title: Fordyce granules and hyperplastic mucosal sebaceous glands as distinctive stigmata in Muir-Torre syndrome patients: characterization with reflectance confocal microscopy.
abstract: BACKGROUND
  The Muir-Torre syndrome (MTS), a variant of Lynch syndrome (LS), is characterized by the presence of sebaceous skin adenomas and/or carcinomas and keratoacanthomas associated with visceral malignancies. Fordyce granules (FGs) are oral mucosal lesions previously found in association with LS. The aim of this study was to analyze the specific frequency of FGs in sporadic individuals and gene carriers patients with MTS of known mismatch repair genes mutations. The secondary aim was to characterize FGs by means of reflectance confocal microscopy (RCM).
  
  
  METHODS
  A total of 13 patients belonging to nine different genetically unrelated MTS kindreds (MLH1 gene mutation n = 2; MSH2 gene mutation n = 11) and 140 genetically unrelated healthy controls were examined. Depending on the clinical examination of the oral mucosa surface, subjects were categorized as either FGs positive or FGs negative.
  
  
  RESULTS
  FGs were diagnosed in 13 of 13 (100%) of MMR gene carriers patients with MTS vs. 9 of 140 (6.4%) controls. The most common site for FGs in MTS was the vestibular oral mucosa, compared with the gingival mandibular and retromandibular pad in controls. RCM examination found multiple sebaceous acinar cells that appear as round or oval hyper-refractive globules and that create a lobular aspects of the sebaceous glands defined as 'moruliform' or 'berry-like' structures.
  
  
  CONCLUSIONS
  Clinical and RCM evidences of our study suggest that an activation of the sebaceous glands system occurs in patients with MTS. Fordyce granules and intra-oral sebaceous hyperplasia may constitute an additional clinical parameter, which may be adopted to distinguish individuals with highest likelihood of being affected from MTS.
authors.affiliation: Department of Diagnostic and Clinical Medicine and Public Health, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Ponti
authors.affiliation: Department of Dermatology, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Meschieri
authors.affiliation: Department of Neurosciences, University of Padua, Padua, Italy.
authors.forename: Annamaria
authors.initials: A
authors.lastname: Pollio
authors.affiliation: Department of Dermatology, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Cristel
authors.initials: C
authors.lastname: Ruini
authors.affiliation: Department of Dermatology, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Manfredini
authors.affiliation: Dermatology and Skin Cancer Unit, Arcispedale S. Maria Nuova, IRCCS, Reggio Emilia, Italy.
authors.forename: Caterina
authors.initials: C
authors.lastname: Longo
authors.affiliation: Department of Dermatology, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Victor D
authors.initials: VD
authors.lastname: Mandel
authors.affiliation: Department of Dermatology, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Silvana
authors.initials: S
authors.lastname: Ciardo
authors.affiliation: Department of Diagnostic and Clinical Medicine and Public Health, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Aldo
authors.initials: A
authors.lastname: Tomasi
authors.affiliation: Department of Paediatric Dentistry, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Giannetti
authors.affiliation: Department of Dermatology, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Pellacani
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D000328:Adult; D000368:Aged; D053843:DNA Mismatch Repair; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D018613:Microscopy, Confocal / Q000379:methods; D008875:Middle Aged; D009092:Mucous Membrane / Q000473:pathology; D055653:Muir-Torre Syndrome / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein / Q000235:genetics; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics; D015995:Prevalence; D012626:Sebaceous Gland Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology*; D012627:Sebaceous Glands / Q000378:metabolism / Q000473:pathology*; D055815:Young Adult
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D004268:DNA-Binding Proteins; C094443:G-T mismatch-binding protein; C501486:MLH1 protein, human; D009687:Nuclear Proteins; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein
keywords: Fordyce granules; Muir-Torre syndrome; lynch syndrome; mismatch repair genes