Objectives: Plasmacytoid urothelial carcinoma (PUC) of the bladder is a rare histologic variant. We retrospectively analyzed a large series of bladder PUC from a single institution. Methods: The patients consisted of 44 men and five women with a mean age of 62 years (range, 45-86 years). Results: PUC was pure in 23 cases and mixed with other histologic types in 26 cases. All PUCs diffusely invaded the bladder wall. Most PUCs lacked immunoreactivity for the retinoblastoma (RB) gene protein (12/32) and E-cadherin (8/30). Of the 44 patients with follow-up information, 25 died of PUC at a mean of 23 months, whereas 19 patients were alive at a mean of 22 months. Conclusions: Our findings support that bladder PUC is a highly aggressive disease. The lack of E-cadherin expression in PUCs may underlie the distinct discohesive histologic appearance, and abnormal function of the RB gene may be implicated in the development of PUC.

We report a comprehensive molecular analysis of 34 cases of small cell carcinoma (SCC) and 84 cases of conventional urothelial carcinoma (UC), with The Cancer Genome Atlas cohort of 408 conventional UC bladder cancers used as the reference. SCCs showed mutational landscapes characterized by nearly uniform inactivation of TP53 and were dominated by Sanger mutation signature 3 associated with loss of BRCA1/2 function. SCCs were characterized by downregulation of luminal and basal markers and were referred to as double-negative. Transcriptome analyses indicated that SCCs displayed lineage plasticity driven by a urothelial-to-neural phenotypic switch with a dysregulated epithelial-to-mesenchymal transition network. SCCs were depleted of immune cells, and expressed high levels of the immune checkpoint receptor, adenosine receptor A2A (ADORA2A), which is a potent inhibitor of immune infiltration. Our observations have important implications for the prognostication and development of more effective therapies for this lethal bladder cancer variant.