Head and neck paragangliomas (HNPGLs) are rare neuroendocrine tumors, comprising only 3% of all head and neck tumors. Early diagnosis forms an integral part of the management of these tumors. The two main aims of any treatment approach are long-term tumor control and minimal cranial nerve morbidity. The scope of this article is to present our case series of HNPGLs to stress most important clinical aspects of their presentation as well as critical issues of their complex management. Thirty patients with suspected HNPGLs were referred to our otorhinolaryngology clinic for surgical consultation between 2016-2020. We assessed the demographical pattern, clinicoradiological correlation, as well as type and outcome of treatment. A total of 42 non-secretory tumors were diagnosed-16.7% were incidental findings and 97% patients had benign tumors. Six patients had multiple tumors. Jugular paragangliomas were the most commonly treated tumors. Tumor control was achieved in nearly 96% of operated patients with minimal cranial nerve morbidity. Surgery is curative in most cases and should be considered as frontline treatment modality in experienced hands for younger patients, hereditary and secretory tumors. Cranial nerve dysfunction associated with tumor encasement is a negative prognostic factor for both surgery and radiotherapy. Multifocal tumors and metastasis are difficult to treat, even with early detection using genetic analysis. Detecting malignancy in HNPGLs is challenging due to the lack of histomorphological criteria; therefore, limited lymph node dissection should be considered, even in the absence of clinical and radiological signs of metastasis in carotid body, vagal, and jugular paragangliomas.

Department of Otorhinolaryngology University Hospital Kralovske Vinohrady 3rd Faculty of Medicine Charles University 10034 Prague Czech Republic

See more in PubMed

Whalen R.K., Althausen A.F., Daniels G.H. Extra-Adrenal Pheochromocytoma. J. Urol. 1992;147:1–10. doi: 10.1016/S0022-5347(17)37119-7. PubMed DOI

Lloyd R.V., Osamura R.Y., Kloppel G., Rosai J., editors. WHO Classification of Tumours of Endocrine Organs. 4th ed. International Agency for Research on Cancer (IARC); Lyon, France: 2017. Head and neck paragangliomas; pp. 190–192.

Taïeb D., Kaliski A., Boedeker C.C., Martucci V., Fojo T., Adler J.R., Jr., Pacak K. Current Approaches and Recent Developments in the Management of Head and Neck Paragangliomas. Endocr. Rev. 2014;35:795–819. doi: 10.1210/er.2014-1026. PubMed DOI PMC

Wasserman P.G., Savargaonkar P. Paragangliomas. Otolaryngol. Clin. N. Am. 2001;34:845–862. doi: 10.1016/S0030-6665(05)70351-0. PubMed DOI

Offergeld C., Brase C., Yaremchuk S., Mader I., Rischke H.C., Gläsker S., Schmid K.W., Wiech T., Preuss S.F., Suárez C., et al. Head and Neck Paragangliomas: Clinical and Molecular Genetic Classification. Clinics. 2012;67((Suppl. 1)):19–28. doi: 10.6061/clinics/2012(Sup01)05. PubMed DOI PMC

Guha A., Musil Z., Vicha A., Zelinka T., Pacak K., Astl J., Chovanec M. A Systematic Review on the Genetic Analysis of Paragangliomas: Primarily Focused on Head and Neck Paragangliomas. Neoplasma. 2019;66:671–680. doi: 10.4149/neo_2018_181208N933. PubMed DOI PMC

Boedeker C.C., Hensen E.F., Neumann H.P.H., Maier W., van Nederveen F.H., Suárez C., Kunst H.P., Rodrigo J.P., Takes R.P., Pellitteri P.K., et al. Genetics of Hereditary Head and Neck Paragangliomas: Hereditary Head and Neck Paragangliomas. Head Neck. 2014;36:907–916. doi: 10.1002/hed.23436. PubMed DOI

