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Pathology for Urologists

Urothelial Carcinoma In Situ (CIS)


Image A
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Image B
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  • Flat lesion composed of malignant urothelial cells confined to the basement membrane, either with full or partial thickness involvement of urothelium.
  • Most commonly in men in 50's to 70's.
  • Three clinical forms:
    • Primary (de novo) CIS: Isolated CIS without prior or concurrent papillary neoplasm (rare).
    • Secondary CIS: In patients with prior papillary neoplasm.
    • Concurrent CIS: Identified on bladder mucosa with concomitant papillary neoplasm or invasive carcinoma.
  • Multifocality is common.
  • Associated with amplification/mutation of p53 and RB genes.
  • Histology:
    • Diagnosis requires unequivocal high-grade cytology (image A) & (image B).
    • Cellular crowding and loss of polarity (see normal urothelium for comparison).
    • Marked nucleomegaly, coarse dark chromatin and abundant mitosis.
    • Cellular dyscohesion and denudation may occur with few residual attached CIS cells present (Clinging CIS).
    • May spread into adjacent benign urothelium as individual malignant cells (Pagetoid CIS) or as clusters of malignant cells covered by benign urothelium (Undermining CIS).
  • Immunohistochemistry:
    • Aberrant full thickness CK20+, basal or absent CD44+ and higher (>50%) p53+.
    • In contrast, benign urothelium will have CK20+ in umbrella cells only, and higher CD44+ and lower p53 staining.
  • ~ Half of patients develop invasive carcinoma within 5 years.

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