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]} Relatives of patients should receive genetic counseling.

Next: Pathophysiology

Pathophysiology

MTS is considered to be a subtype of hereditary nonpolyposis colorectal cancer (HNPCC; Lynch syndrome).^{[5, 6]}It is associated with an inherited defect in one copy of a DNA mismatch repair (MMR) gene (MMR), which leads to microsatellite instability.^[7]The two major MMR proteins involved are hMLH1 and hMSH2. Approximately 70% of tumors associated with the MTS have microsatellite instability. In HNPCC, germline disruption of hMLH1 and hMSH2 is evenly distributed; however, in MTS, disruption of hMSH2 is seen in more than 90% of patients.^[8]Two other proteins involved in MTS are MSH6 and PMS2.

Next: Pathophysiology

Etiology

The main anomaly detected in MTS patients is the alteration in the MMR genes, particularly MSH2 on chromosome 2 and MLH1 on chromosome 3.^{[9, 10, 11]}Other genes are MSH6,^[12]MLH3, and PMS2. Loss of two of the retinoid receptors (RXR-beta and RXR-gamma) seems apparent in sebaceous carcinoma.^[13](See Pathophysiology.)

Next: Pathophysiology

Epidemiology

MTS is a rare disorder,^[14]with only a few hundred patients reported. Families with MTS are probably more common than has been reported. Patient age at presentation of MTS ranges from young adulthood to advance age (median age, 53 y).^[15] MTS occurs in both sexes, with a male-to-female ratio of 3:2.

Next: Pathophysiology

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 5 years of excision. Recurrence rates have been estimated to be around 30%.^[16] A two-center study (N = 63; 67 cases; 7 MTS cases) found that independent predictors of recurrent sebaceous carcinoma included noncomplete circumferential peripheral and deep margin assessment methods and large lesion size, but not anatomic subtype or MTS status.^[17]

Clinical Presentation

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Media Gallery

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

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#author-disclosures{display:block}#author-disclosures.modal-layer{position:relative}#author-disclosures .modal-content{max-height:none}#author-disclosures .close-modal{display:none}

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 / Castle (consultant regarding MyPath test in melanocytic lesions); Orlucent (consultant); .

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

Prognosis

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