Neumann H.P.H., Bausch B., McWhinney S.R., Bender B.U., Gimm O., Franke G., Schipper J., Klisch J., Altehoefer C., Zerres K., et al. Germ-Line Mutations in Nonsyndromic Pheochromocytoma. N. Engl. J. Med. 2002;346:1459–1466. doi: 10.1056/NEJMoa020152. PubMed DOI

Boedeker C.C. Paragangliomas and Paraganglioma Syndromes. GMS Curr. Top. Otorhinolaryngol. Head Neck Surg. 2011;10:Doc03. PubMed PMC

Patetsios P., Gable D.R., Garrett W.V., Lamont J.P., Kuhn J.A., Shutze W.P., Kourlis H., Grimsley B., Pearl G.J., Smith B.L., et al. Management of Carotid Body Paragangliomas and Review of a 30-Year Experience. Ann. Vasc. Surg. 2002;16:331–338. doi: 10.1007/s10016-001-0106-8. PubMed DOI

Suárez C., Rodrigo J.P., Ferlito A., Cabanillas R., Shaha A.R., Rinaldo A. Tumours of Familial Origin in the Head and Neck. Oral Oncol. 2006;42:965–978. doi: 10.1016/j.oraloncology.2006.03.002. PubMed DOI

Erickson D., Kudva Y.C., Ebersold M.J., Thompson G.B., Grant C.S., van Heerden J.A., Young W.F., Jr. Benign Paragangliomas: Clinical Presentation and Treatment Outcomes in 236 Patients. J. Clin. Endocrinol. Metab. 2001;86:5210–5216. doi: 10.1210/jcem.86.11.8034. PubMed DOI

Robertson V., Poli F., Hobson B., Saratzis A., Ross Naylor A. A Systematic Review and Meta-Analysis of the Presentation and Surgical Management of Patients with Carotid Body Tumours. Eur. J. Vasc. Endovasc. Surg. 2019;57:477–486. doi: 10.1016/j.ejvs.2018.10.038. PubMed DOI

Shamblin W.R., ReMine W.H., Sheps S.G., Harrison E.G., Jr. Carotid Body Tumor (Chemodectoma) Am. J. Surg. 1971;122:732–739. doi: 10.1016/0002-9610(71)90436-3. PubMed DOI

Smith J.D., Harvey R.N., Darr O.A., Prince M.E., Bradford C.R., Wolf G.T., Else T., Basura G.J. Head and Neck Paragangliomas: A Two-Decade Institutional Experience and Algorithm for Management. Laryngoscope Investig. Otolaryngol. 2017;2:380–389. doi: 10.1002/lio2.122. PubMed DOI PMC

Rinaldo A., Myssiorek D., Devaney K.O., Ferlito A. Which Paragangliomas of the Head and Neck Have a Higher Rate of Malignancy? Oral Oncol. 2004;40:458–460. doi: 10.1016/j.oraloncology.2003.08.018. PubMed DOI

Biller H.F., Lawson W., Som P., Rosenfeld R. Glomus Vagale Tumors. Pt 1Ann. Otol. Rhinol. Laryngol. 1989;98:21–26. doi: 10.1177/000348948909800105. PubMed DOI

Hamersley E.R.S., Barrows A., Perez A., Schroeder A., Castle J.T. Malignant Vagal Paraganglioma. Head Neck Pathol. 2016;10:201–205. doi: 10.1007/s12105-015-0621-5. PubMed DOI PMC

Granato L., Próspero J.D., Filho D.M. Nasal Paraganglioma: A Case Report and Literature Review. Int. Arch. Otorhinolaryngol. 2013;17:92–95. PubMed PMC

Barnes L. Paraganglioma of the Larynx. A Critical Review of the Literature. ORL J. Otorhinolaryngol. Relat. Spec. 1991;53:220–234. doi: 10.1159/000276221. PubMed DOI

Connor S.E.J., Gleeson M.J., Odell E. Extracranial Glomus Faciale Tumour. J. Laryngol. Otol. 2008;122:986–989. doi: 10.1017/S0022215107000126. PubMed DOI

