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World J Gastroenterol. Jan 21, 2014; 20(3): 684-698
Published online Jan 21, 2014. doi: 10.3748/wjg.v20.i3.684
Role of Helicobacter pylori in gastric mucosa-associated lymphoid tissue lymphomas
Marta-Isabel Pereira, José Augusto Medeiros
Marta-Isabel Pereira, Clinical Hematology Department, Coimbra University Hospital Center, 3000-075 Coimbra, Portugal
Marta-Isabel Pereira, José Augusto Medeiros, Institute of Physiology, Faculty of Medicine, University of Coimbra, Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal
Author contributions: Pereira MI and Medeiros JA contributed equally to this work.
Correspondence to: José Augusto Medeiros, MD, PhD, Institute of Physiology, Faculty of Medicine, University of Coimbra, Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal. jmedeiros@fmed.uc.pt
Telephone: +351-919-502495 Fax: +351-239-855051
Received: September 29, 2013
Revised: November 19, 2013
Accepted: December 5, 2013
Published online: January 21, 2014
Processing time: 142 Days and 20.9 Hours
Abstract

Mucosa-associated lymphoid tissue (MALT) lymphoma is an indolent extranodal marginal zone B-cell lymphoma, originating in acquired MALT that is induced in mucosal barriers as part of a normal adaptive immune response to a chronic immunoinflammatory stimulus, most notably chronic infection by Helicobacter pylori (H. pylori). This antigenic stimulation initially leads to lymphoid hyperplasia; the acquisition of additional genetic aberrations culminates in the activation of intracellular survival pathways, with disease progression due to proliferation and resistance to apoptosis, and the emergence of a malignant clone. There are descriptions of MALT lymphomas affecting practically every organ and system, with a marked geographic variability partially attributable to the epidemiology of the underlying risk factors; nevertheless, the digestive system (and predominantly the stomach) is the most frequently involved location, reflecting the gastrointestinal tract’s unique characteristics of contact with foreign antigens, high mucosal permeability, large extension and intrinsic lymphoid system. While early-stage gastric MALT lymphoma can frequently regress after the therapeutic reversal of the chronic immune stimulus through antibiotic eradication of H. pylori infection, the presence of immortalizing genetic abnormalities, of advanced disease or of eradication-refractoriness requires a more aggressive approach which is, presently, not consensual. The fact that MALT lymphomas are rare neoplasms, with a worldwide incidence of 1-1.5 cases per 105 population, per year, limits the ease of accrual of representative series of patients for robust clinical trials that could sustain informed evidence-based therapeutic decisions to optimize the quality of patient care.

Keywords: Mucosa-associated lymphoid tissue lymphoma; Marginal zone lymphoma; Helicobacter pylori; Gastric lymphoma; Eradication therapy; Nuclear factor-kappa B pathway

Core tip: Mucosa-associated lymphoid tissue (MALT) lymphomas are indolent B-cell lymphomas, originating in acquired MALT induced as a response to a chronic immunoinflammatory stimulus, notably infection by Helicobacter pylori (H. pylori). Antigenic stimulation determines lymphoid hyperplasia; additional genetic aberrations activate survival pathways, with the emergence of a malignant clone. The digestive system (predominantly the stomach) is the most frequent location, reflecting contact with foreign antigens, mucosal permeability and intrinsic lymphoid system. Early-stage gastric MALT lymphoma can regress through the eradication of H. pylori. Immortalizing genetic abnormalities, advanced disease or eradication-refractoriness require treatment alternatives, presently not consensual. Representative clinical trials are needed to optimize patient care.