Muir-Torre syndrome

Muir-Torre syndrome (MTS) is a rare hereditary cancer predisposition disorder characterized by the co-occurrence of at least one sebaceous gland neoplasm of the skin and at least one internal (visceral) malignancy. It is considered a phenotypic variant of Lynch syndrome (hereditary nonpolyposis colorectal cancer, or HNPCC). Sebaceous skin tumors include sebaceous adenomas, sebaceous epitheliomas, sebaceous carcinomas, and keratoacanthomas with sebaceous differentiation. The most commonly associated internal malignancies are colorectal cancers, followed by genitourinary cancers (particularly endometrial, ovarian, and urological cancers), breast cancer, and hematologic malignancies. Skin lesions may appear before, simultaneously with, or after the diagnosis of visceral malignancies. Muir-Torre syndrome is caused by germline mutations in DNA mismatch repair (MMR) genes, most commonly MSH2 (accounting for approximately 90% of cases), followed by MLH1, and less frequently MSH6 or PMS2. These mutations lead to microsatellite instability (MSI), which can be detected in both the skin tumors and visceral cancers. Loss of MMR protein expression on immunohistochemistry of sebaceous neoplasms is an important screening tool for identifying patients who may carry these mutations. Management of Muir-Torre syndrome involves a multidisciplinary approach. Patients require regular cancer surveillance protocols similar to those used in Lynch syndrome, including colonoscopy every one to two years beginning at age 20–25, gynecological screening for women, and urological monitoring. Skin lesions are typically managed with surgical excision. Genetic counseling is essential for affected individuals and their at-risk family members. Early detection of visceral malignancies through rigorous surveillance significantly improves outcomes. There is no cure for the underlying genetic predisposition, but awareness and proactive screening remain the cornerstone of care.

Common questions about Muir-Torre syndrome