Introduction
Background
In 1967, Muir and Torre each reported on patients with multiple cutaneous tumors (including sebaceous neoplasms and other tumors) and visceral malignancies (including gastrointestinal and other sites). Muir-Torre syndrome (MTS) is a syndrome that combines at least one sebaceous neoplasm (sebaceous adenoma, sebaceous epithelioma, or sebaceous carcinoma) and at least one visceral malignancy (usually gastrointestinal or genitourinary carcinomas). MTS has an autosomal dominant pattern of inheritance in 59% of cases and has a high degree of penetrance and variable expression.
Pathophysiology
MTS is considered a subtype of the more common hereditary nonpolyposis colorectal cancer syndrome (HNPCC). This condition is associated with an inherited defect in one copy of a DNA mismatch repair gene (MMR), which eventually leads to microsatellite instability (MSI). The 2 major MMR proteins involved are hMLH1 and hMSH2. Approximately 70% of tumors associated with the MTS have MSI. While germline disruption of hMLH1 and hMSH2 is evenly distributed in HNPCC, disruption of hMSH2 is seen in greater than 90% of MTS patients.Frequency
United States
MTS is a rare disorder, with approximately 200 patients reported. Families with MTS are probably more common than reported.
Mortality/Morbidity
In many patients, the skin cancers associated with MTS tend to have a nonaggressive course. Despite this, approximately 60% of patients reportedly develop metastatic disease, with a 50% survival rate calculated at 12 years. Those lesions outside the head and neck may have a more aggressive behavior.
Sex
MTS occurs in both sexes, with a male-to-female ratio of 3:2.
Age
The patient's age at presentation ranges from young adulthood to elderly patients, with a median age of 53 years.
Clinical
History
- A positive family history of MTS can be found in roughly 50% of patients.
- An association with a family history of colon cancer has also been documented.
- Cutaneous sebaceous neoplasms can precede or follow a diagnosis of visceral malignancy.
- MTS is associated with HNPCC, an autosomal dominant cancer genetic syndrome. The diagnostic criteria (Amsterdam criteria) include the following:
- Three or more relatives with an HNPCC-associated cancer (ie, colorectal, cancer of the endometrium, small bowel, ureter, or renal pelvis)
- Cancer affecting at least 2 successive generations
- One person with cancer is a first-degree relative of the other 2, at least 1 case of colorectal cancer younger than age 50 years, a diagnosis of familial adenomatous polyposis has been excluded, tumors are verified by examination in a pathology laboratory
Physical
Criteria for the diagnosis of MTS include the presence of at least one sebaceous adenoma, sebaceous epithelioma, or sebaceous carcinoma (sebaceous hyperplasia and nevus sebaceus of Jadassohn are generally excluded), and at least one visceral cancer. Keratoacanthoma, squamous cell carcinoma, and multiple follicular cysts are sometimes included in the cutaneous tumors. The skin lesions may precede the presentation of internal malignancy, although they often develop later. Cutaneous nodules occurring on the face, the trunk, and the extremities are found in various other disorders, including Gardner syndrome, Cowden syndrome, multiple trichoepitheliomas, basal cell nevus syndrome, eruptive keratoacanthomas, and tuberous sclerosis. Many of these syndromes are also associated with visceral tumors.
- Sebaceous adenoma is the most characteristic marker of MTS. These fairly rare benign tumors usually appear as yellow papules or nodules in adult patients. In the sporadic cases, most tumors are located on the head (particularly on the face, the scalp, and the eyelids), with the remaining minority scattered over the rest of the body. In MTS, lesions on the trunk may be more common. The clinical features of sebaceous epithelioma are similar. The nomenclature for sebaceous neoplasms is controversial. Some authors use the term sebaceoma for indolent tumors composed of mature sebocytes and undifferentiated basaloid germinative cells. This subset of tumors corresponds to lesions traditionally classified as sebaceous epithelioma.
