Poster Presentation ESA-SRB 2023 in conjunction with ENSA

Hereditary paraganglioma associated with SDHB mutation (#355)

Rachael Zuzek 1 , Tegan Van Gemert 1 , Alexia Pape 1
  1. Wollongong Hospital, Figtree, NSW, Australia

Background: Paragangliomas are rare neuroendocrine tumours derived from autonomic ganglia. Whilst most are sporadic, up to 40% of cases are hereditary [1], often associated with multiple lesions and younger onset.

Case: A 25-year-old female presented with a non-productive cough and palpitations. On examination she was hypertensive (162/110mmHg). Imaging revealed a large right paravertebral mass from T7-T9. Plasma metanephrines were elevated 7,180pmol/L, as was 24-hour urinary noradrenaline 4,211nmol/L and normetanephrine 17.6µmol/d. Ga-68 DOTATATE PET/CT confirmed intense activity at the lesion, with two further areas of activity in the neck and adjacent to the left adrenal gland. The patient underwent resection of all three lesions. Plasma metanephrines normalised after resection of the paravertebral tumour. Histopathology revealed a Zellballen pattern consistent with paraganglioma. Immunohistochemistry was positive for chromogranin with loss of SDH-B, suggestive of succinate dehydrogenase (SDH) deficiency. Genetic testing confirmed a SDHB mutation. There was no evidence of metastatic disease.

Discussion: Pathogenic genetic variants in SDH enzyme subunits are a common cause of hereditary paragangliomas [2]. SDHB mutations at locus 1p36.1-35 are the second most common and confer a 25% risk of developing a paraganglioma or pheochromocytoma by age 50 [3]. Patients tend to develop disease at a younger age compared with sporadic lesions [4]. There is no family history in the majority of patients, though the rate of de novo mutations is not known [5]. SDHB paragangliomas can be multiple, are often sympathetic and secrete noradrenaline, and more common in the abdomen/thorax [6]. SDHB mutations increase the risk of recurrent lesions and the likelihood of malignant transformation [2,4-6], requiring surveillance imaging. Furthermore, there is a 5% risk of renal cell carcinoma and 1% risk of gastric gastrointestinal stromal tumour [3].  In summary, there is increasing recognition of genetic factors in paraganglioma development, which has implications for prognosis and follow up.

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