003 | PMID = 25281026 }}</ref>
*[[Malignant mesothelioma]]s (58%<ref name=pmid24145643/>).
*Most [[T-lymphocytes]].<ref name=pmid19151747>{{cite journal |vauthors=Ho IC, Tai TS, Pai SY |title=GATA3 and the T-cell lineage: essential functions before and after T-helper-2-cell differentiation |journal=Nat. Rev. Immunol. |volume=9 |issue=2 |pages=125–35 |date=February 2009 |pmid=19151747 |pmc=2998182 |doi=10.1038/nri2476 |url=}}</ref> Used as part of a wider panel of IHC to sub-type peripheral T-cell lymphoma, NOS.<ref name=pmid31562134>{{cite journal |vauthors=Amador C, Greiner TC, Heavican TB, Smith LM, Galvis KT, Lone W, Bouska A, D'Amore F, Pedersen MB, Pileri S, Agostinelli C, Feldman AL, Rosenwald A, Ott G, Mottok A, Savage KJ, de Leval L, Gaulard P, Lim ST, Ong CK, Ondrejka SL, Song J, Campo E, Jaffe ES, Staudt LM, Rimsza LM, Vose J, Weisenburger DD, Chan WC, Iqbal J |title=Reproducing the molecular subclassification of peripheral T-cell lymphoma-NOS by immunohistochemistry |journal=Blood |volume=134 |issue=24 |pages=2159–2170 |date=December 2019 |pmid=31562134 |doi=10.1182/blood.2019000779 |url=}}</ref>

===Images===
*[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3444740/figure/F1/ GATA3 nuclear staining - urothelial carcinoma (nih.gov)].<ref name=pmid22982890/>

==Negative==
*[[Prostate carcinoma]].
**Positive in benign prostate glands with radiation atypia.<ref name=pmid28316088>{{cite journal |vauthors=Tian W, Dorn D, Wei S, Sanders RD, Matoso A, Shah RB, Gordetsky J |title=GATA3 expression in benign prostate glands with radiation atypia: a diagnostic pitfall |journal=Histopathology |volume=71 |issue=1 |pages=150–155 |date=July 2017 |pmid=28316088 |doi=10.1111/his.13214 |url=}}</ref>
*[[Squamous cell carcinoma of the lung]].<ref name=pmid22982890/>

==See also==
*[[Immunohistochemistry]].

==References==
{{Reflist|1}}

[[Category:Immunohistochemistry]]

Prostate-specific antigen

2020-07-29T20:12:34Z

Mark: reference for PSA expression in female genital tract

[[Image:Advanced prostate carcinoma - PSA - 2 -- very high mag.jpg|thumb|200px|[[Micrograph]] showing a PSA immunostain marking [[prostate carcinoma]].]]
'''Prostate-specific antigen''', abbreviated '''PSA''', is marker that is quite [[specificity|specific]] for the prostate.

==General==
*Quantity in the serum used to screen for [[prostate cancer]] and follow patients with a history of prostate cancer.
*PSA [[immunostain]] useful for classifying a carcinoma as prostate carcinoma.

===Serum PSA===
*Normal - typically <= 4.0 ng/ml.
**[[Sensitivity]]: 82% (whites), 90% (blacks).<ref name=pmid8998182>{{Cite journal | last1 = Henderson | first1 = RJ. | last2 = Eastham | first2 = JA. | last3 = Culkin | first3 = DJ. | last4 = Kattan | first4 = MW. | last5 = Whatley | first5 = T. | last6 = Mata | first6 = J. | last7 = Venable | first7 = D. | last8 = Sartor | first8 = O. | title = Prostate-specific antigen (PSA) and PSA density: racial differences in men without prostate cancer. | journal = J Natl Cancer Inst | volume = 89 | issue = 2 | pages = 134-8 | month = Jan | year = 1997 | doi = | PMID = 8998182 }}
</ref>
**[[Specificity]]: 52% (whites), 38% (blacks).<ref name=pmid8998182/>
*Increases with age.<ref name=pmid12350489>{{cite journal |author=Ku JH, Ahn JO, Lee CH, ''et al.'' |title=Distribution of serum prostate-specific antigen in healthy Korean men: influence of ethnicity |journal=Urology |volume=60 |issue=3 |pages=475–9 |year=2002 |month=September |pmid=12350489 |doi= |url=}}</ref>

Age-normal:
*40s - 2.5 ng/ml.
*50s - 3.5 ng/ml.
*60s - 4.5 ng/ml.
*70s - 6.5 ng/ml.

Note:
*The units for PSA may also be μg/L; note that 1 μg/L = 1 ng/ml.

====Prostate-specific antigen density====
:Abbreviated ''PSAD''.

Normal is often considered to be: <0.15 ng/ml2.
*Approximately 8% of individuals below the cut-point (0.15 ng/ml) have medium or high-grade cancer.<ref name=pmid12973074>{{Cite journal | last1 = Boulos | first1 = MT. | last2 = Rifkin | first2 = MD. | last3 = Ross | first3 = J. | title = Should prostate-specific antigen or prostate-specific antigen density be used as the determining factor when deciding which prostates should undergo biopsy during prostate ultrasound. | journal = Ultrasound Q | volume = 17 | issue = 3 | pages = 177-80 | month = Sep | year = 2001 | doi = | PMID = 12973074 }}
</ref>
*In another series, 48% of individuals with cancer had a PSAD >0.15 ng/ml2.<ref name=pmid22482342>{{Cite journal | last1 = Aganovic | first1 = D. | last2 = Prcic | first2 = A. | last3 = Kulovac | first3 = B. | last4 = Hadziosmanovic | first4 = O. | title = Influence of the prostate volume, prostate specific antigen density and number of biopsy samples on prostate cancer detection. | journal = Med Arh | volume = 66 | issue = 1 | pages = 41-4 | month = | year = 2012 | doi = | PMID = 22482342 }}
</ref>
*Differences between races have been noted in one study; in those without prostate cancer:<ref name=pmid8998182/>
**0.19 +/- 0.03 ng/ml2 (blacks).
**0.11 +/- 0.01 ng/ml2 (whites).

PSAD is a better predictor than (unadjusted) serum PSA for:
*Gleason score upgrading on [[prostatectomy]].<ref>{{cite journal |author=Sfoungaristos S, Katafigiotis I, Perimenis P |title=The role of PSA density to predict a pathological tumour upgrade between needle biopsy and radical prostatectomy for low risk clinical prostate cancer in the modified Gleason system era |journal=Can Urol Assoc J |volume=7 |issue=11-12 |pages=E722–7 |year=2013 |pmid=24282465 |pmc=3840515 |doi=10.5489/cuaj.374 |url=}}</ref>
*Benign prostate gland versus [[prostate cancer]].<ref name=pmid1371554>{{cite journal |author=Benson MC, Whang IS, Pantuck A, ''et al.'' |title=Prostate specific antigen density: a means of distinguishing benign prostatic hypertrophy and prostate cancer |journal=J. Urol. |volume=147 |issue=3 Pt 2 |pages=815–6 |year=1992 |month=March |pmid=1371554 |doi= |url=}}</ref><ref>{{cite journal |author=Verma A, St Onge J, Dhillon K, Chorneyko A |title=PSA density improves prediction of prostate cancer |journal=Can J Urol |volume=21 |issue=3 |pages=7312–21 |year=2014 |month=June |pmid=24978363 |doi= |url=}}</ref>

=====A forumla for PSAD=====
Benson ''et al.'':<ref name=pmid1371554>{{cite journal |author=Benson MC, Whang IS, Pantuck A, ''et al.'' |title=Prostate specific antigen density: a means of distinguishing benign prostatic hypertrophy and prostate cancer |journal=J. Urol. |volume=147 |issue=3 Pt 2 |pages=815–6 |year=1992 |month=March |pmid=1371554 |doi= |url=}}</ref>
:<math>PASD = \frac{serum PSA}{volume}</math>

Where:
:<math>volume = \frac{\pi}{6} H \times W \times L</math>.<ref>{{Cite journal | last1 = Eri | first1 = LM. | last2 = Thomassen | first2 = H. | last3 = Brennhovd | first3 = B. | last4 = Håheim | first4 = LL. | title = Accuracy and repeatability of prostate volume measurements by transrectal ultrasound. | journal = Prostate Cancer Prostatic Dis | volume = 5 | issue = 4 | pages = 273-8 | month = | year = 2002 | doi = 10.1038/sj.pcan.4500568 | PMID = 12627211 }}
</ref>
:H, W, L are the height, width and length.

An alternate estimation of the volume is:
:<math>volume = \frac{1}{2} D1 \times D2 \times D3</math>.
:D1, D2, D3 are the major axes.

Notes:
*The volume of an ellipsoid is:
::<math>\frac{4}{3}\pi D1 \times D1 \times D3</math>.
*As 1 cm3 is equal to 1 ml, the units of PSAD are (ng/ml)/cm3 or ng/ml2.

===Immunostain===
*Relatively specific for prostate
*May be found in normal pancreatic, salivary gland, Skene's glands and lactating breast tissue.<ref name=pmid21979599>{{cite journal |vauthors=Kelly P, McBride HA, Kennedy K, Connolly LE, McCluggage WG |title=Misplaced Skene's glands: glandular elements in the lower female genital tract that are variably immunoreactive with prostate markers and that encompass vaginal tubulosquamous polyp and cervical ectopic prostatic tissue |journal=Int. J. Gynecol. Pathol. |volume=30 |issue=6 |pages=605–12 |date=November 2011 |pmid=21979599 |doi=10.1097/PGP.0b013e31821713b6 |url=}}</ref>
*In women, positive in up to 30-40% of breast cancers and also in tubulo-squamous polyps of the vagina.

==Microscopic==
Features - PSA immunostain:
*Granular cytoplasmic staining.

Notes:
*May be very weak -- need to look at high power.

<gallery>
Image: Advanced prostate carcinoma - PSA -- high mag.jpg | Adv Pca - weak PSA - high mag. (WC)
Image: Advanced prostate carcinoma - PSA -- very high mag.jpg | Adv Pca - weak PSA - very high mag. (WC)
Image: Advanced prostate carcinoma - PSA - 2 -- high mag.jpg | Adv Pca - PSA - high mag. (WC)
Image: Advanced prostate carcinoma - PSA - 2 -- very high mag.jpg | Adv Pca - PSA - very high mag. (WC)
</gallery>

==See also==
*[[Prostate cancer]].
*[[Prostatic-specific acid phosphatase]].

==References==
{{Reflist|1}}

[[Category:Clinical]]
[[Category:Genitourinary pathology]]

POEMS syndrome

2020-07-26T14:14:09Z

Mark: list formatting

'''POEMS syndrome''' is a constellation of findings, best thought of as a paraneoplastic syndrome due to clonal plasma cells:<ref name=pmid18477219>{{cite journal |author=Yuri T, Yamazaki F, Takasu K, Shikata N, Tsubura A |title=Glomeruloid hemangioma |journal=Pathol. Int. |volume=58 |issue=6 |pages=390–5 |year=2008 |month=June |pmid=18477219 |doi=10.1111/j.1440-1827.2008.02241.x |url=}}</ref>
*Polyneuropathy.
*Organomegaly.
*Endocrinopathy.
*M-protein.
*Skin changes.

Diagnostic criteria requires both mandatory criteria and at least one each from major and minor criteria:<ref name=pmid31012139>{{cite journal |vauthors=Dispenzieri A |title=POEMS Syndrome: 2019 Update on diagnosis, risk-stratification, and management |journal=Am. J. Hematol. |volume=94 |issue=7 |pages=812–827 |date=July 2019 |pmid=31012139 |doi=10.1002/ajh.25495 |url=}}</ref>
''Mandatory:''
;1. Polyneuropathy (typically demyelinating)
;2. Monoclonal plasma cell proliferation (usually lambda)
''Major:''
;3. [[Castleman disease]]
;4. Sclerotic bone lesions
;5. Vascular endothelial growth factor elevation
''Minor:''
;6. Organomegaly (splenomegaly, hepatomegaly or lymphadenopathy)
;7. Extravascular volume overload
;8. Endocrinopathy
;9. Sking changes
;10. Papilloedema
;11. Thrombocytosis/polycythemia

POEMS syndrome is unusual in causing osteosclerotic bone deposits, so-called osteosclerotic myeloma, in contrast to the lytic lesions seen in more conventional [[plasma cell myeloma]].

==Pathology==
*The [[pathologist]] may come across an undiagnosed case in the form of a ''[[glomeruloid hemangioma]]''; however, glomeruloid [[hemangioma]]s are not always associated with the POEMS syndrome.<ref name=pmid19077091>{{cite journal |author=González-Guerra E, Haro MR, Fariña MC, Martín L, Manzarbeitia L, Requena L |title=Glomeruloid haemangioma is not always associated with POEMS syndrome |journal=Clin. Exp. Dermatol. |volume=34 |issue=7 |pages=800–3 |year=2009 |month=October |pmid=19077091 |doi=10.1111/j.1365-2230.2008.02997.x |url=}}</ref>

==See also==
*[[POEM]] - a treatment for [[achalasia]].

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

[[Category:Syndromes]]

POEMS syndrome

2020-07-26T14:13:07Z

Mark: diagnostic criteria

'''POEMS syndrome''' is a constellation of findings, best thought of as a paraneoplastic syndrome due to clonal plasma cells:<ref name=pmid18477219>{{cite journal |author=Yuri T, Yamazaki F, Takasu K, Shikata N, Tsubura A |title=Glomeruloid hemangioma |journal=Pathol. Int. |volume=58 |issue=6 |pages=390–5 |year=2008 |month=June |pmid=18477219 |doi=10.1111/j.1440-1827.2008.02241.x |url=}}</ref>
*Polyneuropathy.
*Organomegaly.
*Endocrinopathy.
*M-protein.
*Skin changes.

Diagnostic criteria requires both mandatory criteria and at least one each from major and minor criteria:<ref name=pmid31012139>{{cite journal |vauthors=Dispenzieri A |title=POEMS Syndrome: 2019 Update on diagnosis, risk-stratification, and management |journal=Am. J. Hematol. |volume=94 |issue=7 |pages=812–827 |date=July 2019 |pmid=31012139 |doi=10.1002/ajh.25495 |url=}}</ref>
Mandatory:
1. Polyneuropathy (typically demyelinating)
2. Monoclonal plasma cell proliferation (usually lambda)
Major:
3. [[Castleman disease]]
4. Sclerotic bone lesions
5. Vascular endothelial growth factor elevation
Minor:
6. Organomegaly (splenomegaly, hepatomegaly or lymphadenopathy)
7. Extravascular volume overload
8. Endocrinopathy
9. Sking changes
10. Papilloedema
11. Thrombocytosis/polycythemia

POEMS syndrome is unusual in causing osteosclerotic bone deposits, so-called osteosclerotic myeloma, in contrast to the lytic lesions seen in more conventional [[plasma cell myeloma]].

