Identification of Muir–Torre Syndrome among Patients with Sebaceous Tumors and Keratoacanthomas

Division of Internal Medicine, University of Modena and Reggio Emilia, Modena, Italy.
Cancer (Impact Factor: 4.89). 04/2005; 103(5):1018-25. DOI: 10.1002/cncr.20873
Source: PubMed


The Muir-Torre syndrome (MTS) is an autosomal-dominant genodermatosis characterized by the presence of sebaceous gland tumors, with or without keratoacanthomas, associated with visceral malignancies. A subset of patients with MTS is considered a variant of the hereditary nonpolyposis colorectal carcinoma, which is caused by mutations in mismatch-repair genes. The objective of the current study was to evaluate whether a combined clinical, immunohistochemical, and biomolecular approach could be useful for the identification of Muir-Torre syndrome among patients with a diagnosis of sebaceous tumors and keratoacanthomas.
The authors collected sebaceous skin lesions and keratoacanthomas recorded in the files of the Pathology Department of the University of Modena during the period 1986-2000. Through interviews and examination of clinical charts, family trees were drawn for 120 patients who were affected by these skin lesions.
Seven patients also were affected by gastrointestinal tumors, thus meeting the clinical criteria for the diagnosis of MTS. In the MTS families, a wide phenotypic variability was evident, both in the spectrum of visceral tumors and in the type of skin lesions. Microsatellite instability was found in five MTS patients: These patients showed concordance with immunohistochemical analysis; moreover, a constitutional mutation in the MSH2 gene was found in 1 patient. Lack of expression of MSH2/MSH6 or MLH1 proteins was evident in the skin lesions and in the associated internal malignancies of 3 patients and 2 patients with MTS, respectively.
The clinical, biomolecular, and immunohistochemical characterization of sebaceous skin lesions and keratoacanthomas may be used as screening for the identification of families at risk of MTS, a disease that is difficult to recognize and diagnose.

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Available from: Piero Benatti, Oct 06, 2015
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    • "Of note, the proportion of mutations involving MSH2 and MLH1 is almost equal in HNPCC, while in MTS, mutations in the MSH2 gene is implicated in the overwhelming majority of time.[914] Microsatellite-stable neoplasms, however, do occur in patients with MTS, prompting researchers to postulate that a second variant of MTS exists, with its genetic basis potentially involving other gene sequences or promoter hypermethylation.[2021] "
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    ABSTRACT: Muir-Torre syndrome (MTS) is an autosomal dominant syndrome characterized by neoplasms of the sebaceous gland or keratoacanthomas, in addition to visceral malignancies. Cerebral neoplasms in patients with hereditary nonpolyposis colorectal cancer (HNPCC) or familial adenomatous polyposis suffer from Turcot's syndrome. Genetic mutations in MutS homolog (MSH)-2, MutL homolog (MLH)-1, and MutS homolog (MSH)-6 DNA mismatch repair genes are the most common in MTS with MSH-2 being the most predominant. In HNPCC MLH-1 and MSH-2 mutations are approximately equal in prevalence. We present the case of a 58-year-old male with a prior history of being treated for colonic adenocarcinoma and skin lesions leading to a diagnosis of MTS. The patient later developed a World Health Organization (WHO) grade 4 glioma requiring surgical resection. Pathology revealed mutations in MSH-2 and MSH-6 mismatch repair genes. This case represents the first report of Turcot's and MTS with extensive molecular testing on the cerebral neoplasm demonstrating a molecular relationship between Turcot's and MTS and only the second published report of simultaneous Turcot's and MTS.
    Surgical Neurology International 04/2013; 4(1):52. DOI:10.4103/2152-7806.110512 · 1.18 Impact Factor
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    • "To date, there are few studies addressing MMR protein levels in human skin cancer samples. Varying levels of microsatellite instability are observed in melanoma and basal cell carcinoma; however, this indicates that MMR function has probably been lost, but not that loss of MMR is involved in the etiology of the disease (Hussein et al., 2001a, b; Korabiowska et al., 2000, 2004; Kroiss et al., 2001; Ponti et al., 2005; Sardi et al., 2000; Staibano et al., 2001). "
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    ABSTRACT: The mechanisms by which the post-replicative DNA mismatch repair (MMR) enzyme MSH2 is involved in the complex response mechanisms to UV damage are yet to be clarified. Here, we show increased levels of MSH2 mRNA in malignant melanoma, metastases of melanoma, and melanoma cell (MeWo) lines as compared with melanocytic nevi or primary cultured benign melanocytes. UV-B treatment modulated MSH2 expression and silencing of MSH2 gene expression using small interfering RNA technology regulated UV-B-induced cell cycle arrest and apoptosis in human MeWo. We show that MSH2-deficient non-malignant mouse fibroblasts (MEF-/-) are partially resistant against UV-B-induced apoptosis and show reduced S-Phase accumulation. In addition, we show that an Msh2 point mutation (MEFGA) that affects MMR does not affect UV-B-induced apoptosis. In conclusion, we demonstrate that MSH2 modulates in human melanocytes both UV-B-induced cell cycle regulation and apoptosis, most likely via independent, uncoupled mechanisms.
    Journal of Investigative Dermatology 02/2008; 128(1):203-13. DOI:10.1038/sj.jid.5700941 · 7.22 Impact Factor
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    • "Screening for malignancy at all possible sites is impractical in MTS given the wide range of associated malignancies, and should probably concentrate on the colorectum, female genital tract and possibly the renal tract. In some families, the occurrence of certain other tumours would be an indication for other screening modalities, for example, upper gastrointestinal endoscopy [14]. Cohen et al. [11] suggested that a search for internal malignancies should be undertaken in those with MTS-associated sebaceous gland tumour, those with MTS, and in family members of an MTS patient. "
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    ABSTRACT: Sebaceous gland tumours are rare and their presence should be considered as a marker for Muir-Torre Syndrome, alerting to search for an occult malignancy. A 43-year-old Caucasian female patient underwent excision of a sebaceous cyst. Histopathology confirmed a sebaceous carcinoma. Further investigations revealed multiple intra-abdominal malignancies. She has been under regular follow-up in the relevant clinics. Sebaceous carcinoma should be excised completely and followed-up for the detection of possible metastases. Surgical removal of primary or metastatic cancers may be curative and should be attempted wherever possible. It is very important for clinicians not to miss such skin lesions as they may precede the presentation of internal malignancies.
    Journal of Medical Case Reports 02/2008; 2:276. DOI:10.1186/1752-1947-2-276
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