Difference between revisions of "Urothelium"

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Urothelium (view source)

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


===Sign out===
===Sign out===
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| -
| -
|-
|-
| '''Urothelial dysplasia'''
| '''[[Urothelial dysplasia]]'''
| moderate (3x)
| moderate (3x)
| small, some multiple
| small, some multiple
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| -
| -
|-
|-
| '''UCC in situ'''
| '''[[Urothelial carcinoma in situ]]'''
| '''signif. (4-5x)'''
| '''signif. (4-5x)'''
| +/-large
| +/-large
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| -
| -
|-
|-
| '''Invasive UCC'''
| '''[[Urothelial carcinoma|Invasive UCC]]'''
| signif. (4-5X)
| signif. (4-5X)
| +/-large
| +/-large
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*Flat urothelial hyperplasia.
*Flat urothelial hyperplasia.
*Urothelial atypia of unknown significance.
*Urothelial atypia of unknown significance.
*Urothelial dysplasia (low-grade dysplasia).
*[[Urothelial dysplasia]] (low-grade dysplasia).
*Urothelial carcinoma in situ (high-grade dysplasia).
*Urothelial carcinoma in situ (high-grade dysplasia).
*Invasive urothelial carcinoma.
*Invasive urothelial carcinoma.
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*May be confused with [[urothelial carcinoma in situ]].<ref name=Ref_Amin2-57>{{Ref Amin|2-57}}</ref>
*May be confused with [[urothelial carcinoma in situ]].<ref name=Ref_Amin2-57>{{Ref Amin|2-57}}</ref>
*Uncommon.
*Uncommon.
*Considered to be [[normal urothelium]].


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


DDx:
DDx:<ref>URL: [http://pathology.jhu.edu/bladder/definitions.cfm http://pathology.jhu.edu/bladder/definitions.cfm]. Accessed on: 8 January 2014.</ref>
*[[Urothelial carcinoma in situ]].
*[[Urothelial carcinoma in situ]].
*[[Urothelial dysplasia]].
====Images====
<gallery>
Image: Benign urothelium with large superficial cells -- intermed mag.jpg | Benign large superf. cells - intermed. mag. (WC)
Image: Benign urothelium with large superficial cells -- high mag.jpg | Benign large superf. cells - high mag. (WC)
Image: Benign urothelium with large superficial cells -- very high mag.jpg | Benign large superf. cells - very high mag. (WC) 
</gallery>


===IHC===
===IHC===
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*p53 -ve.
*p53 -ve.


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


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


Note:
====Micro====
*The urothelium may be "depleted", i.e. exist only of rare large cells on the basement membrane.
The sections show small fragments of urothelial mucosa with enlarged benign superficial epithelial cells. The lamina propria has a mild lymphocytic infiltrate. No papillary structures are identified. There is no significant nuclear atypia.  Superficial small blood vessels appear congested.
**This is known as ''clinging urothelial carcinoma in situ''.<ref>{{Ref Amin|2-55}}</ref>


===IHC===
==Urothelial dysplasia==
Features:<ref>{{Cite journal  | last1 = Lopez-Beltran | first1 = A. | last2 = Jimenez | first2 = RE. | last3 = Montironi | first3 = R. | last4 = Patriarca | first4 = C. | last5 = Blanca | first5 = A. | last6 = Menendez | first6 = CL. | last7 = Algaba | first7 = F. | last8 = Cheng | first8 = L. | title = Flat urothelial carcinoma in situ of the bladder with glandular differentiation. | journal = Hum Pathol | volume = 42 | issue = 11 | pages = 1653-9 | month = Nov | year = 2011 | doi = 10.1016/j.humpath.2010.12.024 | PMID = 21531007 }}</ref>
*[[AKA]] ''low-grade (urothelial) dysplasia''.
*p53 +ve.
{{Main|Urothelial dysplasia}}
*Ki-67 high.


