European Archives of Oto-Rhino-Laryngology

, Volume 272, Issue 8, pp 2045–2053 | Cite as

A two-decade experience of head and neck paragangliomas in a whole population-based single centre cohort

  • T. Anttila
  • V. Häyry
  • T. Nicoli
  • J. Hagström
  • K. Aittomäki
  • P. Vikatmaa
  • M. Niemelä
  • K. Saarilahti
  • A. Mäkitie
  • L. J. Bäck
Head and Neck
First Online:
Received:
Accepted:

Abstract

Paragangliomas are rare neuroendocrine tumours arising from neural crest-derived tissue. In the head and neck region typical locations are the carotid bifurcation, vagal nerve or jugulotympanic region. Paragangliomas are normally benign, and malignant transformation is rare. During the past decade the understanding of the genetic and molecular aetiology has had an important clinical impact on the management of PGs. This is a retrospective review of all histologically verified paragangliomas diagnosed and managed at an academic tertiary care referral centre between 1990 and 2010. Data on age, sex, symptoms, tumour location, management and follow-up were recorded. There were 64 patients with 74 tumours. Thirty-six per cent of the tumours were located in the carotid body region, 48 % in the jugulotympanic region and 15 % in the vagal nerve. One tumour was located in the dorsal neck. Most (95 %) of the patients were treated primarily with surgery and with curative intent. Definitive radiation therapy was primarily given to two patients. Recurrent or residual tumours were treated with surgery in three patients and with radiation therapy in nine patients. The typical long-term post-operative sequel was vocal cord paralysis. Local recurrence was found in 6 % of patients. Symptoms and findings related to paragangliomas are variable and management should be individualized. Surgery remains the primary choice of the current treatment options, but often is challenging and warrants a multidisciplinary approach. We present an algorithm on the management of head and neck paragangliomas based on current knowledge.

Keywords

Head and neck neoplasms Paraganglioma Surgery Genetic testing Mutation Succinate dehydrogenase 
This is a preview of subscription content, log in to check access.

Notes

Acknowledgments

The following are acknowledged: The Helsinki University Central Hospital Research Funds: Pekka Ranta, Elina Nikanne, Tommi Torkkeli, Jouko Nieminen, Erkki Hopsu, Kristofer Nyman and Matti Hynynen.

Conflict of interest

This research was funded by The Helsinki University Central Hospital Research Funds.

