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The '''urothelium''' lines the upper portion of the genitourinary tract... 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.


==Extent of urothelium==
=Normal urothelium=
===Urethra in males===
===Gross===
*Pre-prostatic urethra - transistional epithelium.
====Extent of urothelium====
*Prostatic urethra - transistional epithelium.
*[[Ureters]].
*Membranous urethra (from apex of prostate to bulb of penis (bulb of the corpus spongiosusm)) - pseudostrat. columnar epithelium.
*Renal pelvis.
*Spony urethra - pseudostratified columnar epi. (proximal) & strat. squamous (distal).
*[[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).


==Normal histology==
===Microscopic===
*Prominent nucleoli (???).
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]].


*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.


===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=
==Where to start==
==Where to start==
July 1st PGY-2:
July 1st PGY-2:
Line 28: Line 60:
#Fibrovascular cores = papillae... may be cancer!
#Fibrovascular cores = papillae... may be cancer!


==Note about terminology==
==A checklist-like approach==
*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''.<ref name=pmid19160695>{{Cite journal  | last1 = Van der Kwast | first1 = TH. | last2 = Zlotta | first2 = AR. | last3 = Fleshner | first3 = N. | last4 = Jewett | first4 = M. | last5 = Lopez-Beltran | first5 = A. | last6 = Montironi | first6 = R. | title = Thirty-five years of noninvasive bladder carcinoma: a plea for the use of papillary intraurothelial neoplasia as new terminology. | journal = Anal Quant Cytol Histol | volume = 30 | issue = 6 | pages = 309-15 | month = Dec | year = 2008 | doi =  | PMID = 19160695 }}</ref>
**If the terminology in the urinary bladder were applied to the colon, we'd call all ''adenomas'', i.e. pre-malignant lesions, ''carcinomas''.
 
==Approach==
# Papillary structure - with fibrovascular cores?
# Papillary structure - with fibrovascular cores?
#* Nuclear pleomorphism?
#* Nuclear pleomorphism?
Line 46: Line 73:
#* 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?


Pitfalls:
Pitfalls:
*Urothelial carcinoma of the bladder may be confused with a ''paraganglioma of the bladder''.
*Urothelial carcinoma of the bladder may be confused with a ''[[paraganglioma]] of the bladder''.
**Way to differentiate: paraganglioma = ''stippled chromatin'', UCC = ''single nucleoli''.
**Way to differentiate: paraganglioma = ''stippled chromatin'', UCC = ''single nucleoli''.


==Risk factors for UCC==
===Note about terminology===
Risk factors for UCC:
*The bladder is rather unique in that "carcinoma" is a label used for things that are non-invasive.
*[[Smoking]].
**It has been suggested that many things that are called ''papillary urothelial carcinoma'', would be better described as ''papillary intraurothelial neoplasia''.<ref name=pmid19160695>{{Cite journal  | last1 = Van der Kwast | first1 = TH. | last2 = Zlotta | first2 = AR. | last3 = Fleshner | first3 = N. | last4 = Jewett | first4 = M. | last5 = Lopez-Beltran | first5 = A. | last6 = Montironi | first6 = R. | title = Thirty-five years of noninvasive bladder carcinoma: a plea for the use of papillary intraurothelial neoplasia as new terminology. | journal = Anal Quant Cytol Histol | volume = 30 | issue = 6 | pages = 309-15 | month = Dec | year = 2008 | doi = | PMID = 19160695 }}</ref>
*Toxins.
**If the terminology in the urinary bladder were applied to the colon, we'd call all ''adenomas'', i.e. pre-malignant lesions, ''carcinomas''.
*Drugs, e.g. cyclophosphamide.
*Marijuana.<ref name=pmid16413342>PMID 16413342.</ref>
*Chinese Herbs.<ref>URL: [http://content.nejm.org/cgi/content/full/343/17/1268 http://content.nejm.org/cgi/content/full/343/17/1268]. Accessed on: 27 May 2010.</ref>
 
==Premalignant/Hyperplasic/Reactive changes==
Several different benign/premalignant diagnoses can be made:
*Reactive atypia.
*Flat urothelial hyperplasia.
*Urothelial dysplasia.


