Brain Metastases in Diffuse Pleural Mesothelioma: Clinical, Histologic, and Molecular Correlates

Brain metastases (BrMs) are poorly studied and likely underreported in diffuse pleural mesothelioma (DPM), limiting understanding of risk factors associated with their development. We evaluated the genomic, histologic, and clinical landscapes of patients with DPM and BrMs.

We retrospectively reviewed all patients with a mesothelioma diagnosis treated at the Memorial Sloan Kettering Cancer Center between January 1, 2010, and May 1, 2025, with cross-sectional brain imaging. Clinicopathologic data and treatment outcomes were annotated for patients with BrMs.

Among 194 patients with mesothelioma and brain imaging, 16 (8%) had BrMs. Half (n = 8) had tumors of epithelioid histology, 44% (n = 7) biphasic, and 6% (n = 1) sarcomatoid. Compared with our DPM cohort regardless of BrMs (n = 194) or a DPM cohort from The Cancer Genome Atlas (n = 74), patients with DPM and BrMs had a higher prevalence of LATS2 alterations (46% versus 7% versus 12%, respectively [p < 0.00001]). BrMs were typically (88%, n = 14) diagnosed after neurologic symptoms prompting imaging. Among patients with BrMs, the median overall survival from initial mesothelioma diagnosis was 35.4 (95% confidence interval, 19.3-not reached) months and 3.7 (95% confidence interval, 3.5-not reached) months from BrM diagnosis.

Our findings suggest that BrM develops relatively late in DPM, is more common than previously reported, and may be enriched in patients with LATS2 alterations. Prospective, multi-institutional studies with standardized brain imaging are needed to further characterize the incidence of BrMs in DPM and associated risk factors. Routine brain surveillance at diagnosis and with symptoms should be considered for patients with DPM.