Official reprint from UpToDate®
www.uptodate.com ©2017 UpToDate, Inc. and/or its affiliates. All Rights Reserved.

Muir-Torre syndrome

Patricia Tai, MB, BS, DABR, FRCR, FRCPC
Section Editor
June K Robinson, MD
Deputy Editor
Rosamaria Corona, MD, DSc


Muir-Torre syndrome (MIM #158320) is a rare autosomal dominant condition characterized by the association of at least one sebaceous skin tumor and at least one visceral malignancy [1,2]. Muir-Torre syndrome is caused by germline mutations in the DNA mismatch repair genes and is considered a phenotypic variant of hereditary nonpolyposis colorectal carcinoma syndrome (HNPCC, Lynch syndrome). Internal malignancies most frequently associated with Muir-Torre syndrome include colorectal, endometrial, ovarian, and urothelial cancers [3,4].

This topic will discuss the pathogenesis, clinical features, diagnosis, and management of Muir-Torre syndrome. Lynch syndrome is discussed separately. (See "Lynch syndrome (hereditary nonpolyposis colorectal cancer): Clinical manifestations and diagnosis" and "Lynch syndrome (hereditary nonpolyposis colorectal cancer): Screening and management".)


Muir-Torre syndrome is caused by germline mutations in one allele of the DNA mismatch repair (MMR) genes MLH1, MSH2, or MSH6. The MMR system consists of human mutS homolog 2 (hMSH2), human mutS homolog 3 (hMSH3), human mutS homolog 6 (hMSH6), human mutL homolog 1 (hMLH1), and human postmeiotic segregation increased 2 (hPMS2) proteins. They are responsible for maintaining the genomic integrity by correcting base substitution mismatches and small insertion-deletion mismatches generated by errors in base pairing during DNA replication.

Microsatellite instability (MSI) is the hallmark of MMR gene deficiency. Microsatellites are short repetitive DNA sequences, typically mononucleotide or dinucleotide tandem repeats, that are susceptible to mutations during DNA replication. The loss of DNA mismatch repair function due to germline and/or somatic inactivating mutations of MMR genes leads to the accumulation of mutations across the genome and mainly in the microsatellite repetitive sequences, creating a molecular phenotype known as microsatellite instability.

Mutations in MLH1 and MSH2 have the most severe effect, producing a high-frequency MSI phenotype (MSI-H). An MSI-H phenotype can be demonstrated in nearly all cutaneous and visceral tumors from patients with Muir-Torre syndrome [5,6].

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:

Subscribers log in here

Literature review current through: Oct 2017. | This topic last updated: Nov 30, 2016.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2017 UpToDate, Inc.
  1. Ponti G, Ponz de Leon M. Muir-Torre syndrome. Lancet Oncol 2005; 6:980.
  2. John AM, Schwartz RA. Muir-Torre syndrome (MTS): An update and approach to diagnosis and management. J Am Acad Dermatol 2016; 74:558.
  3. Schwartz RA, Torre DP. The Muir-Torre syndrome: a 25-year retrospect. J Am Acad Dermatol 1995; 33:90.
  4. Cohen PR, Kohn SR, Davis DA, Kurzrock R. Muir-Torre syndrome. Dermatol Clin 1995; 13:79.
  5. Machin P, Catasus L, Pons C, et al. Microsatellite instability and immunostaining for MSH-2 and MLH-1 in cutaneous and internal tumors from patients with the Muir-Torre syndrome. J Cutan Pathol 2002; 29:415.
  6. Kruse R, Rütten A, Lamberti 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 1998; 63:63.
  7. Singh RS, Grayson W, Redston M, et al. Site and tumor type predicts DNA mismatch repair status in cutaneous sebaceous neoplasia. Am J Surg Pathol 2008; 32:936.
  8. Ponti G, Losi L, Di Gregorio C, et al. Identification of Muir-Torre syndrome among patients with sebaceous tumors and keratoacanthomas: role of clinical features, microsatellite instability, and immunohistochemistry. Cancer 2005; 103:1018.
  9. Ponti G, Meschieri A, Pollio A, et al. Fordyce granules and hyperplastic mucosal sebaceous glands as distinctive stigmata in Muir-Torre syndrome patients: characterization with reflectance confocal microscopy. J Oral Pathol Med 2015; 44:552.
  10. Tailor IK, Cook J, Reilly JT, et al. Acute myeloid leukaemia associated with Muir-Torre variant of hereditary non-polyposis colon cancer (HNPCC): implications for inherited and acquired mutations in DNA mismatch repair genes. Br J Haematol 2012; 156:289.
  11. Kamisasanuki T, Uchino E, Fukushima J, et al. A case of Muir-Torre syndrome with multiple cancers of bilateral eyelids and breast. Korean J Ophthalmol 2013; 27:204.
  12. Tanyi M, Olasz J, Lukács G, et al. A new mutation in Muir-Torre syndrome associated with familiar transmission of different gastrointestinal adenocarcinomas. Eur J Surg Oncol 2009; 35:1128.
  13. Nolan L, Eccles D, Cross E, et al. First case report of Muir-Torre syndrome associated with non-small cell lung cancer. Fam Cancer 2009; 8:359.
  14. Vernez M, Hutter P, Monnerat C, et al. A case of Muir-Torre syndrome associated with mucinous hepatic cholangiocarcinoma and a novel germline mutation of the MSH2 gene. Fam Cancer 2007; 6:141.
  15. Cohen PR. Muir-Torre syndrome in patients with hematologic malignancies. Am J Hematol 1992; 40:64.
  16. Roberts ME, Riegert-Johnson DL, Thomas BC, et al. A clinical scoring system to identify patients with sebaceous neoplasms at risk for the Muir-Torre variant of Lynch syndrome. Genet Med 2014; 16:711.
  17. Ponti G, Losi L, Pedroni M, et al. 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 2006; 126:2302.
  18. Moreira L, Balaguer F, Lindor N, et al. Identification of Lynch syndrome among patients with colorectal cancer. JAMA 2012; 308:1555.
  19. Everett JN, Raymond VM, Dandapani M, et al. Screening for germline mismatch repair mutations following diagnosis of sebaceous neoplasm. JAMA Dermatol 2014; 150:1315.
  20. Boennelycke M, Thomsen BM, Holck S. Sebaceous neoplasms and the immunoprofile of mismatch-repair proteins as a screening target for syndromic cases. Pathol Res Pract 2015; 211:78.
  21. Abbas O, Mahalingam M. Cutaneous sebaceous neoplasms as markers of Muir-Torre syndrome: a diagnostic algorithm. J Cutan Pathol 2009; 36:613.
  22. Chhibber V, Dresser K, Mahalingam M. MSH-6: extending the reliability of immunohistochemistry as a screening tool in Muir-Torre syndrome. Mod Pathol 2008; 21:159.
  23. Entius MM, Keller JJ, Drillenburg P, et al. Microsatellite instability and expression of hMLH-1 and hMSH-2 in sebaceous gland carcinomas as markers for Muir-Torre syndrome. Clin Cancer Res 2000; 6:1784.
  24. Fernandez-Flores A. Considerations on the performance of immunohistochemistry for mismatch repair gene proteins in cases of sebaceous neoplasms and keratoacanthomas with reference to Muir-Torre syndrome. Am J Dermatopathol 2012; 34:416.
  25. Ponti G, Pellacani G, Ruini C, et al. Muir-Torre syndrome or phenocopy? The value of the immunohistochemical expression of mismatch repair proteins in sebaceous tumors of immunocompromised patients. Fam Cancer 2014; 13:553.
  26. Landis MN, Davis CL, Bellus GA, Wolverton SE. Immunosuppression and sebaceous tumors: a confirmed diagnosis of Muir-Torre syndrome unmasked by immunosuppressive therapy. J Am Acad Dermatol 2011; 65:1054.
  27. Plocharczyk EF, Frankel WL, Hampel H, Peters SB. Mismatch repair protein deficiency is common in sebaceous neoplasms and suggests the importance of screening for Lynch syndrome. Am J Dermatopathol 2013; 35:191.
  28. Giardiello FM, Allen JI, Axilbund JE, et al. Guidelines on genetic evaluation and management of Lynch syndrome: a consensus statement by the US Multi-Society Task Force on Colorectal Cancer. Dis Colon Rectum 2014; 57:1025.