Lymphoma

Abstract

The term lymphoma identifies two distinct groups of tumors: Hodgkin’s disease (HD) and non-Hodgkin’s lymphoma (NHL). Since the late 1970s, significant progress has been made in the elucidation of the pathogenesis of NHL as a clonal malignant expansion of B or T cells. B lymphocytes are generated in the bone marrow as a result of a multistep differentiation process. On entering the germinal center (GC), B cells activate into centroblasts, proliferate, and mature into centrocytes. Cells that have exited the GC have two fates: differentiation into either plasma cells or into memory B cells. Based on the absence or presence of somatic immunoglobulin (Ig) hypermutation, B-cell NHL can be grouped into two broad histogenetic categories: One derived from pre-GC B cells and devoid of Ig mutations (mantle cell lymphoma, chronic lymphocytic leukemia/small lymphocytic lymphoma), and the other derived from B cells that have transited through the GC and harbor Ig mutations (follicular lymphoma, lymphoplasmacytoid lymphoma, mucosa-associated lymphoid tissue lymphoma, diffuse large cell lymphoma, Burkitt’s lymphoma). The pathogenesis of lymphoma represents a multistep process involving the progressive and clonal accumulation of multiple genetic lesions affecting protooncogenes and tumor suppressor genes. The genome of lymphoma cells is relatively stable and is characterized by few nonrandom chromosomal abnormalities, commonly represented by chromosomal translocations. A new classification, called the Revised European-American Lymphoma, was created in the early 1990s to establish definitions for distinct lymphomatous diseases based on morphologic, clinical, immunophenotypic, and molecular genetic features (Table 28.1).