References

  1. 1.
    Martin TP, Irving RM, Maher ER (2007) The genetics of paragangliomas: a review. Clin Otolaryngol 32(1):7–11. doi: 10.1111/j.1365-2273.2007.01378.x PubMedCrossRefGoogle Scholar
  2. 2.
    Lenders JW, Eisenhofer G, Mannelli M, Pacak K (2005) Phaeochromocytoma. Lancet 366(9486):665–675 pii:S0140-6736(05)67139-5PubMedCrossRefGoogle Scholar
  3. 3.
    Fliedner SM, Lehnert H, Pacak K (2010) Metastatic paraganglioma. Semin Oncol 37(6):627–637. doi: 10.1053/j.seminoncol.2010.10.017 PubMedCentralPubMedCrossRefGoogle Scholar
  4. 4.
    Baysal BE (2002) Hereditary paraganglioma targets diverse paraganglia. J Med Genet 39(9):617–622. doi: 10.1136/jmg.39.9.617 PubMedCentralPubMedCrossRefGoogle Scholar
  5. 5.
    Fishbein L, Nathanson KL (2012) Pheochromocytoma and paraganglioma: understanding the complexities of the genetic background. Cancer Genet 205(1–2):1–11. doi: 10.1016/j.cancergen.2012.01.009 PubMedCentralPubMedCrossRefGoogle Scholar
  6. 6.
    Boedeker CC, Ridder GJ, Schipper J (2005) Paragangliomas of the head and neck: diagnosis and treatment. Fam Cancer 4(1):55–59. doi: 10.1007/s10689-004-2154-z PubMedCrossRefGoogle Scholar
  7. 7.
    Lee JH, Barich F, Karnell LH et al (2002) National Cancer Data Base report on malignant paragangliomas of the head and neck. Cancer 94(3):730–737. doi: 10.1002/cncr.10252 PubMedCrossRefGoogle Scholar
  8. 8.
    DeLellis R, Lloyd R, Heitz P (2004) World Health Organization classification of tumours. IARC Press, LyonGoogle Scholar
  9. 9.
    Salmenkivi K, Heikkila P, Haglund C, Arola J (2004) Malignancy in pheochromocytomas. Apmis 112(9):551–559. doi: 10.1111/j.1600-0463.2004.apm1120901.x PubMedCrossRefGoogle Scholar
  10. 10.
    Jafri M, Whitworth J, Rattenberry E et al (2013) Evaluation of SDHB, SDHD and VHL gene susceptibility testing in the assessment of individuals with non-syndromic phaeochromocytoma, paraganglioma and head and neck paraganglioma. Clin Endocrinol (Oxf) 78(6):898–906. doi: 10.1111/cen.12074 CrossRefGoogle Scholar
  11. 11.
    Baysal BE, Ferrell RE, Willett-Brozick JE et al (2000) Mutations in SDHD, a mitochondrial complex II gene. Hered Paraganglioma Sci 287(5454):848–851Google Scholar
  12. 12.
    Astuti D, Latif F, Dallol A et al (2001) Gene mutations in the succinate dehydrogenase subunit SDHB cause susceptibility to familial pheochromocytoma and to familial paraganglioma. Am J Hum Genet 69(1):49–54. doi: 10.1086/321282 PubMedCentralPubMedCrossRefGoogle Scholar
  13. 13.
    Boedeker CC, Hensen EF, Neumann HP et al (2013) Genetics of hereditary head and neck paragangliomas. Head Neck. doi: 10.1002/hed.23436 PubMedGoogle Scholar
  14. 14.
    Hensen EF, Jordanova ES, van Minderhout IJ et al (2004) somatic loss of maternal chromosome 11 causes parent-of-origin-dependent inheritance in SDHD-linked paraganglioma and phaeochromocytoma families. Oncogene 23(23):4076–4083. doi: 10.1038/sj.onc.1207591 PubMedCrossRefGoogle Scholar
  15. 15.
    Kunst HP, Rutten MH, de Monnink JP et al (2011) SDHAF2 (PGL2-SDH5) and hereditary head and neck paraganglioma. Clin Cancer 17(2):247–254. doi: 10.1158/1078-0432.CCR-10-0420 CrossRefGoogle Scholar
  16. 16.
    Myssiorek D, Ferlito A, Silver CE, Rodrigo JP, Baysal BE, Fagan JJ, Suarez C, Rinaldo A (2008) Screening for familial paragangliomas. Oral Oncol 44(6):532–537. doi: 10.1016/j.oraloncology.2007.06.010 PubMedCrossRefGoogle Scholar
  17. 17.
    Offergeld C, Brase C, Yaremchuk S et al (2012) Head and neck paragangliomas: clinical and molecular genetic classification. Clinics (Sao.Paulo) 67((Suppl 1)):19–28CrossRefGoogle Scholar
  18. 18.
    Kollert M, Minovi AA, Draf W, Bockmuhl U (2006) Cervical paragangliomas-tumor control and long-term functional results after surgery. Skull Base 16(4):185–191. doi: 10.1055/s-2006-950386 PubMedCentralPubMedCrossRefGoogle Scholar
  19. 19.
