Lynch syndrome (LS) is a hereditary cancer predisposition condition. We report a rare case of malignant pleural mesothelioma occurring in a patient with this syndrome. The interplay between genetic susceptibility and environmental exposure remains underrecognized. We describe a case of a patient with multiple primary malignancies, including mesothelioma. A 70-year-old woman, with a history of endometrial, breast, and colorectal cancers, developed malignant pleural mesothelioma following 15 years of residence in a mining area with probable asbestos exposure. Immunohistochemistry revealed a loss of PMS2 expression, supporting a defect in MMR. This report documents an exceptional coexistence of malignant pleural mesothelioma and LS, suggesting that impaired DNA repair may lower the carcinogenic threshold for asbestos exposure. Clinicians should consider LS in patients with multiple or atypical malignancies, including mesothelioma, and recommend comprehensive MMR testing and genetic counseling for at-risk relatives.
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