MON-536 - Functional Head and Neck Paraganglioma in A Patient with SDHB Mutation Background

Background

Pheochromocytomas (PCCs) and paragangliomas (PGLs) are rare neuroendocrine tumors secreting catecholamines and their metabolites. While most cases are sporadic, 40% are associated with hereditary syndromes, including MEN2, VHL, NF, and PGL1-5. PCCs produce both metanephrine and normetanephine, whereas PGLs predominantly produce normetanephrine. About 40% of all PGLs are functional, but only 5% of parasympathetic PGLs are, typically secreting dopamine and its metabolite methoxytyramine and arising from the carotid body or vagal nerve. This case describes a rare functional, normetanephrine-producing parapharyngeal PGL, unrelated to the carotid body, in a patient with an SDHB mutation.

Clinical Case

A 36-year-old male with a family history of PCC and suspected SDHB mutation presented with hypertensive urgency. Cross-sectional imaging showed a 3.5 cm heterogeneous left adrenal mass (40 pre-contrast Hounsfield units). Biochemical profile showed plasma total metanephrines 2742 pg/mL ( < 205), free normetanephrine 2687 pg/mL ( < 148), free metanephrine 55 pg/mL ( < 57), dopamine 106 pg/mL ( < 16), and urine metanephrines 3521 mcg/24h (115-695). Genetic testing confirmed a pathogenic SDHB variant (p.R46*) consistent with PGL4 syndrome.

After alpha-adrenergic blockade with doxazosin, he underwent left adrenalectomy. Pathology revealed a 4.3 cm moderately differentiated PCC (GAPP 6). Post-operatively HTN and elevated catecholamines persisted: plasma total metanephrines 1249 pg/mL, free normetanephrine 1249 pg/mL, free metanephrine < 25 pg/mL, dopamine 31 pg/mL suggesting residual or metastatic disease. Functional imaging with 68Ga-DOTATATE PET/CT showed an avid 3.7 cm right parapharyngeal mass, suspicious for a PGL. Neck MRI confirmed a well-defined 3.9 cm enhancing soft tissue right parapharyngeal mass.

He resumed alpha-adrenergic blockade and underwent surgical resection of the mass. Pathology confirmed a 3 cm PGL (Ki-67 2%). Three days post-resection, plasma total metanephrines and free normetanephrines both decreased to 152 pg/mL and free metanephrines normalized. At his 2 month follow-up, these results remained stable and the patient was normotensive on low-dose amlodipine.

Conclusion

This case describes a rare functional normetanephrine-secreting parapharyngeal PGL in an SDHB mutation carrier, highlighting the need to consider functional HNPGLs in these patients with persistent catecholamine elevations post-adrenalectomy. The vast majority of HNPGLs are non-functional, and those that are functional tend to be dopamine-producing. Normetanephrine-secreting PGLs are exceedingly rare and usually of carotid-body or vagal nerve origin. Patients with familial SHDB mutations require lifelong surveillance for recurrent PGLs, RCC, GIST with ongoing biochemical monitoring, comprehensive genetic evaluation, and advanced functional imaging.

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