Histological variants of urothelial carcinoma: Diagnostic, prognostic, and therapeutic implications

The majority (more than 90%) of malignant neoplasms arising in the bladder are pure urothelial (transitional cell) carcinomas, and the rest (less than 10%) consist of histological variants of bladder cancer, including urothelial carcinoma admixed with other histologic patterns (squamous/glandular differentiation, nested, microcystic, clear cell, plasmacytoid, lymphoepithelioma-like, micropapillary, sarcomatoid variants, etc.) and pure forms of non-urothelial carcinoma (squamous cell carcinoma, adenocarcinoma, small cell carcinoma, etc.). These histological variants of bladder cancer have been described in a number of case series for several years and have been recognized in the 2004 World Health Organization Classification of urothelial cancers. These histological variants of bladder cancer have clinical significance at various levels, including diagnostic, that is, recognition of the morphological variant is necessary in order to avoid diagnostic misinterpretations; prognostic for patient risk stratification; and therapeutic, where a diagnosis of a particular variant may be associated with the administration of a therapy distinctive from that used in conventional urothelial carcinoma. In this article, we will chiefly review the literature on the histological variants of urothelial carcinoma with a focus on the prognostic and therapeutic implications of histological variants for the management of patients with bladder cancer.