Difference between revisions of "Urothelium"

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Urothelium (view source)

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=====Urethra in males=====
=====Urethra in males=====
{{Main|Urethra}}
*Pre-prostatic urethra - transitional epithelium.
*Pre-prostatic urethra - transitional epithelium.
*[[Prostate gland|Prostatic]] urethra - transitional epithelium.
*[[Prostate gland|Prostatic]] urethra - transitional epithelium.
**Cancer arising at this site is ''[[prostatic urothelial carcinoma]]''.
*Membranous urethra (from apex of prostate to bulb of penis (bulb of the corpus spongiosusm)) - pseudostratified columnar epithelium.
*Membranous urethra (from apex of prostate to bulb of penis (bulb of the corpus spongiosusm)) - pseudostratified columnar epithelium.
*Spongy urethra - pseudostratified columnar epithelium (proximal) & stratified squamous (distal).
*Spongy urethra - pseudostratified columnar epithelium (proximal) & stratified squamous (distal).
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*Should '''not''' have a papillary architecture -- if it does it is likely [[cancer]]!
*Should '''not''' have a papillary architecture -- if it does it is likely [[cancer]]!
**If it is 'papillary' -- it must have fibrovascular cores.
**If it is 'papillary' -- it must have fibrovascular cores.
===IHC===
*Rare superficial [[CK20]] staining.
====Image====
<gallery>
Image: Benign urothelium - CK20 -- high mag.jpg | Benign urothelium - CK20 - high mag. (WC)
</gallery>


===Sign out===
===Sign out===
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| -
| -
|-
|-
| '''Urothelial dysplasia'''
| '''[[Urothelial dysplasia]]'''
| moderate (3x)
| moderate (3x)
| small, some multiple
| small, some multiple
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| -
| -
|-
|-
| '''UCC in situ'''
| '''[[Urothelial carcinoma in situ]]'''
| '''signif. (4-5x)'''
| '''signif. (4-5x)'''
| +/-large
| +/-large
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| -
| -
|-
|-
| '''Invasive UCC'''
| '''[[Urothelial carcinoma|Invasive UCC]]'''
| signif. (4-5X)
| signif. (4-5X)
| +/-large
| +/-large
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=Flat urothelial lesions=
=Flat urothelial lesions=
==Overview==
==Overview==
Several different benign & pre-malignant diagnoses can be made:
Several different benign & pre-malignant diagnoses can be made.
*Reactive atypia.
 
The World Health Organization classification is:<ref name=pmid19762067>{{Cite journal  | last1 = Hodges | first1 = KB. | last2 = Lopez-Beltran | first2 = A. | last3 = Davidson | first3 = DD. | last4 = Montironi | first4 = R. | last5 = Cheng | first5 = L. | title = Urothelial dysplasia and other flat lesions of the urinary bladder: clinicopathologic and molecular features. | journal = Hum Pathol | volume = 41 | issue = 2 | pages = 155-62 | month = Feb | year = 2010 | doi = 10.1016/j.humpath.2009.07.002 | PMID = 19762067 }}</ref>
*Reactive urothelial atypia.
*Flat urothelial hyperplasia.
*Flat urothelial hyperplasia.
*Urothelial dysplasia.
*Urothelial atypia of unknown significance.
*Urothelial carcinoma in situ.
*[[Urothelial dysplasia]] (low-grade dysplasia).
*Urothelial carcinoma in situ (high-grade dysplasia).
*Invasive urothelial carcinoma.
*Invasive urothelial carcinoma.


==Urothelial carcinoma in situ==
==Mild urothelial atypia in normal urothelium==
*Abbreviated ''CIS''.
===General===
===General===
*Lack papillae.
*May be confused with [[urothelial carcinoma in situ]].<ref name=Ref_Amin2-57>{{Ref Amin|2-57}}</ref>
*Uncommon.
*Considered to be [[normal urothelium]].


===Microscopic===
===Microscopic===
Features:
Features:<ref name=Ref_Amin2-57>{{Ref Amin|2-57}}</ref>
*Nuclear changes '''key feature'''.
*Umbrella cells have:
**Enlargement of nuclei (often 4-5x the size of stromal lymphocytes) -- diagnostic.<ref name=Ref_GUP161>{{Ref GUP|161}}</ref>
**Mild nuclear enlargement ~3-4x lymphocyte.
***Normal urothelium approx. 2x the size of stromal lymphocytes.
**Round/regular nuclear membranes.
**Nuclear pleomorphism - marked variation in size of nuclei.
**+/-Multi-nucleation.
*+/-Disordered arrangement/crowding of cells.
**Focally clear cytoplasm with cobwebs.
**In normal urothelium the cell line-up on the basement membrane.
***Clear cytoplasm with eosinophilic reticulations.
*Umbrella cells often absent.
*+/-Inflammation.
*+/-Mitoses present.
*No mitotic activity.
*+/-Enlarged nucleoli.
 
DDx:<ref>URL: [http://pathology.jhu.edu/bladder/definitions.cfm http://pathology.jhu.edu/bladder/definitions.cfm]. Accessed on: 8 January 2014.</ref>
*[[Urothelial carcinoma in situ]].
*[[Urothelial dysplasia]].


