Muir-Torre Syndrome: Background, Pathophysiology, Epidemiology

Sections

Overview

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.

Pathophysiology

Muir-Torre syndrome (MTS) is considered to be a subtype of HNPCC.^{[2, 3]}This condition is associated with an inherited defect in one copy of a DNA mismatch repair gene (MMR), which leads to microsatellite instability.^[4]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.^[5]Two other proteins involved in MTS are MSH6 and PMS2.

Frequency

Muir-Torre syndrome (MTS) is a rare disorder,^[6]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.^[7]

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.^[8]

Patient Education

Relatives of patients should receive genetic counseling.

Clinical Presentation

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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].
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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].
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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.

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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: Nothing to disclose.

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

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