Management of H. Pylori-associated Gastric MALT-lymphoma

Management of H. Pylori-associated Gastric MALT-lymphoma

Abstract and Introduction

Abstract

Background Helicobacter pylori infection is the main cause of gastric mucosa-associated lymphoid tissue (MALT) lymphoma.
Aim To review several common misconceptions in the management of H. pylori-associated gastric MALT-lymphoma.
Methods Bibliographical searches were performed in MEDLINE up to June 2011.
Results If adequate diagnostic methods are used, and if only low-grade lymphomas are considered, the prevalence of H. pylori infection is very high (almost 90%). H. pylori eradication is effective in treating approximately 80% of patients with early stage lymphoma. In H. pylori-positive gastric high-grade lymphomas, antibiotic therapy should always be prescribed, as approximately 50% of them regress after H. pylori eradication. Patients with early stage MALT lymphoma negative for H. pylori might still benefit from antibiotic treatment as the sole treatment. Complete remission of gastric MALT lymphoma after H. pylori eradication can take even >12 months. PCR assay for the detection of monoclonal B cells remains positive in many cases after complete remission has been reached. Patients with a persistent clonal band should not be treated unless the lymphoma can be histologically demonstrated. Synchronous occurrence of gastric adenocarcinoma and MALT lymphoma has been repeatedly reported. In some patients in complete remission, eradication of H. pylori does not prevent later development of early gastric cancer. Gastric lymphoma recurrence occurs in some patients after both bacterial and lymphoma regression. H. pylori reinfection does not constitute a prerequisite for lymphoma recurrence.
Conclusions The present article states several misconceptions in the management of H. pylori-associated gastric MALT-lymphoma in clinical practice, reviews the related scientific evidence and proposes the adequate attitude in each case.

Introduction

Primary gastric lymphoma is a rare tumour, accounting for <5% of primary gastric neoplasms. However, it is the most common extranodal lymphoma, representing 4–20% of all extranodal lymphomas. Mucosa-associated lymphoid tissue (MALT) lymphoma is an extranodal lymphoma comprising morphologically heterogeneous small B-cells including marginal zone (centrocyte-like) cells, cells resembling monocytoid cells, small lymphocytes and scattered immunoblast and centroblast-like cells. In epithelial tissues, the neoplastic cells typically infiltrate the epithelium forming lymphoepithelial lesions. In biopsy specimens, the hallmark of MALT lymphoma is the lymphoepithelial lesion that results from tissue invasion by atypical lymphocytes as well as reactive lymphoid follicles.

In 1991, Wotherspoon et al., for the first time demonstrated that patients with primary gastric MALT lymphoma are regularly infected by Helicobacter pylori. In addition to histomorphological studies, recent epidemiological, molecular biological and experimental data clearly indicate that H. pylori plays a decisive role in the development and progression of gastric MALT lymphoma. The discovery of a relation between gastric MALT lymphomas and H. pylori infection has profoundly influenced our understanding of the pathogenesis of lymphomas and revolutionised our approach to their management. For the first time in the history of medical oncology, tumours have been cured by antibiotic therapy.

Gastric MALT lymphoma is the paradigm of lymphomas developing in extranodal areas after antigen stimulation. In the stomach, H. pylori colonisation induces the appearance of MALT and, eventually, MALT-derived lymphoma. Under normal conditions there is no evidence of organised lymphoid tissue in the gastric mucosa, where only the presence of a few lymphocytes has been described. However, as previously mentioned, this is the most common site for extranodal lymphomas. The clue to correctly explain this paradox is MALT development after H. pylori colonisation.

Gastric lymphomas are usually staged by endoscopic ultrasonography, according to the modified Ann Arbor staging system by Musshoff and Radaszkiewicz et al. Here, 'E' means primary extranodal site. Stage E-I means the localised involvement of one or more gastrointestinal (GI) sites on one side of the diaphragm without lymph node infiltration. Stage E-I is further characterised as E-I1 (lymphoma confined to mucosa and submucosa) or as E-I2 (lymphoma extending beyond submucosa). Stage E-II means the localized involvement of one or more GI sites on one side of the diaphragm with lymph node infiltration. Then, stage E-III means the localised involvement of the GI tract and/or lymph nodes on both sides of the diaphragm and stage E-IV means the localized GI bulk of lymphoma with or without infiltration of associated involvement of non-GI tract organs or tissues.

Unlike the slow acceptance of the role of H. pylori in gastric adenocarcinoma development by clinicians, the evidence linking this micro-organism to gastric MALT lymphomas was so strong, and the regression of the tumours following H. pylori eradication so impressive, that testing for and treating H. pylori rapidly became the standard of care for gastric MALT lymphoma management. Indeed, the observational and anecdotal data were deemed so overwhelming that no randomised clinical trial was ever done to evaluate the role of H. pylori eradication in this disease; placing patients in the placebo arm of such a study would now be considered unethical.

Daily clinical practice requires constant decision-making, and each is open to possible errors. Misconceptions are very common in clinical practice, but can be prevented. Our aim was to review several common misconceptions in the management of H. pylori-associated gastric MALT-lymphoma. This article's approach is to state the most commonly found misconceptions in clinical practice, to review the related scientific evidence and finally propose the adequate attitude in each case.

Bibliographical searches were performed in MEDLINE electronic database up to June 2011 looking for the following words (all fields): (H. pylori) and (lymphoma-associated lymphoid tissue or MALT). Articles published in any language were included. Reference lists from the studies selected by electronic searching were hand searched to identify further relevant articles. Abstracts of the articles selected in each of these multiple searches were reviewed and those meeting the inclusion criteria (that is, providing data regarding MALT lymphoma and H. pylori infection) were recorded. References of reviews on H. pylori-associated gastric MALT-lymphoma, and from the articles selected for the study, were also examined for articles meeting inclusion criteria.