Difference between revisions of "Urothelium"

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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=
===Gross===
====Extent of urothelium====
*[[Ureters]].
*Renal pelvis.
*[[Urinary bladder]].
*Part of the urethra.
=====Urethra in males=====
{{Main|Urethra}}
*Pre-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.
*Spongy urethra - pseudostratified columnar epithelium (proximal) & stratified squamous (distal).
 
===Microscopic===
Features:
*Maturation (cuboidal at base - squamoid at surface).
*Maturation (cuboidal at base - squamoid at surface).
**Surface cells called 'umbrella cells' (umbrella cells CK20+).
**Surface cells called 'umbrella cells' (umbrella cells CK20 +ve).
*Urothelium should be 4-5 cell layers thick.
*Urothelium should be 4-5 cell layers thick.
*+/-Prominent nucleoli.
*+/-Prominent [[nucleoli]].


*Should NOT have papillary architecture -- if it does it is likely [[cancer]]!
Note:
*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.


==Extent of urothelium==
===IHC===
*[[Ureters]].
*Rare superficial [[CK20]] staining.
*Renal pelvis.
 
*[[Urinary bladder]].
====Image====
*Part of the urethra.
<gallery>
Image: Benign urothelium - CK20 -- high mag.jpg | Benign urothelium - CK20 - high mag. (WC)
===Urethra in males===
</gallery>
*Pre-prostatic urethra - transistional epithelium.
 
