Gastric Mucosa-Associated Lymphoid Tissue Lymphomas: More Than a Fascinating Model

Extract

Information about mucosa-associated lymphoid tissue (MALT) has accumulated progressively over the past decade. MALT lymphoma is usually associated with a pre-existing disorder in sites where lymphocytes are not normally present and where an acquired MALT develops in response to either infectious conditions (i.e., in the stomach) or to autoimmune processes (i.e., in salivary glands or the thyroids). In the context of these prolonged, lymphoid-reactive proliferations, the outgrowth of a pathologic clone can progressively replace the normal lymphocytes ( 1 , 2 ). MALT lymphoma has been included in the Revised European—American Classification of Lymphoid neoplasms (R.E.A.L. classification) as a specific subtype, i.e., the extranodal marginal-zone B-cell lymphomas ( 3 ). Marginal-zone B-cell MALT lymphomas comprised 7.6% of more than 1400 non-Hodgkin's lymphomas in a recent international evaluation of the clinical significance of the REAL classification ( 4 ).

Several lines of evidence, including sequence analysis of the immunoglobulin variable-region heavy-chain genes, strongly suggest that Helicobacter pylori provides the antigenic stimulus for sustaining the growth of MALT lymphomas in the stomach ( 5 – 7 ). This antigen-driven clonal expansion, which is mediated by mucosal T cells, may explain the tendency of low-grade MALT lymphomas to remain localized in the mucosal sites and to regress after H. pylori eradication ( 8 , 9 ). During this clonal expansion, genetic alterations continue to occur until a point is reached when autonomous (i.e., H. pylori -independent) growth is possible, while additional alterations can then result in high-grade transformation.