SAT-186 Metastatic Paraganglioma Secondary to SDHB Gene Mutation: A Case Report and Review of New Therapies

Abstract

Background: Paragangliomas (PGL) are rare neuroendocrine tumors that arise from the extra-adrenal autonomic paraganglia, majority of which are benign. 0-36% of PGL patients can develop metastatic disease, depending on the genetic mutation. We present a case of a patient with metastatic PGL due to an SDHB gene mutation. We then summarize published and ongoing trials of therapies for metastatic pheochromocytoma/PGL. Clinical Case: A 54 years old male presented to the Emergency Department with severe left lower quadrant pain. He additionally reported recent episodes of headaches and uncontrolled hypertension, as well as an approximate weight loss of 50 pounds in the preceding two years.A CT abdomen and pelvis demonstrated an 8 cm left peri-aortic retroperitoneal mass, along with a 2 cm solitary hepatic lesion concerning for metastatic disease. Normetanephrine levels were elevated at 1210 pg/mL (normal 0-145 pg/mL). Endoscope-guided biopsy of the retroperitoneal mass demonstrated findings consistent with a PGL.The patient was referred to a genetic counsellor where he underwent PGLNext testing. He tested positive for a c.418G>T mutation in the SDHB gene, consistent with a diagnosis of hereditary paraganglioma - pheochromocytoma (PGL-Pheo) syndrome.Patient was planned for surgical debulking of his PGL, and was treated pre-operatively with Phenoxybenzamine, followed by B-blockers. He underwent resection of the retroperitoneal mass and wedge resection of the hepatic mass. Surgical pathology revealed a 10.5 cm extra adrenal PGL and a 2 cm metastatic PGL involving the liver with negative margins of resection.Patient did well in the post-operative period, and was discharged with plans to repeat plasma metanephrines in 6-8 weeks. The patient was referred to the National Cancer Institute (NCI) for enrollment in a clinical trial using Lu-177-DOTATATE. Conclusion: Though rare, pheochromocytomas (pheo) and PGL can be lethal if not diagnosed and managed appropriately. As of 2019, at least 19 genes have been identified that predispose to familial pheochromocytoma/PGL. Importantly, PGL that are associated with SDHB, the mutation our patient had, are more likely to appear in the abdomen (rather than the head and neck), are usually secretory (most commonly norepinephrine) and are more likely to become metastatic (21-79%).Patients with metastatic pheo/PGL require complex care in specialized centers by a multidisciplinary team of specialists. Patients with advanced or non-resectable metastatic pheo/PGL should preferably be offered a referral to NCI or an NCI designated cancer center for enrollment in a clinical trial of targeted therapies.