FaCD Online Syndrome Fact Sheet

Last updated: 25 May 2009

Name: Muir-Torre syndrome

Mode of Inheritance: AD

Genes

MLH1, mapped to 3p21.3
MSH2, mapped to 2p21-p22
MSH6, mapped to 2p16

Tumor features

biliary tract cancer (incl. gallbladder)
endometrial cancer
gastrointestinal adenomas
gastrointestinal cancer
gastrointestinal polyps
glioma of the brain
hepatocellular cancer (hepatoma)
keratoacanthoma
lung/bronchial cancer
ovarian cancer (i.e. epithelial origin)
pancreatic adenocarcinoma
renal pyelum cancer
sebaceous adenoma
sebaceous carcinoma
sebaceous epithelioma
ureter cancer

Tumor features (possible)

breast cancer
laryngeal cancer
leukemia
sarcoma

Comment

The combination of sebaceous tumors and internal malignancies has been named Muir-Torre syndrome (MTS) after early reports on patients with this combination by Muir and Torre[1-3]. This syndrome should be regarded as a variant of Lynch syndrome, because the extra-dermal phenotype of MTS fits well within the Lynch syndrome spectrum, with the possible exception of hematological malignancies[4-7] and germline mutations in similar genes have been observed[14]. Importantly, isolated cases meeting the MTS criteria have been observed within Lynch syndrome families[8,14]. In further support of the overlap between Lynch syndrome and MTS is the fact that MSH2 deficient mice exhibit MTS-like-skin lesions in 7% of cases[9]. A case of non-small cell lung cancer in Muir-Torre syndrome, which showed microsatellite instability and loss of MSH2 staining has been reported[21].

Interestingly, Ponti et al reported a patient with multiple sebaceous gland adenmomas, early onset colon and papillary thyroid cancer, multiple colorectal adenomas and bi-allelic MUTYH mutations[20] which suggests that MAP can present with a MTS-like phenotype.

Kruse et al.[10] detected a germline hMLH1 mutation in a patient with an isolated cystic sebaceous tumor (no personal history of other tumors and the patient’s father had died from gastric cancer at the age of 36). The authors state that patients with a cystic sebaceous tumor are very likely to have MTS, whereas non-cystic sebaceous gland tumors can also occur in the absence of MTS/HNPCC. In some cases, sebaceous carcinoma may present clinically as a breast tumor[11].

Criteria: 3 different sets of criteria have been formulated in the past and, at that time, did not include any criterion with respect to molecular diagnosis:

Cohen and Kohn[4]:
Diagnosis requires at least 1 sebaceous gland tumor (adenoma, epithelioma, carcinoma) + at least 1 internal malignancy.

Schwartz and Torre[12]:
Diagnosis requires

• a) 1 criterion from group A + 1 from group B, or
• b) all criteria from group C

• a) 1 major criterion + 2 second criteria, or
• b) 1 major criterion + 1 second criterion + 1 third criterion