Langerman A., Athavale S.M., Rangarajan S.V., Sinard R.J., Netterville J.L. Natural History of Cervical Paragangliomas: Outcomes of Observation of 43 Patients. Arch. Otolaryngol. Head Neck Surg. 2012;138:341–345. PubMed

Von Dobschuetz E., Leijon H., Schalin-Jäntti C., Schiavi F., Brauckhoff M., Peczkowska M., Spiazzi G., Demattè S., Cecchini M.E., Sartorato P., et al. A Registry-Based Study of Thyroid Paraganglioma: Histological and Genetic Characteristics. Endocr. Relat. Cancer. 2015;22:191–204. doi: 10.1530/ERC-14-0558. PubMed DOI

Levy M.T., Braun J.T., Pennant M., Thompson L.D.R. Primary Paraganglioma of the Parathyroid: A Case Report and Clinicopathologic Review. Head Neck Pathol. 2010;4:37–43. doi: 10.1007/s12105-009-0157-7. PubMed DOI PMC

Harries K., Nunn T., Shah V., Richards D., Manson J.M. First Reported Case of Esophageal Paraganglioma. A Review of the Literature of Gastrointestinal Tract Paraganglioma Including Gangliocytic Paraganglioma. Dis. Esophagus. 2004;17:191–195. doi: 10.1111/j.1442-2050.2004.00386.x. PubMed DOI

Guha A., Vicha A., Zelinka T., Musil Z., Chovanec M. Genetic Variants in Patients with Multiple Head and Neck Paragangliomas: Dilemma in Management. Biomedicines. 2021;9:626. doi: 10.3390/biomedicines9060626. PubMed DOI PMC

Papaspyrou K., Mewes T., Rossmann H., Fottner C., Schneider-Raetzke B., Bartsch O., Schreckenberger M., Lackner K.J., Amedee R.G., Mann W.J. Head and Neck Paragangliomas: Report of 175 Patients (1989–2010) Head Neck. 2012;34:632–637. doi: 10.1002/hed.21790. PubMed DOI

Piccini V., Rapizzi E., Bacca A., Di Trapani G., Pulli R., Giachè V., Zampetti B., Lucci-Cordisco E., Canu L., Corsini E., et al. Head and Neck Paragangliomas: Genetic Spectrum and Clinical Variability in 79 Consecutive Patients. Endocr. Relat. Cancer. 2012;19:149–155. doi: 10.1530/ERC-11-0369. PubMed DOI

Nölting S., Ullrich M., Pietzsch J., Ziegler C.G., Eisenhofer G., Grossman A., Pacak K. Current Management of Pheochromocytoma/Paraganglioma: A Guide for the Practicing Clinician in the Era of Precision Medicine. Cancers. 2019;11:1505. doi: 10.3390/cancers11101505. PubMed DOI PMC

Crona J., Taïeb D., Pacak K. New Perspectives on Pheochromocytoma and Paraganglioma: Toward a Molecular Classification. Endocr. Rev. 2017;38:489–515. doi: 10.1210/er.2017-00062. PubMed DOI PMC

Santhanam P., Taïeb D. Role of (18) F-FDOPA PET/CT Imaging in Endocrinology. Clin. Endocrinol. 2014;81:789–798. doi: 10.1111/cen.12566. PubMed DOI

Van Berkel A., Vriens D., Visser E.P., Janssen M.J.R., Gotthardt M., Hermus A.R.M.M., de Geus-Oei L.-F., Timmers H.J.L.M. Metabolic Subtyping of Pheochromocytoma and Paraganglioma by 18F-FDG Pharmacokinetics Using Dynamic PET/CT Scanning. J. Nucl. Med. 2019;60:745–751. doi: 10.2967/jnumed.118.216796. PubMed DOI PMC

Lenders J.W.M., Duh Q.-Y., Eisenhofer G., Gimenez-Roqueplo A.-P., Grebe S.K.G., Murad M.H., Naruse M., Pacak K., Young W.F., Jr., Endocrine Society Pheochromocytoma and Paraganglioma: An Endocrine Society Clinical Practice Guideline. J. Clin. Endocrinol. Metab. 2014;99:1915–1942. doi: 10.1210/jc.2014-1498. PubMed DOI

