Background

In 1967, Muir and Torre each reported patients with multiple cutaneous tumors along with visceral malignancies. Muir-Torre syndrome (MTS) is the combination of neoplasms of the skin (usually sebaceous adenoma, sebaceous epithelioma, or sebaceous carcinoma but also keratoacanthoma) and a visceral malignancy (usually colorectal, endometrial, small intestine, and urothelial).^[1]

MTS has an autosomal dominant pattern of inheritance in 59% of cases and has a high degree of penetrance and variable expression.^{[2, 3, 4, 5]}

Pathophysiology

Muir-Torre syndrome (MTS) is considered to be a subtype of HNPCC.^{[6, 7]}This condition is associated with an inherited defect in one copy of a DNA mismatch repair gene (MMR), which leads to microsatellite instability.^[8]The 2 major MMR proteins involved are hMLH1 and hMSH2. Approximately 70% of tumors associated with the MTS have microsatellite instability. While germline disruption of hMLH1 and hMSH2 is evenly distributed in HNPCC, disruption of hMSH2 is seen in greater than 90% of MTS patients.^[9]Two other proteins involved in MTS are MSH6 and PMS2.

Etiology

See Pathophysiology. The main anomaly detected in Muir-Torre syndrome (MTS) patients is the alteration in the mismatch repair genes, particularly MSH2 on chromosome 2 and MLH1 on chromosome 3.^[10]Other genes are MSH-6, MLH-3, and PMS-2.^[11]Loss of 2 of the retinoid receptors (RXR-beta and RXR-gamma) seems apparent in sebaceous carcinoma.^[12]

Frequency

Muir-Torre syndrome (MTS) is a rare disorder,^[13]with approximately 200 patients reported. Families with MTS are probably more common than reported.

Sex

MTS occurs in both sexes, with a male-to-female ratio of 3:2.

Age

The patient's age at presentation of MTS ranges from young adulthood to elderly patients, with a median age of 53 years.^[14]

Prognosis

Sebaceous carcinoma is an aggressive neoplasm, which can recur locally after excision and can metastasize. When local recurrences develop, they usually do so within the first five years of excision. Recurrence rates are estimated to be around 30% range.^[15]

Patient Education

Relatives of patients should receive genetic counseling.

