paragangliomas

Paragangliomas are rare neuroendocrine tumors arising from paraganglia of the autonomic nervous system. When located outside the adrenal glands they are paragangliomas; when in the adrenal medulla they are pheochromocytomas. Most paragangliomas occur in the head and neck along the carotid body or at the jugulotympanic region; others arise in the abdomen or pelvis from sympathetic paraganglia and may secrete catecholamines.

Approximately 30–40% are hereditary. Mutations in SDHB, SDHD, SDHC, and SDHA, as well as VHL, RET, NF1, and MAX, predispose to disease. SDHB mutations are associated with higher malignancy risk. SDHD shows paternal imprinting. Patients may harbor multiple tumors in familial cases.

Secretory tumors can cause hypertension, headaches, palpitations, and sweating; nonsecretory tumors may present as a mass or due to local effects. Diagnosis uses biochemical testing of plasma free metanephrines or urinary fractionated metanephrines, followed by anatomical imaging with MRI or CT. Functional imaging (e.g., 68Ga-DOTATATE PET/CT) is highly sensitive; MIBG or FDG PET may help in selected situations.

Localized disease is treated by surgical resection, with preoperative alpha-adrenergic blockade for catecholamine-secreting tumors. Radiotherapy is an option for unresectable or residual lesions. Metastatic disease may respond to chemotherapy (e.g., cyclophosphamide, vincristine, dacarbazine) or targeted radioligand therapy in somatostatin receptor–positive tumors.

Prognosis varies; head and neck tumors without metastasis have favorable outcomes, whereas metastatic disease carries poorer prognosis. Because of hereditary risk, patients require lifelong follow-up with periodic biochemistry and imaging, and family members should be offered genetic counseling and testing.