Teaching Topic 

Pheochromocytoma and Paraganglioma 

REVIEW ARTICLE

Pheochromocytoma and Paraganglioma

H.P.H. Neumann, W.F. Young, Jr., and C. Eng

     

With the widespread use of cross-sectional imaging, the incidental discovery of an adrenal mass is becoming common. In addition, asymptomatic cases of pheochromocytoma and paraganglioma are increasingly being discovered on the basis of family and germline-mutation testing.

Clinical Pearls

  What percentage of patients presenting with pheochromocytoma or paraganglioma carry germline mutations?

The evidence to date shows that more than 40% of patients presenting with pheochromocytoma or paraganglioma, irrespective of age at onset and family history, carry germline mutations. Ideally, all persons presenting with these neoplasms should undergo gene-panel testing in the context of genetic counseling, so that prospective gene-specific management can be initiated proactively. If a patient is found to carry a mutation, all first-degree relatives should be offered mutation-specific testing.

  What mutations are common among patients with heritable pheochromocytoma in whom metastatic disease develops?

Most patients with metastatic pheochromocytoma or paraganglioma have sporadic tumors, whereas among patients with heritable pheochromocytoma in whom metastatic disease develops, tumors caused by SDHB mutations account for up to 43% of cases, followed by VHL, SDHD, and NF1 mutations.

Morning Report Questions

Q. What are some of the hallmarks of hereditary pheochromocytoma and paraganglioma?

A. In addition to family history, classic hallmarks of hereditary pheochromocytoma and paraganglioma include an early age at onset, extraadrenal and multiple primary tumors, and associated nonparaganglial tumors. Paragangliomas occurring in an unusual location, such as the organ of Zuckerkandl, thorax, or urinary bladder, should suggest the possibility that the patient has a syndrome associated with the tumor. Anatomical locations of paragangliomas differ widely among the syndromes. In patients with mutations in VHL, NF1, MAX, and TMEM127, pheochromocytomas are common, but retroperitoneal paragangliomas are also observed. Patients with SDHx mutations frequently have head-and-neck paragangliomas, but pheochromocytomas and retroperitoneal paragangliomas are seen mainly in carriers of SDHD, SDHB, and SDHA mutations. The rare thoracic paragangliomas are associated mostly with mutations in SDHB, SDHD, or VHL.

Q. What is the standard surgical approach for pheochromocytoma?

A. Until 1996, the surgical approach for pheochromocytoma was open laparotomy and removal of the entire adrenal gland with the tumor. On the basis of anecdotal evidence from many centers in the United States, Europe, and Asia, this procedure is still frequently performed. In 1996, Gagner and colleagues removed a pheochromocytoma endoscopically. Over the subsequent decades, endoscopic technology with transabdominal or retroperitoneal access replaced the open surgical approach and became standard practice. An important question is whether screening for mutations should be performed before a pheochromocytoma is resected. Bilateral adrenal tumors can occur metachronously, with intervals of more than a decade, especially in patients with RET germline mutations. Thus, operative planning for preservation of sufficient adrenal cortex will be guided by the results of gene testing. Approximately one third of one adrenal gland is sufficient for normal glucocorticoid and mineralocorticoid secretion.