Difference between revisions of "Urothelium"

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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 hyperplasia.
*Flat urothelial hyperplasia.
*Urothelial atypia of unknown significance.
*Urothelial atypia of unknown significance.
*Urothelial dysplasia (low-grade dysplasia).
*[[Urothelial dysplasia]] (low-grade dysplasia).
*Urothelial carcinoma in situ (high-grade dysplasia).
*Urothelial carcinoma in situ (high-grade dysplasia).
*Invasive urothelial carcinoma.
*Invasive urothelial carcinoma.
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*May be confused with [[urothelial carcinoma in situ]].<ref name=Ref_Amin2-57>{{Ref Amin|2-57}}</ref>
*May be confused with [[urothelial carcinoma in situ]].<ref name=Ref_Amin2-57>{{Ref Amin|2-57}}</ref>
*Uncommon.
*Uncommon.
*Considered to be [[normal urothelium]].


===Microscopic===
===Microscopic===
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**Mild nuclear enlargement ~3-4x lymphocyte.
**Mild nuclear enlargement ~3-4x lymphocyte.
**Round/regular nuclear membranes.
**Round/regular nuclear membranes.
**+/-Multi-nucleation.
**Focally clear cytoplasm with cobwebs.
**Focally clear cytoplasm with cobwebs.
***Clear cytoplasm with eosinophilic reticulations.
***Clear cytoplasm with eosinophilic reticulations.
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*No mitotic activity.
*No mitotic activity.


DDx:
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 carcinoma in situ]].
*[[Urothelial dysplasia]].
====Images====
<gallery>
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===
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*p53 -ve.
*p53 -ve.


==Urothelial carcinoma in situ==
===Sign out===
*Abbreviated ''CIS''.
<pre>
===General===
URINARY BLADDER, TRANSURETHRAL BIOPSY:
*Lack papillae.
- UROTHELIAL MUCOSA WITH MILD CHRONIC INFLAMMATION.
- NO EVIDENCE OF MALIGNANCY.


===Microscopic===
COMMENT:
Features:
Levels were cut and show large benign umbrella cells.
*Nuclear changes '''key feature'''.
</pre>
**Enlargement of nuclei (often 4-5x the size of stromal lymphocytes) -- diagnostic.<ref name=Ref_GUP161>{{Ref GUP|161}}</ref>
***Normal urothelium approx. 2x the size of stromal lymphocytes.
**Nuclear pleomorphism - marked variation in size of nuclei.
*+/-Disordered arrangement/crowding of cells.
**In normal urothelium the cell line-up on the basement membrane.
*Umbrella cells often absent.
*+/-Mitoses present.
*+/-Enlarged nucleoli.


Note:
====Micro====
*The urothelium may be "depleted", i.e. exist only of rare large cells on the basement membrane.
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.
**This is known as ''clinging urothelial carcinoma in situ''.<ref>{{Ref Amin|2-55}}</ref>


===IHC===
==Urothelial dysplasia==
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>
*[[AKA]] ''low-grade (urothelial) dysplasia''.
*p53 +ve.
{{Main|Urothelial dysplasia}}
*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>
==Urothelial carcinoma in situ==
*CK20 +ve in deep cells (23/26 cases).
*Abbreviated ''CIS''.
**Normal urothelium -- only the umbrella cells.
*[[AKA]] ''high-grade (urothelial) dysplasia''.
*Ki-67 ~50% of cells - deep and superficial.
{{Main|Urothelial carcinoma in situ}}
**Normal ~10% of cells, confined to basal aspect.
 
===Sign out===
<pre>
URINARY BLADDER LESION ("TUMOUR"), TRANSURETHRAL RESECTION URINARY BLADDER TUMOUR (TURBT):
- UROTHELIAL CARCINOMA IN SITU.
- MUSCULARIS PROPRIA PRESENT.
</pre>


==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>
 
DDx:
*[[Pseudocarcinomatous urothelial hyperplasia]].
 
====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]].
*[[Low grade papillary urothelial carcinoma]] with lamina propria invasion.
 
