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).
The diagnosis of Muir-Torre syndrome was confirmed by molecular genetic investigation that revealed an identical germline mutation in MSH2 gene in several family members, some of whom had colorectal tumors.
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.
In this study, we report a 74-year-old man with known Muir-Torre syndrome with confirmed MSH2 germline mutation, diagnosed with pleomorphic liposarcoma of the right buttock in a previous radiation field.
Most examples of hereditary non-polyposis cancer syndrome (Lynch syndrome), including the Muir-Torre syndrome, are associated with microsatellite instability (MSI) and germline mutations in mismatch repair genes-most commonly MLH1 or MSH2.
Families who carried the c.942+3A>T MSH2 gene mutation had a higher frequency of Muir-Torre syndrome than families who carried other mutations in the MSH2 gene (75% vs 25%; P = .026).
Families who carried the c.942+3A>T MSH2 gene mutation had a higher frequency of Muir-Torre syndrome than families who carried other mutations in the MSH2 gene (75% vs 25%; P = .026).
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.
Haplotype analysis showed that the kindreds C and V+Va (both from northeastern Italy, both displaying clinical features of the Muir-Torre syndrome) shared a seven-locus haplotype, indicating that the MSH2 1-6 deletion is probably a founder mutation.
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].
We report a case of Muir-Torre syndrome associated with intrahepatic cholangiocarcinoma, a location not previously described, and associated with a novel missense mutation of the MSH2 gene (c.2026T > C), predicted to disrupt the function of the gene.
This patient presented with intriguing squamous lesions including keratoacanthoma-like squamous cell carcinoma that showed venous invasion and actinic keratosis, and associated loss of hMSH2 expression, in addition to the sebaceous neoplasms typical of Muir-Torre syndrome.
Value of MLH1 and MSH2 mutations in the appearance of Muir-Torre syndrome phenotype in HNPCC patients presenting sebaceous gland tumors or keratoacanthomas.
Loss of DNA mismatch repair proteins in skin tumors from patients with Muir-Torre syndrome and MSH2 or MLH1 germline mutations: establishment of immunohistochemical analysis as a screening test.
Thus, we could show in a sample of sebaceous tumors from patients with genetically proven Muir-Torre syndrome that loss of heterozygosity most probably is not the preferred mode of somatic inactivation of the second MSH2 allele.