We read with interest the report by Raderer and colleagues (Gut 2006;55:616–18). The authors reported on six patients with localised gastric Helicobacter pylori negative mucosa associated lymphoid tissue (MALT) lymphoma, successfully treated with eradication therapy. They suggest that patients with early stage H pylori negative gastric MALT lymphoma might benefit from antibiotics as the sole treatment modality and, as explanation for their findings, they propose the hypothesis of a role in gastric MALT lymphoma of bacteria other than H pylori and potential immunomodulatory effects of antibiotics.
We are surprised that the authors did not consider the possibility of false negative diagnostic tests for H pylori. As no single test is accepted as the gold standard for diagnosis of H pylori infection,1,2 they correctly used more than one: histology, urea breath test, stool antigen test, and serology. However, none of these tests has a sensitivity of 100%,1,2 and all but serology may be affected by an altered gastric microenvironment, such as hypochlorhydria.1,3,4 The authors give no information about previous use of antisecretory drugs in their patients but it is highly probable that patients with leading symptoms such as epigastric pain and bleeding were treated with proton pump inhibitors or H2 antagonists before diagnosis of MALT lymphoma and this treatment may have led to negative results for the urea breath test, stool antigen test, and histology for H pylori infection.
Also, serology, in particular enzyme linked immunosorbent assay (ELISA), may give negative results in patients with previous exposure to H pylori infection.1 In fact, in patients with gastric cancer and atrophic body gastritis, immunoblotting can document past H pylori infection in patients classified as H pylori negative by ELISA serology.5,6 The authors do not mention what type of serological approach they used, but it is plausible that sera immunoblotting might have revealed a previous contact to H pylori in their MALT lymphoma patients.
Furthermore, neutrophils are a very sensitive indicator of the presence or absence of H pylori and disappear within days of cure of infection.7 Thus it would be interesting to compare this histological feature before and after eradication treatment as a reduction in the inflammatory activity after treatment may be interpreted as the presence of H pylori infection before therapy.
Finally, in H pylori negative MALT lymphoma patients, a high rate of t(11;18)(q12;q21) has been reported,8 which has been described as identifying patients whose lymphoma will not regress following antibiotic treatment.9 In the case series of Raderer et al, only one of the patients showed this genetic alteration. The very low presence of genetic changes together with the good response to antibiotics is another reason to question H pylori negativity.
In conclusion, we believe that the authors' interpretation of their results is incomplete as in our opinion the hypothesis—that H pylori infection was present but not revealed due to intrinsic limits of diagnostic methods—is more plausible than that given by the authors regarding bacteria other than H pylori or immunomodulatory effects of antibiotics.
Footnotes
Conflict of interest: None declared.
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