Note:
====Images====
*The urothelium may be "depleted", i.e. exist only of rare large cells on the basement membrane.
<gallery>
**This is known as ''clinging urothelial carcinoma in situ''.<ref>{{Ref Amin|2-55}}</ref>
Image: Benign urothelium with large superficial cells -- intermed mag.jpg | Benign large superf. cells - intermed. mag. (WC)
Image: Benign urothelium with large superficial cells -- high mag.jpg | Benign large superf. cells - high mag. (WC)
Image: Benign urothelium with large superficial cells -- very high mag.jpg | Benign large superf. cells - very high mag. (WC) 
</gallery>


===IHC===
===IHC===
Features:<ref>{{Cite journal  | last1 = Lopez-Beltran | first1 = A. | last2 = Jimenez | first2 = RE. | last3 = Montironi | first3 = R. | last4 = Patriarca | first4 = C. | last5 = Blanca | first5 = A. | last6 = Menendez | first6 = CL. | last7 = Algaba | first7 = F. | last8 = Cheng | first8 = L. | title = Flat urothelial carcinoma in situ of the bladder with glandular differentiation. | journal = Hum Pathol | volume = 42 | issue = 11 | pages = 1653-9 | month = Nov | year = 2011 | doi = 10.1016/j.humpath.2010.12.024 | PMID = 21531007 }}</ref>
*Ki-67 low.
*p53 +ve.
*p53 -ve.
*Ki-67 high.
 
Benign urothelium vs. CIS:<ref name=pmid16932015>{{Cite journal  | last1 = Yin | first1 = H. | last2 = He | first2 = Q. | last3 = Li | first3 = T. | last4 = Leong | first4 = AS. | title = Cytokeratin 20 and Ki-67 to distinguish carcinoma in situ from flat non-neoplastic urothelium. | journal = Appl Immunohistochem Mol Morphol | volume = 14 | issue = 3 | pages = 260-5 | month = Sep | year = 2006 | doi =  | PMID = 16932015 }}</ref>
*CK20 +ve in deep cells (23/26 cases).
**Normal urothelium -- only the umbrella cells.
*Ki-67 ~50% of cells - deep and superficial.
**Normal ~10% of cells, confined to basal aspect.


===Sign out===
===Sign out===
<pre>
<pre>
URINARY BLADDER LESION ("TUMOUR"), TRANSURETHRAL RESECTION URINARY BLADDER TUMOUR (TURBT):  
URINARY BLADDER, TRANSURETHRAL BIOPSY:
- UROTHELIAL CARCINOMA IN SITU.
- UROTHELIAL MUCOSA WITH MILD CHRONIC INFLAMMATION.
- MUSCULARIS PROPRIA PRESENT.
- NO EVIDENCE OF MALIGNANCY.
 
COMMENT:
Levels were cut and show large benign umbrella cells.
</pre>
</pre>
====Micro====
The sections show small fragments of urothelial mucosa with enlarged benign superficial epithelial cells.  The lamina propria has a mild lymphocytic infiltrate.  No papillary structures are identified.  There is no significant nuclear atypia.  Superficial small blood vessels appear congested.
==Urothelial dysplasia==
*[[AKA]] ''low-grade (urothelial) dysplasia''.
{{Main|Urothelial dysplasia}}
==Urothelial carcinoma in situ==
*Abbreviated ''CIS''.
*[[AKA]] ''high-grade (urothelial) dysplasia''.
{{Main|Urothelial carcinoma in situ}}


==Urothelial cell carcinoma==
==Urothelial cell carcinoma==
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*Abbreviated ''UCC''.
*Abbreviated ''UCC''.
*[[AKA]] ''urothelial carcinoma''.
*[[AKA]] ''urothelial carcinoma''.
 
{{Main|Urothelial carcinoma}}
===General===
*These lesions lack papillae and are typical flat.
*Clinically, it may not be possible to differentiate renal pelvis urothelial carcinoma and [[renal cell carcinoma]].
 
===Microscopic===
Features:
*Nuclear pleomorphism - '''key feature'''.
**Compare nuclei to one another.
*Increased N/C ratio.
*Lack of maturation to surface (important).
 
*Cells become dyscohesive.
**Mostly useless in my experience.
 
Invasion vs. in situ:
Useful features - present in invasion:<ref>Sternberg, SE. Histology for Pathologists. P.2047.</ref>
*Thin-walled vessels.
*Stromal reaction (hypercellularity).
*Retraction artefact around the tumour cell nests.
 
Note:
*The presence/absence of muscle should be commented on in biopsy specimens.
*Adipose tissue may be seen in the lamina propria; tumour adjacent to adipose tissue on a biopsy does '''not''' imply invasion deep to the muscularis propria.<ref name=pmid7879346>{{Cite journal  | last1 = Bochner | first1 = BH. | last2 = Nichols | first2 = PW. | last3 = Skinner | first3 = DG. | title = Overstaging of transitional cell carcinoma: clinical significance of lamina propria fat within the urinary bladder. | journal = Urology | volume = 45 | issue = 3 | pages = 528-31 | month = Mar | year = 1995 | doi = 10.1016/S0090-4295(99)80030-2 | PMID = 7879346 }}</ref>
 
====Staging====
*T1 - lamina propria.
**Several subdivisions of T1 exist:
***T1a - superficial or in muscularis mucosae.
***T1b - beyond muscularis mucosae - into submucosa.
*T2 - muscularis propria.
 
