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World J Gastroenterol. Jul 14, 2015; 21(26): 8014-8020
Published online Jul 14, 2015. doi: 10.3748/wjg.v21.i26.8014
Helicobacter pylori-negative gastric mucosa-associated lymphoid tissue lymphomas: A review
Naoki Asano, Katsunori Iijima, Tomoyuki Koike, Akira Imatani, Tooru Shimosegawa
Naoki Asano, Katsunori Iijima, Tomoyuki Koike, Akira Imatani, Tooru Shimosegawa, Division of Gastroenterology, Tohoku University Graduate School of Medicine, Aoba-ku Sendai Miyagi 980-8574, Japan
Author contributions: Asano N, Iijima K, Koike T, Imatani A and Shimosegawa T were involved in editing the manuscript.
Conflict-of-interest statement: The authors declare no conflict of interests.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Naoki Asano, MD, PhD, Division of Gastroenterology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku Sendai Miyagi 980-8574, Japan. asanon@med.tohoku.ac.jp
Telephone: +81-22-7177171 Fax: +81-22-7177177
Received: March 18, 2015
Peer-review started: March 19, 2015
First decision: April 13, 2015
Revised: April 30, 2015
Accepted: June 9, 2015
Article in press: June 10, 2015
Published online: July 14, 2015
Abstract

Since Isaacson and Wright first reported on the extra-nodal marginal zone B-cell lymphoma of the stomach in 1983, following studies have clarified many aspects of this disease. We now know that the stomach is the most affected organ by this disease, and approximately 90% of gastric mucosa-associated lymphoid tissue (MALT) lymphomas are related to Helicobacter pylori (H. pylori) infection. This implies that approximately 10% of gastric MALT lymphomas occur independent of H. pylori infection. The pathogenesis of these H. pylori-negative gastric MALT lymphomas remains unclear. To date, there have been several speculations. One possibility is that genetic alterations result in nuclear factor-kappa B (NF-κB) activation. Among these alterations, t(11;18)(q21;q21) is more frequently observed in H. pylori-negative gastric MALT lymphomas, and such translocation results in the synthesis of fusion protein API2-MALT1, which causes canonical and noncanonical NF-κB activation. Another possibility is infection with bacteria other than H. pylori. This could explain why H. pylori eradication therapy can cure some proportions of H. pylori-negative gastric MALT lymphoma patients, although the bacteria responsible for MALT lymphomagenesis are yet to be defined. Recent advances in endoscopy suggest magnifying endoscopy with narrow band imaging as a useful tool for both detecting gastric MALT lymphoma lesions and judging the response to treatment. A certain proportion of H. pylori-negative gastric MALT lymphoma patients respond to eradication therapy; hence, H. pylori eradication therapy could be considered as a first-line treatment for gastric MALT lymphomas regardless of their H. pylori infection status.

Keywords: Helicobacter pylori, Mucosa-associated lymphoid tissue lymphoma, API2-MALT1, Antibiotics, Endoscopy

Core tip: Although the majority of gastric mucosa-associated lymphoid tissue (MALT) lymphoma patients are infected with Helicobacter pylori (H. pylori), approximately 10% of patients do not have H. pylori infection. Recent studies have demonstrated that eradication therapy for H. pylori is effective not only for H. pylori-positive but also for H. pylori-negative gastric MALT lymphoma patients.