S5843 From Mystery to Clarity: A Case of a Neuroendocrine G-NET Mimicking Adenocarcinoma on Esophagogastroduodenoscopy

Introduction: Gastric neuroendocrine tumors (G-NETs) are rare neoplasms originating from enterochromaffin-like cells in the gastric mucosa. While often small and asymptomatic, some G-NETs can present with aggressive behavior and mimic more common malignancies such as gastric adenocarcinoma. G-NETs are classified into types I, II, and III based on clinical features and underlying pathophysiology. Accurate diagnosis depends on histopathology and immunohistochemistry. Case Description/Methods: A 72-year-old man with a history of prostate cancer, type II diabetes, and prior alcohol use presented with fatigue, anorexia, and melena. Computed tomography imaging revealed an ulcerated gastric mass and extensive liver metastases. Esophagogastroduodenoscopy demonstrated a 3–4 cm ulcerated, infiltrative mass in the gastric body, raising suspicion for gastric adenocarcinoma based on gross morphology. However, biopsy revealed a well-differentiated neuroendocrine tumor (NET) characterized by trabecular architecture, round to oval nuclei, and moderate cytoplasm. Giemsa stain was negative for H. pylori. A targeted liver lesion biopsy confirmed metastatic NET of the same histology. Laboratory evaluation revealed hemoglobin of 9.6 g/dL, elevated serum gastrin at 1,432 pg/mL, and urinary 5-HIAA of 2.4 mg/24 hrs. Despite hypergastrinemia, histology did not show chronic atrophic gastritis, arguing against type I or II G-NETs. After holding proton pump inhibitor (PPI) therapy, repeat serum gastrin decreased to 312 pg/mL, and the pH of gastric aspirate was 4.0—findings that do not support Zollinger-Ellison syndrome (ZE). The absence of gastric atrophy, lack of MEN1/ZE, and presence of metastatic disease supported a diagnosis of type III G-NET, a sporadic, gastrin-independent subtype with more aggressive behavior. Nuclear Medicine Positron Emission Tomography Computed Tomography (NM PET-CT) showed multiple areas of somatostatin receptor overexpression. Discussion: This case illustrates the diagnostic challenge of G-NETs, which may visually mimic adenocarcinoma on endoscopy. Type III G-NETs often present as large, ulcerated lesions with early metastatic spread and carry the worst prognosis among G-NETs. In contrast, type I G-NETs are associated with autoimmune atrophic gastritis and hypergastrinemia, typically presenting as small lesions with low malignant potential. Type II G-NETs occur in the setting of MEN1 and Zollinger-Ellison syndrome, also associated with hypergastrinemia but with intermediate malignant potential.