The gastric marginal zone B-cell lymphoma of MALT type.

Extranodal marginal zone B-cell lymphoma is a discrete clinicopathological entity arising in mucosa-associated lymphoid tissue (MALT) that has commanded increasing attention in recent years because of its unique pathogenetic, histologic, and clinical features.1-3 Two types of MALT can be identified in disparate organs that do not correspond to peripheral sites of the immune system. The native type consists of lymphoid tissue physiologically present in the gut (eg, Peyer’s patches), whereas acquired MALT develops in sites of inflammation in response to either infectious conditions, such as Helicobacter pylori gastritis, or autoimmune processes, such as myoepithelial sialadenitis (MESA), associated with Sjögren’s syndrome or Hashimoto’s thyroiditis.4-6 In the context of these prolonged lymphoid reactive proliferations, the outgrowth of a pathological clone can progressively replace the normal lymphoid population, giving rise to a MALT lymphoma.7-11 The group of lymphomas classified as low-grade MALT lymphomas include a number of extranodal B-cell lymphomas, composed mostly of small cells, that share similar clinical, pathological, and molecular features; these lymphomas are defined as extranodal marginal zone B-cell lymphomas of MALT type in the Revised European-American Classification of Lymphoid neoplasms (REAL classification)12 and in the last World Health Organization (WHO) Classification of Neoplastic Diseases of the Hematopoietic and Lymphoid Tissue.13 The histologic features of low-grade B-cell lymphomas of MALT type are similar regardless of site of origin. In this review we will deal with gastric MALT lymphoma because the stomach is by far the most common and best-studied site. Far from being rare, extranodal marginal zone B-cell lymphomas accounted for 7.6% of 1378 cases of non-Hodgkin lymphoma (NHL) in an international evaluation of the clinical significance of the REAL classification.14 The highest incidence of gastric MALT lymphoma has been reported in northeastern Italy (13.2 per 100 000 per year, 13 times higher than in corresponding communities in the United Kingdom), suggesting the existence of important geographic variations.15 It has been speculated that the extraordinarily high number of primary gastric lymphomas in northeastern Italy is related to the very high rate of Helicobacter pylori infection observed in the examined population. In the United States, the incidence has been estimated as between 1:30 000 and 1:80 000 in the H pylori–infected population.16 However, additional unknown genetic, environmental, or dietary factors may also play a role. In fact, in some cases an infection from H pylori cannot be documented. Most gastric lymphomas in historical series were of diffuse, large-cell type, and only a few cases of low-grade histology were reported. In more recent series of primary gastric lymphomas, however, the low-grade MALT lymphomas appear to account for approximately 40% of the cases.17-19 Indeed, in the past, most cases would have been misinterpreted as pseudolymphomas. However, many features contribute to its definition as a malignant condition: monoclonality is usually demonstrable,20-22 nonrandom chromosomal aberration23-29 can be detected, and histologic transformation into a high-grade lymphoma, with the possibility of dissemination to the regional lymph nodes and to the bone marrow, has also been described.30,31