SWI/SNF-deficient undifferentiated/rhabdoid carcinoma of the gallbladder carrying a POLE mutation in a 30-year-old woman: a case report

Diagn Pathol. 2021 Jun 12;16(1):52. doi: 10.1186/s13000-021-01112-4.

Abstract

Background: Undifferentiated carcinoma of the biliary tract are highly aggressive malignancies. In other organs, a subgroup of undifferentiated carcinoma related to SWI/SNF complex-deficiency have been described.

Case presentation: A 30-year-old woman presented with rising inflammatory markers (C-reactive protein (CRP)). Ultrasound examination revealed a large tumor of the liver. A computed tomography scan was performed and was primarily interpreted as a tumor-forming liver abscess, possibly caused by gallbladder perforation. Subsequent liver segment resection was performed. Microscopic examination showed an undifferentiated carcinoma with rhabdoid morphology and prominent inflammatory infiltrate in the gallbladder base. With SWI/SNF immunohistochemistry, intact expression of SMARCB1, SMARCA4, ARID1A, but loss of SMARCA2 and PBRM1 was detected. Next-generation-sequencing detected KRAS, PBRM1 and ARID1B mutations, a deleterious splice-site mutation in the POLE-gene and a mutation in the TP53-gene.

Conclusions: We were able to demonstrate loss of SMARCA2 expression and mutations characteristic of an SWI/SNF-deficient carcinoma in a tumor derived from the gallbladder. This is the first reported case of an undifferentiated carcinoma with rhabdoid features in the gallbladder carrying a POLE mutation and SWI/SNF-deficiency of PBRM1 and SMARCA2.

Keywords: Case report; Gallbladder carcinoma; Rhabdoid; SMARCA4; SWI/SNF-deficiency.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Biomarkers, Tumor* / deficiency
  • Biomarkers, Tumor* / genetics
  • Cell Differentiation
  • Chromosomal Proteins, Non-Histone / deficiency*
  • DNA Mutational Analysis
  • DNA Polymerase II / genetics*
  • DNA-Binding Proteins / deficiency
  • Fatal Outcome
  • Female
  • Gallbladder Neoplasms / chemistry
  • Gallbladder Neoplasms / genetics
  • Gallbladder Neoplasms / pathology*
  • Gallbladder Neoplasms / surgery
  • Genetic Predisposition to Disease
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Immunohistochemistry
  • Mutation*
  • Phenotype
  • Poly-ADP-Ribose Binding Proteins / genetics*
  • Rhabdoid Tumor / chemistry
  • Rhabdoid Tumor / genetics
  • Rhabdoid Tumor / pathology*
  • Rhabdoid Tumor / surgery
  • Transcription Factors / deficiency*
  • Treatment Outcome

Substances

  • Biomarkers, Tumor
  • Chromosomal Proteins, Non-Histone
  • DNA-Binding Proteins
  • PBRM1 protein, human
  • Poly-ADP-Ribose Binding Proteins
  • SMARCA2 protein, human
  • SWI-SNF-B chromatin-remodeling complex
  • Transcription Factors
  • DNA Polymerase II
  • POLE protein, human