*Prostatic urethra - transistional epithelium.
===Sign out===
*Membranous urethra (from apex of prostate to bulb of penis (bulb of the corpus spongiosusm)) - pseudostrat. columnar epithelium.
<pre>
*Spony urethra - pseudostratified columnar epi. (proximal) & strat. squamous (distal).
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?
Line 73: Line 99:
===Flat urothelial lesions===
===Flat urothelial lesions===
Comparison urothelial changes - flat epithelium - benign/premalignant/cancerous:<ref>{{Ref GUP|155-163}}</ref>
Comparison urothelial changes - flat epithelium - benign/premalignant/cancerous:<ref>{{Ref GUP|155-163}}</ref>
{| class="wikitable"
{| class="wikitable sortable"
| ||'''Normal'''||'''Reactive atypia'''||'''Flat urothelial hyperplasia'''||'''Urothelial dysplasia'''||'''UCC in situ'''||'''Invasive UCC'''
! Diagnosis
|-
! Nuclear enlargement<br>(X stromal lymphocyte)
|Nuclear enlargement<br>(X stromal lymphocyte) ||none (2x) ||moderate, prominent (3x) ||none (2x) ||moderate (3x) ||'''signif. (4-5x)'''|| signif. (4-5X)
! Nucleoli
|-
! size var., shape
|Nucleoli ||small ||prominent ||small ||small, some multiple ||+/-large ||+/-large
! Polarity
! Mitoses
! Thickness
! Inflammation
! Other
|-
|-
|size var., shape ||none, round ||none, round ||none, round ||mod. variation, some irregularity ||marked, irregular ||marked, irregular
| '''Normal'''
| none (2x)
| small
| none, round
| matures to surface
| none/minimal
| 4-5 cells
| none
| -
|-
|-
|Polarity ||matures to surface ||as normal ||as normal ||'''lost''' ||lost ||lost
|'''Reactive atypia'''
| moderate, prominent (3x)
| prominent
| none, round
| as normal
| some, none atypical
| as normal
| '''severe, acute or chronic'''
| -
|-
|-
|Mitoses ||none/minimal ||some, none atypical ||as normal ||rare, none atypical ||common, atypical ||common, atypical
| '''Flat urothelial hyperplasia'''
| none (2x)
| small
| none, round
| as normal
| as normal
| '''increased'''
| usu. none
| -
|-
|-
|Thickness ||4-5 cells ||as normal ||'''increased''' ||as normal ||thin, thick or norm. ||thin, thick or norm.
| '''[[Urothelial dysplasia]]'''
| moderate (3x)
| small, some multiple
| mod. variation, some irregularity
| '''lost'''
| rare, none atypical
| as normal
| usu. none
| -
|-
|-
|Inflammation ||none ||'''severe, acute or chronic''' ||usu. none ||usu. none ||+/- ||+/-
| '''[[Urothelial carcinoma in situ]]'''
| '''signif. (4-5x)'''
| +/-large
| marked, irregular
| lost
| common, atypical
| thin, thick or norm.
| +/-
| -
|-
|-
|Other ||- ||- ||- ||- ||- ||'''stromal invasion'''
| '''[[Urothelial carcinoma|Invasive UCC]]'''
| signif. (4-5X)
| +/-large
| marked, irregular
| lost
| common, atypical
| thin, thick or norm.
| +/-
| '''stromal invasion'''
|-
|-
|}
|}
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===Papillary urothelial lesions===
===Papillary urothelial lesions===
Urothelial cells in papillae - benign/premalignant/cancerous:<ref>{{Ref GUP|166-175}}</ref><ref name=Ref_WMSP310>{{Ref WMSP|310}}</ref>
Urothelial cells in papillae - benign/premalignant/cancerous:<ref>{{Ref GUP|166-175}}</ref><ref name=Ref_WMSP310>{{Ref WMSP|310}}</ref>
{| class="wikitable"
{| class="wikitable sortable"
|
! Diagnosis
| '''Papilloma'''
! Papillae features
| '''PUNLMP'''
! Papillae branching
| '''low grade PUCC'''
! Papillae fusion
| '''high grade PUCC'''
! Nuclear size
! Mitoses
! DDx
! IHC
! Other
! Key feature
|-
| [[Urothelial papilloma|Papilloma]]
| '''fat papillae''', <br>'''thick FV core'''
| rare
| none
| normal (2x lymphocyte)
| very rare basal
| [[PUNLMP]], low gr. PUCC
| p53-, CK20+ umbrella cells
| cytologically normal
| normal cells,<br>fat papillae
|-
|-
| papillae features
| [[PUNLMP]]
| '''fat papillae''', <br>'''thick FV core'''
| '''slender FV core'''
| '''slender FV core'''
| uncommon
| slender FV core, <br>'''thick epithelium'''
| rare
| mixed population
| '''enlarged - uniform'''
| rare basal only
| papilloma, low gr.
| CK20+ umbrella
| low cellular density (@ low power) vs. low gr.<ref>GAG. 26 February 2009.</ref>
| uniformly enlarged cell pop., <br>slender papillae
|-
|-
| papillae branching
| [[Low grade papillary urothelial carcinoma|Low grade PUCC]]
| rare
| slender FV core, <br>'''thick epithelium'''
| uncommon
| frequent
| frequent
| some
| common
| '''enlarged with variation'''
| infreq., usually basal
| PUNLMP, high gr.
| -/+ p53, CK20+ umbrella
| +/- small nucleoli
| nuc. pleomorphism, <br> thick epithelium
|-
|-
| papillae fusion
| [[High grade papillary urothelial carcinoma|High grade PUCC]]
| none
| mixed population
| rare
| common
| some
| common
| common
|-
| nuclear size
| normal (2x lymphocyte) |
| '''enlarged - uniform'''
| '''enlarged with variation'''
| '''4-5x lymphocyte,'''<br>'''marked pleomorphism'''
| '''4-5x lymphocyte,'''<br>'''marked pleomorphism'''
|-
| common, everywhere
| mitoses
| low gr., invasive UCC
| very rare basal
| '''diffuse CK20+''', p53+ in 50%
| rare basal only
| infreq., usually basal
| common, everywhere
|-
| DDx
| PUNLMP, low gr. PUCC
| papilloma, low gr.
| PUNLMP, high gr.
| low gr., invasive UCC
|-
|IHC
| p53-, CK20+ umbrella cells
| CK20+ umbrella
| -/+ p53, CK20+ umbrella
| '''diffuse CK20+''', p53+ in 50%
|-
|Other
| cytologically normal
| low cellular density (@ low power) vs. low gr.<ref>GAG. 26 February 2009.</ref>
| +/- small nucleoli
| nucleoli prominent
| nucleoli prominent
|-
|Key feature
| normal cells,<br>fat papillae
| uniformly enlarged cell pop., <br>slender papillae
| nuc. pleomorphism, <br> thick epithelium
| marked nuclear pleomorphism
| marked nuclear pleomorphism
|-
|-
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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====
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=
Line 336: Line 334:


