Large Retroperitoneal Paraganglioma Associated with Germline Mutation of the Succinate Dehydrogenase Gene

Abstract

Paragangliomas (PGLs) are rare neural tumors that can be benign or malignant and often associated with familial syndromes. We present a case of a 23-year-old male with a large retroperitoneal PGL found incidentally during the workup of elevated liver enzymes. After surgical excision, the patient was found to have an autosomal dominant mutation in the succinate dehydrogenase B (SDHB) gene, which when compared to sporadic PGLs or other familial syndromes is associated with a higher risk of tumor recurrence, occult metastasis, and development of other cancers. The patient’s first-degree relatives were recommended to undergo screening for the genetic mutation.

A Rare Case of Thoracoabdominal Paraganglioma: A Case Report and Literature Review

“…The genetic test detected a germline mutation in the SDHB gene (c.73-8A>G) of uncertain significance, but the immunohistochemistry of the tumoral tissue detected an absence of SDHB expression, which confirmed the functional consequence of the germline mutation detected. Although the molecular pathogenesis of paraganglioma is incompletely understood, there is some data to support the involvement of hypoxia-inducible factor (HIF), a transcription factor that regulates the expression of genes responsible for angiogenesis, cell proliferation, metastasis, and cell dedifferentiation [ 4 , 14 , 15 ]. The succinate dehydrogenase is composed of four subunits (A, B, C, and D) and converts succinate to fumarate in the Krebs cycle [ 14 , 15 ].…”

“…Although the molecular pathogenesis of paraganglioma is incompletely understood, there is some data to support the involvement of hypoxia-inducible factor (HIF), a transcription factor that regulates the expression of genes responsible for angiogenesis, cell proliferation, metastasis, and cell dedifferentiation [ 4 , 14 , 15 ]. The succinate dehydrogenase is composed of four subunits (A, B, C, and D) and converts succinate to fumarate in the Krebs cycle [ 14 , 15 ]. When a mutation in the B subunit is present this conversion is disrupted leading to a buildup of succinate [ 14 , 15 ].…”

“…The succinate dehydrogenase is composed of four subunits (A, B, C, and D) and converts succinate to fumarate in the Krebs cycle [ 14 , 15 ]. When a mutation in the B subunit is present this conversion is disrupted leading to a buildup of succinate [ 14 , 15 ]. The excess succinate subsequently inhibits prolyl hydroxylase which stabilizes the HIF [ 14 , 15 ].…”

“…When a mutation in the B subunit is present this conversion is disrupted leading to a buildup of succinate [ 14 , 15 ]. The excess succinate subsequently inhibits prolyl hydroxylase which stabilizes the HIF [ 14 , 15 ]. SDH mutations are seen in several family clusters of paraganglioma, which are described and defined as paragangliomas syndrome one (PGL1) through five (PGL5) depending on the mutated subunit of SDH [ 3 , 4 , 14 ].…”

“…The excess succinate subsequently inhibits prolyl hydroxylase which stabilizes the HIF [ 14 , 15 ]. SDH mutations are seen in several family clusters of paraganglioma, which are described and defined as paragangliomas syndrome one (PGL1) through five (PGL5) depending on the mutated subunit of SDH [ 3 , 4 , 14 ]. PGL4 is associated with pathogenic variants in the SDHB gene and is the second most common type of familial paraganglioma [ 3 , 4 , 14 ].…”