Presented by: Lauren Ogrich, MD and Mark Abdelmalek, MD
Drexel University College of Medicine
May 16, 2016
Muir-Torre syndrome is a disorder characterized by at least one sebaceous tumor and visceral malignancy. It is a phenotypic variant of hereditary nonpolyposis colorectal carcinoma syndrome (HPNCC) or Lynch syndrome (LS).
Cutaneous neoplasms associated with MTS include sebaceous carcinomas, sebaceous adenomas, keratoacanthomas, and basal cell carcinoma with sebaceous differentiation. Visceral malignancies associated with MTS include colorectal adenocarcinoma, urogenital tract cancers, breast cancer, and hematologic malignancies.
In two-thirds of cases, often referred to as MTSI, the pathogenicity of Muir-Torre syndrome stems from a germline mutation in mismatch repair genes and is inherited in an autosomal dominant fashion. These inherited mutations in MLH1 and MSH2 result in severe microsatellite instability with MSH2 comprising 90% of identifiable mutations. Other identifiable germline mutations include mismatch repair genes MSH6 and PMS2.
Around one-third of sebaceous tumors associated with MTS do not show microsatellite instability. In these cases, MTSII is caused by biallelic inactivation of MYH, a base excision repair gene, and is inherited in an autosomal recessive manner.
Any patient who is diagnosed with a sebaceous neoplasm should undergo immunohistology instability analysis. If a lesion demonstrates mismatch repair protein instability, the patient should undergo germline mutation analysis.
Patients diagnosed with MTS and first degree relatives should undergo a vigorous preventive cancer screening program including annual skin exams, annual colonoscopies beginning at the age of 25, annual gynecologic screening and transvaginal ultrasound beginning at age 30, and annual urinalysis and cytologic exam beginning at age 30.
Case reports suggest patients with MTS may benefit from switching to sirolimus as it may halt progression of further sebaceous neoplasms.
John AM, S. R. (2016). Muir-Torre syndrome (MTS): An update and approach to diagnosis and management. J Am Acad Dermatol., 74(3), 558-566.
Landis MN, D. C., Bellus GA, Wolverton SE. (2011). Immunosuppresion and sebaceous tumors: a confirmed diagnosis of Muir-Torre syndrome unmasked by immunosuppressive therapy. J Am Acad Dermatol., 65(5), 1054-1058.
Ponti G, P. d. L. M. (2005). Muir-Torre syndrome. Lancet Oncol., 6(12), 980-987.