Chapter 64: Marginal Zone B-Cell Lymphoma

DEFINITION AND CLASSIFICATION

• The marginal zone lymphomas (MZLs) are derived from memory-type or antigen-experienced B cells that reside in regions contiguous to the outer part of the mantle zones of B-cell follicles

• MZL cells are usually small to medium-sized lymphocytes with irregularly shaped nuclei with dispersed chromatin and inconspicuous nucleoli.

• The World Health Organization (WHO) defines three separate MZL entities, namely, the extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (known as MALT lymphoma) (70%), the splenic marginal zone B-cell lymphoma (SMZL) (20%), and the nodal marginal zone B-cell lymphoma (NMZL) (<10%).

• Lymphoepithelial lesions characterized by invasion or necrotic destruction of the glandular epithelium by infiltrating lymphoma cells are characteristic of MALT lymphomas, especially those affecting the stomach.

• The WHO also recognize three provisional entities:

  — Extranodal marginal zone lymphoma (EMZL) of the MALT type.

  — Splenic marginal zone lymphoma (SMZL).

  — Nodal marginal zone lymphoma (NMZL).

EPIDEMIOLOGY

• MZLs account for about 10% of all non-Hodgkin lymphomas in the United States and Western Europe.

• There is a slight female predominance.

• Median age of presentation is about 60 years.

PATHOPHYSIOLOGY

• MALT lymphomas arise from mucosa-associated lymphoid tissues in the context of chronic inflammation.

• Gastric MALT lymphoma is one of the best examples of a microbiologic (Helicobacter pylori) cause of a human malignancy.

• In addition to H pylori, other bacteria are probably implicated in the pathogenesis of MZLs arising in the skin (Borrelia burgdorferi), in the ocular adnexa (Chlamydophila psittaci), and in the small intestine (Campylobacter jejuni).

• Hepatitis C virus (HCV) may be involved in the pathogenesis of several types of MZL.

• There is great geographic variation in the strength of these associations that is not satisfactorily explained.

• An increased risk of developing MALT lymphoma has also been reported in individuals affected by autoimmune disorders, especially Sjögren syndrome and systemic lupus erythematosus.

• Several recurrent chromosomal translocations have been described in extranodal MZLs. Three of them—[t(11;18)(q21;q21), t(1;14)(p22;q32), and t(14;18)(q32;q21)]—are the best characterized; they each affect the same signaling pathway, activating nuclear factor-kappa B (NF-κB), a transcription factor that plays a major role in immunity, inflammation, and apoptosis (Table 64–1).