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Inherited Mutations in Pheochromocytoma and Paraganglioma: Why All Patients Should Be Offered Genetic Testing

  • Endocrine Tumors
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

Pheochromocytomas (PCC) and paragangliomas (PGL) are neuroendocrine tumors that, although rare, are an important cause of secondary hypertension because of the high morbidity and mortality. PCC/PGL are still thought of as the “tumor of tens,” with 10 % being hereditary; however, recent population based studies suggest that up to 32 % of patients have a germline mutation in one of the known common susceptibility genes (including NF1, VHL, RET, SDHB, SDHD, and SDHC). Despite this, most patients in the United States are not referred for clinical genetic testing by their physicians. We aimed to examine the mutation prevalence in a clinic-based population in the United States.

Methods

We performed a retrospective chart review of 139 consecutive patients with PCC/PGL from the medical genetics clinic at the hospital of the University of Pennsylvania from January 2004 through February 2012.

Results

We found a 41 % overall mutation detection rate. Twenty-six percent of the cohort had a mutation in the SDHB or SDHD genes. Of patients with at least one PGL tumor outside the adrenal gland, 53 % had an identified mutation.

Conclusions

Forty-one percent of the cohort had a heritable mutation. The most commonly mutated gene was SDHB, which carries the highest risk of malignancy. These data, together with American Society of Clinical Oncology guidelines suggesting that genetic testing be performed if the risk of a hereditable mutation is at least 10 % or if it will affect medical management, strongly suggest that all patients with PCC/PGL should undergo clinical genetic testing.

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Acknowledgment

Supported in part by the PheoPara Alliance and 2-T32-DK007314-31.

Disclosure

The authors declare no conflict of interest.

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Correspondence to Katherine L. Nathanson MD.

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Fishbein, L., Merrill, S., Fraker, D.L. et al. Inherited Mutations in Pheochromocytoma and Paraganglioma: Why All Patients Should Be Offered Genetic Testing. Ann Surg Oncol 20, 1444–1450 (2013). https://doi.org/10.1245/s10434-013-2942-5

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  • DOI: https://doi.org/10.1245/s10434-013-2942-5

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