====Subtypes of urothelial carcinoma====
There are numerous subtypes:<ref>URL: [http://www.nature.com/modpathol/journal/v22/n2s/full/modpathol200926a.html http://www.nature.com/modpathol/journal/v22/n2s/full/modpathol200926a.html]. Accessed on: 19 August 2011.</ref>
*Squamous differentiation.
*Clear cell.
*Plasmacytoid.
*Micropapillary.
**Small nests (< ~10 cells/nest).
*Sarcomatoid.
**Images: [http://path.upmc.edu/cases/case615.html UCC with sarcomatoid differentiation (upmc.edu)].
*Many others...
 
Benign patterns - mnemonic ''Much GIN'':
*'''M'''icrocystic.
*Small tubular/'''g'''landular.
*'''I'''nverted.
*'''N'''ested.
 
=====Plasmacytoid urothelial cell carcinoma=====
Features:
*Abundant gray cytoplasm, eccentric nucleus.
 
Images:
*[http://path.upmc.edu/cases/case267.html Plasmacytoid UCC - several images (upmc.edu)].
 
=====Nested urothelial cell carcinoma=====
*[[AKA]] ''nested variant urothelial cell carcinoma''.
 
Features:<ref name=pmid2712189>{{Cite journal  | last1 = Talbert | first1 = ML. | last2 = Young | first2 = RH. | title = Carcinomas of the urinary bladder with deceptively benign-appearing foci. A report of three cases. | journal = Am J Surg Pathol | volume = 13 | issue = 5 | pages = 374-81 | month = May | year = 1989 | doi =  | PMID = 2712189 }}</ref>
*High density of well-circumscribed nests.
*Mild-to-moderate nuclear atypia.
*+/-Foci of unequivocal conventional urothelial carcinoma.
**Focally solid or gland fusion.
**Moderate-to-severe nuclear atypia +/- abundant mitoses.
*+/-Extension into the muscularis propria.
 
DDx:
*[[von Brunn nests]].
 
====Images====
<gallery>
Image:Nested_variant_of_urothelial_carcinoma_-_intermed_mag.jpg | Nested variant of urothelial carcinoma - intermed. mag. (WC/Nephron)
Image:Nested_variant_of_urothelial_carcinoma_-_high_mag.jpg | Nested variant of urothelial carcinoma - high mag. (WC/Nephron)
Image:Nested_variant_of_urothelial_carcinoma_-_very_high_mag.jpg | Nested variant of urothelial carcinoma - very high mag. (WC/Nephron)
</gallery>
www:
*[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3282447/figure/F2/ Several images of NUCC (nih.gov)].<ref name=pmid22355497>{{Cite journal  | last1 = Terada | first1 = T. | title = Nested variant of urothelial carcinoma of the urinary bladder. | journal = Rare Tumors | volume = 3 | issue = 4 | pages = e42 | month = Oct | year = 2011 | doi = 10.4081/rt.2011.e42 | PMID = 22355497 | PMC = 3282447 }}</ref>
 
===[[IHC]]===
Features:
*CK7 +ve CK20 +ve.
**CK20 may be negative.
 
UCC vs. Prostate:
*UCC: p63+, PSA-, PSAP-, CK7+, CK20+.
*Prostate: p63-, PSA+, PSAP+, CK7-, CK20-.
 
UCC vs. RCC:
*UCC: p63+.<ref>{{Cite journal  | last1 = Langner | first1 = C. | last2 = Ratschek | first2 = M. | last3 = Tsybrovskyy | first3 = O. | last4 = Schips | first4 = L. | last5 = Zigeuner | first5 = R. | title = P63 immunoreactivity distinguishes upper urinary tract transitional-cell carcinoma and renal-cell carcinoma even in poorly differentiated tumors. | journal = J Histochem Cytochem | volume = 51 | issue = 8 | pages = 1097-9 | month = Aug | year = 2003 | doi =  | PMID = 12871991 }}
</ref>
 
===Molecular===
Not used for diagnosis.
 
Changes:
*9p deletion -- site of CDKN2A<ref name=omim600160>{{OMIM|600160}}</ref> (AKA p16).
*17p deletion -- site of PT53 (AKA p53).
 
===Sign out===
 
====High grade UCC====
<pre>
URINARY BLADDER LESION ("TUMOUR"), TRANSURETHRAL RESECTION URINARY BLADDER TUMOUR (TURBT):
- INVASIVE HIGH-GRADE PAPILLARY UROTHELIAL CARCINOMA WITH SQUAMOUS DIFFERENTIATION AT LEAST INTO MUSCULARIS PROPRIA.
- LYMPHOVASCULAR INVASION PRESENT.
</pre>
 
====Nested variant====
<pre>
URINARY BLADDER LESION ("TUMOUR"), TRANSURETHRAL RESECTION OF BLADDER TUMOUR (TURBT):
- INVASIVE LOW-GRADE UROTHELIAL CARCINOMA, NESTED VARIANT.
- TUMOUR PRESENT AT EDGE OF TISSUE.
- NO MUSCULARIS PROPRIA IDENTIFIED.
</pre>


=Papillary urothelial lesions=
=Papillary urothelial lesions=
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==Urothelial papilloma==
==Urothelial papilloma==
===General===
{{Main|Urothelial papilloma}}
*Very rare diagnosed.
**If the person has a history of a low grade papillary urothelial carcinoma... it is a low grade papillary urothelial carcinoma.
**These cases are a consensus diagnosis, i.e. you show it to a colleague... if they agree you can call it.
 
