Testing for BAP1 loss and CDKN2A/p16 homozygous deletion improves the accurate diagnosis of mesothelial proliferations in effusion cytology

Abstract

Background: A number of ancillary tests have been developed that aid in the diagnosis of mesothelioma in cytology specimens. The aim of this retrospective study was to determine whether testing for BAP1 and CDKN2A/p16 status in effusion specimens preceding the tissue diagnosis of mesothelioma would improve diagnostic accuracy and allow an earlier diagnosis of malignancy. Methods: The study cohort included 99 matched cytology fluid specimens from 74 patients with a surgical specimen diagnosis of malignant mesothelioma (67 epithelioid, 7 biphasic, 55 pleural, and 19 peritoneal). BAP1 immunohistochemistry and p16 fluorescence in situ hybridization (FISH) were performed retrospectively. Results: BAP1 or p16 FISH testing revealed a loss in 7 of 18 (39%) samples originally categorized as benign/reactive, 20 of 33 (61%) interpretable samples categorized as atypical, and 10 of 14 (71%) cases suspicious for mesothelioma. In some cases, the diagnosis of mesothelioma could have been made up to 9 months before biopsy. Similarly, loss of BAP1 or p16 was found in 28 of 30 (93%) samples categorized as malignant, with some cases diagnosable up to 6 months before biopsy. Overall, loss of BAP1 and/or CDKN2A/p16 homozygous deletion would change the diagnostic interpretation in 37 of 60 (62%) (P =.07) effusion specimens, particularly in pleural effusions (32 of 48 samples) (P =.002). The sensitivity of morphologic interpretation alone was 30.3%; however, adding testing for BAP1 and p16 resulted in an increase in sensitivity to 68.7%. (P