American Urological Association - Urothelial Carcinoma in Situ
Urothelial Carcinoma in Situ
- 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.
- 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).
- 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.