===Microscopic===
Features:<ref name=Ref_WMSP310>{{Ref WMSP|310}}</ref>
*Papillary fronds.
*Minimal branching or fusion.
*Cytological features of normal urothelium.
**Normal urothelium approx. 2x the size of stromal lymphocytes.<ref name=Ref_GUP161>{{Ref GUP|161}}</ref>
*No mitoses.
*Thickness < 7 cells.{{fact}}
 
DDx:
*[[Low grade papillary urothelial carcinoma]].
*[[PUNLMP]].


==Inverted urothelial papilloma==
==Inverted urothelial papilloma==
*[[AKA]] ''[[inverted papilloma]]''.
*[[AKA]] ''[[inverted papilloma]]''.
{{Main|Inverted urothelial papilloma}}


===General===
*May be confused with papillary urothelial carcinoma with an inverted growth pattern.
===Microscopic===
Features:
*Like papillomas... but grow downward.<ref name=Ref_WMSP310>{{Ref WMSP|310}}</ref>
*According to THvdK,<ref>THvdK. 21 June 2010.</ref> ''inverted papillomas'' '''never''' have an exophytic component; if an exophytic component is present it is urothelial carcinoma.  This is disputed by one paper from Mexico that examines two cases.<ref name=pmid19433293>{{cite journal |author=Albores-Saavedra J, Chable-Montero F, Hernández-Rodríguez OX, Montante-Montes de Oca D, Angeles-Angeles A |title=Inverted urothelial papilloma of the urinary bladder with focal papillary pattern: a previously undescribed feature |journal=Ann Diagn Pathol |volume=13 |issue=3 |pages=158–61 |year=2009 |month=June |pmid=19433293 |doi=10.1016/j.anndiagpath.2009.02.009 |url=}}</ref>
*Nests have peripheral palisading of nuclei - '''important'''.
DDx:
*[[Low grade papillary urothelial carcinoma]] with an inverted growth pattern.
====Images====
<gallery>
Image:Inverted_papilloma_high_mag.jpg | Inverted papilloma - high mag. (WC/Nephron)
Image:Inverted_papilloma_intermed_mag.jpg | Inverted papilloma - intermed. mag. (WC/Nephron)
</gallery>
==Papillary urothelial neoplasm of low malignant potential==
==Papillary urothelial neoplasm of low malignant potential==
*Abbreviated ''PUNLMP''.
*Abbreviated ''PUNLMP''.
**This is pronounced ''pun-lump''.
{{Main|Papillary urothelial neoplasm of low malignant potential}}


===General===
==Low-grade papillary urothelial carcinoma==
*Uncommon: prevalence ~ 0-3.5%.<ref name=pmid19346063>{{cite journal |author=May M, Brookman-Amissah S, Roigas J, ''et al.'' |title=Prognostic Accuracy of Individual Uropathologists in Noninvasive Urinary Bladder Carcinoma: A Multicentre Study Comparing the 1973 and 2004 World Health Organisation Classifications |journal=Eur. Urol. |volume= 57|issue= 5|pages= 850|year=2009 |month=March |pmid=19346063 |doi=10.1016/j.eururo.2009.03.052 |url=}}</ref>
*PUNLMP vs. [[low grade papillary urothelial carcinoma]] has a poor inter-rater reliability.<ref name=pmid17095142>{{cite journal |author=MacLennan GT, Kirkali Z, Cheng L |title=Histologic grading of noninvasive papillary urothelial neoplasms |journal=Eur. Urol. |volume=51 |issue=4 |pages=889–97; discussion 897–8 |year=2007 |month=April |pmid=17095142 |doi=10.1016/j.eururo.2006.10.037 |url=}}</ref>
 
Treatment:
*Excision and on-going follow-up - like non-invasive [[low grade papillary urothelial carcinoma]] (LGPUC).<ref name=pmid16697785>{{cite journal |author=Jones TD, Cheng L |title=Papillary urothelial neoplasm of low malignant potential: evolving terminology and concepts |journal=J. Urol. |volume=175 |issue=6 |pages=1995–2003 |year=2006 |month=June |pmid=16697785 |doi=10.1016/S0022-5347(06)00267-9 |url=}}</ref>
**Cheng ''et al.'' have advocated abandoning the term as they are treated like [[LGPUC]]s.<ref name=pmid22542126>{{Cite journal  | last1 = Cheng | first1 = L. | last2 = Maclennan | first2 = GT. | last3 = Lopez-Beltran | first3 = A. | title = Histologic grading of urothelial carcinoma: a reappraisal. | journal = Hum Pathol | volume = 43 | issue = 12 | pages = 2097-108 | month = Dec | year = 2012 | doi = 10.1016/j.humpath.2012.01.008 | PMID = 22542126 }}</ref>
 
===Microscopic===
Features:<ref name=Ref_WMSP310>{{Ref WMSP|310}}</ref>
*Rare fused papillae.
*Infrequent mitoses.
*Nuclei larger than papilloma - but monotonous.<ref name=Ref_GUP170>{{Ref GUP|170}}</ref>
 
DDx:
*[[Low grade papillary urothelial carcinoma]].
*[[Urothelial papilloma|Papilloma]].
 
