A thyroid nodule revealing a paraganglioma in a patient with a new germline mutation in the succinate dehydrogenase B gene

Abstract

A 32-year-old asymptomatic female was diagnosed with an isolated thyroid nodule of 2.5 cm diameter. Fine needle aspiration suggested a medullary thyroid carcinoma. Consequently, a total thyroidectomy was performed. The nodule stained positive for chromogranin A, neurone-specific enolase and synaptophysin, but not for calcitonin. Finally, pathological analysis showed a thyroid paraganglioma. Although the tumour appeared to be sporadic in a patient with no personal or familial history of paraganglioma and/or pheochromocytoma, we have identified a new mutation (392delC) of the succinate dehydrogenase-B (SDHB) gene in the genomic DNA extracted from the leukocytes of the patient. That mutation induced a shift in the reading frame of the gene creating a premature stop codon (P131fsX135) which was predicted to result in a truncated SDHB protein of 135 amino acids. This report highlights the difficulties of this unexpected diagnosis of hereditary thyroid paraganglioma. It also discusses the clinical involvements in terms of familial screening and the necessary follow-up of the patient.

Primary thyroid paraganglioma mimicking medullary thyroid carcinoma: A case report

“…Although irradiation has been demonstrated to be effective for enlarging and symptomatic paragangliomas (12,13), an indication for primary radiotherapy is established rarely, and only if a surgical procedure is likely to involve a high risk of damage to several vessels and nerves (14). Moreover, as the present patient was negative for RET, SDHB or SDHD mutations (15,16), a left hemithyroidectomy without radiotherapy was appropriate.…”

Non-pheochromocytoma (PCC)/paraganglioma (PGL) tumors in patients with succinate dehydrogenase-related PCC–PGL syndromes: a clinicopathological and molecular analysis

“…According to prior studies from three large multinational and/or multicenter cohorts (22,35,47), examining 110, 116, and 358 SDHB/SDHD mutation carriers respectively, only six thyroid tumors were identified: two PTCs (35), one thyroid PGL (47,48), as well as three thyroid tumors of unknown histopathology (22). Given the high PTC incidence rates (incidence of PTC estimated at 7.3/100 000) (49,50), it is no surprise that thyroid tumors are relatively frequently encountered as incidental findings in patients who are under active surveillance.…”

Primary Paraganglioma of Thyroid Gland: A Clinicopathologic and Immunohistochemical Analysis of Three Cases with a Review of the Literature

“…Possibly due to the rarity and unexpected occurrence in the thyroid gland, this tumor type has remained underrecognized. A comprehensive search of the PubMed showed that only 35 cases have been reported in the English literature [1][2][3][4][5]. To better understand this rare entity, we undertook a brief review of the existing literature.…”

“…Given these important implications, it is suggested that all patients with these rare tumors undergo possibly genetic testing. However, germline mutation testing in primary thyroid paraganglioma is seldom performed, with only one report by Zantour et al [1] discovering a new germline mutation in SDHB gene. We also failed to perform genetic testing of germline mutations in these genes.…”

“…Paraganglioma is a neuroendocrine tumor that originates from the neural crest-derived paraganglia of the autonomic nervous system, which is located from the skull base to the pelvic floor [1]. Although the tumor can occur in a wide variety of sites, the majority arise in the head and neck region, the superior mediastinum and the abdomen [2].…”