Clonality analyses in gastric MALT (mucosa-associated lymphoid tissue)

B-cell clonality, assessed by PCR for amplification of the VDJ region of the immunoglobulin heavy chain gene (IgH), is used to support the diagnosis of gastric mucosa-associated lymphoid tissue (MALT) lymphoma (GML). It has also been described in simple gastritis cases, without any histological hint for lymphoma, especially in the presence of lymphoid follicles. We analyzed a randomly selected series of 130 gastric biopsies with histologically described lymphoid follicle formation and investigated these for the prevalence of B-cell clonality using different PCR-based methods to discuss its usefulness in the differential diagnosis of GML. A seminested PCR for the IgH gene was performed and evaluated by agarose gel electrophoresis, GeneScan technique, and melting-curve analysis. The majority of cases revealed histologically chronic active Helicobacter pylori gastritis. Monoclonality was detected in 7.5% (10 of 130) and 7% (9 of 130) of samples using GeneScan technique and melting-curve analysis, respectively. In eight of eight samples investigated, monoclonality was not demonstrated in deeper sections of the same biopsy using GeneScan technique, favoring the diagnosis of a reactive process rather than overt lymphoma. Electrophoresis proved more difficult to interpret and revealed clonal cases in 14% (18 of 130). We conclude that GeneScan technique and melting curve analysis are the methods of choice for clonality analysis in gastric biopsies. Analyses of different deep sections with advanced PCR technology might be the method of choice for future analyses. In our opinion, the question of whether detected monoclonality can be interpreted as malignant lymphoma is still open.