====Images====
<gallery>
Image:Punlmp1.jpg | PUNLMP - low mag. (WC/Nephron)
Image:Punlmp2.jpg | PUNLMP - high mag. (WC/Nephron)
</gallery>
==Low grade papillary urothelial carcinoma==
*Abbreviated ''LGPUC''.<ref name=pmid22857755>{{Cite journal  | last1 = Watts | first1 = KE. | last2 = Montironi | first2 = R. | last3 = Mazzucchelli | first3 = R. | last4 = van der Kwast | first4 = T. | last5 = Osunkoya | first5 = AO. | last6 = Stephenson | first6 = AJ. | last7 = Hansel | first7 = DE. | title = Clinicopathologic characteristics of 23 cases of invasive low-grade papillary urothelial carcinoma. | journal = Urology | volume = 80 | issue = 2 | pages = 361-6 | month = Aug | year = 2012 | doi = 10.1016/j.urology.2012.04.010 | PMID = 22857755 }}</ref>
*Abbreviated ''LGPUC''.<ref name=pmid22857755>{{Cite journal  | last1 = Watts | first1 = KE. | last2 = Montironi | first2 = R. | last3 = Mazzucchelli | first3 = R. | last4 = van der Kwast | first4 = T. | last5 = Osunkoya | first5 = AO. | last6 = Stephenson | first6 = AJ. | last7 = Hansel | first7 = DE. | title = Clinicopathologic characteristics of 23 cases of invasive low-grade papillary urothelial carcinoma. | journal = Urology | volume = 80 | issue = 2 | pages = 361-6 | month = Aug | year = 2012 | doi = 10.1016/j.urology.2012.04.010 | PMID = 22857755 }}</ref>
*[[AKA]] ''low grade papillary urothelial cell carcinoma''.
*[[AKA]] ''low-grade papillary urothelial cell carcinoma''.
{{Main|Low-grade papillary urothelial carcinoma}}


===General===
==High-grade papillary urothelial carcinoma==
*Very common.
*Very good prognosis - if it is non-invasive.
 
===Microscopic===
Features:<ref name=Ref_WMSP310>{{Ref WMSP|310}}</ref>
*Fused papillae.
*Papillae branch.
*Larger nuclei than PUNLMPs.
*+/-Invasion into the lamina propria.
 
Note:
*The presence/absence of muscle should be commented on in biopsy specimens.
*Adipose tissue may be seen in the lamina propria; tumour adjacent to adipose tissue on a biopsy does '''not''' imply invasion deep to the muscularis propria.<ref name=pmid7879346>{{Cite journal  | last1 = Bochner | first1 = BH. | last2 = Nichols | first2 = PW. | last3 = Skinner | first3 = DG. | title = Overstaging of transitional cell carcinoma: clinical significance of lamina propria fat within the urinary bladder. | journal = Urology | volume = 45 | issue = 3 | pages = 528-31 | month = Mar | year = 1995 | doi = 10.1016/S0090-4295(99)80030-2 | PMID = 7879346 }}</ref>
 
DDx:
*[[PUNLMP]].
*[[High grade papillary urothelial carcinoma]].
**Often under-diagnosed (~15% in one series) when reassessed by experts.<ref name=pmid20670136>{{Cite journal  | last1 = Miyamoto | first1 = H. | last2 = Brimo | first2 = F. | last3 = Schultz | first3 = L. | last4 = Ye | first4 = H. | last5 = Miller | first5 = JS. | last6 = Fajardo | first6 = DA. | last7 = Lee | first7 = TK. | last8 = Epstein | first8 = JI. | last9 = Netto | first9 = GJ. | title = Low-grade papillary urothelial carcinoma of the urinary bladder: a clinicopathologic analysis of a post-World Health Organization/International Society of Urological Pathology classification cohort from a single academic center. | journal = Arch Pathol Lab Med | volume = 134 | issue = 8 | pages = 1160-3 | month = Aug | year = 2010 | doi = 10.1043/2009-0403-OA.1 | PMID = 20670136 }}</ref>
**The three most predictive features of high-grade are ''architectural complexity'', ''nuclear size variation'', and ''absence of umbrella cells''.<ref name=pmid21980608>{{Cite journal  | last1 = Isfoss | first1 = BL. | last2 = Majak | first2 = B. | last3 = Busch | first3 = C. | last4 = Braathen | first4 = GJ. | title = Simplification of grading papillary urothelial neoplasia using a reduced set of diagnostic features. | journal = Anal Quant Cytol Histol | volume = 33 | issue = 2 | pages = 68-74 | month = Apr | year = 2011 | doi =  | PMID = 21980608 }}</ref>
*[[Inverted urothelial papilloma]] - often have peripheral palisading.
*[[Urothelial papilloma]].
 
