Comparative pathogenesis and management of orbital/conjunctival and gastric MALT lymphoma: Microbial drivers, molecular mechanisms, and therapeutic implications

Mucosa-associated lymphoid tissue (MALT) lymphoma is a subtype of indolent extranodal B-cell non-Hodgkin lymphoma. Orbital and conjunctival MALT lymphomas (OAML) are the most common primary ocular adnexal lymphomas, while gastric MALT lymphoma remains a prototypical site linked to Helicobacter pylori infection. Despite the disparate anatomical locations, mounting evidence suggests a shared pathogenesis, including chronic antigenic stimulation, lymphoid accumulation, and genetic events. We explore the epidemiologic, pathophysiologic, and molecular connections between OAML and gastric MALT lymphoma, with particular emphasis on the therapeutic implications. The role of H. pylori as a driver of gastric lymphomagenesis is well-established, and antibiotic eradication therapy has revolutionized treatment. By contrast, the evidence for microbial triggers and antibiotic responsiveness in OAML remains equivocal, although Chlamydia psittaci has been proposed in some populations. We comprehensively evaluate treatment modalities for OAML, including watchful waiting, antibiotic therapy, low-dose radiotherapy, immunochemotherapy (e.g., rituximab, bendamustine), and targeted agents. The differences in natural history, treatment response, and relapse patterns between gastric and ocular MALTomas are reviewed, and a proposed treatment algorithm is presented. Finally, we highlight knowledge gaps and future directions, including molecular profiling, predictive biomarkers, and microbiome-targeted interventions.