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Urothelial carcinoma in situ (view source)

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#redirect [[Urothelium#Urothelial_carcinoma_in_situ]]
{{ Infobox diagnosis
| Name      = {{PAGENAME}}
| Image      = Urothelial carcinoma in situ -- very high mag.jpg
| Width      =
| Caption    = Urothelial carcinoma in situ. [[H&E stain]].
| Synonyms  = urothelial cell carcinoma in situ, high-grade dysplasia
| Micro      = nuclear changes (enlargement of nuclei (often 4-5x the size of stromal lymphocytes), nuclear pleomorphism - marked variation in size of nuclei), +/-disordered arrangement/crowding of cells, +/-mitoses, +/-enlarged nucleoli
| Subtypes  =
| LMDDx      = [[urothelial carcinoma]], [[urothelial dysplasia]], urothelial atypia of unknown significance
| Stains    =
| IHC        = CK20 +ve (full thickness), Ki-67 high, p53 +ve, CD44 -ve, CK7 +ve
| EM        =
| Molecular  =
| IF        =
| Gross      =
| Grossing  =
| Site      = [[urothelium]] - [[urinary bladder]], [[ureter]], renal pelvis, prostatic [[urethra]]
| Assdx      =
| Syndromes  =
| Clinicalhx =
| Signs      = +/-hematuria
| Symptoms  =
| Prevalence = relatively uncommon
| Bloodwork  =
| Rads      =
| Endoscopy  = erythema or edema, may be unremarkable
| Prognosis  =
| Other      =
| ClinDDx    = invasive (flat) [[urothelial carcinoma]], inflammation (cystitis)
| Tx        =
}}
'''Urothelial carcinoma in situ''', also known as '''high-grade (urothelial) dysplasia''', a non-invasive [[urothelium|urothelial]] neoplasm without papillae.
 
It is also known as '''[[carcinoma in situ]]''' (abbreviated '''CIS''') and '''urothelial cell carcinoma in situ''' (abbreviated '''UCC in situ''').  ''Urothelial carcinoma in situ'' may be abbreviated '''UCIS'''.
 
==General==
*Lack papillae.
*Uncommon in relation to other urothelial lesions.
**Less common than invasive flat urothelial carcinoma ~3-4x more common than UCIS.<ref name=pmid24122346>{{Cite journal  | last1 = Nielsen | first1 = ME. | last2 = Smith | first2 = AB. | last3 = Meyer | first3 = AM. | last4 = Kuo | first4 = TM. | last5 = Tyree | first5 = S. | last6 = Kim | first6 = WY. | last7 = Milowsky | first7 = MI. | last8 = Pruthi | first8 = RS. | last9 = Millikan | first9 = RC. | title = Trends in stage-specific incidence rates for urothelial carcinoma of the bladder in the United States: 1988 to 2006. | journal = Cancer | volume = 120 | issue = 1 | pages = 86-95 | month = Jan | year = 2014 | doi = 10.1002/cncr.28397 | PMID = 24122346 }}</ref>
 
===Classification of flat urothelial lesions===
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]].
 
==Gross==
*Flat lesion - erythema or edema, may be unremarkable.<ref name=pmid19176205>{{Cite journal  | last1 = Nese | first1 = N. | last2 = Gupta | first2 = R. | last3 = Bui | first3 = MH. | last4 = Amin | first4 = MB. | title = Carcinoma in situ of the urinary bladder: review of clinicopathologic characteristics with an emphasis on aspects related to molecular diagnostic techniques and prognosis. | journal = J Natl Compr Canc Netw | volume = 7 | issue = 1 | pages = 48-57 | month = Jan | year = 2009 | doi =  | PMID = 19176205 }}</ref>
 
==Microscopic==
Features:
*Nuclear changes '''key feature'''.
**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:
*The urothelium may be "depleted", i.e. exist only of rare large cells on the basement membrane.
**This is known as ''clinging urothelial carcinoma in situ''.<ref>{{Ref Amin|2-55}}</ref>
 
DDx:
*Urothelial atypia of unknown significance - [[waffle diagnosis]].
*[[Urothelial dysplasia]].
*[[Urothelial carcinoma]], invasive.
===Images===
<gallery>
Image: Urothelial carcinoma in situ -- intermed mag.jpg | UCIS - intermed. mag. (WC)
Image: Urothelial carcinoma in situ -- high mag.jpg | UCIS - high mag. (WC)
Image: Urothelial carcinoma in situ - alt -- high mag.jpg | UCIS - high mag. (WC)
Image: Urothelial carcinoma in situ -- very high mag.jpg | UCIS - very high mag. (WC)
</gallery>
<gallery>
Image: Urothelial CIS -- low mag.jpg | UCIS - low mag. (WC)
Image: Urothelial CIS -- intermed mag.jpg | UCIS - intermed. mag. (WC)
Image: Urothelial CIS -- high mag.jpg | UCIS - high mag. (WC)
 
Image: Urothelial CIS - CK20 -- intermed mag.jpg | UCIS - CK20 - intermed. mag. (WC)
Image: Urothelial CIS - p63 -- intermed mag.jpg | UCIS - p63 - intermed. mag. (WC)
Image: Urothelial CIS - Ki67 -- high mag.jpg | UCIS - Ki-67 - high mag. (WC)
</gallery>
====www====
*[http://www.webpathology.com/image.asp?n=7&Case=57 Urothelial CIS (webpathology.com)].
*[http://www.webpathology.com/image.asp?n=10&Case=57 Urothelial CIS with shedding (webpathology.com)].
*[http://www.webpathology.com/image.asp?n=8&Case=57 Urothelial CIS - high mag. (webpathology.com)].
 