===Sign out===
<pre>
URINARY BLADDER LESION ("TUMOUR"), TRANSURETHRAL RESECTION OF BLADDER TUMOUR (TURBT):
- LOW-GRADE PAPILLARY UROTHELIAL CARCINOMA.
- NEGATIVE FOR LAMINA PROPRIA INVASION.
- NO MUSCULARIS PROPRIA IDENTIFIED.
</pre>
 
<pre>
URINARY BLADDER LESION ("TUMOUR"), TRANSURETHRAL RESECTION OF BLADDER TUMOUR (TURBT):
- LOW-GRADE PAPILLARY UROTHELIAL CARCINOMA.
- NEGATIVE FOR LAMINA PROPRIA INVASION.
- MUSCULARIS PROPRIA PRESENT.
</pre>
 
==High grade papillary urothelial carcinoma==
*Abbreviated ''HGPUC''.
*Abbreviated ''HGPUC''.
*[[AKA]] ''high grade papillary urothelial cell carcinoma'', abbreviated ''HGPUCC''.  
*[[AKA]] ''high-grade papillary urothelial cell carcinoma'', abbreviated ''HGPUCC''.
{{Main|High-grade papillary urothelial carcinoma}}


===General===
==Papillary urothelial hyperplasia==
*Aggressive.
*[[AKA]] ''papillary hyperplasia''.
*[[AKA]] ''reactive papillary hyperplasia''.
{{Main|Papillary urothelial hyperplasia}}


===Microscopic===
=Benign urothelial lesions=
Features:<ref name=Ref_WMSP310>{{Ref WMSP|310}}</ref>
===Cystitis===
*"High grade nuclear features":
*Inflammation of the [[urinary bladder]].
**Nuclear pleomorphism - often 4-5x the size of stromal lymphocytes.<ref name=Ref_GUP161>{{Ref GUP|161}}</ref>
*Comes in many forms (see below).
*Architectural complexity.
*Typically a [[clinical diagnosis]] under the more general term [[urinary tract infection]].
**Fused papillary common.
**Papillae branch.
*Mitoses common.
*+/-Invasion into the lamina propria.


Note:
Note:
*The presence/absence of muscle should be commented on in biopsy specimens.
*So called "[[giant cell cystitis]]" is dealt with separately; it is a benign non-pathologic change that may or may not be associated with inflammation.<ref name=Ref_Amin2_6>{{Ref Amin|2:6}}</ref>
*Adipose tissue may be seen in the lamina propria; tumour adjacent to adipose tissue on a biopsy does '''not''' imply invasion deep to the muscularis propria.<ref name=pmid7879346>{{Cite journal  | last1 = Bochner | first1 = BH. | last2 = Nichols | first2 = PW. | last3 = Skinner | first3 = DG. | title = Overstaging of transitional cell carcinoma: clinical significance of lamina propria fat within the urinary bladder. | journal = Urology | volume = 45 | issue = 3 | pages = 528-31 | month = Mar | year = 1995 | doi = 10.1016/S0090-4295(99)80030-2 | PMID = 7879346 }}</ref>
 
DDx:
*[[Low grade papillary urothelial carcinoma]].
 
===Sign out===
<pre>
URINARY BLADDER LESION ("TUMOUR"), TRANSURETHRAL RESECTION URINARY BLADDER TUMOUR (TURBT):
- INVASIVE HIGH-GRADE PAPILLARY UROTHELIAL CARCINOMA WITH LAMINA PROPRIA INVASION.
- MUSCULARIS PROPRIA NEGATIVE FOR INVASIVE MALIGNANCY.
- NEGATIVE FOR LYMPHOVASCULAR INVASION.
</pre>
 
====Invasion into the muscularis propria====
<pre>
URINARY BLADDER LESION ("TUMOUR"), TRANSURETHRAL RESECTION URINARY BLADDER TUMOUR (TURBT):
- INVASIVE HIGH-GRADE PAPILLARY UROTHELIAL CARCINOMA AT LEAST INTO MUSCULARIS PROPRIA.
- LYMPHOVASCULAR INVASION PRESENT.
</pre>
 
====Low-grade versus high-grade====
<pre>
URINARY BLADDER LESION ("TUMOUR"), TRANSURETHRAL RESECTION URINARY BLADDER TUMOUR (TURBT):
- HIGH-GRADE PAPILLARY UROTHELIAL CARCINOMA, SEE COMMENT.
- NEGATIVE FOR LAMINA PROPRIA INVASION.
- NO MUSCULARIS PROPRIA PRESENT.
 
COMMENT:
The sections show papillary branching, papillary fusion and scattered large cells (~4-5 a
resting lymphocyte). Atypical for a high-grade lesion is that mitotic activity is scarce
and prominent nucleoli are not present.
</pre>
 
=====Micro=====
The sections show a small fragment of urothelial mucosa with two papillary structures,
enlarged nuclei (~3-4x resting lymphocyte) and moderate nuclear size variation.  Mitotic activity is seen focally. Umbrella
cells are seen only focally.


A mild lymphocyte-predominant inflammatory infiltrate is present. The lamina propria
===The big table of cystitis===
contains a nest with smaller cells, cystic spaces and no appreciable mitoses
(cystitis cystica).
 
=Benign urothelial lesions=
The big table of cystitis:
{| class="wikitable sortable"  
{| class="wikitable sortable"  
! Type
! Type
Line 642: Line 423:


==Interstitial cystitis==
==Interstitial cystitis==
*[[AKA]] ''painful bladder syndrome''.<ref name=pmid21609485>{{Cite journal  | last1 = Tanaka | first1 = T. | last2 = Nitta | first2 = Y. | last3 = Morimoto | first3 = K. | last4 = Nishikawa | first4 = N. | last5 = Nishihara | first5 = C. | last6 = Tamada | first6 = S. | last7 = Kawashima | first7 = H. | last8 = Nakatani | first8 = T. | title = Hyperbaric oxygen therapy for painful bladder syndrome/interstitial cystitis resistant to conventional treatments: long-term results of a case series in Japan. | journal = BMC Urol | volume = 11 | issue =  | pages = 11 | month =  | year = 2011 | doi = 10.1186/1471-2490-11-11 | PMID = 21609485 }}</ref><ref name=pmid21568251>{{Cite journal  | last1 = French | first1 = LM. | last2 = Bhambore | first2 = N. | title = Interstitial cystitis/painful bladder syndrome. | journal = Am Fam Physician | volume = 83 | issue = 10 | pages = 1175-81 | month = May | year = 2011 | doi =  | PMID = 21568251 }}</ref>
{{Main|Interstitial cystitis}}
===General===
*Chronic cystitis, culture negative.
*Treatment difficult.<ref name=pmid21609485/>
 
Epidemiology:<ref name=pmid21568251/>
*Women > men.
 
