Hematology 2001 241 MALT Lymphomas Franco Cavalli, Peter G. Isaacson, Randy D. Gascoyne, and Emanuele Zucca This review addresses the biology and the treat- ment of lymphomas arising from mucosa-associ- ated lymphoid tissue (MALT). This entity, first described in 1983, represents about 8% of all non- Hodgkin’s lymphomas and was recently re-classi- fied as “extranodal marginal zone lymphomas of MALT-type.” The term marginal zone lymphoma (MZL) encompasses the three closely related lymphoma subtypes of nodal, primary splenic and extranodal lymphomas of MALT type: the latter represent the vast majority of MZL. These lympho- mas arise at different anatomic sites, are com- posed of mature B-cells lacking expression of CD5 and CD10, often present with overlapping morpho- logic features, but typically quite distinct clinical behaviors. Only very recently cytogenetic/molecu- lar genetic observations have underlined the distinctiveness of these three lymphoid neoplasms, which in both the R.E.A.L. and WHO-classifications are included in the general term of MZL. MALT lymphomas arise in numerous extranodal sites, but gastric MALT lymphoma is the most common and best studied and is, therefore, the paradigm for the group as a whole. Dr. Isaacson describes the principal histologi- cal features of these lymphomas, including criteria to distinguish this entity from other small B-cell lymphomas. Several lines of evidence suggest that gastric lymphoma arises from MALT acquired as the result of a H. pylori infection. However, at least 1/3 of cases do not respond to eradication of H. pylori. Very recent data suggest that both t(11;18) (q21;q21) and bcl10 nuclear expression are associ- ated with failure to respond to this treatment. Dr. Gascoyne discusses the biologic function of proteins deregulated through the different translo- cations, which play a role in pathogenesis of MALT lymphomas, emphasizing particularly their influ- ence in disrupting the apoptotic pathway. Dr. Zucca reviews findings suggesting that MALT lymphoma is an antigen driven neoplasm. He also presents specific guidelines for treatment of gastric lymphomas trying to shed some light on the amazingly inconsistent and confusing data in the literature. Taking advantage on the more than 300 non- gastric MALT lymphomas collected by the Interna- tional Extranodal Lymphoma Study Group (ILESG), Dr. Cavalli compares gastric lymphomas with those arising in many other sites. Overall, the data presented in this session will underline the fact, that MALT lymphomas are characterized by some unique biological properties. I. THE PATHOLOGY OF GASTRIC MALT LYMPHOMA AND ITS RESPONSE TO ERADICATION OF HELICOBACTER PYLORI Peter G. Isaacson, MBChB* The observation that the histology of certain extranodal lymphomas was related to mucosa associated lymphoid tissue (MALT) rather than that of peripheral lymph nodes was first made by Isaacson and Wright in 1983. 1 These authors noted similarities between the histology of the condition known as immunoproliferative small intesti- nal disease (IPSID), a subtype of primary intestinal B- cell lymphoma, and primary low-grade gastric B-cell lymphoma. However, their histology differed from that of comparable low-grade nodal B-cell lymphomas in that their overall structure and cytology resembled those of MALT rather than lymph nodes. These observations were later extended to include other extranodal low-grade B- cell lymphomas, especially those of salivary gland, lung and thyroid. 2 The collective histological features of these lymphomas recapitulated the features of the principal B-cell component of MALT as exemplified by the Peyer’s patch. 3,4 MALT lymphomas, recently re-classified as “extranodal marginal zone lymphomas of MALT-type,” 5 arise in numerous extranodal sites, but gastric MALT lymphoma is the commonest and best studied and is, therefore, the paradigm for the group as a whole. *University College London Medical School, Department of Histopathology, Rockefeller Building, University Street, London SC1E 6JJ, United Kingdom