Extranodal Marginal Zone Bcell Lymphoma Of Mucosaassociated Lymphoid Tissue

General: Mucosa-associated lymphoid tissue (MALT) lymphomas are extranodal lymphomas that commonly involve mucosal sites in adults with a median age of 61 years.1 These are often associated with autoimmune disorders such as Sjögren syndrome and Hashimoto thyroiditis. These lymphomas comprise approximately 7.6% of NHLs. The most common site is the gastrointestinal tract (51%) with the stomach accounting for the great majority of those cases. Other common sites include lung (10%), orbit (12%), skin (9%), salivary gland (6%), and thyroid (5%).25

Gastric MALT lymphomas can serve as a prototype of antigen driven lymphomas with Helicobacter pylori present in up to 90% of cases.26 Subsequent studies have shown the organism is responsible for antigen stimulation of the lymphoma, which is dependent on T-cell help while B-cells react to autoantigens.27-29 Treatment for Helicobacter is now part of the therapy in gastric MALT lymphomas and can, in some cases, cause regression and cure of disease.30

Most (66%) patients present with low stage (1 or 2) disease but up to 30% may have disseminated disease at diagnosis.131 This is an indolent lymphoma with a 5 year survival of 85%.31

Pathology: MALT lymphomas recapitulate normal MALT in that they can have an organized architecture in mucosal sites with hyperplastic germinal centers, expansion of marginal zone cells, and superficial plasma cell differentiation. Occasionally, the plasma cell differentiation can be extreme, mimicking a plas-macytoma. Using a gastric MALT lymphoma as the example, the mucosa is infiltrated by a dense lym-phoid infiltrate consisting of small lymphocytes with round to slightly irregular contours and moderate amounts of pale cytoplasm (marginal zone cells or "centrocyte-like" cells). Nucleoli are inconspicuous. There are admixed larger centroblastic cells present and plasma cells vary in number

The marginal zone cells can infiltrate epithelium and destroy the glandular structures. These are termed lymphoepithelial lesions (LELs) and are a hallmark of this disease (Figure 52.7). Marginal zone cells can invade the reactive germinal centers in a process termed follicular colonization.

Figure 52.7 Gastric MALT lymphoma with LELs (left center). The inset shows H. pylori organisms in Giemsa staining

Immunophenotype: MALT lymphoma cells express CD19, CD20, and surface immunoglobulin. They lack CD5 and CD10. CD43, an antigen not normally expressed on B-cells can be seen in up to approximately 60% of cases.32 Cytoplasmic immunoglobulin can be detected in minority (20%) of cases. Cases with t(11;18)(q21;q21) and t(1;14)(p22;q32) express nuclear bcl-10.33

Molecular genetics: Much has been learned about the molecular genetics of MALT lymphomas. A t(11;18)(q21;q21) is the most common recurrent cytogenetic abnormality in MALT lymphomas, occurring in approximately 20% of MALT lymphomas. The frequency varies by site, being most common in lung (38%) and stomach (25%) and uncommon in the salivary gland and thyroid (Table 52.3).3435

This translocation results in a fusion of the API2 and MLT1 genes that appears to activate NFkB.36 Detection of this translocation has clinical significance since those cases of gastric MALT lymphoma with the t(11;18)(q21;q21) do not respond to anti-Helicobacter therapy and are associated with infection by CAG-A+ strains of the organism. A t(14;18)(q32;q21) resulting in an IGH/MLT1 translocation has also been recently described in MALT lymphomas, particularly in those MALT lymphomas with low incidence of API2/MLT1.37

Another recurrent translocation is seen in MALT lymphomas. The t(1;14)(p22;q32) is an uncommon translocation in MALT lymphoma. It juxtaposes IGH

Frequency of API2/MLT1 translocation in MALT lymphoma











Skin, salivary, thyroid


and BCL10 genes, resulting in nuclear expression of bcl-10. Recently, bcl-10 has been shown to interact with MLT1 protein. These two proteins are also capable of activating NFkB via 1KB kinase (IKK) activation. Thus, it appears that both these translocations have a common mechanism of action, namely to activate NFkB, which may play a major role in lymphomagenesis.38

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