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Paragangliomas: Epidemiology, clinical presentation, diagnosis, and histology

Sally E Carty, MD, FACS
William F Young, Jr, MD, MSc
Section Editors
Patrick Y Wen, MD
Jay S Loeffler, MD
André Lacroix, MD
Deputy Editor
Sadhna R Vora, MD


Paragangliomas are rare neuroendocrine tumors that arise from the extraadrenal autonomic paraganglia, small organs consisting mainly of neuroendocrine cells that are derived from the embryonic neural crest and have the ability to secrete catecholamines (figure 1).

Paragangliomas are closely related to pheochromocytomas (which are sometimes referred to as intraadrenal paragangliomas) [1] and are indistinguishable at the cellular level. Sympathetic paragangliomas usually secrete catecholamines and are located in the sympathetic paravertebral ganglia of thorax, abdomen, and pelvis. In contrast, most parasympathetic paragangliomas are nonfunctional and located along the glossopharyngeal and vagal nerves in the neck and at the base of the skull. Catecholamine-secreting paragangliomas often present clinically like pheochromocytomas with hypertension, episodic headache, sweating, and tachycardia. However, the distinction between pheochromocytoma and paraganglioma is an important one because of implications for associated neoplasms, risk for malignancy, and genetic testing.

Even with modern genetic testing, the majority of paragangliomas appear to be sporadic. However, approximately one-third to one-half (in recent series) [2,3] are associated with an inherited syndrome. Some hereditary paragangliomas, particularly those arising in the head and neck, have been linked to mutations in the genes encoding different subunits of the succinate dehydrogenase (SDH) enzyme complex. In addition, susceptibility to pheochromocytomas and paragangliomas is an established component of four genetic syndromes, multiple endocrine neoplasia types 2A and 2B (MEN2), neurofibromatosis type 1 (NF1), von Hippel Lindau (VHL), and Carney-Stratakis dyad.

This topic review will cover the epidemiology, risk factors, molecular pathogenesis, histology, clinical manifestations, diagnosis, and genetic screening issues of paragangliomas arising at a variety of sites in the body. Treatment of paragangliomas, and the genetics, clinical presentation, and treatment of pheochromocytomas are covered elsewhere. (See "Paragangliomas: Treatment of locoregional disease" and "Clinical presentation and diagnosis of pheochromocytoma" and "Pheochromocytoma in genetic disorders" and "Treatment of pheochromocytoma in adults" and "Pheochromocytoma and paraganglioma in children".)


The terms used to describe paragangliomas have varied over time. An adrenal catecholamine-secreting tumor is widely referred to as "pheochromocytoma," although the 2004 World Health Organization (WHO) classification of tumors of endocrine organs designated these tumors as "intraadrenal paragangliomas" rather than pheochromocytomas [1]. Some authors use the term “extra-adrenal pheochromocytoma” to describe a catecholamine-secreting tumor that arises from sympathetic paraganglia outside of the adrenal gland. Others use the collective term pheochromocytoma to describe all tumors arising in the paraganglia of the abdomen (both adrenal and extra-adrenal) and thorax [4]. However, the 2004 WHO classification used the term “extra-adrenal paraganglioma” to denote an extra-adrenal tumor of sympathetic or parasympathetic paraganglia origin, regardless of secretory status [1]. For the purpose of this review, the term paraganglioma will be used to designate both functioning (catecholamine-secreting) and nonfunctioning tumors arising in the paraganglia outside of the adrenal gland, with the term pheochromocytoma limited to those tumors that arise in the adrenal glands.

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Literature review current through: Nov 2017. | This topic last updated: Aug 15, 2017.
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