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Date Published:
09/10/2023
Online Published:
09/10/2023
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Views PDF: 1268
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Tran, V. B., Nguyen, D. M., & Le, T. T. (2023). The state of the art in diagnosis and management of head and neck paragangliomas. Vietnam Journal of Otorhinolaryngology - Head and Neck Surgery, 68(61), 41-57. https://doi.org/10.60137/tmhvn.v68i61.64
The state of the art in diagnosis and management of head and neck paragangliomas
Main Article Content
Abstract
Background: The management of head and neck paragangliomas has changed significantly as a result of increased understanding of the genetic and pathophysiologic basis of this disease. Objective: We summarize the recent advances regarding molecular genetics, along with updated recommendations on workup, treatment, and surveillance of these tumors. Method: The literature search was undertaken with PubMed. The search terms "paraganglioma", "glomus tumor", "head and neck", "genetics", "endocrinology", "investigation", and "treatment" were used. Results: HNPGLs are predominantly associated with germline mutations in the succinate dehydrogenase (SDHx) gene family, in which germline SDHD and SDHB mutations carry an increased risk for multifocal primary disease and metastatic disease, respectively. Genetic testing is recommended for all patients. Gallium 68 tetraazacyclododecane tetraacetic acid-octreotate has high sensitivity and is recommended as first-line imaging in patients with head and neck paragangliomas with concern for multifocal and metastatic disease, and in candidates for targeted peptide-receptor therapy. Conservative management is the first choice treatment for small asymptomatic non secreting paragangliomas, otherwise, resection is preferred for catecholamine-secreting tumors and those that are locally symptomatic from tumor bulk. Radiotherapy is indicated for non-catecholamine secreting paragangliomas where resection would require extensive sacrifice of critical vascular and/or neural structures, and for those with recurrent tumors after previous surgery. Theranostics is proving to be a promising and viable option for patients with locally unresectable or metastatic disease. Patients with SDHx mutations should undergo long-term biochemical screening and whole-body imaging. Conclusion: Head and neck paragangliomas are rare, typically indolent neuroendocrine tumors and predominantly associated with germline mutations in the SDHx gene family. Recently, the management paradigms have changed significantly due to a better understanding regarding pathophysiologic and natural course of these tumors. Keeping abreast of the latest recommendations will help otolaryngologists appropriately manage this challenging disease.
Article Details
Keywords
paraganglioma, glomus jugulare, glomus tympanicum, carotid body tumor, SDHx
References
1. El-Naggar AK, C.J., Grandis JR, Takata T, Slootweg PJ, editors, WHO classification of tumours of the head and neck. 4th ed. 2017, Lyon: IARC Press.
2. Carty, S.E. and W.F. Young, Paragangliomas: Epidemiology, clinical presentation, diagnosis, and histology, in Uptodate, P.Y. Wen, et al., Editors. 2018. Available from: https://www.uptodate.com/contents/paragangliomas-epidemiology-clinical-presentation-diagnosis-and-histology.
3. Williams, M.D., Paragangliomas of the Head and Neck: An Overview from Diagnosis to Genetics. Head Neck Pathol, 2017. 11(3): p. 278-287.
4. Cass, N.D., et al., The Changing Paradigm of Head and Neck Paragangliomas: What Every Otolaryngologist Needs to Know. Ann Otol Rhinol Laryngol, 2020. 129(11): p. 1135-1143.
5. Lin, E.P., et al., Head and Neck Paragangliomas: An Update on the Molecular Classification, State-of-the-Art Imaging, and Management Recommendations. Radiol Imaging Cancer, 2022. 4(3): p. e210088.
6. Cleere, E.F., et al., Contemporary management of paragangliomas of the head and neck. Laryngoscope Investig Otolaryngol, 2022. 7(1): p. 93-107.
7. Rao, A.B., K.K. Koeller, and C.F. Adair, From the archives of the AFIP. Paragangliomas of the head and neck: radiologic-pathologic correlation. Armed Forces Institute of Pathology. Radiographics, 1999. 19(6): p. 1605-32.
