Diagnostic utility of BAP1 for malignant pleural mesothelioma in pleural fluid specimens with atypical morphology

Cytopathology. 2022 Jan;33(1):84-92. doi: 10.1111/cyt.13015. Epub 2021 Jun 15.

Abstract

Objective: To assess the utility of BRCA1-associated protein 1 (BAP1) immunohistochemistry (IHC) for the diagnosis of malignant pleural mesothelioma (MPM) in fluid samples with atypical cytology.

Methods: Pleural fluid samples with an atypical mesothelial proliferation (diagnostic categories: 'atypical' and 'suspicious') received between January 2015 and March 2018 at a tertiary referral centre were identified. Results of routine IHC testing were recorded for each case. BAP1 by IHC was performed and a final diagnosis sought from subsequent pathology specimens, medical records, or consensus clinical diagnosis.

Results: Of 50 cases identified, 41 were reported as atypical and 9 as suspicious. Seven (14%) demonstrated loss of BAP1 staining, 40 retained BAP1 staining, 1 had heterogeneous staining, and 2 had insufficient cells for analysis. All seven cases with BAP1 loss were diagnosed with MPM on follow-up. Of those with retained BAP1, 52.5% (21) were subsequently diagnosed with MPM, while 40% (16) had non-MPM diagnoses after a median follow-up of 24 months. Three cases were not further investigated based on patient and clinician decision. The case with heterogeneous staining was diagnosed as mesothelioma by clinical consensus.

Conclusions: BAP1 IHC loss is highly specific for malignancy and has value as a rule-in test. Even in a tertiary centre with clinical interest in the cytological diagnosis of MPM this investigation was able to increase diagnostic accuracy beyond routine IHC studies. Cytological criteria remain valuable, as retained BAP1 in an atypical or suspicious mesothelial proliferation cannot exclude malignancy.

Keywords: BAP1 immunohistochemistry; cytology; malignant mesothelioma; pleural effusion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / metabolism
  • Humans
  • Lung Neoplasms* / diagnosis
  • Lung Neoplasms* / genetics
  • Lung Neoplasms* / metabolism
  • Mesothelioma* / pathology
  • Mesothelioma, Malignant*
  • Pleural Neoplasms* / pathology
  • Tumor Suppressor Proteins / genetics
  • Ubiquitin Thiolesterase / genetics

Substances

  • BAP1 protein, human
  • Biomarkers, Tumor
  • Tumor Suppressor Proteins
  • Ubiquitin Thiolesterase