Muir-Torre syndrome

J. COLDRON and I. REID
Department of Surgery, Victoria Infirmary, Langside Road, Glasgow, UK

Muir-Torre syndrome is a rare autosomal dominant condition in which multiple primary malignancies occur together with a sebaceous gland tumour. Early recognition of the syndrome in patients with sebaceous gland tumours should facilitate early detection of subsequent malignancies if the patient is entered into appropriate screening programmes. A case occurring in Scotland is described and implications for management, screening for members of the family are discussed.

Keywords: Genodermatoses, hereditary non-polyposis colon cancer (HNPCC), Muir-Torre syndrome

Distinguishing cutaneous signs which are associated with hereditary cancer syndromes are known as cancer-associated genodermatoses. Muir-Torre syndrome (MTS) is an example, and is defined by the combination of at least one sebaceous adenoma, epithelioma or carcinoma and at least one visceral carcinoma occurring in the same individual in the absence of other precipitating factors such as radiotherapy or AIDS.¹ Individuals with the syndrome may develop multiple primary malignancies at different sites. MTS has not previously been described in Scotland but its diagnosis has implications for cancer screening and surveillance in the affected individual and his or her relatives.

A 40-year-old man presented in 1986 with a Duke’s C adenocarcinoma of the descending colon, and was treated by surgical resection without adjuvant therapy. He commenced on a colonoscopic surveillance programme and had benign colonic polyps excised endoscopically in 1986 and 1990. In March 1999, he was referred to the surgical outpatient department with a subcutaneous lesion on his left shoulder. After excision under local anaesthetic the lesion was reported to be a sebaceous epithelioma, and the diagnosis of MTS was suggested. On routine follow-up in September 1999 an enlarged right supraclavicular node was detected, and on subsequent excision showed metastatic transitional cell carcinoma. Intra-venous urography and abdominal computed tomography (CT) scan showed a left renal mass and paraaortic lymphadenopathy. A left nephro-ureterectomy was performed, and histology confirmed a transitional cell carcinoma of the left renal pelvis with involved para-aortic nodes. Screening for further malignancy including chest radiography, upper GI endoscopy and repeat colonoscopy were all negative. The patient is currently undergoing chemotherapy. He has two daughters both of whom are in their twenties and currently healthy. His only sibling was a sister who died of a gynaecological cancer in her forties. His mother had a colon resection in her forties for colon cancer and died in her seventies of a second colon cancer. Further family history is less clear but the patient believes that his mother had nine siblings, eight of whom died of cancers at various sites.

Muir-Torre syndrome was first described independently by Muir in 1967 and Torre in 1968, and it has since been recognised as a subtype of Lynch Type II hereditary nonpolyposis colon cancer (HNPCC).^2,3 The most recent review by Akhtar et al (1999) identified a total of 205 reported cases in the world literature.⁴ The defining feature of this syndrome is the combination of sebaceous gland tumours and at least one visceral cancer.

Typical skin tumours associated with this syndrome include sebaceous adenomas, epitheliomas and carcinomas. Keratoacanthomas and basal cell carcinomas with sebaceous differentiation also occur. All these sebaceous gland tumours are rare in the general population; the finding of such a tumour is a marker for MTS and should prompt a search for occult malignancy. Fifty-six per cent of skin lesions in MTS occur after diagnosis of the first malignancy, 6% occur concomitantly and 22% of skin lesions occur as the first malignancy of the syndrome.⁴ The cutaneous lesion may occur as much as 25 years before or 37 years after the internal malignancy.⁵ Multiple primary carcinomas at different sites are characteristic of MTS, and up to 9 visceral cancers in one individual have been reported. Colorectal cancer is the commonest visceral neoplasm to occur in MTS, and the most frequent initial cancer.^1,5 In common with other forms of HNPCC, colorectal cancers in MTS are usually proximal in location and tend to have a more indolent course than other forms of colorectal cancer.⁵ Fifty-one per cent of MTS patients develop at least one colorectal cancer, and multiple colorectal cancers are common; genito-urinary cancers occur in 24% of individuals, mainly transitional cell carcinomas. Carcinomas of the endometrium, ovary, breast, parotid, upper GI tract and larynx, and haematological malignancies are also associated with MTS. As in the Lynch II syndrome, cancers occur at a relatively young age. Colonic polyps are found in more than 25% of MTS patients, and are especially prevalent in patients with colorectal carcinoma.

The genetic disorder in MTS is an autosomal dominant inherited germline mutation in one of the DNA mismatch repair genes, most commonly hMSH2.⁶ It is inherited with a high degree of penetrance and variable expression. The male:female ratio is 3:2. Children of an MTS individual, therefore, have a 50% risk of inheriting the cancer predisposition. In families where the germline mutation can be identified, those individuals who have inherited the mutation should be offered regular screening examinations. In those who can be demonstrated not to have inherited the germline mutation cancer surveillance is not necessary. Screening for malignancy at all possible sites is impractical in MTS given the wide range of associated malignancies, and screening should probably concentrate on the colorectum, female genital tract and possibly renal tract. In some families the occurrence of certain other tumours would be an indication for other screening modalities, for example upper GI endoscopy. Isotretinoin may prevent the development of cutaneous malignancies in this syndrome.^1,7

The indolent course of cancers occurring as part of MTS is often commented on but has not been shown in any prospective fashion. It has been suggested that because of their relatively good prognosis surgical removal of primary or metastatic cancers may be curative and should be attempted where possible.

Cohen et al (1991) suggested that a search for internal malignancy should be undertaken in the following: 1) a patient in whom an MTS-associated sebaceous gland tumour has been documented; 2) a patient in whom MTS has been diagnosed and 3) family members of an MTS patient.⁵ Their suggested surveillance programme for patients with MTS or MTS-associated sebaceous gland tumours included annual clinical examination, CEA, cervical smear, chest radiography, and urine cytology, colonoscopy or barium enema every 3-5 years, and for female patients mammography 1-2 yearly to age 50 and annually thereafter, and endometrial biopsy every 3-5 years. Other authors have suggested that colonoscopy should be more frequent in view of the high frequency of colonic cancer and its proximal predominance, and advocate annual colonoscopy from the age of 25 years.¹

Families with MTS are probably more common than is recognised, but sebaceous gland tumours are rare and the diagnosis of such a tumour should suggest the possibility of the syndrome and prompt a search for associated malignancies, and for the underlying genetic mutation.

Correspondence: Miss I. Reid, Senior Lecturer/Consultant Surgeon, Victoria Infirmary NHS Trust, Langside Road, Glasgow G42 9TY, UK