====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 in over 50% of cases with metastases.<ref name=pmid11419977>{{Cite journal  | last1 = Jiang | first1 = J. | last2 = Ulbright | first2 = TM. | last3 = Younger | first3 = C. | last4 = Sanchez | first4 = K. | last5 = Bostwick | first5 = DG. | last6 = Koch | first6 = MO. | last7 = Eble | first7 = JN. | last8 = Cheng | first8 = L. | title = Cytokeratin 7 and cytokeratin 20 in primary urinary bladder carcinoma and matched lymph node metastasis. | journal = Arch Pathol Lab Med | volume = 125 | issue = 7 | pages = 921-3 | month = Jul | year = 2001 | doi = 10.1043/0003-9985(2001)1250921:CACIPU2.0.CO;2 | PMID = 11419977 }}</ref>
 
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>
 
===IHC===
May be useful versus inverted growth pattern UCC:<ref name=pmid18043040>{{Cite journal  | last1 = Jones | first1 = TD. | last2 = Zhang | first2 = S. | last3 = Lopez-Beltran | first3 = A. | last4 = Eble | first4 = JN. | last5 = Sung | first5 = MT. | last6 = MacLennan | first6 = GT. | last7 = Montironi | first7 = R. | last8 = Tan | first8 = PH. | last9 = Zheng | first9 = S. | title = Urothelial carcinoma with an inverted growth pattern can be distinguished from inverted papilloma by fluorescence in situ hybridization, immunohistochemistry, and morphologic analysis. | journal = Am J Surg Pathol | volume = 31 | issue = 12 | pages = 1861-7 | month = Dec | year = 2007 | doi = 10.1097/PAS.0b013e318060cb9d | PMID = 18043040 }}</ref>
*Ki-67 -ve.
*CK20 -ve.
*p53 -ve (rarely +ve).


==Papillary urothelial neoplasm of low malignant potential==
==Papillary urothelial neoplasm of low malignant potential==
*Abbreviated ''PUNLMP''.
*Abbreviated ''PUNLMP''.
**This is pronounced ''pun-lump''.
**This is pronounced ''pun-lump''.
 
{{Main|Papillary urothelial neoplasm of low malignant potential}}
===General===
*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==
==Low-grade papillary urothelial carcinoma==
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*[[AKA]] ''high-grade papillary urothelial cell carcinoma'', abbreviated ''HGPUCC''.
*[[AKA]] ''high-grade papillary urothelial cell carcinoma'', abbreviated ''HGPUCC''.
{{Main|High-grade papillary urothelial carcinoma}}
{{Main|High-grade papillary urothelial carcinoma}}
==Papillary urothelial hyperplasia==
*[[AKA]] ''papillary hyperplasia''.
*[[AKA]] ''reactive papillary hyperplasia''.
{{Main|Papillary urothelial hyperplasia}}


=Benign urothelial lesions=
=Benign urothelial lesions=
The big table of cystitis:
===Cystitis===
*Inflammation of the [[urinary bladder]]. 
*Comes in many forms (see below).
*Typically a [[clinical diagnosis]] under the more general term [[urinary tract infection]].
 
Note:
*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>
 
===The big table of cystitis===
{| class="wikitable sortable"  
{| class="wikitable sortable"  
! Type
! Type
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==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==
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==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]].
*Called ''urethritis cystica'' if it happens in the [[urethera]].<ref name=pmid22397870>{{Cite journal  | last1 = Conces | first1 = MR. | last2 = Williamson | first2 = SR. | last3 = Montironi | first3 = R. | last4 = Lopez-Beltran | first4 = A. | last5 = Scarpelli | first5 = M. | last6 = Cheng | first6 = L. | title = Urethral caruncle: clinicopathologic features of 41 cases. | journal = Hum Pathol | volume = 43 | issue = 9 | pages = 1400-4 | month = Sep | year = 2012 | doi = 10.1016/j.humpath.2011.10.015 | PMID = 22397870 }}</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.
 
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==
{{ Infobox external links
{{Main|Cystitis glandularis}}
| Name          = Cystitis cystica et glandularis
| EHVSC          = 10173
| pathprotocols  =
| wikipedia      =
| pathoutlines  =
}}
:''Cystitis cystica et glandularis'' redirects to here.
===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>
 
====Micro====
The sections show urothelial mucosa with bland nests within the lamina propria with cyst formation. The stroma is edematous and has a mixed inflammatory infiltrate consisting of plasma cells, eosinophils, lymphocytes and neutrophils.


==Malakoplakia==
==Malakoplakia==

Latest revision as of 21:35, 2 November 2016

The urothelium lines the upper portion of the genitourinary tract, i.e. ureters, urinary bladder), and a bit of the lower part.

