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BMC Med Genet. 2018 Aug 15;19(1):144. doi: 10.1186/s12881-018-0651-4.

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.

Author information

1
Department of General, Visceral and Transplant Surgery, University Hospital Tübingen, Hoppe-Seyler-Str. 3, 72076, Tübingen, Germany.
2
Interfaculty Institute for Cell Biology, Department of Immunology, University of Tübingen, Auf der Morgenstelle 15, 72076, Tübingen, Germany.
3
German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ) partner site Tübingen, Tübingen, Germany.
4
Institute of Pathology and Neuropathology, University Hospital Tübingen, Liebermeisterstr. 8, 72076, Tübingen, Germany.
5
Institute of Medical Genetics and Applied Genomics, University of Tübingen, Calwerstr. 7, 72076, Tübingen, Germany.
6
Internal Medicine, Department for Oncology, Hematology, Immunology, Rheumatology and Pulmonology, University of Tübingen, Otfried-Müller-Str. 10, 72076, Tübingen, Germany.
7
Institute of Medical Genetics and Applied Genomics, University of Tübingen, Calwerstr. 7, 72076, Tübingen, Germany. christopher.schroeder@med.uni-tuebingen.de.

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.

KEYWORDS:

Case Report; Hereditary Tumor Syndrome; Malignant Peritoneal Mesothelioma; PTEN-Hamartoma-Tumor-Syndrome; Verrucous Carcinoma

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