Pulmonary mucosa-associated lymphoid tissue lymphoma revisited

From the authors:

We thank E. Catherinot and colleagues for their comments and the additional data they provided to our recent review on pulmonary mucosa-associated lymphoid tissue (MALT) lymphoma [1]. Using 16S ribosomal DNA PCR, they did not find any traces of DNA from mycobacteria in eight samples of pulmonary MALT lymphoma. They only found DNA from environmental bacteria and Propionibacterium acnes, both in MALT lymphoma and control samples.

Since the discovery of Helicobacter pylori in gastric MALT lymphoma, to find a pathogen associated with pulmonary MALT lymphoma appeared to be the quest for the holy grail [2]. However, numerous questions have to be answered before to succeed.

1) On which samples should we work? Not only lymphoma specimens but also peri-tumoural lesions have to be included in the molecular analysis, as tumoural cells are not infected by H. pylori in gastric lymphoma.

2) Are there different kinds of pulmonary MALT lymphomas? In pulmonary MALT lymphoma, being a rare disease, it is challenging to individualise pathophysiological subgroups. However, we probably need to make a case-by-case analysis of patients when retrieving the results of microbiological analysis. We maybe have to get back to clinical (context or not of autoimmune disease), and histological and molecular (presence of not of gene rearrangement) characteristics when looking for a subgroup of patients within pulmonary MALT lymphomas.

3) As usual, a control group is mandatory. E. Catherinot and colleagues chose to include “normal lung” and lung cancer in their study. Other pulmonary diseases, such as granulomatous or idiopathic interstitial lung diseases, should be tested as well as specimens from other, nonpulmonary MALT lymphoma.

4) Finally – and this is probably the crux of the problem – what method should be used? As suggested by E. Catherinot and colleagues, a nontargeted approach, with next-generation DNA sequencing, should be considered. However, methods are continuously changing at almost every steps of analysis and negative or positive results should then be carefully discussed.

In this context, regrouping our strengths could help to answer to this apparently simple but still unresolved question.