==Pathology==
*The [[pathologist]] may come across an undiagnosed case in the form of a ''[[glomeruloid hemangioma]]''; however, glomeruloid [[hemangioma]]s are not always associated with the POEMS syndrome.<ref name=pmid19077091>{{cite journal |author=González-Guerra E, Haro MR, Fariña MC, Martín L, Manzarbeitia L, Requena L |title=Glomeruloid haemangioma is not always associated with POEMS syndrome |journal=Clin. Exp. Dermatol. |volume=34 |issue=7 |pages=800–3 |year=2009 |month=October |pmid=19077091 |doi=10.1111/j.1365-2230.2008.02997.x |url=}}</ref>

==See also==
*[[POEM]] - a treatment for [[achalasia]].

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

[[Category:Syndromes]]

POEMS syndrome

2020-07-26T14:04:01Z

Mark: osteosclerotic lesions

'''POEMS syndrome''' is a constellation of findings:<ref name=pmid18477219>{{cite journal |author=Yuri T, Yamazaki F, Takasu K, Shikata N, Tsubura A |title=Glomeruloid hemangioma |journal=Pathol. Int. |volume=58 |issue=6 |pages=390–5 |year=2008 |month=June |pmid=18477219 |doi=10.1111/j.1440-1827.2008.02241.x |url=}}</ref>
*Polyneuropathy.
*Organomegaly.
*Endocrinopathy.
*M-protein.
*Skin changes.

POEMS syndrome is unusual in causing osteosclerotic bone deposits, so-called osteosclerotic myeloma, in contrast to the lytic lesions seen in more conventional [[plasma cell myeloma]].

==Pathology==
*The [[pathologist]] may come across an undiagnosed case in the form of a ''[[glomeruloid hemangioma]]''; however, glomeruloid [[hemangioma]]s are not always associated with the POEMS syndrome.<ref name=pmid19077091>{{cite journal |author=González-Guerra E, Haro MR, Fariña MC, Martín L, Manzarbeitia L, Requena L |title=Glomeruloid haemangioma is not always associated with POEMS syndrome |journal=Clin. Exp. Dermatol. |volume=34 |issue=7 |pages=800–3 |year=2009 |month=October |pmid=19077091 |doi=10.1111/j.1365-2230.2008.02997.x |url=}}</ref>

==See also==
*[[POEM]] - a treatment for [[achalasia]].

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

[[Category:Syndromes]]

POEMS

2020-07-26T14:02:36Z

Mark: redirect

#REDIRECT[[POEMS syndrome]]

Castleman disease

2020-07-26T14:02:02Z

Mark: some references

{{ Infobox diagnosis
| Name = {{PAGENAME}}
| Image = Castleman_disease_-_high_mag.jpg
| Width =
| Caption = Castleman disease (hyaline-vascular variant). [[H&E stain]].
| Synonyms =
| Micro =
| Subtypes = hyaline-vascular variant (HVV), plasma cell variant (PCV)
| LMDDx = HVV: [[mantle cell lymphoma]]
| Stains =
| IHC = HVV: cyclin D1 -ve, other stains to exclude lymphoma; PCV: HHV-8 +ve
| EM =
| Molecular =
| IF =
| Gross =
| Grossing =
| Site = [[lymph node]] - see ''[[lymph node pathology]]''
| Assdx =
| Syndromes =
| Clinicalhx =
| Signs =
| Symptoms =
| Prevalence = rare
| Bloodwork =
| Rads =
| Endoscopy =
| Prognosis =
| Other =
| ClinDDx =
| Tx =
}}
'''Castleman disease''', abbreviated '''CD''', is a rare [[Lymph node pathology|pathology of the lymph node]].

It is also known as '''angiofollicular lymph node hyperplasia''' and '''giant lymph node hyperplasia'''.<ref>URL: [http://www.mayoclinic.com/health/castleman-disease/DS01000 http://www.mayoclinic.com/health/castleman-disease/DS01000]. Accessed on: 17 June 2010.</ref>

==General==
*Benign.
*Hyaline vascular variant (classic Castleman disease) - a pathology of the follicular dendritic cells.<ref>{{Cite journal | last1 = Cokelaere | first1 = K. | last2 = Debiec-Rychter | first2 = M. | last3 = De Wolf-Peeters | first3 = C. | last4 = Hagemeijer | first4 = A. | last5 = Sciot | first5 = R. | title = Hyaline vascular Castleman's disease with HMGIC rearrangement in follicular dendritic cells: molecular evidence of mesenchymal tumorigenesis. | journal = Am J Surg Pathol | volume = 26 | issue = 5 | pages = 662-9 | month = May | year = 2002 | doi = | PMID = 11979097 }}</ref>

===Classification===
By site of involvement:
*Unicentric (one lymph node or a cluster of nodes at one site)
**~75% hyaline vascular variant
**~25% Plasma cell variant
*Multicentric often associated with splenomegaly (75%) and hepatomegaly (50%)
**>90% plasma cell variant
**<10% hyaline vascular variant

CD is grouped by histologic appearance:<ref name=Ref_ILNP228>{{Ref ILNP|228}}</ref>
#Hyaline vascular (HV) variant (described by Castleman).
#*Usually unicentric.
#*Typically mediastinal or axial.
#*More common than plasma cell variant; represents 80-90% of CD cases.
#*May be associated with [[follicular dendritic cell neoplasia]].<ref name=Ref_WMSP_596>{{Ref WMSP|596}}</ref>
#Plasma cell (PC) variant.
#*Usually multicentric, may be unicentric.
#*Abundant plasma cells.
#*50-60% associated with [[HHV-8]] infection (the same virus implicated in ''Kaposi's sarcoma''). The virus produces an IL-6 analogue which drives many of the systemic features.

Some divide the multicentric pattern into
#[[POEMS]]-associated CD
#HHV8+ CD
#*HIV+
#*HIV-
#HHV8- CD, further sub-divided into
#*TAFRO syndrome associated
#Others

Notes:
*The subclassification of CD is in some flux. Some authors advocate splitting-out ''HHV-8'' and ''multicentric'' as separate subtypes.<ref name=pmid19546611>{{Cite journal | last1 = Cronin | first1 = DM. | last2 = Warnke | first2 = RA. | title = Castleman disease: an update on classification and the spectrum of associated lesions. | journal = Adv Anat Pathol | volume = 16 | issue = 4 | pages = 236-46 | month = Jul | year = 2009 | doi = 10.1097/PAP.0b013e3181a9d4d3 | PMID = 19546611 }}</ref>

==Microscopic==
===Hyaline-vascular variant===
Features:<ref>URL: [http://www.ispub.com/journal/the_internet_journal_of_otorhinolaryngology/volume_9_number_2_11/article/a_rare_case_of_castleman_s_disease_presenting_as_cervical_neck_mass.html http://www.ispub.com/journal/the_internet_journal_of_otorhinolaryngology/volume_9_number_2_11/article/a_rare_case_of_castleman_s_disease_presenting_as_cervical_neck_mass.html]. Accessed on: 15 June 2010.</ref><ref name=Ref_ILNP236>{{Ref ILNP|236}}</ref><ref name=pmid28100459>{{cite journal |vauthors=Yu L, Tu M, Cortes J, Xu-Monette ZY, Miranda RN, Zhang J, Orlowski RZ, Neelapu S, Boddu PC, Akosile MA, Uldrick TS, Yarchoan R, Medeiros LJ, Li Y, Fajgenbaum DC, Young KH |title=Clinical and pathological characteristics of HIV- and HHV-8-negative Castleman disease |journal=Blood |volume=129 |issue=12 |pages=1658–1668 |date=March 2017 |pmid=28100459 |pmc=5364343 |doi=10.1182/blood-2016-11-748855 |url=}}</ref>

*Pale concentric (expanded) mantle zone lymphocytes - '''key feature'''.
**"Regressed follicles" - germinal center (pale area) is small.
*"Lollipops":
**Germinal centers fed by prominent (radially penetrating sclerotic) vessels; lollipop-like appearance.
*Two germinal centers in one follicle, so called "twinning".
*Hyaline material (pink acellular stuff on H&E) in germinal center.
*Sinuses effaced (lost).
*Mitoses absent.

====Images====
<gallery>
Image:Castleman_disease_-_high_mag.jpg | CD HVV - "lollipop" sign - high mag. (WC)
Image:Castleman_disease_-_intermed_mag.jpg | CD HVV - showing expanded mantle zone - intermed. mag. (WC)
</gallery>
www:
*[http://path.upmc.edu/cases/case115.html CD HVV - case 1 - several images (upmc.edu)].
*[http://path.upmc.edu/cases/case301.html CD HVV - case 2 - several images (upmc.edu)].

===Plasma cell variant===
Features:<ref name=Ref_ILNP236>{{Ref ILNP|236}}</ref>
*Interfollicular sheets of plasma cells - '''key feature'''.
*Active germinal centers - mitoses present.
*Sinus preserved.
*In HHV8-negative cases, several other conditions can give a Castleman-like appearance, listed comprehensively in the consensus criteria for HHV8-negative CD:
<ref name=pmid28087540>{{cite journal |vauthors=Fajgenbaum DC, Uldrick TS, Bagg A, Frank D, Wu D, Srkalovic G, Simpson D, Liu AY, Menke D, Chandrakasan S, Lechowicz MJ, Wong RS, Pierson S, Paessler M, Rossi JF, Ide M, Ruth J, Croglio M, Suarez A, Krymskaya V, Chadburn A, Colleoni G, Nasta S, Jayanthan R, Nabel CS, Casper C, Dispenzieri A, Fosså A, Kelleher D, Kurzrock R, Voorhees P, Dogan A, Yoshizaki K, van Rhee F, Oksenhendler E, Jaffe ES, Elenitoba-Johnson KS, Lim MS |title=International, evidence-based consensus diagnostic criteria for HHV-8-negative/idiopathic multicentric Castleman disease |journal=Blood |volume=129 |issue=12 |pages=1646–1657 |date=March 2017 |pmid=28087540 |pmc=5364342 |doi=10.1182/blood-2016-10-746933 |url=}}</ref>
**Autoimmune diseases
**Infections
**Malignancies

==IHC==
Hyaline-vascular variant:
*Stains to exclude [[mantle cell lymphoma]]:
**Cyclin D1.

Plasma cell variant:
*HHV-8 +ve.

==See also==
*[[Lymph node pathology]].

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

[[Category:Diagnosis]]
[[Category:Lymph node pathology]]

Paired box gene 8

2020-07-05T11:32:46Z

Mark: PAX8 polyclonal antibodies can cross react with PAX5 = false positive

{{ Infobox immunostain
| Name = {{PAGENAME}}
| Image = Poorly differentiated carcinoma -- PAX8 - intermed mag.jpg
| Width =
| Caption = PAX8 staining in a poorly differentiated [[carcinoma]].
| Abbrev = PAX8
| Synonyms =
| Similar =
| Clones =
| Use = RCC versus other, gynecologic tract malignancy versus other
| Subspecial = [[gynecologic pathology]], [[genitourinary pathology]]
| Pattern = nuclear stain
| Positive = [[renal cell carcinoma]]s, [[renal oncocytoma]], thyroid tumours, [[serous carcinoma]], [[endometrial carcinoma]]s
| Negative =
| Other =
}}
'''Paired box gene 8''', commonly known by the abbreviation '''PAX8''', is a commonly used [[immunostain]] in [[gynecologic pathology]] and [[genitourinary pathology]].

==Tumours with positive staining==
*Thyroid tumours ~ 90%.<ref name=pmid21552115>{{Cite journal | last1 = Laury | first1 = AR. | last2 = Perets | first2 = R. | last3 = Piao | first3 = H. | last4 = Krane | first4 = JF. | last5 = Barletta | first5 = JA. | last6 = French | first6 = C. | last7 = Chirieac | first7 = LR. | last8 = Lis | first8 = R. | last9 = Loda | first9 = M. | title = A comprehensive analysis of PAX8 expression in human epithelial tumors. | journal = Am J Surg Pathol | volume = 35 | issue = 6 | pages = 816-26 | month = Jun | year = 2011 | doi = 10.1097/PAS.0b013e318216c112 | PMID = 21552115 }}</ref>
*[[Renal cell carcinoma]]s ~ 90%.<ref name=pmid21552115/>
*[[Renal oncocytoma]]s ~ 80%.<ref name=pmid21552115/>
*High-grade [[ovarian serous carcinoma]]s ~ 99%.<ref name=pmid21552115/>
*Nonserous epithelial [[ovarian tumours|ovarian neoplasms]] ~ 70%.<ref name=pmid21552115/>
*[[Endometrial carcinoma]]s ~ 98%.<ref name=pmid21552115/>
*[[Pancreatic neuroendocrine tumour]] ~ 74%.<ref name=pmid20890270>{{Cite journal | last1 = Sangoi | first1 = AR. | last2 = Ohgami | first2 = RS. | last3 = Pai | first3 = RK. | last4 = Beck | first4 = AH. | last5 = McKenney | first5 = JK. | last6 = Pai | first6 = RK. | title = PAX8 expression reliably distinguishes pancreatic well-differentiated neuroendocrine tumors from ileal and pulmonary well-differentiated neuroendocrine tumors and pancreatic acinar cell carcinoma. | journal = Mod Pathol | volume = 24 | issue = 3 | pages = 412-24 | month = Mar | year = 2011 | doi = 10.1038/modpathol.2010.176 | PMID = 20890270 }}</ref>
**Can help differentiate from lung NETs.
*Epithelial component of thymic tumors 77-100% depending on sub-type<ref name=pmid21552115/><ref name=pmid21836478>{{cite journal |vauthors=Weissferdt A, Moran CA |title=Pax8 expression in thymic epithelial neoplasms: an immunohistochemical analysis |journal=Am. J. Surg. Pathol. |volume=35 |issue=9 |pages=1305–10 |date=September 2011 |pmid=21836478 |doi=10.1097/PAS.0b013e3182260735 |url=}}</ref>

==Negative staining==
[[Image:Lymphoma - lung - PAX8 -- intermed mag.jpg|thumb|right|300px|Negative PAX8 staining in a lymphoma.]]
*[[Urothelial carcinoma]] - can be positive (3 positive/18 bladder tumours<ref name=pmid21552115/>).
*[[Lymphoma]] (beware false positive staining due to polyclonal PAX8 antibodies cross-reacting with PAX5)<ref name=pmid22037256>{{cite journal |vauthors=Moretti L, Medeiros LJ, Kunkalla K, Williams MD, Singh RR, Vega F |title=N-terminal PAX8 polyclonal antibody shows cross-reactivity with N-terminal region of PAX5 and is responsible for reports of PAX8 positivity in malignant lymphomas |journal=Mod. Pathol. |volume=25 |issue=2 |pages=231–6 |date=February 2012 |pmid=22037256 |doi=10.1038/modpathol.2011.162 |url=}}</ref>
*[[Malignant melanoma]].<ref name=pmid21285870>{{Cite journal | last1 = Tacha | first1 = D. | last2 = Zhou | first2 = D. | last3 = Cheng | first3 = L. | title = Expression of PAX8 in normal and neoplastic tissues: a comprehensive immunohistochemical study. | journal = Appl Immunohistochem Mol Morphol | volume = 19 | issue = 4 | pages = 293-9 | month = Jul | year = 2011 | doi = 10.1097/PAI.0b013e3182025f66 | PMID = 21285870 }}</ref>

==See also==
*[[Immunostains]].

