Clonal evolution of gastric lymphoma of mucosa-associated lymphoid tissue type.

Development of multiple lesions is frequent in gastric lymphoma of mucosa-associated lymphoid tissue (MALT) type. Presence of clonal components in multiple lesions was examined on the resected samples from 18 cases by using PCR-based method for immunoglobulin heavy-chain gene rearrangement. There were two or more lesions in 10 cases, and 2 to 12 samples were obtained from each lesion. The remaining eight cases had a single large lesion, from which two to six samples were collected from separate areas from each other. A total of 86 samples were analyzed. Histologic findings in each sample were categorized as follows: proliferation of exclusively centrocyte-like cells (CCL), large cells, and combined CCL and large cells. Monoclonal or biclonal pattern (single or two bands) was observed in 42 samples, oligoclonal pattern (three or more bands) in 30, polyclonal (smear) in 11, and no products in 3. Large-cell-type lesions showed fewer bands than those with other histologic types, and 75% of cases with large-cell type had mono- or biclonal proliferation. Common clones were found among lesions in about 60% of cases. Especially in 4 cases including 2 cases with large-cell type, every lesion in the same case contained the common clones. These findings suggested that gastric MALT lymphoma started as multi- or oligoclonal proliferation of cells, in which separate lesions composed of different clones from each other. As disease advances, dominant clones appear in some lesion and disseminate to other lesions via homing properties of the proliferating B lymphocytes.