Gastric MALT lymphoma: a model of chronic inflammation-induced tumor development

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Abstract

Mucosa-associated lymphoid tissue (MALT) lymphoma, or extranodal marginal zone lymphoma of MALT, is an indolent B-cell non-Hodgkin lymphoma arising in lymphoid infiltrates that are induced by chronic inflammation in extranodal sites. The stomach is the most commonly affected organ, in which MALT lymphoma pathogenesis is clearly associated with Helicobacter pylori gastroduodenitis. Gastric MALT lymphoma has attracted attention because of the involvement of genetic aberrations in the nuclear factor κB (NFκB) pathway, one of the most investigated pathways in the fields of immunology and oncology. This Review presents gastric MALT lymphoma as an outstanding example of the close pathogenetic link between chronic inflammation and tumor development, and describes how this information can be integrated into daily clinical practice. Gastric MALT lymphoma is considered one of the best models of how genetic events lead to oncogenesis, determine tumor biology, dictate clinical behavior and represent viable therapeutic targets. Moreover, in view of the association of gastric MALT lymphoma with dysregulation of the NFκB pathway, this signaling pathway will be discussed in depth in both normal and pathological conditions, highlighting strategies to identify new therapeutic targets in this lymphoma.

Key Points

  • Diagnosis of gastric mucosa-associated lymphoid tissue (MALT) lymphoma is made by morphologic analysis of endoscopic mucosal biopsy samples and supported by molecular genetic analysis

  • Gastric MALT lymphoma is caused by Helicobacter pylori infection; therefore, every diagnosis of this lymphoma should prompt a thorough investigation for the presence of H. pylori

  • To date, gastric MALT lymphoma is the only malignancy for which antibiotics are the first choice of therapy with curative intent

  • General screening for the chromosomal translocation t(11;18)(q21;q21) is not recommended; however, its presence can aid diagnosis of gastric MALT lymphoma and predict resistance to H. pylori eradication treatment

  • A subgroup of gastric MALT lymphomas is characterized by chromosomal translocations that affect genes encoding molecules involved in activation of nuclear factor κB, which might represent attractive therapeutic targets

  • A watch-and-wait policy is now considered adequate management for patients with minimal residual disease after successful H. pylori eradication therapy

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Figure 1: Morphologic and immunohistochemical features of gastric MALT lymphoma.
Figure 2: Hypothetical model of gastric MALT lymphoma pathogenesis.
Figure 3: The BIRC3MALT1 fusion gene.
Figure 4: The canonical NFκB signaling pathway.

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