- Sebaceous carcinomas most commonly occur on the eyelids, where they generally arise from the meibomian glands and the glands of Zeiss. They may also occur almost anywhere on the skin, including the ears, the feet, the penis, and the labia. On the eyelids, the tumor appears as a firm, yellow nodule with a tendency to ulcerate (see Media Files 1-2). Clinically, these lesions are often mistaken for chalazia, chronic blepharoconjunctivitis, or carbuncles. Sebaceous carcinoma of the eyelid can invade the orbit and can frequently metastasize and cause death. Extraocular tumors can also metastasize but are less likely to cause death.
Sebaceous carcinoma of the upper eyelid. Courtesy of Mark S. Brown, MD, University of South Alabama Medical Center.
Sebaceous carcinoma as viewed from the conjunctival side (same patient as in Media File 1). Courtesy of Mark S. Brown, MD, University of South Alabama Medical Center.
- Keratoacanthoma, whether solitary or multiple, is frequently seen in MTS. Keratoacanthoma usually starts as a red papule that rapidly grows to become a skin-colored, shiny nodule with telangiectases and a central horny plug covered by a crust. Common sites of involvement include the face and the dorsum of the hands, but they can occur anywhere on the body. The tumors have a tendency to regress, ultimately leaving a scar.
- The most common visceral neoplasm in MTS is colorectal cancer, occurring in almost one half of patients. The tumors are usually proximal to the splenic flexure. The second most common site is the genitourinary tract, representing approximately one quarter of visceral cancers. A wide variety of other cancers, including breast cancer, lymphoma and rarely leukemia, salivary gland tumors, lower and upper respiratory tract tumors, and chondrosarcoma, are reported. Intestinal polyps occur in at least one quarter of patients. Other benign tumors described in MTS include ovarian granulosa cell tumor, hepatic angioma, benign schwannoma of the small bowel, and uterine leiomyomas.
Causes
See Pathophysiology. The main anomaly detected in these patients is the alteration in the mismatch repair genes (MSH2 on chromosome 2 and MLH1 on chromosome 3).
More on Muir-Torre Syndrome |
 Overview: Muir-Torre Syndrome |
| Differential Diagnoses & Workup: Muir-Torre Syndrome |
| Treatment & Medication: Muir-Torre Syndrome |
| Follow-up: Muir-Torre Syndrome |
| Multimedia: Muir-Torre Syndrome |
| References |
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References
Kruse R, Rutten A, Schweiger N, Jakob E, Mathiak M, Propping P, et al. Frequency of microsatellite instability in unselected sebaceous gland neoplasias and hyperplasias. J Invest Dermatol. May 2003;120(5):858-64. [Medline].
Mathiak M, Rutten A, Mangold E, Fischer HP, Ruzicka T, Friedl W, et al. Loss of DNA mismatch repair proteins in skin tumors from patients with Muir-Torre syndrome and MSH2 or MLH1 germline mutations: establishment of immunohistochemical analysis as a screening test. Am J Surg Pathol. Mar 2002;26(3):338-43. [Medline].
Ponti G, Losi L, Di Gregorio C, Roncucci L, Pedroni M, Scarselli A, et al. Identification of Muir-Torre syndrome among patients with sebaceous tumors and keratoacanthomas: role of clinical features, microsatellite instability, and immunohistochemistry. Cancer. Mar 1 2005;103(5):1018-25. [Medline].
Graefe T, Wollina U, Schulz H, Burgdorf W. Muir-Torre syndrome - treatment with isotretinoin and interferon alpha-2a can prevent tumour development. Dermatology. 2000;200(4):331-3. [Medline].
Abbas O, Mahalingam M. Cutaneous sebaceous neoplasms as markers of Muir-Torre syndrome: a diagnostic algorithm. J Cutan Pathol. Jun 2009;36(6):613-9. [Medline].
Barana D, van der Klift H, Wijnen J, Longa ED, Radice P, Cetto GL, et al. Spectrum of genetic alterations in Muir-Torre syndrome is the same as in HNPCC. Am J Med Genet A. Mar 15 2004;125(3):318-9. [Medline].
