Helicobacter pylori are gram-negative spiral microaerophilic organisms that belong to the Campylobacterales order, Helicobacteracea family. They are capable of colonizing the harsh environment of the human stomach. Over 50% of the world’s population carries this infection. 1 H pylori have colonized the human stomach since time immemorial. 2 In virtually all infected individuals, H pylori causes inflammation in the form of chronic active gastritis, which progresses in 10%–20% of affected persons to peptic ulcer disease, gastric adenocarcinoma, and/or mucosa-associated lymphoid tissue (MALT) lymphoma. However, only a very small minority (1%–2%) of infected individuals will develop a malignant disease. 3 One of the most distinctive features of H pylori is the genetic diversity it displays between clinical isolates. 4 H pylori isolates are highly diverse, with evidence of a constantly changing genome, primarily caused by point mutations, substitutions, insertions, and/or deletions. 5,6 Moreover, mixed infections are frequent and may lead to exchange of DNA fragments between H pylori strains in a single host. This suggests co-evolution of H pylori with its human host and that disease may be caused both by strain-specific properties that increase virulence and by host susceptibility. Such strains possibly evolve through exercising significant flexibility in gene content and gene regulation. Among many of the host–pathogen interactions that potentially could occur, some could prove beneficial in which the co-evolved bacteria and the host reach an almost symbiotic relationship. H pylori may not be just a bad bug in all instances. A large body of data have implicated H pylori in the pathogenesis of gastric MALT lymphoma, including epidemiologic, biological, and molecular genetic studies. Interestingly, both H pylori and MALT lymphoma were born almost simultaneously, when H pylori was described by Marshall and Warren 7 and MALT lymphoma was recognized as a distinct entity by Isaacson and Wright. 8 These latter investigators noted morphologic similarities between the histology of the condition known as immunoproliferative small intestinal disease, a subtype of primary intestinal B-cell lymphoma, and primary low-grade gastric B-cell lymphoma. Moreover, the histologic features differed from that of comparable nodal low-grade B-cell lymphomas in that the overall architecture and cytology of these lymphomas bore a resemblance to normal MALT tissue rather than recapitulating the structure of lymph nodes. Roughly one third of all non-Hodgkin’s lymphomas in adults are of extranodal origin. MALT lymphomas, by definition arising at mucosal/epithelial sites, collectively account for approximately 8% of all non-Hodgkin’s lymphomas, with gastric MALT lymphoma being the most common extranodal site. This review summarizes the published data that support a causative role for H pylori infection in the pathogenesis of gastric MALT lymphomas. The epidemiology of H pylori is discussed and its role in the pathogenesis, including factors affecting the infectious organism and the host. A major focus of this review addresses the relationship between the immune response, H pylori, and MALT lymphomas. This is followed by a description of the morphology, phenotype, and unifying concepts of the molecular genetics of MALT lymphomas. Treatment strategies of gastric MALT lymphoma are not discussed because these are beyond the scope of this review. Finally, we conclude with a brief discussion of H pylori–negative MALT lymphomas, preventative measures for reducing infection, and the direction of future research into MALT lymphomas.
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Jan 18, 2006
Marijn M.S Mulder + 7
Open Access