The malignancy rate of pheochromocytoma is about 10%. The malignancy rate of paraganglioma is approximately 35%(1).
What Is The Difference Between Paraganglioma & Pheochromocytoma?
Paraganglioma and pheochromocytoma are both neuroendocrine tumors arising from the chromaffin cells, which secrete catecholamine (epinephrine and norepinephrine). They are rare tumors occurring in 2-8 per 1 million persons per year and 0.1% of hypertensive patients.
According to WHO, these tumors are classified based on their location/origin, so they are classified as adrenal medulla tumors or extra-adrenal paraganglia tumors. Pheochromocytoma is the term given to the chromaffin cell tumors found in the adrenal gland, which makes up nearly 85% of all the tumors. The tumors outside of the adrenal gland are known as extra-adrenal pheochromocytomas or paragangliomas, which constitute 15% of all chromaffin cell tumors(1),(2).
While most of these tumors are sporadic, approximately 35% of these are familial in origin making them strongly hereditary. Most of these tumors are found within the abdomen comprising 98% of all the tumors, including both pheochromocytoma and paraganglioma. Paragangliomas can be found anywhere between the base of the skull to the pelvic region, including the head and neck region (along the vagal and glossopharyngeal nerve; also known as carotid body and glomus jugulare body), chest, urinary bladder wall, heart, mediastinum, the organ of Zuckerkandl (around the origin of the inferior mesenteric artery). While pheochromocytomas are mostly sympathetic, paragangliomas can be both sympathetic and parasympathetic. The parasympathetic paragangliomas do not secrete catecholamines and are mostly found in the head and neck region along the vagal and glossopharyngeal nerves(1),(2).
Potential For Malignancy
Paragangliomas are more aggressive with a malignancy rate of around 35%; whereas, pheochromocytomas only show a 10% malignancy rate. It is difficult to isolate a benign tumor from a malignant one. The risk factors for the metastatic disease include tumor size of primary tumor >5 cm (in SDHB related tumors >3.5 cm), extra-adrenal location, presence of SDHB (succinate dehydrogenase subunit genes) mutations, younger age of initial diagnosis and elevated levels of 3-MT. The most common sites of metastasis include the liver, lungs, bones, and lymph nodes. The overall 5-year survival of malignant tumors is approximately 60%(1),(2).
Clinical Features Of Paragangliomas And Pheochromocytomas
Headache is the most common symptom afflicting about 90% of the patients along with excessive sweating (mostly truncal) in about 60-70% of the patients, and pallor in around 27%. The most common triad of symptoms, which include headache, palpitations, and sweating found in patients suffering from hypertension should raise the alarm for these tumors. Other symptoms that the patients may complain of include anxiety, flushing, tremors, weakness, nausea, vomiting, shortness of breath, weight loss, fatigue, panic attacks, and nervousness. Other less common symptoms include fever and constipation. Hypertension is mostly paroxysmal with instances of normal blood pressure, but can also be prolonged hypertension. Some patients may also experience hypotension (due to increased levels of adrenaline there is excessive stimulation of beta-adrenoceptors), postural hypotension, or alternating hypertension and hypotension episodes(2).
These signs and symptoms may occur in severe spells that may frequent from several times a day to few times in a month, their duration may last from few minutes to several days at a time and with time these attacks may become more frequent and the severity also increases with the increase in the size of the tumor. During an attack, patients may experience visual problems and extreme tiredness along with increased urination after an attack(1).
Excess catecholamines may lead to cardiovascular complications, including severe hypertension, cardiac arrhythmias, acute myocardial infarction, pulmonary edema, shock, and heart failure(2).
Management Of Paragangliomas And Pheochromocytomas
The surgical removal of the tumor is the treatment of choice. However, it is important to manage the patients with medications before the surgery to control the levels of circulating catecholamines, which may lead to hypertensive crisis and arrhythmias. The 5-year survival rate of benign pheochromocytoma is greater than 95%(1),(2).