Symptoms:<ref name=pmid21568251/>
*Urgency.
*Frequency.
*Pain.
 
===Microscopic===
Features:<ref name=Ref_GUP124>{{Ref GUP|124}}</ref>
*+/-Ulceration (uncommon).
 
Note:
*[[Diagnosis]] requires clinical correlation.
 
DDx:
*Urothelial CIS.


==Follicular cystitis==
==Follicular cystitis==
Line 723: Line 483:


==Cystitis cystica==
==Cystitis cystica==
===General===
{{Main|Cystitis cystica}}
*Benign.
*Can be thought of as [[von Brunn nests]] with cystic change.<ref name=Ref_WMSP304>{{Ref WMSP|304}}</ref>
*Called ''[[ureteritis cystica]]'' if it happens in a [[ureter]].
 
===Microscopic===
Features:<ref name=Ref_PBoD1028>{{Ref PBoD|1028}}</ref>
*Nests of urothelium within the lamina propria with cyst formation, i.e. lumens are present.
 
Note:
*Nests should '''not''' extend into the muscularis propria.
 
DDx:
*[[Nested urothelial carcinoma]].<ref name=pmid19800100>{{Cite journal  | last1 = Wasco | first1 = MJ. | last2 = Daignault | first2 = S. | last3 = Bradley | first3 = D. | last4 = Shah | first4 = RB. | title = Nested variant of urothelial carcinoma: a clinicopathologic and immunohistochemical study of 30 pure and mixed cases. | journal = Hum Pathol | volume = 41 | issue = 2 | pages = 163-71 | month = Feb | year = 2010 | doi = 10.1016/j.humpath.2009.07.015 | PMID = 19800100 }}
</ref>
 
Image:
*[http://www.webpathology.com/image.asp?n=1&Case=50 Cystitis cystica (webpathology.com)].
 
===Sign out===
<pre>
URINARY BLADDER, BIOPSY:
- CYSTITIS CYSTICA.
- NEGATIVE FOR MALIGNANCY.
</pre>


==Cystitis glandularis==
==Cystitis glandularis==
:''Cystitis cystica et glandularis'' redirects to here.
{{Main|Cystitis glandularis}}
===General===
*Benign.
*Can be thought of as [[cystitis cystica]] with mucin-secreting cells lining the cystic spaces.<ref name=Ref_WMSP304>{{Ref WMSP|304}}</ref>
*When seen in conjunction with ''cystitis cystica'' it is called ''cystitis cystica et glandularis''.
 
Note:
*There are case reports of ''urethritis glandularis'' - the same lesion in the [[urethra]].<ref name=pmid11104631>{{Cite journal  | last1 = Chan | first1 = YM. | last2 = Ka-Leung Cheng | first2 = D. | last3 = Nga-Yin Cheung | first3 = A. | last4 = Yuen-Sheung Ngan | first4 = H. | last5 = Wong | first5 = LC. | title = Female urethral adenocarcinoma arising from urethritis glandularis. | journal = Gynecol Oncol | volume = 79 | issue = 3 | pages = 511-4 | month = Dec | year = 2000 | doi = 10.1006/gyno.2000.5968 | PMID = 11104631 }}</ref><ref name=pmid17825180>{{Cite journal  | last1 = Yin | first1 = G. | last2 = Liu | first2 = YQ. | last3 = Gao | first3 = P. | last4 = Wang | first4 = XH. | title = Male urethritis glandularis: case report. | journal = Chin Med J (Engl) | volume = 120 | issue = 16 | pages = 1460-1 | month = Aug | year = 2007 | doi =  | PMID = 17825180 }}</ref>
 
===Microscopic===
Features:<ref name=Ref_PBoD1028>{{Ref PBoD|1028}}</ref>
*Nests of urothelium within the lamina propria with cyst formation, i.e. lumens are present.
*Cyst lining cells are cuboidal and/or columnar epithelium.
**Produce mucin.
*+/-Goblet cells, i.e. intestinal metaplasia.<ref name=Ref_WMSP304>{{Ref WMSP|304}}</ref>
 
Note:
*Nests should '''not''' extend into the muscularis propria.
 
Image:
*[http://www.webpathology.com/image.asp?n=2&Case=50 Cystitis glandularis (webpathology.com)].
 
===Sign out===
<pre>
URINARY BLADDER NECK, BIOPSY:
- CYSTITIS CYSTICA ET GLANDULARIS.
- NEGATIVE FOR MALIGNANCY.
</pre>


==Malakoplakia==
==Malakoplakia==
Line 783: Line 492:


==Nephrogenic adenoma==
==Nephrogenic adenoma==
*[[AKA]] ''mesonephric adenoma'',<ref name=pmid21716880>{{Cite journal  | last1 = Singh | first1 = KJ. | title = Mesonephric adenoma in remnant ureteric stump: A rare entity. | journal = Indian J Urol | volume = 27 | issue = 1 | pages = 140-1 | month = Jan | year = 2011 | doi = 10.4103/0970-1591.78414 | PMID = 21716880 }}</ref> [[AKA]] ''nephrogenic metaplasia''.
*[[AKA]] ''mesonephric adenoma''.
 