Clinical Presentation

John AM, Schwartz RA. Muir-Torre syndrome (MTS): An update and approach to diagnosis and management. J Am Acad Dermatol. 2016 Mar. 74 (3):558-66. [Medline].
de Angelis de Carvalho N, Niitsuma BN, Kozak VN, Costa FD, de Macedo MP, Kupper BEC, et al. Clinical and Molecular Assessment of Patients with Lynch Syndrome and Sarcomas Underpinning the Association with MSH2 Germline Pathogenic Variants. Cancers (Basel). 2020 Jul 9. 12 (7):[Medline].
Gay JT, Troxell T, Gross GP. Muir-Torre Syndrome. StatPearls [Internet]. 2020 Jan. [Medline]. [Full Text].
Dany M. The DNA mismatch repair system in sebaceous tumors: an update on the genetics and workup of Muir-Torre syndrome. Cutis. 2020 Mar. 105 (3):E34-E37. [Medline].
Chen Q, Wang M, Xu Z, Wang M, Jin S, Tian S, et al. Muir-Torre Syndrome With a Frame-shift Mutation in the MSH2 Gene: A Rare Case Report and Literature Review. Int J Gynecol Pathol. 2020 Mar. 39 (2):136-140. [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. 2004 Mar 15. 125A(3):318-9. [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. 2008 Dec 15. 113(12):3372-81. [Medline]. [Full Text].
Honchel R, Halling KC, Schaid DJ, Pittelkow M, Thibodeau SN. Microsatellite instability in Muir-Torre syndrome. Cancer Res. 1994 Mar 1. 54(5):1159-63. [Medline].
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 Oct. 126(10):2302-7. [Medline].
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 Oct. 35(10):1128-30. [Medline].
Kacerovska D, Cerna K, Martinek P, Grossmann P, Michal M, Ricar J, et al. MSH6 Mutation in a Family Affected by Muir-Torre Syndrome. Am J Dermatopathol. 2012 Aug. 34(6):648-52. [Medline].
Chakravarti N, El-Naggar AK, Lotan R, Anderson J, Diwan AH, Saadati HG, et al. Expression of retinoid receptors in sebaceous cell carcinoma. J Cutan Pathol. 2006 Jan. 33(1):10-7. [Medline].
Hare HH, Mahendraker N, Sarwate S, Tangella K. Muir-Torre syndrome: a rare but important disorder. Cutis. 2008 Oct. 82(4):252-6. [Medline].
Burger B, Itin P. Muir-Torre syndrome. Dermatology. 2008. 217(1):56-7; author reply 57. [Medline].
Nelson BR, Hamlet KR, Gillard M, Railan D, Johnson TM. Sebaceous carcinoma. J Am Acad Dermatol. 1995 Jul. 33(1):1-15; quiz 16-8. [Medline].
Ingram JR, Griffiths AP, Roberts DL. All patients with sebaceous gland neoplasms should be screened for Muir-Torre syndrome. Clin Exp Dermatol. 2009 Mar. 34(2):264-6. [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. 1985 Sep. 113(3):295-301. [Medline].
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 Jul. 63(1):63-70. [Medline]. [Full Text].
Vasen HF, Mecklin JP, Khan PM, Lynch HT. The International Collaborative Group on Hereditary Non-Polyposis Colorectal Cancer (ICG-HNPCC). Dis Colon Rectum. 1991 May. 34(5):424-5. [Medline].
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 Jun. 32(6):936-42. [Medline].
Ivan D, Prieto VG, Esmaeli B, Wistuba II, Tang X, Lazar AJ. Epidermal growth factor receptor (EGFR) expression in periocular and extraocular sebaceous carcinoma. J Cutan Pathol. 2010 Feb. 37(2):231-6. [Medline].
Kazakov DV, Kutzner H, Spagnolo DV, Rütten A, Mukensnabl P, Michal M. Discordant architectural and cytological features in cutaneous sebaceous neoplasms--a classification dilemma: report of 5 cases. Am J Dermatopathol. 2009 Feb. 31(1):31-6. [Medline].
Kacerovska D, Drlik L, Slezakova L, Michal M, Stehlik J, Sedivcova M, et al. Cutaneous Sebaceous Lesions in a Patient With MUTYH-Associated Polyposis Mimicking Muir-Torre Syndrome. Am J Dermatopathol. 2016 Dec. 38 (12):915-923. [Medline].
Kuwabara K, Suzuki O, Chika N, Kumamoto K, Minabe T, Fukuda T, et al. Prevalence and molecular characteristics of DNA mismatch repair protein-deficient sebaceous neoplasms and keratoacanthomas in a Japanese hospital-based population. Jpn J Clin Oncol. 2018 Jun 1. 48 (6):514-521. [Medline].
Le S, Ansari U, Mumtaz A, Malik K, Patel P, Doyle A, et al. Lynch Syndrome and Muir-Torre Syndrome: An update and review on the genetics, epidemiology, and management of two related disorders. Dermatol Online J. 2017 Nov 15. 23 (11):[Medline].
Mojtahed A, Schrijver I, Ford JM, Longacre TA, Pai RK. A two-antibody mismatch repair protein immunohistochemistry screening approach for colorectal carcinomas, skin sebaceous tumors, and gynecologic tract carcinomas. Mod Pathol. 2011 Jul. 24(7):1004-14. [Medline].
Svec J, Schwarzová L, Janošíková B, Stekrová J, Mandys V, Kment M, et al. Synchronous gastric and sebaceous cancers, a rare manifestation of MLH1-related Muir-Torre syndrome. Int J Clin Exp Pathol. 2014. 7 (8):5196-202. [Medline].
Moscarella E, Argenziano G, Longo C, et al. Clinical, dermoscopic and reflectance confocal microscopy features of sebaceous neoplasms in Muir-Torre syndrome. J Eur Acad Dermatol Venereol. 2012 Apr 4. [Medline].
Therkildsen C, Ladelund S, Rambech E, Persson A, Petersen A, Nilbert M. Glioblastomas, astrocytomas and oligodendrogliomas linked to Lynch syndrome. Eur J Neurol. 2015 Apr. 22 (4):717-24. [Medline].
Ho VH, Ross MI, Prieto VG, Khaleeq A, Kim S, Esmaeli B. Sentinel lymph node biopsy for sebaceous cell carcinoma and melanoma of the ocular adnexa. Arch Otolaryngol Head Neck Surg. 2007 Aug. 133(8):820-6. [Medline].
Flux K. Sebaceous Neoplasms. Surg Pathol Clin. 2017 Jun. 10 (2):367-382. [Medline].
Shalin SC, Sakharpe A, Lyle S, Lev D, Calonje E, Lazar AJ. p53 staining correlates with tumor type and location in sebaceous neoplasms. Am J Dermatopathol. 2012 Apr. 34(2):129-35; quiz 136-8. [Medline]. [Full Text].
Dahlhoff M, Camera E, Picardo M, Zouboulis CC, Chan L, Chang BH, et al. PLIN2, the major perilipin regulated during sebocyte differentiation, controls sebaceous lipid accumulation in vitro and sebaceous gland size in vivo. Biochim Biophys Acta. 2013 Oct. 1830(10):4642-9. [Medline]. [Full Text].
Ostler DA, Prieto VG, Reed JA, Deavers MT, Lazar AJ, Ivan D. Adipophilin expression in sebaceous tumors and other cutaneous lesions with clear cell histology: an immunohistochemical study of 117 cases. Mod Pathol. 2010 Apr. 23(4):567-73. [Medline].
Kruse R, Rütten A, Schweiger N, et al. Frequency of microsatellite instability in unselected sebaceous gland neoplasias and hyperplasias. J Invest Dermatol. 2003 May. 120(5):858-64. [Medline].
Mathiak M, Rütten 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. 2002 Mar. 26(3):338-43. [Medline].
Ponti G, Losi L, Di Gregorio C, Roncucci L, et al. Identification of Muir-Torre syndrome among patients with sebaceous tumors and keratoacanthomas: role of clinical features, microsatellite instability, and immunohistochemistry. Cancer. 2005 Mar 1. 103(5):1018-25. [Medline].
Mahalingam M. MSH6, Past and Present and Muir-Torre Syndrome-Connecting the Dots. Am J Dermatopathol. 2017 Apr. 39 (4):239-249. [Medline].
Lee BA, Yu L, Ma L, Lind AC, Lu D. Sebaceous neoplasms with mismatch repair protein expressions and the frequency of co-existing visceral tumors. J Am Acad Dermatol. 2012 Apr 30. [Medline].
Spielvogel RL, DeVillez RL, Roberts LC. Oral isotretinoin therapy for familial Muir-Torre syndrome. J Am Acad Dermatol. 1985 Mar. 12(3):475-80. [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].
Umar A, Loomans-Kropp HA. Immuno-Interception for Patients with High-Risk Cancer. Cancer Prev Res (Phila). 2020 Jun. 13 (6):493-496. [Medline].
Pancholi A, Collins D, Lindley R, Gandhi P. Muir-Torre syndrome: a case report and screening recommendations. Ann R Coll Surg Engl. 2008 Nov. 90(8):W9-10. [Medline]. [Full Text].

