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Clinical characteristics and outcomes of SDHB-related pheochromocytoma and paraganglioma in children and adolescents



Pheochromocytomas/paragangliomas (PHEOs/PGLs) are rare in children with only a few SDHB mutation-related cases. Previous studies on children were conducted in small cohorts. This large set of pediatric patients provides robust data in the evaluation of clinical outcomes.


Sixty-four pediatric PHEO/PGL patients with SDHB germline mutations were included in the present study. The clinical presentation, disease course, and survival rate were evaluated.


Thirty-eight males and 26 females were diagnosed with PHEO/PGL at a median age of 13 years. The majority of patients displayed norepinephrine hypersecretion and 73.44% initially presented with a solitary tumor. Metastases developed in 70% of patients at the median age of 16 years and were mostly diagnosed first 2 years and in years 12–18 post-diagnosis. The presence of metastases at the time of diagnosis had a strong negative impact on survival in males but not in females. The estimated 5-, 10-, and 20-year survival rates were 100%, 97.14%, and 77.71%, respectively.


The present report has highlighted several important aspects in the management of pediatric patients with SDHB mutations associated-PHEO/PGL. Initial diagnostic evaluation of SDHB mutation carriers should be started at age of 5–6 years with initial work-up focusing on abdominal region. Thorough follow-up is crucial first 2 years post-diagnosis and more frequent follow-ups are needed in years 10–20 post-diagnosis due to the increased risk of metastases. Although this age group developed metastasis as early as 5 years from diagnosis, we have shown that the overall 20-year prognosis and survival are good.

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  1. Amar L, Bertherat J, Baudin E et al (2005) Genetic testing in pheochromocytoma or functional paraganglioma. J Clin Oncol 23:8812–8818.

  2. Amar L, Baudin E, Burnichon N et al (2007) Succinate dehydrogenase B gene mutations predict survival in patients with malignant pheochromocytomas or paragangliomas. J Clin Endocrinol Metab 92:3822–3828.

  3. Armstrong R, Sridhar M, Greenhalgh KL et al (2008) Phaeochromocytoma in children. Arch Dis Child 93:899–904.

  4. Assadipour Y, Sadowski SM, Alimchandani M et al (2017) SDHB mutation status and tumor size but not tumor grade are important predictors of clinical outcome in pheochromocytoma and abdominal paraganglioma. Surgery 161:230–239.

  5. Babic B, Patel D, Aufforth R et al (2017) Pediatric patients with pheochromocytoma and paraganglioma should have routine preoperative genetic testing for common susceptibility genes in addition to imaging to detect extra-adrenal and metastatic tumors. Surgery 161:220–227.

  6. Barontini M, Levin G, Sanso G (2006) Characteristics of pheochromocytoma in a 4- to 20-year-old population. Ann NY Acad Sci 1073:30–37.

  7. Bausch B, Wellner U, Bausch D et al (2014) Long-term prognosis of patients with pediatric pheochromocytoma. Endocr Relat Cancer 21:17–25.

  8. Baysal BE, Willett-Brozick JE, Lawrence EC et al (2002) Prevalence of SDHB, SDHC, and SDHD germline mutations in clinic patients with head and neck paragangliomas. J Med Genet 39:178–183.

  9. Beltsevich DG, Kuznetsov NS, Kazaryan AM, Lysenko MA (2004) Pheochromocytoma surgery: epidemiologic peculiarities in children. World J Surg 28:592–596.

  10. Benn DE, Gimenez-Roqueplo AP, Reilly JR et al (2006) Clinical presentation and penetrance of pheochromocytoma/paraganglioma syndromes. J Clin Endocrinol Metab 91:827–836.

  11. Bissada NK, Safwat AS, Seyam RM et al (2008) Pheochromocytoma in children and adolescents: a clinical spectrum. J Pediatr Surg 43:540–543.

  12. Brouwers FM, Eisenhofer G, Tao JJ, Kant JA, Adams KT, Linehan WM, Pacak K (2006) High frequency of SDHB germline mutations in patients with malignant catecholamine-producing paragangliomas: implications for genetic testing. J Clin Endocrinol Metab 91:4505–4509.

  13. Cascon A, Inglada-Pérez L, Comino-Méndez I et al (2013) Genetics of pheochromocytoma and paraganglioma in Spanish pediatric patients. Endocr Relat Cancer 20:L1–6.

