The Joint Annual Scientific Meetings of the Endocrine Society of Australia and the Society for Reproductive Biology 2018

Prevalence of hereditary pheochromocytoma and paraganglioma and associated genotypes within a paediatric and adolescent population: a review of patients presenting to familial cancer services within NSW between 1994-2017. (#171)

Amanda Seabrook 1 , Kathy Tucker 2 , Diana (Dindy) Benn 3 4 , Judy Kirk 5 , Allan Spigelman 6 7 , Rory Clifton-Bligh 3 4
  1. Familial Cancer Service, Royal North Shore Hospital, Sydney, NSW, Australia
  2. Hereditary Cancer Service, Prince of Wales Hospital, Sydney, NSW
  3. Cancer Genetics, The Kolling Institute of Medical Research, Sydney, NSW, Australia
  4. The University of Sydney, Sydney, NSW, Australia
  5. Familial Cancer Service, Westmead Hospital, Sydney, NSW, Australia
  6. Familial Cancer Centre, Hunter New England Local Health District, Newcastle, NSW, Australia
  7. Cancer Genetics Unit, St. Vincent's Hospital , Sydney, NSW, Australia

Phaeochromocytoma and paraganglioma (PPGL) syndromes associated with germline mutations are highly morbid. Published data has consistently demonstrated a high occurrence of tumours due to hereditary PPGL in childhood with a predominance of cluster 1 mutations (VHL and genes relating to the SDH complex). This cluster is associated with more aggressive features including bilateral, multiple and extra-adrenal tumours.1,2,3

As knowledge of these rare syndromes continues to develop and new implicated genes have only recently been discovered, data relating to hereditary PPGL has not been captured in the Australian Paediatric Cancer Registry. The findings of this study will therefore establish for the first time accurate prevalence of PPGL within this demographic within Australia. The outcomes will also give further insight into genotype-phenotype correlations and contribute to the body of evidence used to develop genotype-specific surveillance guidelines.

Objective: The retrospective element of this study established the prevalence of hereditary PPGL, including underlying genotype. Genotypes included VHL, SDHB, SDHD, SDHC, SDHA, RET, NF1, TMEM127 and MAX. In those patients who had not been exhaustively investigated to exclude a germline mutation, multi-gene panel testing was performed.

Methods: Information was collected through ‘TrakGene’. Patient characteristics included age at diagnosis, gender, clinical features. Tumours were classified by hormone secretion profile, tumour number, anatomical location, histological features and benign/malignant. Stored DNA was accessed for further testing, if appropriate. 

Results(prelim): Results from a single centre identified 13 paediatric patients. 9 (69%) carried a germline pathogenic variant: 6 SDHB (of which 5 were extra-adrenal, 5 were multi-focal and 2 were metastatic) and 3 VHL.

Conclusions: PPGLs diagnosed in children and adolescents in Australia are likely to be associated with germline pathogenic variants in VHL or SDHB. These patients should be referred to specialist services for comprehensive perioperative work-up, detection of bilateral, multifocal or metastatic disease, and family counselling.

  1. Pamporaki C, et al.Characteristics of Pediatric vs Adult Pheochromocytomas and Paragangliomas. J Clin Endocrinol Metab. 2017 Apr 1;102(4):1122-1132. doi: 10.1210/jc.2016-3829.
  2. Bausch B, et al. Long-term prognosis of patients with pediatric pheochromocytoma. Endocr Relat Cancer. 2013 Dec 16;21(1):17-25. doi: 10.1530/ERC-13-0415. Print 2014 Feb
  3. King KS, Prodanov T, Kantorovich V, et al. Metastatic Pheochromocytoma/Paraganglioma Related to Primary Tumor Development in Childhood or Adolescence: Significant Link to SDHB Mutations. Journal of Clinical Oncology. 2011;29(31):4137-4142. doi:10.1200/JCO.2011.34.6353.