Molecular pathogenesis and histologic and clinical features of extranodal marginal zone lymphomas of mucosa-associated lymphoid tissue type.

Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT) type (EMZL) is considered an antigen driven lymphoid malignancy associated with protracted antigenic stimulation by microbial pathogens, auto-antigens or other unknown stimuli, which trigger a sustained lymphoid proliferation at sites normally devoid of lymphoid tissue. With the progression of disease, chromosomal aberrations may occur. They result in aberrant activation of signaling pathways which lead to the lymphoproliferation becoming independent of antigenic stimulation. The nuclear factor κB (NF-κB) pathway plays a central role in the lymphomagenesis of EMZL. Four mutually exclusive chromosomal translocations have been identified that lead to the up-regulation of either BCL10 or MALT1 or the generation of a fusion protein, cIAP2-MALT1, and induce aberrant activation of the NF-κB pathway. In translocation-negative EMZL, inactivation of the global NF-κB inhibitor A20 might play an important role. These genetic abnormalities alone are insufficient for malignant transformation. Other factors, such as cell surface and chemokine receptors and factors involved with immune and inflammatory response, play their own unique role in the development of a malignant EMZL and may determine its unique clinico-pathological presentation. This review provides an overview of the histologic and clinical features of EMZL and discusses the current insights into the molecular mechanisms underlying the development of EMZL.