What is pheochromocytoma?

What is Pheochromocytoma

Pheochromocytoma is a catecholamine-producing neuroendocrine tumor arising from chromaffin cells of the adrenal medulla, with an incidence of 2-8 cases per million per year. 1

Tumor Origin and Classification

• Pheochromocytomas originate specifically from chromaffin cells within the adrenal medulla, distinguishing them from paragangliomas which arise from extra-adrenal paraganglia. 1
• When tumors arise outside the adrenal gland in sympathetic or parasympathetic nervous system tissue, they are termed paragangliomas, leading to the combined designation of pheochromocytomas and paragangliomas (PPGLs). 1
• These are rare neuroendocrine tumors derived from neural crest cells. 2

Hormonal Activity and Clinical Significance

• The defining characteristic is excess catecholamine production, including epinephrine, norepinephrine, dopamine, and their metabolites (metanephrine, normetanephrine, and 3-methoxytyramine). 2
• These tumors can induce life-threatening hypertensive crises, requiring specific management before any surgical or diagnostic intervention. 1
• The potent cardiovascular effects of secreted catecholamines cause serious and potentially lethal complications. 3

Clinical Presentation

• Classic symptoms include paroxysmal or sustained hypertension, severe headaches, palpitations, and profuse sweating resulting from catecholamine excess. 4, 3
• The presentation is highly variable and can mimic many other diseases, making them easy to miss clinically. 4
• Some patients present with adrenal incidentalomas discovered on imaging for unrelated reasons. 3

Malignant Potential

• According to the WHO classification, all PPGLs should be considered to have some malignant potential. 1
• Malignancy can only be definitively diagnosed by the presence of metastases at sites where chromaffin tissue is normally absent (liver, bone, lungs, or lymph nodes). 1
• No single histological or immunohistochemical parameter can predict clinical behavior. 1
• Risk factors for metastatic disease include tumor size ≥5 cm, extra-adrenal location, SDHB germline mutation, and plasma methoxytyramine more than threefold above reference intervals. 1

Genetic Considerations

• Approximately one out of four pheochromocytomas are hereditary entities, making genetic screening important. 4
• Hereditary syndromes include multiple endocrine neoplasia type 2, von Hippel-Lindau syndrome, neurofibromatosis type 1, and succinate dehydrogenase gene mutations. 3
• SDHB mutations are particularly associated with poor prognosis and higher malignancy risk. 1

Diagnostic Approach

• Diagnosis requires biochemical confirmation by measuring plasma-free or urinary-fractionated metanephrines before any imaging or intervention. 1, 5, 6
• Fine needle biopsy is contraindicated due to the risk of hypertensive crisis and tumor spillage. 1, 5, 6
• Imaging with CT or MRI localizes the tumor, while functional imaging (FDG-PET, MIBG scintigraphy, or DOTATATE-PET) helps assess metastatic disease. 1, 5

Treatment Implications

• All patients require preoperative alpha-blockade for at least 10-14 days before surgery to prevent hypertensive crises. 6
• Laparoscopic surgical excision following adequate medical preparation is the definitive treatment and usually curative for benign disease. 4, 7
• Prognosis is excellent with timely removal of benign tumors, but remains poor for metastatic disease. 7, 3