*[[AKA]] ''nephrogenic metaplasia''.
===General===
{{Main|Nephrogenic adenoma}}
Features:<ref name=pmid12118115>{{Cite journal  | last1 = Gokaslan | first1 = ST. | last2 = Krueger | first2 = JE. | last3 = Albores-Saavedra | first3 = J. | title = Symptomatic nephrogenic metaplasia of ureter: a morphologic and immunohistochemical study of four cases. | journal = Mod Pathol | volume = 15 | issue = 7 | pages = 765-70 | month = Jul | year = 2002 | doi = 10.1097/01.MP.0000019578.51568.24 | PMID = 12118115 | url = http://www.nature.com/modpathol/journal/v15/n7/full/3880603a.html }}</ref>
*Benign.
**May mimic adenocarcinoma!
*Classic location is the [[urinary bladder]].
**Also reported in ureter and prostatic urethra.
*It is thought to result from displacement of renal tubular cells, as this entity in renal transplant recipients is graft derived.<ref>{{Cite journal  | last1 = Mazal | first1 = PR. | last2 = Schaufler | first2 = R. | last3 = Altenhuber-Müller | first3 = R. | last4 = Haitel | first4 = A. | last5 = Watschinger | first5 = B. | last6 = Kratzik | first6 = C. | last7 = Krupitza | first7 = G. | last8 = Regele | first8 = H. | last9 = Meisl | first9 = FT. | title = Derivation of nephrogenic adenomas from renal tubular cells in kidney-transplant recipients. | journal = N Engl J Med | volume = 347 | issue = 9 | pages = 653-9 | month = Aug | year = 2002 | doi = 10.1056/NEJMoa013413 | PMID = 12200552 }}</ref>
 
===Microscopic===
Features:<ref name=pmid12118115>{{Cite journal  | last1 = Gokaslan | first1 = ST. | last2 = Krueger | first2 = JE. | last3 = Albores-Saavedra | first3 = J. | title = Symptomatic nephrogenic metaplasia of ureter: a morphologic and immunohistochemical study of four cases. | journal = Mod Pathol | volume = 15 | issue = 7 | pages = 765-70 | month = Jul | year = 2002 | doi = 10.1097/01.MP.0000019578.51568.24 | PMID = 12118115 | url = http://www.nature.com/modpathol/journal/v15/n7/full/3880603a.html }}</ref>
*Tubular structures - '''key feature'''.
**Hobnailed cells.
**+/-Thick eosinophilic basement membrane.
**Microcystic appearance.
*Usually associated with chronic inflammation.
 
Notes:
*May mimic vascular/lymphatic channels - can be sorted-out with IHC.
 
DDx:
*[[Urothelial carcinoma]], microcystic and nested variants.
*[[Prostatic adenocarcinoma]].
*[[Clear cell adenocarcinoma]].
 
====Images====
<gallery>
Image:Nephrogenic_adenoma_-_intermed_mag.jpg | Nephrogenic adenoma - intermed. mag. (WC/Nephron)
Image:Nephrogenic_adenoma_-_very_high_mag.jpg | Nephrogenic adenoma - very high mag. (WC/Nephron)
</gallery>
www:
*[http://www.archivesofpathology.org/action/showFullPopup?id=i1543-2165-134-10-1455-f01&doi=10.1043%2F2010-0226-CR.1 NA (archivesofpathology.org)].<ref name=pmid20923300>{{Cite journal  | last1 = Kunju | first1 = LP. | title = Nephrogenic adenoma: report of a case and review of morphologic mimics. | journal = Arch Pathol Lab Med | volume = 134 | issue = 10 | pages = 1455-9 | month = Oct | year = 2010 | doi = 10.1043/2010-0226-CR.1 | PMID = 20923300 }}</ref>
===IHC===
Features:<ref name=pmid22415059>{{Cite journal  | last1 = Alexiev | first1 = BA. | last2 = Levea | first2 = CM. | title = Nephrogenic Adenoma of the Urinary Tract: A Review. | journal = Int J Surg Pathol | volume =  | issue =  | pages =  | month = Mar | year = 2012 | doi = 10.1177/1066896912439095 | PMID = 22415059 }}</ref>
*CK7 +ve.
*PAX2 +ve.
*PAX8 +ve.
*AMACR +ve/-ve.
 
Others:<ref name=pmid12118115>{{Cite journal  | last1 = Gokaslan | first1 = ST. | last2 = Krueger | first2 = JE. | last3 = Albores-Saavedra | first3 = J. | title = Symptomatic nephrogenic metaplasia of ureter: a morphologic and immunohistochemical study of four cases. | journal = Mod Pathol | volume = 15 | issue = 7 | pages = 765-70 | month = Jul | year = 2002 | doi = 10.1097/01.MP.0000019578.51568.24 | PMID = 12118115 }}</ref>
*p53 -ve.
*CEA -ve.
*Ki-67 low (<5%).


=See also=
=See also=
Michael
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