Thompson M.J., Parameswaran V., Burgess J.R. Clinical Utility of Chromogranin A for the Surveillance of Succinate Dehydrogenase B- and Succinate Dehydrogenase D-Related Paraganglioma. Ann. Clin. Biochem. 2019;56:163–169. doi: 10.1177/0004563218811865. PubMed DOI

Hsiao R.J., Neumann H.P., Parmer R.J., Barbosa J.A., O’Connor D.T. Chromogranin A in Familial Pheochromocytoma: Diagnostic Screening Value, Prediction of Tumor Mass, and Post-Resection Kinetics Indicating Two-Compartment Distribution. Am. J. Med. 1990;88:607–613. doi: 10.1016/0002-9343(90)90526-J. PubMed DOI

Jansen J.C., van den Berg R., Kuiper A., van der Mey A.G., Zwinderman A.H., Cornelisse C.J. Estimation of Growth Rate in Patients with Head and Neck Paragangliomas Influences the Treatment Proposal. Cancer. 2000;88:2811–2816. doi: 10.1002/1097-0142(20000615)88:12<2811::AID-CNCR21>3.0.CO;2-7. PubMed DOI

Wieneke J.A., Smith A. Diagnostic Imaging: Head and Neck. Elsevier; Amsterdam, The Netherlands: 2017. Carotid Body Paraganglioma; pp. 140–143.

Chaloupka J.C., Mangla S., Huddle D.C., Roth T.C., Mitra S., Ross D.A., Sasaki C.T. Evolving Experience with Direct Puncture Therapeutic Embolization for Adjunctive and Palliative Management of Head and Neck Hypervascular Neoplasms. Laryngoscope. 1999;109:1864–1872. doi: 10.1097/00005537-199911000-00028. PubMed DOI

Sanna M., Piazza P., Shin S.-H., Flanagan S., Mancini F., editors. Microsurgery of Skull Base Paragangliomas. 1st ed. Thieme Medical; New York, NY, USA: 2013. Embolization of paragangliomas.

Gemmete J.J., Chaudhary N., Pandey A., Gandhi D., Sullivan S.E., Marentette L.J., Chepeha D.B., Ansari S.A. Usefulness of Percutaneously Injected Ethylene-Vinyl Alcohol Copolymer in Conjunction with Standard Endovascular Embolization Techniques for Preoperative Devascularization of Hypervascular Head and Neck Tumors: Technique, Initial Experience, and Correlation with Surgical Observations. AJNR Am. J. Neuroradiol. 2010;31:961–966. doi: 10.3174/ajnr.a1936. PubMed DOI PMC

Pedicelli A., Lozupone E., Valente I., Snider F., Rigante M., D’Argento F., Alexandre A., Garignano G., Chiumarulo L., Paludetti G., et al. Pre-Operative Direct Puncture Embolization of Head and Neck Hypervascular Tumors Using SQUID 12. Interv. Neuroradiol. 2020;26:346–353. doi: 10.1177/1591019919895882. PubMed DOI PMC

Suárez C., Rodrigo J.P., Bödeker C.C., Llorente J.L., Silver C.E., Jansen J.C., Takes R.P., Strojan P., Pellitteri P.K., Rinaldo A., et al. Jugular and Vagal Paragangliomas: Systematic Study of Management with Surgery and Radiotherapy. Head Neck. 2013;35:1195–1204. doi: 10.1002/hed.22976. PubMed DOI

Kollert M., Minovi A., Mangold R., Hendus J., Draf W., Bockmühl U. Paragangliome des Kopf-Hals-Bereiches—Tumorkontrolle, funktionelle Ergebnisse und Lebensqualität nach Operation. Laryngorhinootologie. 2006;85:649–656. doi: 10.1055/s-2006-925234. PubMed DOI

