S6339 Déjà Virus, When EBV Shows up Late to the Gastric Party: A Case Report of EBV-Positive Gastric Adenocarcinoma Following EBV-Negative Gastric Cancer

Introduction: Epstein-Barr virus associated gastric cancer (EBVaGC) is now recognized as a distinct molecular subtype of gastric adenocarcinoma, accounting for approximately 8-10% of cases. They typically show a higher prevalence in males, predilection for the proximal stomach (cardia and body), and is often associated with lymphoepithelioma-like or prominent lymphoid histology. Clinically this subtype of gastric adenocarcinoma exhibits a lower frequency of lymph node metastasis and is associated with relatively favorable prognosis. We present a case of EBV-positive gastric adenocarcinoma in a patient with a history of EBV-negative gastric cancer, who presented with abdominal pain. Case Description/Methods: A 62-year-old woman with a past medical history of cerebral palsy, cholecystectomy, and EBV negative gastric adenocarcinoma status post partial gastrectomy in 2012 was under routine surveillance by gastroenterology. A surveillance esophagogastroduodenoscopy (EGD) in 2017 revealed gastric polyps, but biopsies at that time were negative for malignancy. In 2023, during follow-up, the patient reported persistent abdominal pain. A repeat EGD identified gastric polyps at the anastomosis site, and biopsies confirmed the presence of gastric adenocarcinoma. Molecular testing was positive for EBV and negative for H. pylori. The patient subsequently underwent a subtotal gastrectomy. Surgical biopsy revealed a 2.5 cm gastric adenocarcinoma with a lymphoid stroma invading the lamina propria, and all sampled lymph nodes were negative for metastasis. The patient’s symptoms improved following the surgery, and she continues to be monitored by GI. Discussion: EBV-infected gastric epithelial cells undergo clonal proliferation, with viral proteins and microRNAs promoting oncogenesis through mechanisms such as DNA hypermethylation, PIK3CA mutations, and amplification of immune regulatory genes such as JAK2 and PD-L1/PD-L2. These molecular alterations may account for the increased sensitivity of EBVaGC to immunotherapy, making it a promising option for recurrent or refractory cases. Studies indicate that EBV status can change between primary and recurrent tumors, suggesting either de novo infection or selection of EBV-infected clones during tumor evolution, which could explain the change in EBV status observed in our patient. This case highlights the importance of recognizing EBV positive gastric adenocarcinoma as a unique entity, even in recurrent disease and in patients outside the typical demographic profile.