==References==
{{Reflist|1}}

[[Category:Immunohistochemistry]]

Paired box gene 8

2020-07-05T11:28:23Z

Mark: fixed duplicated reference

{{ Infobox immunostain
| Name = {{PAGENAME}}
| Image = Poorly differentiated carcinoma -- PAX8 - intermed mag.jpg
| Width =
| Caption = PAX8 staining in a poorly differentiated [[carcinoma]].
| Abbrev = PAX8
| Synonyms =
| Similar =
| Clones =
| Use = RCC versus other, gynecologic tract malignancy versus other
| Subspecial = [[gynecologic pathology]], [[genitourinary pathology]]
| Pattern = nuclear stain
| Positive = [[renal cell carcinoma]]s, [[renal oncocytoma]], thyroid tumours, [[serous carcinoma]], [[endometrial carcinoma]]s
| Negative =
| Other =
}}
'''Paired box gene 8''', commonly known by the abbreviation '''PAX8''', is a commonly used [[immunostain]] in [[gynecologic pathology]] and [[genitourinary pathology]].

==Tumours with positive staining==
*Thyroid tumours ~ 90%.<ref name=pmid21552115>{{Cite journal | last1 = Laury | first1 = AR. | last2 = Perets | first2 = R. | last3 = Piao | first3 = H. | last4 = Krane | first4 = JF. | last5 = Barletta | first5 = JA. | last6 = French | first6 = C. | last7 = Chirieac | first7 = LR. | last8 = Lis | first8 = R. | last9 = Loda | first9 = M. | title = A comprehensive analysis of PAX8 expression in human epithelial tumors. | journal = Am J Surg Pathol | volume = 35 | issue = 6 | pages = 816-26 | month = Jun | year = 2011 | doi = 10.1097/PAS.0b013e318216c112 | PMID = 21552115 }}</ref>
*[[Renal cell carcinoma]]s ~ 90%.<ref name=pmid21552115/>
*[[Renal oncocytoma]]s ~ 80%.<ref name=pmid21552115/>
*High-grade [[ovarian serous carcinoma]]s ~ 99%.<ref name=pmid21552115/>
*Nonserous epithelial [[ovarian tumours|ovarian neoplasms]] ~ 70%.<ref name=pmid21552115/>
*[[Endometrial carcinoma]]s ~ 98%.<ref name=pmid21552115/>
*[[Pancreatic neuroendocrine tumour]] ~ 74%.<ref name=pmid20890270>{{Cite journal | last1 = Sangoi | first1 = AR. | last2 = Ohgami | first2 = RS. | last3 = Pai | first3 = RK. | last4 = Beck | first4 = AH. | last5 = McKenney | first5 = JK. | last6 = Pai | first6 = RK. | title = PAX8 expression reliably distinguishes pancreatic well-differentiated neuroendocrine tumors from ileal and pulmonary well-differentiated neuroendocrine tumors and pancreatic acinar cell carcinoma. | journal = Mod Pathol | volume = 24 | issue = 3 | pages = 412-24 | month = Mar | year = 2011 | doi = 10.1038/modpathol.2010.176 | PMID = 20890270 }}</ref>
**Can help differentiate from lung NETs.
*Epithelial component of thymic tumors 77-100% depending on sub-type<ref name=pmid21552115/><ref name=pmid21836478>{{cite journal |vauthors=Weissferdt A, Moran CA |title=Pax8 expression in thymic epithelial neoplasms: an immunohistochemical analysis |journal=Am. J. Surg. Pathol. |volume=35 |issue=9 |pages=1305–10 |date=September 2011 |pmid=21836478 |doi=10.1097/PAS.0b013e3182260735 |url=}}</ref>

==Negative staining==
[[Image:Lymphoma - lung - PAX8 -- intermed mag.jpg|thumb|right|300px|Negative PAX8 staining in a lymphoma.]]
*[[Urothelial carcinoma]] - can be positive (3 positive/18 bladder tumours<ref name=pmid21552115/>).
*[[Lymphoma]].
*[[Malignant melanoma]].<ref name=pmid21285870>{{Cite journal | last1 = Tacha | first1 = D. | last2 = Zhou | first2 = D. | last3 = Cheng | first3 = L. | title = Expression of PAX8 in normal and neoplastic tissues: a comprehensive immunohistochemical study. | journal = Appl Immunohistochem Mol Morphol | volume = 19 | issue = 4 | pages = 293-9 | month = Jul | year = 2011 | doi = 10.1097/PAI.0b013e3182025f66 | PMID = 21285870 }}</ref>

==See also==
*[[Immunostains]].

==References==
{{Reflist|1}}

[[Category:Immunohistochemistry]]

Paired box gene 8

2020-07-05T11:27:36Z

Mark: positive in epithelial component of thymic tumours

{{ Infobox immunostain
| Name = {{PAGENAME}}
| Image = Poorly differentiated carcinoma -- PAX8 - intermed mag.jpg
| Width =
| Caption = PAX8 staining in a poorly differentiated [[carcinoma]].
| Abbrev = PAX8
| Synonyms =
| Similar =
| Clones =
| Use = RCC versus other, gynecologic tract malignancy versus other
| Subspecial = [[gynecologic pathology]], [[genitourinary pathology]]
| Pattern = nuclear stain
| Positive = [[renal cell carcinoma]]s, [[renal oncocytoma]], thyroid tumours, [[serous carcinoma]], [[endometrial carcinoma]]s
| Negative =
| Other =
}}
'''Paired box gene 8''', commonly known by the abbreviation '''PAX8''', is a commonly used [[immunostain]] in [[gynecologic pathology]] and [[genitourinary pathology]].

==Tumours with positive staining==
*Thyroid tumours ~ 90%.<ref name=pmid21552115>{{Cite journal | last1 = Laury | first1 = AR. | last2 = Perets | first2 = R. | last3 = Piao | first3 = H. | last4 = Krane | first4 = JF. | last5 = Barletta | first5 = JA. | last6 = French | first6 = C. | last7 = Chirieac | first7 = LR. | last8 = Lis | first8 = R. | last9 = Loda | first9 = M. | title = A comprehensive analysis of PAX8 expression in human epithelial tumors. | journal = Am J Surg Pathol | volume = 35 | issue = 6 | pages = 816-26 | month = Jun | year = 2011 | doi = 10.1097/PAS.0b013e318216c112 | PMID = 21552115 }}</ref>
*[[Renal cell carcinoma]]s ~ 90%.<ref name=pmid21552115/>
*[[Renal oncocytoma]]s ~ 80%.<ref name=pmid21552115/>
*High-grade [[ovarian serous carcinoma]]s ~ 99%.<ref name=pmid21552115/>
*Nonserous epithelial [[ovarian tumours|ovarian neoplasms]] ~ 70%.<ref name=pmid21552115/>
*[[Endometrial carcinoma]]s ~ 98%.<ref name=pmid21552115/>
*[[Pancreatic neuroendocrine tumour]] ~ 74%.<ref name=pmid20890270>{{Cite journal | last1 = Sangoi | first1 = AR. | last2 = Ohgami | first2 = RS. | last3 = Pai | first3 = RK. | last4 = Beck | first4 = AH. | last5 = McKenney | first5 = JK. | last6 = Pai | first6 = RK. | title = PAX8 expression reliably distinguishes pancreatic well-differentiated neuroendocrine tumors from ileal and pulmonary well-differentiated neuroendocrine tumors and pancreatic acinar cell carcinoma. | journal = Mod Pathol | volume = 24 | issue = 3 | pages = 412-24 | month = Mar | year = 2011 | doi = 10.1038/modpathol.2010.176 | PMID = 20890270 }}</ref>
**Can help differentiate from lung NETs.
*Epithelial component of thymic tumors 77-100% depending on sub-type<ref name=pmid21552115>{{cite journal |vauthors=Laury AR, Perets R, Piao H, Krane JF, Barletta JA, French C, Chirieac LR, Lis R, Loda M, Hornick JL, Drapkin R, Hirsch MS |title=A comprehensive analysis of PAX8 expression in human epithelial tumors |journal=Am. J. Surg. Pathol. |volume=35 |issue=6 |pages=816–26 |date=June 2011 |pmid=21552115 |doi=10.1097/PAS.0b013e318216c112 |url=}}</ref><ref name=pmid21836478>{{cite journal |vauthors=Weissferdt A, Moran CA |title=Pax8 expression in thymic epithelial neoplasms: an immunohistochemical analysis |journal=Am. J. Surg. Pathol. |volume=35 |issue=9 |pages=1305–10 |date=September 2011 |pmid=21836478 |doi=10.1097/PAS.0b013e3182260735 |url=}}</ref>

==Negative staining==
[[Image:Lymphoma - lung - PAX8 -- intermed mag.jpg|thumb|right|300px|Negative PAX8 staining in a lymphoma.]]
*[[Urothelial carcinoma]] - can be positive (3 positive/18 bladder tumours<ref name=pmid21552115/>).
*[[Lymphoma]].
*[[Malignant melanoma]].<ref name=pmid21285870>{{Cite journal | last1 = Tacha | first1 = D. | last2 = Zhou | first2 = D. | last3 = Cheng | first3 = L. | title = Expression of PAX8 in normal and neoplastic tissues: a comprehensive immunohistochemical study. | journal = Appl Immunohistochem Mol Morphol | volume = 19 | issue = 4 | pages = 293-9 | month = Jul | year = 2011 | doi = 10.1097/PAI.0b013e3182025f66 | PMID = 21285870 }}</ref>

==See also==
*[[Immunostains]].

==References==
{{Reflist|1}}

[[Category:Immunohistochemistry]]

TFE3

2020-02-06T21:27:36Z

Mark: other tumours

{{ Infobox immunostain
| Name = {{PAGENAME}}
| Image =
| Width =
| Caption =
| Abbrev =
| Synonyms =
| Similar =
| Clones =
| Use = screen to detect TFE3 rearrangements
| Subspecial = [[urologic pathology]], [[soft tissue pathology]]
| Pattern = nuclear stain
| Positive = [[Xp11.2 translocation carcinoma]], [[alveolar soft part sarcoma]]
| Negative = normal tissues
| Other =
}}
'''TFE3''' is an [[immunostain]] used in [[uropathology]] and [[soft tissue pathology]].

==Negative==
*Normal tissue.<ref>URL: [http://www.ihcworld.com/_newsletter/2003/focus_jul_2003.pdf http://www.ihcworld.com/_newsletter/2003/focus_jul_2003.pdf]. Accessed on: September 11, 2017.</ref>
**Staining in normal tissue described as "extremely rare" - negative in adrenal gland, breast, colon, gallbaldder, lymph node, liver, prostate and skin.<ref name=pmid12766578>{{Cite journal | last1 = Argani | first1 = P. | last2 = Lal | first2 = P. | last3 = Hutchinson | first3 = B. | last4 = Lui | first4 = MY. | last5 = Reuter | first5 = VE. | last6 = Ladanyi | first6 = M. | title = Aberrant nuclear immunoreactivity for TFE3 in neoplasms with TFE3 gene fusions: a sensitive and specific immunohistochemical assay. | journal = Am J Surg Pathol | volume = 27 | issue = 6 | pages = 750-61 | month = Jun | year = 2003 | doi = | PMID = 12766578 }}</ref>

==Positive==
*[[Xp11.2 translocation carcinoma]].
*[[Alveolar soft part sarcoma]].
* YAP-TFE3 translocated [[epithelioid hemangioendothelioma]]
*[[Epithelioid angiomyolipoma]]
*[[Granular cell tumor]]<ref>{{cite journal |vauthors=Chamberlain BK, McClain CM, Gonzalez RS, Coffin CM, Cates JM |title=Alveolar soft part sarcoma and granular cell tumor: an immunohistochemical comparison study |journal=Hum. Pathol. |volume=45 |issue=5 |pages=1039–44 |date=May 2014 |pmid=24746209 |doi=10.1016/j.humpath.2013.12.021 |url=}}</ref>

==See also==
*[[Chromosomal translocations]].

==References==
{{Reflist|1}}

[[Category:Immunohistochemistry]]

Mesenchymal chondrosarcoma

2020-01-11T22:12:26Z

Mark: /* Molecular */

'''Mesenchymal chondrosarcoma''' is a rare type of [[chondrosarcoma]] that is found in the [[soft tissue lesions|soft tissue]].

==General==
*Rare variant of [[chondrosarcoma]].
*2–10% of primary chondrosarcomas.
*Adolescents and young adults.
*Female predilection.
*Most commonly intraosseous but can occur in extraskeletal sites especially the central nervous system (from the meninges).
*The ''mesenchymal'' in the name refers to the ability to arise in soft tissues.<ref name=pmid14161087>{{cite journal |author=Dowling EA |title=Mesenchymal chondrosarcoma |journal=J Bone Joint Surg Am |volume=46 |issue= |pages=747–54 |year=1964 |month=June |pmid=14161087 |doi= |url=http://www.ejbjs.org/cgi/reprint/46/4/747.pdf}}</ref>
*Conceptualized as originating from a pleuripotential mesenchymal cell with foci recapitulating enchondral ossification.
*The small cells appear to be an undifferentiated cartilage stem cell which “differentiate” into benign cartilage.<ref name=pmid20138330>{{Cite journal | last1 = Fanburg-Smith | first1 = JC. | last2 = Auerbach | first2 = A. | last3 = Marwaha | first3 = JS. | last4 = Wang | first4 = Z. | last5 = Rushing | first5 = EJ. | title = Reappraisal of mesenchymal chondrosarcoma: novel morphologic observations of the hyaline cartilage and endochondral ossification and beta-catenin, Sox9, and osteocalcin immunostaining of 22 cases. | journal = Hum Pathol | volume = 41 | issue = 5 | pages = 653-62 | month = May | year = 2010 | doi = 10.1016/j.humpath.2009.11.006 | PMID = 20138330 }}</ref>

==Gross==
Pink and fleshy with foci of calcification.

