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{{ 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. | '''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]]''' | 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== | ==General== | ||
*Lack papillae. | *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== | ==Microscopic== | ||
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**This is known as ''clinging urothelial carcinoma in situ''.<ref>{{Ref Amin|2-55}}</ref> | **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=== | ===Images=== | ||
<gallery> | |||
Image: Urothelial carcinoma in situ -- intermed mag.jpg | UCIS - intermed. mag. (WC) | |||
*[http://www.webpathology.com/image.asp?n= | Image: Urothelial carcinoma in situ -- high mag.jpg | UCIS - high mag. (WC) | ||
*[http://www.webpathology.com/image.asp? | Image: Urothelial carcinoma in situ - alt -- high mag.jpg | UCIS - high mag. (WC) | ||
*[http://www.webpathology.com/image.asp?n= | 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== | ==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. | *p53 +ve. | ||
* | *CD44 -ve. | ||
**Positive in ''indeterminant'' and ''negative''. | |||
===Another panel=== | |||
*CK20 +ve in deep cells (23/26 cases). | 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. | **Normal urothelium -- only the umbrella cells. | ||
*Ki-67 ~50% of cells - deep and superficial. | *Ki-67 ~50% of cells - deep and superficial. | ||
**Normal ~10% of cells, confined to basal aspect. | **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== | ==Sign out== | ||
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URINARY BLADDER LESION ("TUMOUR"), TRANSURETHRAL RESECTION URINARY BLADDER TUMOUR (TURBT): | URINARY BLADDER LESION ("TUMOUR"), TRANSURETHRAL RESECTION URINARY BLADDER TUMOUR (TURBT): | ||
- UROTHELIAL CARCINOMA IN SITU. | - UROTHELIAL CARCINOMA IN SITU. | ||
- MUSCULARIS PROPRIA PRESENT. | - 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> | </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== | ==See also== |
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