A Case of Muir-Torre Syndrome in a Patient with Colon Cancer

초록

Muir-Torre syndrome (MTS) is a rare hereditary autosomal dominant disease associated with development of sebaceous neoplasms and internal malignancy affecting mainly the colon, rectum, and urogenital tract1. Sebaceous adenoma is the most distinctive skin lesion occurring in MTS. The most common internal malignancy associated with MTS is colorectal adenocarcinoma, although a wide tumor spectrum exists1. MTS is a variant of hereditary nonpolyposis colorectal cancer syndrome, which is caused by mutations in the mismatch repair genes leading to DNA mutations and microsatellite instability. A 55-year-old man with a history of colon cancer presented with multiple erythematous erosive papules with central umbilication on his nose for several years (Fig. 1). Histopathologic examination revealed a well-circumscribed symmetric neoplasm with immature follicular germinative cells and mature cells showing sebaceous differentiation, which was diagnosed as sebaceous adenoma (Fig. 2A∼D). Additional history taking revealed that his mother and older brother died from a brain tumor and a biliary tract cancer, respectively, and his sister also had a history of colon cancer. To confirm microsatellite instability, MLH-1, MSH-2, MSH-6, and PMS-2 staining was performed. Immunohistochemical examination revealed loss of MSH-2 and MSH-6 (Fig. 2E∼H). These findings indicate possible visceral malignancies associated with MTS, and the patient was diagnosed with MTS2-4. Additional DNA sequencing analysis was not performed. It is important for clinicians to recognize that a sebaceous adenoma may be associated with an internal malignancy in patients with MTS, as it has been reported that between 20% and 30% of patients with MTS first present with a sebaceous neoplasm and then later acquire a visceral malignancy. One study of 205 cases of MTS documented sebaceous tumors appearing before internal malignancy in 22% of cases, concurrently in 6% of cases, and after in 56% of cases; 16% of cases demonstrated no temporal relationship2. When a base mismatch or error occurs during DNA replication in the repetitive sequences, it is repaired in a healthy individual by a series of enzymes known as DNA mismatch repair proteins. However, mismatch repair proteins (encoded by MSH-2, MSH-6, MLH-1, PMS-2 genes, and others) are deficient in the genome of MTS patients, leading to accumulated mutations in microsatellites3. Correlations between mismatch repair nuclear protein expressions by immunohistochemistry and germline sequencing in cutaneous sebaceous and visceral neoplasms have demonstrated the utility of immunohistochemistry in determining mismatch repair deficiency3. Loss of staining for combinations of certain gene products (MLH-1, MSH-2, and MSH-6) appears to give a 100% positive predictive value that the patient has MTS4. Because sebaceous neoplasms are considered to be cutaneous markers, a dermatopathologist can play an important role in the early recognition of MTS. Also, immunohistochemical staining for MLH-1, MSH-2, and MSH-6 could be a useful screening tool for patients with sebaceous neoplasm located outside the head and neck area in a young patient (＜50 years of age) or patients with an inherited cancer predisposition4,5. Herein, we report a case of MTS in a patient with a familial and personal history of internal malignancy.

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