Benign urothelium vs. CIS:<ref name=pmid16932015>{{Cite journal  | last1 = Yin | first1 = H. | last2 = He | first2 = Q. | last3 = Li | first3 = T. | last4 = Leong | first4 = AS. | title = Cytokeratin 20 and Ki-67 to distinguish carcinoma in situ from flat non-neoplastic urothelium. | journal = Appl Immunohistochem Mol Morphol | volume = 14 | issue = 3 | pages = 260-5 | month = Sep | year = 2006 | doi =  | PMID = 16932015 }}</ref>
==Urothelial carcinoma in situ==
*CK20 +ve in deep cells (23/26 cases).
*Abbreviated ''CIS''.
**Normal urothelium -- only the umbrella cells.
*[[AKA]] ''high-grade (urothelial) dysplasia''.
*Ki-67 ~50% of cells - deep and superficial.
{{Main|Urothelial carcinoma in situ}}
**Normal ~10% of cells, confined to basal aspect.
 
===Sign out===
<pre>
URINARY BLADDER LESION ("TUMOUR"), TRANSURETHRAL RESECTION URINARY BLADDER TUMOUR (TURBT):
- UROTHELIAL CARCINOMA IN SITU.
- MUSCULARIS PROPRIA PRESENT.
</pre>


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


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


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


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


===General===
==Low-grade papillary urothelial carcinoma==
*Uncommon: prevalence ~ 0-3.5%.<ref name=pmid19346063>{{cite journal |author=May M, Brookman-Amissah S, Roigas J, ''et al.'' |title=Prognostic Accuracy of Individual Uropathologists in Noninvasive Urinary Bladder Carcinoma: A Multicentre Study Comparing the 1973 and 2004 World Health Organisation Classifications |journal=Eur. Urol. |volume= 57|issue= 5|pages= 850|year=2009 |month=March |pmid=19346063 |doi=10.1016/j.eururo.2009.03.052 |url=}}</ref>
*PUNLMP vs. [[low grade papillary urothelial carcinoma]] has a poor inter-rater reliability.<ref name=pmid17095142>{{cite journal |author=MacLennan GT, Kirkali Z, Cheng L |title=Histologic grading of noninvasive papillary urothelial neoplasms |journal=Eur. Urol. |volume=51 |issue=4 |pages=889–97; discussion 897–8 |year=2007 |month=April |pmid=17095142 |doi=10.1016/j.eururo.2006.10.037 |url=}}</ref>
 
Treatment:
*Excision and on-going follow-up - like non-invasive [[low grade papillary urothelial carcinoma]] (LGPUC).<ref name=pmid16697785>{{cite journal |author=Jones TD, Cheng L |title=Papillary urothelial neoplasm of low malignant potential: evolving terminology and concepts |journal=J. Urol. |volume=175 |issue=6 |pages=1995–2003 |year=2006 |month=June |pmid=16697785 |doi=10.1016/S0022-5347(06)00267-9 |url=}}</ref>
**Cheng ''et al.'' have advocated abandoning the term as they are treated like [[LGPUC]]s.<ref name=pmid22542126>{{Cite journal  | last1 = Cheng | first1 = L. | last2 = Maclennan | first2 = GT. | last3 = Lopez-Beltran | first3 = A. | title = Histologic grading of urothelial carcinoma: a reappraisal. | journal = Hum Pathol | volume = 43 | issue = 12 | pages = 2097-108 | month = Dec | year = 2012 | doi = 10.1016/j.humpath.2012.01.008 | PMID = 22542126 }}</ref>
 
===Microscopic===
Features:<ref name=Ref_WMSP310>{{Ref WMSP|310}}</ref>
*Rare fused papillae.
*Infrequent mitoses.
*Nuclei larger than papilloma - but monotonous.<ref name=Ref_GUP170>{{Ref GUP|170}}</ref>
 
DDx:
*[[Low grade papillary urothelial carcinoma]].
*[[Urothelial papilloma|Papilloma]].
 
