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.

Figure 1

Different scanning methods with CT. (A) A contrast chest CT that is not gated to the cardiac cycle demonstrates the blurriness of the cardiac silhouette. Contrast can be seen entering into the superior vena cava. (B) Non-contrast gated CT demonstrates the difficulty in seeing the mass next to the superior vena cava. (C) A contrasted gated CT allows better visualization of the mass (red arrows) impinging onto the superior vena cava without blurring of the cardiac silhouette. Ao: Aortic root, LA: left atrium, RVOT: right ventricular outflow tract.

Figure 2

(A) Cardiac MRI steady state free precession image in the 4-chamber view demonstrating an oval mass (red arrows) posterior to the left atrium (LA) abutting the right lower pulmonary vein (asterisk); (B) with turbo spin echo, the blood signal can be nulled to enhance the appearance of surrounding structures such as the mass (B). LA: left atrium, LV: left ventricle, RA: right atrium, RV: right ventricle.

Figure 3

Functional imaging of cardiac PGLs from different patients. (A) Octreotide (¹¹¹In-pentetreotide) scan demonstrating increased uptake in the neck and heart. There is also increased uptake in the liver, kidneys, spleen, gallbladder, and urinary bladder, which are physiologic. (B) ¹⁸F-FDOPA (¹⁸F-fluorodihdyroxyphenylalanine) PET demonstrating a large cardiac paraganglioma at the base of the heart near the root of the great vessels. (C-E) ¹⁸F-FDG PET/CT of a mass in the right atrioventricular groove. (C) Non-contrast CT scan for localization; (D) ¹⁸F-FDG PET showing an area of high activity; (E) fused PET/CT image.