Genetic and Immunohistochemical Profiling of Malignant Mesothelioma With Brain Metastasis: A Report of Two Cases

BACKGROUND: Brain metastasis (BM) occurs in < 3% of malignant mesothelioma (MM) cases and is associated with an aggressive disease course. While genomic profiling has provided insight into molecular alterations in MM, the characteristics of MM with brain involvement remain unexplored. Data are particularly limited for MM of pericardial origin, an exceedingly rare tumor which comprises < 1% of mesotheliomas. CASES: We describe the clinical course and genetic profiles of two patients with BM from MM, both of whom exhibited atypical presentations, including neurological symptoms, diagnosis at extremes of age for this condition, and absence of prior asbestos exposure. In Case 1, a 20-25-year-old male with pericardial MM presented for left arm shaking, with brain MRI at this time revealing 14 total lesions, 85.7% of which had vasogenic edema. He underwent whole-brain radiotherapy (WBRT), passing away 21.25 months following initial diagnosis. In Case 2, an 85-90-year-old male reported expressive aphasia and was found to have a large hemorrhagic frontotemporal lesion. He was subsequently diagnosed with pleural MM and received stereotactic radiosurgery (SRS) for management of BM, with a favorable treatment response on follow-up imaging. He succumbed to systemic progression 6 months after diagnosis of BM. Next-generation sequencing identified a missense mutation in RAD51C in Case 1, and NF2 splice-site and TP53 frameshift mutations in Case 2. CONCLUSION: To our knowledge, this represents the first reported genetic profiling of MM with BM. The TP53 frameshift mutation is unusual for MM, and its potential association with rapid disease progression warrants further investigation. Given the aggressive nature of MM, SRS may be preferable to WBRT due to its shorter treatment time and ease of combination with systemic regimens.