Paragangliom

Paraganglioma, or paragangliom in some languages, is a rare neuroendocrine tumor arising from paraganglia—clusters of neural crest–derived cells associated with the autonomic nervous system. When these tumors occur outside the adrenal medulla they are called extra-adrenal pheochromocytomas or paragangliomas. Most paragangliomas are benign at presentation, but a subset can metastasize. Some secrete catecholamines, causing hypertension and other adrenergic symptoms.

Anatomical distribution: The majority occur in the head and neck region (head and neck paragangliomas, HNPGL), especially the carotid body, glomus jugulare, glomus tympanicum, and vagal paragangliomas. Abdominal and pelvic paragangliomas arise along the sympathetic chain, including the organ of Zuckerkandl near the aorta. Carotid body tumors are the most common HNPGLs.

Genetics: A substantial proportion are familial. Mutations in SDHx genes (SDHB, SDHD, SDHC, SDHA) are common, with SDHB mutations linked to a higher risk of malignancy. Other susceptibility genes include VHL, RET, NF1, and MAX. Genetic testing is recommended for all patients because of implications for relatives and ongoing surveillance.

Clinical features: Head and neck tumors often present as a slow-growing neck mass or cranial nerve deficits, and may cause pulsatile tinnitus or hearing loss when near the ear. Sympathetic (abdominal/pelvic) paragangliomas may secrete catecholamines, causing episodic hypertension, headache, sweating, and palpitations.

Diagnosis: Biochemical testing for catecholamine excess (plasma free metanephrines or urinary fractionated metanephrines) is used if functional disease is suspected. Imaging includes high-resolution MRI or CT for localization, with functional imaging such as 68Ga-DOTATATE PET/CT or 18F-FDOPA PET and MIBG scintigraphy as adjuncts.

Management: Treatment is individualized. Small nonfunctional tumors may be observed. Surgery is the primary option when feasible, sometimes preceded by embolization. Radiotherapy is used for unresectable or skull-base lesions. Perioperative alpha-blockade is used for catecholamine-secreting tumors, with long-term follow-up due to recurrence and risk of bilateral disease.