MALT lymphoma is one of the most common B cell neoplasms and arises by definition at an extranodal site. As a distinct disease entity listed in the WHO classification, the definition of MALT lymphoma is supposed to be a combination of morphology, immunophenotype, and genetic and clinical features. While the genetic changes specific for or at least closely associated with the disease—that is, translocations t(1;14)(p22;q32), t(11;18)(q21;q21), and t(14;18) (q32;q21)—have been studied extensively in gastric MALT lymphoma, no analysis of their frequency in the less common intestinal MALT lymphomas has been undertaken. The major goal of the present study was therefore to analyse MALT lymphomas involving the intestine for all the three MALT lymphoma associated structural aberrations—t(11;18)(q21;q21), t(14;18)(q32;q21), and t(1;14)(p22;q32) —and additionally to screen for the most common numerical aberrations (trisomy 3 and trisomy 18).
Thirty patients with MALT lymphoma involving the intestine were identified from our records. In keeping with the notion that intestinal MALT lymphoma reflects secondary dissemination in a high proportion of patients, only 16 cases were judged to be primary MALT lymphomas by extensive staging. In the remaining 14 cases, seven initially presented with intestinal lymphoma and were diagnosed as having gastric MALT lymphoma during subsequent staging. In the other seven patients, gastric lymphoma (6) and pulmonary lymphoma (1) preceded the diagnosis of intestinal manifestations. Therefore, these data again underscore the importance of consequent staging in patients with MALT lymphoma, especially in those diagnosed with extragastric lymphomas.12
A current problem in assessing disease extent, however, is the relative inaccessibility of the small intestine with standard staging. Thus discrete infiltrates might be still be missed and could be more accurately detected with capsule endoscopy22
or double balloon enteroscopy, which offers the potential advantage of obtaining biopsies for histological assessment.
The genetic analyses of the 16 primary and the 14 secondary intestinal MALT lymphomas clearly demonstrated striking differences among the two groups. All primary intestinal MALT lymphomas harboured at least one of the five aberrations examined, among which trisomies 3 and 18, separately or together, were the most prevalent, occurring in 13 of the 16 cases (81.5%), and might be regarded as a genetic hallmark of the disease. Conversely, we detected the t(11;18)(q21;q21) in only two of the 16 primary intestinal MALT lymphomas. Interestingly, Ye et al
did not find the translocation in any of their 22 cases of immunoproliferative small intestinal disease, which by definition arises in the intestine and represents a variant of MALT lymphoma.1,20
By contrast, secondary intestinal MALT lymphoma showed a significantly higher frequency of t(11;18)(q21;q21) which is not unexpected because of its association with primary gastric and hence more advanced disease. This finding might be of diagnostic and prognostic relevance because in the appropriate histological and immunohistological setting, t(11;18)(q21;q21) warrants very thorough examination of the stomach including multiple biopsies and endosonography to rule out gastric MALT lymphoma. The markedly different genetic profiles of primary intestinal and primary gastric MALT lymphoma—though detected in lesions arising in the same organ system, the gastrointestinal tract—most probably reflect different preceding diseases.
Aneuploidy, most commonly trisomy 3 or trisomy 18 or both, often occurs in MALT lymphoma.9
In our series, primary intestinal MALT lymphoma was characterised by significantly higher frequency of trisomy 3 or 18 (81% v
0.024; 81% v
14%, p<0.001), in contrast to secondary intestinal MALT lymphoma and localised gastric MALT lymphoma. The high frequency of both numerical aberrations in primary intestinal MALT lymphomas suggests that one or more genes in chromosomes 3 and 18 are involved in the pathogenesis of these neoplasms. As opposed to t(11;18)(q21;q21), the presence of trisomies 3 and 18 appears to be associated with localised intestinal disease. The presence of t(11;18)(q21;q21) in gastric lymphoma has repeatedly been reported as a negative prognostic factor in terms of lymphoma regression following H pylori
Interestingly, it has recently been suggested that t(11;18)(q21;q21) positive patients have a longer time to relapse than those without the translocation.24
The current report, however, is the first to define trisomies 3 and 18 as genetic hallmarks of intestinal lymphoma. Because of the relative rarity of the disease, the potential prognostic implications of these genetic aberrations in intestinal MALT lymphoma have not been studied so far and should be addressed in future series involving larger numbers of patients.
Taken together, our data show that MALT lymphoma in the intestine reflects secondary spread from gastric MALT lymphoma in a high percentage of patients as judged by extensive staging. Primary intestinal MALT lymphoma, however, appears to be characterised by different genetic changes from secondary intestinal or localised gastric MALT lymphoma, probably reflecting a different pathogenesis.