==Microscopic==
Features:
*Malignant tumour with a characteristic biphasic pattern.
**Cellular poorly differentiated [[small round blue cell tumours|small round blue cells]].
**Islands of well-differentiated hyaline [[cartilage]].
***Progressive maturation of cartilage towards the center.
***Central calcification or [[bone]] formation.
**Can have a [[staghorn vessels|hemangiopericytomatous vascular pattern]].

Notes:
*May be described as ''white clouds in a dark blue sky''.

===DDX===
*[[Hemangiopericytoma]] - no cartilage.
*[[Lymphoma]] - Sox9 negative, CD45 positive.
*Metaplastic [[glioblastoma]] - usually older adults - GFAP positive.
*[[Chondrosarcoma]] (NOS) - usually older adults - hyaline cartilage is malignant.
*[[Small cell osteosarcoma]] - Sox10 negative, no cartilage.
*[[Ewing sarcoma]] - both are CD99 positive but ES is Sox9 negative, no cartilage.
*Monophasic [[synovial sarcoma]] - also can have the hemangiopericytomatous vasculature.

Note:
*Depends a bit on where the tumour is located and how much cartilage is readily visible.

===Images===
<gallery>
Image:Bone Chondrosarcoma Mesenchymal MP5 PA.JPG|Islands of cartilage in a background of small blue cells.(SKB)
Image:Bone Chondrosarcoma Mesenchymal MP PA.JPG|Islands of cartilage in a background of small blue cells.(SKB)
Image:Bone Chondrosarcoma Mesenchymal LP2 PA.JPG|Islands of cartilage in a background of small blue cells.(SKB)
Image:Bone Chondrosarcoma Mesenchymal HP5 PA.JPG|Islands of cartilage in a background of small blue cells.(SKB)
Image:Bone Chondrosarcoma Mesenchymal MP2 PA.JPG|Islands of cartilage in a background of small blue cells.(SKB)
Image:Bone Chondrosarcoma Mesenchymal MP7.JPG|Islands of cartilage in a background of small blue cells.(SKB)
Image:Bone Chondrosarcoma Mesenchymal HP3 PA.JPG|Small blue cells predominate.(SKB)
</gallery>
www:
*[http://moon.ouhsc.edu/kfung/jty1/opaq/PathQuiz/S0A001-PQ01-M.htm Mesenchymal chondrosarcoma (ouhsc.edu)].
*Pathology Outlines - Hemangiopericytomatous example [http://pathologyoutlines.com/wick/chondrosarcoma%20mesenchymal%20type%20micro0007.jpg]
*Sarcoma Images - [http://www.sarcomaimages.com/index.php?v=Mesenchymal-Chondrosarcoma]
*CNS Atlas - [http://www.cnsatlas.com/medicalatlas/images/370/800_poIB6FYZQ73wh.jpg]
*CNS Atlas - [http://www.cnsatlas.com/medicalatlas/images/370/800_9oJtTQXXxaEB3.jpg]
*CNS Atlas - [http://www.cnsatlas.com/medicalatlas/images/370/800_8h2C7upeOj3EB.jpg]

==IHC==
*SOX9 (positive in small cells and chondrocytes).<ref name=pmid21914343>{{Cite journal | last1 = Pang | first1 = ZG. | last2 = He | first2 = XZ. | last3 = Wu | first3 = LY. | last4 = Wei | first4 = W. | last5 = Liu | first5 = XY. | last6 = Liao | first6 = DY. | last7 = Li | first7 = FY. | last8 = Zhang | first8 = XL. | title = [Clinicopathologic and immunohistochemical study of 23 cases of mesenchymal chondrosarcoma]. | journal = Zhonghua Bing Li Xue Za Zhi | volume = 40 | issue = 6 | pages = 368-72 | month = Jun | year = 2011 | doi = | PMID = 21914343 }}</ref>
*S100 (positive in chondrocytes not in small cells).
*Osteocalcin (negative in small cells).
*CD99 - (positive in small cells)

==Molecular==
*t(8;8)(q21.1;q13.3) HEY1-NCOA2.<ref name=pmid24839999>{{Cite journal | last1 = Panagopoulos | first1 = I. | last2 = Gorunova | first2 = L. | last3 = Bjerkehagen | first3 = B. | last4 = Boye | first4 = K. | last5 = Heim | first5 = S. | title = Chromosome aberrations and HEY1-NCOA2 fusion gene in a mesenchymal chondrosarcoma. | journal = Oncol Rep | volume = 32 | issue = 1 | pages = 40-4 | month = Jul | year = 2014 | doi = 10.3892/or.2014.3180 | PMID = 24839999 }}</ref>
*Less commonly t(1;5)(q42;q32) IRF2BP2-CDX1<ref>{{cite journal |vauthors=Nyquist KB, Panagopoulos I, Thorsen J, Haugom L, Gorunova L, Bjerkehagen B, Fosså A, Guriby M, Nome T, Lothe RA, Skotheim RI, Heim S, Micci F |title=Whole-transcriptome sequencing identifies novel IRF2BP2-CDX1 fusion gene brought about by translocation t(1;5)(q42;q32) in mesenchymal chondrosarcoma |journal=PLoS ONE |volume=7 |issue=11 |pages=e49705 |date=2012 |pmid=23185413 |pmc=3504151 |doi=10.1371/journal.pone.0049705 |url=}}</ref>

==See also==
*[[Cartilage]].
*[[Chondrosarcoma]].

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

==External links==
*[http://www.webpathology.com/image.asp?case=332&n=41 Mesenchymal chondrosarcoma - images (webpathology.com)].
*[http://www.pathologyoutlines.com/topic/bonemesenchymalchondrosarcoma.html Mesenchymal chondrosarcoma (pathologyoutlines.com)].

[[Category:Diagnosis]]
[[Category:Chondro-osseous tumours]]

Medullary colorectal carcinoma

2019-12-31T21:38:24Z

Mark: missing tags

'''Medullary colorectal carcinoma''' is a rare type of [[colorectal carcinoma]].

==General==
*Rare subtype of colorectal carcinoma.
*Typically has [[MSI|Microsatellite instability]].<ref name=pmid24815832 >{{cite journal |vauthors=Cunningham J, Kantekure K, Saif MW |title=Medullary carcinoma of the colon: a case series and review of the literature |journal=In Vivo |volume=28 |issue=3 |pages=311–4 |date=2014 |pmid=24815832 |doi= |url=}}</ref>
*Prognostic significance dependent on study.
**A small series suggests the prognosis of medullary carcinoma with MSI is worse that conventional colorectal carcinoma without MSI.<ref>{{cite journal |vauthors=Gómez-Álvarez MA, Lino-Silva LS, Salcedo-Hernández RA, Padilla-Rosciano A, Ruiz-García EB, López-Basave HN, Calderillo-Ruiz G, Aguilar-Romero JM, Domínguez-Rodríguez JA, Herrera-Gómez Á, Meneses-García A |title=Medullary colonic carcinoma with microsatellite instability has lower survival compared with conventional colonic adenocarcinoma with microsatellite instability |journal=Prz Gastroenterol |volume=12 |issue=3 |pages=208–214 |date=2017 |pmid=29123583 |pmc=5672702 |doi=10.5114/pg.2016.64740 |url=}}</ref>
**A series with 102 cases suggests a better prognosis when compared on the basis of other pathological characteristics.<ref name=pmid25572685>{{cite journal |vauthors=Knox RD, Luey N, Sioson L, Kedziora A, Clarkson A, Watson N, Toon CW, Cussigh C, Pincott S, Pillinger S, Salama Y, Evans J, Percy J, Schnitzler M, Engel A, Gill AJ |title=Medullary colorectal carcinoma revisited: a clinical and pathological study of 102 cases |journal=Ann. Surg. Oncol. |volume=22 |issue=9 |pages=2988–96 |date=September 2015 |pmid=25572685 |doi=10.1245/s10434-014-4355-5 |url=}}</ref>

==Gross==
*Well-circumscribed.

==Microscopic==
Features:
*Poorly differentiated carcinoma:
**Noninfiltrative border.
**Solid pattern/nests.
**No gland formation.
**Lymphocytic infiltrate.

DDx:
*Other (poorly differentiated) [[colorectal carcinoma]]s.
*Carcinomas with neuroendocrine differentiation.

==IHC==
Features:<ref name=pmid24815832/>
*CDX2 +ve.
*Beta-catenin +ve.
*MLH1 loss of staining.
*Calretinin (67%-73%)<ref>{{cite journal |vauthors=Winn B, Tavares R, Fanion J, Noble L, Gao J, Sabo E, Resnick MB |title=Differentiating the undifferentiated: immunohistochemical profile of medullary carcinoma of the colon with an emphasis on intestinal differentiation |journal=Hum. Pathol. |volume=40 |issue=3 |pages=398–404 |date=March 2009 |pmid=18992917 |pmc=2657293 |doi=10.1016/j.humpath.2008.08.014 |url=}}</ref><ref>{{cite journal |vauthors=Lin F, Shi J, Zhu S, Chen Z, Li A, Chen T, Wang HL, Liu H |title=Cadherin-17 and SATB2 are sensitive and specific immunomarkers for medullary carcinoma of the large intestine |journal=Arch. Pathol. Lab. Med. |volume=138 |issue=8 |pages=1015–26 |date=August 2014 |pmid=24437456 |doi=10.5858/arpa.2013-0452-OA |url=}}</ref>

Note:
*CDX2, beta-catenin, MLH1 useful for differentiating from poorly differentiated colorectal carcinoma.

==See also==
*[[Colorectal adenocarcinoma]].

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

[[Category:Diagnosis]]
[[Category:Gastrointestinal pathology]]

Medullary colorectal carcinoma

2019-12-31T21:37:32Z

Mark: calretinin

'''Medullary colorectal carcinoma''' is a rare type of [[colorectal carcinoma]].

==General==
*Rare subtype of colorectal carcinoma.
*Typically has [[MSI|Microsatellite instability]].<ref name=pmid24815832 >{{cite journal |vauthors=Cunningham J, Kantekure K, Saif MW |title=Medullary carcinoma of the colon: a case series and review of the literature |journal=In Vivo |volume=28 |issue=3 |pages=311–4 |date=2014 |pmid=24815832 |doi= |url=}}</ref>
*Prognostic significance dependent on study.
**A small series suggests the prognosis of medullary carcinoma with MSI is worse that conventional colorectal carcinoma without MSI.<ref>{{cite journal |vauthors=Gómez-Álvarez MA, Lino-Silva LS, Salcedo-Hernández RA, Padilla-Rosciano A, Ruiz-García EB, López-Basave HN, Calderillo-Ruiz G, Aguilar-Romero JM, Domínguez-Rodríguez JA, Herrera-Gómez Á, Meneses-García A |title=Medullary colonic carcinoma with microsatellite instability has lower survival compared with conventional colonic adenocarcinoma with microsatellite instability |journal=Prz Gastroenterol |volume=12 |issue=3 |pages=208–214 |date=2017 |pmid=29123583 |pmc=5672702 |doi=10.5114/pg.2016.64740 |url=}}</ref>
**A series with 102 cases suggests a better prognosis when compared on the basis of other pathological characteristics.<ref name=pmid25572685>{{cite journal |vauthors=Knox RD, Luey N, Sioson L, Kedziora A, Clarkson A, Watson N, Toon CW, Cussigh C, Pincott S, Pillinger S, Salama Y, Evans J, Percy J, Schnitzler M, Engel A, Gill AJ |title=Medullary colorectal carcinoma revisited: a clinical and pathological study of 102 cases |journal=Ann. Surg. Oncol. |volume=22 |issue=9 |pages=2988–96 |date=September 2015 |pmid=25572685 |doi=10.1245/s10434-014-4355-5 |url=}}</ref>

==Gross==
*Well-circumscribed.

==Microscopic==
Features:
*Poorly differentiated carcinoma:
**Noninfiltrative border.
**Solid pattern/nests.
**No gland formation.
**Lymphocytic infiltrate.

DDx:
*Other (poorly differentiated) [[colorectal carcinoma]]s.
*Carcinomas with neuroendocrine differentiation.

==IHC==
Features:<ref name=pmid24815832/>
*CDX2 +ve.
*Beta-catenin +ve.
*MLH1 loss of staining.
*Calretinin (67%-73%){{cite journal |vauthors=Winn B, Tavares R, Fanion J, Noble L, Gao J, Sabo E, Resnick MB |title=Differentiating the undifferentiated: immunohistochemical profile of medullary carcinoma of the colon with an emphasis on intestinal differentiation |journal=Hum. Pathol. |volume=40 |issue=3 |pages=398–404 |date=March 2009 |pmid=18992917 |pmc=2657293 |doi=10.1016/j.humpath.2008.08.014 |url=}}{{cite journal |vauthors=Lin F, Shi J, Zhu S, Chen Z, Li A, Chen T, Wang HL, Liu H |title=Cadherin-17 and SATB2 are sensitive and specific immunomarkers for medullary carcinoma of the large intestine |journal=Arch. Pathol. Lab. Med. |volume=138 |issue=8 |pages=1015–26 |date=August 2014 |pmid=24437456 |doi=10.5858/arpa.2013-0452-OA |url=}}

Note:
*CDX2, beta-catenin, MLH1 useful for differentiating from poorly differentiated colorectal carcinoma.

==See also==
*[[Colorectal adenocarcinoma]].

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

[[Category:Diagnosis]]
[[Category:Gastrointestinal pathology]]

BRAF V600E mutation

2019-01-24T23:05:26Z

Mark: metanephric adenoma

[[Image:BRAF_V600E_mutant_melanoma.jpg|thumb|300px|right|BRAF V600E positivity in [[malignant melanoma]]. VE1 immunostain.]]
The '''BRAF V600E mutation''', also '''BRAF V600E''', is a common recurrent mutation in the BRAF gene that is seen in many types of tumours and [[cancer]].<ref name=pmid21638088/>

A more general discussion about ''BRAF'' is in ''[[BRAF mutation]]''.

