We performed an immunohistochemical study with antibodies against MSH6, MSH2, MLH1, and PMS2, which demonstrated preserved nuclear expression of the mismatch repair proteins, therefore ruling out Muir-Torre syndrome.
Mutations reported to cause Muir-Torre syndrome (MTS) have previously been reported in the mismatch repair genes MLH1 and MSH2 and more recently, in MYH [1].
The eponymous Muir-Torre syndrome (MTS) is a clinical variant of hereditary non polyposis colorectal cancer, and is defined as an autosomal dominant condition with simultaneous sebaceous neoplasms of the skin and visceral malignant disease resulting from germline mutations in the DNA mismatch repair (MMR) genes.
Hereditary non-polyposis colorectal cancer (HNPCC), also known as Lynch syndrome types I and II, and the related subtypes Turcot and Muir-Torre syndrome, have all been associated with inheritance of germ line mutations in the DNA mismatch repair (MMR) genes.
Certain MMR gene mutations predispose to combined occurrence of cutaneous sebaceous gland neoplasms and visceral malignancies, which is known as Muir-Torre syndrome (MTS) and regarded as a phenotypic variant of HNPCC.
Biopsy specimens of periocular sebaceous gland carcinoma obtained from six patients (mean age, 60 +/- 17 years; range, 38 to 83 years, 5 male, 1 female) with Muir-Torre syndrome and histopathologically proven sebaceous gland carcinoma were studied immunohistochemically for the presence of fragile histidine triad protein.
All 10 sporadic periocular sebaceous carcinomas maintained strong staining of the 4 mismatch repair genes, while tumor from the patient with Muir-Torre syndrome showed loss of staining for the mismatch repair genes MSH2 and MSH6.
Evidence indicating microsatellite stability in three of 17 patients with a clinical history indicative of Muir-Torre syndrome and a mutation in only MSH-6 suggests that the phenotype of a germline MSH-6 mutation differs from that of MLH-1 and MSH-2 mutations and further supports the use of immunohistochemistry as a screening tool in patients with Muir-Torre syndrome with an extended panel that includes MSH-6.
Having a high probability for MSI, she was found to be heterozygous for a germline point mutation in MSH2 gene, where a pathologic variant, c.1165C > T (p.Arg389*), determined by sequencing confirmed Muir-Torre syndrome (MTS).