Paraganglioma

Paraganglia are groups of neural crest-derived neuroendocrine cells classified as adrenal or extra-adrenal. Paragangliomas, rare and highly vascular tumors, originate from sympathetic or parasympathetic extra-adrenal autonomic paraganglia. Some refer to them as extra-adrenal pheochromocytomas, while others might designate a pheochromocytoma as an intra-adrenal paraganglioma. About 86% of paragangliomas located outside of the head and neck are sympathetic, secreting norepinephrine, unlike the more differentiated intraabdominal adrenal medulla tumors neuroblastoma and pheochromocytoma which primarily secrete epinephrine. Associated symptoms are episodic hypertension, tachycardia, headache, and diaphoresis. Sympathetic paragangliomas arise anywhere along the sympathetic chain, from the skull base to the bladder and prostate. Most commonly, they occur at the vena cava and the left renal vein junction or the aortic bifurcation near the take-off of the inferior mesenteric artery known as the organ of Zuckerkandl.  Tumors originating from parasympathetic origin are usually asymptomatic and inactive, predominantly located in the neck and skull base along the distribution of the vagus and glossopharyngeal nerves. Most parasympathetic paragangliomas arise from the carotid body (see Carotid Artery Tumor), but some originate from the jugulotympanic and vagal paraganglia. Rarely one originates from the laryngeal paraganglia. Only about 5% of tumors in the neck and skull base secrete catecholamines. Jugulotympanic paragangliomas and carotid body paragangliomas comprise approximately 80% of the paragangliomas in the head and neck.  Paragangliomas commonly present as a single, benign, unilateral tumor, but 1% of sporadic and 20% to 80% of familial cases may have multiple tumors. Instances of malignancy and metastasis are rare. Early identification leading to complete surgical resection is often curative and carries a favorable prognosis. Detecting distant metastases is the only reliable way to assess the biological aggressiveness of paragangliomas.  Paragangliomas are primarily sporadic, although 30% to 50% of cases are familial. Some familial forms may be associated with genetic syndromes, such as variations in the genes encoding different subunits of the succinate dehydrogenase (SDH) enzyme, Carney-Stratakis dyad, neurofibromatosis type 1 (NF1), von Hippel-Lindau (VHL), and multiple endocrine neoplasia types 2A and 2B (MEN2). A surgical biopsy performed during resection is the gold standard for confirming the diagnosis. However, it does not distinguish between pheochromocytomas and paragangliomas. Typically, clinical correlation suffices for diagnosis, aided by imaging and pathological findings of the lesion.