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

OBJECTIVE To assess the utility of BRCA-1 associated protein 1 (BAP1) immunohistochemistry (IHC) for the diagnosis of malignant pleural mesothelioma (MPM) in pleural fluid samples with atypical cytology. METHODS Pleural fluid samples received between January 2015 and March 2018 at a tertiary referral centre with a diagnosis of atypical mesothelial proliferation (diagnostic categories: 'atypical' and 'suspicious') 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 50 cases were identified, 41 cases were reported as atypical and 9 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 can increase diagnostic accuracy beyond routine IHC studies. Cytological criteria remain valuable as retained BAP1 in an atypical or suspicious mesothelial proliferation cannot exclude malignancy.