Normal urothelium

Gross

Extent of urothelium

Urethra in males
Main article: Urethra
  • Pre-prostatic urethra - transitional epithelium.
  • Prostatic urethra - transitional 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).

Microscopic

Features:

  • Maturation (cuboidal at base - squamoid at surface).
    • Surface cells called 'umbrella cells' (umbrella cells CK20 +ve).
  • Urothelium should be 4-5 cell layers thick.
  • +/-Prominent nucleoli.

Note:

  • Should not have a papillary architecture -- if it does it is likely cancer!
    • If it is 'papillary' -- it must have fibrovascular cores.

IHC

  • Rare superficial CK20 staining.

Image

  • Benign urothelium - CK20 - high mag. (WC)

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URINARY BLADDER LESION, TRANSURETHRAL RESECTION:
- UROTHELIAL MUCOSA WITHIN NORMAL LIMITS.
- NEGATIVE FOR MALIGNANCY.

Micro

The sections shows urothelium with underlying tissue. The urothelium is 4-5 cells thick. Umbrella cells are present. Few mononuclear inflammatory cells are seen in the subepithelial tissue.

The urothelium has no nuclear hyperchromasia and no significant nuclear enlargement. Mitotic activity is not identified. No papillary structures are present.

Approach

Where to start

July 1st PGY-2:

  1. Urothelial carcinoma - essentially defined by increased nuclear size +/- irreg. nuclear contour.
    • Nucleoli are common in urothelium.
      • This can be confusing... prostate carcinoma has nucleoli.
    • Mitosis - these are key if the nuclear enlargement is not present.[1]
    • Cell-depleted urothelium, where the cells have shed-off--but a few remain, should raise suspicions to cancer.
      • Thickness of the urothelium, otherwise, isn't very useful for diagnosing cancer.
  2. Round structures should make you think of papillae and prompt looking for fibrovascular cores.
  3. Fibrovascular cores = papillae... may be cancer!

A checklist-like approach

  1. Papillary structure - with fibrovascular cores?
    • Nuclear pleomorphism?
      • Yes - high grade (4-5x lymphocyte) --> Dx: high grade papillary urothelial carcinoma
      • No - low grade or normal (2-3x lymphocyte) --> DDx: low grade papillary urothelial carcinoma, PUNLMP, papilloma
  2. Flat lesions?
    • Nuclear pleomorphism?
  3. Maturation to surface?
    • No --> Dx: sectioning artefact vs. flat UCC.
    • Yes --> likely benign.
  4. Normal thickness?
    • Normal is 4-5 cell layers.
  5. Nests of glandular cells
  6. Inflammation?
    • Michaelis-Gutman bodies?

Pitfalls:

  • Urothelial carcinoma of the bladder may be confused with a paraganglioma of the bladder.
    • Way to differentiate: paraganglioma = stippled chromatin, UCC = single nucleoli.

Note about terminology

  • The bladder is rather unique in that "carcinoma" is a label used for things that are non-invasive.
    • It has been suggested that many things that are called papillary urothelial carcinoma, would be better described as papillary intraurothelial neoplasia.[2]
    • If the terminology in the urinary bladder were applied to the colon, we'd call all adenomas, i.e. pre-malignant lesions, carcinomas.

Overview in tables

General categorization

Urothelial lesions can broadly be divided into:

  1. Flat lesions.
    • Lack papillae.
    • Tend to be more aggressive.
  2. Papillary lesions.
    • Must have true papillae.
    • Very common.
    • More often benign/indolent.

Flat urothelial lesions

Comparison urothelial changes - flat epithelium - benign/premalignant/cancerous:[3]

Diagnosis Nuclear enlargement
(X stromal lymphocyte) 		Nucleoli size var., shape Polarity Mitoses Thickness Inflammation Other
Normal none (2x) small none, round matures to surface none/minimal 4-5 cells none -
Reactive atypia moderate, prominent (3x) prominent none, round as normal some, none atypical as normal severe, acute or chronic -
Flat urothelial hyperplasia none (2x) small none, round as normal as normal increased usu. none -
Urothelial dysplasia moderate (3x) small, some multiple mod. variation, some irregularity lost rare, none atypical as normal usu. none -
Urothelial carcinoma in situ signif. (4-5x) +/-large marked, irregular lost common, atypical thin, thick or norm. +/- -
Invasive UCC signif. (4-5X) +/-large marked, irregular lost common, atypical thin, thick or norm. +/- stromal invasion

The bold entry is considered the key feature.

