SAT-089 - Head and Neck Paraganglioma: The NIH Experience.

Background:
Head and neck paragangliomas (HNPGLs) are rare neuroendocrine tumors arising from parasympathetic paraganglia, most commonly involving the carotid body, jugulotympanic region, and vagal nerve. Although typically non-secretory, HNPGLs are increasingly recognized as part of hereditary paraganglioma–pheochromocytoma (PPGL) syndromes, with a high prevalence of germline mutations in succinate dehydrogenase (SDHx) genes, particularly SDHD and SDHB.

Methods:
We conducted a retrospective analysis of 123 patients diagnosed and treated for head and neck paragangliomas at the National Institutes of Health (Bethesda, Maryland) between 2000 and 2025.

Results:
Of the 123 patients, 71 (57.7%) were female and 52 (42.3%) were male. The mean age at primary tumor diagnosis was 36.5 ± 37years. At initial presentation, 61 patients (49.6%) had solitary tumors, 23 (18.7%) had bilateral HNPGLs, 20 (16.3%) had multiple PGLs including adrenal and extra-adrenal PGLs, and 19 (15.4%) had metastatic disease. All patients with metastatic disease were diagnosed with metastases at initial presentation. The mean size of the primary HNPGL was 2.9 cm. Treatment included surgery in 66% of patients, radiation therapy in 12%, CVD chemotherapy in 4%, and active surveillance in 12%. Thirteen patients were deceased, including two deaths attributable to surgical complications.
Of the 123 patients, 103 (83.7%) harbored identifiable germline mutations in known susceptibility genes, while 18 patients (14.6%) tested negative on a standard PPGL gene panel. Two patients did not undergo genetic testing due to insufficient samples.
SDHD was the most frequently mutated gene, identified in 54 cases (43.9%), followed by SDHB in 34 cases (27.6%). SDHC mutations were present in 8 cases (6.5%), and SDHA in 2 cases (1.6%), with one patient harboring dual SDHA and TMEM127 variants. Collectively, SDHx mutations (SDHA, SDHB, SDHC, and SDHD) accounted for 98 cases (79.6% of the total cohort). VHL mutations were identified in 4 cases (3.2%). Additional rare variants included CHEK2, EGLN2, RET, SUCLG2, and KIF1B, each identified in single patients.
Sixty-one patients (49.5%) demonstrated elevated catecholamines and/or metanephrines at some point in time.
Head and neck paragangliomas demonstrate significant genetic heterogeneity, with a predominance of SDHx mutation. Early identification of hereditary disease and metastatic potential is critical, supporting universal genetic testing, biochemical surveillance, and individualized treatment strategies in patients with HNPGLs.

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