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

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

Research output: Contribution to journalArticle

4 Citations (Scopus)

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 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-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.

Original languageEnglish (US)
Pages (from-to)190-195
Number of pages6
JournalEndocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists
Volume22
Issue number2
DOIs
StatePublished - Feb 1 2016

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Paraganglioma
Temporal Bone
Skull Base
Hypoxia-Inducible Factor 1
Primary Hyperparathyroidism
Normetanephrine
Germ-Line Mutation
Tyrosine 3-Monooxygenase
Mutation
Catecholamines
Metanephrine
Succinate Dehydrogenase
Genetic Testing
Neoplasms
Norepinephrine
Radiotherapy
Immunohistochemistry
Urine
Radiation
Staining and Labeling

ASJC Scopus subject areas

  • Medicine(all)

Cite this

AN AGGRESSIVE TEMPORAL BONE SDHC PARAGANGLIOMA ASSOCIATED WITH INCREASED HIF-2α SIGNALING. / Isaacson, Brandon; Bullova, Petra; Frone, Megan; Click, Arielle; Hamplova, Barbora; Rabaglia, Jennifer; Woodruff, Stacey; Nwariaku, Fiemu; Kathuria, Amita; Pacak, Karel; Ghayee, Hans K.

In: Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists, Vol. 22, No. 2, 01.02.2016, p. 190-195.

Research output: Contribution to journalArticle

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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 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-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.",
author = "Brandon Isaacson and Petra Bullova and Megan Frone and Arielle Click and Barbora Hamplova and Jennifer Rabaglia and Stacey Woodruff and Fiemu Nwariaku and Amita Kathuria and Karel Pacak and Ghayee, {Hans K.}",
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AU - Isaacson, Brandon

AU - Bullova, Petra

AU - Frone, Megan

AU - Click, Arielle

AU - Hamplova, Barbora

AU - Rabaglia, Jennifer

AU - Woodruff, Stacey

AU - Nwariaku, Fiemu

AU - Kathuria, Amita

AU - Pacak, Karel

AU - Ghayee, Hans K.

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N2 - 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 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-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.

AB - 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 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-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.

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