Histologic variants of urothelial bladder cancer and nonurothelial histology in bladder cancer

Abstract

Bladder cancer can be classified histologically as urothelial ornon-urothelial. Urothelial cancer has a propensity for divergentdifferentiation, which has increasingly been recognized in recentyears due to heightened awareness and improved immunohistochemistrytechniques. Furthermore, the recent World HealthOrganization classification of urothelial cancers improved clarityon this issue, with its listing of 13 histologic variants of urothelialcancer. The divergent differentiation patterns include, amongstothers, squamous, glandular, micropapillary, nested, lymphepithelioma-like, plasmacytoid and sarcomatoid variants of urothelialcancer. Attempts to quantify the amount of divergent differentiationpresent, such as using the nonconventional differentiationnumber, have been made recently, which will improve the abilityto compare publications from different centres. Genetic-basedstudies have indicated that the histologic variants of urothelialcancer arise from a common clonal precursor. Mostly, the currentevidence suggests that urothelial cancer with divergent differentiationhas a worse prognosis when compared with pure urothelialcancer. This article will review the current literature on varianthistologies of urothelial cancer, and well as new developmentsin pure squamous cell carcinoma, small cell carcinoma and adenocarcinomaof the bladder.