The WHO classification of 2004 defines new histological and molecular variants of urothelial carcinoma. However there are limited data available on the clinico-pathological characteristics or prognosis of these variants. We present histopathological, molecular and clinical data of 32 plasmacytoid carcinomas of the bladder (PUC) showing that PUC is a high-grade tumor with molecular features of aggressive urothelial carcinoma, usually diagnosed in advanced pathological stage (64% pT3, 23% pT4) showing metastases in 60 % of the patients. Average survival of our cohort of PUC treated with radical cystectomy and adjuvant chemotherapy was lower than what is typically seen for comparable conventional urothelial carcinomas. 87% of the PUCs showed a negative or strongly reduced membranous staining of E-cadherin. Beta-catenin staining was negative in 22.5% and 16.7% of the remaining tumors showed nuclear accumulation. Aberrant CK20 expression (negative or > 10% of cells stained) and negative CK7 staining was found in 100% and 22.6%, respectively. 97% revealed positive staining for PAN-CK. CD138 was positive in 78 %, whereas MUM-1 expression was negative in all cases. Multi-target fluorescence in situ hybridization showed all PUCs to be highly aneuploid and polysomic. Deletions on chromosome 9p21 seem to play an important role in this variant. FGFR3 and PIK3CA mutation analyses yielded no mutations in any of the PUCs analyzed. TP53 mutation analysis showed mutations in 29%. In summary, PUC is a aggressive variant of bladder cancer with molecular features of advanced bladder cancer and evidence of WNT pathway activation in some of the cases.
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