Cancer
=Overview in tables=
*Urothelial carcinoma in situ.
==General categorization==
*Invasive UCC.
Urothelial lesions can broadly be divided into:
#Flat lesions.
#*Lack papillae.
#*Tend to be more aggressive.
#Papillary lesions.
#*Must have true papillae.
#*Very common.
#*More often benign/indolent.


===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)
! 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'''
| -
|-
|-
|Nuclear enlargement<br>(X stromal lymphocyte) ||none (2x) ||moderate, prominent (3x) ||none (2x) ||moderate (3x) ||'''signif. (4-5x)'''|| signif. (4-5X)
| '''Flat urothelial hyperplasia'''
| none (2x)
| small
| none, round
| as normal
| as normal
| '''increased'''
| usu. none
| -
|-
|-
|Nucleoli ||small ||prominent ||small ||small, some multiple ||+/-large ||+/-large
| '''[[Urothelial dysplasia]]'''
| moderate (3x)
| small, some multiple
| mod. variation, some irregularity
| '''lost'''
| rare, none atypical
| as normal
| usu. none
| -
|-
|-
|size var., shape ||none, round ||none, round ||none, round ||mod. variation, some irregularity ||marked, irregular ||marked, irregular
| '''[[Urothelial carcinoma in situ]]'''
| '''signif. (4-5x)'''
| +/-large
| marked, irregular
| lost
| common, atypical
| thin, thick or norm.
| +/-
| -
|-
|-
|Polarity ||matures to surface ||as normal ||as normal ||'''lost''' ||lost ||lost
| '''[[Urothelial carcinoma|Invasive UCC]]'''
| signif. (4-5X)
| +/-large
| marked, irregular
| lost
| common, atypical
| thin, thick or norm.
| +/-
| '''stromal invasion'''
|-
|-
|Mitoses ||none/minimal ||some, none atypical ||as normal ||rare, none atypical ||common, atypical ||common, atypical
|}
The '''bold''' entry is considered the key feature.
 
===Papillary urothelial lesions===
Urothelial cells in papillae - benign/premalignant/cancerous:<ref>{{Ref GUP|166-175}}</ref><ref name=Ref_WMSP310>{{Ref WMSP|310}}</ref>
{| class="wikitable sortable"
! Diagnosis
! Papillae features
! Papillae branching
! Papillae fusion
! 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
|-
|-
|Thickness ||4-5 cells ||as normal ||'''increased''' ||as normal ||thin, thick or norm. ||thin, thick or norm.
| [[PUNLMP]]
| '''slender FV core'''
| uncommon
| rare
| '''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
|-
|-
|Inflammation ||none ||'''severe, acute or chronic''' ||usu. none ||usu. none ||+/- ||+/-
| [[Low grade papillary urothelial carcinoma|Low grade PUCC]]
| slender FV core, <br>'''thick epithelium'''
| frequent
| some
| '''enlarged with variation'''
| infreq., usually basal
| PUNLMP, high gr.
| -/+ p53, CK20+ umbrella
| +/- small nucleoli
| nuc. pleomorphism, <br> thick epithelium
|-
|-
|Other ||- ||- ||- ||- ||- ||'''stromal invasion'''
| [[High grade papillary urothelial carcinoma|High grade PUCC]]
| mixed population
| common
| common
| '''4-5x lymphocyte,'''<br>'''marked pleomorphism'''
| common, everywhere
| low gr., invasive UCC
| '''diffuse CK20+''', p53+ in 50%
| nucleoli prominent
| marked nuclear pleomorphism
|-
|-
|}
|}
The '''bold''' entry is considered the key feature.
Notes:
*FV core = fibrovascular core.
*PUCC = papillary urothelial carcinoma.
 
