First case report of malignant peritoneal mesothelioma and oral verrucous carcinoma in a patient with a germline PTEN mutation: a combination of extremely rare diseases with probable further implications
Abstract Background The PTEN-hamartoma-tumor-syndrome (PHTS) is caused by germline mutations in Phosphatase and Tensin homolog (PTEN) and predisposes to the development of several typical malignancies. Whereas PTEN mutations have been implicated in the occurrence of malignant mesotheliomas, the gene...
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| Format: | Article |
| Language: | English |
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BMC
2018-08-01
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| Series: | BMC Medical Genetics |
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| Online Access: | http://link.springer.com/article/10.1186/s12881-018-0651-4 |
| _version_ | 1818426802153979904 |
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| author | Markus W. Löffler Julia Steinhilber Franz J. Hilke Sebastian P. Haen Hans Bösmüller Ivonne-Aidee Montes-Mojarro Irina Bonzheim Antje Stäbler Ulrike Faust Ute Grasshoff Ingmar Königsrainer Hans-Georg Rammensee Lothar Kanz Alfred Königsrainer Stefan Beckert Olaf Riess Christopher Schroeder |
| author_facet | Markus W. Löffler Julia Steinhilber Franz J. Hilke Sebastian P. Haen Hans Bösmüller Ivonne-Aidee Montes-Mojarro Irina Bonzheim Antje Stäbler Ulrike Faust Ute Grasshoff Ingmar Königsrainer Hans-Georg Rammensee Lothar Kanz Alfred Königsrainer Stefan Beckert Olaf Riess Christopher Schroeder |
| author_sort | Markus W. Löffler |
| collection | DOAJ |
| description | Abstract Background The PTEN-hamartoma-tumor-syndrome (PHTS) is caused by germline mutations in Phosphatase and Tensin homolog (PTEN) and predisposes to the development of several typical malignancies. Whereas PTEN mutations have been implicated in the occurrence of malignant mesotheliomas, the genetic landscape of verrucous carcinomas (VC) is largely uncharted. Both VC and malignant peritoneal mesotheliomas (MPM) are exceedingly rare and a potential link between these malignancies and PHTS has never been reported. Case presentation We here describe the clinical course of a PHTS patient who, in addition to a typical thyroid carcinoma at the age of 36 years, developed a highly-differentiated oral VC and an epithelioid MPM six years later. The patient with a history of occupational asbestos exposure underwent cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for MPM. The clinical diagnosis of PHTS was consequently corroborated by a germline PTEN deletion. Sequencing of tumor tissue revealed a second hit in PTEN in the thyroid carcinoma and VC, confirmed by a PTEN loss and activation of the PI3K/AKT pathway in immunohistochemistry. Furthermore, additional somatic mutations in the thyroid carcinoma as well as in the VC were detected, whereas the genetics of MPM remained unrevealing. Discussion and conclusions We here report the very unusual clinical course of a patient with rare tumors that have a germline mutation first hit in PTEN in common. Since this patient was exposed to asbestos and current evidence suggests molecular mechanisms that might render PHTS patients particularly susceptible to mesothelioma, we strongly recommend PHTS patients to avoid even minimal exposure. |
| first_indexed | 2024-12-14T14:35:37Z |
| format | Article |
| id | doaj.art-14202282ec32442784f1870558b375db |
| institution | Directory Open Access Journal |
| issn | 1471-2350 |
| language | English |
| last_indexed | 2024-12-14T14:35:37Z |
| publishDate | 2018-08-01 |
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| series | BMC Medical Genetics |
| spelling | doaj.art-14202282ec32442784f1870558b375db2022-12-21T22:57:39ZengBMCBMC Medical Genetics1471-23502018-08-011911710.1186/s12881-018-0651-4First case report of malignant peritoneal mesothelioma and oral verrucous carcinoma in a patient with a germline PTEN mutation: a combination of extremely rare diseases with probable further implicationsMarkus W. Löffler0Julia Steinhilber1Franz J. Hilke2Sebastian P. Haen3Hans Bösmüller4Ivonne-Aidee Montes-Mojarro5Irina Bonzheim6Antje Stäbler7Ulrike Faust8Ute Grasshoff9Ingmar Königsrainer10Hans-Georg Rammensee11Lothar Kanz12Alfred Königsrainer13Stefan Beckert14Olaf Riess15Christopher Schroeder16Department of General, Visceral and Transplant Surgery, University Hospital TübingenInstitute of Pathology and Neuropathology, University Hospital TübingenInstitute of Medical Genetics and Applied Genomics, University of TübingenInterfaculty Institute for Cell Biology, Department of Immunology, University of TübingenInstitute of Pathology and Neuropathology, University Hospital TübingenInstitute of Pathology and Neuropathology, University Hospital TübingenInstitute of Pathology and Neuropathology, University Hospital TübingenInstitute of Medical