title: The plasmacytoid carcinoma of the bladder--rare variant of aggressive urothelial carcinoma.
abstract: The WHO 2004 classification defines new histological and molecular variants of urothelial carcinoma. However, there are limited data available on the clinicopathological 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. Eighty-seven percent of the PUCs showed a negative or strongly reduced membranous staining of E-cadherin. β-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. Ninety-seven percent revealed positive staining for PAN-CK. CD138 was positive in 78%, whereas MUM-1 expression was negative in all cases. Multitarget 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 an aggressive variant of bladder cancer with molecular features of advanced bladder cancer and evidence of WNT pathway activation in some of the cases.
authors.affiliation: Department of Urology, University Erlangen, Erlangen, Germany. bastian.keck@uk-erlangen.de
authors.forename: Bastian
authors.initials: B
authors.lastname: Keck
authors.forename: Robert
authors.initials: R
authors.lastname: Stoehr
authors.forename: Sven
authors.initials: S
authors.lastname: Wach
authors.forename: Anja
authors.initials: A
authors.lastname: Rogler
authors.forename: Ferdinand
authors.initials: F
authors.lastname: Hofstaedter
authors.forename: Jan
authors.initials: J
authors.lastname: Lehmann
authors.forename: Rodolfo
authors.initials: R
authors.lastname: Montironi
authors.forename: Mathilde
authors.initials: M
authors.lastname: Sibonye
authors.forename: Hans M
authors.initials: HM
authors.lastname: Fritsche
authors.forename: Antonio
authors.initials: A
authors.lastname: Lopez-Beltran
authors.forename: Jonathan I
authors.initials: JI
authors.lastname: Epstein
authors.forename: Bernd
authors.initials: B
authors.lastname: Wullich
authors.forename: Arndt
authors.initials: A
authors.lastname: Hartmann
mesh_terms: D002295:Carcinoma, Transitional Cell / Q000188:drug therapy / Q000235:genetics* / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D002986:Clinical Trials as Topic; D015331:Cohort Studies; D015653:Cystectomy; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics*; D051498:Receptor, Fibroblast Growth Factor, Type 3 / Q000235:genetics*; D016019:Survival Analysis; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000601:surgery
chemical_list: D016159:Tumor Suppressor Protein p53; D019869:Phosphatidylinositol 3-Kinases; D051498:Receptor, Fibroblast Growth Factor, Type 3