====Images====
<gallery>
Image:Punlmp1.jpg | PUNLMP - low mag. (WC/Nephron)
Image:Punlmp2.jpg | PUNLMP - high mag. (WC/Nephron)
</gallery>
==Low grade papillary urothelial carcinoma==
*Abbreviated ''LGPUC''.<ref name=pmid22857755>{{Cite journal  | last1 = Watts | first1 = KE. | last2 = Montironi | first2 = R. | last3 = Mazzucchelli | first3 = R. | last4 = van der Kwast | first4 = T. | last5 = Osunkoya | first5 = AO. | last6 = Stephenson | first6 = AJ. | last7 = Hansel | first7 = DE. | title = Clinicopathologic characteristics of 23 cases of invasive low-grade papillary urothelial carcinoma. | journal = Urology | volume = 80 | issue = 2 | pages = 361-6 | month = Aug | year = 2012 | doi = 10.1016/j.urology.2012.04.010 | PMID = 22857755 }}</ref>
*Abbreviated ''LGPUC''.<ref name=pmid22857755>{{Cite journal  | last1 = Watts | first1 = KE. | last2 = Montironi | first2 = R. | last3 = Mazzucchelli | first3 = R. | last4 = van der Kwast | first4 = T. | last5 = Osunkoya | first5 = AO. | last6 = Stephenson | first6 = AJ. | last7 = Hansel | first7 = DE. | title = Clinicopathologic characteristics of 23 cases of invasive low-grade papillary urothelial carcinoma. | journal = Urology | volume = 80 | issue = 2 | pages = 361-6 | month = Aug | year = 2012 | doi = 10.1016/j.urology.2012.04.010 | PMID = 22857755 }}</ref>
*[[AKA]] ''low grade papillary urothelial cell carcinoma''.
*[[AKA]] ''low-grade papillary urothelial cell carcinoma''.
 
{{Main|Low-grade papillary urothelial carcinoma}}
===General===
*Very common.
*Very good prognosis - if it is non-invasive.
 
===Microscopic===
Features:<ref name=Ref_WMSP310>{{Ref WMSP|310}}</ref>
*Fused papillae.
*Papillae branch.
*Larger nuclei than PUNLMPs.
*+/-Invasion into the lamina propria.
 
Note:
*The presence/absence of muscle should be commented on in biopsy specimens.
*Adipose tissue may be seen in the lamina propria; tumour adjacent to adipose tissue on a biopsy does '''not''' imply invasion deep to the muscularis propria.<ref name=pmid7879346>{{Cite journal  | last1 = Bochner | first1 = BH. | last2 = Nichols | first2 = PW. | last3 = Skinner | first3 = DG. | title = Overstaging of transitional cell carcinoma: clinical significance of lamina propria fat within the urinary bladder. | journal = Urology | volume = 45 | issue = 3 | pages = 528-31 | month = Mar | year = 1995 | doi = 10.1016/S0090-4295(99)80030-2 | PMID = 7879346 }}</ref>
 
