Rates of Hereditary Paraganglioma Syndromes and Secretory Head and Neck Paragangliomas: A Single-Institution Experience

Abstract

Objective

This study aimed to characterize the rate of secretory tumors and the rate and types of genetic variations identified in patients diagnosed with head and neck (HN) paragangliomas.

Study Design

A retrospective case review.

Setting

Tertiary referral center.

Participants

About 74 patients with HN paragangliomas treated with gamma knife radiosurgery.

Main Outcome Measures

Genetics testing via the Ambry Genetics Hereditary Paraganglioma and Pheochromocytoma Panel, and 24-hour urine metanephrine and catecholamine levels, were obtained. Pathogenic and likely pathogenic variations were tabulated. Levels of 24-hour urinary epinenephrine, norepinephrine, metanephrine, normetanephrine, and dopamine were recorded and correlated with rates of genetic variations.

Results

Of 74 patients, 46 (62.2%) and 38 (51.4%) underwent laboratory and genetics testing, respectively; 29 (39.2%) completed both. Nine (19.6%) had abnormally elevated 24-hour urine metanephrine/catecholamine, of whom eight (88.9%) had elevated normetanephrine levels. Pathogenic/likely pathogenic variations were found in 15/38 (39.5%) patients. Among those with both genetics and laboratory testing, 4/12 (33.3%) with a pathogenic variation had evidence of secretory tumors, compared with 1/17 (5.9%) of those without a variation. Conversely, 80% (4/5) of patients with abnormally elevated metanephrine or catecholamine studies had a pathogenic genetic variation, compared with 33.3% (8/24) with normal laboratory results.

Conclusion

This is a single-institution cohort with HN paragangliomas who underwent genetic testing and urine catecholamine and metanephrine studies. We demonstrate that a large fraction of patients presenting with HN paragangliomas have pathogenic genetic variations and secreting tumors. Genetic testing and counseling, and laboratory studies, should thus be performed in patients diagnosed with HN paragangliomas.

Keywords

head and neck paraganglioma - genetic testing - catecholamine - metanephrine

Previous Presentation

This manuscript was presented as a scientific oral presentation at the AAO-HNSF 2024 Annual Meeting and OTO Experience, Miami, FL, September 28–October 1, 2024.