8. Gulya, A.J., The glomus tumor and its biology. Laryngoscope, 1993. 103(11 Pt 2 Suppl 60): p. 7-15.
9. Harrison, L. and R. Corbridge, Active surveillance management of head and neck paragangliomas: case series and review of the literature. J Laryngol Otol, 2017. 131(7): p. 580-584.
10. Papathomas, T.G., et al., SDHB/SDHA immunohistochemistry in pheochromocytomas and paragangliomas: a multicenter interobserver variation analysis using virtual microscopy: a Multinational Study of the European Network for the Study of Adrenal Tumors (ENS@T). Mod Pathol, 2015. 28(6): p. 807-21.
11. Lenders, J.W., et al., Pheochromocytoma and paraganglioma: an endocrine society clinical practice guideline. J Clin Endocrinol Metab, 2014. 99(6): p. 1915-42.
12. Lloyd, S., et al., British Skull Base Society Clinical Consensus Document on Management of Head and Neck Paragangliomas. Otolaryngol Head Neck Surg, 2020. 163(3): p. 400-409.
13. Smith, J.D., et al., Head and neck paragangliomas: A two-decade institutional experience and algorithm for management. Laryngoscope Investig Otolaryngol, 2017. 2(6): p. 380-389.
14. Neumann, H.P.H., W.F. Young, Jr., and C. Eng, Pheochromocytoma and Paraganglioma. N Engl J Med, 2019. 381(6): p. 552-565.
15. Taieb, D. and K. Pacak, New Insights into the Nuclear Imaging Phenotypes of Cluster 1 Pheochromocytoma and Paraganglioma. Trends Endocrinol Metab, 2017. 28(11): p. 807-817.
16. Galan, S.R. and P.H. Kann, Genetics and molecular pathogenesis of pheochromocytoma and paraganglioma. Clin Endocrinol (Oxf), 2013. 78(2): p. 165-75.
17. Boedeker, C.C., et al., Genetics of hereditary head and neck paragangliomas. Head Neck, 2014. 36(6): p. 907-16.
18. Carty, S.E., W.F. Young, and K. Oh, Paragangliomas: Treatment of locoregional disease, in Uptodate, P.Y. wen, et al., Editors. 2018. Available from: https://www.uptodate.com/contents/paragangliomas-treatment-of-locoregional-disease.
19. Lenders, J.W., et al., Biochemical diagnosis of pheochromocytoma: which test is best? JAMA, 2002. 287(11): p. 1427-34.
20. Taieb, D., et al., Current approaches and recent developments in the management of head and neck paragangliomas. Endocr Rev, 2014. 35(5): p. 795-819.
21. Thelen, J. and A.A. Bhatt, Multimodality imaging of paragangliomas of the head and neck. Insights Imaging, 2019. 10(1): p. 29.
22. Taieb, D., et al., European Association of Nuclear Medicine Practice Guideline/Society of Nuclear Medicine and Molecular Imaging Procedure Standard 2019 for radionuclide imaging of phaeochromocytoma and paraganglioma. Eur J Nucl Med Mol Imaging, 2019. 46(10): p. 2112-2137.
23. Ryder, S.J., et al., PET detectives: Molecular imaging for phaeochromocytomas and paragangliomas in the genomics era. Clin Endocrinol (Oxf), 2021. 95(1): p. 13-28.
24. Janssen, I., et al., 68Ga-DOTATATE PET/CT in the Localization of Head and Neck Paragangliomas Compared with Other Functional Imaging Modalities and CT/MRI. J Nucl Med, 2016. 57(2): p. 186-91.
25. Janssen, I., et al., Superiority of [68Ga]-DOTATATE PET/CT to Other Functional Imaging Modalities in the Localization of SDHB-Associated Metastatic Pheochromocytoma and Paraganglioma. Clin Cancer Res, 2015. 21(17): p. 3888-95.
26. Chang, C.A., et al., (68)Ga-DOTATATE and (18)F-FDG PET/CT in Paraganglioma and Pheochromocytoma: utility, patterns and heterogeneity. Cancer Imaging, 2016. 16(1): p. 22.
