B‐CELL LYMPHOMA OF MALT TYPE: A REVIEW WITH SPECIAL EMPHASIS ON DIAGNOSTIC AND MANAGEMENT PROBLEMS OF LOW‐GRADE GASTRIC TUMOURS

The concept of mucosa-associated lymphoid tissue (MALT) has progressively developed over the past 10 years with respect to the lymphoid component observed in various organs that do not correspond to peripheral sites of the immune system (Isaacson & Wright, 1983, 1984; Isaacson & Spencer, 1987; Isaacson, 1995a). Two types of MALT tissue can be identified (Isaacson, 1994; Pileri et al, 1994), the ‘native’ type which consists of the lymphoid tissue physiologically present in the gut, and the ‘acquired’ MALT type which develops after phlogistic events in response to either infectious conditions such as Helicobacter pylori gastritis in the stomach, or autoimmune processes like Hashimoto’s thyroiditis and myo-epithelial sialadenitis (MESA), usually due to Sjogren’s syndrome. In the context of these prolonged lymphoid reactive proliferations a pathological clone can progressively replace the normal lymphoid population, giving rise to a malignant lymphoma of MALT type. Low-grade MALT lymphoma was initially interpreted as a form of follicular centre cell lymphoma but is now considered a separate entity originating from the marginal-zone B cells, distinct from other low-grade lymphomas (Harris et al, 1994; Isaacson, 1995a). MALT lymphoma has come to be widely accepted as a distinct entity within the group of extra-nodal nonHodgkin’s lymphomas, challenging the previous concept of it as a pseudolymphoma, and has been included in the Revised European–American Classification of Lymphoid neoplasms (R.E.A.L. classification) as a distinct subtype, the extranodal marginal-zone B-cell lymphomas (Harris et al, 1994; Pileri et al, 1994). In fact, monoclonality is usually demonstrable (Wotherspoon et al, 1993; Diss et al, 1993a; Pan et al, 1994) and, moreover, non-random chromosomal abnormalities can be detected (Wotherspoon et al, 1992b, 1995; Horsman et al, 1992; Whang-Peng et al, 1994; Dierlamm et al, 1996; Brynes et al, 1996), as well as a possible histologic transformation into a high-grade lymphoma (Montalban et al, 1995b), contributing to its definition as a malignant entity. Moreover, MALT lymphomas can disseminate to the regional lymph nodes and sometimes to the bone marrow. The MALT lymphoma concept, as it has come to be known, has grown to include a number of low-grade extranodal B-cell lymphomas which share similar clinical, pathological and molecular features. Gastric MALT lymphoma is the most common and the most frequently studied and can be taken as representative of the group as a whole. The clinicopathological features of gastric lymphomas appear to be more closely related to the structure and function of MALT than of peripheral lymph nodes. In the gastrointestinal tract MALT consists of four components, the organized mucosal lymphoid nodules (distributed throughout the small intestine, the appendix, and the colorectum, and concentrated in the terminal ileum to form the Peyer’s patches), the lamina propria, the intra-epithelial lymphocytes which may be involved in antigen recognition, and the mesenteric lymph nodes (Isaacson, 1995b). In contrast to peripheral lymph nodes, which are adapted to dealing with antigens carried from afferent lymphatics, the lymphoid tissue of the gut and other mucosae appears to have evolved to protect mucosal tissue which is directly in contact with antigens in the external environment, thereby suggesting that the mucosae could be considered a common mucosal immune system (McDermott & Biemenstock, 1979). Following antigenic stimulation MALT B cells may leave the mucosa via efferent lymphatics, pass through the mesenteric lymph nodes into the thoracic duct and enter the circulation. These B cells possess specific homing receptors that recognize site-specific addressins on the endothelium that mediate preferential ‘home back’ to the gut mucosa as plasma cells or memory B cells (Berg et al, 1989). A preferential expression of the mucosal homing receptor integrin a4b7 was recently demonstrated in gastrointestinal lymphomas (Drillenburg et al, 1997). The lymphocytes’ ‘homing’ mechanism is still incompletely understood (Butcher & Pickert, 1996) but it could be relevant for clarifying the behaviour of B-cell lymphomas of MALT type which tend to remain localized in the mucosal sites (Isaacson & Spencer, 1995; Drillenburg et al, 1997). Paradoxically, MALT lymphoma usually arises as a consequence of a pre-existing disorder in sites such as the stomach, salivary gland, and thyroid where MALT is not normally present. This is well illustrated by MALT lymphomas of the salivary gland and thyroid which arise in the context of MESA and Hashimoto’s thyroiditis, respectively (Hyjek et al, 1988; Hyjek & Isaacson, 1988). The onset of MALT lymphomas in the stomach is preceded by the acquisition of MALT as a result of Helicobacter pylori infection. The micro-organism can be found in the gastric mucosa in nearly all instances, with several lines of evidence suggesting a link between H. pylori chronic gastritis and MALT lymphoma of the stomach. A close association has British Journal of Haematology, 1998, 100, 3–14