S6469 Incidentally Detected H. pylori-Negative, t(11;18)-Negative Gastric MALT Lymphoma With Complete Response to Radiation

Introduction: Gastric mucosa-associated lymphoid tissue (MALT) lymphoma is typically associated with Helicobacter pylori infection and frequently regresses with eradication therapy. However, H. pylori-negative and t(11;18)-negative MALT lymphomas are uncommon, raising questions regarding optimal management and prognosis in this molecularly distinct subset. Case Description/Methods: A 74-year-old man with a history of Barrett’s esophagus on proton pump inhibitor therapy underwent surveillance esophagogastroduodenoscopy (EGD). He denied dyspepsia, weight loss, or constitutional symptoms. Endoscopy revealed patchy mucosal abnormalities in the gastric body. Biopsies demonstrated extranodal marginal zone B-cell lymphoma of MALT type. Immunohistochemistry was negative for H. pylori and fluorescence in situ hybridization (FISH) testing showed no evidence of the t(11;18)(q21;q21)/BIRC3-MALT1 translocation. Staging computed tomography (CT) imaging revealed no nodal or systemic involvement (stage IE). The patient was referred to hematology and treated with involved-site radiation therapy (ISRT), receiving 30 Gy in 20 fractions. He remained asymptomatic post-treatment. Follow-up EGDs at 6 and 24 months demonstrated endoscopic and histologic remission, with no clonal IgH rearrangement detected on molecular testing of surveillance biopsies. Discussion: This case illustrates a rare presentation of gastric MALT lymphoma in an H. pylori-negative, t(11;18)-negative patient—highlighting the importance of biopsy in endoscopic abnormalities, even in asymptomatic individuals. In the absence of H. pylori or translocation-driven lymphomagenesis, localized disease can still respond favorably to ISRT. Though the prognosis of H. pylori-negative MALT lymphoma is less well defined, radiation therapy remains a highly effective modality in early-stage disease. As noted in the HELYX II trial, there were excellent outcomes showing complete eradication of MALT lymphoma in H. pylori-negative patients with 24–30 Gy radiotherapy. While surveillance intervals aren’t standardized in current literature, most guidelines are recommending endoscopic monitoring every 3–6 months for 2 years, then every 6–12 months, with long-term follow-up due to late relapse risk. This case reinforces the role of personalized management based on molecular and staging data.