27. Lenders, J.W.M., et al., Genetics, diagnosis, management and future directions of research of phaeochromocytoma and paraganglioma: a position statement and consensus of the Working Group on Endocrine Hypertension of the European Society of Hypertension. J Hypertens, 2020. 38(8): p. 1443-1456.
28. van Nederveen, F.H., et al., An immunohistochemical procedure to detect patients with paraganglioma and phaeochromocytoma with germline SDHB, SDHC, or SDHD gene mutations: a retrospective and prospective analysis. Lancet Oncol, 2009. 10(8): p. 764-71.
29. Valero, C., I. Ganly, and J.P. Shah, Head and neck paragangliomas: 30-year experience. Head Neck, 2020. 42(9): p. 2486-2495.
30. Szymanska, A., et al., Diagnosis and management of multiple paragangliomas of the head and neck. Eur Arch Otorhinolaryngol, 2015. 272(8): p. 1991-9.
31. Myssiorek, D., et al., Screening for familial paragangliomas. Oral Oncol, 2008. 44(6): p. 532-7.
32. Capatina, C., et al., The management of head-and-neck paragangliomas. Endocr Relat Cancer, 2013. 20(5): p. R291-305.
33. Jackson, R.S., et al., The Effects of Preoperative Embolization on Carotid Body Paraganglioma Surgery: A Systematic Review and Meta-analysis. Otolaryngol Head Neck Surg, 2015. 153(6): p. 943-50.
34. Rijken, J.A., et al., Evolving management strategies in head and neck paragangliomas: A single-centre experience with 147 patients over a 60-year period. Clin Otolaryngol, 2019. 44(5): p. 836-841.
35. Lozano, F.S., et al., Simple and complex carotid paragangliomas. Three decades of experience and literature review. Head Neck, 2020. 42(12): p. 3538-3550.
36. Jansen, T.T.G., et al., A meta-analysis on the surgical management of paraganglioma of the carotid body per Shamblin class. Clin Otolaryngol, 2018. 43(4): p. 1104-1116.
37. Robertson, V., et al., 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(4): p. 477-486.
38. Shamblin, W.R., et al., Carotid body tumor (chemodectoma). Clinicopathologic analysis of ninety cases. Am J Surg, 1971. 122(6): p. 732-9.
39. Morton, R.P., et al., A role for ipsilateral, selective neck dissection in carotid body tumours. J Laryngol Otol, 2009. 123(8): p. 934-6.
40. Patnaik, U., et al., Long term surgical and hearing outcomes in the management of tympanomastoid paragangliomas. Am J Otolaryngol, 2015. 36(3): p. 382-9.
41. Makiese, O., et al., Jugular foramen paragangliomas: management, outcome and avoidance of complications in a series of 75 cases. Neurosurg Rev, 2012. 35(2): p. 185-94; discussion 194.
42. Suarez, C., et al., Jugular and vagal paragangliomas: Systematic study of management with surgery and radiotherapy. Head Neck, 2013. 35(8): p. 1195-204.
43. Huy, P.T., et al., Evolving concepts in the management of jugular paraganglioma: a comparison of radiotherapy and surgery in 88 cases. Skull Base, 2009. 19(1): p. 83-91.
44. Fayad, J.N., B. Keles, and D.E. Brackmann, Jugular foramen tumors: clinical characteristics and treatment outcomes. Otol Neurotol, 2010. 31(2): p. 299-305.
45. Jansen, T.T.G., et al., Surgery, radiotherapy or a combined modality for jugulotympanic paraganglioma of Fisch class C and D. Clin Otolaryngol, 2018. 43(6): p. 1566-1572.
46. Hinerman, R.W., et al., Definitive radiotherapy in the management of paragangliomas arising in the head and neck: a 35-year experience. Head Neck, 2008. 30(11): p. 1431-8.
47. Ivan, M.E., et al., A meta-analysis of tumor control rates and treatment-related morbidity for patients with glomus jugulare tumors. J Neurosurg, 2011. 114(5): p. 1299-305.
