Sebaceous neoplasms such as adenoma, sebaceoma, and carcinoma, although sporadic in their occurrence, are clinically significant because of their association with Muir–Torre syndrome (MTS). MTS is a rare autosomal dominant genodermatosis characterized by the occurrence of sebaceous neoplasms and/or keratoacanthomas and visceral malignancies. MTS is usually the result of germline mutations in the DNA mismatch repair genes MSH2 and, albeit less commonly, MLH1. Although less know, MSH6 is yet another key player. Evidence from Lynch syndrome indicates that pathogenic germline mutations in MSH6 are typically microsatellite stable and have a clinical presentation that differs from that associated with germline mutations in MSH2 and/or MLH1. Given this unique mutator phenotype of MSH6, the primary aim of this review was to underscore the clinical manifestations associated with pathogenic mutations in MSH6 in patients with MTS. As the current clinical and laboratory work-up of MTS is geared toward patients harboring a germline mutation in MSH2 and/or MLH1, an additional aim was to provide a scaffolding for the work-up of a patient presenting with an isolated germline mutation in MSH6.
Dermatopathology Section Chief, Dermatopathology Section, Department of Pathology and Laboratory Medicine (113), VA Consolidated Laboratories, West Roxbury, MA.
Reprints: Meera Mahalingam, MD, PhD, FRCPath, Dermatopathology Section Chief, Dermatopathology Section, Department of Pathology and Laboratory Medicine (113), VA Consolidated Laboratories, 1400 VFW PKWY, West Roxbury, MA 02132 (e-mail: firstname.lastname@example.org).
The author and staff in a position to control the content of this CME activity and her spouse have disclosed that they have no financial relationships with, or financial interests in, any commercial organizations pertaining to this educational activity.
Presented in part and by invitation, at the Royal College of Pathologists, December 4, 2015.