Microsatellite instability, immunohistochemistry and germline mismatch repair gene mutations for the diagnosis of Muir-Torre syndrome in immunosuppressed patients

Although rare sebaceous tumors and keratoacanthomas are clinical criteria for Muir-Torre syndrome (MTS), they can also be found in the context of immunosuppression. We present here two patients who underwent organ transplantation in which immunosuppression unmasked MTS through the early appearance of the cutaneous sebaceous neoplasms. In all of their sebaceous tumors we detected microsatellite instability (MSI) e loss of mutS protein homolog 2 (MSH2) and 6 (MSH6) expression at immunohistochemistry (IHC). Although in the absence of visceral MTS phenotype, we performed the sequencing analysis for mismatch repair genes (MMR) identifying two novel MSH2 and MSH6 germline mutations. The combination of MSI and IHC status can therefore be considered useful for the recognition of MTS, even in case of incomplete MTS phenotype and/or in immunosuppressed patients. It would allow a costeffective approach to identify individuals who should undergo MMR genes direct sequencing.