SAT-319 Long-term Follow-up of Two Unrelated Boys With SDHB-Related Malignant Paragangliomas

Background: Paragangliomas (PGLs) are rare neuroendocrine cell tumors and due to its rarity, there is no current standardized treatment and optimal long-term follow-up for metastatic disease. We report two cases of SDHB-related malignant PGL in boys with more than 5 years of follow-up. Clinical case: Patient 1 (P1) presented at the age of 13 with hypertension crisis, after a history of paroxystic tachycardia and sweating since 9. Fractionated 24-hour urinary metanephrines showed high Normetanephrine (NMT). CT showed bilateral lung lesions, the largest in right basis (6.1x5.3cm) in close contact with the 7/8th ribs and vertebrae, enlarged thoracic lymph nodes, and a 2.2 cm tumor near the left carotid. The patient went through a debulking surgery of the tumors. Patient 2 (P2) presented with abdominal pain at the age of 7. CT showed an abdominal tumor that was surgically resected. In both cases immunohistochemistry was compatible with PGL. P2 tumor was a non-secreting PGL, with high plasma chromogranin A prior to surgery. Both subsequently developed multiple bone metastases, and in case 2, additional recurrent retroperitoneal metastases. Adjuvant therapeutic (131)I-MIBG, until a total dose of 900mCi (P1) and 950mCi (P2,) was performed. Over a 5- and 7-year follow-up, respectively, sustained stable disease has been documented, with control of tumor burden, despite the presence of several metastatic foci, mostly in bones. P1 has maintained mild hypertension controlled with diltiazem 30mg bid and has been annually tested for urinary NMT, which is decreasing though still mildly elevated, plus imaging (MRI and/or PET-CT). Case 2 has been clinically asymptomatic with six-monthly chromogranin A determinations currently in the normal range, and annual imaging (MIBG scintigraphy, MRI and/or PET-CT). As both cases have bone metastatic disease, 5mg intravenous zoledronic acid was recently started. Sequencing of the coding exons and exon-intron boundaries of the SDHB gene found no mutations in P1, whereas a heterozygous frameshift deletion in exon 4 was found in P2 (c393delA). In P1, complementary Multiple Ligand-Binding Probe Amplification revealed a heterozygous deletion of SDHB exon 1. P1’s mother genetic screening was negative and the father refused testing. Six P2’s relatives were found to harbor the mutation, while 3 developed PGLs so far. Conclusion: Two cases of SDHB-related malignant PGL diagnosed at early ages were presented: one apparently sporadic (P1) and one familial (P2). Despite aggressive disease, with multiple disseminated bone metastases, a long-term survival has been achieved so far, with stable disease after high cumulative (I131)-MIBG doses and absence of significant adverse effects. Considering the rarity of the disease especially in children, these cases significantly add to the literature regarding the long-term course of malignant PGL and treatment options.