SAT-080 - A Rare Cause of Paraganglioma

Teaching points:

1. Identify SDHAF2 mutations as a rare cause of multifocal head and neck paragangliomas in familial cases.
2. Define the phenotypic variability associated with SDHAF2-associated paragangliomas and its clinical implications.


Case presentation:
A 58-year-old Uruguayan female with no past medical history presented for evaluation of painless bilateral neck swelling for one year. Carotid ultrasonography revealed bilateral carotid artery masses. Fine-needle aspiration of the right-sided lesion demonstrated atypical cells, prompting further evaluation. MRI showed bilateral avidly enhancing carotid body masses, at the left and right carotid bifurcations. A PET-CT with Dotatate demonstrated intensely avid lesions at the left jugular foramen and bilateral carotid bifurcations, consistent with multifocal paragangliomas. Additional asymmetric radiotracer uptake was noted in the left adrenal gland. Adrenal biochemical evaluation for pheochromocytoma was negative. A repeat biopsy of the neck showed a neuroendocrine tumor with neoplastic changes. As her identical twin had a similar tumor a few years prior, genetic testing was done, revealing a G78R missense mutation of the SDHAF2 gene. The patient remains asymptomatic.

Discussion:
Paragangliomas are rare neuroendocrine tumors, approximately 30–40% of which are associated with germline mutations in succinate dehydrogenase (SDH)–related genes. SDHAF2 mutations are exceptionally rare, accounting for < 1% of hereditary paraganglioma cases, and have been described in only a limited number of families worldwide. Tumor development follows paternal transmission consistent with genomic imprinting. The G78R (Gly78Arg) variant, identified in our patient, has been reported in only two previously described families, highlighting its extreme rarity (PMID 20071235). SDHAF2-associated paragangliomas typically present early in life, in contrast to our patient and her monozygotic twin, both diagnosed in middle age. These tumors are characteristically nonfunctional, thus asymptomatic, and often multifocal, most commonly involving the carotid body or vagal region (PMID 40079348). Active surveillance is appropriate for asymptomatic patients with small tumors, while surgical resection should be considered for larger carotid body lesions, particularly in otherwise healthy individuals. In addition, yearly screening of metanephrines, dopamine and and 3-methoxytyramine levels should be done to assess for adrenal tumors.

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