Chapter 64: Marginal Zone B-Cell Lymphoma

INTRODUCTION

• 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.

• The World Health Organization (WHO) defines three separate MZL entities, namely, the extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (currently known as MALT lymphoma), the nodal marginal zone B-cell lymphoma (previously termed monocytoid lymphoma), and the splenic marginal zone B-cell lymphoma (with or without circulating villous lymphocytes).

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

PATHOPHYSIOLOGY

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

• Other bacterial infections are possibly 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) appears involved in the pathogenesis of splenic MZL through antigen-driven stimulation of the lymphoma clone.

• There is, however, a great and incompletely explained geographic variation in the strength of these associations.

• An increased risk of developing MALT lymphoma has been also 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 most characterized, and, interestingly, they all appear to 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.

CLINICAL FEATURES

• The most common site of MALT lymphoma is the stomach, encompassing at least one-third of all cases.

• Extranodal MZLs may also arise at many other sites, including the salivary gland, the thyroid, the upper airways, the lung, the ocular adnexa (lacrimal gland, conjunctiva, eyelid, orbital soft tissue), the breast, the liver, the urogenital system, the skin and other soft tissues, and even the dura.

• As a general rule, the presenting symptoms of extranodal MZLs are related to the primary location.

• Elevated serum lactic acid dehydrogenase (LDH) or serum β₂-microglobulin levels, as well as constitutional B symptoms, are extremely rare at presentation.

• MALT lymphoma can remain localized for a prolonged period within the tissue of origin, but regional lymph nodes can sometimes be infiltrated and dissemination at multiple sites is not uncommon, occurring in up to one-fourth of cases.

DIAGNOSIS

• The presence H. pylori must be determined by histochemistry or, alternatively, urea breath test.

• The B cells of MZLs show the immunophenotype of the normal marginal zone B cells present in spleen, Peyer patches, and in lymph nodes. Therefore, the tumor B cells express surface immunoglobulins and pan-B antigens (CD19, CD20, and CD79a), express the marginal zone-associated antigens CD35 and CD21, and lack expression of ...