Muir-Torre Syndrome

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Article initiated by:

John Thompson, MD

All contributors:

Jonathan S. Williams, Zachary Harbin, Jill Wells, MD, Michael T Yen, MD, Preeti Thyparampil, MD, John Thompson, MD

Assigned editor:

Preeti Thyparampil, MD, Sara Lally, MD

Review:

Assigned status Up to Date

 by Preeti Thyparampil, MD on October 29, 2024.

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Muir-Torre Syndrome

DiseasesDB

31385

OMIM

158320

MeSH

D055653

Disease Entity

Disease

Muir-Torre Syndrome (MTS) is a variant of Lynch syndrome that was first described in 1967 by Dr. Muir and in 1968 by Dr. Torre. It is characterized as the presence of at least one cutaneous sebaceous neoplasm and one visceral malignancy, most commonly colon cancer.

Epidemiology

The disease is present in 9.2% of individuals with HNPCC/Lynch syndrome. Demographic information is largely limited to Caucasians. M:F 3:2. Onset of malignancy from age 23-89 with median of 53. It generally results from AD mutations in DNA mismatch repair genes including MSH2 (90%), MLH1 (<10%), and MSH6 with high penetrance and variable expression that result in microsatellite instability. There have also been reports of MTS without microsatellite instability from MYH mutations. Sporadic cases have been described in solid organ transplant (most commonly renal) and immunosuppressed patients, specifically with tacrolimus and cyclosporine.

Diagnosis

Criteria: (1) at least a single sebaceous gland tumor, including adenoma, epithelioma or carcinoma, (2) at least one internal malignancy. Sebaceous hyperplasia alone is generally seen as not sufficient for the first criterion.

History

• Obtain a detailed family cancer history including colorectal, urogenital, endometrial, hepatobiliary cancers. Similar to other familial colon cancer syndromes, the colon cancer is generally found at or proximal to the splenic flexure, unlike in sporadic cases.
• Personal or family history of sebaceous neoplasm including sebaceous adenomas, epitheliomas (a.k.a. sebaceoma), carcinomas, basal cell carcinoma (BCC) with sebaceous differentiation and seboacanthomas.
• Sebaceous tumors can precede, be concurrent with, or, most commonly, follow visceral malignancy.
• Sebaceous adenoma is most common with a frequency of 68%, followed by carcinoma 30%, and epithelioma 27%.

Physical examination

• Painless, slow growing pink or yellow papules or nodules which are generally found on the eyelid or nose. They can have central umbilication and ulceration. Lesions found below the neck are less likely to be sporadic tumors. Additionally, multiple keratoacanthomas with or without concurrent sebaceous neoplasms should raise suspicion.

Diagnostic procedures

Histopathology

Sebaceous tumors have cells with coarsely vacuolated cytoplasm and starry nuclei and have been described as ‘mulberry cells’. Sebaceous cells will react immunologically to epithelial membrane antigen.

• A sebaceous adenoma is composed of multiple irregularly shaped sebaceous lobules with incomplete differentiation which are surrounded by a layer of small basaloid cells. It does not have a central draining duct which allows differentiation from sebaceous hyperplasia.
• A sebaceoma is a variant of sebaceous adenoma which is composed of >/=50% basaloid epithelial cells.
• Carcinomas have features more typical of malignancy including cellular atypia, high mitotic activity, infiltrative growth, etc. Peripheral pallisading and cleft formation are generally absent, unlike in BCC. Positive fat staining can support this diagnosis. Pagetoid spread through the epidermis can also sometimes be seen.
• Keratoacanthoma and BCC with sebaceous differentiation will react to epithelial membrane antigen in areas of sebaceous proliferation along with their individual typical features.

Immunohistochemistry

In one study, mutations in MLH-1 showed a positive predictive value (PPD) of 88%, while MSH-2 and MSH-6 showed 55% and 67%, respectively, while the combinations of MLH-1 with MSH-6 showed 100% PPD. Another recent study suggested using MLH-1, MSH-6, and PMS2 plus or minus MSH-2. These mutations can arise sporadically and thus clinical evidence or history of a corresponding visceral cancer must also be present to make diagnosis.

Differential diagnosis

MUTYH polyposis, Familial adenomatous polyposis Gardner syndrome, Cowden syndrome, tuberous sclerosis, Ferguson-Smith syndrome, Brooke-Spiegler syndrome, basal cell nevus syndrome.

Management

General treatment

Complete excision of most cutaneous tumors, however, sebaceous carcinomas require wide local excision. Radiation can be used as adjunctive therapy.

Medical follow up

• Genetic and family counseling along with the option for first degree relatives to be genetically tested.
• Women with genetically proven MTS should undergo yearly breast and pelvic exams as well as a transvaginal ultrasound and an endometrial biopsy. Men should undergo yearly testicle and prostate exams. Both sexes should obtain yearly endoscopy/colonoscopies.
• In family members with MTS, colonoscopies can start as early as 18 years of age.
• A complete neurological exam with low threshold for imaging if any neurological deficits develop.

Prognosis

Dependent on the associated visceral cancer or on sebaceous carcinoma metastasis. One study found that MTS patients often had ‘multiple, low-grade primary neoplasms and prolonged survival’ following the diagnosis of their original malignancy.