  14. Choat H, Derrevere K, Knight L, Brown W, Mack EH (2014) SDHB-associated paraganglioma in a pediatric patient and literature review on hereditary pheochromocytoma-paraganglioma syndromes. Case Rep Endocrinol 2014:502734.

  15. Ciftci AO, Tanyel FC, Senocak ME, Buyukpamukcu N (2001) Pheochromocytoma in children. J Pediatr Surg 36:447–452.

  16. Comino-Mendez I, Gracia-Aznárez FJ, Schiavi F et al (2011) Exome sequencing identifies MAX mutations as a cause of hereditary pheochromocytoma. Nat Genet 43:663–667.

  17. Crona J, Lamarca A, Ghosal S, Welin S, Skogseid B, Pacak K (2019) Genotype-phenotype correlations in pheochromocytoma and paraganglioma. Endocr Relat Cancer.

  18. Darr R, Zöphel K, Eisenhofer G et al (2012) Combined use of 68Ga-DOTATATE and 18F-FDG PET/CT to localize a bronchial carcinoid associated with ectopic ACTH syndrome. J Clin Endocrinol Metab 97:2207–2208.

  19. De Krijger RR, Van Nederveen FH, Korpershoek E, De Herder WW, De Muinck Keizer-Schrama SM, Dinjens WN (2006) Frequent genetic changes in childhood pheochromocytomas. Ann NY Acad Sci 1073:166–176.

  20. Ein SH, Shandling B, Wesson D, Filler R (1990) Recurrent pheochromocytomas in children. J Pediatr Surg 25:1063–1065.

  21. Fishbein L, Leshchiner I, Walter V et al (2017) Comprehensive molecular characterization of pheochromocytoma and paraganglioma. Cancer Cell 31:181–193.

  22. Gimenez-Roqueplo AP, Favier J, Rustin P et al (2003) Mutations in the SDHB gene are associated with extra-adrenal and/or malignant phaeochromocytomas. Cancer Res 63:5615–5621

  23. Gimenez-Roqueplo AP, Dahia PL, Robledo M (2012) An update on the genetics of paraganglioma, pheochromocytoma, and associated hereditary syndromes. Horm Metab Res 44(5):328–333.

  24. Hensen EF, Bayley JP (2011) Recent advances in the genetics of SDH-related paraganglioma and pheochromocytoma. Fam Cancer 10:355–363.

  25. Hescot S, Curras-Freixes M, Deutschbein T et al (2019) Prognosis of malignant pheochromocytoma and paraganglioma (MAPP-Prono Study): a European network for the study of adrenal tumors retrospective study. J Clin Endocrinol Metab 104:2367–2374.

  26. Jha A, Ling A, Millo C et al (2018) Superiority of (68)Ga-DOTATATE over (18)F-FDG and anatomic imaging in the detection of succinate dehydrogenase mutation (SDHx )-related pheochromocytoma and paraganglioma in the pediatric population. Eur J Nucl Med Mol Imaging 45:787–797.

  27. Jochmanova I, Wolf KI, King KS et al (2017) SDHB-related pheochromocytoma and paraganglioma penetrance and genotype-phenotype correlations. J Cancer Res Clin Oncol 143:1421–1435.

  28. Kaufman BH, Telander RL, van Heerden JA, Zimmerman D, Sheps SG, Dawson B (1983) Pheochromocytoma in the pediatric age group: current status. J Pediatr Surg 18:879–884.

  29. King KS, Prodanov T, Kantorovich V et al (2011) Metastatic pheochromocytoma/paraganglioma related to primary tumor development in childhood or adolescence: significant link to SDHB mutations. J Clin Oncol 29:4137–4142.

  30. Kong G, Grozinsky-Glasberg S, Hofman MS et al (2017) Efficacy of peptide receptor radionuclide therapy for functional metastatic paraganglioma and pheochromocytoma. J Clin Endocrinol Metab 102:3278–3287.

  31. Lloyd RV, Osamura RY, Klöppel G, Rosai J (eds) (2017) WHO classification of tumours of endocrine organs WHO/IARC classification of Tumours, 4th edn. International Agency for Research on Cancer, Lyon

  32. Maher ER, Eng C (2002) The pressure rises: update on the genetics of phaeochromocytoma. Hum Mol Genet 11(2347–2354):1.

