Rates of Hereditary Paraganglioma Syndromes and Secretory Tumors in Head and Neck Paragangliomas—A Single Institution Experience

Introduction: Paragangliomas of the head and neck are benign and often nonfunctional neuroendocrine neoplasms. Rarely, they are associated with hereditary paraganglioma-pheochromocytoma syndromes and inherited in an autosomal dominant fashion, with mutations in SDHD mainly associated with head and neck paragangliomas. We aimed to characterize the rate of secretory tumors and the rate and different types of genetic mutations identified in patients diagnosed with head and neck paragangliomas.

Methods: All patients diagnosed with head and neck paragangliomas and treated with stereotactic radiation from 2009 to 2020 at a single institution were identified. A retrospective chart review was performed to record relevant laboratory results, including 24-hour urine metanephrine and catecholamine laboratory values, as well as plasma metanephrine results. Genetic testing was obtained via the Ambry Genetics Hereditary Paraganglioma and Pheochromocytoma genetics panel.

Results: Thirty-nine patients with 49 head and neck paragangliomas were identified. All patients received 25 Gy in 5 fractions every other day, and 14/49 tumors received radiation postoperatively. Of the 39 patients, 26 (66.7%) and 25 (64.1%) underwent laboratory and genetics testing, respectively. Five patients (19.2%) had abnormally elevated 24-hour urine metanephrine or catecholamine results when they initially presented to our institution; elevated 24-hour urine normetanephrine was found in five patients (mean 609 mcg/24 hours, normal range 128–484). Among those with genetic testing, 11 (44.0%) had identifiable pathogenic or likely pathogenic mutations, and two (8.0%) were variants of undetermined significance. [Table 1] details the identified gene mutations.

Conclusion: This is a single institution cohort of patients with head and neck paragangliomas who underwent genetic testing as well as urinary catecholamine and metanephrine studies. We demonstrate that a large fraction of patients presenting with head and neck paragangliomas have pathogenic or likely pathogenic genetic mutations and functional tumors. Genetic testing and counseling, as well as laboratory studies, should thus be performed in patients diagnosed with head and neck paragangliomas.

Gene	Number of Patients	Mutations
SDHB	4	p.R46Q, p.R46*, c.541-2A>G, p.W200C
SDHD	4	p.P81L
SDHC	2	p.R72L, p.H127R
SDHA	1	p.R31*
MET	1	p.A347Ta
RET	1	c.405C>T (p.G135G)1

Publication History

Article published online:
05 February 2024