Pathogenesis of Marginal Zone Lymphoma (MZL)

MZL is thought to arise due to chronic immune stimulation. This may be due to infections, autoimmunity, or genetic changes.1,2

Infections

  • Hepatitis C is reported in ~22-35% of patients with NMZL, SMZL, and nongastric MALT lymphomas1
  • H. pylori infection plays a critical role in the pathogenesis of gastric MALT lymphomas, and its eradication can lead to tumor remission1

Other infections that have been associated with non-gastric MALT lymphoma include: Chlamydia psittaci, Campylobacter jejuni, and Borrelia burgdorferi.1

Autoimmune Diseases

Autoimmune diseases (eg, systemic lupus erythematosus [SLE], rheumatoid arthritis) increase the risk of developing nongastric MALT lymphomas; activated B cells infiltrate and proliferate in normally non-lymphoid tissues.2

Genetic Factors

Genomic abnormalities are often present in MZL. These can arise during chronic inflammation and can create antigen-independent dysregulation of B cell proliferation.2 Some chromosomal translocations (a genetic change in which a piece of one chromosome breaks off and attaches to another chromosome) found in MZL include1:

  • t(11;18)
    • Most common translocation, especially in gastric and pulmonary MALT lymphomas
    • Results in API2-MALT1 fusion
    • Less likely to respond to H. pylori eradiation
  • t(1;14)
    • Present in 1-2% of MALT lymphomas
    • Results in overexpression of BCL10
    • Less likely to respond to H. pylori eradiation
  • t(14;18)
    • Present in 15-20% of MALT lymphomas
    • Results in deregulated expression of MALT1
  • t(3;14)
    • Results in upregulation of FOXP1

MALT, mucosa-associated lymphoid tissue.

References: 1. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for B-Cell Lymphomas V.4.2019. © National Comprehensive Cancer Network, Inc. 2019. All rights reserved. Accessed July 10, 2019. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way. 2. Zinzani PL. The many faces of marginal zone lymphoma. Hematol Am Soc Hematol Educ Program. 2012;(1):426-432.