=Risk factors for urothelial carcinoma=
*[[Smoking]].
*Toxins.
*Drugs, e.g. cyclophosphamide.
*Marijuana.<ref name=pmid16413342>{{Cite journal  | last1 = Chacko | first1 = JA. | last2 = Heiner | first2 = JG. | last3 = Siu | first3 = W. | last4 = Macy | first4 = M. | last5 = Terris | first5 = MK. | title = Association between marijuana use and transitional cell carcinoma. | journal = Urology | volume = 67 | issue = 1 | pages = 100-4 | month = Jan | year = 2006 | doi = 10.1016/j.urology.2005.07.005 | PMID = 16413342 }}</ref>
*Chinese Herbs.<ref>URL: [http://content.nejm.org/cgi/content/full/343/17/1268 http://content.nejm.org/cgi/content/full/343/17/1268]. Accessed on: 27 May 2010.</ref>
 
Others:
*[[Lynch syndrome]].
**Should be considered in ureteral cancers.<ref name=pmid21419447>{{Cite journal  | last1 = Crockett | first1 = DG. | last2 = Wagner | first2 = DG. | last3 = Holmäng | first3 = S. | last4 = Johansson | first4 = SL. | last5 = Lynch | first5 = HT. | title = Upper urinary tract carcinoma in Lynch syndrome cases. | journal = J Urol | volume = 185 | issue = 5 | pages = 1627-30 | month = May | year = 2011 | doi = 10.1016/j.juro.2010.12.102 | PMID = 21419447 }}</ref>
 
=Flat urothelial lesions=
==Overview==
Several different benign & pre-malignant diagnoses can be made.
 
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.
*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===
*May be confused with [[urothelial carcinoma in situ]].<ref name=Ref_Amin2-57>{{Ref Amin|2-57}}</ref>
*Uncommon.
*Considered to be [[normal urothelium]].


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


==Urothelial cell carcinoma UCC (flat)==
DDx:<ref>URL: [http://pathology.jhu.edu/bladder/definitions.cfm http://pathology.jhu.edu/bladder/definitions.cfm]. Accessed on: 8 January 2014.</ref>
*Nuclear pleomorphism.
*[[Urothelial carcinoma in situ]].
**Most important feature.
*[[Urothelial dysplasia]].
**Compare nuclei to one another.
*Increased N/C ratio.
*Lack of maturation to surface (important).


*Cells become dyscohesive.
====Images====
**Mostly useless in my experience.
<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===
Features:
*Ki-67 low.
*CK7 +ve CK20 +ve.
*p53 -ve.
**CK20 may be negative.
 
===Sign out===
<pre>
URINARY BLADDER, TRANSURETHRAL BIOPSY:
- UROTHELIAL MUCOSA WITH MILD CHRONIC INFLAMMATION.
- NO EVIDENCE OF MALIGNANCY.
 
COMMENT:
Levels were cut and show large benign umbrella cells.
</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}}


UCC vs. Prostate:
==Urothelial carcinoma in situ==
*UCC: p63+, PSA-, PSAP-, CK7+, CK20+.
*Abbreviated ''CIS''.
*Prostate: p63-, PSA+, PSAP+, CK7-, CK20-.
*[[AKA]] ''high-grade (urothelial) dysplasia''.
{{Main|Urothelial carcinoma in situ}}


UCC vs. RCC:
==Urothelial cell carcinoma==
*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 }}
:See ''[[Urine_cytopathology#Urothelial_cell_carcinoma|urine cytology]]'' for the [[cytopathology]].
</ref>
*Abbreviated ''UCC''.
*[[AKA]] ''urothelial carcinoma''.
{{Main|Urothelial carcinoma}}