==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]].<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>
 
===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===
==High-grade papillary urothelial carcinoma==
*Very common.
*Abbreviated ''HGPUC''.
*Very good prognosis - if it is non-invasive.
*[[AKA]] ''high-grade papillary urothelial cell carcinoma'', abbreviated ''HGPUCC''.
{{Main|High-grade papillary urothelial carcinoma}}


===Microscopic===
==Papillary urothelial hyperplasia==
Features:<ref name=Ref_WMSP310>{{Ref WMSP|310}}</ref>
*[[AKA]] ''papillary hyperplasia''.
*Fused papillae.
*[[AKA]] ''reactive papillary hyperplasia''.
*Papillae branch.
{{Main|Papillary urothelial hyperplasia}}
*Larger nuclei than PUNLMPs.
*+/-Invasion into the lamina propria.


Note:
=Benign urothelial lesions=
*The presence/absence of muscle should be commented on in biopsy specimens.
===Cystitis===
*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>
*Inflammation of the [[urinary bladder]]. 
 
*Comes in many forms (see below).
DDx:
*Typically a [[clinical diagnosis]] under the more general term [[urinary tract infection]].
*[[PUNLMP]]
*[[High grade papillary urothelial carcinoma]].
 
===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==
*[[AKA]] ''high grade urothelial cell carcinoma''.
**Abbreviated ''high grade UCC''.
 
===General===
*Aggressive.
 
===Microscopic===
Features:<ref name=Ref_WMSP310>{{Ref WMSP|310}}</ref>
*"High grade nuclear features":
**Nuclear pleomorphism - often 4-5x the size of stromal lymphocytes.<ref name=Ref_GUP161>{{Ref GUP|161}}</ref>
*Architectural complexity.
**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 AT LEAST INTO MUSCULARIS PROPRIA.
- LYMPHOVASCULAR INVASION PRESENT.
</pre>
 
=Benign urothelial lesions=
The big table of cystitis:
{| class="wikitable sortable"  
{| class="wikitable sortable"  
! Type
! Type
Line 484: Line 386:
| <ref name=Ref_GUP120>{{Ref GUP|120}}</ref>
| <ref name=Ref_GUP120>{{Ref GUP|120}}</ref>
|-
|-
|Bullous cystitis.
|Bullous cystitis
| wide base, height < base  
| wide base, height < base  
| papillary cystitis, polypoid cystitis
| papillary cystitis, polypoid cystitis
Line 494: Line 396:
| <ref name=Ref_GUP120>{{Ref GUP|120}}</ref>
| <ref name=Ref_GUP120>{{Ref GUP|120}}</ref>
|-
|-
|Interstitial cystitis
|[[Interstitial cystitis]]
| +/-ulceration (uncommon) - requires clinical correlation
| +/-ulceration (uncommon) - requires clinical correlation
| urothelial CIS
| urothelial CIS
Line 519: Line 421:
| <ref name=Ref_GUP138>{{Ref GUP|138}}</ref>
| <ref name=Ref_GUP138>{{Ref GUP|138}}</ref>
|}
|}
==Interstitial cystitis==
{{Main|Interstitial cystitis}}


==Follicular cystitis==
==Follicular cystitis==
Line 531: Line 436:
<pre>
<pre>
URINARY BLADDER, BIOPSY:
URINARY BLADDER, BIOPSY:
- UROTHELIAL MUCOSA WITH CHRONIC INFLAMMATION AND BENIGN LYMPHOID FOLLICLES.
- UROTHELIAL MUCOSA WITH CHRONIC INFLAMMATION AND BENIGN LYMPHOID NODULES WITH GERMINAL CENTRE FORMATION.
- MUSCULARIS PROPRIA PRESENT.
- MUSCULARIS PROPRIA PRESENT.
- NEGATIVE FOR UROTHELIAL CARCINOMA IN SITU AND NEGATIVE FOR MALIGNANCY.
- NEGATIVE FOR UROTHELIAL CARCINOMA IN SITU AND NEGATIVE FOR MALIGNANCY.
Line 570: 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 577: 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 620: 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=

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)

Sign out

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.

Sign out

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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