Recent developments in our understanding of gastric lymphomas.

The histopathologic features of low-grade primary gastric lymphoma recapitulate the structure of Peyer's patches [mucosa-associated lymphoid tissue (MALT)] rather than that of lymph nodes. Transformation of low-grade MALT lymphoma to high-grade disease is well recognized, and it is likely that most high-grade primary gastric lymphomas evolve from low-grade lymphoma of the MALT type and are therefore derived from the same B-cell lineage. Molecular genetic studies of gastric MALT lymphomas have shown that these lymphomas do not share any of the features common to nodal lymphomas but, instead, exhibit a marked increase in the frequency of trisomy 3. Gastric MALT lymphomas also differ from their nodal counterparts with respect to their clinical behavior, which is remarkably favorable. The histologic features of gastric MALT lymphomas suggest that one explanation for their favorable behavior may be that their growth is influenced by antigen. That lymphoma should arise from gastric mucosa is paradoxical, because there is no lymphoid tissue in normal stomach. However, several studies have shown that lymphoid tissue accumulates in gastric mucosa almost exclusively as a consequence of Helicobacter pylori infection and that this lymphoid tissue has MALT characteristics. These findings suggested that H. pylori might provide the antigenic stimulus for the growth of gastric MALT lymphoma. Further evidence for this was the finding of H. pylori in more than 90% of cases of gastric MALT lymphoma. Subsequently, evidence supporting an etiologic role for the organism has steadily accumulated. The incidence of gastric lymphoma is greater in communities with a high prevalence of H. pylori, and a case control study has shown that gastric lymphoma is more common in patients infected with the organism; moreover, the infection precedes the onset of lymphoma. Laboratory studies have shown that the growth of tumor cells from low-grade gastric lymphomas can be stimulated by H. pylori and that the effect is strain-specific and is mediated by contact-dependent help from H. pylori-specific T cells. Parallel clinical studies have shown that cases of low-grade gastric lymphoma, when confined to the mucosa, may regress after eradication of H. pylori from the patient's stomach. It remains to be shown whether deeply penetrating or high-grade tumors will respond in the same way. Other outstanding questions relate to the optimal interval between eradication of H. pylori and final evaluation of the response and to the expected duration of the response. On the basis of these laboratory experiments and clinical findings, it is possible to suggest a scheme for the pathogenesis of gastric MALT lymphoma.