Malignant Pleural Mesothelioma in a Young Patient with Neurofibromatosis 2 and Acquired BAP1 Loss: A Case Report

• We present a BAP1 mutant malignant pleura mesothelioma in a patient with NF2 • Somatic NF2 mutations are common in mesothelioma but not germline loss • Diagnosis was complicated by unusual presentation and non-diagnostic biopsies • We still observe response to dual immunotherapy 14 months after starting treatment Neurofibromatosis type 2 (NF2) is a rare genetic disorder resulting from germline loss of the NF2 tumor suppressor gene characterized by the development of multiple benign central nervous system tumors. Malignant pleural mesothelioma (MPM) is a rare and aggressive cancer arising from the pleura. We present a 32-year-old male with NF2 diagnosed with MPM found to have acquired BAP1 loss. We present a 33-year-old male patient with previously known NF2 who was found to have BAP1 and NF2 mutant MPM. The patient denied history of asbestos exposure or chest radiation. He presented with a persistent cough and tachycardia for which he underwent a computed tomography angiogram of the chest which discovered pleural effusion and pleural nodules. After a complicated diagnostic course involving 2 negative biopsies, a 3rd surgical biopsy finally showed sarcomatoid MPM, and molecular testing revealed mutations in BAP1 and NF2 . The patient was initiated on dual checkpoint immunotherapy and has a durable response 14 months since treatment initiation. This is the first case reported, to our knowledge, for which an NF2 patient was diagnosed with MPM at a young age and without known traditional risk factors. Somatic mutations in NF2 are often observed in MPM, but germline NF2 loss is not classically associated with MPM. However, in the setting of concomitant acquired BAP1 loss, germline NF2 loss could predispose a patient to MPM. This case highlights the importance of better understanding how genetic variants in tumor suppressor genes influence cancer risk.