Papillary urothelial lesions

Urothelial cells in papillae - benign/premalignant/cancerous:[4][5]

Diagnosis Papillae features Papillae branching Papillae fusion Nuclear size Mitoses DDx IHC Other Key feature
Papilloma fat papillae,
thick FV core 		rare none normal (2x lymphocyte) very rare basal PUNLMP, low gr. PUCC p53-, CK20+ umbrella cells cytologically normal normal cells,
fat papillae
PUNLMP slender FV core uncommon rare enlarged - uniform rare basal only papilloma, low gr. CK20+ umbrella low cellular density (@ low power) vs. low gr.[6] uniformly enlarged cell pop.,
slender papillae
Low grade PUCC slender FV core,
thick epithelium 		frequent some enlarged with variation infreq., usually basal PUNLMP, high gr. -/+ p53, CK20+ umbrella +/- small nucleoli nuc. pleomorphism,
thick epithelium
High grade PUCC mixed population common common 4-5x lymphocyte,
marked pleomorphism 		common, everywhere low gr., invasive UCC diffuse CK20+, p53+ in 50% nucleoli prominent marked nuclear pleomorphism

Notes:

  • FV core = fibrovascular core.
  • PUCC = papillary urothelial carcinoma.

Risk factors for urothelial carcinoma

  • Smoking.
  • Toxins.
  • Drugs, e.g. cyclophosphamide.
  • Marijuana.[7]
  • Chinese Herbs.[8]

Others:

Flat urothelial lesions

Overview

Several different benign & pre-malignant diagnoses can be made.

The World Health Organization classification is:[10]

  • Reactive urothelial atypia.
  • Flat urothelial hyperplasia.
  • Urothelial atypia of unknown significance.
  • Urothelial dysplasia (low-grade dysplasia).
  • Urothelial carcinoma in situ (high-grade dysplasia).
  • Invasive urothelial carcinoma.

Mild urothelial atypia in normal urothelium

General

Microscopic

Features:[11]

  • Umbrella cells have:
    • Mild nuclear enlargement ~3-4x lymphocyte.
    • Round/regular nuclear membranes.
    • +/-Multi-nucleation.
    • Focally clear cytoplasm with cobwebs.
      • Clear cytoplasm with eosinophilic reticulations.
  • +/-Inflammation.
  • No mitotic activity.

DDx:[12]

Images

  • Benign large superf. cells - intermed. mag. (WC)

  • Benign large superf. cells - high mag. (WC)

  • Benign large superf. cells - very high mag. (WC)

IHC

  • Ki-67 low.
  • p53 -ve.

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URINARY BLADDER, TRANSURETHRAL BIOPSY:
- UROTHELIAL MUCOSA WITH MILD CHRONIC INFLAMMATION.
- NO EVIDENCE OF MALIGNANCY.

COMMENT:
Levels were cut and show large benign umbrella cells.

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 article: Urothelial dysplasia

Urothelial carcinoma in situ

  • Abbreviated CIS.
  • AKA high-grade (urothelial) dysplasia.
Main article: Urothelial carcinoma in situ

Urothelial cell carcinoma

See urine cytology for the cytopathology.
  • Abbreviated UCC.
  • AKA urothelial carcinoma.
Main article: Urothelial carcinoma

Papillary urothelial lesions

Papillary urothelial lesions are grouped into one of five categories (listed from good to bad prognosis):[5]

  1. Urothelial papilloma.
  2. Inverted papilloma.
  3. Papillary urothelial neoplasm of low malignant potential (PUNLMP).
    • PUNLMP is pronouced "pun-lump".
  4. Low grade papillary urothelial carcinoma.
  5. High grade papillary urothelial carcinoma.

Key characteristics:

  1. Nuclear - size/pleomorphism.
  2. Papillae branching.
  3. Papillae fusion.

Urothelial papilloma

Main article: Urothelial papilloma

Inverted urothelial papilloma

Main article: Inverted urothelial papilloma

Papillary urothelial neoplasm of low malignant potential

  • Abbreviated PUNLMP.
    • This is pronounced pun-lump.
Main article: Papillary urothelial neoplasm of low malignant potential

Low-grade papillary urothelial carcinoma

  • Abbreviated LGPUC.[13]
  • AKA low-grade papillary urothelial cell carcinoma.
Main article: Low-grade papillary urothelial carcinoma