References

[1] Muir EG, Yates Bell AJ, Barlow KA. Multiple primary carcinomata of the colon, duodenum, and larynx associated with kerato-acanthomata of the face. Br J Surg 1967; 54:191-195.
[2] Smith PAJ. Multiple sebaceous papillomas. Proc R Soc Med 1958; 51:709-710.
[3] Torre D. Multiple sebaceous tumors. Arch Dermatol 1968; 98(5):549-551.
[4] Cohen PR, Kohn SR, Kurzrock R. Association of sebaceous gland tumors and internal malignancy: the Muir-Torre syndrome. Am J Med 1991; 90(5):606-613.
[5] Cohen PR, Kohn SR, Davis DA, Kurzrock R. Muir-Torre syndrome. Dermatol Clin 1995; 13(1):79-89.
[6] Lynch HT, Fusaro RM. Muir-Torre syndrome: heterogeneity, natural history, diagnosis, and management. Probl Gen Surg 1993; 10(4):765-778.
[7] Cohen PR. Muir-Torre syndrome in patients with hematologic malignancies. Am J Hematol 1992; 40(1):64-65.
[8] Weitzer M, Pokos V, Jeevaratnam P, van de Water NS, Browett PJ, Jass JR. Isolated expression of the Muir-Torre phenotype in a member of a family with hereditary non-polyposis colorectal cancer. Histopathology 1995; 27:573-575.
[9] Reitmair AH, Redston M, Cai JC, Chuang TCY, Bjerknes M, Cheng H, Hay K, Gallinger S, Bapat B, Mak TW. Spontaneous intestinal carcinomas and skin neoplasms in Msh2- deficient mice. Cancer Res 56[16], 3842-3849. 1996.
[10] Kruse R, Rutten A, Malayeri HRH, Gunzl HJ, Friedl W, Propping P. A novel germline mutation in the hMLH1 DNA mismatch repair gene in a patient with an isolated cystic sebaceous tumor. J Invest Dermatol 112[1], 117-118. 1999.
[11] Propeck PA, Warner T, Scanlan KA. Sebaceous carcinoma of the breast in a patient with Muir-Torre syndrome. Am J Roentgenol 2000; 174(2):541-542.
[12] Schwartz RA, Torre DP. The Muir-Torre syndrome: A 25-year retrospect. J Am Acad Dermatol 1995; 33:90-104.
[13] Hartig C, Stieler W, Stadler R. Mui-Torre-syndrom: Diagnosekriterien und literaturubersicht. Hautarzt 1995; 46:107-113.
[14] South CD, Hampel H, Comeras I, Westman JA, Frankel WL, de la Chapelle A. The frequency of Muir-Torre syndrome among Lynch syndrome families. Journal of the National Cancer Institute 2008; 100(4):277-81.
[15] Ponti G, Losi L, Pedroni M, Lucci-Cordisco E, Di Gregorio C, Pellacani G, Seidenari S. Value of MLH1 and MSH2 mutations in the appearance of Muir-Torre syndrome phenotype in HNPCC patients presenting sebaceous gland tumors or keratoacanthomas. The Journal of investigative dermatology 2006; 126(10):2302-7.
[16] Ponti G, Ponz de Leon M. Muir-Torre syndrome. The lancet oncology 2005; 6(12):980-7.
[17] Ponti G, Losi L, Di Gregorio C, Roncucci L, Pedroni M, Scarselli A, Benatti P, Seidenari S, Pellacani G, Lembo L, Rossi G, Marino M, Lucci-Cordisco E, Ponz de Leon M. Identification of Muir-Torre syndrome among patients with sebaceous tumors and keratoacanthomas: role of clinical features, microsatellite instability, and immunohistochemistry. Cancer 2005; 103(5):1018-25.
[18] Pettey AA, Walsh JS. Muir-Torre syndrome: a case report and review of the literature. Cutis; cutaneous medicine for the practitioner 2005; 75(3):149-55.
[19] Nishizawa A, Nakanishi Y, Sasajima Y, Yamazaki N, Yamamoto A. Muir-torre syndrome with intriguing squamous lesions: a case report and review of the literature. The American Journal of dermatopathology 2006; 28(1):56-9.
[20] Ponti G, Ponz de Leon M, Maffei S, Pedroni M, Losi L, Di Gregorio C, Gismondi V, Scarselli A, Benatti P, Roncari B, Seidenari S, Pellacani G, Varotti C, Prete E, Varesco L, Roncucci L. Attenuated familial adenomatous polyposis and Muir-Torre syndrome linked to compound biallelic constitutional MYH gene mutations. Clinical genetics 2005; 68(5):442-7.
[21] Nolan L, Eccles D, Cross E, Crawford G, Beck N, Bateman A, Ottensmeier C. First case report of Muir-Torre syndrome associated with non-small cell lung cancer. Fam Cancer. 2009 May 16. [Epub ahead of print]