SUN-264 Head and Neck Paragangliomas in Two Patients With Multiple Endocrine Neoplasia 2B

Abstract Disclosure: J.M. Kaplan: None. C. Jimenez: None. S. Hosseini: None. S.G. Waguespack: None. Background: Multiple endocrine neoplasia type 2B (MEN2B) is a hereditary tumor syndrome primarily caused by the germline p.M918T RET pathogenic variant. It is characterized by nearly 100% penetrance of medullary thyroid carcinoma (MTC) and extra-endocrine features, with pheochromocytoma (PHEO) occurring in 50% of cases. While extra-adrenal paragangliomas (PGL) have been reported in MEN2, to date no cases of head and neck PGL have been described in MEN2B. Case 1: A 30-year-old woman with MEN2B, stage IVC MTC, and PHEO presented for routine follow-up of MTC. Computed tomography (CT) showed slow progression of metastatic disease in the lungs and intrathoracic lymph nodes, with stably rising biochemical tumor markers. However, a newly recognized supraglottic mass, previously subtle and deemed non-pathologic, was noted on imaging. Due to its growth rate and location, surgical excision was pursued. Immunohistochemical evaluation revealed positive staining for synaptophysin, chromogranin, and GATA-3, supporting a diagnosis of paraganglioma; immunohistochemistry for MTC (CEA, TTF1, PAX8) was negative. Follow-up CT at 6 months showed minimal residual tissue at the PGL site. Case 2: A 27-year-old man with MEN2B and stage IVA MTC presented for routine follow-up. He was diagnosed with ACTH-dependent hypercortisolism, manifested by weight gain and hypertension. CT imaging and tumor markers indicated stable MTC and no evidence of PHEO. Given the known association of MTC with ectopic ACTH syndrome, a gallium-68 DOTATATE positron emission tomography scan was performed to identify occult MTC sites. No MTC sites were identified; instead, an intensely avid lesion was detected in the left jugular foramen, consistent with PGL, which was confirmed on magnetic resonance imaging. Serum normetanephrines and metanephrines were within normal limits. The PGL has remained asymptomatic and stable on subsequent investigations. Discussion: These cases represent the first documented instances of head and neck PGLs in MEN2B, both incidentally identified in the third decade of life. Similar to other head and neck paragangliomas, both tumors were hormonally inactive and benign. As survival in patients with MEN2B improves, novel neoplastic findings may start to emerge. Clinicians should consider head and neck PGLs as a potential component of MEN2B clinical phenotype. Presentation: Sunday, July 13, 2025