A possible association between mycosis fungoides and Muir-Torre syndrome: Two disorders with microsatellite instability

ECP: extracorporeal photopheresis HNPCC: hereditary nonpolyposis colorectal carcinoma ICL: interstrand crosslink MF: mycosis fungoides MMR: mismatch repair MSI: microsatellite instability MSI-H: high levels of microsatellite instability MTS: Muir-Torre syndrome PUVA: psoralen plus ultraviolet A INTRODUCTION Muir-Torre syndrome (MTS) is a rare, hereditary, autosomal dominant cancer syndrome that is a variant of hereditary nonpolyposis colorectal carcinoma (HNPCC) or Lynch syndrome. MTS is characterized by sebaceous neoplasms and HNPCC-associated malignancies such as colorectal, endometrial, and urothelial cancers. The underlying genetic causes of MTS are mutations in or, more rarely, hypermethylation of DNA mismatch repair (MMR) genes, such as MLH1, MSH2, and MSH6. Impaired MMR leads to errors in DNA repair during replication, which can cause microsatellite instability (MSI) and subsequent carcinogenesis. Loss of MMR function leading to MSI has also been identified in a number of leukemias and lymphomas, including mycosis fungoides (MF), a subtype of cutaneous T-cell lymphoma. Little is known about the molecular pathogenesis of MF, and unlike nodal lymphomas, specific chromosomal translocations have not been detected for MF. However, MSI might play a pivotal role in causing MF. In fact, there is evidence of MLH1 promoter hypermethylation and loss of MSH2 expression in MF. Although MSI has been identified in both MF and MTS, there is no known association between the 2 disorders to date. Herein, we describe a 65-year-old man with a 7-year history of MF who was later also diagnosed with MTS, and we suggest a possible association between MF and MTS.