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In order to communicate data about various lymphomas, it is necessary that we all speak the same language. To this end, many lymphoma classification schemes have been devised over the years. The most recent and current “official” lymphoma classification is that proposed by the World Health Organization (WHO).1,2 It differs very little from the previous “official” classification, the REAL (Revised European-American Lymphoma classification).3 Because the WHO classification is explicit, it is easy to follow and, if used correctly, studies using WHO terms should be reproducible and easy to interpret. However, when authors use language and classification schemes that are not widely accepted, they risk misinterpretation or that their data may be overlooked.
In the early 1980s, authors began referring to low grade B cell lymphomas that arise in mucosal locations as either “marginal zone” or mucosa associated lymphoid tissue (“MALT”) lymphomas.4,5 Being the catchier of the two terms “MALToma” became dominant in the common parlance. However, this led to some confusion because the “MALT” descriptor has the connotation that there is only one type of lymphoma that arises in mucosal locations. In terms of biological behaviour however there are two common lymphomas that arise in mucosal locations, one indolent and one aggressive. As a descriptive rubric, the term “MALT” would encompass both entities and blur the line between them. This is one reason why the authors of the REAL and WHO classifications chose the term “extranodal marginal zone lymphoma” for the indolent entity—to distinguish it from diffuse large B cell lymphoma, the aggressive entity.1–3 The acronym “MALT” is fine for shorthand but should not be used without reference to the official name for the indolent neoplasm “extranodal marginal zone lymphoma”.1–3
In the paper by Nakamura and colleagues (
), the authors use the terms “high grade MALT” and “low grade MALT” without reference to official classifications. The use of such terminology is confusing, especially as the connotation of the materials and methods is that the authors called any lymphoma with large cells comprising “1% or more of the neoplastic population” a “high grade” lymphoma. In response to my inquiry about this problem, published on the Gut website, the authors partially cleared up this confusion by explaining that in order to be considered a “high grade MALT” in their study, a lymphoma must contain 10% large cells. One problem with this scheme is that typical low grade “MALT” lymphomas usually contain benign germinal centres composed of sheets of large cells in the background. Did the authors specifically look for and exclude benign germinal centres in their classification? Also, the percentage of large cells in each case is not provided in the paper.
Moreover, the WHO classification explicitly states that marginal zone lymphomas should not be graded.1,2 Large cell lesions such as those depicted by Nakamura et al in their online response should be referred to as “diffuse large B cell lymphoma.” In that online response, the authors state that “our cases with high grade MALT lymphoma were categorised into diffuse large B cell lymphoma plus areas of marginal zone/MALT lymphoma”. Again, this is confusing because the REAL/WHO classification terms “marginal zone lymphoma” and “diffuse large B cell lymphoma” were not used in the paper.
In closing, one important point should be reiterated: in order for readers to derive meaningful information from lymphoma studies, those studies must use widely accepted lymphoma classification terminology. In studies where deviation from such terminology is necessary, the materials and methods must explain the classification scheme precisely and explicitly.6
Are Nakamura et al saying that gastric diffuse large B cell lymphoma can be cured by anti-Helicobacter pylori therapy?
In our paper (Gut 2001;48:454–60), the recently proposed WHO classification of lymphoid neoplasms1 was not applied as our study was conducted during the period 1994–1998, and our manuscript was submitted in 1999. As we have previously responded to Dr Ely on the Gut website, the five cases with high grade mucosa associated lymphoid tissue (MALT) lymphoma in our study were categorised as diffuse large B cell lymphoma plus areas of marginal zone/MALT-type lymphoma, according to the WHO classification. The percentage of neoplastic large cells in these five cases was as follows: 30% and 40% each in two cases which regressed after eradication of Helicobacter pylori and 30%, 70%, and 90% each in three cases which did not respond to eradication therapy. It took for granted that reactive germinal centres were not overestimated.
To date, more than 20 cases of gastric diffuse large B cell lymphoma with or without areas of low grade MALT lymphoma have been reported to have regressed after H pylori eradication.2–10 Based on these observations, we consider that high grade MALT lymphoma/diffuse large B cell lymphoma with areas of marginal zone lymphoma in the early stage possibly responds to H pylori eradication. To determine whether or not patients with a response to H pylori eradication relapse in the future, a longer follow up study in a large number of patients would be necessary.
In addition, recent publications have shown that gastric diffuse large B cell lymphoma with areas of marginal zone lymphoma (high grade MALT lymphoma in our classification) had a better survival compared with that without evidence of MALT lymphoma.11–13 Many investigators still use the term “high grade MALT lymphoma”.4,6–11 Whichever term is accepted widely in the future, we believe that gastric diffuse large B cell lymphoma with areas of marginal zone lymphoma should be distinguished from that without MALT lymphoma.