Neurofibromatosis Type 1 With Ampullary Somatostatinoma, Small Bowel GISTs, and Extraadrenal Composite Pheochromocytoma-Ganglioneuroma

Abstract

Background: Neurofibromatosis type 1 (NF1) is an autosomal dominant hereditary tumor syndrome. Increased risk of GI tumors including neurofibromas, GISTs, and periampullary carcinoids is reported. Periampullary somatostatinomas as well as true neurogenic tumors including extra-adrenal pheochromocytomas (paragangliomas) and ganglioneuromas have also been reported. This case study reviews a patient with NF1 and multiple intra-abdominal neoplasms. Case: A 32 year old male presented with six months of jaundice, dark urine, and weight loss. CT showed dilated intrahepatic ducts, and elevated bilirubin and ALP. ERCP with biopsy of the ampulla was positive for invasive malignancy with neuroendocrine differentiation. Pancreaticoduodenectomy showed lowgrade somatostatinoma of the ampulla and an incidental duodenal GIST. CT scan at year two found an enlarging upper abdominal mass concerning for nodal metastasis. Ex-lap removal found a paraganglioma in association with ganglioneuroma. Given the pathology, the diagnosis of NF1 was confirmed with mutation analysis showing a truncating mutation in the NF1 gene. His exam showed multiple café au lait spots on the trunk and upper extremities, multiple neurofibromas, and axillary freckling. Years later he had a progressive right adrenal nodule and elevated plasma/urine metanephrines. Resection of a paracaval functional paraganglioma and partial right adrenalectomy with postoperative XRT to the right adrenal bed was performed. One year later, CT and OctreoScan showed a tumor corresponding with nodularity in the jejunal limb and pancreaticobiliary anastomosis. Surgery confirmed proximal and distal jejunal GISTs. Systemic octreotide treatment is under consideration. Discussion: Alterations in the NF1 gene (tumor suppressor) encodes for the protein neurofibromin. Unlike sporadic GISTs, NF1 associated GISTs do not usually harbor c-KIT or PDGFRA mutations. Pheochromocytomas reportedly affect 0.1-6% of NF1 patients. 3/14 reported cases of composite pheochromocytoma-ganglioneuroma were associated with NF1. The combination of pheochromocytoma and GIST has been described in 14 NF1 case. Periampullary tumors in NF1 patients are most commonly carcinoid, but most do not develop somatostatinoma syndrome. To our knowledge this if the first case of a patient with NF1 diagnosed with ampullary somatostatinoma, small bowel GISTs, and extra-adrenal composite pheochromocytoma-ganglioneuroma occurring together.Figure 1