Gastric low-grade mucosa-associated lymphoid tissue lymphomas: their histogenesis and high-grade transformation.

Gastric low-grade mucosa-associated lymphoid tissue (MALT) lymphoma is a unique disease. A vast majority of lymphoma cells are centrocyte-like cells or resemble monocytoid B cells, and occasionally show plasmacytic differentiation. Immunophenotypical and immunogenotypical examinations have indicated that they are in the differentiation stage of memory B cells, whose normal counterparts are marginal zone lymphocytes or monocytoid B cells in the lymphoid tissues. It arises from chronic gastritis closely associated with Helicobacter pylori (H. pylori) infection. Mucosa-associated lymphoid tissue lymphomas of other organs are also based on acquired MALT associated with chronic inflammation or autoimmune diseases. Interestingly, the majority of gastric low-grade MALT lymphomas regress by the eradication of H. pylori. The lymphoma cells, however, are not derived from B cells reacting with H. pylori itself but from autoreactive B cells. Although the mechanism of their oncogenesis has not been clarified, previous data suggest that autoreactive B cells proliferate in response to H. pylori-specific T cells, presumably with some cytokines. The genetic instability of such B cells then induces chromosomal abnormalities including trisomy 3 and/or other genetic changes. These B cells have the ability of autonomic proliferation and, even so, they might be sensitive to T cell stimuli. Low-grade gastric lymphomas occasionally progress to high-grade malignancy. The high-grade component of MALT lymphomas are composed of large-sized lymphoma cells that are morphologically indistinguishable from nodal large B cell lymphomas. This high-grade transformation is associated with p53 abnormalities or Bcl-6 overexpression. Gastric MALT lymphoma may provide a useful model in understanding multistep lymphomagenesis.