==General==
The ''BRAF gene'', formally known as ''v-RAF murine sarcoma viral oncogene homolog B1'', is a serine threonine kinase.<ref>{{OMIM|164757}}</ref>

The mutation can be demonstrated with [[Molecular pathology tests|molecular testing]] ([[ARMS]]). Also, a mutation specific [[immunostain]] (''VE1'') is available.<ref name=pmid21638088>{{Cite journal | last1 = Capper | first1 = D. | last2 = Preusser | first2 = M. | last3 = Habel | first3 = A. | last4 = Sahm | first4 = F. | last5 = Ackermann | first5 = U. | last6 = Schindler | first6 = G. | last7 = Pusch | first7 = S. | last8 = Mechtersheimer | first8 = G. | last9 = Zentgraf | first9 = H. | title = Assessment of BRAF V600E mutation status by immunohistochemistry with a mutation-specific monoclonal antibody. | journal = Acta Neuropathol | volume = 122 | issue = 1 | pages = 11-9 | month = Jul | year = 2011 | doi = 10.1007/s00401-011-0841-z | PMID = 21638088 }}</ref>

==Positive==
===Commonly mutated===
*[[Malignant melanoma]] (55%).<ref name=pmid22012135>{{Cite journal | last1 = Capper | first1 = D. | last2 = Berghoff | first2 = AS. | last3 = Magerle | first3 = M. | last4 = Ilhan | first4 = A. | last5 = Wöhrer | first5 = A. | last6 = Hackl | first6 = M. | last7 = Pichler | first7 = J. | last8 = Pusch | first8 = S. | last9 = Meyer | first9 = J. | title = Immunohistochemical testing of BRAF V600E status in 1,120 tumor tissue samples of patients with brain metastases. | journal = Acta Neuropathol | volume = 123 | issue = 2 | pages = 223-33 | month = Feb | year = 2012 | doi = 10.1007/s00401-011-0887-y | PMID = 22012135 }}</ref>
*[[Papillary thyroid carcinoma]] (79%).<ref>{{Cite journal | last1 = Ilie | first1 = MI. | last2 = Lassalle | first2 = S. | last3 = Long-Mira | first3 = E. | last4 = Bonnetaud | first4 = C. | last5 = Bordone | first5 = O. | last6 = Lespinet | first6 = V. | last7 = Lamy | first7 = A. | last8 = Sabourin | first8 = JC. | last9 = Haudebourg | first9 = J. | title = Diagnostic value of immunohistochemistry for the detection of the BRAF(V600E) mutation in papillary thyroid carcinoma: comparative analysis with three DNA-based assays. | journal = Thyroid | volume = 24 | issue = 5 | pages = 858-66 | month = May | year = 2014 | doi = 10.1089/thy.2013.0302 | PMID = 24417277 }}</ref>
*[[Ganglioglioma]] (58%).<ref>{{Cite journal | last1 = Koelsche | first1 = C. | last2 = Wöhrer | first2 = A. | last3 = Jeibmann | first3 = A. | last4 = Schittenhelm | first4 = J. | last5 = Schindler | first5 = G. | last6 = Preusser | first6 = M. | last7 = Lasitschka | first7 = F. | last8 = von Deimling | first8 = A. | last9 = Capper | first9 = D. | title = Mutant BRAF V600E protein in ganglioglioma is predominantly expressed by neuronal tumor cells. | journal = Acta Neuropathol | volume = 125 | issue = 6 | pages = 891-900 | month = Jun | year = 2013 | doi = 10.1007/s00401-013-1100-2 | PMID = 23435618 }}</ref>
*[[Pleomorphic xanthoastrocytoma]] (78%).<ref>{{Cite journal | last1 = Koelsche | first1 = C. | last2 = Sahm | first2 = F. | last3 = Wöhrer | first3 = A. | last4 = Jeibmann | first4 = A. | last5 = Schittenhelm | first5 = J. | last6 = Kohlhof | first6 = P. | last7 = Preusser | first7 = M. | last8 = Romeike | first8 = B. | last9 = Dohmen-Scheufler | first9 = H. | title = BRAF-mutated pleomorphic xanthoastrocytoma is associated with temporal location, reticulin fiber deposition and CD34 expression. | journal = Brain Pathol | volume = 24 | issue = 3 | pages = 221-9 | month = Apr | year = 2014 | doi = 10.1111/bpa.12111 | PMID = 24345274 }}</ref>
*[[Hairy cell leukemia]] (>90%)
*Histiocytic disorders: [[Langerhans cell histiocytosis]] and [[Erdheim-Chester disease]]
*Metanephric adenoma <ref name=pmid22727996>{{Cite journal | last1 = Choueiri | first1 = TK. | last2 = Cheville | first2 = J. | last3 = Palescandolo | first3 = E. | last4 = Fay | first4 = AP. | last5 = Kantoff | first5 = PW. | last6 = Atkins | first6 = MB. | last7 = McKenney | first7 = JK. | last8 = Brown | first8 = V. | last9 = Lampron | first9 = ME. | title = BRAF mutations in metanephric adenoma of the kidney. | journal = Eur Urol | volume = 62 | issue = 5 | pages = 917-22 | month = Nov | year = 2012 | doi = 10.1016/j.eururo.2012.05.051 | PMID = 22727996 }}</ref><ref name=pmid25602792>{{Cite journal | last1 = Udager | first1 = AM. | last2 = Pan | first2 = J. | last3 = Magers | first3 = MJ. | last4 = Palapattu | first4 = GS. | last5 = Morgan | first5 = TM. | last6 = Montgomery | first6 = JS. | last7 = Weizer | first7 = AZ. | last8 = Hafez | first8 = KS. | last9 = Miller | first9 = DC. | title = Molecular and immunohistochemical characterization reveals novel BRAF mutations in metanephric adenoma. | journal = Am J Surg Pathol | volume = 39 | issue = 4 | pages = 549-57 | month = Apr | year = 2015 | doi = 10.1097/PAS.0000000000000377 | PMID = 25602792 }}</ref>

===Less commonly mutated===
*[[Colorectal cancer]] (5.5%).<ref name=pmid22012135>{{Cite journal | last1 = Capper | first1 = D. | last2 = Berghoff | first2 = AS. | last3 = Magerle | first3 = M. | last4 = Ilhan | first4 = A. | last5 = Wöhrer | first5 = A. | last6 = Hackl | first6 = M. | last7 = Pichler | first7 = J. | last8 = Pusch | first8 = S. | last9 = Meyer | first9 = J. | title = Immunohistochemical testing of BRAF V600E status in 1,120 tumor tissue samples of patients with brain metastases. | journal = Acta Neuropathol | volume = 123 | issue = 2 | pages = 223-33 | month = Feb | year = 2012 | doi = 10.1007/s00401-011-0887-y | PMID = 22012135 }}</ref>
*[[Ovarian cancer]] (7%).<ref name=pmid22012135>{{Cite journal | last1 = Capper | first1 = D. | last2 = Berghoff | first2 = AS. | last3 = Magerle | first3 = M. | last4 = Ilhan | first4 = A. | last5 = Wöhrer | first5 = A. | last6 = Hackl | first6 = M. | last7 = Pichler | first7 = J. | last8 = Pusch | first8 = S. | last9 = Meyer | first9 = J. | title = Immunohistochemical testing of BRAF V600E status in 1,120 tumor tissue samples of patients with brain metastases. | journal = Acta Neuropathol | volume = 123 | issue = 2 | pages = 223-33 | month = Feb | year = 2012 | doi = 10.1007/s00401-011-0887-y | PMID = 22012135 }}</ref>
*[[Lung adenocarcinoma]] (5%).<ref name=pmid23131393>{{Cite journal | last1 = Ilie | first1 = M. | last2 = Long | first2 = E. | last3 = Hofman | first3 = V. | last4 = Dadone | first4 = B. | last5 = Marquette | first5 = CH. | last6 = Mouroux | first6 = J. | last7 = Vignaud | first7 = JM. | last8 = Begueret | first8 = H. | last9 = Merlio | first9 = JP. | title = Diagnostic value of immunohistochemistry for the detection of the BRAFV600E mutation in primary lung adenocarcinoma Caucasian patients. | journal = Ann Oncol | volume = 24 | issue = 3 | pages = 742-8 | month = Mar | year = 2013 | doi = 10.1093/annonc/mds534 | PMID = 23131393 }}</ref>

==See also==
*[[Immunohistochemistry]].
*[[Molecular pathology tests]].
*[[KRAS mutation]].
*[[Cancer Hotspot Panel v2]].
*[[BRAF mutation]].

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

[[Category:Immunohistochemistry]]

Nodular lymphocyte-predominant Hodgkin lymphoma

2018-12-05T16:25:36Z

Mark: add image

{{ Infobox diagnosis
| Name = Nodular lymphocyte-predominant Hodgkin lymphoma
| Image = Popcorn_cell_in_nodular_lymphocyte_predominant_Hodgkin_lymphoma_-_very_high_mag_cropped.jpg
| Width =
| Caption = Popcorn cell in nodular lymphocyte-predominant Hodgkin lymphoma
| Micro = Popcorn cells (relatively) small (compared to classic RSCs) - have lobulated nucleus (key feature), small nucleoli; subtle nodularity at low power
| Subtypes = none
| LMDDx = [[diffuse large B cell lymphoma]] (esp. ''T-cell/histiocytic-rich LBCL''), [[anaplastic large cell lymphoma]],
B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and classical Hodgkin lymphoma, classical Hodgkin lymphoma
| Stains =
| IHC = LCA (CD45) +ve, CD20 +ve, CD10 +ve, Bcl-6 +ve, EMA +ve, CD30 -ve, CD15 -ve
| EM =
| Molecular =
| IF =
| Gross =
| Grossing =
| Site = usu. [[lymph node]]
| Assdx =
| Syndromes =
| Clinicalhx =
| Signs = lymphadenopathy
| Symptoms =
| Prevalence = uncommon
| Bloodwork =
| Rads =
| Endoscopy =
| Prognosis = good
| Other =
| ClinDDx =
}}
*AKA ''lympho-histiocytic variant''.
*Abbreviated ''NLPHL''.
*Different IHC and morphologic appearance than classic HL.
*Significant risk for transformation into [[diffuse large B cell lymphoma]] (DLBCL); 10-year cumulative transformation rate (to DLBCL) in one study was 12%.<ref name=pmid20029973 >{{cite journal |author=Biasoli I, Stamatoullas A, Meignin V, ''et al.'' |title=Nodular, lymphocyte-predominant Hodgkin lymphoma: a long-term study and analysis of transformation to diffuse large B-cell lymphoma in a cohort of 164 patients from the Adult Lymphoma Study Group |journal=Cancer |volume=116 |issue=3 |pages=631–9 |year=2010 |month=February |pmid=20029973 |doi=10.1002/cncr.24819 |url=}}</ref>

==Microscopy==
Features (nodular lymphocyte-predominant Hodgkin's lymphoma):
*''Popcorn cell'' (previously known as ''Lymphocytic & histiocytic'' cell (L&H cell)<ref name=pmid9499174>{{cite journal |author=Küppers R, Rajewsky K, Braeuninger A, Hansmann ML |title=L&H cells in lymphocyte-predominant Hodgkin's disease |journal=N. Engl. J. Med. |volume=338 |issue=11 |pages=763–4; author reply 764–5 |year=1998 |month=March |pmid=9499174 |doi=10.1056/NEJM199803123381113 |url=}}</ref>) - variant of RSC:
**Cells (relatively) small (compared to classic RSCs).
**Lobulated nucleus - '''key feature'''.
**Small nucleoli.
*Subtle nodularity at low power (2.5x or 5x objective).

==IHC==
Abbreviated panel:<ref name=Ref_WMSP568>{{Ref_WMSP|568}}</ref>
*CD30 Reed-Sternberg cells (RSCs) +ve ~98%
*CD15 Reed-Sternberg cells +ve ~80%, stains neutrophils.
*CD45 '''often negative''' in RSCs.
*CD20 may stain RSCs.
*PAX5 +ve.<ref name=Ref_APBR683>{{Ref APBR|683}}</ref>

Additional - for completeness:
*CD3 (T lymphocytes)

NLPHL IHC '''differs''' from the classical HL:<ref name=Ref_APBR683>{{Ref APBR|683}}</ref>
*LCA +ve.
*CD20 +ve.
*CD10 +ve.
*Bcl-6 +ve.
*[[EMA]] +ve.
*CD30 -ve
*CD15 -ve.

===A panel===
{| class="wikitable"
|Antibody || NLPHL || CHL
|-
|CD45 || +ve || -ve
|-
|CD20 || +ve || -ve
|-
|BCL6 || ||
|-
|MUM1<ref>URL: [http://www.ncbi.nlm.nih.gov/omim/601900 http://www.ncbi.nlm.nih.gov/omim/601900]. Accessed on: 10 August 2010.</ref> || -ve ||
|-
|CD30 || -ve || +ve (most sensitive).
|-
|CD15 || -ve || +ve
|-
|CD21 || networks present || no networks
|-
|[[CD23]] || networks present || no networks
|-
|OCT-2 || +ve || -ve
|-
|PAX5 || +ve || +ve (proves B cell linage)
|-
|CD3 || usu. < benign B cell || usu. > benign B cell component
|-
|CD57 || rosettes around malign. cells || -
|-
|EBER || -ve || +ve/-ve
|-
|EMA || +ve/-ve || -ve
|-
|4 unstained || ||
|}

====Images (NLPHL)====
www:
*[http://webpathology.com/image.asp?case=388&n=16 Popcorn cell (webpathology.com)].
<gallery>
Image:Popcorn_cell_in_nodular_lymphocyte_predominant_Hodgkin_lymphoma_-_very_high_mag_cropped.jpg | Popcorn cell. (WC)
Image:Nodular lymphocyte predominant Hodgkin's lymphoma.jpg | LP/popcorn cells (WC)]]

</gallery>

Hodgkin lymphoma

2018-12-04T22:01:42Z

Mark: fill in BCL6 and MUM1 in comparison table

{{ Infobox diagnosis
| Name = Classical Hodgkin lymphoma
| Image = Hodgkin_lymphoma_cytology_large.jpg
| Width =
| Caption = HL mixed cellularity - cytology.
| Micro = Reed-Sternberg cell (large binucleated cell (>= 45 micrometres), +/-multinucleated, +/-horseshoe-like shape, [[macronucleolus]] - approximately the size of a RBC (~8 micrometers)), well-defined cell border, abundant cytoplasm.
| Subtypes = nodular sclerosis CHL, mixed cellularity CHL, lymphocyte-rich CHL, lymphocyte-depleted CHL
| LMDDx = [[diffuse large B cell lymphoma]] (esp. ''T-cell/histiocytic-rich LBCL''), [[anaplastic large cell lymphoma]],
B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and classical Hodgkin lymphoma, nodular lymphocyte-predominant Hodgkin lymphoma
| Stains =
| IHC = CD30 Reed-Sternberg cells (RSCs) +ve ~98%, CD15 Reed-Sternberg cells +ve ~80% (also stains neutrophils), CD45 ''often negative'' in RSCs, CD20 -ve/+ve, PAX5 +ve
| EM =
| Molecular =
| IF =
| Gross =
| Grossing =
| Site = usu. [[lymph node]] - classically in the neck
| Assdx =
| Syndromes =
| Clinicalhx = young adults, older adults (bimodal distribution)
| Signs = lymphadenopathy - usu. neck, +/-[[B symptoms]] (fever, night sweats, weight loss)
| Symptoms =
| Prevalence = common
| Bloodwork =
| Rads =
| Endoscopy =
| Prognosis = usu. good, dependent on stage
| Other =
| ClinDDx =
}}
'''Hodgkin [[lymphoma]]''', abbreviated '''HL''', is a haematological [[malignancy]]. If not otherwise specified, Hodgkin lymphoma generally refers to classical Hodgkin lymphoma (CHL) rather than [[nodular lymphocyte-predominant Hodgkin lymphoma]] (NLPHL). The latter accounts for only about 5% of the loose label of Hodgkin lymphoma<ref name=Ref_WMSP567/> and shows a sufficiently different biology and immunophenotype that is essentially a different disease (see [[nodular lymphocyte-predominant Hodgkin lymphoma|main article on NLPHL]]). The common feature is large atypical cells: Hodgkin/Reed-Sternberg cells in the case of classical Hodgkin lymphoma and "popcorn"/lymphohistiocytic/L&H cells in NLPHL. However, at least in typical cases, there are morphological and immunophenotypic differences.

