Difference between revisions of "Urothelial carcinoma in situ"
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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. | ||
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==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=== | ===Classification of flat urothelial lesions=== | ||
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*Urothelial carcinoma in situ (high-grade dysplasia). | *Urothelial carcinoma in situ (high-grade dysplasia). | ||
*Invasive [[urothelial carcinoma]]. | *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== | ||
Line 36: | Line 72: | ||
*[[Urothelial carcinoma]], invasive. | *[[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. | ||
Line 54: | Line 108: | ||
*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> | *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''. | **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== |
Latest revision as of 04:56, 23 November 2016
Urothelial carcinoma in situ, also known as high-grade (urothelial) dysplasia, a non-invasive urothelial neoplasm without papillae.
Urothelial carcinoma in situ | |
---|---|
Diagnosis in short | |
Urothelial carcinoma in situ. H&E stain. | |
| |
Synonyms | urothelial cell carcinoma in situ, high-grade dysplasia |
| |
LM | 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 |
LM DDx | urothelial carcinoma, urothelial dysplasia, urothelial atypia of unknown significance |
IHC | CK20 +ve (full thickness), Ki-67 high, p53 +ve, CD44 -ve, CK7 +ve |
Site | urothelium - urinary bladder, ureter, renal pelvis, prostatic urethra |
| |
Signs | +/-hematuria |
Prevalence | relatively uncommon |
Endoscopy | erythema or edema, may be unremarkable |
Clin. DDx | invasive (flat) urothelial carcinoma, inflammation (cystitis) |
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.[1]
Classification of flat urothelial lesions
The World Health Organization classification is:[2]
- 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.[3]
Microscopic
Features:
- Nuclear changes key feature.
- Enlargement of nuclei (often 4-5x the size of stromal lymphocytes) -- diagnostic.[4]
- Normal urothelium approx. 2x the size of stromal lymphocytes.
- Nuclear pleomorphism - marked variation in size of nuclei.
- Enlargement of nuclei (often 4-5x the size of stromal lymphocytes) -- diagnostic.[4]
- +/-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.[5]
DDx:
- Urothelial atypia of unknown significance - waffle diagnosis.
- Urothelial dysplasia.
- Urothelial carcinoma, invasive.
Images
www
IHC
- 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:[7]
- 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.[8]
- Positive in indeterminant and negative.
Others
- AMACR +ve (80% and 50% of untreated and treated CIS respectively[8]).
Images
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URINARY BLADDER LESION ("TUMOUR"), TRANSURETHRAL RESECTION URINARY BLADDER TUMOUR (TURBT): - UROTHELIAL CARCINOMA IN SITU. - BENIGN MUSCULARIS PROPRIA PRESENT.
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.
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
References
- ↑ Nielsen, ME.; Smith, AB.; Meyer, AM.; Kuo, TM.; Tyree, S.; Kim, WY.; Milowsky, MI.; Pruthi, RS. et al. (Jan 2014). "Trends in stage-specific incidence rates for urothelial carcinoma of the bladder in the United States: 1988 to 2006.". Cancer 120 (1): 86-95. doi:10.1002/cncr.28397. PMID 24122346.
- ↑ 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.
- ↑ Nese, N.; Gupta, R.; Bui, MH.; Amin, MB. (Jan 2009). "Carcinoma in situ of the urinary bladder: review of clinicopathologic characteristics with an emphasis on aspects related to molecular diagnostic techniques and prognosis.". J Natl Compr Canc Netw 7 (1): 48-57. PMID 19176205.
- ↑ Zhou, Ming; Magi-Galluzzi, Cristina (2006). Genitourinary Pathology: A Volume in Foundations in Diagnostic Pathology Series (1st ed.). Churchill Livingstone. pp. 161. ISBN 978-0443066771.
- ↑ Amin, Mahul B. (2010). Diagnostic Pathology: Genitourinary (1st ed.). Amirsys. pp. 2-55. ISBN 978-1931884280.
- ↑ Amin MB, Epstein JI, Ulbright TM, et al. (August 2014). "Best practices recommendations in the application of immunohistochemistry in urologic pathology: report from the international society of urological pathology consensus conference". Am. J. Surg. Pathol. 38 (8): 1017–22. doi:10.1097/PAS.0000000000000254. PMID 25025364.
- ↑ Yin, H.; He, Q.; Li, T.; Leong, AS. (Sep 2006). "Cytokeratin 20 and Ki-67 to distinguish carcinoma in situ from flat non-neoplastic urothelium.". Appl Immunohistochem Mol Morphol 14 (3): 260-5. PMID 16932015.
- ↑ 8.0 8.1 Aron, M.; Luthringer, DJ.; McKenney, JK.; Hansel, DE.; Westfall, DE.; Parakh, R.; Mohanty, SK.; Balzer, B. et al. (Dec 2013). "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.". Am J Surg Pathol 37 (12): 1815-23. doi:10.1097/PAS.0000000000000114. PMID 24225842.