Details

Autor(en) / Beteiligte

• Isaacson, Brandon
• Bullova, Petra
• Frone, Megan
• Click, Arielle
• Hamplova, Barbora
• Rabaglia, Jennifer
• Woodruff, Stacey
• Nwariaku, Fiemu
• Kathuria, Amita
• Pacak, Karel
• Ghayee, Hans K

Titel

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

Ist Teil von

• Endocrine practice, 2016-02, Vol.22 (2), p.190-195

Ort / Verlag

United States

Erscheinungsjahr

2016

Quelle

MEDLINE

Beschreibungen/Notizen

• 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). 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). 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 levels significantly decreased after surgery and radiation. 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-2α but not of HIF-1α 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.