Muir Torre Syndrome

The Skin Center

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Case Report of Muir-Torre Syndrome and Review of the Literature

 

 

 

Abstract

Muir-Torre Syndrome (MTS), a possible variant of Hereditary Nonpolyposis Colorectal Cancer (HNPCC), presents as an internal malignancy associated with sebaceous skin tumors.  A single biopsy proven sebaceous adenoma may warrant evaluation for Muir-Torre Syndrome. We report the case of a 76 year-old male with a marked family history of colon carcinoma, and personal history of  colon carcinoma status post partial colectomy, and multiple cutaneous neoplasms including sebaceous adenomas, sebaceous hyperplasias, and basal and squamous cell carcinomas. This article provides a review of the literature describing Muir-Torre Syndrome and highlights the important role of dermatologists in the potential early detection and diagnosis of familial or hereditary colon cancer in patients presenting with cutaneous sebaceous adenomas.

 

Case report
A 76 year-old white male presented to our center with a past medical history significant for colon cancer (status post partial resection).  A strong family history of colon cancer in 5 first-degree relatives had been contributory for the patient’s diagnosis of colon cancer in 1987.  A diagnosis of Muir-Torre Syndrome (MTS) was made in 2003 after a shave biopsy revealed a solitary sebaceous adenoma of the right nasolabial fold.  In the 5 years following the diagnosis of MTS, the patient has required multiple dermatological procedures including greater than 15 biopsies of sebaceous adenomas, sebaceous gland hyperplasia, basal cell carcinomas (BCC), squamous cell carcinomas (SCC), and keratoacanthomas on his face, neck, trunk, and arms (Figure 1).  Figure 2 shows the histopathology of a sebaceous adenoma. The patient has consistently declined the option of chemoprophylaxis with oral soriatane or isotretinoin. He continues to have regular colonoscopy at 3 year intervals and regular skin surveillance with his dermatologists every 3-4 months. He currently remains colon cancer free at a 20 year follow up, however, he has extensive actinic keratosis and severe actinic damage for which he undergoes periodic cryotherapy and photodynamic therapy with Aminolevulinic acid 20% and blue light (417nm).

 

Comment
First described by Muir et al in 1967 and Torre in 1968, Muir-Torre Syndrome (MTS) is a genodermatosis that is characterized by the association of internal malignancies and sebaceous skin tumors, with or without keratoacanthomas.1,2  It may be inherited as autosomal dominant with high penetrance and variable expression.3   Occurrence and diagnosis of the cutaneous lesions may precede or follow that of the internal malignancy.  Of 205 patients with common presentation of sebaceous tumors with a low-grade visceral malignancy, the sebaceous tumors appeared before the internal malignancy in 22%, concurrently in 6%, and after in 56% (a temporal relationship was not reported for the remaining 16%).4  Muir-Torre Syndrome occurs with a slightly higher prevalence in males, and patients have ranged in age from 37 to 89 years at diagnosis.3

The clinical features of Muir-Torre Syndrome include at least one sebaceous adenoma, sebaceous epithelioma, basal cell epithelioma with sebaceous differentiation, or sebaceous carcinoma and at least one low-grade visceral cancer (with or without colonic polyps).  Sebaceous hyperplasia and Nevus Sebaceous of Jadassohn, with or without a sebaceous epithelioma within it, do not contribute to diagnostic criteria.  Multiple keratoacanthomas associated with two or more internal malignancies in a patient with family history of MTS, or a keratoacanthoma with histological sebaceous differentiation are also markers for the syndrome.3   Multiple sebaceous neoplasms, whether adenomas, epitheliomas, or carcinomas increase the possibility of future development of MTS, even if no internal malignancy is evident at the time of initial screening.3,4

Colorectal cancer is the most common primary internal malignancy associated with Muir-Torre Syndrome (56% of the tumors), followed by cancers of the genitourital system (22%).4  Of patients with colorectal cancer, more than half had tumors proximal to or at the splenic flexure.5 Other organs, such as the uterus and breast, can also be sites of malignancy.  Keratoacanthomas were noted in 23% of patients, and neoplasms in the meibomian gland comprise 23% of sebaceous carcinomas.4  Presence of a sebaceous carcinoma in the meibomian glands may therefore be grounds for screening for MTS.

Genetic research suggests that Muir-Torre Syndrome is related to the cancer family syndrome, or Lynch Syndrome, also known as Hereditary Nonpolyposis Colorectal Cancer (HNPCC).6,7  Observations of Muir-Torre Syndrome associated with germline deletions in DNA mismatch repair genes MSH2 and MLH1 in Lynch syndrome suggest that MTS may be a variant of Lynch syndrome, which predisposes individuals to develop colorectal and other visceral malignancies associated with germline mutations in DNA mismatch repair genes.6  Existence of DNA microsatellite instability in MTS and Lynch syndrome supports the idea these two conditions may be related as well.8

Clinical, biomolecular, and immunohistochemical characterization of sebaceous skin lesions and keratoacanthomas may be used to screen for families at risk of Muir-Torre Syndrome.  In one study, adenomatous polyps; colon, gastric, bladder, and renal pelvis carcinomas; non-Hodgkin lymphoma; and laryngeal tumors were detected in first-degree relatives of two patients with MTS.9  These findings show the significance of family testing, genetic counseling, and vigilance.

