OTHR-22. Malignant mesothelioma (MM) as second cancer in childhood brain tumor survivors: the first child with neurofibromatosis type 2 and concurrent MM

Abstract We report two cases of malignant mesothelioma (MM) in childhood brain tumor survivors. A 40-year-old man, who was treated at the age of ten with chemotherapy and craniospinal radiotherapy (up to 54.5 Gy) for a pineal secreting non-germinomatous germ cell tumor, had persistent fever, fatigue, and weight loss. A total body CT scan revealed several pulmonary and abdominal wall nodularities. The histological examination on a biopsy diagnosed a biphasic MM. The karyotype and array-CGH of peripheral blood were normal; a FISH of tumor cells showed a breakage of locus EWSR1 (22q12.2). In this case, environmental exposure was identified (asbestos in public water tanks). His MM followed an aggressive course and resulted in death after three months. A twelve-year-old boy affected by severe neurofibromatosis type 2 (NF2) already treated with several neurosurgical exeresis and chemotherapy lines (hydroxycarbamide, bevacizumab, sirolimus), developed multiple abdominal lesions, associated with pleural effusion and weight loss. The CT scan showed the thickening of the left pleura and multiple peritoneal nodules. The cytological examination on thoracentesis diagnosed an epithelioid MM. The karyotype on paracentesis-obtained cells revealed monosomy of chromosomes 14 and 22, loss of Y, and trisomy of 6, 10, 11, 16, and 20. NGS is currently ongoing to exclude germline or somatic second hits. Importantly, no exposure to asbestos was found. Less than 2% of MMs occur below 45 years of age; it is a rare secondary tumor in cancer survivors and environmental or genetic contributing causes are often detectable on a careful investigation. Variants in NF2 are considered to be the second most common after those in BAP1. To our knowledge, this is the first child with NF2 and concurrent MM reported to date. Compared to the expected prognosis, his MM has followed a mild course, and one year after diagnosis he is still alive.