A Novel <i>GLCCI1::BRAF</i> Fusion With Independent <i>MYC</i> and <i>MYCN</i> Amplifications in Pediatric Pancreatic Acinar Cell Carcinoma

Pediatric pancreatic acinar cell carcinoma (PACC) is a rare malignancy, comprising 5-15% of pediatric pancreatic tumors. <i>BRAF</i> rearrangement is found in 20%-30% of PACC cases. We report a case of PACC with a novel <i>GLCCI1::BRAF</i> fusion and independent amplifications in <i>MYC</i> and <i>MYCN</i>. A 10-year-old male presented with 6 months of weight loss, back pain, and loose stools. Imaging demonstrated concentric soft tissue thickening around the superior mesenteric artery, prompting biopsy of a periaortic lymph node showing metastatic PACC. Pancreaticoduodenectomy revealed PACC and metastatic deposits in multiple lymph nodes and retroperitoneal soft tissue. Fluorescence <i>in situ</i> hybridization of both the periaortic lymph node and pancreaticoduodenectomy specimens demonstrated <i>BRAF</i> gene rearrangement, with the partner identified as <i>GLCCI1</i> by next generation sequencing and fusion assays. Chromosomal microarray analysis demonstrated amplification of <i>MYC</i> in the periaortic lymph node biopsy and amplification of <i>MYCN</i> in the resection specimen. The patient was treated with neoadjuvant chemotherapy, radiation, and a pan-RAF inhibitor, but developed new widespread metastasis and was deceased 22 months after presentation. The combination of the primary <i>GLCCI1::BRAF</i> fusion with secondary amplification of <i>MYC</i> and <i>MYCN</i> is likely to drive the aggressive behavior and metastasis in this case of PACC.