Burger B, Itin P. Muir-Torre syndrome. Dermatology. 2008;217(1):56-7; author reply 57. [Medline].
Cohen PR, Kohn SR, Kurzrock R. Association of sebaceous gland tumors and internal malignancy: the Muir-Torre syndrome. Am J Med. May 1991;90(5):606-13. [Medline].
Dores GM, Curtis RE, Toro JR, Devesa SS, Fraumeni JF Jr. Incidence of cutaneous sebaceous carcinoma and risk of associated neoplasms: insight into Muir-Torre syndrome. Cancer. Dec 15 2008;113(12):3372-81. [Medline].
Hare HH, Mahendraker N, Sarwate S, Tangella K. Muir-Torre syndrome: a rare but important disorder. Cutis. Oct 2008;82(4):252-6. [Medline].
Honchel R, Halling KC, Schaid DJ, Pittelkow M, Thibodeau SN. Microsatellite instability in Muir-Torre syndrome. Cancer Res. Mar 1 1994;54(5):1159-63. [Medline].
Ingram JR, Griffiths AP, Roberts DL. All patients with sebaceous gland neoplasms should be screened for Muir-Torre syndrome. Clin Exp Dermatol. Mar 2009;34(2):264-6. [Medline].
Kruse R, Rutten A, Lamberti C, Hosseiny-Malayeri HR, Wang Y, Ruelfs C, et al. Muir-Torre phenotype has a frequency of DNA mismatch-repair-gene mutations similar to that in hereditary nonpolyposis colorectal cancer families defined by the Amsterdam criteria. Am J Hum Genet. Jul 1998;63(1):63-70. [Medline].
Lynch HT, Fusaro RM, Roberts L, Voorhees GJ, Lynch JF. Muir-Torre syndrome in several members of a family with a variant of the Cancer Family Syndrome. Br J Dermatol. Sep 1985;113(3):295-301. [Medline].
Pancholi A, Collins D, Lindley R, Gandhi P. Muir-Torre syndrome: a case report and screening recommendations. Ann R Coll Surg Engl. Nov 2008;90(8):W9-10. [Medline].
Ponti G, Losi L, Pedroni M, Lucci-Cordisco E, Di Gregorio C, Pellacani G. Value of MLH1 and MSH2 mutations in the appearance of Muir-Torre syndrome phenotype in HNPCC patients presenting sebaceous gland tumors or keratoacanthomas. J Invest Dermatol. Oct 2006;126(10):2302-7. [Medline].
Rao NA, Hidayat AA, McLean IW, Zimmerman LE. Sebaceous carcinomas of the ocular adnexa: A clinicopathologic study of 104 cases, with five-year follow-up data. Hum Pathol. Feb 1982;13(2):113-22. [Medline].
Schwartz RA, Torre DP. The Muir-Torre syndrome: a 25-year retrospect. J Am Acad Dermatol. Jul 1995;33(1):90-104. [Medline].
Spielvogel RL, DeVillez RL, Roberts LC. Oral isotretinoin therapy for familial Muir-Torre syndrome. J Am Acad Dermatol. Mar 1985;12(3):475-80. [Medline].
Tanyi M, Olasz J, Lukács G, Tanyi JL, Tóth L, Antal-Szalmás P, et al. A new mutation in Muir-Torre syndrome associated with familiar transmission of different gastrointestinal adenocarcinomas. Eur J Surg Oncol. May 5 2009;[Medline].
Wick MR, Goellner JR, Wolfe JT 3rd, Su WP. Adnexal carcinomas of the skin. II. Extraocular sebaceous carcinomas. Cancer. Sep 1 1985;56(5):1163-72. [Medline].
Keywords
Muir-Torre syndrome, MTS, sebaceous adenoma, sebaceous epithelioma, sebaceous carcinoma, gastrointestinal carcinoma, genitourinary carcinoma, colonic carcinoma, colorectal cancer, cutaneous sebaceous neoplasms, hereditary nonpolyposis colorectal cancer syndrome, HNPCC
