Urothelial Carcinoma In Situ (CIS): New Insights

Abstract

Urothelial carcinoma in situ (CIS) is a high-grade noninvasive malignancy with a high tendency of progression. Although it is typically grouped with other nonmuscle invasive bladder cancers, its higher grade and aggressiveness make it a unique clinical entity. Urothelial CIS is histologically characterized by replacement of the urothelium by cells which fulfill the morphologic criteria of malignancy including nuclear pleomorphism, hyperchromasia, prominent nucleoli, and increased numbers of normal and abnormal mitoses. Urothelial CIS may be categorized as primary when it is not associated with any past or present urothelial carcinoma. It is termed as secondary when there is concomitant or previous urothelial carcinoma in the patient. In recent years detailed molecular studies have provided valuable data for intrinsic molecular subclassification of urothelial carcinoma into 2 broad categories namely luminal and basal types with significant implications for prognosis and therapy. Similar studies on urothelial CIS are limited but have provided crucial insight into the molecular basis of CIS. These studies have revealed that urothelial CIS may also be divided into luminal and basal subtypes, but luminal subtype is much more common. It has also been shown that in many cases, luminal type of urothelial CIS may undergo a class switch to basal type during progression to an invasive carcinoma. Additional studies may be required to confirm and further elaborate these findings.