Once detected, treatment options for the cutaneous lesions in Muir-Torre syndrome include cryosurgery, electrodessication and curettage, surgical excision, Mohs micrographic surgery,  and radiotherapy. Possible combination treatments with topical retinoids and/or oral retinoids like isotretinoin or soriatane may be advisable. Routine surveillance examinations for gastrointestinal and genitorurinary cancers are advised, such as annual colonoscopy because of the high frequency of colorectal cancer.3  More data on retinoids are needed, though studies indicate topical retinoids may have some effect in treating actinic keratoses10 and oral retinoids including acitretin may prevent skin cancers in solid organ transplant recipients, who tend to develop more aggressive skin cancers (including cardiac transplantation and renal transplantation).11-13  Oral retinoids appear promising for patients with Muir-Torre syndrome if the preventative benefit can be extended.  Efficacy of oral isotretinoin for MTS may indeed suggest a possible treatment and a preventative function for future cutaneous lesions in maintaining patients with MTS.14,15
Conclusions:

A single biopsy proven sebaceous adenoma may warrant evaluation for Muir-Torre Syndrome.  Patients with multiple cutaneous sebaceous adenomas should be questioned about relevant family history and be referred for screening colonoscopy and gastrointestinal evaluation.  Muir-Torre Syndrome is another dermatologic sign of a serious internal disease. Dermatologists can thus aid in the potential early diagnosis, treatment, and possible life-saving surgical cure of colon cancer.
References

1. Muir EG, Bell AJY, Barlow KA. Multiple primary carcinomata of colon duodenum and larynx associated with kerato-acanthomata of face. British Journal of Surgery. 1967;54(3):191-195.

2. Torre D. Multiple Sebaceous tumors. Arch Dermatol. 1968;98:549-551.

3. Schwartz RA, Torre DP. The Muir-Torre syndrome: a 25 year retrospect. J Am Acad Dermatol. 1995;33:90-104.

4. Akhtar S, Oza KK, Khan SA, Wright J. Muir-Torre syndrome: Case report of a patient with concurrent jejunal and ureteral cancer and a review of the literature. J Am Acad Dermatol. 1999;41(5):681-686.

5. 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.

6. South CD, Hampel H, Comeras I, Westman JA, Frankel WL, de la Chapelle A. The frequency of Muir-Torre syndrome among lynch syndrome families. J Natl Cancer Inst. 2008;100(4):277-281.

7. Barana D, Cetto GL, Oliani C, et al. Spectrum of genetic alterations in Muir-Torre syndrome is the same as in HNPCC. Am J Med Genet A. 2004;125A(3):318-319.

8. Aaltonen LA, Peltomaki P, Leach FS, et al. Clues to the pathogenesis of familial colorectal-cancer. Science. 1993;260(5109):812-816.

9. 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):1018-1025.

10. De Graaf YG, Euvrard S, Bouwes Bavinck JN. Systemic and topical retinoids in the management of skin cancer in organ transplant recipients. Dermatol Surg. 2004;30(4Pt2):656-661.

11. Chen K, Craig JC, Shumack S. Oral retinoids for the prevention of skin cancers in solid organ transplant recipients: a systematic review of randomized controlled trials. Br J Dermatol. 2005;152(3):518-523.

12. McNamara IR, Muir J, Galbraith AJ. Acitretin for prophylaxis of cutaneous malignancies after cardiac transplantation. J Heart Lung Transplant. 2002;21(11):1201-1205.

13. McKenna DB, Murphy GM. Skin cancer chemoprophylaxis in renal transplant recipients: 5 years of experience using low-dose acitretin. Br J Dermatol. 1999;140(4):656-660.

14. Spielvogel RL, DeVillez RL, Roberts LC. Oral isotretinoin therapy for familial Muir-Torre syndrome. J Am Acad Dermatol. 1985;12(3):475-480.

15. 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):331-333.

 

 

 

Figure Captions:

Figure 1.  Multiple sebaceous tumors and actinic neoplasms on the face.

Figure 2.  Sebaceous adenoma of the right upper jawline showing a proliferation of sebaceous and epithelial cells in a circumscribed manner (H&E, original magnification ´ x0)

 

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Dr. Gary Cole and Dr. Nili Alai are Board-Certified Dermatologists.
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