Compartment analysis of T cell receptor gamma--and immunoglobulin V(H) rearrangements by microdissection in patients with malt lymphoma and chronic gastritis with lymphatic hyperplasia.

The interpretation of clonality within H.pylori-associated gastritis and low-grade MALT lymphoma remains controversial. Due to the observation of MALT lymphoma regression after H.pylori eradication, new definitions concerning the border between benign reactive lesions and malignant gastric lymphoma are needed. Gene rearrangements for immunoglobulin heavy-chain in low-grade MALT lymphoma (N= 12) and H.pylori-associated chronic gastritis with lymphatic hyperplasia (N= 13) were analyzed by microdissection and polymerase chain reaction. Furthermore, T cell receptor-γ chain rearrangements were analyzed by gene scan analysis. In 11 of 12 cases with initial low-grade MALT lymphoma, intraepithelial and subepithelial B cell rearrangements showed a restricted usage of the immunoglobulin heavy-chain 3. In H.pylori-associated chronic gastritis, the intraepithelial B cell compartment showed an oligoclonal the immunoglobulin heavy-chain rearrangement pattern with a predominance of VH3. The subepithelial compartment did not show any restrictive immunoglobulin heavy-chain gene usage. Additionally a mono- to oligoclonal rearrangement pattern of the T cell receptor-γ chain was observed in low-grade MALT lymphoma, whereas an oligoclonal pattern was observed in chronic gastritis. Our data provide evidence that low-grade MALT lymphoma may start within the epithelium and subsequently infiltrate the subepithelial compartment. The observation of a mono- to oligoclonal TCR-γ rearrangement suggests that an antigen selecting process also takes place within reactive T cells. Combining TCR-γ gene scan analysis with IgH chain rearrangement analysis might help in discriminating between chronic gastritis and initial MALT lymphoma in questionable cases.