Hinerman R.W., Mendenhall W.M., Amdur R.J., Stringer S.P., Antonelli P.J., Cassisi N.J. Definitive Radiotherapy in the Management of Chemodectomas Arising in the Temporal Bone, Carotid Body, and Glomus Vagale. Head Neck. 2001;23:363–371. doi: 10.1002/hed.1045. PubMed DOI

Krych A.J., Foote R.L., Brown P.D., Garces Y.I., Link M.J. Long-Term Results of Irradiation for Paraganglioma. Int. J. Radiat. Oncol. Biol. Phys. 2006;65:1063–1066. doi: 10.1016/j.ijrobp.2006.02.020. PubMed DOI

Ibrahim R., Ammori M.B., Yianni J., Grainger A., Rowe J., Radatz M. Gamma Knife Radiosurgery for Glomus Jugulare Tumors: A Single-Center Series of 75 Cases. J. Neurosurg. 2017;126:1488–1497. doi: 10.3171/2016.4.JNS152667. PubMed DOI

Netterville J.L., Civantos F.J. Rehabilitation of Cranial Nerve Deficits after Neurotologic Skull Base Surgery. Laryngoscope. 1993;103:45–54. doi: 10.1002/lary.1993.103.s60.45. PubMed DOI

Sen C., Hague K., Kacchara R., Jenkins A., Das S., Catalano P. Jugular Foramen: Microscopic Anatomic Features and Implications for Neural Preservation with Reference to Glomus Tumors Involving the Temporal Bone. Neurosurgery. 2001;48:838–847. PubMed

Gottfried O.N., Liu J.K., Couldwell W.T. Comparison of Radiosurgery and Conventional Surgery for the Treatment of Glomus Jugulare Tumors. Neurosurg. Focus. 2004;17:22–30. doi: 10.3171/foc.2004.17.2.4. PubMed DOI

Lalwani A.K., Jackler R.K., Gutin P.H. Lethal Fibrosarcoma Complicating Radiation Therapy for Benign Glomus Jugulare Tumor. Am. J. Otol. 1993;14:398–402. PubMed

Preissig S.H., Bohmfalk G.L., Reichel G.W., Smith M.T. Anaplastic Astrocytoma Following Radiation for a Glomus Jugular Tumor. Cancer. 1979;43:2243–2247. doi: 10.1002/1097-0142(197906)43:6<2243::AID-CNCR2820430614>3.0.CO;2-K. PubMed DOI

Lekovic G.P., Mehta G.U., Maxwell A.K., Peng K.A., Brackmann D.E. Radiation-Induced Malignant Peripheral Nerve Sheath Tumor of the Vagus Nerve Following Radiation Treatment of Cervical Paraganglioma. J. Neurol. Surg. Rep. 2020;81:e66–e70. doi: 10.1055/s-0040-1718408. PubMed DOI PMC

Na A.F., Lai L.T., Kaye A.H. Radiation Induced Brainstem Glioblastoma in a Patient Treated for Glomus Jugulare Tumour. J. Clin. Neurosci. 2015;22:219–221. doi: 10.1016/j.jocn.2014.06.003. PubMed DOI

Springate S.C., Weichselbaum R.R. Radiation or Surgery for Chemodectoma of the Temporal Bone: A Review of Local Control and Complications. Head Neck. 1990;12:303–307. doi: 10.1002/hed.2880120405. PubMed DOI

Muracciole X., Régis J. Radiosurgery and Carcinogenesis Risk. Prog. Neurol. Surg. 2008;21:207–213. PubMed

Suárez C., Rodrigo J.P., Mendenhall W.M., Hamoir M., Silver C.E., Grégoire V., Strojan P., Neumann H.P.H., Obholzer R., Offergeld C., et al. Carotid Body Paragangliomas: A Systematic Study on Management with Surgery and Radiotherapy. Eur. Arch. Otorhinolaryngol. 2014;271:23–34. doi: 10.1007/s00405-013-2384-5. PubMed DOI