Genetic alterations underlying the pathogenesis of MALT lymphoma.

Extranodal marginal zone B-cell lymphoma is a discrete clinicopathologic entity arising in mucosaassociated lymphoid tissue (MALT), characterised by unique pathogenic, histologic and clinical features. MALT B-cell lymphoma occurs more frequently in organs, such as stomach, salivary glands, or thyroid, which acquire lymphoid tissue only after chronic phlogistic events. This occurs in response to either infectious conditions such as Helicobacter pyloriassociated chronic gastritis, or autoimmune processes like myo-epithelial sialadenitis and Hashimoto's thyroiditis. Within these prolonged lymphoid reactive proliferations, an abnormal B cell clone arises and replaces the normal population, giving rise to the MALT lymphoma. Clinical studies have shown that gastric MALT lymphoma can regress after anti-H. pylori antibiotic treatment, even if it is still not known whether antibiotics alone might induce de®nitive cure of the lymphoma. The molecular events underlying MALT lymphoma pathogenesis have become clearer during these last years and, at least for gastric lymphoma, a model can be drawn (Figure 1). Two distinct pathways seem to occur. MALT lymphoma might develop through a series of genetic lesions underlying the progression from a H. pylori-dependent lymphoma, with the presence of H. pylori strain-speci®c T cells necessary for the growth of lymphoma cells, to a H. pyloriindependent lesion. In contrast, the occurrence of the translocation t(11;18) would give rise to a MALT lymphoma, already H. pylori-independent. t(11;18)(q21;q21): API2-MALT1 fusion protein