Urothelial carcinoma in situ

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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 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

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.

Classification of flat urothelial lesions

The World Health Organization classification is:[1]

  • 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.

Microscopic

Features:

  • Nuclear changes key feature.
    • Enlargement of nuclei (often 4-5x the size of stromal lymphocytes) -- diagnostic.[2]
      • 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.[3]

DDx:

Images

www:

IHC

Features:[4]

  • p53 +ve.
  • Ki-67 high.

Benign urothelium vs. CIS:[5]

  • 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.[6]
    • Positive in indeterminant and negative.

Sign out

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

  1. 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.
  2. 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.
  3. Amin, Mahul B. (2010). Diagnostic Pathology: Genitourinary (1st ed.). Amirsys. pp. 2-55. ISBN 978-1931884280.
  4. Lopez-Beltran, A.; Jimenez, RE.; Montironi, R.; Patriarca, C.; Blanca, A.; Menendez, CL.; Algaba, F.; Cheng, L. (Nov 2011). "Flat urothelial carcinoma in situ of the bladder with glandular differentiation.". Hum Pathol 42 (11): 1653-9. doi:10.1016/j.humpath.2010.12.024. PMID 21531007.
  5. 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.
  6. 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.