==UCC (papillary lesions)==
=Papillary urothelial lesions=
Papillary urothelial lesions are grouped into one of five categories (listed from bad to good prognosis):<ref name=Ref_WMSP310>{{Ref WMSP|310}}</ref>
Papillary urothelial lesions are grouped into one of five categories (listed from good to bad prognosis):<ref name=Ref_WMSP310>{{Ref WMSP|310}}</ref>
*High grade papillary.
#[[Urothelial papilloma]].
*Low grade papillary.
#[[Inverted urothelial papilloma|Inverted papilloma]].
*Papillary urothelial neoplasm of low malignant potential (PUNLMP).
#[[Papillary urothelial neoplasm of low malignant potential]] (PUNLMP).
**''PUNLMP'' is pronouced "pun-lump".
#*''PUNLMP'' is pronouced "pun-lump".
*Inverted papilloma.
#[[Low grade papillary urothelial carcinoma]].
*Urothelial papilloma.
#[[High grade papillary urothelial carcinoma]].


Key characteristics:
Key characteristics:
Line 144: Line 333:
#Papillae fusion.
#Papillae fusion.


===High grade papillary UCC===
==Urothelial papilloma==
Micro.<ref name=Ref_WMSP310>{{Ref WMSP|310}}</ref>
{{Main|Urothelial papilloma}}
*"High grade nuclear features":
 
**Nuclear pleomorphism - often 4-5x the size of stromal lymphocytes.<ref name=Ref_GUP161>{{Ref GUP|161}}</ref>
==Inverted urothelial papilloma==
*Architectural complexity.
*[[AKA]] ''[[inverted papilloma]]''.
**Fused papillary common.
{{Main|Inverted urothelial papilloma}}
**Papillae branch.
*Mitoses common.


===Low grade papillary UCC===
==Papillary urothelial neoplasm of low malignant potential==
Micro.<ref name=Ref_WMSP310>{{Ref WMSP|310}}</ref>
*Abbreviated ''PUNLMP''.
*Fused papillae.
**This is pronounced ''pun-lump''.
*Papillae branch.
{{Main|Papillary urothelial neoplasm of low malignant potential}}
*Larger nuclei than PUNLMPs.


===PUNLMP===
==Low-grade papillary urothelial carcinoma==
Microscopic:<ref name=Ref_WMSP310>{{Ref WMSP|310}}</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>
*Rare fused papillae.
*[[AKA]] ''low-grade papillary urothelial cell carcinoma''.
*Infrequent mitoses.
{{Main|Low-grade papillary urothelial carcinoma}}
*Nuclei larger than papilloma - but monotonous.<ref name=Ref_GUP170>{{Ref GUP|170}}</ref>


===Papilloma===
==High-grade papillary urothelial carcinoma==
Micro.<ref name=Ref_WMSP310>{{Ref WMSP|310}}</ref>
*Abbreviated ''HGPUC''.
*Papillary fronds.
*[[AKA]] ''high-grade papillary urothelial cell carcinoma'', abbreviated ''HGPUCC''.
*Minimal branching or fusion.
{{Main|High-grade papillary urothelial carcinoma}}
*Cytological features of normal urothelium.
**Normal urothelium approx. 2x the size of stromal lymphocytes.<ref name=Ref_GUP161>{{Ref GUP|161}}</ref>
*No mitoses.


===Inverted papilloma===
==Papillary urothelial hyperplasia==
*Like papillomas... but grow downward.<ref name=Ref_WMSP310>{{Ref WMSP|310}}</ref>
*[[AKA]] ''papillary hyperplasia''.
*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>
*[[AKA]] ''reactive papillary hyperplasia''.
{{Main|Papillary urothelial hyperplasia}}


Images:
=Benign urothelial lesions=
*[http://commons.wikimedia.org/wiki/File:Inverted_papilloma_high_mag.jpg Inverted papilloma - high mag. (WC)].
===Cystitis===
*[http://commons.wikimedia.org/wiki/File:Inverted_papilloma_intermed_mag.jpg Inverted papilloma - intermed. mag. (WC)].
*Inflammation of the [[urinary bladder]].
*Comes in many forms (see below).
*Typically a [[clinical diagnosis]] under the more general term [[urinary tract infection]].


