Urothelial carcinoma-in-situ (CIS), light micrograph. Urothelial CIS is defined as the presence of overtly malignant cells with flat urothelium. The cancer's cells are discohesive and readily shed into the urine where they can be detected by cytological examination. Urothelial CIS is frequently multifocal and can show widespread involvement of the bladder lining with extension into the ureters and urethra. In the absence of treatment, about two-thirds to three-quarters of cases progress to invasive cancer. This photomicrograph shows pagetoid spread of urothelial CIS. The malignant cells have enlarged nuclei with prominent nucleoli (dark purple). They are seen infiltrating in between benign urothelial cells with small nuclei.