48. Gilbo, P., et al., Radiotherapy for benign head and neck paragangliomas: a 45-year experience. Cancer, 2014. 120(23): p. 3738-43.
49. Lee, J.H., et al., National Cancer Data Base report on malignant paragangliomas of the head and neck. Cancer, 2002. 94(3): p. 730-7.
50. Hamidi, O., et al., Malignant Pheochromocytoma and Paraganglioma: 272 Patients Over 55 Years. J Clin Endocrinol Metab, 2017. 102(9): p. 3296-3305.
51. Javidiparsijani, S., et al., Is Regional Lymph Node Metastasis of Head and Neck Paraganglioma a Sign of Aggressive Clinical Behavior: A Clinical/Pathologic Review. Ear Nose Throat J, 2021. 100(6): p. 447-453.
52. Huang, H., et al., Treatment of malignant pheochromocytoma/paraganglioma with cyclophosphamide, vincristine, and dacarbazine: recommendation from a 22-year follow-up of 18 patients. Cancer, 2008. 113(8): p. 2020-8.
53. Moskovic, D.J., et al., Malignant head and neck paragangliomas: is there an optimal treatment strategy? Head Neck Oncol, 2010. 2: p. 23.
54. Fanciulli, G., et al., Emerging Therapies in Pheochromocytoma and Paraganglioma: Immune Checkpoint Inhibitors in the Starting Blocks. J Clin Med, 2020. 10(1).
55. Jungels, C. and I. Karfis, 131I-metaiodobenzylguanidine and peptide receptor radionuclide therapy in pheochromocytoma and paraganglioma. Curr Opin Oncol, 2021. 33(1): p. 33-39.
56. Jaiswal, S.K., et al., 177Lu-DOTATATE therapy in metastatic/inoperable pheochromocytoma-paraganglioma. Endocr Connect, 2020. 9(9): p. 864-873.
57. Pryma, D.A., et al., Efficacy and Safety of High-Specific-Activity (131)I-MIBG Therapy in Patients with Advanced Pheochromocytoma or Paraganglioma. J Nucl Med, 2019. 60(5): p. 623-630.
58. Satapathy, S., B.R. Mittal, and A. Bhansali, 'Peptide receptor radionuclide therapy in the management of advanced pheochromocytoma and paraganglioma: A systematic review and meta-analysis'. Clin Endocrinol (Oxf), 2019. 91(6): p. 718-727.
59. Zandee, W.T., et al., Treatment of inoperable or metastatic paragangliomas and pheochromocytomas with peptide receptor radionuclide therapy using 177Lu-DOTATATE. Eur J Endocrinol, 2019. 181(1): p. 45-53.
60. Kong, G., et al., Efficacy of Peptide Receptor Radionuclide Therapy for Functional Metastatic Paraganglioma and Pheochromocytoma. J Clin Endocrinol Metab, 2017. 102(9): p. 3278-3287.
61. Plouin, P.F., et al., European Society of Endocrinology Clinical Practice Guideline for long-term follow-up of patients operated on for a phaeochromocytoma or a paraganglioma. Eur J Endocrinol, 2016. 174(5): p. G1-G10.
62. Daniel, E., et al., Rapid-sequence MRI for long-term surveillance for paraganglioma and phaeochromocytoma in patients with succinate dehydrogenase mutations. Eur J Endocrinol, 2016. 175(6): p. 561-570.
2. Carty, S.E. and W.F. Young, Paragangliomas: Epidemiology, clinical presentation, diagnosis, and histology, in Uptodate, P.Y. Wen, et al., Editors. 2018. Available from: https://www.uptodate.com/contents/paragangliomas-epidemiology-clinical-presentation-diagnosis-and-histology.
3. Williams, M.D., Paragangliomas of the Head and Neck: An Overview from Diagnosis to Genetics. Head Neck Pathol, 2017. 11(3): p. 278-287.
4. Cass, N.D., et al., The Changing Paradigm of Head and Neck Paragangliomas: What Every Otolaryngologist Needs to Know. Ann Otol Rhinol Laryngol, 2020. 129(11): p. 1135-1143.
