Contribution of BAP1 loss and p16 (CDKN2A) deletion analysis to the definitive diagnosis of mesothelioma in effusion cytology

OBJECTIVE: The cytological diagnosis of mesothelioma is a controversial is-sue, and definitive diagnosis often requires ancillary tests. The aim of this study was to investigate the contribution of BRCA1-associated protein (1) (BAP1) loss and p16 (CDKN2A) homozygous deletion (HD) on the early diagnosis of mesothelioma in effusion fluids. MATERIALS AND METHODS: Between 2019-2022, 21 pleural and peritoneal fluid samples di-agnosed with atypical mesothelial proliferation in our institution were included in the study. The slides of the cases that underwent BAP1 immu-nohistochemistry (IHC) were retrieved from the archive and re-examined. Homozygous deletion (HD) of p16 (CDKN2A) was investigated by the fluorescence in situ hybridization (FISH) method in cell blocks of cytology samples. At least 100 atypical mesothelial cells were counted in each case, and the HD threshold value was >10%. RESULTS: The mean age of the cases was 63.47 years (34-90 years), female/male ratio was 3/1. Of the pleural mesothelioma cases, 16 were epithelioid, 2 were biphasic, and 1 were sarco-matoid. Two cases were diagnosed with perito-neal well-differentiated papillary mesothelioma (WDPM). BAP1 loss was observed in 11 (69%) of 16 cases. HD deletion of p16 (CDKN2A) was seen in 11 (58%) patients with FISH. The HD threshold value was 10-20% in 6 of the cases, 30-50% in 3 cases, and above 90% in 2 cases. While HD de-letion was observed in p16 (CDKN2A) in all bi-phasic and sarcomatoid cases (n=3), no deletion was observed in peritoneal WDPM (n=2). Positiv-ity was observed with at least one method in 12 (86%) of 14 pleural mesotheliomas who under-went both BAP1 IHC and p16 (CDKN2A) FISH. Due to technical reasons, the FISH signal could not be obtained in two cell blocks, so no results could be obtained. CONCLUSIONS: Asbestos exposure in ar-eas where mesothelioma is endemic and/or the presence of proliferating mesothelial cells in cy-tological examination are important clues for diagnosis. In controversial cases, BAP1 IHC should be the first step in an ancillary test. Al-though the FISH method applied to cell blocks has cytology-specific limitations and difficul-ties, investigating the p16 (CDKN2A) deletion with FISH in selected cases will contribute to the diagnosis.