Malignant pheochromocytomas arise from the medulla (the central portion of the adrenal gland that is surrounded by the adrenal cortex). These cells produce epinephrine, norepinephrine and dopamine.
About 10% of pheochromocytomas are malignant (cancer). The only way to tell if a pheochromocytoma is malignant is by noting invasion of the tumor into the tissues surrounding the tumor or noting evidence of spread to other parts of the body.
Genetic Mutations
Given that up to 20-30% of patients diagnosed with pheochromocytoma (benign or malignant) harbor a genetic mutation responsible for formation of these tumors, genetic testing is recommended for most patients.
Certain mutations are associated with a higher chance of malignancy. Some mutations leading to the development of a pheochromocytoma also cause other disorders elsewhere in the body.
Common genetic mutations and syndromes associated with pheochromocytoma include:
- Multiple Endocrine Neoplasia types 2A and 2B are caused by a mutation of the RET proto-oncogene on chromosome 10. In addition to developing pheochromocytomas, other tumors may develop in the thyroid, parathyroid glands and elsewhere. Lesions on the skin (café-au-lait spots) and mucosal ganglioneuromas may also appear.
- Von-Hippel Lindau syndrome is caused by a mutation in the VHL gene on chromosome 3. In addition to pheochromocytoma, mutations in the VHL gene lead to retinal angiomas; hemangioblastomas; renal cell carcinomas; islet tumors of the pancreas; and cysts and cystadenomas of the kidney, pancreas and epididymis.
- Neurofibromatosis type 1 (von Recklinghausen’s disease) is caused by a mutation in the NF1 gene on chromosome 17. NF1 is associated with café-au-lait spots, cutaneous neurofibromas, inguinal or axillary freckles, iris hamartomas (Lish nodules), optic-nerve gliomas, dysplasia of sphenoid bone and/or pseudoarthrosis.
- Familial Paraganglioma syndrome is caused by mutations in succinate dehydrogenase A, B, C or D. These mutations cause development of pheochromocytomas and paragangliomas (neuroendocrine tumors outside the adrenal glands that may or may not produce excess adrenaline). Mutations of SDHB are associated with a higher risk of malignant pheochromocytomas and paragangliomas.
- TMEM127 is a gene residing on chromosome 2. It is the most recently described gene associated with development of pheochromocytoma when mutated.
How Is Malignant Pheochromocytoma Discovered?
Pheochromocytomas are most often diagnosed during evaluation for causes of high blood pressure. In other cases, an adrenal mass may be identified on imaging studies ordered to evaluate a different presenting sign or symptom.
If you have been diagnosed with an adrenal disorder or adrenal cancer, would like a second opinion or would like to speak with an endocrine specialist on our Comprehensive Adrenal Program team, please call 614-293-7171 to make an appointment.
Related Resources
Malignant Pheochromocytoma Diagnosis & Staging
Malignant Pheochromocytoma Treatment
Malignant Pheochromocytoma Prognosis
Malignant Pheochromocytoma Treatment Team