  33. Mei L, Khurana A, Al-Juhaishi T, Faber A, Celi F, Smith S, Boikos S (2019) Prognostic factors of malignant pheochromocytoma and paraganglioma: a combined SEER and TCGA databases review. Horm Metab Res 51:451–457.

  34. Neumann HP, Bausch B, McWhinney SR et al (2002) Germ-line mutations in nonsyndromic pheochromocytoma. N Engl J Med 346:1459–1466.

  35. Neumann HP, Pawlu C, Peczkowska M (2004) Distinct clinical features of paraganglioma syndromes associated with SDHB and SDHD gene mutations. JAMA 292:943–951.

  36. Niemeijer ND, Rijken JA, Eijkelenkamp K et al (2017) The phenotype of SDHB germline mutation carriers: a nationwide study. Eur J Endocrinol 177:115–125.

  37. Pamporaki C, Därr R, Bursztyn M et al (2013) Plasma-free vs deconjugated metanephrines for diagnosis of phaeochromocytoma. Clin Endocrinol (Oxf) 79:476–483.

  38. Pham TH, Moir C, Thompson GB et al (2006) Pheochromocytoma and paraganglioma in children: a review of medical and surgical management at a tertiary care center. Pediatrics 118:1109–1117.

  39. Rijken JA, Niemeijer ND, Corssmit EP, Jonker MA, Leemans CR, Menko FH, Hensen EF (2016) Low penetrance of paraganglioma and pheochromocytoma in an extended kindred with a germline SDHB exon 3 deletion. Clin Genet 89:128–132.

  40. Ross JH (2000) Pheochromocytoma. Special considerations in children. Urol Clin N Am 27:393–402.

  41. Schovanek J, Martucci V, Wesley R et al (2014) The size of the primary tumor and age at initial diagnosis are independent predictors of the metastatic behavior and survival of patients with SDHB-related pheochromocytoma and paraganglioma: a retrospective cohort study. BMC Cancer 14:523.

  42. Solis DC, Burnichon N, Timmers HJ et al (2009) Penetrance and clinical consequences of a gross SDHB deletion in a large family. Clin Genet 75:354–363.

  43. Spoudeas HA (ed) (2005) Paediatric endocrine tumours. A multi-disciplinary consensus statement of best practice from a working group convened under the auspices of the BSPED and UKCCSG (rare tumour working groups). Novo Nordisk Ltd, West Sussex

  44. Stackpole RH, Melicow MM, Uson AC (1963) Pheochromocytoma in children Report of 9 case and review of the first 100 published cases with follow-up studies. J Pediatr 63:314–330.

  45. Timmers HJ, Kozupa A, Eisenhofer G et al (2007) Clinical presentations, biochemical phenotypes, and genotype-phenotype correlations in patients with succinate dehydrogenase subunit B-associated pheochromocytomas and paragangliomas. J Clin Endocrinol Metab 92:779–786.

  46. Timmers HJ, Gimenez-Roqueplo AP, Mannelli M, Pacak K (2009) Clinical aspects of SDHx-related pheochromocytoma and paraganglioma. Endocr Relat Cancer 16:391–400.

  47. Turkova H, Prodanov T, Maly M et al (2016) Characteristics and outcomes of metastatic SDHB and sporadic pheochromocytoma/paraganglioma: an national institutes of health study. Endocr Pract 22:302–314.

  48. Vicha A, Musil Z, Pacak K (2013) Genetics of pheochromocytoma and paraganglioma syndromes: new advances and future treatment options. Curr Opin Endocrinol Diabetes Obes 20:186–191.

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This work was supported by the Intramural Research Program of the Eunice Kennedy Shriver NICHD, NIH (Grant Z1AHD008735).

Author information

All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by IJ, AMTA, RJSG, CLPM, RW, TP, and KP. The first draft of the manuscript was written by IJ and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Correspondence to Karel Pacak.

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Jochmanova, I., Abcede, A.M.T., Guerrero, R.J.S. et al. Clinical characteristics and outcomes of SDHB-related pheochromocytoma and paraganglioma in children and adolescents. J Cancer Res Clin Oncol (2020).

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  • Pheochromocytoma
  • Paraganglioma
  • SDHB mutation
  • Pediatric oncology