title: Cutaneous Sebaceous Lesions in a Patient With MUTYH-Associated Polyposis Mimicking Muir-Torre Syndrome.
abstract: A 76-year-old white male with a history of adenocarcinoma of the rectosigmoideum and multiple colonic polyps removed at the age of 38 and 39 years by an abdominoperitoneal amputation and total colectomy, respectively, presented with multiple whitish and yellowish papules on the face and a verrucous lesion on the trunk. The lesions were surgically removed during the next 3 years and a total of 13 lesions were investigated histologically. The diagnoses included 11 sebaceous adenomas, 1 low-grade sebaceous carcinoma, and 1 squamous cell carcinoma. In some sebaceous lesions, squamous metaplasia, intratumoral heterogeneity, mucinous changes, and peritumoral lymphocytes as sometimes seen in sebaceous lesions in Muir-Torre syndrome were noted. Mutation analysis of the peripheral blood revealed a germline mutation c.692G>A,p.(Arg231His) in exon 9 and c.1145G>A, p.(Gly382Asp) in exon 13 of the MUTYH gene. A KRAS mutation G12C (c.34G>T, p.Gly12Cys) was detected in 1 sebaceous adenoma and a NRAS mutation Q61K (c.181C>A, p.Gln61Lys) was found in 2 other sebaceous adenomas. No germline mutations in MLH1, MSH2, MSH6 and PMS2 genes, no microsatellite instability, no aberrant methylation of MLH1 promoter, and no somatic mutations in MSH2 and MSH6 were found. An identical MUTYH germline mutation was found in the patient's daughter. Despite striking clinicopathological similarities with Muir-Torre syndrome, the molecular biologic testing confirmed the final diagnosis of MUTYH-associated polyposis.
authors.affiliation: *Sikl's Department of Pathology, Medical Faculty in Pilsen, Charles University in Prague, Prague, Czech Republic; †Bioptical Laboratory, Pilsen, Czech Republic; and ‡Department of Dermatology, Regional Hospital, Sumperk, Czech Republic.
authors.forename: Denisa
authors.initials: D
authors.lastname: Kacerovska
authors.forename: Lubomir
authors.initials: L
authors.lastname: Drlik
authors.forename: Lenka
authors.initials: L
authors.lastname: Slezakova
authors.forename: Michal
authors.initials: M
authors.lastname: Michal
authors.forename: Jan
authors.initials: J
authors.lastname: Stehlik
authors.forename: Monika
authors.initials: M
authors.lastname: Sedivcova
authors.forename: Ladislav
authors.initials: L
authors.lastname: Hadravsky
authors.forename: Dmitry V
authors.initials: DV
authors.lastname: Kazakov
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D001706:Biopsy; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D045647:DNA Glycosylases / Q000235:genetics*; D004252:DNA Mutational Analysis; D003937:Diagnosis, Differential; D005091:Exons; D020022:Genetic Predisposition to Disease; D040941:Heredity; D006801:Humans; D008297:Male; D055653:Muir-Torre Syndrome / Q000235:genetics* / Q000473:pathology; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D012626:Sebaceous Gland Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; D045647:DNA Glycosylases; C061738:mutY adenine glycosylase