65 YEARS OF THE DOUBLE HELIX: Genetics informs precision practice in the diagnosis and management of pheochromocytoma.

Hartmut P Neumann, William F Young, Tobias Krauss, Jean-Pierre Bayley, Francesca Schiavi, Giuseppe Opocher, Carsten C Boedeker, Amit Tirosh, Frederic Castinetti, Juri Ruf, Dmitry Beltsevich, Martin Walz, Harald-Thomas Groeben, Ernst von Dobschuetz, Oliver Gimm, Nelson Wohllk, Marija Pfeifer, Delmar M Lourenço, Mariola Peczkowska, Attila Patocs, Joanne Ngeow, Özer Makay, Nalini S Shah, Arthur Tischler, Helena Leijon, Gianmaria Pennelli, Karina Villar Gómez de Las Heras, Thera P Links, Birke Bausch, Charis Eng

Journal: Endocrine-related cancer 2019;25(8):T201-T219

PMID: 29794110

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Abstract

Although the authors of the present review have contributed to genetic discoveries in the field of pheochromocytoma research, we can legitimately ask whether these advances have led to improvements in the diagnosis and management of patients with pheochromocytoma. The answer to this question is an emphatic ! In the field of molecular genetics, the well-established axiom that familial (genetic) pheochromocytoma represents 10% of all cases has been overturned, with >35% of cases now attributable to germline disease-causing mutations. Furthermore, genetic pheochromocytoma can now be grouped into five different clinical presentation types in the context of the ten known susceptibility genes for pheochromocytoma-associated syndromes. We now have the tools to diagnose patients with genetic pheochromocytoma, identify germline mutation carriers and to offer gene-informed medical management including enhanced surveillance and prevention. Clinically, we now treat an entire family of tumors of the paraganglia, with the exact phenotype varying by specific gene. In terms of detection and classification, simultaneous advances in biochemical detection and imaging localization have taken place, and the histopathology of the paraganglioma tumor family has been revised by immunohistochemical-genetic classification by gene-specific antibody immunohistochemistry. Treatment options have also been substantially enriched by the application of minimally invasive and adrenal-sparing surgery. Finally and most importantly, it is now widely recognized that patients with genetic pheochromocytoma/paraganglioma syndromes should be treated in specialized centers dedicated to the diagnosis, treatment and surveillance of this rare neoplasm.

Address: Section for Preventive MedicineUniversity Medical Center, Albert-Ludwigs-University, Freiburg, Germany.; Division of EndocrinologyDiabetes, Metabolism, and Nutrition, Mayo Clinic, Rochester, New York, USA.; Department of RadiologyMedical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.; Department of Human GeneticsLeiden University Medical Center, Leiden, The Netherlands.; Familial Cancer Clinic and OncoendocrinologyVeneto Institute of Oncology, IRCCS, Padova, Italy.; Department of OtorhinolaryngologyHELIOS Hanseklinikum Stralsund, Stralsund, Germany.; Sackler Faculty of MedicineTel Aviv University, Tel Aviv, Israel.; Department of EndocrinologyAix-Marseille Université, Institut National de la Santé et de la Recherche Médicale (INSERM), U1251, Marseille Medical Genetics (MMG), Marseille, France.; Assistance Publique - Hôpitaux de Marseille (AP-HM)Hôpital de la Conception, Centre de Référence des Maladies Rares Hypophysaires HYPO, Marseille, France.; Department of Nuclear MedicineFaculty of Medicine, Albert-Ludwigs-University, Freiburg, Germany.; Department of SurgeryEndocrinology Research Center, Moscow, Russia.; Department of Surgery and Center of Minimally-Invasive SurgeryKliniken Essen-Mitte, Essen, Germany.; Department of AnesthesiologyKliniken Essen-Mitte, Essen, Germany.; Section of Endocrine SurgeryClinic of General, Visceral and Thoracic Surgery, Krankenhaus Reinbek, Academic Teaching Hospital University of Hamburg, Reinbek, Germany.; Department of Clinical and Experimental MedicineFaculty of Health Sciences, Linköping University, Linköping, Sweden.; Department of SurgeryRegion Östergötland, Linköping, Sweden.; Endocrine SectionUniversidad de Chile, Hospital del Salvador, Santiago de Chile, Chile.; Department of EndocrinologyUniversity Medical Center Ljubljana, Ljubljana, Slovenia.; Endocrine Genetics UnitEndocrinology Division, Hospital das Clínicas, University of São Paulo School of Medicine (FMUSP), Endocrine Oncology Division, Institute of Cancer of the State of São Paulo, FMUSP, São Paulo, Brazil.; Department of HypertensionInstitute of Cardiology, Warsaw, Poland.; HSA-SE 'Lendület' Hereditary Endocrine Tumor Research GroupHungarian Academy of Sciences and Semmelweis University, Budapest, Hungary.; Lee Kong Chian School of MedicineNanyang Technological University Singapore and Cancer Genetics Service, National Cancer Centre Singapore, Singapore, Singapore.; Division of Endocrine SurgeryDepartment of General Surgery, Ege University, Izmir, Turkey.; Department of EndocrinologySeth G S Medical College, K.E.M. Hospital, Parel, Mumbai, India.; Department of Pathology and Laboratory MedicineTufts Medical Center and Tufts University School of Medicine, Boston, Massachusetts, USA.; Department of PathologyUniversity of Helsinki, and HUSLAB, Helsinki University Hospital, Helsinki, Finland.; Department of Medicine (DIMED)Surgical Pathology Unit, University of Padua, Padua, Italy.; Central ServicesServicio de Salud de Castilla-La Mancha (SESCAM), Toledo, Spain.; Department of EndocrinologyUniversity of Groningen, University Medical Center Groningen, Groningen, The Netherlands.; Department of Medicine IIMedical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany [email protected].; Genomic Medicine InstituteLerner Research Institute and Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio, USA.

DOI: 10.1530/ERC-18-0085