5. Lin, E.P., et al., Head and Neck Paragangliomas: An Update on the Molecular Classification, State-of-the-Art Imaging, and Management Recommendations. Radiol Imaging Cancer, 2022. 4(3): p. e210088.
6. Cleere, E.F., et al., Contemporary management of paragangliomas of the head and neck. Laryngoscope Investig Otolaryngol, 2022. 7(1): p. 93-107.
7. Rao, A.B., K.K. Koeller, and C.F. Adair, From the archives of the AFIP. Paragangliomas of the head and neck: radiologic-pathologic correlation. Armed Forces Institute of Pathology. Radiographics, 1999. 19(6): p. 1605-32.
8. Gulya, A.J., The glomus tumor and its biology. Laryngoscope, 1993. 103(11 Pt 2 Suppl 60): p. 7-15.
9. Harrison, L. and R. Corbridge, Active surveillance management of head and neck paragangliomas: case series and review of the literature. J Laryngol Otol, 2017. 131(7): p. 580-584.
10. Papathomas, T.G., et al., SDHB/SDHA immunohistochemistry in pheochromocytomas and paragangliomas: a multicenter interobserver variation analysis using virtual microscopy: a Multinational Study of the European Network for the Study of Adrenal Tumors (ENS@T). Mod Pathol, 2015. 28(6): p. 807-21.
11. Lenders, J.W., et al., Pheochromocytoma and paraganglioma: an endocrine society clinical practice guideline. J Clin Endocrinol Metab, 2014. 99(6): p. 1915-42.
12. Lloyd, S., et al., British Skull Base Society Clinical Consensus Document on Management of Head and Neck Paragangliomas. Otolaryngol Head Neck Surg, 2020. 163(3): p. 400-409.
13. Smith, J.D., et al., Head and neck paragangliomas: A two-decade institutional experience and algorithm for management. Laryngoscope Investig Otolaryngol, 2017. 2(6): p. 380-389.
14. Neumann, H.P.H., W.F. Young, Jr., and C. Eng, Pheochromocytoma and Paraganglioma. N Engl J Med, 2019. 381(6): p. 552-565.
15. Taieb, D. and K. Pacak, New Insights into the Nuclear Imaging Phenotypes of Cluster 1 Pheochromocytoma and Paraganglioma. Trends Endocrinol Metab, 2017. 28(11): p. 807-817.
16. Galan, S.R. and P.H. Kann, Genetics and molecular pathogenesis of pheochromocytoma and paraganglioma. Clin Endocrinol (Oxf), 2013. 78(2): p. 165-75.
17. Boedeker, C.C., et al., Genetics of hereditary head and neck paragangliomas. Head Neck, 2014. 36(6): p. 907-16.
18. Carty, S.E., W.F. Young, and K. Oh, Paragangliomas: Treatment of locoregional disease, in Uptodate, P.Y. wen, et al., Editors. 2018. Available from: https://www.uptodate.com/contents/paragangliomas-treatment-of-locoregional-disease.
19. Lenders, J.W., et al., Biochemical diagnosis of pheochromocytoma: which test is best? JAMA, 2002. 287(11): p. 1427-34.
20. Taieb, D., et al., Current approaches and recent developments in the management of head and neck paragangliomas. Endocr Rev, 2014. 35(5): p. 795-819.
21. Thelen, J. and A.A. Bhatt, Multimodality imaging of paragangliomas of the head and neck. Insights Imaging, 2019. 10(1): p. 29.
22. Taieb, D., et al., European Association of Nuclear Medicine Practice Guideline/Society of Nuclear Medicine and Molecular Imaging Procedure Standard 2019 for radionuclide imaging of phaeochromocytoma and paraganglioma. Eur J Nucl Med Mol Imaging, 2019. 46(10): p. 2112-2137.
23. Ryder, S.J., et al., PET detectives: Molecular imaging for phaeochromocytomas and paragangliomas in the genomics era. Clin Endocrinol (Oxf), 2021. 95(1): p. 13-28.