==IHC==
[[ISUP]] consensus panel:<ref name=pmid25025364 >{{cite journal |author=Amin MB, Epstein JI, Ulbright TM, ''et al.'' |title=Best practices recommendations in the application of immunohistochemistry in urologic pathology: report from the international society of urological pathology consensus conference |journal=Am. J. Surg. Pathol. |volume=38 |issue=8 |pages=1017–22 |year=2014 |month=August |pmid=25025364 |doi=10.1097/PAS.0000000000000254 |url=}}</ref>
*CK20 +ve in deep cells.
**Normal urothelium -- only the umbrella cells.
*p53 +ve.
*CD44 -ve.
**Positive in ''indeterminant'' and ''negative''.
 
===Another panel===
Another panel for benign urothelium versus 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>
*[[CK20]] +ve in deep cells (23/26 cases).
**Normal urothelium -- only the umbrella cells.
*Ki-67 ~50% of cells - deep and superficial.
**Normal ~10% of cells, confined to basal aspect.
*CD44 -ve.<ref name=pmid24225842>{{Cite journal  | last1 = Aron | first1 = M. | last2 = Luthringer | first2 = DJ. | last3 = McKenney | first3 = JK. | last4 = Hansel | first4 = DE. | last5 = Westfall | first5 = DE. | last6 = Parakh | first6 = R. | last7 = Mohanty | first7 = SK. | last8 = Balzer | first8 = B. | last9 = Amin | first9 = MB. | title = Utility of a triple antibody cocktail intraurothelial neoplasm-3 (IUN-3-CK20/CD44s/p53) and α-methylacyl-CoA racemase (AMACR) in the distinction of urothelial carcinoma in situ (CIS) and reactive urothelial atypia. | journal = Am J Surg Pathol | volume = 37 | issue = 12 | pages = 1815-23 | month = Dec | year = 2013 | doi = 10.1097/PAS.0000000000000114 | PMID = 24225842 }}</ref>
**Positive in ''indeterminant'' and ''negative''.
 
====Others====
*AMACR +ve (80% and 50% of untreated and treated CIS respectively<ref name=pmid24225842/>).
 
===Images===
<gallery>
Image: Urothelial carcinoma in situ - CK20 -- intermed mag.jpg | UCIS - CK20 - intermed. mag.
Image: Urothelial carcinoma in situ - CK20 -- high mag.jpg | UCIS - CK20 - high mag.
Image: Urothelial carcinoma in situ - CK20 -- very high mag.jpg | UCIS - CK20 - very high mag.
Image: Benign urothelium - CK20 -- high mag.jpg | Benign urothelium - CK20 - high mag.
</gallery>
<gallery>
Image: Urothelial carcinoma in situ - Ki-67 -- intermed mag.jpg | UCIS - Ki-67 - intermed. mag.
Image: Urothelial carcinoma in situ - Ki-67 -- high mag.jpg | UCIS - Ki-67 - high mag.
Image: Urothelial carcinoma in situ - Ki-67 -- very high mag.jpg | UCIS - Ki-67 - very high mag.
</gallery>
 
==Sign out==
<pre>
URINARY BLADDER LESION ("TUMOUR"), TRANSURETHRAL RESECTION URINARY BLADDER TUMOUR (TURBT):
- UROTHELIAL CARCINOMA IN SITU.
- BENIGN MUSCULARIS PROPRIA PRESENT.
</pre>
 
<pre>
URINARY BLADDER, RANDOM BIOPSIES:
- UROTHELIAL CARCINOMA IN SITU, SEE COMMENT.
-- NO EVIDENCE OF LAMINA PROPRIA INVASION.
- CHRONIC INFLAMMATION, MILD.
- BENIGN MUSCULARIS PROPRIA PRESENT.
 
COMMENT:
A CK20 immunostain marks the full thickness of the urothelium in atypical areas. A p53
immunostain moderately marks up to 20% of atypical cells focally.  A Ki-67 immunostain
marks 20-50% of the cells in the atypical areas.
</pre>
 
===Micro===
The sections show multiple fragments of urothelium with nuclear hyperchromasia, nuclear
crowding, mild-to-moderate nuclear enlargement, several atypical mitoses, and lack of
maturation to the surface. There is no evidence of invasion. Benign muscularis propria is
present.
 
==See also==
*[[Urothelium]].
 
==References==
{{Reflist|2}}


[[Category:Diagnosis]]
[[Category:Diagnosis]]
[[Category:Urothelium]]
Michael
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