The cutaneous neoplasms that have been reported in Muir-Torre syndrome include sebaceous adenomas, sebaceous epitheliomas, sebaceous carcinomas, cystic sebaceous tumors, basal cell carcinomas with sebaceous differentiation, and keratoacanthomas usually displaying some sebaceous differentiation. Sebaceous adenomas are the most common among these tumors. The criteria to obtain a diagnosis of Muir-Torre syndrome include at least one sebaceous neoplasm and at least one internal malignancy at some point in the patient’s life, without other causative factors such as radiotherapy or immunosuppression. The diagnosis also can be made in the combined setting of multiple keratoacanthomas, visceral malignancy, and family history of MTS. Of note, sebaceous hyperplasia and nevus sebaceous of Jadassohn are not considered features of Muir-Torre syndrome.

The clinical presentation can differ due to the variable expression of defects in the mismatch repair genes, and the number of sebaceous neoplasms can range from a solitary lesion to hundreds. Sebaceous lesions often present as slow-growing, painless, yellowish-colored papules or nodules which may or may not have ulceration. The most common location is the face, but any part of the skin with a sebaceous gland can develop a tumor. The majority of sporadic sebaceous tumors in patients without Muir-Torre syndrome are seen on the nose and eyelid, and any sebaceous tumor below the neck should raise suspicion of Muir-Torre syndrome. The clinical presentation of keratoacanthomas is similar to the sporadic counterpart, and they may be seen as solitary lesions or multiple.

A thorough history should be performed in the evaluation of any patient suspected of having Muir-Torre syndrome. While the most common malignancy is colon carcinoma, numerous other cancers have been described in association with Muir-Torre syndrome including malignancies involving the endometrium, cervix, ovaries, breast, small bowel, bone, hepatobiliary tract, brain, pancreas, upper uroepithelial tract, blood (lymphoma and leukemia), and lung.

Immunohistochemistry (IHC) can be performed on sebaceous neoplasms to identify defects in the mismatch repair genes commonly implicated in Muir-Torre syndrome, and current recommendations advocate this test. This method, however, is not diagnostic of Muir-Torre syndrome as there have been reports of mismatch repair gene mutations in sebaceous neoplasms in patients who did not have the defect in other cells elsewhere in the body. This finding suggests that the gene defects were somatic rather than germline mutations. In these patients, the higher risk of visceral malignancy is not seen. Due to the diagnostic limitations of IHC for Muir-Torre syndrome, several authors advocate IHC testing on sebaceous neoplasms for mismatch repair genes in conjunction with obtaining thorough personal and family histories. If the IHC result reveals mismatch repair gene mutations, genetic testing is then warranted before further work-up such as screening tests for malignancy are performed. Once the diagnosis of Muir-Torre syndrome is confirmed with genetic testing, annual evaluations for malignancy should be performed. A lower threshold for biopsy of clinically apparent sebaceous tumors should be adopted in patients with Muir-Torre syndrome because sebaceous carcinomas often initially present similarly to the benign counterparts, and this often leads to a delay in diagnosis. A lower threshold is particularly relevant for periocular lesions as this is the most common location for sebaceous carcinoma; however, sebaceous carcinomas can arise from any sebaceous gland.

Once the diagnosis has been established, Muir-Torre syndrome patients should undergo annual surveillance for visceral and cutaneous malignancy. Upper and lower gastrointestinal endoscopy should be performed. Colonoscopy may begin as early as 18 years while upper endoscopy is recommended around 25 to 30 years. Men should undergo annual testicular and prostate exams, and women should have annual breast and pelvic exams along with transvaginal ultrasound and endometrial sampling for suspicious findings. Other potentially beneficial tests would include chest x-ray, cervical and urine cytology, carcinoembryonic antigen levels, fecal occult blood testing, liver function tests, and complete blood counts. 

The cutaneous manifestations of Muir-Torre syndrome can be difficult to treat due to the potential number and disfigurement that numerous sebaceous neoplasms can cause. Reassurance should be offered for benign lesions. Local excision and cryotherapy may be performed for patients desiring removal of benign lesions. Keratoacanthomas should also be managed conservatively with local excision. Sebaceous carcinomas have the potential for local and distant metastasis and should be managed more aggressively with wide local excision with 5 to 6 millimeter margins or Mohs micrographic surgery. Radiation may also be employed but only as adjuvant therapy after excision of a recurrent sebaceous carcinoma, or regional metastasis. Radiation as monotherapy for primary cutaneous sebaceous carcinoma has been associated with higher rates of mortality and recurrence. Additionally, interferon-alpha in conjunction with oral isotretinoin has been reported to decrease the development of cutaneous and visceral malignancies.

The differential diagnosis of Muir-Torre syndrome would include other syndromes in which multiple cutaneous papules and nodules appear on the face and/or body, such as Cowden syndrome, Birt-Hogg-Dube syndrome, Tuberous Sclerosis, Brooke-Spiegler syndrome, and Gorlin syndrome. Syndromes such as the Gryzbowski-type generalized eruptive keratoacanthomas and the Ferguson-Smith-type multiple eruptive keratoacanthomas should be considered in patients with numerous keratoacanthomas. The sporadic versions of sebaceous tumors and keratoacanthomas also should also be considered although the former is not common in the general population. As noted previously, sporadic sebaceous neoplasms occur most often on the head while they are rarely seen below the neck. Sebaceous neoplasms found below the neck should raise suspicion of Muir-Torre syndrome.

MTS is a rare syndrome associated with various dermal and visceral malignancies. These patients are best managed by an interprofessional team that includes oncology nurses. Once the diagnosis is made Muir-Torre syndrome patients should undergo annual surveillance for visceral and cutaneous malignancy. Upper and lower gastrointestinal endoscopy should be performed. Colonoscopy may begin as early as 18 years while upper endoscopy is recommended around 25 to 30 years. Men should undergo annual testicular and prostate exams, and women should have annual breast and pelvic exams along with transvaginal ultrasound and endometrial sampling for suspicious findings. Other potentially beneficial tests would include chest x-ray, cervical and urine cytology, carcinoembryonic antigen levels, fecal occult blood testing, liver function tests, and complete blood counts. 

The skin lesions are managed with topical ablative therapies or surgical excision. The prognosis for these patients is poor as most succumb to malignancies.[2]