24. Janssen, I., et al., 68Ga-DOTATATE PET/CT in the Localization of Head and Neck Paragangliomas Compared with Other Functional Imaging Modalities and CT/MRI. J Nucl Med, 2016. 57(2): p. 186-91.
25. Janssen, I., et al., Superiority of [68Ga]-DOTATATE PET/CT to Other Functional Imaging Modalities in the Localization of SDHB-Associated Metastatic Pheochromocytoma and Paraganglioma. Clin Cancer Res, 2015. 21(17): p. 3888-95.
26. Chang, C.A., et al., (68)Ga-DOTATATE and (18)F-FDG PET/CT in Paraganglioma and Pheochromocytoma: utility, patterns and heterogeneity. Cancer Imaging, 2016. 16(1): p. 22.
27. Lenders, J.W.M., et al., Genetics, diagnosis, management and future directions of research of phaeochromocytoma and paraganglioma: a position statement and consensus of the Working Group on Endocrine Hypertension of the European Society of Hypertension. J Hypertens, 2020. 38(8): p. 1443-1456.
28. van Nederveen, F.H., et al., An immunohistochemical procedure to detect patients with paraganglioma and phaeochromocytoma with germline SDHB, SDHC, or SDHD gene mutations: a retrospective and prospective analysis. Lancet Oncol, 2009. 10(8): p. 764-71.
29. Valero, C., I. Ganly, and J.P. Shah, Head and neck paragangliomas: 30-year experience. Head Neck, 2020. 42(9): p. 2486-2495.
30. Szymanska, A., et al., Diagnosis and management of multiple paragangliomas of the head and neck. Eur Arch Otorhinolaryngol, 2015. 272(8): p. 1991-9.
31. Myssiorek, D., et al., Screening for familial paragangliomas. Oral Oncol, 2008. 44(6): p. 532-7.
32. Capatina, C., et al., The management of head-and-neck paragangliomas. Endocr Relat Cancer, 2013. 20(5): p. R291-305.
33. Jackson, R.S., et al., The Effects of Preoperative Embolization on Carotid Body Paraganglioma Surgery: A Systematic Review and Meta-analysis. Otolaryngol Head Neck Surg, 2015. 153(6): p. 943-50.
34. Rijken, J.A., et al., Evolving management strategies in head and neck paragangliomas: A single-centre experience with 147 patients over a 60-year period. Clin Otolaryngol, 2019. 44(5): p. 836-841.
35. Lozano, F.S., et al., Simple and complex carotid paragangliomas. Three decades of experience and literature review. Head Neck, 2020. 42(12): p. 3538-3550.
36. Jansen, T.T.G., et al., A meta-analysis on the surgical management of paraganglioma of the carotid body per Shamblin class. Clin Otolaryngol, 2018. 43(4): p. 1104-1116.
37. Robertson, V., et al., 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(4): p. 477-486.
38. Shamblin, W.R., et al., Carotid body tumor (chemodectoma). Clinicopathologic analysis of ninety cases. Am J Surg, 1971. 122(6): p. 732-9.
39. Morton, R.P., et al., A role for ipsilateral, selective neck dissection in carotid body tumours. J Laryngol Otol, 2009. 123(8): p. 934-6.
40. Patnaik, U., et al., Long term surgical and hearing outcomes in the management of tympanomastoid paragangliomas. Am J Otolaryngol, 2015. 36(3): p. 382-9.
41. Makiese, O., et al., Jugular foramen paragangliomas: management, outcome and avoidance of complications in a series of 75 cases. Neurosurg Rev, 2012. 35(2): p. 185-94; discussion 194.
42. Suarez, C., et al., Jugular and vagal paragangliomas: Systematic study of management with surgery and radiotherapy. Head Neck, 2013. 35(8): p. 1195-204.
43. Huy, P.T., et al., Evolving concepts in the management of jugular paraganglioma: a comparison of radiotherapy and surgery in 88 cases. Skull Base, 2009. 19(1): p. 83-91.
44. Fayad, J.N., B. Keles, and D.E. Brackmann, Jugular foramen tumors: clinical characteristics and treatment outcomes. Otol Neurotol, 2010. 31(2): p. 299-305.
