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Helicobacter pylori infection in gastric extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT) lymphoma: a re-evaluation
  1. Larissa Sena Teixeira Mendes,
  2. Ayoma D Attygalle,
  3. Andrew C Wotherspoon
  1. Department of Histopathology, Royal Marsden Hospital, London, UK
  1. Correspondence to Dr Andrew C Wotherspoon, Department of Histopathology, Royal Marsden Hospital, Fulham Road, London SW3 6JJ, UK; andrew.wotherspoon{at}

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In 1991 Wotherspoon et al 1 showed a close association between Helicobacter pylori infection and gastric mucosa-associated lymphoid tissue (MALT) lymphoma (GML) with the organism present in 92% of cases. Other studies have shown this association to be varying between 42% and 100%. In vitro studies at that time showed that lymphoma cell proliferation was associated with the presence of H. pylori mediated through specific tumour infiltrating T cells in a contact dependant manner. In the light of this finding Wotherspoon et al 1 were able to demonstrate that eradication of H. pylori induced lymphoma regression.

In a recent Gut article, Nakamura et al 2 demonstrated that H. pylori eradication therapy can result in durable lymphoma regression in the majority of cases. However, absence of H. pylori infection is a known predictive factor for eradication resistance.3

Prevalence of H. pylori has shown signs of decrease especially among Western populations. A decline in the number of GML H. pylori-positive has also been reported.4–7 To address these issues, we performed a retrospective review to analyse the H. pylori infection status in patients diagnosed with GML in our institution from 1995 to 2013. One hundred and four patients diagnosed with GML were identified. Of these, 98 were available for review. The overall prevalence of H. pylori infection was 50%. When pure MALT lymphomas (without large cell components) are considered (88%, n=86) the H. pylori prevalence remains the same (table 1).

Table 1

Overview of Helicobacter pylori prevalence in patients diagnosed with GML 1995–2013

In comparison with the study from 1991,1 subjects from our study are 11.2 times more likely to have H. pylori-negative GML (95% CI 5.1 to 24.7). When the diagnostic time frame was divided in two periods: from 1995 to 2004 and from 2005 to 2013, the prevalence of H. pylori infection found was 60.6% (n=37/61) and 32.4% (n=12/37), respectively.

A significant reduction in H. pylori infection rates across the groups could be established using a logistic regression model (p<0.001). The prevalence OR of H. pylori infection amidst the three periods showed that subjects in the second group (1995–2004) are 7.3 times more likely to have H. pylori-negative GML (95% CI 3.1 to 17.1) than subjects in the 1991 group (p<0.001); while subjects in the third group (2005–2013) are 23.4 times more likely to have H. pylori-negative GML (95% CI 8.9 to 61.6) than subjects in the 1991 group (p<0.001) (table 2).

Table 2

Logistic regression analyses: OR for Helicobacter pylori-negative GML across the three groups analysed

This study shows that the overall association of GML with H. pylori infection is significantly reduced when compared with the original prevalence study by Wotherspoon et al 1 even though the demographics of the study population in both investigations are likely to be very similar. When the diagnostic time frame was further split the decrease in the proportion of cases of H. pylori-associated GML was even more pronounced (2005–2013) (table 2).

We suggest that our findings are due to the reduction in H. pylori infection in the general population consequently resulting in an alteration of GML epidemiology. Several studies have demonstrated reduced acquisition rates of H. pylori especially among children.5 ,7 An additional factor may be deliberate H. pylori eradication in increased numbers of individuals, or possibly the unintentional eradication following the widespread use of antibiotics and acid suppressing medications.8

These findings have significant implications in the management of GML, as eradication therapy is rarely successful in H. pylori-negative cases. It is proposed that a reduced background prevalence of H. pylori infection will result in lower numbers of H. pylori-related GML while the number of H. pylori-unrelated cases will remain stable. Although eradication therapy is recommended in the first instance this induces complete remission in only 15–33% of H. pylori-negative cases9 (Raderer personnel communication) and the majority of cases treated with curative intent will require more conventional therapies including immunotherapy, chemotherapy or radiotherapy. The information given to patients with GML will need modification in order to manage their expectation for success of eradication therapy and the potential need for more intensive management.


The authors acknowledge support from the NIHR RM/ICR Biomedical Research Centre, and the fundamental help of Claire Peckitt in the statistical analysis of the data.



  • Contributors LSTM and ACW (study guarantor) performed the research, analysed the data and wrote the paper; ADA analysed the data and revised the manuscript critically. All authors had full access to all of the data (including statistical reports and tables) in the study and can take responsibility for the integrity and accuracy of the data.

  • Competing interests All authors (LSTM, ADA and ACW) have completed the Unified Competing Interest form at and declare no financial support/sponsors for the submitted work; LSTM, ADA and ACW declare no relationships that might have an interest in the submitted work in the previous 3 years; spouses, partners or children have no financial relationships that may be relevant to the submitted work; and LSTM, ADA and ACW have no financial interests that may be relevant to the submitted work.

  • Provenance and peer review Not commissioned; internally peer reviewed.

  • Transparency declaration The lead author declares that the manuscript is an honest, accurate and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study have been explained.