Characterization of Malignant Head and Neck Paragangliomas at a Single Institution Across Multiple Decades

Abstract

IMPORTANCE Malignant head and neck paragangliomas (HNPGLs) are rare entities, and there are limited data regarding optimal treatment recommendations to improve clinical outcomes. OBJECTIVE To classify succinate dehydrogenase (SDH) germline mutations associated with malignant HNPGLs, evaluate time from diagnosis to identification of malignant tumor, describe locations of metastases and the functional status of malignant HNPGLs, and determine the role of selective neck dissection at the time of initial surgical resection. DESIGN, SETTING, AND PARTICIPANTS A retrospective cohort study was completed of patients diagnosed with paragangliomas on various sites on the body at an academic tertiary cancer hospital between the years 1963 and 2018. A subanalysis of HNPGLs was also completed. Data regarding diagnosis, gene and mutation, tumor characteristics and location, and treatments used were reviewed between February 2017 and March 2018. MAIN OUTCOMES AND MEASURES Mutations of SDH genes associated with benign and malignant HNPGLs, treatments used, time to the discovery of malignancy, and location of metastasis. RESULTS Of the 70 patients included in the study, 40 (57%) were male, and the mean (SD) age was 47 (21.1) years. Of patients with tumors isolated to the head and neck, 38 (54%) had benign HNPGLs, which were associated with mutations in the genes SDH subunit B (SDHB) (n = 18; 47%), SDH subunit C (n = 2; 5%), and SDH subunit D (n = 18; 47%). Among those with malignant HNPGLs, all but 1 patient had mutations in SDHB (n = 5; 83%); 1 patient had no mutation associated with their disease. The average age at diagnosis for malignant HNPGLs was 35 years, while benign tumors were diagnosed at an average age at 36 years. All patients with malignant disease underwent surgery. Four patients were found to have metastasis at the time of selective neck dissection. Among patients with malignant HNPGLs, 5 (83%) were treated with adjuvant radiation, and 1 (17%) was treated with adjuvant chemotherapy. CONCLUSIONS AND RELEVANCE Malignant HNPGLs are rare entities that are difficult to diagnose and are typically identified by the presence of regional or distant metastasis. The results of this study found the prevalence of malignant HNPGLs to be 9%. These data suggest that it is beneficial to perform a selective neck dissection at the time of tumor excision. All patients with malignant HNPGLs but 1 had SDHB mutations.

Carotid paragangliomas: case report and imaging review

“…Carotid paragangliomas generally affect women [1,19,28,30,34], are bilateral in about 10% of cases [6], and the involvement of hereditary factors is described in 4-9% of cases [28,30,34].…”

“…Carotid body tumors are paragangliomas that show high malignant capacity, a feature that occurs in 6-12% of cases [14,19,28,34]. In the absence of specific histopathological criteria, malignancy is marked by the anatomical presence of metastases [10], with a predilection for regional lymph nodes, and very rare distant metastases [3].…”

“…Carotid paragangliomas (CPs), also known as carotid body tumors, are neuroendocrine tumors originating in the parenchymal cells of the neuroectoderm and neural crests, but also in the mesodermal elements of the third branchial arch [1,17,19,28,30]. Thus, the cells that make up paragangliomas are similar to the cells in the APUD (amine precursor uptake and decarboxylation) system and can release catecholamines, cholecystokinin, serotonin, somatostatin, and vasoactive intestinal peptide [20].…”

“…Head and neck paragangliomas can show the following topography: carotid (carotid glomus), tympanic (glomus tympani), jugular (glomus jugulare) or vagal (glomus vagale) [22]. These tumors are rare [1,26,30], can be single or multifocal tumors, and are considered benign but with malignant potential in 6-12% of cases [14,19,28,34].…”

Recurrent Primary Intrasellar Paraganglioma

“…The typical workup, if the patient is suspected to have a PGL or pheochromocytoma, consists of an MRI or CT of the abdomen and pelvis, a serum calcitonin level, 24-hour urine collection to measure catecholamine levels, and plasma-free fractionated metanephrines [ 6 ]. Of head and neck PGLs, 6–19% are malignant [ 15 ]. The diagnosis of malignant paraganglioma is currently debated.…”