Diffuse Pleural Mesothelioma in Young (Age ≤50 Years) and Very Young (Age ≤35 Years) Patients: Clinical Characteristics, Genomics, and Survival.

Abstract

Although we typically consider diffuse pleural mesothelioma (DPM) as a disease of elderly males with a history of asbestos exposure, young individuals are also affected. Given the increasing incidence of cancer in young individuals, we investigated the characteristics and underlying biology of young patients with DPM. We identified patients with DPM age ≤50 years from Memorial Sloan Kettering Cancer Center (1990-2023). Clinicopathologic and genetic characteristics were compared between very young (≤35 years) and young (36-50 years) patients. We identified 273 patients with DPM age ≤50 years; 39% were female, 40% had a history of self-reported occupational asbestos exposure (very young, 16% <i>v</i> young, 45%; <i>P</i> < .01), 16% had a personal history of cancer (very young, 7% <i>v</i> young, 18%; <i>P</i> = .07), and 70% had a family history of cancer (most commonly breast, lung, and colon). Most frequently altered somatic genes (51/273 tested; 46/51 positive) included <i>BAP1</i> (22/47, 47%), <i>NF2</i>(18/47, 38%), <i>CDKN2A/B</i> (12/48, 25%), and <i>TP53</i> (10/48, 21%). Very young patients had less somatic alterations in <i>BAP1</i> (13% <i>v</i> 63%, <i>P</i> < .01) and a lower tumor mutational burden (0.9 <i>v</i> 1.8 mut/mB, <i>P</i> < .01); they were less frequently carriers of germline alterations (0% [0/8] <i>v</i> 43% [6/14], <i>P</i> = .05). Somatic alterations in <i>CDKN2B</i> were more frequent among females (females 42% <i>v</i> males 12%, <i>P</i> = .03). Young patients with DPM have strong personal and family histories of cancer, and heterogeneous somatic and germline alterations, indicating divergent underlying biology. With the increasing prevalence of young adults with cancers, mesotheliomas, although uncommon, should be on the differential for patients even without asbestos exposure history in this age group.