AN AGGRESSIVE TEMPORAL BONE SDHC PARAGANGLIOMA ASSOCIATED WITH INCREASED HIF-2α SIGNALING

ABSTRACT Objective: To describe a patient with a germline succinate dehydrogenase (SDHC) gene mutation presenting with primary hyperparathyroidism and a large catecholamine-producing temporal bone paraganglioma (PGL). Methods: Evaluation of a SDHC mutation–positive PGL tumor biology using staining for tyrosine hydroxylase (TH), hypoxia-inducible factors 1α (HIF-1α) and 2α (HIF-2α). Results: A 66-year-old man was noted to have a lytic skull base mass during work-up for his primary hyperparathyroidism. Biochemical evaluation with 24-hour urine catecholamines and metanephrines revealed marked elevation of norepinephrine and normetanephrine. Genetic testing revealed a germline SDHC mutation. A partial excision of skull base tumor was performed, which upon further examination revealed PGL. Immunohistochemistry of skull base PGL demonstrated heavy expression of TH and HIF-2α but reduced expression of HIF-1α. The remaining skull base PGL was treated with adjuvant radiation therapy. The patient's normetanephrine ...