===Tabular comparison of papillary lesions===
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>


Urothelial cells in papillae - benign/premalignant/cancerous:<ref>{{Ref GUP|166-175}}</ref><ref name=Ref_WMSP310>{{Ref WMSP|310}}</ref>
===The big table of cystitis===
{| class="wikitable"
{| class="wikitable sortable"  
| ||'''Papilloma''' ||'''PUNLMP''' ||'''low grade PUCC''' ||'''high grade PUCC'''
! Type
! Key feature
! DDx
! Reference
|-
|-
|papillae features ||'''fat papillae''', <br>'''thick FV core''' ||'''slender FV core''' ||slender FV core, <br>'''thick epithelium''' ||mixed population
|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
| <ref name=Ref_GUP113>{{Ref GUP|113}}</ref>
|-
|-
|papillae branching ||rare ||uncommon ||frequent ||common
|[[Polypoid cystitis]]
| wide base, height > base
| papillary cystitis, bullous cystitis
| <ref name=Ref_GUP120>{{Ref GUP|120}}</ref>
|-
|-
|papillae fusion ||none ||rare ||some ||common
|Bullous cystitis
| wide base, height < base
| papillary cystitis, polypoid cystitis
| <ref name=Ref_GUP120>{{Ref GUP|120}}</ref>
|-
|-
|nuclear size ||normal (2x lymphocyte) ||'''enlarged - uniform''' ||'''enlarged with variation''' ||'''4-5x lymphocyte,'''<br>'''marked pleomorphism'''
|Papillary cystitis
| narrow base, height > base
| polypoid cystitis, bullous cystitis
| <ref name=Ref_GUP120>{{Ref GUP|120}}</ref>
|-
|-
|mitoses ||very rare basal || rare basal only ||infreq., usually basal ||common, everywhere
|[[Interstitial cystitis]]
| +/-ulceration (uncommon) - requires clinical correlation
| urothelial CIS
| <ref name=Ref_GUP124>{{Ref GUP|124}}</ref>
|-
|-
|DDx ||PUNLMP, low gr. PUCC ||papilloma, low gr. ||PUNLMP, high gr. ||low gr., invasive UCC
|Follicular cystitis
| lymphoid follicles
| non-Hodgkin [[lymphoma]]
| <ref name=Ref_GUP122>{{Ref GUP|122}}</ref>
|-
|-
|IHC ||p53-, CK20+ umbrella cells ||CK20+ umbrella ||-/+ p53, CK20+ umbrella ||'''diffuse CK20+''', p53+ in 50%
|Infectious cystitis
|-
| dependent cause (bacterial, viral, fungal)
|Other ||cytologically normal ||low cellular density (@ low power) vs. low gr.<ref>GAG. 26 February 2009.</ref> ||+/- small nucleoli ||nucleoli prominent
|  
|-
| <ref name=Ref_GUP127>{{Ref GUP|127}}</ref>
|Key feature ||normal cells,<br>fat papillae ||uniformly enlarged cell pop., <br>slender papillae ||nuc. pleomorphism, <br> thick epithelium ||marked nuclear pleomorphism
|-
|-
|Granulomatous cystitis
| [[granuloma]]s
| [[tuberculosis]], [[schistosomiasis]], [[fungi|fungal infection]], post-BCG
| <ref name=Ref_GUP127>{{Ref GUP|127}}</ref>
|-
|Radiation cystitis
| edema, vascular congestion, +/- [[erosion]]s -- acute; fibrosis in LP and detrusor -- chronic
|
| <ref name=Ref_GUP138>{{Ref GUP|138}}</ref>
|}
|}
Notes:
*FV core = fibrovascular core.
*PUCC = papillary urothelial carcinoma.


==Benign==
==Interstitial cystitis==
Brunn nests:<ref name=Ref_PBoD1028>{{Ref PBoD|1028}}</ref>
{{Main|Interstitial cystitis}}
*Benign inbudding nests of urothelium.
**Should lead to consideration of "inverted papilloma".


