title: Identification of Muir-Torre syndrome among patients with sebaceous tumors and keratoacanthomas: role of clinical features, microsatellite instability, and immunohistochemistry.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Internal Medicine, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Ponti
authors.forename: Lorena
authors.initials: L
authors.lastname: Losi
authors.forename: Carmela
authors.initials: C
authors.lastname: Di Gregorio
authors.forename: Luca
authors.initials: L
authors.lastname: Roncucci
authors.forename: Monica
authors.initials: M
authors.lastname: Pedroni
authors.forename: Alessandra
authors.initials: A
authors.lastname: Scarselli
authors.forename: Piero
authors.initials: P
authors.lastname: Benatti
authors.forename: Stefania
authors.initials: S
authors.lastname: Seidenari
authors.forename: Giovanni
authors.initials: G
authors.lastname: Pellacani
authors.forename: Luigi
authors.initials: L
authors.lastname: Lembo
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Rossi
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Marino
authors.forename: Emanuela
authors.initials: E
authors.lastname: Lucci-Cordisco
authors.forename: Maurizio
authors.initials: M
authors.lastname: Ponz de Leon
mesh_terms: D000328:Adult; D000368:Aged; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000175:diagnosis / Q000235:genetics; D005260:Female; D042822:Genomic Instability; D006801:Humans; D007150:Immunohistochemistry; D007636:Keratoacanthoma / Q000175:diagnosis* / Q000235:genetics; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D012626:Sebaceous Gland Neoplasms / Q000175:diagnosis* / Q000235:genetics; D012878:Skin Neoplasms / Q000175:diagnosis; D013577:Syndrome