Final Diagnosis -- Paraganglioma


Paraganglioma with one of eight (1/8) lymph nodes involved by metastatic paraganglioma


By convention, tumors in the adrenal gland are known as pheochromocytomas (PCC) and extra-adrenal tumors are termed paragangliomas (PGL). Paragangliomas are sub-categorized as sympathetic or parasympathetic neoplasms. The sympathetic paragangliomas secrete excess catecholamines that result in hypertension, sweating, palpitations, headaches, and apprehension or anxiety. The paragangliomas that are classified as parasympathetic are most often non-secretory. Approximately 30% of pheochromocytomas and paraganglionoma occur in the context of a germline RET, Von Hippel-Lindau, neurofibromatosis type 1, and succinate dehydrogenase (SDH) mutations. Distinguishing clinical features of each gene mutation can be found in Table 1.

Neoplasms arising from genetic alterations of the SDH gene are categorized by the mutations in the four subunits of the mitochondrial enzyme succinate dehydrogenase: SDHA, SDHB, SDHC, and SDHD. Each gene is associated with an individual hereditary paraganglioma/pheochromocytoma syndrome identified as: PGL 1 (SDHD), PGL 2 (SDHAF2, sometimes referred to as SDH5), PGL 3 (SDHC), PGL 4 (SDHB), and PGL 5 (SDHA). Table 2 provides a summary of molecular genetic testing used in Hereditary PGL/PCC syndromes.

After further testing, this patient was found to have a mutation in the SDH gene with a B subunit mutation (SDHB). The SDHB mutation is an autosomal dominant mutation with approximately one-third of the patients having a family history. They are associated with extra-adrenal sympathetic paragangliomas. The risk of malignancy is 34-97% and is the highest among the SDH mutations. Treatment should include prompt resection of the neoplasm to remove excess catecholamine secretion and as a result of their tendency to metastasize.


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Contributed by Waseem Anani, MD and Anil Parwani, MD, PhD

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