Genetics and Applied Genomics, University of TübingenInstitute of Medical Genetics and Applied Genomics, University of TübingenInstitute of Medical Genetics and Applied Genomics, University of TübingenDepartment of General, Visceral and Transplant Surgery, University Hospital TübingenInterfaculty Institute for Cell Biology, Department of Immunology, University of TübingenInternal Medicine, Department for Oncology, Hematology, Immunology, Rheumatology and Pulmonology, University of TübingenDepartment of General, Visceral and Transplant Surgery, University Hospital TübingenDepartment of General, Visceral and Transplant Surgery, University Hospital TübingenInstitute of Medical Genetics and Applied Genomics, University of TübingenInstitute of Medical Genetics and Applied Genomics, University of TübingenAbstract Background The PTEN-hamartoma-tumor-syndrome (PHTS) is caused by germline mutations in Phosphatase and Tensin homolog (PTEN) and predisposes to the development of several typical malignancies. Whereas PTEN mutations have been implicated in the occurrence of malignant mesotheliomas, the genetic landscape of verrucous carcinomas (VC) is largely uncharted. Both VC and malignant peritoneal mesotheliomas (MPM) are exceedingly rare and a potential link between these malignancies and PHTS has never been reported. Case presentation We here describe the clinical course of a PHTS patient who, in addition to a typical thyroid carcinoma at the age of 36 years, developed a highly-differentiated oral VC and an epithelioid MPM six years later. The patient with a history of occupational asbestos exposure underwent cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for MPM. The clinical diagnosis of PHTS was consequently corroborated by a germline PTEN deletion. Sequencing of tumor tissue revealed a second hit in PTEN in the thyroid carcinoma and VC, confirmed by a PTEN loss and activation of the PI3K/AKT pathway in immunohistochemistry. Furthermore, additional somatic mutations in the thyroid carcinoma as well as in the VC were detected, whereas the genetics of MPM remained unrevealing. Discussion and conclusions We here report the very unusual clinical course of a patient with rare tumors that have a germline mutation first hit in PTEN in common. Since this patient was exposed to asbestos and current evidence suggests molecular mechanisms that might render PHTS patients particularly susceptible to mesothelioma, we strongly recommend PHTS patients to avoid even minimal exposure.http://link.springer.com/article/10.1186/s12881-018-0651-4Malignant Peritoneal MesotheliomaPTEN-Hamartoma-Tumor-SyndromeHereditary Tumor SyndromeVerrucous CarcinomaCase Report |
| spellingShingle | Markus W. Löffler Julia Steinhilber Franz J. Hilke Sebastian P. Haen Hans Bösmüller Ivonne-Aidee Montes-Mojarro Irina Bonzheim Antje Stäbler Ulrike Faust Ute Grasshoff Ingmar Königsrainer Hans-Georg Rammensee Lothar Kanz Alfred Königsrainer Stefan Beckert Olaf Riess Christopher Schroeder First case report of malignant peritoneal mesothelioma and oral verrucous carcinoma in a patient with a germline PTEN mutation: a combination of extremely rare diseases with probable further implications BMC Medical Genetics Malignant Peritoneal Mesothelioma PTEN-Hamartoma-Tumor-Syndrome Hereditary Tumor Syndrome Verrucous Carcinoma Case Report |
| title | First case report of malignant peritoneal mesothelioma and oral verrucous carcinoma in a patient with a germline PTEN mutation: a combination of extremely rare diseases with probable further implications |
| title_full | First case report of malignant peritoneal mesothelioma and oral verrucous carcinoma in a patient with a germline PTEN mutation: a combination of extremely rare diseases with probable further implications |
| title_fullStr | First case report of malignant peritoneal mesothelioma and oral verrucous carcinoma in a patient with a germline PTEN mutation: a combination of extremely rare diseases with probable further implications |
| title_full_unstemmed | First case report of malignant peritoneal mesothelioma and oral verrucous carcinoma in a patient with a germline PTEN mutation: a combination of extremely rare diseases with probable further implications |
| title_short | First case report of malignant peritoneal mesothelioma and oral verrucous carcinoma in a patient with a germline PTEN mutation: a combination of extremely rare diseases with probable further implications |
| title_sort | first case report of malignant peritoneal mesothelioma and oral verrucous carcinoma in a patient with a germline pten mutation a combination of extremely rare diseases with probable further implications |
| topic | Malignant Peritoneal Mesothelioma PTEN-Hamartoma-Tumor-Syndrome Hereditary Tumor Syndrome Verrucous Carcinoma Case Report |
| url | http://link.springer.com/article/10.1186/s12881-018-0651-4 |
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