Plasmacytoid/Signet Ring Cell Bladder Carcinoma (SRCBC)

Overview

Plasmacytoid/signet ring cell bladder carcinoma (SRCBC) is an aggressive histologic variant of bladder cancer defined by plasmacytoid or signet-ring-cell morphology. In the OncoTree hierarchy it is a child of BLADDER. It is excluded from the TCGA bladder urothelial carcinoma cohort (BLCA), which restricts to urothelial carcinoma NOS. The variant is distinguished from conventional bladder urothelial carcinoma (BLCA) by nearly universal E-cadherin loss (driven predominantly by somatic CDH1 truncating mutations), a distinctive peritoneal pattern of spread, and a worse prognosis.

Cohorts in the corpus

Recurrent alterations

  • CDH1 — truncating somatic mutations (nonsense, frameshift) in 84% of plasmacytoid-variant tumors (vs 0% in 127 TCGA urothelial NOS); promoter hypermethylation accounts for 4/5 mutation-negative cases; E-cadherin loss universal by IHC across all 31 cases PMID:26901067
  • TP53 — frequently mutated at rates comparable to conventional urothelial carcinoma PMID:26901067
  • RB1 — frequently mutated at rates comparable to conventional urothelial carcinoma PMID:26901067
  • ARID1A — recurrent chromatin-remodeler alterations PMID:26901067
  • ERBB2, PIK3CA, TSC1 — recurrent, clinically actionable alterations flagged by the authors PMID:26901067
  • PTEN, NOTCH2, FAT4 — detected as plasmacytoid-component-specific alterations in a mixed tumor alongside a CDH1 frameshift PMID:26901067

Subtypes

  • Mixed plasmacytoid/urothelial NOS tumors occur; multi-region sequencing of one case showed shared truncal mutations (CDKN1A A45fs, PIK3C2G S48R) with the NOS component and CDH1 mutation private to the plasmacytoid component, consistent with a common precursor PMID:26901067

Therapeutic landscape

  • No CDH1-targeted therapy exists; the pathognomonic CDH1 truncation is a loss-of-function event not directly druggable PMID:26901067
  • Recurrent ERBB2, PIK3CA, and TSC1 alterations support early use of anti-HER2, PI3K-pathway, or mTOR-pathway agents in the context of multi-modality treatment PMID:26901067
  • Patients have higher cumulative incidence of local recurrence and cancer-specific mortality than urothelial NOS; authors recommend more aggressive multi-modality treatment PMID:26901067

Sources

  • PMID:26901067 — Al-Ahmadie et al., MSKCC plasmacytoid bladder cancer WES + targeted sequencing study

This page was processed by crosslinker on 2026-05-14.