    Chino JP, Sampson JH, Tucci DL, Brizel DM, Kirkpatrick JP (2009) Paraganglioma of the head and neck: long-term local control with radiotherapy. Am J Clin Oncol 32(3):304–307. doi: 10.1097/COC.0b013e318187dd94 PubMedCrossRefGoogle Scholar
  20. 20.
    King KS, Chen CC, Alexopoulos DK et al (2011) Functional imaging of SDHx-related head and neck paragangliomas: comparison of 18F-fluorodihydroxyphenylalanine, 18F-fluorodopamine, 18F-fluoro-2-deoxy-d-glucose PET, 123I-metaiodobenzylguanidine scintigraphy, and 111In-pentetreotide scintigraphy. J Clin Endocrinol Metab 96(9):2779–2785. doi: 10.1210/jc.2011-0333 PubMedCentralPubMedCrossRefGoogle Scholar
  21. 21.
    Shamblin WR, ReMine WH, Sheps SG, Harrison EG Jr (1971) Carotid body tumor (chemodectoma). Clinicopathologic analysis of ninety cases. Am J Surg 122(6):732–739PubMedCrossRefGoogle Scholar
  22. 22.
    Kunzel J, Iro H, Hornung J, Koch M, Brase C, Klautke G, Zenk J (2012) Function-preserving therapy for jugulotympanic paragangliomas: a retrospective analysis from 2000 to 2010. Laryngoscope 122(7):1545–1551. doi: 10.1002/lary.23268 PubMedCrossRefGoogle Scholar
  23. 23.
    Suarez C, Rodrigo JP, Boedeker CC et al (2013) Jugular and vagal paragangliomas: systematic study of management with surgery and radiotherapy. Head Neck 35(8):1195–1204. doi: 10.1002/hed.22976 PubMedCrossRefGoogle Scholar
  24. 24.
    Suarez C, Rodrigo JP, Mendenhall WM et al (2014) Carotid body paragangliomas: a systematic study on management with surgery and radiotherapy. Eur Arch Otorhinolaryngol 271(1):23–34. doi: 10.1007/s00405-013-2384-5 PubMedCrossRefGoogle Scholar
  25. 25.
    Charlson ME, Pompei P, Ales KL, MacKenzie CR (1987) A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis 40(5):373–383PubMedCrossRefGoogle Scholar
  26. 26.
    U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER) Center for Biologics Evaluation and Research (CBER) (2007) Guidance for industry: clinical trial endpoints for the approval of cancer drugs and biologics. http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm071590.pdf.3/132013
  27. 27.
    Schemper M, Smith TL (1996) A note on quantifying follow-up in studies of failure time. Control Clin Trials 17(4):343–346PubMedCrossRefGoogle Scholar
  28. 28.
    Stoeckli SJ, Schuknecht B, Alkadhi H, Fisch U (2002) Evaluation of paragangliomas presenting as a cervical mass on color-coded Doppler sonography. Laryngoscope 112(1):143–146. doi: 10.1097/00005537-200201000-00025 PubMedCrossRefGoogle Scholar
  29. 29.
    Mendenhall WM, Amdur RJ, Vaysberg M, Mendenhall CM, Werning JW (2011) Head and neck paragangliomas. Head Neck 33(10):1530–1534. doi: 10.1002/hed.21524 PubMedCrossRefGoogle Scholar
  30. 30.
    Parry DM, Li FP, Strong LC, Carney JA, Carney JA, Schottenfeld D, Reimer RR, Grufferman S (1982) Carotid body tumors in humans: genetics and epidemiology. J Natl Cancer Inst 68(4):573–578PubMedGoogle Scholar
  31. 31.
    Neskey DM, Hatoum G, Modh R, Civantos F, Telischi FF, Angeli SI, Weed D, Sargi Z (2011) Outcomes after surgical resection of head and neck paragangliomas: a review of 61 patients. Skull Base 21(3):171–176. doi: 10.1055/s-0031-1275251 PubMedCentralPubMedCrossRefGoogle Scholar
  32. 32.
    Lack EE, Cubilla AL, Woodruff JM (1979) Paragangliomas of the head and neck region: a pathologic study of tumors from 71 patients. Hum Pathol 10(2):191–218PubMedCrossRefGoogle Scholar
  33. 33.
    Power AH, Bower TC, Kasperbauer J, Link MJ, Oderich G, Cloft H, Young WF Jr, Gloviczki P (2012) Impact of preoperative embolization on outcomes of carotid body tumor resections. J Vasc Surg 56(4):979–989. doi: 10.1016/j.jvs.2012.03.037 PubMedCrossRefGoogle Scholar
  34. 34.
    Duffis EJ, Gandhi CD, Prestigiacomo CJ et al (2012) Head, neck, and brain tumor embolization guidelines. J Neurointerv Surg 4(4):251–255. doi: 10.1136/neurintsurg-2012-010350 PubMedCentralPubMedCrossRefGoogle Scholar
  35. 35.
