The Muir-Torre syndrome was independently described by Muir in 1967 and Torre in 1968, and has since been recognized as a subtype of Lynch Type II hereditary nonpolyposis colon cancer (HNPCC) [4, 5]. Akhtar et al in their review study identified a total of 205 reported cases in the world literature . In the same study the authors reported that the defining feature of this syndrome is the combination of sebaceous gland tumors and at least one visceral cancer, usually gastrointestinal or genitourinary carcinomas.
Clinically the diagnosis of MTS is based on the presence of at least one sebaceous gland tumor associated with at least one primary visceral malignancy, as it happened in our case. Alternatively, diagnosis of the syndrome can be made if the patient has multiple keratoacanthomas with multiple internal malignancies and a family history of MTS . Muir-Torre syndrome can also be diagnosed by genetic testing. A high proportion of tumors from MTS patients show microsatellite instability (MSI) due to germline mutations in either of two DNA mismatch repair (MMR) proteins .
Typical skin tumors associated with this syndrome include sebaceous adenomas, epitheliomas and carcinomas. Keratoacanthomas and basal cell carcinomas with sebaceous differentiation may also occur. All these sebaceous gland tumors are rare in the general population and the finding of such a tumor may represent a marker for MTS and should prompt a search for occult malignancy . In addition, 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 . The cutaneous lesions may occur as long as 25 years before or 37 years after the internal malignancy and multiple primary carcinomas at different sites are characteristic of MTS so that 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 [3, 10]. In common with other forms of HNPCC, colorectal malignancies in MTS are usually proximal in location and tend to have a more indolent course than other forms of colorectal cancer . Fifty-one per cent of MTS patients develop at least one colorectal cancer, and multiple colorectal cancers are common, genitourinary cancers occur in 24% of individuals, mainly transitional cell carcinomas. Carcinomas of the endometrium, ovary, breast, parotid, upper GI tract and larynx, and hematological 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, MSH1 and MSH2 [8, 12]. It is inherited with a high degree of penetrance and variable expression. The syndrome occurs in both sexes, with a male to female ratio of 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 urinary tract. In some families the occurrence of certain other tumors would be an indication for other screening modalities, for example upper GI endoscopy .
Cohen et al  suggested that a search for internal malignancy should be undertaken in the following: 1) a patient in whom an MTS-associated sebaceous gland tumor has been documented, 2) a patient in whom MTS has been diagnosed and 3) family members of an MTS patient. They also suggested surveillance program for patients with MTS or MTS-associated sebaceous gland tumors 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 . Besides, MTS screening may be laborious but is not universally performed, and a search for mutations in either MSH1 or MSH2 is expensive and time consuming. One attractive alternative is the analysis of mismatch repair (MMR) protein expression as a surrogate for assaying for the respective gene mutations [12, 14].
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 and non-aggressive course, surgical removal of primary or metastatic cancers may be curative and should be attempted wherever possible [6, 15]. Additionally, the combination of interferon (IFN-alpha2a) with retinoids (isotretinoin) seems to be of promise to prevent tumor development in Muir-Torre syndrome . Besides, oral isotretinoin has been reported to prevent the development some of the malignancies in this syndrome. A dosage of as 0.8 mg/kg/d may be effective .
In conclusion sebaceous gland tumors are rare and the diagnosis of such a tumor should suggest the possibility of Muir-Torre syndrome and prompt a search for associated malignancies, and for the underlying genetic mutation. Family members should be monitored to detect early cancers and perhaps should be enrolled in chemoprevention trials. Genetic studies can help identify the inherited molecular defect that causes the Muir-Torre syndrome.