POU2F3-expressing intraepithelial small-cell carcinoma with mixed small-cell carcinoma and conventional-type urothelial carcinoma of the urinary bladder

Based on lineage-specific transcription factors, small-cell neuroendocrine carcinoma (SmCC) of the urinary bladder has recently been subtyped into three molecular subtypes: ASCL1, NEUROD1 and POU2F3. The latter is a master transcriptional regulator of tuft cells (TCs) which are rare solitary cells found in various mucosal epithelia such as the gastrointestinal tract, but which have not been reported in the bladder. The POU2F3 subtype shows low or absent neuroendocrine marker expression. A case of mixed SmCC and conventional-type urothelial carcinoma (CUC) of the urinary bladder with POU2F3-expressing intraepithelial small-cell carcinoma in keeping with a tuft cell phenotype, arising in association with intestinal metaplasia (IM) is described. The presence of POU2F3-expressing cells in normal urothelium, cystitis cystica glandularis and IM of the urinary bladder is demonstrated in separate cases of cystitis cystica glandularis with IM. Also, POU2F3 expression is identified in a subset of bladder SmCC.