Media Gallery

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. Courtesy of Mark S. Brown, MD, University of South Alabama Medical Center.
Gross image of an ear resection due to a deeply invasive sebaceous carcinoma.
Histologic section of sebaceous adenoma showing a predominance of sebaceous cells with prominent cytoplasmic vacuoles.
Histologic section of sebaceous epithelioma showing a predominance of basaloid cells.
Well-differentiated sebocytes in small nests, deeply infiltrating the subcutaneous tissue, thus consistent with sebaceous carcinoma.
Low-power view of a keratoacanthomalike sebaceous adenoma. Well-circumscribed, symmetrical lesion with overlying papillomatosis and prominent hyperkeratosis and showing focal sebaceous differentiation (arrows).
Sebaceous carcinoma typically infiltrates the overlying epithelium in a manner similar to Paget disease. Note in this case how the atypical cells have mostly replaced the normal follicular cells and involve the overlying epidermis.
Normal pattern of expression of MSH-2 (nuclear positivity) in a sebaceous carcinoma from a patient with Muir-Torre syndrome (see also MSH-6).
Significant loss of MSH-6 expression in this sebaceous carcinoma in a patient with Muir-Torre syndrome.

of 10

Author

Victor G Prieto, MD, PhD Ferenc and Phyllis Gyorkey Chair for Research and Education in Pathology, Professor, Departments of Pathology and Dermatology, University of Texas MD Anderson Cancer Center

Victor G Prieto, MD, PhD is a member of the following medical societies: American Association for the Advancement of Science, American Medical Association, American Society for Clinical Pathology, American Society of Dermatopathology, College of American Pathologists, European Society of Pathology, International Society of Dermatopathology, Society for Investigative Dermatology, United States and Canadian Academy of Pathology

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Myriad (consultant regarding MyPath test in melanocytic lesions).

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Warren R Heymann, MD Head, Division of Dermatology, Professor, Department of Internal Medicine, Rutgers New Jersey Medical School

Warren R Heymann, MD is a member of the following medical societies: American Academy of Dermatology, American Society of Dermatopathology, Society for Investigative Dermatology

Disclosure: Nothing to disclose.

Chief Editor

Dirk M Elston, MD Professor and Chairman, Department of Dermatology and Dermatologic Surgery, Medical University of South Carolina College of Medicine

Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

Additional Contributors

Joshua A Zeichner, MD Assistant Professor, Director of Cosmetic and Clinical Research, Mount Sinai School of Medicine; Chief of Dermatology, Institute for Family Health at North General

Joshua A Zeichner, MD is a member of the following medical societies: American Academy of Dermatology, National Psoriasis Foundation

Disclosure: Received consulting fee from Valeant for consulting; Received grant/research funds from Medicis for other; Received consulting fee from Galderma for consulting; Received consulting fee from Promius for consulting; Received consulting fee from Pharmaderm for consulting; Received consulting fee from Onset for consulting.

Acknowledgements

The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous author, Marcelo G. Horenstein, MD, to the development and writing of this article.

Muir-Torre Syndrome

Background

Pathophysiology

Etiology

Epidemiology

Frequency

Sex

Age

Prognosis

Patient Education

References

Tables

Contributor Information and Disclosures

What would you like to print?