The role of BRCA1-associated protein 1 in the diagnosis of malignant mesothelioma in effusion and fine-needle aspiration cytology.

Abstract

Malignant mesothelioma (MM) is a diagnostically challenging entity in cytology specimens due to the lack of architectural context and a cytomorphologic overlap between malignant and reactive mesothelial cells (RMCs). A diagnostic marker with excellent specificity is not currently available in clinical practice. The newly appreciated BRCA1-associated protein 1 (BAP1) antibody may help distinguish MM from RMC based on its immunohistochemical (IHC) staining pattern but its role in cytopathology is controversial. Immunohistochemistry with BAP1 antibody was performed on cell blocks from 39 cytology specimens including 13 cases of RMC and 26 cases of effusion and fine-needle aspiration specimens (FNAC) with tissue-specimen-proven MM. Cases were dichotomised into positive and negative cohorts. Positivity was defined as >50% loss of nuclear BAP1 IHC staining. Of the 26 MM cases, a slight majority (14/26, 54%) showed loss of BAP1 nuclear IHC staining, while all 13 RMC controls showed strong nuclear BAP1 IHC staining. MM was more likely to show loss of BAP1 than RMC (P < .001); and peritoneal MM was more likely to demonstrate loss of BAP1 than pleural MM (P = .04). There was perfect specificity at 1.0 and positive predictive value of 1.0 for loss of nuclear BAP1 IHC staining. However, only modest sensitivity at 0.52 and negative predictive value of 0.50 was seen. These data confirm that absence of BAP1 nuclear staining identifies malignant mesothelial cells. On the other hand, positive BAP1 nuclear staining can occur in both benign and malignant pleural effusions.