Helicobacter pylori and gastric MALT lymphoma: mechanisms of pathogenesis and therapeutic implications

Gastric mucosa-associated lymphoid tissue (MALT) lymphoma represents a distinctive low-grade non-Hodgkin B-cell malignancy and one of the clearest examples of infection-associated carcinogenesis. Accounting for 7–9% of all B-cell lymphomas, this disease demonstrates a unique therapeutic paradigm, as early-stage gastric MALT lymphoma achieves complete remission in approximately 60–90% of patients following Helicobacter pylori eradication alone. This response reflects the tumor’s dependence on chronic antigenic stimulation, though disease progression and treatment resistance are driven by genetic alterations, such as the t(11;18) translocation, that confer antigen-independent growth. This review synthesizes current knowledge on clinical presentation, diagnostic evaluation, immunopathogenesis, prognostic factors, and evidence-based management of gastric MALT lymphoma. This review discusses the molecular mechanisms underlying the transition from antigen-dependent to antigen-independent disease, emerging therapeutic strategies, including targeted molecular therapies and BTK inhibitors, and addresses ongoing challenges in diagnosis, treatment resistance, and surveillance. Additionally, the broader implications of gastric MALT lymphoma to better understand how chronic infection drives lymphomagenesis and how pathogen eradication can lead to regression of antigen-dependent lymphoma, with the aim of providing insights for other microbe-associated malignancies, have been discussed.