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.

• MeSH
• biopsie MeSH
• dědičné nepolypózní kolorektální nádory enzymologie   genetika   patologie   MeSH
• dědičnost MeSH
• diferenciální diagnóza MeSH
• DNA-glykosylasy genetika   MeSH
• exony MeSH
• fenotyp MeSH
• genetická predispozice k nemoci MeSH
• lidé MeSH
• mutace * MeSH
• mutační analýza DNA MeSH
• nádorové biomarkery genetika   MeSH
• nádory mazových žláz enzymologie   genetika   patologie   MeSH
• rodokmen MeSH
• senioři MeSH
• Torrého-Muirův syndrom genetika   patologie   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH

This article reports an unusual case of aggressive extraocular sebaceous carcinoma located on the scalp with subsequent usurpation of the bone and penetrating through the bone and meninges to the brain in a 56-year-old man affected by Muir-Torre syndrome. Microscopically, the sebaceous neoplasm was located in the middle to deep dermis without any connection to the epidermis and showed a multinodular growth with neoplastic nodules with a central comedo-type necrosis separated from each other by fibrovascular stroma. The nodules were composed of varying proportions of mature sebaceous cells and atypical basaloid cells with high degree of atypia, including high nuclear/cytoplasmic ratio, nuclear pleomorphism, macronucleoli, atypical mitoses, and necrosis. The neoplasm was totally removed. Histopathological examinations of the recurrent lesion showed identical morphological features and, in addition, signs of the tumors growing through the periosteum were noted. In the final excision specimen, both the dura mater and the brain tissue were infiltrated by the sebaceous carcinoma. The diagnosis of Muir-Torre syndrome was confirmed by molecular genetic investigation that revealed an identical germline mutation in MSH2 gene in several family members, some of whom had colorectal tumors.

• MeSH
• biopsie MeSH
• dospělí MeSH
• fatální výsledek MeSH
• fenotyp MeSH
• genetická predispozice k nemoci MeSH
• homolog 2 proteinu MutS genetika   MeSH
• imunohistochemie MeSH
• invazivní růst nádoru MeSH
• karcinom genetika   patologie   chirurgie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• magnetická rezonanční tomografie MeSH
• mozek patologie   MeSH
• mutační analýza DNA MeSH
• nádory hlavy a krku genetika   patologie   chirurgie   MeSH
• nádory mazových žláz genetika   patologie   chirurgie   MeSH
• počítačová rentgenová tomografie MeSH
• progrese nemoci MeSH
• rodokmen MeSH
• skalp patologie   chirurgie   MeSH
• Torrého-Muirův syndrom genetika   patologie   chirurgie   MeSH
• zárodečné mutace MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH

Muir-Torre syndrome (MTS), a rare variant of the hereditary non polyposis colorectal cancer syndrome, is an autosomal dominant genodermatosis characterised by coincidence of sebaceous gland neoplasms (sebaceous adenoma, epithelioma, or carcinoma) and at least one internal malignancy. The underlying cause of MTS is a germline mutation in DNA mismatch repair genes MSH2, MLH1 and MSH6. We report the case of a 52-year-old caucasian woman with the development of metachronous colon cancer at the age of 38 years, uterine cancer at the age of 43 years, and unique occurrence of synchronous gastric and sebaceous carcinomas related to germline point mutation c. 2194A>T in the last exon of MLH1 gene, resulting in truncated protein in C-terminal region p. Lys732X due to premature stop codon. This mutation, not previously reported in MTS, disrupts the function of MutL complexes presumably by preventing the interaction with PMS1/PMS2 and impairing the endonuclease active site. This case points out the importance of sebaceous neoplasia, especially sebaceous adenocarcinoma, as cutaneous markers of MTS for timely implementation of cancer screening programs.

• MeSH
• adaptorové proteiny signální transdukční genetika   MeSH
• bodová mutace MeSH
• jaderné proteiny genetika   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mnohočetné primární nádory genetika   patologie   MeSH
• nádory mazových žláz genetika   patologie   MeSH
• nádory žaludku genetika   patologie   MeSH
• sebaceózní adenokarcinom genetika   patologie   MeSH
• Torrého-Muirův syndrom genetika   patologie   MeSH
• zárodečné mutace MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• práce podpořená grantem MeSH

Muir-Torre syndrome (MTS), a phenotypic variant of the more common hereditary nonpolyposis colorectal cancer syndrome, or Lynch syndrome, is an autosomal dominantly inherited condition that combines at least one cutaneous sebaceous neoplasm and at least one visceral malignancy. Most patients (~90%) with MTS carry mutations in the MSH2 gene; less than 10% of the cases are associated with a mutation MLH1 gene, and only 3 MTS patients with a pathogenic MSH6 mutation have been previously documented. We report a family affected with MTS in which 3 members (father and 2 sons) were found to harbor a missense mutation c.2633T>C (p.V878A) in exon 4 of the MSH6 gene.

• MeSH
• DNA vazebné proteiny genetika   MeSH
• dospělí MeSH
• exony genetika   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádory mazových žláz diagnóza   genetika   patologie   MeSH
• regulace genové exprese u nádorů MeSH
• senioři MeSH
• Torrého-Muirův syndrom diagnóza   genetika   patologie   MeSH
• zárodečné mutace genetika   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• práce podpořená grantem MeSH