Plasmacytoid/diffuse urothelial carcinoma: a single-institution immunohistochemical and molecular study of 69 patients

Abstract

Accurate diagnosis of plasmacytoid urothelial carcinoma (PUC) is important given its poor prognosis and frequent presentation at high stage. We aim to assess the clinicopathologic features, molecular aberrations, and follow-up data in a series of PUC cases from a single tertiary cancer center. Seventy-two urinary bladder, ureteral, and renal pelvic specimens with urothelial carcinoma with plasmacytoid differentiation were identified. Immunohistochemical (IHC) stains were performed on 48 cases. Among urinary bladder origin markers, GATA3 was most sensitive (96%). Breast carcinoma markers (ER, mammaglobin) were usually negative, but PR stained 1 case (4%). Neuroendocrine markers CD56 and TTF-1 were each positive in 1 case (4% and 4%, respectively). Gastrointestinal adenocarcinoma marker CDX2 was positive in 4 cases (15%), but nuclear β-catenin was negative in all cases. CD138 was positive in 83% and e-cadherin expression was lost in 57% of cases. Fluorescence in situ hybridization (FISH) using the UroVysion Bladder Cancer Kit and FGFR3 mutational analysis using polymerase chain reaction (PCR) were performed on 15 cases; deletion of chromosome 9p21 was common (60%) and FGFR3 mutations were detected in 60% of cases (5 cases had both deletion 9p21 and FGFR3 mutations). Cases were divided into 3 morphologic groups: classic (29%), desmoplastic (35%), and pleomorphic (36%). The three morphologic subtypes had distinct survival outcomes (p=0.083), with median survival for all patients 18 being months versus 10 months for the desmoplastic group.

Plasmacytoid Urothelial Carcinoma: Response to Chemotherapy and Oncologic Outcomes

“…1), along with the increased frequency of localized and peritoneal recurrence (Table 4) are consistent with this finding. E-cadherin loss in 57% of PUC specimens has also been reported by others, including Perrino et al [19]. These authors described stratification of PUC into desmoplastic, classic and pleomorphic morphology, with loss of E-cadherin being more prominent in the last two categories, while 9p21 deletion and FGFR3 mutations were frequently identified, providing insight on molecular pathogenesis and potential therapeutic targets.…”

Plasmacytoid urothelial carcinoma: a rapid autopsy case report with unique clinicopathologic and genomic profile

“…A previous study by some of our co-authors demonstrated pathogenic CDH1 mutations in the majority of PUC [26]. Deletions of chromosome 9p21 have been reported to play an important role and TP53 mutations are present in a minority of PUC [22, 27]. FGFR3 mutations have been detected in approximately 60% of cases [27].…”

“…Deletions of chromosome 9p21 have been reported to play an important role and TP53 mutations are present in a minority of PUC [22, 27]. FGFR3 mutations have been detected in approximately 60% of cases [27]. In a recent study of 69 cases of PUC, three morphologic subtypes (classic, desmoplastic, and pleomorphic) were identified, and the desmoplastic group was found to have shortest survival (10 months) [27].…”

“…FGFR3 mutations have been detected in approximately 60% of cases [27]. In a recent study of 69 cases of PUC, three morphologic subtypes (classic, desmoplastic, and pleomorphic) were identified, and the desmoplastic group was found to have shortest survival (10 months) [27].…”

Plasmacytoid urothelial carcinoma of renal pelvis with positive zinc finger E–box–binding homeobox 1: a case report

“…In addition, immunohistochemically, the expression of ZEB1 reduced E-cadherin expression in the sarcomatous component of other cancers [11]. In contrast, although it has been reported that a plasmacytoid urothelial carcinoma loses E-cadherin expression [12], there have been no reports stating whether or not ZEB1 contributes to the tumorigenesis of a plasmacytoid urothelial carcinoma.…”