MuirTorre

Muir-Torre syndrome is a rare hereditary cancer syndrome that represents a phenotypic variant of Lynch syndrome. It is defined by the combination of sebaceous skin neoplasms and visceral malignancies, most commonly colorectal and endometrial cancers. The condition is caused by germline mutations in DNA mismatch repair genes and is inherited in an autosomal dominant pattern.

Clinical features typically include sebaceous neoplasms such as sebaceous adenomas, sebaceomas, sebaceous carcinomas, and less commonly keratoacanthomas. These skin tumors can precede, coincide with, or follow the diagnosis of visceral cancers, making dermatologic evaluation an important part of surveillance for at-risk individuals.

Genetically, Muir-Torre syndrome is linked to germline mutations in mismatch repair genes, most often MSH2, with mutations in MLH1, MSH6, and PMS2 also reported. Loss of MMR protein expression and microsatellite instability are common in tumors from affected individuals, guiding genetic testing and tumor profiling. The syndrome overlaps with Lynch syndrome in its cancer risks and screening recommendations.

Diagnosis rests on clinical criteria and genetic testing. Clinically, the presence of at least one sebaceous skin tumor and at least one visceral malignancy supports consideration of Muir-Torre syndrome. Confirmation is achieved through germline testing for MMR gene mutations and/or immunohistochemical loss of MMR proteins in tumor tissue, along with genetic counseling and family risk assessment.

Management emphasizes enhanced cancer surveillance and family cascade testing. Regular colonoscopy and appropriate screening for endometrial, ovarian, urinary tract, and other associated cancers are recommended, tailored to the individual’s mutation. Dermatologic treatment of sebaceous lesions may be pursued, with genetic counseling guiding testing for relatives.