    Li G, Chang S, Adler JR Jr, Lim M (2007) Irradiation of glomus jugulare tumors: a historical perspective. Neurosurg Focus 23(6):E13. doi: 10.3171/FOC-07/12/E13 PubMedCrossRefGoogle Scholar
  36. 36.
    Luna-Ortiz K, Rascon-Ortiz M, Villavicencio-Valencia V, Granados-Garcia M, Herrera-Gomez A (2005) Carotid body tumors: review of a 20-year experience. Oral Oncol 41(1):56–61. doi: 10.1016/j.oraloncology.2004.06.006 PubMedCrossRefGoogle Scholar
  37. 37.
    Kasper GC, Welling RE, Wladis AR, CaJacob DE, Grisham AD, Tomsick TA, Gluckman JL, Muck PE (2006) A multidisciplinary approach to carotid paragangliomas. Vasc Endovascular Surg 40(6):467–474. doi: 10.1177/1538574406290254 PubMedCrossRefGoogle Scholar
  38. 38.
    De Toma G, Nicolanti V, Plocco M, Cavallaro G, Letizia C, Piccirillo G, Cavallaro A (2000) Baroreflex failure syndrome after bilateral excision of carotid body tumors: an underestimated problem. J Vasc Surg 31(4):806–810. doi: 10.1067/mva.2000.103789 PubMedCrossRefGoogle Scholar
  39. 39.
    Burnichon N, Abermil N, Buffet A, Favier J, Gimenez-Roqueplo AP (2012) The genetics of paragangliomas. Eur Ann Otorhinolaryngol Head Neck Dis 129(6):315–318. doi: 10.1016/j.anorl.2012.04.007 PubMedCrossRefGoogle Scholar
  40. 40.
    Hermsen MA, Sevilla MA, Llorente JL et al (2010) Relevance of germline mutation screening in both familial and sporadic head and neck paraganglioma for early diagnosis and clinical management. Cell Oncol 32(4):275–283PubMedGoogle Scholar
  41. 41.
    Lima J, Feijao T, Ferreira da Silva A et al (2007) High frequency of germline succinate dehydrogenase mutations in sporadic cervical paragangliomas in northern Spain: mitochondrial succinate dehydrogenase structure–function relationships and clinical–pathological correlations. J Clin Endocrinol Metab 92(12):4853–4864. doi: 10.1210/jc.2007-0640 PubMedCrossRefGoogle Scholar
  42. 42.
    Timmers HJ, Taieb D, Pacak K (2012) Current and future anatomical and functional imaging approaches to pheochromocytoma and paraganglioma. Horm Metab Res 44(5):367–372. doi: 10.1055/s-0031-1299712 PubMedCrossRefGoogle Scholar
  43. 43.
    Hallett JW Jr, Nora JD, Hollier LH, Cherry KJ Jr, Pairolero PC (1988) Trends in neurovascular complications of surgical management for carotid body and cervical paragangliomas: a fifty-year experience with 153 tumors. J Vasc Surg 7(2):284–291PubMedCrossRefGoogle Scholar
  44. 44.
    Schick B, Draf W, Kahle G (1998) Jugulotympanic paraganglioma: therapy concepts under development. Laryngorhinootologie 77(8):434–443. doi: 10.1055/s-2007-997004 PubMedCrossRefGoogle Scholar
  45. 45.
    Rattenberry E, Vialard L, Yeung A et al (2013) A comprehensive next generation sequencing-based genetic testing strategy to improve diagnosis of inherited pheochromocytoma and paraganglioma. J Clin Endocrinol Metab 98(7):E1248–E1256. doi: 10.1210/jc.2013-1319 PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • T. Anttila
    • 1
  • V. Häyry
    • 1
  • T. Nicoli
    • 1
  • J. Hagström
    • 2
  • K. Aittomäki
    • 3
    • 4
  • P. Vikatmaa
    • 5
  • M. Niemelä
    • 6
  • K. Saarilahti
    • 7
  • A. Mäkitie
    • 1
  • L. J. Bäck
    • 1
  1. 1.Department of Otorhinolaryngology-Head and Neck SurgeryHelsinki University Central Hospital and University of HelsinkiHelsinkiFinland
  2. 2.Department of Pathology and Oral PathologyHaartman Institute and HUSLAB, University of Helsinki and Helsinki University Central HospitalHelsinkiFinland
  3. 3.Department of Clinical GeneticsHUSLAB, Helsinki University Central HospitalHelsinkiFinland
  4. 4.Genome-Scale Biology Research ProgramUniversity of HelsinkiHelsinkiFinland
  5. 5.Department of Vascular SurgeryHelsinki University Central HospitalHelsinkiFinland
  6. 6.Department of NeurosurgeryHelsinki University Central HospitalHelsinkiFinland
  7. 7.Department of OncologyHelsinki University Central HospitalHelsinkiFinland

Personalised recommendations