Muir-Torre syndrome

Definition

A syndrome is a condition in which a certain set of features is regularly seen. In Muir-Torre syndrome, the consistent features are skin tumors (sebaceous neoplasms) and internal organ cancers, most commonly colon cancer .

Description

Muir-Torre syndrome is named for two authors who provided some of the earliest descriptions of the condition, Muir in 1967 and Torre in 1968. Originally thought to be separate conditions, it is now known that Muir-Torre syndrome and hereditary non-polyposis colon cancer (HNPCC), also known as Lynch syndrome, are due to alterations in the same genes. Some of the features of the conditions are the same including increased risk of colorectal cancer (cancer of the colon and rectum) and cancer of other organs. Both conditions are hereditary cancer predisposition syndromes meaning that the risk of cancer has been linked to an inherited tendency for the disease. A unique feature of Muir-Torre syndrome is the skin tumors. The most common skin tumors associated with Muir-Torre syndrome are benign (non-cancerous) or malignant (cancerous) tumors of the oil-secreting (sebaceous) glands of the skin. Another relatively common skin finding is the presence of growths called keratoacanthomas.

Genetic profile

HNPCC and Muir-Torre syndrome are allelic meaning that these disorders are due to changes in the same genes. Genes, the units of instruction for the body, can have changes or mutations that develop over time. Certain mutations are repaired by a class of genes known as mismatch repair genes. When these genes are not functioning properly, there is a higher chance of cancer due to the alterations that accumulate in the genetic material. Heritable mutations in at least five mismatch repair genes have been linked to HNPCC although the majority, over 90%, are in the hMLH1 and hMSH2 genes. Mutations in hMLH1 and hMSH2 also have been reported in Muir-Torre syndrome although most have been hMSH2 mutations. The location of the hMLH1 gene is on chromosome 3 at 3p21.3 while the location of hMSH2 is chromosome 2, 2p22-p21. Genetic testing for hMLH1 and hMSH2 is available but the detection rate for mismatch repair gene mutations is less than 100%. Therefore, diagnosis of Muir-Torre syndrome is not based on genetic testing alone but also on the presence of the typical features of the disease.

Muir-Torre syndrome is inherited in an autosomal dominant fashion. Thus, both men and women can have Muir-Torre syndrome and only one gene of the paired genes, needs to be altered to have the syndrome. Children of individuals with Muir-Torre syndrome have a one in two or 50% chance of inheriting the gene alteration. However, the symptoms of the syndrome are variable and not all individuals with the condition will develop all of the features.

Demographics

At least 250 cases of Muir-Torre syndrome, specifically, have been reported. It is estimated that between one in 200 to one in 2,000 people in Western countries carry an alteration in the genes associated with HNPCC but the rate of Muir-Torre syndrome itself has not been clarified. More males than females appear to exhibit the features of Muir-Torre syndrome. The average age at time of diagnosis of the syndrome is around 55 years.

Signs and symptoms

Skin findings

Sebaceous neoplasms typically appear as yellowish bumps on the skin of the head or neck but can be found on the trunk and other areas. The classification of the different types of sebaceous neoplasms can be difficult so microscopic evaluation is usually required for the final diagnosis. Keratoacanthomas are skin-colored or reddish, firm skin nodules that are distinct from sebaceous neoplasms upon microscopic examination. The skin findings in Muir-Torre syndrome can either appear before, during, or after the development of the internal cancer.

Internal findings

Internal organ cancers are common in Muir-Torre syndrome. Several individuals with Muir-Torre syndrome with multiple types of internal cancers have been reported. The most common internal organ cancer is colorectal cancer. Unlike colon cancers in the general population, the tumors due to Muir-Torre syndrome are more frequently seen around or closer to the right side of an area of the colon known as the splenic flexure. This tumor location, the meeting point of the transverse and the descending colon, is different than the usual location of colon cancer in the general population. Colon polyps, benign growths with the possibility of cancer development, have been reported in individuals with Muir-Torre syndrome; however, the number of polyps typically is limited.

TABLE 1
Screening recommendations for patients with Muir-Torrie syndrome

TABLE 2
Additional screening recommendations for females with Muir-Torriesyndrome

Symptoms of colorectal cancer or polyps may include:

• red blood in stool
• weight loss
• pain or bloating in abdomen
• long-term constipation
• diarrhea
• decrease in stool size

The next most frequent cancer occurrences in Muir-Torre syndrome are those of the genitourinary system including uterine cancer, ovary cancer, and bladder cancer. Other cancers that have been seen with Muir-Torre syndrome include breast cancers, blood cancers, head and neck cancers and cancers of the small intestine.

Diagnosis

Since not all families with the features of Muir-Torre syndrome have identifiable mismatch repair gene alterations, diagnosis is based mainly on the presence of the physical features of the disease. Muir-Torre syndrome is defined by the presence of certain types of sebaceous neoplasms (sebaceous adenomas, sebaceous epitheliomas, sebaceous carcinomas and keratoacanthomas with sebaceous differentiation) and at least one internal organ cancer in the same individual. Muir-Torre syndrome may also be diagnosed if an individual has multiple keratoacanthomas, multiple internal organ cancers and a family history of Muir-Torre syndrome. Testing of the hMLH1 and hMSH2 genes is available and could be done to confirm a diagnosis or to assist in testing at-risk relatives prior to development of symptoms. Given the complexity of this disorder, genetic counseling may be considered before testing.

Screening recommendations have been proposed for individuals with Muir-Torre or at-risk relatives. In addition to regular screening for the skin findings, screening for internal cancers may be considered. The effectiveness of screening for individuals with or at risk for Muir-Torre syndrome has yet to be proven.

Treatment and management

While it is not possible to cure the genetic abnormality that results in Muir-Torre syndrome, it is possible to prevent and treat the symptoms of the syndrome. The skin tumors are removed by freezing or cutting. If lymph nodes, small bean-sized lumps of tissue that are part of the immune system, are involved, these must be removed also. Radiation, high energy rays, to the affected area can be beneficial. A medication, isotretinoin, may reduce the risk of skin tumors. Internal organ cancers are treated in the standard manner, removal by surgery and possible treatment with radiation or cancer-killing medication (chemotherapy). Removal of the colon, colectomy, before colon cancer develops is an option with HNPCC and may be considered for individuals with Muir-Torre syndrome.

Prognosis

The cancers associated with Muir-Torre syndrome are usually diagnosed at earlier ages than typically seen. For instance, the average age at diagnosis of colorectal cancer is 10 years earlier than in the general population. Fortunately, the internal organ cancers seen in Muir-Torre syndrome appear less aggressive. So, the prognosis may be better for a person with colon cancer due to Muir-Torre syndrome than colon cancer in the general population.

Resources

BOOKS

Flanders, Tamar, et al. "Cancers of the digestive system." Inherited Susceptibility: Clinical, predictive and ethical perspectives. edited by William D. Foulkes and Shirley V. Hodgson, Cambridge University Press, 1998. pp.181-185.

ORGANIZATIONS

American Cancer Society. 1599 Clifton Road NE, Atlanta, GA 30329. (800) 227-2345. <http://www.cancer.org>.

National Cancer Institute. Office of Communications, 31 Center Dr. MSC 2580, Bldg. 1 Room 10A16, Bethesda, MD 20892-2580. (800) 422-6237. <http://www.nci.nih.gov>.

WEBSITES

M.D. Anderson Cancer Center. <http://www3.mdanderson.org/depts/hcc>.

Kristin Baker Niendorf, MS, CGC