DDx:
*[[PUNLMP]].
*[[High grade papillary urothelial carcinoma]].
**Often under-diagnosed (~15% in one series) when reassessed by experts.<ref name=pmid20670136>{{Cite journal  | last1 = Miyamoto | first1 = H. | last2 = Brimo | first2 = F. | last3 = Schultz | first3 = L. | last4 = Ye | first4 = H. | last5 = Miller | first5 = JS. | last6 = Fajardo | first6 = DA. | last7 = Lee | first7 = TK. | last8 = Epstein | first8 = JI. | last9 = Netto | first9 = GJ. | title = Low-grade papillary urothelial carcinoma of the urinary bladder: a clinicopathologic analysis of a post-World Health Organization/International Society of Urological Pathology classification cohort from a single academic center. | journal = Arch Pathol Lab Med | volume = 134 | issue = 8 | pages = 1160-3 | month = Aug | year = 2010 | doi = 10.1043/2009-0403-OA.1 | PMID = 20670136 }}</ref>
**The three most predictive features of high-grade are ''architectural complexity'', ''nuclear size variation'', and ''absence of umbrella cells''.<ref name=pmid21980608>{{Cite journal  | last1 = Isfoss | first1 = BL. | last2 = Majak | first2 = B. | last3 = Busch | first3 = C. | last4 = Braathen | first4 = GJ. | title = Simplification of grading papillary urothelial neoplasia using a reduced set of diagnostic features. | journal = Anal Quant Cytol Histol | volume = 33 | issue = 2 | pages = 68-74 | month = Apr | year = 2011 | doi =  | PMID = 21980608 }}</ref>
*[[Inverted urothelial papilloma]] - often have peripheral palisading.
*[[Urothelial papilloma]].


===IHC===
==High-grade papillary urothelial carcinoma==
*Ki-67:
**Rajcani ''et al.'':<ref name=pmid23944616>{{Cite journal  | last1 = Rajcani | first1 = J. | last2 = Kajo | first2 = K. | last3 = Adamkov | first3 = M. | last4 = Moravekova | first4 = E. | last5 = Lauko | first5 = L. | last6 = Felcanova | first6 = D. | last7 = Bencat | first7 = M. | title = Immunohistochemical characterization of urothelial carcinoma. | journal = Bratisl Lek Listy | volume = 114 | issue = 8 | pages = 431-8 | month =  | year = 2013 | doi =  | PMID = 23944616 }}</ref> <25% of tumour cells for low-grade versus >50% tumour cell for high-grade.
**Pich ''et al.'':<ref name=pmid7910097>{{Cite journal  | last1 = Pich | first1 = A. | last2 = Chiusa | first2 = L. | last3 = Comino | first3 = A. | last4 = Navone | first4 = R. | title = Cell proliferation indices, morphometry and DNA flow cytometry provide objective criteria for distinguishing low and high grade bladder carcinomas. | journal = Virchows Arch | volume = 424 | issue = 2 | pages = 143-8 | month =  | year = 1994 | doi =  | PMID = 7910097 }}</ref> 11%/17% for G1/G2 versus 34% for G3.
 
===Molecular===
Molecular changes:<ref name=pmid19468362>{{Cite journal  | last1 = Ehdaie | first1 = B. | last2 = Theodorescu | first2 = D. | title = Molecular markers in transitional cell carcinoma of the bladder: New insights into mechanisms and prognosis. | journal = Indian J Urol | volume = 24 | issue = 1 | pages = 61-7 | month = Jan | year = 2008 | doi = 10.4103/0970-1591.38606 | PMID = 19468362 | PMC = 2684226}}</ref>
*FGFR3
*HRAS
*Loss of heterozygosity - chromosome 9.
 
Note:
*Not currently used diagnostically.
===Sign out===
<pre>
URINARY BLADDER LESION ("TUMOUR"), RESECTION:
- 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.
- NO MUSCULARIS PROPRIA IDENTIFIED.
</pre>
 
<pre>
URINARY BLADDER LESION ("TUMOUR"), TRANSURETHRAL RESECTION OF BLADDER TUMOUR (TURBT):
- LOW-GRADE PAPILLARY UROTHELIAL CARCINOMA.
- NEGATIVE FOR LAMINA PROPRIA INVASION.
- MUSCULARIS PROPRIA PRESENT.
</pre>
 
==High grade papillary urothelial carcinoma==
*Abbreviated ''HGPUC''.
*Abbreviated ''HGPUC''.
*[[AKA]] ''high grade papillary urothelial cell carcinoma'', abbreviated ''HGPUCC''.  
*[[AKA]] ''high-grade papillary urothelial cell carcinoma'', abbreviated ''HGPUCC''.
{{Main|High-grade papillary urothelial carcinoma}}


