Muir-Torre syndrome: Diagnostic and screening guidelines

Area of Science:

• Oncology
• Genetics
• Dermatology

Background:

• Muir-Torre syndrome (MTS) is an autosomal dominant disorder characterized by an increased risk of various cancers, particularly colorectal and endometrial cancers.
• MTS is associated with germline mutations in DNA mismatch repair (MMR) genes, leading to microsatellite instability (MSI).
• Cutaneous manifestations, including sebaceous neoplasms, are common in MTS and can precede the diagnosis of internal malignancies.

Observation:

• A 65-year-old male with a history of resected adenocarcinoma and a family history of colon cancer presented with asymptomatic facial papules.
• Biopsies revealed sebaceous adenomas and epitheliomas, leading to the suspicion of MTS.
• Tumor tissue exhibited microsatellite instability and diminished expression of the MSH2/MSH6 DNA mismatch-repair protein complex.

Findings:

• Genetic analysis confirmed a germline mutation in the MSH2 gene, establishing the diagnosis of Muir-Torre syndrome.
• The patient's presentation with sebaceous tumors and a history of colorectal cancer aligns with the diagnostic criteria for MTS.
• Immunohistochemical findings supported the molecular basis of the syndrome, indicating impaired DNA repair mechanisms.

Implications:

• Early diagnosis of MTS through cutaneous manifestations and genetic testing is crucial for timely cancer screening and management.
• Genetic counseling and screening for first-degree relatives are essential to identify at-risk individuals.
• This case highlights the importance of recognizing the association between sebaceous neoplasms and internal malignancies in the context of MTS.