Difference between revisions of "Urothelium"

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Urothelium (view source)

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The '''urothelium''' lines the upper portion of the genitourinary tract, i.e. [[ureter]]s, [[urinary bladder]]), and a bit of the lower part.
The '''urothelium''' lines the upper portion of the genitourinary tract, i.e. [[ureter]]s, [[urinary bladder]]), and a bit of the lower part.


=Normal histology=
=Normal urothelium=
*Maturation (cuboidal at base - squamoid at surface).
===Gross===
**Surface cells called 'umbrella cells' (umbrella cells CK20+).
====Extent of urothelium====
*Urothelium should be 4-5 cell layers thick.
*+/-Prominent nucleoli.
 
*Should NOT have papillary architecture -- if it does it is likely [[cancer]]!
**If it is 'papillary' -- it must have fibrovascular cores.
 
==Extent of urothelium==
*[[Ureters]].
*[[Ureters]].
*Renal pelvis.
*Renal pelvis.
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*Part of the urethra.
*Part of the urethra.
   
   
===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).
===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====
<gallery>
Image: Benign urothelium - CK20 -- high mag.jpg | Benign urothelium - CK20 - high mag. (WC)
</gallery>
===Sign out===
<pre>
URINARY BLADDER LESION, TRANSURETHRAL RESECTION:
- UROTHELIAL MUCOSA WITHIN NORMAL LIMITS.
- NEGATIVE FOR MALIGNANCY.
</pre>
====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=
=Approach=
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#* Normal is 4-5 cell layers.
#* Normal is 4-5 cell layers.
# Nests of glandular cells
# Nests of glandular cells
#* Consider ''cystitis cystica'', ''cystitis glandularis'', ''cystitis cystica et glandularis'', ''Brunn's nest'', ''inverted papilloma''.
#* Consider ''[[cystitis cystica]]'', ''[[cystitis glandularis]]'', ''cystitis cystica et glandularis'', ''[[von Brunn's nest]]'', ''[[inverted urothelial papilloma|inverted papilloma]]''.
# Inflammation?
# Inflammation?
#* Michaelis-Gutman bodies?
#* Michaelis-Gutman bodies?
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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]].
 
====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>


Note:
===IHC===
*The urothelium may be "depleted", i.e. exist only of rare large cells on the basement membrane.
*Ki-67 low.
**This is known as ''clinging urothelial carcinoma in situ''.<ref>{{Ref Amin|2-55}}</ref>
*p53 -ve.


===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:
*[http://commons.wikimedia.org/wiki/File:Nested_variant_of_urothelial_carcinoma_-_intermed_mag.jpg Nested variant of urothelial carcinoma - intermed. mag. (WC)].
*[http://commons.wikimedia.org/wiki/File:Nested_variant_of_urothelial_carcinoma_-_high_mag.jpg Nested variant of urothelial carcinoma - high mag. (WC)].
*[http://commons.wikimedia.org/wiki/File:Nested_variant_of_urothelial_carcinoma_-_very_high_mag.jpg Nested variant of urothelial carcinoma - very high mag. (WC)].
*[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>


=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:
*[http://commons.wikimedia.org/wiki/File:Inverted_papilloma_high_mag.jpg Inverted papilloma - high mag. (WC)].
*[http://commons.wikimedia.org/wiki/File:Inverted_papilloma_intermed_mag.jpg Inverted papilloma - intermed. mag. (WC)].


==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:
*[http://en.wikipedia.org/wiki/File:Punlmp1.jpg PUNLMP - low mag. (WC)].
*[http://en.wikipedia.org/wiki/File:Punlmp2.jpg PUNLMP - high mag. (WC)].
 
==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===
*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>


===Sign out===
==High-grade papillary urothelial carcinoma==
<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 urothelial cell carcinoma'', abbreviated ''high grade UCC''.  
*[[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:
===The big table of cystitis===
*[[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>
 
=Benign urothelial lesions=
The big table of cystitis:
{| class="wikitable sortable"  
{| class="wikitable sortable"  
! Type
! Type
Line 591: 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 664: Line 475:
*[[Nested urothelial cell carcinoma]].<ref name=pmid12960809>{{Cite journal  | last1 = Volmar | first1 = KE. | last2 = Chan | first2 = TY. | last3 = De Marzo | first3 = AM. | last4 = Epstein | first4 = JI. | title = Florid von Brunn nests mimicking urothelial carcinoma: a morphologic and immunohistochemical comparison to the nested variant of urothelial carcinoma. | journal = Am J Surg Pathol | volume = 27 | issue = 9 | pages = 1243-52 | month = Sep | year = 2003 | doi =  | PMID = 12960809 }}</ref>
*[[Nested urothelial cell carcinoma]].<ref name=pmid12960809>{{Cite journal  | last1 = Volmar | first1 = KE. | last2 = Chan | first2 = TY. | last3 = De Marzo | first3 = AM. | last4 = Epstein | first4 = JI. | title = Florid von Brunn nests mimicking urothelial carcinoma: a morphologic and immunohistochemical comparison to the nested variant of urothelial carcinoma. | journal = Am J Surg Pathol | volume = 27 | issue = 9 | pages = 1243-52 | month = Sep | year = 2003 | doi =  | PMID = 12960809 }}</ref>
*[[Inverted urothelial papilloma|Inverted papilloma]].
*[[Inverted urothelial papilloma|Inverted papilloma]].
*[[Cystitis cystica]] - have lumens, may be focal.


===IHC===
===IHC===
Line 671: 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.


==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.
 
===Sign out===
<pre>
URINARY BLADDER NECK, BIOPSY:
- CYSTITIS CYSTICA ET GLANDULARIS.
- NEGATIVE FOR MALIGNANCY.
</pre>


==Malakoplakia==
==Malakoplakia==
Line 714: 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:
*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>
*[[WC]]:
**[http://commons.wikimedia.org/wiki/File:Nephrogenic_adenoma_-_intermed_mag.jpg Nephrogenic adenoma - intermed. mag. (WC)].
**[http://commons.wikimedia.org/wiki/File:Nephrogenic_adenoma_-_very_high_mag.jpg Nephrogenic adenoma - very high mag. (WC)].
 
===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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