Muir-Torre Syndrome: A Rare But Important Disorder
Muir-Torre syndrome (MTS) is a rare disorder characterized by the presence of at least one sebaceous gland neoplasm and at least one visceral malignancy. Sebaceous adenomas, sebaceous carcinomas, and sebaceomas (sebaceous epitheliomas) are all characteristic glandular tumors of MTS. The most common visceral malignancies associated with MTS are colorectal, followed by genitourinary. These visceral malignancies frequently have a more indolent course in patients with MTS than they would otherwise. Muir-Torre syndrome is an autosomal dominant disorder; however, sporadic cases are known to develop. It often is associated with germ-line mutations in the mutS homolog 2, colon cancer, nonpolyposis type 1 (Escherichia coli) gene, MSH2, and the mutL homolog 1, colon cancer, nonpolyposis type 2 (E coli) gene, MLH1 (similar to hereditary nonpolyposis colon cancer [HNPCC]). The diagnosis of MTS currently is based on clinical criteria; however, immunohistochemical staining for MSH2 and MLH1 can confirm the diagnosis. We report 2 patients with MTS who developed colon adenocarcinomas in conjunction with sebaceous carcinomas. Both patients demonstrated loss of MSH2 expression in tumor cells on immunohistochemical staining. One of these patients later developed gastric carcinoma, a very uncommon malignancy associated with MTS. We conclude that the diagnosis of rare sebaceous lesions associated with MTS may represent a marker of visceral disease and warrants further investigation for internal malignancies in the individual and at-risk family members.
Currently, the diagnosis of MTS is based on clinical criteria. Immunohistochemical staining for MSH2 and MLH1 is a practical initial approach to confirm the diagnosis of MTS. Once a sebaceous skin tumor is noted, the pathologist may perform immunohistochemical staining using antibodies against MSH2 and MLH1 proteins in skin tumor tissue as an initial screening for mismatch repair defects. This procedure is an efficient and cost-effective method of screening and has a high predictive value for the diagnosis of DNA mismatch repair–deficient MTS.22,25 If immunohistochemical staining shows loss of MSH2 or MLH1 protein expression, molecular genetic analysis could then be performed. Moreover, cancer surveillance as well as genetic testing and counseling for the patient and family members can be initiated. Cancers, including both sebaceous neoplasms and visceral malignancies, associated with MTS have a more indolent course than they would if unassociated with this syndrome, even after metastases develop.3,4 Because these low-grade malignancies tend to permit prolonged survival, even metastatic disease may respond well to aggressive surgical treatment. One of our patients (patient 1) remains cancer free 13 years after treatment of her node-positive colon adenocarcinoma, which may reflect the indolent course of visceral malignancies associated with MTS.
Conclusion
We recommend consideration of MTS in any patient who has sebaceous neoplasms, particularly because sebaceous gland neoplasms are rare and cutaneous lesions may be the first sign of the disease. Immunohistochemical stains for MSH2 and MLH1 protein expression in skin tumor tissue should be performed, and patients should have a complete evaluation for gastrointestinal or genitourinary cancers. Because this syndrome has an autosomal dominant inheritance pattern, genetic counseling should be offered to all family members. All relatives who inherit the DNA mismatch repair defect have a substantially increased risk for visceral malignancies and therefore should also undergo routine cancer surveillance. The identification of occult malignancies is especially important in these patients, as the tumors often are amenable to treatment, even in the presence of metastasis.