High-grade papillary urothelial carcinoma

  • Abbreviated HGPUC.
  • AKA high-grade papillary urothelial cell carcinoma, abbreviated HGPUCC.
Main article: High-grade papillary urothelial carcinoma

Papillary urothelial hyperplasia

  • AKA papillary hyperplasia.
  • AKA reactive papillary hyperplasia.
Main article: Papillary urothelial hyperplasia

Benign urothelial lesions

Cystitis

Note:

  • 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.[14]

The big table of cystitis

Type Key feature DDx Reference
Florid proliferative cystitis expanded lamina propria with von Brunn's nests, cystitis cystica et glandularis von Brunn's nests, cystitis cystica et glandularis, low-grade urothelial carcinoma [15]
Polypoid cystitis wide base, height > base papillary cystitis, bullous cystitis [16]
Bullous cystitis wide base, height < base papillary cystitis, polypoid cystitis [16]
Papillary cystitis narrow base, height > base polypoid cystitis, bullous cystitis [16]
Interstitial cystitis +/-ulceration (uncommon) - requires clinical correlation urothelial CIS [17]
Follicular cystitis lymphoid follicles non-Hodgkin lymphoma [18]
Infectious cystitis dependent cause (bacterial, viral, fungal) [19]
Granulomatous cystitis granulomas tuberculosis, schistosomiasis, fungal infection, post-BCG [19]
Radiation cystitis edema, vascular congestion, +/- erosions -- acute; fibrosis in LP and detrusor -- chronic [20]

Interstitial cystitis

Main article: Interstitial cystitis

Follicular cystitis

Microscopic

Features:[18]

  • Lymphoid follicles in the lamina propria.

DDx:

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URINARY BLADDER, BIOPSY:
- UROTHELIAL MUCOSA WITH CHRONIC INFLAMMATION AND BENIGN LYMPHOID NODULES WITH GERMINAL CENTRE FORMATION.
- MUSCULARIS PROPRIA PRESENT.
- NEGATIVE FOR UROTHELIAL CARCINOMA IN SITU AND NEGATIVE FOR MALIGNANCY.

Polypoid cystitis

General

  • Uncommon.
  • Wide age range.
  • Benign.

Microscopic

Features:[16]

  • Polypoid urothelium-covered projections with:
    1. Broad bases.
    2. Height > base.
    3. Extensive edema.

DDx:

  • Papillary cystitis - not a broad base.
  • Bullous cystitis.

Image:

von Brunn nests

General

  • Benign.

Microscopic

Features:[21]

  • Nests of (benign) urothelium budding into the lamina propria.

Note:

  • Nests should not extend into the muscularis propria.

DDx:

IHC

Features:[22]

  • p53 -ve.
  • MIB-1 <3%.

Cystitis cystica

Main article: Cystitis cystica

Cystitis glandularis

Main article: Cystitis glandularis

Malakoplakia

Main article: Malakoplakia

Nephrogenic adenoma

  • AKA mesonephric adenoma.
  • AKA nephrogenic metaplasia.
Main article: Nephrogenic adenoma

