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.