Abstrakt
Objective: To describe a patient with a germline succinate dehydrogenase (SDHC) gene mutation presenting with primary hyperparathyroidism and a large catechol-amine-producing temporal bone paraganglioma (PGL). Methods: Evaluation of a SDHC mutation-positive PGL tumor biology using staining for tyrosine hydroxylase (TH), hypoxia-inducible factors 1 alpha (HIF-1 alpha) and 2 alpha (HIF-2 alpha).
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-2 alpha but reduced expression of HIF-1 alpha. The remaining skull base PGL was treated with adjuvant radiation therapy.
The patient's normetanephrine levels significantly decreased after surgery and radiation. Conclusion: Here, we report an unusual case of a patient presenting with a germline SDHC mutation-related functional PGL along with concomitant primary hyperparathyroidism.
The present case illustrates that overexpression of HIF-2 alpha but not of HIF-1 alpha is linked to the pathogenesis of SDHC mutation-related PGL, and it may be responsible for the aggressive clinical behavior of a usually indolent course of SDHC-related PGLs.