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BMC Medical Genetics
Published in: BMC Medical Genetics 1/2018

Open Access 01-12-2018 | Case report

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

Authors: 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

Published in: BMC Medical Genetics | Issue 1/2018

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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.
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Metadata
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
Authors
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
Publication date
01-12-2018
Publisher
BioMed Central
Published in
BMC Medical Genetics / Issue 1/2018
Electronic ISSN: 1471-2350
DOI
https://doi.org/10.1186/s12881-018-0651-4

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