Cystitis cystica:<ref name=Ref_PBoD1028>{{Ref PBoD|1028}}</ref>
==Follicular cystitis==
*Brunn nests with urothelium.
===Microscopic===
Features:<ref name=Ref_GUP122>{{Ref GUP|122}}</ref>
*Lymphoid follicles in the lamina propria.


cystitis glandularis:<ref name=Ref_PBoD1028>{{Ref PBoD|1028}}</ref>
DDx:
*Brunn nests with cuboidal and columnar epithelium.
*Non-Hodgkin [[lymphoma]].


==Invasive UCC==
===Sign out===
Staging:
<pre>
*T1 - lamina propria.
URINARY BLADDER, BIOPSY:
**Several subdivisions of T1 exist:<ref>Sternberg, H4P 4th Ed., P.2048-9.</ref>
- UROTHELIAL MUCOSA WITH CHRONIC INFLAMMATION AND BENIGN LYMPHOID NODULES WITH GERMINAL CENTRE FORMATION.
***T1a - superficial or in muscularis mucosae.
- MUSCULARIS PROPRIA PRESENT.
***T1b - beyond muscularis mucosae - into submucosa.
- NEGATIVE FOR UROTHELIAL CARCINOMA IN SITU AND NEGATIVE FOR MALIGNANCY.
*T2 - muscularis propria.
</pre>


===Invasion vs. in situ===
==Polypoid cystitis==
Useful features - present in invasion:<ref>Sternberg, H4P, P.2047.</ref>
===General===
*Thin-walled vessels.
*Uncommon.
*Stromal reaction (hypercellularity).
*Wide age range.
*Retraction artefact around the tumour cell nests.
*Benign.


===Subtypes===
===Microscopic===
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>
Features:<ref name=Ref_GUP120>{{Ref GUP|120}}</ref>
*Squamous differentiation.
*Polypoid urothelium-covered projections with:
*Clear cell.
*#Broad bases.
*Plasmacytoid.
*#Height > base.
**Abundant gray cytoplasm, eccentric nucleus.
*#Extensive edema.
*Micropapillary.
**Small nests (< ~10 cells/nest).
*Many others...


==Renal cell carcinoma==
DDx:
{{main|Renal cell carcinoma}}
*Papillary cystitis - not a broad base.
Clinically, it may not be possible to differentiate renal pelvis UCC and RCC.
*Bullous cystitis.


==Nephrogenic metaplasia==
Image:
*[[AKA]] ''nephrogenic adenoma''.
*[http://www.webpathology.com/image.asp?case=51&n=3 Polypoid cystitis (webpathology.com)].


==von Brunn nests==
===General===
===General===
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.
*Benign.
*Classic location is the [[urinary bladder]].
**Also reported in ureter and prostatic urethra.
*May mimic adenocarcinoma


===Microscopic===
===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>
Features:<ref name=Ref_PBoD1028>{{Ref PBoD|1028}}</ref>
*Tubular structures - '''key feature'''.
*Nests of (benign) urothelium budding into the lamina propria.
**Morphologically similar to renal tubules.
 
Note:
*Nests should '''not''' extend into the muscularis propria.
 
DDx:
*[[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]].
*[[Cystitis cystica]] - have lumens, may be focal.
 
===IHC===
Features:<ref name=pmid12960809/>
*p53 -ve.
*MIB-1 <3%.
 
==Cystitis cystica==
{{Main|Cystitis cystica}}
 
==Cystitis glandularis==
{{Main|Cystitis glandularis}}
 
==Malakoplakia==
{{Main|Malakoplakia}}
 
==Nephrogenic adenoma==
*[[AKA]] ''mesonephric adenoma''.
*[[AKA]] ''nephrogenic metaplasia''.
{{Main|Nephrogenic adenoma}}


==See also==
=See also=
*[[Prostate]].
*[[Prostate]].
*[[Genitourinary pathology]].
*[[Genitourinary pathology]].
*[[Kidney tumours]].


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


[[Category:Uropathology]]
[[Category:Genitourinary pathology]]
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