Gastric MALT lymphoma: from aetiology to treatment.
The development of gastric mucosa-associated lymphoid tissue (MALT) lymphoma is dependent on Helicobacter pylori infection. Bacterial colonisation of the gastric mucosa triggers lymphoid infiltration and the formation of acquired MALT. The bacterial infection induces and sustains an actively proliferating B-cell population through direct (autoantigen) and indirect (intratumoral T cells specific for H. pylori) immunological stimulation. Moreover, the bacterial infection provokes a neutrophilic response, which causes the release of oxygen free radicals. These reactive species may promote the acquisition of genetic abnormalities and malignant transformation of reactive B cells. A transformed clone carrying the translocation t(1;18)(q21;q21) forms a MALT lymphoma, the growth of which is independent of H. pylori and will not respond to bacterial eradication. Malignant clones without t(11;18)(q21;q21), but with other genetic abnormalities, such as trisomy 3 or microsatellite instability, depend critically on immune stimulation mediated by H. pylori for their clonal expansion. In the early stages, the tumour can be successfully treated by eradication of the bacterium, whereas at later stages the tumour may escape its growth dependency through acquisition of additional genetic abnormalities such as t(1;14)(p22;q32) and t(1;2)(p22,p12) involving the BCL-10 gene. Finally, further genetic abnormalities, such as inactivation of the tumour suppressor genes, p53 and p16, can lead to high-grade transformation. Detection of these abnormalities may help with the clinical management of patients with gastric MALT lymphoma.
Du
Ming-Qing
MQ
Department of Histopathology, Royal Free and University College Medical School, University College London, UK. m.du@ucl.ac.uk
Isaccson
Peter G
PG
D001707:Biopsy, Needle; D005260:Female; D005753:Gastric Mucosa / Q000382:microbiology / Q000473:pathology; D016481:Helicobacter Infections / Q000175:diagnosis*; D016480:Helicobacter pylori / Q000302:isolation & purification*; D006801:Humans; D018442:Lymphoma, B-Cell, Marginal Zone / Q000382:microbiology* / Q000473:pathology / Q000628:therapy*; D008297:Male; D011230:Precancerous Conditions / Q000473:pathology*; D011379:Prognosis; D018570:Risk Assessment; D012307:Risk Factors; D013274:Stomach Neoplasms / Q000382:microbiology* / Q000473:pathology / Q000628:therapy*