Classical Hodgkin lymphoma has a bi-modal distribution, afflicting young adults and with a further peak in incidence in middle-age. Fortunately, it usually has a good prognosis.

Pathologists say "... it is both the easiest and hardest diagnosis to make." The reason for this is: the diagnosis depends on finding Reed-Sternberg cells (or Popcorn cells); if they are obvious the diagnosis is easy... if you can't find 'em and an alternative diagnosis is not apparent -- you wonder whether you're missing them.

==General==
===Clinical===
Symptoms:<ref name=Ref_WMSP567>{{Ref WMSP|567}}</ref>
*"[[B symptoms]]" - all required:<ref>URL: [http://lymphoma.about.com/od/symptoms/f/bsymptoms.htm http://lymphoma.about.com/od/symptoms/f/bsymptoms.htm]. Accessed on: 11 August 2010.</ref> weight loss, night sweats and fever.
*Infections due to immune dysfunction.

Diagnosis:
*HL cannot be diagnosed with standard [[flow cytometry]] (FC) - but has been diagnosed with specialized FC.<ref>{{cite journal |author=Fromm JR, Thomas A, Wood BL |title=Flow cytometry can diagnose classical hodgkin lymphoma in lymph nodes with high sensitivity and specificity |journal=Am. J. Clin. Pathol. |volume=131 |issue=3 |pages=322–32 |year=2009 |month=March |pmid=19228638 |doi=10.1309/AJCPW3UN9DYLDSPB |url=}}</ref>

Prognosis:
*Usually good.
*Unlike non-Hodgkin lymphomas, it spreads in a predictable pattern; thus, staging plays an important role in determining the therapy.<ref name=PCPBoD8_315>{{Ref PCPBoD8|315}}</ref>
*Clinically classified into early favourable, early unfavourable and late/advanced disease.

===Classic HL sub-types===
====Subtypes of classic HL====
There are four CHL subtypes:<ref name=Ref_WMSP567/>
#Nodular sclerosis CHL - ~70% of CHL.
#*Mixed cellular background - T cell, plasma cells, eosinophils, neutrophils and histiocytes.
#*Nodular sclerosing fibrosis - thick strands fibrosis.
#Mixed cellularity CHL - ~20-25% of CHL.
#*Like nodular sclerosis - but no fibrosis.
#*May be associated with [[HIV]] infection.<ref name=pmid20138008>{{cite journal |author=Sissolak G, Sissolak D, Jacobs P |title=Human immunodeficiency and Hodgkin lymphoma |journal=Transfus. Apher. Sci. |volume=42 |issue=2 |pages=131–9 |year=2010 |month=April |pmid=20138008 |doi=10.1016/j.transci.2010.01.008 |url=}}</ref>
#Lymphocyte-rich CHL - rare.
#*T lymphocytes only (no mix of cells).
#Lymphocyte-depleted CHL - rare.
#*May be associated with HIV infection.<ref name=pmid20138008/>

Memory device:
*The subtypes prevalence is in reverse alphabetical order.

==Gross==
Location:
*Almost always arises from a [[lymph node]] - classically in the neck, but may be in the axilla and mediastinum
*Spleen may be involved
*Bone marrow involvement is unusual (~5% of cases, higher in HIV-associated cases), so bone marrow assessment is usually not performed
*''Extranodal Hodgkin lymphoma'' is (case report) rare.<ref name=pmid11100066>{{Cite journal | last1 = Vadmal | first1 = MS. | last2 = LaValle | first2 = GP. | last3 = DeYoung | first3 = BR. | last4 = Frankel | first4 = WL. | last5 = Marsh | first5 = WL. | title = Primary localized extranodal hodgkin disease of the transverse colon. | journal = Arch Pathol Lab Med | volume = 124 | issue = 12 | pages = 1824-7 | month = Dec | year = 2000 | doi = 10.1043/0003-9985(2000)1241824:PLEHDO2.0.CO;2 | PMID = 11100066 }}</ref>

==Microscopic==
Defined by ''Reed-Sternberg cells'' (RSCs). Morphologically similar mononuclear cells are known as Hodgkin cells. RSCs are:
*Large binucleated cell (>= 45 micrometres).<ref name=Ref_PCPBoD8_329>{{Ref PCPBoD8|329}}</ref>
**May be multinucleated.
**May have a horseshoe-like shape.
*[[Macronucleolus]] - approximately the size of a RBC (~8 micrometers).
*Well-defined cell border.
*Abundant cytoplasm.

RSC may show peri-cellular clearing, making the cells appear within a space. These are called lacunar cells (as they are in a "lake"). Apoptotic RSC may show pyknotic nuclei and scant eosinophilic cytoplasm and are sometimes known as "mummified" cells.

===Images (classic HL)===
<gallery>
Image:CHL mummified cell x40.jpg | "Mummified" RSC. (WC)
Image:CHL lacunar cell x40.jpg | "Lacunar cell". (WC)
Image:16S14098 cHL multinucleate HRS cell x40c.jpg | Multinucleate RSC. (WC)
Image:Hodgkin_lymphoma_cytology_large.jpg | HL mixed cellularity - cytology. (WC)
Image:Hodgkin_lymphoma_cytology_small.jpg | HL mixed cellularity - cytology. (WC)
Image:Hodgkin_lymphoma_%281%29_mixed_cellulary_type.jpg | HL mixed cellularity. (WC)
</gallery>

===DDx both CHL & NLPHL===
*CHL/NLPHL.
*[[Diffuse large B cell lymphoma]] (DLBCL), esp. ''T-cell/histiocytic-rich LBCL''.
*[[Anaplastic large cell lymphoma]] (ALCL).
*B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and classical Hodgkin lymphoma.<ref name=pmid22222636>{{Cite journal | last1 = Gualco | first1 = G. | last2 = Natkunam | first2 = Y. | last3 = Bacchi | first3 = CE. | title = The spectrum of B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and classical Hodgkin lymphoma: a description of 10 cases. | journal = Mod Pathol | volume = | issue = | pages = | month = Jan | year = 2012 | doi = 10.1038/modpathol.2011.200 | PMID = 22222636 | URL = http://www.nature.com/modpathol/journal/vaop/ncurrent/full/modpathol2011200a.html }}</ref> (typically in cases of numerous large atypical cells where the morphology and immunophenotype do not neatly fit into either DLBCL or CHL).

==IHC==
Abbreviated panel:<ref name=Ref_WMSP568>{{Ref_WMSP|568}}</ref>
*CD30 Reed-Sternberg cells (RSCs) +ve ~98% (beware of mis-interpreting CD30+ activated lymphoid cells)
*CD15 Reed-Sternberg cells +ve ~80%, stains neutrophils.
*Both CD30 and CD15 are classically positive in a membranous and Golgi pattern
*MUM1 +ve
*CD45 '''often negative''' in RSCs.
*CD20 may stain RSCs (usually negative, but can be weak).
*PAX5 +ve, though said to be weaker than background normal B-cells<ref name=Ref_APBR683>{{Ref APBR|683}}</ref>

Additional - for completeness:
*CD3 (T lymphocytes) - negative in RSCs
*OCT2/BOB1 negative (co-transcription factors for immunoglobulin production, one or the other is usually negative)
*40% are EBV positive.

NLPHL IHC '''differs''' from the classical HL:<ref name=Ref_APBR683>{{Ref APBR|683}}</ref>
*LCA +ve.
*CD20 +ve.
*CD10 +ve.
*Bcl-6 +ve.
*[[EMA]] +ve (40-50%)
*CD30 -ve
*CD15 -ve.

===A panel===
{| class="wikitable"
|Antibody || NLPHL || CHL
|-
|CD45 || +ve || -ve
|-
|CD20 || +ve || -ve
|-
|BCL6 || +ve || -ve
|-
|MUM1<ref>URL: [http://www.ncbi.nlm.nih.gov/omim/601900 http://www.ncbi.nlm.nih.gov/omim/601900]. Accessed on: 10 August 2010.</ref> || -ve || +ve
|-
|CD30 || -ve || +ve (most sensitive).
|-
|CD15 || -ve || +ve
|-
|CD21 || networks present || no networks
|-
|[[CD23]] || networks present || no networks
|-
|OCT-2 || +ve || -ve
|-
|PAX5 || +ve || +ve (proves B cell linage)
|-
|CD3 || usu. < benign B cell || usu. > benign B cell component
|-
|CD57 || rosettes around malign. cells || -
|-
|EBER || -ve || +ve/-ve
|-
|EMA || +ve/-ve || -ve
|-
|4 unstained || ||
|}

==Sign out==
===Suggestive FNA===
<pre>
Lymph Node, Right Neck, FNA:
- Large binucleated and multinucleated cells with macronucleoli in
a background of abundant lymphocytes, histiocytes, rare eosinophils.

Comment:
A cell block is not available for further work-up. The findings raise the possibility of Hodgkin's lymphoma.

A further biopsy is required for the diagnosis.
</pre>

==See also==
*[[Lymph nodes]].
*[[Lymph node pathology]].
*[[Haematopathology]].

==References==
{{reflist|2}}

[[Category:Haematopathology]]

Sessile serrated adenoma

2018-11-27T21:51:08Z

Mark: ref tags

{{ Infobox diagnosis
| Name = {{PAGENAME}}
| Image = sessile_serrated_adenoma_3_very_high_mag.jpg
| Width =
| Caption = SSA. [[H&E stain]].
| Synonyms = sessile serrated lesion, sessile serrated polyp, sessile serrated adenoma/polyp
| Micro = serrated epithelium, crypt base dilation, crypt branching, boot-shaped glands, horizontal glands
| Subtypes =
| LMDDx = [[hyperplastic polyp]], [[tubular adenoma]] when with dysplasia, [[mucosal prolapse]] for left sided lesions or background of [[diverticulosis]]
| Stains =
| IHC = Chromogranin A (completely) -ve
| EM =
| Molecular =
| IF =
| Gross =
| Grossing =
| Site = [[colon]] - usually cecum or ascending colon
| Assdx = [[colorectal adenocarcinoma]], [[hyperplastic polyp]]
| Syndromes = [[serrated polyposis syndrome]], [[MUTYH polyposis syndrome]]
| Clinicalhx =
| Signs =
| Symptoms =
| Prevalence = common
| Bloodwork =
| Rads =
| Endoscopy = flat, usually > 5 mm, mucinous cap
| Prognosis =
| Other =
| ClinDDx = normal, hyperplastic polyp, other [[intestinal polyps]]
}}
'''Sessile serrated adenoma''', abbreviated ''SSA'', is a premalignant [[GI polyps|polyp]] of the large bowel.

It is also known as '''sessile serrated polyp''' (abbreviated ''SSP''), '''sessile serrated lesion''' and '''sessile serrated adenoma/polyp''' (abbreviated ''SSA/P''). In the United Kingdom, this entity and is known as a sessile serrated lesion, a terminology that is likely to be adopted in the 2019/5th edition WHO Blue Book.

This lesion should not be confused with the ''[[traditional serrated adenoma]]'', previously known as ''[[serrated adenoma]]''.

==General==
*Colonic lesion.
*May be seen in the context of ''[[serrated polyposis syndrome]]''.
*Approximately 5% of SSAs have dysplasia.<ref name=pmid25724036>{{Cite journal | last1 = Yang | first1 = JF. | last2 = Tang | first2 = SJ. | last3 = Lash | first3 = RH. | last4 = Wu | first4 = R. | last5 = Yang | first5 = Q. | title = Anatomic distribution of sessile serrated adenoma/polyp with and without cytologic dysplasia. | journal = Arch Pathol Lab Med | volume = 139 | issue = 3 | pages = 388-93 | month = Mar | year = 2015 | doi = 10.5858/arpa.2013-0523-OA | PMID = 25724036 }}</ref>

Epidemiology:
*Thought to lead to colorectal cancer through a different pathway than most tumours in the left colon/rectum.
*''Microvesicular [[hyperplastic polyp]]s'' are hypothesized to be the the precursor of SSAs.<ref name=pmid21045813>{{Cite journal | last1 = Huang | first1 = CS. | last2 = Farraye | first2 = FA. | last3 = Yang | first3 = S. | last4 = O'Brien | first4 = MJ. | title = The clinical significance of serrated polyps. | journal = Am J Gastroenterol | volume = 106 | issue = 2 | pages = 229-40; quiz 241 | month = Feb | year = 2011 | doi = 10.1038/ajg.2010.429 | PMID = 21045813 }}</ref>

==Gross==
Features:<ref name=pmid22710576/>
*Flat lesions, usually > 5 mm.
*Typically have a "mucous cap" - present ~65% of the time; useful for identification.
*Border not well-demarcated.
*More common in the proximal colon.