45. Jansen, T.T.G., et al., Surgery, radiotherapy or a combined modality for jugulotympanic paraganglioma of Fisch class C and D. Clin Otolaryngol, 2018. 43(6): p. 1566-1572.
46. Hinerman, R.W., et al., Definitive radiotherapy in the management of paragangliomas arising in the head and neck: a 35-year experience. Head Neck, 2008. 30(11): p. 1431-8.
47. Ivan, M.E., et al., A meta-analysis of tumor control rates and treatment-related morbidity for patients with glomus jugulare tumors. J Neurosurg, 2011. 114(5): p. 1299-305.
48. Gilbo, P., et al., Radiotherapy for benign head and neck paragangliomas: a 45-year experience. Cancer, 2014. 120(23): p. 3738-43.
49. Lee, J.H., et al., National Cancer Data Base report on malignant paragangliomas of the head and neck. Cancer, 2002. 94(3): p. 730-7.
50. Hamidi, O., et al., Malignant Pheochromocytoma and Paraganglioma: 272 Patients Over 55 Years. J Clin Endocrinol Metab, 2017. 102(9): p. 3296-3305.
51. Javidiparsijani, S., et al., Is Regional Lymph Node Metastasis of Head and Neck Paraganglioma a Sign of Aggressive Clinical Behavior: A Clinical/Pathologic Review. Ear Nose Throat J, 2021. 100(6): p. 447-453.
52. Huang, H., et al., Treatment of malignant pheochromocytoma/paraganglioma with cyclophosphamide, vincristine, and dacarbazine: recommendation from a 22-year follow-up of 18 patients. Cancer, 2008. 113(8): p. 2020-8.
53. Moskovic, D.J., et al., Malignant head and neck paragangliomas: is there an optimal treatment strategy? Head Neck Oncol, 2010. 2: p. 23.
54. Fanciulli, G., et al., Emerging Therapies in Pheochromocytoma and Paraganglioma: Immune Checkpoint Inhibitors in the Starting Blocks. J Clin Med, 2020. 10(1).
55. Jungels, C. and I. Karfis, 131I-metaiodobenzylguanidine and peptide receptor radionuclide therapy in pheochromocytoma and paraganglioma. Curr Opin Oncol, 2021. 33(1): p. 33-39.
56. Jaiswal, S.K., et al., 177Lu-DOTATATE therapy in metastatic/inoperable pheochromocytoma-paraganglioma. Endocr Connect, 2020. 9(9): p. 864-873.
57. Pryma, D.A., et al., Efficacy and Safety of High-Specific-Activity (131)I-MIBG Therapy in Patients with Advanced Pheochromocytoma or Paraganglioma. J Nucl Med, 2019. 60(5): p. 623-630.
58. Satapathy, S., B.R. Mittal, and A. Bhansali, 'Peptide receptor radionuclide therapy in the management of advanced pheochromocytoma and paraganglioma: A systematic review and meta-analysis'. Clin Endocrinol (Oxf), 2019. 91(6): p. 718-727.
59. Zandee, W.T., et al., Treatment of inoperable or metastatic paragangliomas and pheochromocytomas with peptide receptor radionuclide therapy using 177Lu-DOTATATE. Eur J Endocrinol, 2019. 181(1): p. 45-53.
60. Kong, G., et al., Efficacy of Peptide Receptor Radionuclide Therapy for Functional Metastatic Paraganglioma and Pheochromocytoma. J Clin Endocrinol Metab, 2017. 102(9): p. 3278-3287.
61. Plouin, P.F., et al., European Society of Endocrinology Clinical Practice Guideline for long-term follow-up of patients operated on for a phaeochromocytoma or a paraganglioma. Eur J Endocrinol, 2016. 174(5): p. G1-G10.
62. Daniel, E., et al., Rapid-sequence MRI for long-term surveillance for paraganglioma and phaeochromocytoma in patients with succinate dehydrogenase mutations. Eur J Endocrinol, 2016. 175(6): p. 561-570.