Review of SMARCA4 (BRG1)-deficient carcinomas following a malignant pleural effusion specimen confounded by reduced claudin-4 expression

J Am Soc Cytopathol. 2021 Mar-Apr;10(2):197-207. doi: 10.1016/j.jasc.2020.08.002. Epub 2020 Aug 7.

Abstract

SMARCA4-deficient neoplasms are recently characterized high-grade malignancies associated with a poor prognosis. The SMARCA4 gene encodes BRG1, which is part of the SWI/SNF complex. SMARCA4-deficient neoplasms have an undifferentiated, often rhabdoid morphology, and demonstrate loss of BRG1 nuclear expression on immunohistochemistry. These neoplasms have become increasingly recognized and diagnosed in tissue specimens, but their features in cytologic specimens are poorly defined in the literature. The review is introduced by a diagnostically challenging case of a SMARCA4-deficient carcinoma involving a pleural fluid specimen in which the carcinoma cells demonstrated greatly reduced claudin-4 expression in the setting of strong, diffuse BerEP4 expression. Most of the malignant cells also demonstrated positive cytoplasmic staining for PAS and all were PAS-diastase negative, suggesting that the cytoplasm contained glycogen granules.

Keywords: BRG1; Cancer; INI1; Pleural fluid; Poorly differentiated carcinoma; SMARCA4.

Publication types

  • Case Reports
  • Review

MeSH terms

  • Aged
  • Carcinoma / diagnosis
  • Carcinoma / metabolism
  • Carcinoma / pathology*
  • Claudin-4 / metabolism*
  • DNA Helicases / deficiency*
  • DNA Helicases / metabolism
  • Gastrointestinal Neoplasms / diagnosis
  • Gastrointestinal Neoplasms / metabolism
  • Gastrointestinal Neoplasms / pathology
  • Humans
  • Male
  • Nuclear Proteins / deficiency*
  • Nuclear Proteins / metabolism
  • Pleural Effusion, Malignant / pathology*
  • Thoracic Neoplasms / diagnosis
  • Thoracic Neoplasms / metabolism
  • Thoracic Neoplasms / pathology
  • Transcription Factors / deficiency*
  • Transcription Factors / metabolism

Substances

  • CLDN4 protein, human
  • Claudin-4
  • Nuclear Proteins
  • Transcription Factors
  • SMARCA4 protein, human
  • DNA Helicases