Note:
*Sessile lesions over 1 cm are usually SSAs.<ref name=pmid22710576/>

Image:
*[http://www.nature.com/ajg/journal/v105/n12/fig_tab/ajg2010330f1.html SSA - endoscopy (nature.com)].<ref name=pmid21131934>{{cite journal |author=Rex DK, Hewett DG, Snover DC |title=Editorial: Detection targets for colonoscopy: from variable detection to validation |journal=Am. J. Gastroenterol. |volume=105 |issue=12 |pages=2665–9 |year=2010 |month=December |pmid=21131934 |doi=10.1038/ajg.2010.330 |url=}}</ref>

==Microscopic==
Features:
*Serrated epithelium at the surface and deep in the crypts.
**Saw-tooth appearance, epithelium has jagged appearing edge.
*Crypt dilation at base with serrations - '''key feature'''.
**Very common -- anecdotally the most sensitive feature.
*"Boot"-shape or "L"-shaped glands.
**Shape may be similar to a hockey stick.
*Horizontal crypts = crypt long axis parallel to the muscularis mucosae.
*Crypt branching.
*Submucosal [[lipoma]] or pseudolipoma is often seen in associated with SSA.{{fact}}
*Perineuriomas are also seen in a small proportion of cases

Minimal extent criteria - number of abnormal crypts with the above features:
*''German Society of Pathology'' proposal: at least two abnormal crypts -- crypts do not have to be adjacent.<ref name=pmid23052370>{{Cite journal | last1 = Ensari | first1 = A. | last2 = Bilezikçi | first2 = B. | last3 = Carneiro | first3 = F. | last4 = Doğusoy | first4 = GB. | last5 = Driessen | first5 = A. | last6 = Dursun | first6 = A. | last7 = Flejou | first7 = JF. | last8 = Geboes | first8 = K. | last9 = de Hertogh | first9 = G. | title = Serrated polyps of the colon: how reproducible is their classification? | journal = Virchows Arch | volume = 461 | issue = 5 | pages = 495-504 | month = Nov | year = 2012 | doi = 10.1007/s00428-012-1319-7 | PMID = 23052370 }}</ref><ref name=pmid20617338>{{Cite journal | last1 = Aust | first1 = DE. | last2 = Baretton | first2 = GB. | title = Serrated polyps of the colon and rectum (hyperplastic polyps, sessile serrated adenomas, traditional serrated adenomas, and mixed polyps)-proposal for diagnostic criteria. | journal = Virchows Arch | volume = 457 | issue = 3 | pages = 291-7 | month = Sep | year = 2010 | doi = 10.1007/s00428-010-0945-1 | PMID = 20617338 }}</ref>
*An expert panel lead by ''Rex'' states that one unequivocally altered crypt should prompt calling SSA.<ref name=pmid22710576>{{Cite journal | last1 = Rex | first1 = DK. | last2 = Ahnen | first2 = DJ. | last3 = Baron | first3 = JA. | last4 = Batts | first4 = KP. | last5 = Burke | first5 = CA. | last6 = Burt | first6 = RW. | last7 = Goldblum | first7 = JR. | last8 = Guillem | first8 = JG. | last9 = Kahi | first9 = CJ. | title = Serrated lesions of the colorectum: review and recommendations from an expert panel. | journal = Am J Gastroenterol | volume = 107 | issue = 9 | pages = 1315-29; quiz 1314, 1330 | month = Sep | year = 2012 | doi = 10.1038/ajg.2012.161 | PMID = 22710576 }}</ref>
*The 4th edition of the WHO blue book requires - depending on what you read:
**Three adjacent crypts to be abnormal.<ref>URL: [http://surgpathcriteria.stanford.edu/gitumors/sessile-serrated-polyp-adenoma/ http://surgpathcriteria.stanford.edu/gitumors/sessile-serrated-polyp-adenoma/]. Accessed on: 26 September 2012.</ref>
**Two or three adjacent crypts to be abnormal.<ref name=pmid23052370/>
**The 5th edition is likely to make a single crypt sufficient for diagnosis.

===Dysplasia===
Sessile serrated adenomas typically lack "conventional" nuclear atypia, as seen in adenomata in the tubulovillous spectrum. They are nonetheless neoplastic lesions on account of architectural "dysplasia". Additionally, dysplasia may manifest in more than one way:
;Intestinal or "cytological" dysplasia: As seen in conventional adenomata, i.e. nuclear hyperchromasia and crowding. SSAs with nuclear atypia may be referred to as ''advanced sessile serrated adenomas''
;Serrated dysplasia: Round nuclei, prominent nucleoli and eosinophilic cytoplasm
;Minimal deviation dysplasia: As the name suggests, there is only minor architectural and cytological changes. These areas are associated with loss of MLH1 immunostaining.<ref name=pmid28752838>{{Cite journal | last1 = Liu | first1 = C. | last2 = Walker | first2 = NI. | last3 = Leggett | first3 = BA. | last4 = Whitehall | first4 = VL. | last5 = Bettington | first5 = ML. | last6 = Rosty | first6 = C. | title = Sessile serrated adenomas with dysplasia: morphological patterns and correlations with MLH1 immunohistochemistry. | journal = Mod Pathol | volume = 30 | issue = 12 | pages = 1728-1738 | month = 12 | year = 2017 | doi = 10.1038/modpathol.2017.92 | PMID = 28752838 }}</ref>

===DDx===
*[[Hyperplastic polyp]].
*[[Tubular adenoma of the gastrointestinal tract|Tubular adenoma]] - for ''SSA with dysplasia'', TAs often less than 1 cm (uncommon for SSAs).
*[[Mucosal prolapse]] - especially for left sided lesions and a background of [[diverticulosis]].<ref name=pmid23069257>{{Cite journal | last1 = Huang | first1 = CC. | last2 = Frankel | first2 = WL. | last3 = Doukides | first3 = T. | last4 = Zhou | first4 = XP. | last5 = Zhao | first5 = W. | last6 = Yearsley | first6 = MM. | title = Prolapse-related changes are a confounding factor in misdiagnosis of sessile serrated adenomas in the rectum. | journal = Hum Pathol | volume = 44 | issue = 4 | pages = 480-6 | month = Apr | year = 2013 | doi = 10.1016/j.humpath.2012.06.011 | PMID = 23069257 }}</ref>

===Images===
<gallery>
Image:Sessile_serrated_adenoma.jpg | SSA - low mag. (WC/Nephron)
Image:Sessile_serrated_adenoma2.jpg | SSA - intermed. mag. (WC/Nephron)
Image:Sessile_serrated_adenoma3.jpg | SSA - high mag. (WC/Nephron)
Image:Sessile_serrated_adenoma_3_low_mag.jpg | SSA - low mag. (WC/Nephron)
Image:Sessile_serrated_adenoma_3_intermed_mag.jpg | SSA - intermed. mag. (WC/Nephron)
Image:Sessile_serrated_adenoma_3_very_high_mag.jpg | SSA - very high mag. (WC/Nephron)
</gallery>

==IHC==
*[[Chromogranin A]] -ve; complete loss of staining.<ref>Vitkovski T, Jawale R, Goldblum J ''et al.'' Density of neuroendocrine cells can distinguish hyperplastic polyps from small sessile serrated polyps. Modern Pathology (USCAP Annual Meeting 2018, Abstract Number 865), URL: [https://www.nature.com/articles/modpathol20189.pdf https://www.nature.com/articles/modpathol20189.pdf]. Accessed on: 10 May 2018.</ref>
**Normal colorectal mucosa has scattered Chromogranin A-positive cells.
**[[Hyperplastic polyp]] has increased scattered Chromogranin A-positive cells.

==Sign out==
<pre>
POLYP, CECUM, POLYPECTOMY:
- SESSILE SERRATED ADENOMA.
-- NEGATIVE FOR DYSPLASIA.
</pre>

<pre>
POLYP, ASCENDING COLON, POLYPECTOMY:
- SESSILE SERRATED ADENOMA.
-- NEGATIVE FOR DYSPLASIA.
</pre>

<pre>
POLYP, HEPATIC FLEXURE OF COLON, POLYPECTOMY:
- SESSILE SERRATED ADENOMA.
-- NEGATIVE FOR DYSPLASIA.
</pre>

===Dysplasia present===
<pre>
Polyp, Ascending Colon, Polypectomy or Biopsy:
- Sessile serrated adenoma with low-grade dysplasia, see comment.

Comment:
Sessile serrated adenomas with dysplasia are considered to be advanced lesions that
have an increased propensity to transform to adenocarcinoma. Complete endoscopic removal is recommended. If complete endoscopic removal cannot be achieved, short-term re-endoscopy and biopsy, or surgical resection should be considered.
</pre>

===Block letters===
<pre>
POLYP, ASCENDING COLON, POLYPECTOMY:
- SESSILE SERRATED ADENOMA WITH DYSPLASIA.
</pre>

The above mirrors the Canadian consensus.<ref name=driman>{{cite journal | last1 = Driman | first1 = DK. | last2 = Marcus | first2 = VA. | last3 = Hilsden | first3 = RJ | last4 = Owen | first4 = DA |title=Pathologic reporting of colorectal polyps: pan-Canadian consensus guidelines |journal=Canadian Journal of Pathology |volume=4 |issue=3 |pages=81-90 |year=2012 |month= |pmid= |doi= |url=http://andrewjohnpublishing.com/images/cjp%204-3.pdf }}</ref>

====Sign out comment====
The Canadian consensus<ref name=driman/> also advocates use of a comment, like the following statement:
<pre>
Sessile serrated adenomas with dysplasia are considered to be advanced lesions that
have an increased propensity to transform to adenocarcinoma. Complete endoscopic removal
is recommended. If complete endoscopic removal cannot be achieved, short-term re-endoscopy
and biopsy, or surgical resection should be considered.
</pre>

===Micro===
The section shows a small polypoid fragment of colonic mucosa with a serrated epithelium that focally extends to the crypt base. Several dilated crypt bases are seen. One horizontal crypt and one boot-shaped crypt are present. The epithelium matures to the surface. A small amount of submucosa is present and contains a benign lymphoid aggregate.

==See also==
*[[Colorectal polyps]].

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

[[Category:Gastrointestinal pathology]]
[[Category:Diagnosis]]

Sessile serrated adenoma

2018-11-27T19:39:14Z

Mark: patterns of dysplasia; WHO 2019 likely to required just 1 crypt

{{ Infobox diagnosis
| Name = {{PAGENAME}}
| Image = sessile_serrated_adenoma_3_very_high_mag.jpg
| Width =
| Caption = SSA. [[H&E stain]].
| Synonyms = sessile serrated lesion, sessile serrated polyp, sessile serrated adenoma/polyp
| Micro = serrated epithelium, crypt base dilation, crypt branching, boot-shaped glands, horizontal glands
| Subtypes =
| LMDDx = [[hyperplastic polyp]], [[tubular adenoma]] when with dysplasia, [[mucosal prolapse]] for left sided lesions or background of [[diverticulosis]]
| Stains =
| IHC = Chromogranin A (completely) -ve
| EM =
| Molecular =
| IF =
| Gross =
| Grossing =
| Site = [[colon]] - usually cecum or ascending colon
| Assdx = [[colorectal adenocarcinoma]], [[hyperplastic polyp]]
| Syndromes = [[serrated polyposis syndrome]], [[MUTYH polyposis syndrome]]
| Clinicalhx =
| Signs =
| Symptoms =
| Prevalence = common
| Bloodwork =
| Rads =
| Endoscopy = flat, usually > 5 mm, mucinous cap
| Prognosis =
| Other =
| ClinDDx = normal, hyperplastic polyp, other [[intestinal polyps]]
}}
'''Sessile serrated adenoma''', abbreviated ''SSA'', is a premalignant [[GI polyps|polyp]] of the large bowel.

It is also known as '''sessile serrated polyp''' (abbreviated ''SSP''), '''sessile serrated lesion''' and '''sessile serrated adenoma/polyp''' (abbreviated ''SSA/P''). In the United Kingdom, this entity and is known as a sessile serrated lesion, a terminology that is likely to be adopted in the 2019/5th edition WHO Blue Book.

This lesion should not be confused with the ''[[traditional serrated adenoma]]'', previously known as ''[[serrated adenoma]]''.

==General==
*Colonic lesion.
*May be seen in the context of ''[[serrated polyposis syndrome]]''.
*Approximately 5% of SSAs have dysplasia.<ref name=pmid25724036>{{Cite journal | last1 = Yang | first1 = JF. | last2 = Tang | first2 = SJ. | last3 = Lash | first3 = RH. | last4 = Wu | first4 = R. | last5 = Yang | first5 = Q. | title = Anatomic distribution of sessile serrated adenoma/polyp with and without cytologic dysplasia. | journal = Arch Pathol Lab Med | volume = 139 | issue = 3 | pages = 388-93 | month = Mar | year = 2015 | doi = 10.5858/arpa.2013-0523-OA | PMID = 25724036 }}</ref>

Epidemiology:
*Thought to lead to colorectal cancer through a different pathway than most tumours in the left colon/rectum.
*''Microvesicular [[hyperplastic polyp]]s'' are hypothesized to be the the precursor of SSAs.<ref name=pmid21045813>{{Cite journal | last1 = Huang | first1 = CS. | last2 = Farraye | first2 = FA. | last3 = Yang | first3 = S. | last4 = O'Brien | first4 = MJ. | title = The clinical significance of serrated polyps. | journal = Am J Gastroenterol | volume = 106 | issue = 2 | pages = 229-40; quiz 241 | month = Feb | year = 2011 | doi = 10.1038/ajg.2010.429 | PMID = 21045813 }}</ref>

==Gross==
Features:<ref name=pmid22710576/>
*Flat lesions, usually > 5 mm.
*Typically have a "mucous cap" - present ~65% of the time; useful for identification.
*Border not well-demarcated.
*More common in the proximal colon.

Note:
*Sessile lesions over 1 cm are usually SSAs.<ref name=pmid22710576/>

Image:
*[http://www.nature.com/ajg/journal/v105/n12/fig_tab/ajg2010330f1.html SSA - endoscopy (nature.com)].<ref name=pmid21131934>{{cite journal |author=Rex DK, Hewett DG, Snover DC |title=Editorial: Detection targets for colonoscopy: from variable detection to validation |journal=Am. J. Gastroenterol. |volume=105 |issue=12 |pages=2665–9 |year=2010 |month=December |pmid=21131934 |doi=10.1038/ajg.2010.330 |url=}}</ref>

==Microscopic==
Features:
*Serrated epithelium at the surface and deep in the crypts.
**Saw-tooth appearance, epithelium has jagged appearing edge.
*Crypt dilation at base with serrations - '''key feature'''.
**Very common -- anecdotally the most sensitive feature.
*"Boot"-shape or "L"-shaped glands.
**Shape may be similar to a hockey stick.
*Horizontal crypts = crypt long axis parallel to the muscularis mucosae.
*Crypt branching.

