title: Succinate dehydrogenase gene mutations in cardiac paragangliomas.
abstract: Pheochromocytomas and paragangliomas are chromaffin cell tumors arising from neuroendocrine cells. At least 1/3 of paragangliomas are related to germline mutations in 1 of 17 genes. Although these tumors can occur throughout the body, cardiac paragangliomas are very rare, accounting for <0.3% of mediastinal tumors. The purpose of this study was to determine the clinical characteristics of patients with cardiac paragangliomas, particularly focusing on their genetic backgrounds. A retrospective chart analysis of 15 patients with cardiac paragangliomas was performed to determine clinical presentation, genetic background, diagnostic workup, and outcomes. The average age at diagnosis was 41.9 years. Typical symptoms of paraganglioma (e.g., hypertension, sweating, palpitations, headache) were reported at initial presentation in 13 patients (86.7%); the remaining 2, as well as 4 symptomatic patients, initially presented with cardiac-specific symptoms (e.g., chest pain, dyspnea). Genetic testing was done in 13 patients (86.7%); 10 (76.9%) were positive for mutations in succinate dehydrogenase (SDHx) subunits B, C, or D. Thirteen patients (86.7%) underwent surgery to remove the paraganglioma with no intraoperative morbidity or mortality; 1 additional patient underwent surgical resection but experienced intraoperative complications after removal of the tumor due to co-morbidities and did not survive. SDHx mutations are known to be associated with mediastinal locations and malignant behavior of paragangliomas. In this report, the investigators extend the locations of predominantly SDHx-related paragangliomas to cardiac tumors. In conclusion, cardiac paragangliomas are frequently associated with underlying SDHx germline mutations, suggesting a need for genetic testing of all patients with this rare tumor.
authors.affiliation: Program in Reproductive and Adult Endocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland.
authors.forename: Victoria L
authors.initials: VL
authors.lastname: Martucci
authors.affiliation: Cardiothoracic Surgery Research Program, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Abbas
authors.initials: A
authors.lastname: Emaminia
authors.affiliation: Program in Reproductive and Adult Endocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland.
authors.forename: Jaydira
authors.initials: J
authors.lastname: del Rivero
authors.affiliation: Division of Endocrinology, Diabetes and Metabolism, Tufts Medical Center, Boston, Massachusetts.
authors.forename: Ronald M
authors.initials: RM
authors.lastname: Lechan
authors.affiliation: Division of Endocrinology, Diabetes and Metabolism, Tufts Medical Center, Boston, Massachusetts.
authors.forename: Bindiya T
authors.initials: BT
authors.lastname: Magoon
authors.affiliation: Program in Reproductive and Adult Endocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland; Section of Endocrinology and Metabolism, University of Santo Tomas Hospital, Manila, Philippines.
authors.forename: Analyza
authors.initials: A
authors.lastname: Galia
authors.affiliation: Medical Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Tito
authors.initials: T
authors.lastname: Fojo
authors.affiliation: Cardiovascular and Pulmonary Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland; Division of Cardiovascular Medicine, Department of Medicine, University of Kentucky, Lexington, Kentucky.
authors.forename: Steve
authors.initials: S
authors.lastname: Leung
authors.affiliation: Cardiac Surgery Unit, Spedali Civili Hospital, Brescia, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Lorusso
authors.affiliation: Department of Endocrine Neoplasia and Hormonal Disorders, University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Camilo
authors.initials: C
authors.lastname: Jimenez
authors.affiliation: Division of Nuclear Medicine, St. Jude Children's Research Hospital, Memphis, Tennessee.
authors.forename: Barry L
authors.initials: BL
authors.lastname: Shulkin
authors.affiliation: Cardiovascular and Pulmonary Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Audibert
authors.affiliation: Program in Reproductive and Adult Endocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland.
authors.forename: Karen T
authors.initials: KT
authors.lastname: Adams
authors.affiliation: Cardiovascular and Pulmonary Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Douglas R
authors.initials: DR
authors.lastname: Rosing
authors.affiliation: Division of Endocrinology, Diabetes, and Hypertension, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Anand
authors.initials: A
authors.lastname: Vaidya
authors.affiliation: Division of Endocrinology, Diabetes, and Hypertension, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Robert G
authors.initials: RG
authors.lastname: Dluhy
authors.affiliation: Cardiothoracic Surgery Research Program, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Keith A
authors.initials: KA
authors.lastname: Horvath
authors.affiliation: Program in Reproductive and Adult Endocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland. Electronic address: karel@mail.nih.gov.
authors.forename: Karel
authors.initials: K
authors.lastname: Pacak
mesh_terms: D000328:Adult; D003952:Diagnostic Imaging; D005260:Female; D006338:Heart Neoplasms / Q000175:diagnosis / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D010235:Paraganglioma / Q000175:diagnosis / Q000378:metabolism*; D012189:Retrospective Studies; D013385:Succinate Dehydrogenase / Q000235:genetics*
chemical_list: D013385:Succinate Dehydrogenase