See also

References

  1. ↑ JS. 9 June 2010.
  2. ↑ Van der Kwast, TH.; Zlotta, AR.; Fleshner, N.; Jewett, M.; Lopez-Beltran, A.; Montironi, R. (Dec 2008). "Thirty-five years of noninvasive bladder carcinoma: a plea for the use of papillary intraurothelial neoplasia as new terminology.". Anal Quant Cytol Histol 30 (6): 309-15. PMID 19160695.
  3. ↑ Zhou, Ming; Magi-Galluzzi, Cristina (2006). Genitourinary Pathology: A Volume in Foundations in Diagnostic Pathology Series (1st ed.). Churchill Livingstone. pp. 155-163. ISBN 978-0443066771.
  4. ↑ Zhou, Ming; Magi-Galluzzi, Cristina (2006). Genitourinary Pathology: A Volume in Foundations in Diagnostic Pathology Series (1st ed.). Churchill Livingstone. pp. 166-175. ISBN 978-0443066771.
  5. ↑ 5.0 5.1 Humphrey, Peter A; Dehner, Louis P; Pfeifer, John D (2008). The Washington Manual of Surgical Pathology (1st ed.). Lippincott Williams & Wilkins. pp. 310. ISBN 978-0781765275.
  6. ↑ GAG. 26 February 2009.
  7. ↑ Chacko, JA.; Heiner, JG.; Siu, W.; Macy, M.; Terris, MK. (Jan 2006). "Association between marijuana use and transitional cell carcinoma.". Urology 67 (1): 100-4. doi:10.1016/j.urology.2005.07.005. PMID 16413342.
  8. ↑ URL: http://content.nejm.org/cgi/content/full/343/17/1268. Accessed on: 27 May 2010.
  9. ↑ Crockett, DG.; Wagner, DG.; Holmäng, S.; Johansson, SL.; Lynch, HT. (May 2011). "Upper urinary tract carcinoma in Lynch syndrome cases.". J Urol 185 (5): 1627-30. doi:10.1016/j.juro.2010.12.102. PMID 21419447.
  10. ↑ Hodges, KB.; Lopez-Beltran, A.; Davidson, DD.; Montironi, R.; Cheng, L. (Feb 2010). "Urothelial dysplasia and other flat lesions of the urinary bladder: clinicopathologic and molecular features.". Hum Pathol 41 (2): 155-62. doi:10.1016/j.humpath.2009.07.002. PMID 19762067.
  11. ↑ 11.0 11.1 Amin, Mahul B. (2010). Diagnostic Pathology: Genitourinary (1st ed.). Amirsys. pp. 2-57. ISBN 978-1931884280.
  12. ↑ URL: http://pathology.jhu.edu/bladder/definitions.cfm. Accessed on: 8 January 2014.
  13. ↑ Watts, KE.; Montironi, R.; Mazzucchelli, R.; van der Kwast, T.; Osunkoya, AO.; Stephenson, AJ.; Hansel, DE. (Aug 2012). "Clinicopathologic characteristics of 23 cases of invasive low-grade papillary urothelial carcinoma.". Urology 80 (2): 361-6. doi:10.1016/j.urology.2012.04.010. PMID 22857755.
  14. ↑ Amin, Mahul B. (2010). Diagnostic Pathology: Genitourinary (1st ed.). Amirsys. pp. 2:6. ISBN 978-1931884280.
  15. ↑ Zhou, Ming; Magi-Galluzzi, Cristina (2006). Genitourinary Pathology: A Volume in Foundations in Diagnostic Pathology Series (1st ed.). Churchill Livingstone. pp. 113. ISBN 978-0443066771.
  16. ↑ 16.0 16.1 16.2 16.3 Zhou, Ming; Magi-Galluzzi, Cristina (2006). Genitourinary Pathology: A Volume in Foundations in Diagnostic Pathology Series (1st ed.). Churchill Livingstone. pp. 120. ISBN 978-0443066771.
  17. ↑ Zhou, Ming; Magi-Galluzzi, Cristina (2006). Genitourinary Pathology: A Volume in Foundations in Diagnostic Pathology Series (1st ed.). Churchill Livingstone. pp. 124. ISBN 978-0443066771.
  18. ↑ 18.0 18.1 Zhou, Ming; Magi-Galluzzi, Cristina (2006). Genitourinary Pathology: A Volume in Foundations in Diagnostic Pathology Series (1st ed.). Churchill Livingstone. pp. 122. ISBN 978-0443066771.
  19. ↑ 19.0 19.1 Zhou, Ming; Magi-Galluzzi, Cristina (2006). Genitourinary Pathology: A Volume in Foundations in Diagnostic Pathology Series (1st ed.). Churchill Livingstone. pp. 127. ISBN 978-0443066771.
  20. ↑ Zhou, Ming; Magi-Galluzzi, Cristina (2006). Genitourinary Pathology: A Volume in Foundations in Diagnostic Pathology Series (1st ed.). Churchill Livingstone. pp. 138. ISBN 978-0443066771.
  21. ↑ Cotran, Ramzi S.; Kumar, Vinay; Fausto, Nelson; Nelso Fausto; Robbins, Stanley L.; Abbas, Abul K. (2005). Robbins and Cotran pathologic basis of disease (7th ed.). St. Louis, Mo: Elsevier Saunders. pp. 1028. ISBN 0-7216-0187-1.
  22. ↑ 22.0 22.1 Volmar, KE.; Chan, TY.; De Marzo, AM.; Epstein, JI. (Sep 2003). "Florid von Brunn nests mimicking urothelial carcinoma: a morphologic and immunohistochemical comparison to the nested variant of urothelial carcinoma.". Am J Surg Pathol 27 (9): 1243-52. PMID 12960809.
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