Minimal extent criteria - number of abnormal crypts with the above features:
*''German Society of Pathology'' proposal: at least two abnormal crypts -- crypts do not have to be adjacent.<ref name=pmid23052370>{{Cite journal | last1 = Ensari | first1 = A. | last2 = Bilezikçi | first2 = B. | last3 = Carneiro | first3 = F. | last4 = Doğusoy | first4 = GB. | last5 = Driessen | first5 = A. | last6 = Dursun | first6 = A. | last7 = Flejou | first7 = JF. | last8 = Geboes | first8 = K. | last9 = de Hertogh | first9 = G. | title = Serrated polyps of the colon: how reproducible is their classification? | journal = Virchows Arch | volume = 461 | issue = 5 | pages = 495-504 | month = Nov | year = 2012 | doi = 10.1007/s00428-012-1319-7 | PMID = 23052370 }}</ref><ref name=pmid20617338>{{Cite journal | last1 = Aust | first1 = DE. | last2 = Baretton | first2 = GB. | title = Serrated polyps of the colon and rectum (hyperplastic polyps, sessile serrated adenomas, traditional serrated adenomas, and mixed polyps)-proposal for diagnostic criteria. | journal = Virchows Arch | volume = 457 | issue = 3 | pages = 291-7 | month = Sep | year = 2010 | doi = 10.1007/s00428-010-0945-1 | PMID = 20617338 }}</ref>
*An expert panel lead by ''Rex'' states that one unequivocally altered crypt should prompt calling SSA.<ref name=pmid22710576>{{Cite journal | last1 = Rex | first1 = DK. | last2 = Ahnen | first2 = DJ. | last3 = Baron | first3 = JA. | last4 = Batts | first4 = KP. | last5 = Burke | first5 = CA. | last6 = Burt | first6 = RW. | last7 = Goldblum | first7 = JR. | last8 = Guillem | first8 = JG. | last9 = Kahi | first9 = CJ. | title = Serrated lesions of the colorectum: review and recommendations from an expert panel. | journal = Am J Gastroenterol | volume = 107 | issue = 9 | pages = 1315-29; quiz 1314, 1330 | month = Sep | year = 2012 | doi = 10.1038/ajg.2012.161 | PMID = 22710576 }}</ref>
*The 4th edition of the WHO blue book requires - depending on what you read:
**Three adjacent crypts to be abnormal.<ref>URL: [http://surgpathcriteria.stanford.edu/gitumors/sessile-serrated-polyp-adenoma/ http://surgpathcriteria.stanford.edu/gitumors/sessile-serrated-polyp-adenoma/]. Accessed on: 26 September 2012.</ref>
**Two or three adjacent crypts to be abnormal.<ref name=pmid23052370/>
**The 5th edition is likely to make a single crypt sufficient for diagnosis.

*Submucosal [[lipoma]] or pseudolipoma is often seen in associated with SSA.{{fact}}
*Perineuriomas are also seen in a small proportion of cases

===Dysplasia===
Sessile serrated adenomas typically lack "conventional" nuclear atypia, as seen in adenomata in the tubulovillous spectrum. There are nonetheless neoplastic lesions based on architectural "dysplasia". Additionally, dysplasia may manifest in more than one way:
;Intestinal or "cytological" dysplasia: As seen in conventional adenomata, i.e. nuclear hyperchromasia and crowding. SSAs with nuclear atypia may be referred to as ''advanced sessile serrated adenomas''
;Serrated dysplasia: Round nuclei, prominent nucleoli and eosinophilic cytoplasm
;Minimal deviation dysplasia: As the name suggests, there is only minor architectural and cytological changes. These areas are associated with loss of MLH1 immunostaining.{{Cite journal | last1 = Liu | first1 = C. | last2 = Walker | first2 = NI. | last3 = Leggett | first3 = BA. | last4 = Whitehall | first4 = VL. | last5 = Bettington | first5 = ML. | last6 = Rosty | first6 = C. | title = Sessile serrated adenomas with dysplasia: morphological patterns and correlations with MLH1 immunohistochemistry. | journal = Mod Pathol | volume = 30 | issue = 12 | pages = 1728-1738 | month = 12 | year = 2017 | doi = 10.1038/modpathol.2017.92 | PMID = 28752838 }}

===DDx===
*[[Hyperplastic polyp]].
*[[Tubular adenoma of the gastrointestinal tract|Tubular adenoma]] - for ''SSA with dysplasia'', TAs often less than 1 cm (uncommon for SSAs).
*[[Mucosal prolapse]] - especially for left sided lesions and a background of [[diverticulosis]].<ref name=pmid23069257>{{Cite journal | last1 = Huang | first1 = CC. | last2 = Frankel | first2 = WL. | last3 = Doukides | first3 = T. | last4 = Zhou | first4 = XP. | last5 = Zhao | first5 = W. | last6 = Yearsley | first6 = MM. | title = Prolapse-related changes are a confounding factor in misdiagnosis of sessile serrated adenomas in the rectum. | journal = Hum Pathol | volume = 44 | issue = 4 | pages = 480-6 | month = Apr | year = 2013 | doi = 10.1016/j.humpath.2012.06.011 | PMID = 23069257 }}</ref>

===Images===
<gallery>
Image:Sessile_serrated_adenoma.jpg | SSA - low mag. (WC/Nephron)
Image:Sessile_serrated_adenoma2.jpg | SSA - intermed. mag. (WC/Nephron)
Image:Sessile_serrated_adenoma3.jpg | SSA - high mag. (WC/Nephron)
Image:Sessile_serrated_adenoma_3_low_mag.jpg | SSA - low mag. (WC/Nephron)
Image:Sessile_serrated_adenoma_3_intermed_mag.jpg | SSA - intermed. mag. (WC/Nephron)
Image:Sessile_serrated_adenoma_3_very_high_mag.jpg | SSA - very high mag. (WC/Nephron)
</gallery>

==IHC==
*[[Chromogranin A]] -ve; complete loss of staining.<ref>Vitkovski T, Jawale R, Goldblum J ''et al.'' Density of neuroendocrine cells can distinguish hyperplastic polyps from small sessile serrated polyps. Modern Pathology (USCAP Annual Meeting 2018, Abstract Number 865), URL: [https://www.nature.com/articles/modpathol20189.pdf https://www.nature.com/articles/modpathol20189.pdf]. Accessed on: 10 May 2018.</ref>
**Normal colorectal mucosa has scattered Chromogranin A-positive cells.
**[[Hyperplastic polyp]] has increased scattered Chromogranin A-positive cells.

==Sign out==
<pre>
POLYP, CECUM, POLYPECTOMY:
- SESSILE SERRATED ADENOMA.
-- NEGATIVE FOR DYSPLASIA.
</pre>

<pre>
POLYP, ASCENDING COLON, POLYPECTOMY:
- SESSILE SERRATED ADENOMA.
-- NEGATIVE FOR DYSPLASIA.
</pre>

<pre>
POLYP, HEPATIC FLEXURE OF COLON, POLYPECTOMY:
- SESSILE SERRATED ADENOMA.
-- NEGATIVE FOR DYSPLASIA.
</pre>

===Dysplasia present===
<pre>
Polyp, Ascending Colon, Polypectomy or Biopsy:
- Sessile serrated adenoma with low-grade dysplasia, see comment.

Comment:
Sessile serrated adenomas with dysplasia are considered to be advanced lesions that
have an increased propensity to transform to adenocarcinoma. Complete endoscopic removal is recommended. If complete endoscopic removal cannot be achieved, short-term re-endoscopy and biopsy, or surgical resection should be considered.
</pre>

===Block letters===
<pre>
POLYP, ASCENDING COLON, POLYPECTOMY:
- SESSILE SERRATED ADENOMA WITH DYSPLASIA.
</pre>

The above mirrors the Canadian consensus.<ref name=driman>{{cite journal | last1 = Driman | first1 = DK. | last2 = Marcus | first2 = VA. | last3 = Hilsden | first3 = RJ | last4 = Owen | first4 = DA |title=Pathologic reporting of colorectal polyps: pan-Canadian consensus guidelines |journal=Canadian Journal of Pathology |volume=4 |issue=3 |pages=81-90 |year=2012 |month= |pmid= |doi= |url=http://andrewjohnpublishing.com/images/cjp%204-3.pdf }}</ref>

====Sign out comment====
The Canadian consensus<ref name=driman/> also advocates use of a comment, like the following statement:
<pre>
Sessile serrated adenomas with dysplasia are considered to be advanced lesions that
have an increased propensity to transform to adenocarcinoma. Complete endoscopic removal
is recommended. If complete endoscopic removal cannot be achieved, short-term re-endoscopy
and biopsy, or surgical resection should be considered.
</pre>

===Micro===
The section shows a small polypoid fragment of colonic mucosa with a serrated epithelium that focally extends to the crypt base. Several dilated crypt bases are seen. One horizontal crypt and one boot-shaped crypt are present. The epithelium matures to the surface. A small amount of submucosa is present and contains a benign lymphoid aggregate.

==See also==
*[[Colorectal polyps]].

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

[[Category:Gastrointestinal pathology]]
[[Category:Diagnosis]]

Cytomegalovirus colitis

2018-09-30T17:17:09Z

Mark: more images

{{ Infobox diagnosis
| Name = {{PAGENAME}}
| Image = CMV colitis - high mag - cropped.jpg
| Width =
| Caption = CMV colitis. [[H&E stain]]. (WC)
| Synonyms =
| Micro = enlarged nucleus - classically in endothelial cells, +/-cytoplasmic inclusions
| Subtypes =
| LMDDx = [[infectious colitis]]
| Stains =
| IHC = CMV +ve
| EM =
| Molecular =
| IF =
| Gross =
| Grossing =
| Staging =
| Site = [[colon]]
| Assdx = +/-[[HIV]] infection
| Syndromes =
| Clinicalhx = +/-immunosuppression, +/-immune incompetent (e.g. transplant recipients)
| Signs =
| Symptoms =
| Prevalence = rare
| Bloodwork =
| Rads =
| Endoscopy =
| Prognosis =
| Other =
| ClinDDx =
| Tx =
}}
'''Cytomegalovirus colitis''' is a type of [[colitis]] caused by [[cytomegalovirus]].

==General==
*Uncommon.
*Immunosuppressed population at risk, e.g. transplant recipients, individuals with [[HIV]].
*Typically self-limited in immunocompetent patients.<ref name=pmid21226839>{{Cite journal | last1 = Kim | first1 = SH. | last2 = Kim | first2 = YS. | last3 = Kim | first3 = HW. | last4 = Yoon | first4 = HE. | last5 = Kim | first5 = HK. | last6 = Kim | first6 = YO. | last7 = Yoon | first7 = SA. | title = A case of cytomegalovirus colitis in an immunocompetent hemodialysis patient. | journal = Hemodial Int | volume = 15 | issue = 2 | pages = 297-300 | month = Apr | year = 2011 | doi = 10.1111/j.1542-4758.2010.00520.x | PMID = 21226839 }}</ref>

==Microscopic==
Features:
*Enlarged nucleus - typically in endothelial cells.
**Nucleus classically has peripheral clearing - described as "owl's eye".
**Epithelial cells and lamina propria cells may also be affected.<ref>URL: [http://www.annalsgastro.gr/index.php/annalsgastro/article/view/579 http://www.annalsgastro.gr/index.php/annalsgastro/article/view/579]. Accessed on: 8 February 2016.</ref>

DDx:
*[[Infectious colitis]] without a distinctive morphology.
*CMV colitis superimposed on [[inflammatory bowel disease]].

===Images===
<gallery>
Image:CMV_colitis_-_intermed_mag.jpg | CMV colitis - intermed. mag. (WC/Nephron)
Image:CMV_colitis_-_high_mag.jpg | CMV colitis - high mag. (WC/Nephron)
Image:CMV colitis vessel high mag.jpg | CMV nuclear inclusions in submucosal vessel - high mag. (WC/MO)
Image:CMV colitis submucosa high mag.jpg | CMV nuclear inclusions in submucosa of colon - high mag. (WC/MO)
</gallery>
www:
*[http://www.flickr.com/photos/lunarcaustic/4615988256/ CMV colitis (flickr.com/lunar caustic)].
*[http://www.flickr.com/photos/lunarcaustic/4615988164/ CMV colitis (flickr.com/lunar caustic)]
*[http://alf3.urz.unibas.ch/pathopic/e/getpic-fra.cfm?id=000500 CMV colitis (unibas.ch)].

==IHC==
*CMV +ve.
**Increases the [[sensitivity]] (compared to H&E alone).<ref name=pmid9170416>{{Cite journal | last1 = Beaugerie | first1 = L. | last2 = Cywiner-Golenzer | first2 = C. | last3 = Monfort | first3 = L. | last4 = Girard | first4 = PM. | last5 = Carbonnel | first5 = F. | last6 = Ngô | first6 = Y. | last7 = Cosnes | first7 = J. | last8 = Rozenbaum | first8 = W. | last9 = Nicolas | first9 = JC. | title = Definition and diagnosis of cytomegalovirus colitis in patients infected by human immunodeficiency virus. | journal = J Acquir Immune Defic Syndr Hum Retrovirol | volume = 14 | issue = 5 | pages = 423-9 | month = Apr | year = 1997 | doi = | PMID = 9170416 }}</ref>

Others:
*HSV-1.
*HSV-2.
*VZV.
*[[EBV]].

===Images===
*[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4354615/figure/f2-ijgm-8-097/ CMV colitis - IHC (nih.gov)].<ref name=pmid25767404>{{Cite journal | last1 = Harano | first1 = Y. | last2 = Kotajima | first2 = L. | last3 = Arioka | first3 = H. | title = Case of cytomegalovirus colitis in an immunocompetent patient: a rare cause of abdominal pain and diarrhea in the elderly. | journal = Int J Gen Med | volume = 8 | issue = | pages = 97-100 | month = | year = 2015 | doi = 10.2147/IJGM.S63771 | PMID = 25767404 }}</ref>

==See also==
*[[Colitis]].
*[[Colon]].

==References==
{{Reflist|1}}

[[Category:Diagnosis]]
[[Category:Colon]]