Publikationsverlauf

Eingereicht: 22. Dezember 2024

Angenommen: 12. Mai 2025

Artikel online veröffentlicht:
26. Mai 2025

• References

• 1 Wasserman PG, Savargaonkar P. Paragangliomas: classification, pathology, and differential diagnosis. Otolaryngol Clin North Am 2001; 34 (05) 845-862 , v–vi
• 2 Erickson D, Kudva YC, Ebersold MJ. et al. Benign paragangliomas: clinical presentation and treatment outcomes in 236 patients. J Clin Endocrinol Metab 2001; 86 (11) 5210-5216
• 3 Moore MG, Netterville JL, Mendenhall WM, Isaacson B, Nussenbaum B. Head and neck paragangliomas: An update on evaluation and management. Otolaryngol Head Neck Surg 2016; 154 (04) 597-605
• 4 Carlson ML, Sweeney AD, Wanna GB, Netterville JL, Haynes DS. Natural history of glomus jugulare: a review of 16 tumors managed with primary observation. Otolaryngol Head Neck Surg 2015; 152 (01) 98-105
• 5 Prasad SC, Mimoune HA, D'Orazio F. et al. The role of wait-and-scan and the efficacy of radiotherapy in the treatment of temporal bone paragangliomas. Otol Neurotol 2014; 35 (05) 922-931
• 6 Langerman A, Athavale SM, Rangarajan SV, Sinard RJ, Netterville JL. Natural history of cervical paragangliomas: outcomes of observation of 43 patients. Arch Otolaryngol Head Neck Surg 2012; 138 (04) 341-345
• 7 Hinerman RW, Amdur RJ, Morris CG, Kirwan J, Mendenhall WM. Definitive radiotherapy in the management of paragangliomas arising in the head and neck: a 35-year experience. Head Neck 2008; 30 (11) 1431-1438
• 8 Gilbo P, Morris CG, Amdur RJ. et al. Radiotherapy for benign head and neck paragangliomas: a 45-year experience. Cancer 2014; 120 (23) 3738-3743
• 9 Sager O, Dincoglan F, Beyzadeoglu M. Stereotactic radiosurgery of glomus jugulare tumors: current concepts, recent advances and future perspectives. CNS Oncol 2015; 4 (02) 105-114
• 10 Muth A, Crona J, Gimm O. et al. Genetic testing and surveillance guidelines in hereditary pheochromocytoma and paraganglioma. J Intern Med 2019; 285 (02) 187-204
• 11 Fishbein L, Leshchiner I, Walter V. et al.; Cancer Genome Atlas Research Network. Comprehensive molecular characterization of pheochromocytoma and paraganglioma. Cancer Cell 2017; 31 (02) 181-193
• 12 Fishbein L, Merrill S, Fraker DL, Cohen DL, Nathanson KL. Inherited mutations in pheochromocytoma and paraganglioma: why all patients should be offered genetic testing. Ann Surg Oncol 2013; 20 (05) 1444-1450
• 13 Cleere EF, Martin-Grace J, Gendre A, Sherlock M, O'Neill JP. Contemporary management of paragangliomas of the head and neck. Laryngoscope Investig Otolaryngol 2021; 7 (01) 93-107
• 14 Hampel H, Bennett RL, Buchanan A, Pearlman R, Wiesner GL. Guideline Development Group, American College of Medical Genetics and Genomics Professional Practice and Guidelines Committee and National Society of Genetic Counselors Practice Guidelines Committee. A practice guideline from the American College of Medical Genetics and Genomics and the National Society of Genetic Counselors: referral indications for cancer predisposition assessment. Genet Med 2015; 17 (01) 70-87
• 15 Neumann HP, Pawlu C, Peczkowska M. et al.; European-American Paraganglioma Study Group. Distinct clinical features of paraganglioma syndromes associated with SDHB and SDHD gene mutations. JAMA 2004; 292 (08) 943-951
• 16 Erlic Z, Neumann HP. When should genetic testing be obtained in a patient with phaeochromocytoma or paraganglioma?. Clin Endocrinol (Oxf) 2009; 70 (03) 354-357
• 17 Amar L, Bertherat J, Baudin E. et al. Genetic testing in pheochromocytoma or functional paraganglioma. J Clin Oncol 2005; 23 (34) 8812-8818
• 18 Badenhop RF, Jansen JC, Fagan PA. et al. The prevalence of SDHB, SDHC, and SDHD mutations in patients with head and neck paraganglioma and association of mutations with clinical features. J Med Genet 2004; 41 (07) e99
• 19 Neumann HP, Erlic Z, Boedeker CC. et al. Clinical predictors for germline mutations in head and neck paraganglioma patients: cost reduction strategy in genetic diagnostic process as fall-out. Cancer Res 2009; 69 (08) 3650-3656
• 20 Smith JD, Ellsperman SE, Basura GJ, Else T. Re-evaluating the prevalence and factors characteristic of catecholamine secreting head and neck paragangliomas. Endocrinol Diabetes Metab 2021; 4 (03) e00256
• 21 Isaacs M, Lee P. Preoperative alpha-blockade in phaeochromocytoma and paraganglioma: is it always necessary?. Clin Endocrinol (Oxf) 2017; 86 (03) 309-314
• 22 Corssmit EP, Romijn JA. Clinical management of paragangliomas. Eur J Endocrinol 2014; 171 (06) R231-R243
• 23 van Duinen N, Steenvoorden D, Kema IP, Jansen JC, Vriends AH, Bayley JP, Smit JW, Romijn JA, Corssmit EP. Increased urinary excretion of 3-methoxytyramine in patients with head and neck paragangliomas. J Clin Endocrinol Metab 2010; 95 (01) 209-14
• 24 Lenders JW, Duh QY, Eisenhofer G. et al.; Endocrine Society. Pheochromocytoma and paraganglioma: an endocrine society clinical practice guideline. J Clin Endocrinol Metab 2014; 99 (06) 1915-1942
• 25 Schwaber MK, Glasscock ME, Nissen AJ, Jackson CG, Smith PG. Diagnosis and management of catecholamine secreting glomus tumors. Laryngoscope 1984; 94 (08) 1008-1015
• 26 Myssiorek D, Ferlito A, Silver CE. et al. Screening for familial paragangliomas. Oral Oncol 2008; 44 (06) 532-537
• 27 Smith JD, Harvey RN, Darr OA. et al. Head and neck paragangliomas: A two-decade institutional experience and algorithm for management. Laryngoscope Investig Otolaryngol 2017; 2 (06) 380-389
• 28 Smith JD, Bellile EL, Else T, Basura G. Head and neck paragangliomas: patterns of otolaryngology referrals for genetic testing over 2 decades. OTO Open 2021; 5 (01) X21995453