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

It is well established that invasive urothelial carcinoma, involving the urinary bladder and renal pelvis, has marked propensity for divergent differentiation. In recent years, several ‘variant’ morphologies have been described and most have been recognized in the 2004 World Health Organization Classification. These histological variants of urothelial carcinoma have clinical significance at various levels, including diagnostic, that is, awareness of the morphological variant is essential in order to avoid diagnostic misinterpretations; prognostic for patient risk stratification; and therapeutic, where a diagnostic assignment of a particular variant may be associated with the administration of a therapy distinctive from that used in conventional invasive urothelial carcinoma. The diagnoses of micropapillary urothelial carcinoma, small-cell carcinoma, lymphoepithelioma-like carcinoma and sarcomatoid carcinoma are prime examples where treatment protocols may be different than the usual muscle-invasive bladder cancer. This review discusses the variants of urothelial carcinoma, outlining for each the diagnostic features, differential diagnostic considerations and the clinical significance.