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


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


Note:
Note:
*The presence/absence of muscle should be commented on in biopsy specimens.
*So called "[[giant cell cystitis]]" is dealt with separately; it is a benign non-pathologic change that may or may not be associated with inflammation.<ref name=Ref_Amin2_6>{{Ref Amin|2:6}}</ref>
*Adipose tissue may be seen in the lamina propria; tumour adjacent to adipose tissue on a biopsy does '''not''' imply invasion deep to the muscularis propria.<ref name=pmid7879346>{{Cite journal  | last1 = Bochner | first1 = BH. | last2 = Nichols | first2 = PW. | last3 = Skinner | first3 = DG. | title = Overstaging of transitional cell carcinoma: clinical significance of lamina propria fat within the urinary bladder. | journal = Urology | volume = 45 | issue = 3 | pages = 528-31 | month = Mar | year = 1995 | doi = 10.1016/S0090-4295(99)80030-2 | PMID = 7879346 }}</ref>
 
DDx:
*[[Low grade papillary urothelial carcinoma]].
 
===IHC===
*Ki-67 >50% of tumour cells.<ref name=pmid23944616>{{Cite journal  | last1 = Rajcani | first1 = J. | last2 = Kajo | first2 = K. | last3 = Adamkov | first3 = M. | last4 = Moravekova | first4 = E. | last5 = Lauko | first5 = L. | last6 = Felcanova | first6 = D. | last7 = Bencat | first7 = M. | title = Immunohistochemical characterization of urothelial carcinoma. | journal = Bratisl Lek Listy | volume = 114 | issue = 8 | pages = 431-8 | month =  | year = 2013 | doi =  | PMID = 23944616 }}</ref>
**Low-grade UCC <25% of tumour cells positive.
 
===Molecular===
Molecular changes:<ref name=pmid19468362>{{Cite journal  | last1 = Ehdaie | first1 = B. | last2 = Theodorescu | first2 = D. | title = Molecular markers in transitional cell carcinoma of the bladder: New insights into mechanisms and prognosis. | journal = Indian J Urol | volume = 24 | issue = 1 | pages = 61-7 | month = Jan | year = 2008 | doi = 10.4103/0970-1591.38606 | PMID = 19468362 | PMC = 2684226}}</ref>
*p53.
*p21.
*RB.
*E-cadherin - decreased bad.
*RhoGD12 - increased bad.
*VEGF - increased bad.
 
===Sign out===
<pre>
URINARY BLADDER LESION ("TUMOUR"), TRANSURETHRAL RESECTION:
- HIGH-GRADE PAPILLARY UROTHELIAL CARCINOMA.
- NO LAMINA PROPRIA INVASION APPARENT.
- NEGATIVE FOR LYMPHOVASCULAR INVASION.
- NO MUSCULARIS PROPRIA IDENTIFIED.
</pre>
 
====Invasion into the lamina propria====
<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====
===The big table of cystitis===
<pre>
URINARY BLADDER LESION ("TUMOUR"), TRANSURETHRAL RESECTION URINARY BLADDER TUMOUR (TURBT):
- INVASIVE HIGH-GRADE PAPILLARY UROTHELIAL CARCINOMA AT LEAST INTO MUSCULARIS PROPRIA.
- LYMPHOVASCULAR INVASION PRESENT.
</pre>
 
====Low-grade versus high-grade====
<pre>
URINARY BLADDER LESION ("TUMOUR"), TRANSURETHRAL RESECTION URINARY BLADDER TUMOUR (TURBT):
- HIGH-GRADE PAPILLARY UROTHELIAL CARCINOMA, SEE COMMENT.
- NEGATIVE FOR LAMINA PROPRIA INVASION.
- NO MUSCULARIS PROPRIA PRESENT.
 
