Rare histolopathologic variants in bladder cancer

The heterogeneous spectrum of bladder cancer comprises the coexistence of conventional urothelial carcinoma (UC) with its variants as well as the non-urothelial carcinoma (including squamous and glandular tumors). Since the official classification of rare histologic subtypes, by the World Health Organization (WHO) in 2004, uropathologists and urologists are paying more attention to the role of these subtypes as potential prognostic markers. Most of these rare variants have been associated with increased risk of progression and poor prognosis. Therefore, patients diagnosed with some of the histologic subtypes, have been classified to “the very high risk group” of recurrence and progression, although it has not yet been clarified if this is due to advanced stages at presentation and underdiagnosis or due to the aggressiveness of each variant, as an independent factor. This review discusses the most common variants of bladder cancer (urothelial carcinoma with squamous and/or glandular differentiation, pure squamous carcinoma, pure adenocarcinoma, urachal carcinoma, nested pattern, microcystic, micropapillary, small cell carcinoma, plasmacytoid, sarcomatoid, and lymphoepithelial like carcinoma), outlining the recent advances regarding the diagnosis, differential diagnosis, treatment and clinical significance for each one. High index of suspicious is required by the uropathologists for detection of these variants and well-designed multi-institutional studies are necessary in order the specific treatment strategies for these patients to be established.