COMMENT:
The sections show papillary branching, papillary fusion and scattered large cells (~4-5 a
resting lymphocyte). Atypical for a high-grade lesion is that mitotic activity is scarce
and prominent nucleoli are not present.
</pre>
 
=====Micro=====
The sections show a small fragment of urothelial mucosa with two papillary structures,
enlarged nuclei (~3-4x resting lymphocyte) and moderate nuclear size variation.  Mitotic activity is seen focally. Umbrella
cells are seen only focally.
 
A mild lymphocyte-predominant inflammatory infiltrate is present. The lamina propria
contains a nest with smaller cells, cystic spaces and no appreciable mitoses
(cystitis cystica).
 
=Benign urothelial lesions=
The big table of cystitis:
{| class="wikitable sortable"  
{| class="wikitable sortable"  
! Type
! Type
Line 709: 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 790: Line 483:


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


==Cystitis glandularis==
==Cystitis glandularis==
{{ Infobox external links
{{Main|Cystitis glandularis}}
| Name          = Cystitis cystica et glandularis
| EHVSC          = 10173
| pathprotocols  =
| wikipedia      =
| pathoutlines  =
}}
:''Cystitis cystica et glandularis'' redirects to here.
===General===
*Benign.
*Can be thought of as [[cystitis cystica]] with mucin-secreting cells lining the cystic spaces.<ref name=Ref_WMSP304>{{Ref WMSP|304}}</ref>
*When seen in conjunction with ''cystitis cystica'' it is called ''cystitis cystica et glandularis''.
 
Note:
*There are case reports of ''urethritis glandularis'' - the same lesion in the [[urethra]].<ref name=pmid11104631>{{Cite journal  | last1 = Chan | first1 = YM. | last2 = Ka-Leung Cheng | first2 = D. | last3 = Nga-Yin Cheung | first3 = A. | last4 = Yuen-Sheung Ngan | first4 = H. | last5 = Wong | first5 = LC. | title = Female urethral adenocarcinoma arising from urethritis glandularis. | journal = Gynecol Oncol | volume = 79 | issue = 3 | pages = 511-4 | month = Dec | year = 2000 | doi = 10.1006/gyno.2000.5968 | PMID = 11104631 }}</ref><ref name=pmid17825180>{{Cite journal  | last1 = Yin | first1 = G. | last2 = Liu | first2 = YQ. | last3 = Gao | first3 = P. | last4 = Wang | first4 = XH. | title = Male urethritis glandularis: case report. | journal = Chin Med J (Engl) | volume = 120 | issue = 16 | pages = 1460-1 | month = Aug | year = 2007 | doi =  | PMID = 17825180 }}</ref>
 
===Microscopic===
Features:<ref name=Ref_PBoD1028>{{Ref PBoD|1028}}</ref>
*Nests of urothelium within the lamina propria with cyst formation, i.e. lumens are present.
*Cyst lining cells are cuboidal and/or columnar epithelium.
**Produce mucin.
*+/-Goblet cells, i.e. intestinal metaplasia.<ref name=Ref_WMSP304>{{Ref WMSP|304}}</ref>
 
Note:
*Nests should '''not''' extend into the muscularis propria.
 
Image:
*[http://www.webpathology.com/image.asp?n=2&Case=50 Cystitis glandularis (webpathology.com)].
 
===Sign out===
<pre>
URINARY BLADDER NECK, BIOPSY:
- CYSTITIS CYSTICA ET GLANDULARIS.
- NEGATIVE FOR MALIGNANCY.
</pre>
 
====Micro====
The sections show urothelial mucosa with bland nests within the lamina propria with cyst formation. The stroma is edematous and has a mixed inflammatory infiltrate consisting of plasma cells, eosinophils, lymphocytes and neutrophils.


==Malakoplakia==
==Malakoplakia==
Line 860: Line 492:


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


=See also=
=See also=
Michael
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