Pathogenesis Lymphoma

Overall, the vast majority of NHLs are derived from B-cells. In Southeast Asia and the Caribbean, there is an increased incidence of T-cell lymphomas. The most current lymphoma classification is the World Health Organization (WHO) schema (2). It includes a large number of heterogeneous entities defined according to morphology, immunopheno-type, cytogenetics, molecular features, and clinical behavior. The resulting classification attempts to relate specific entities to their normal cellular counterparts. B-cell lymphomas can be categorized according to whether the cell of origin has transitioned through the lymph-node germinal center (GC). After undergoing heavy and light chain gene rearrangements and when selected by antigen binding within the GC, somatic hypermutation occurs. The use of somatic hypermutation as a marker allows the determination of whether a specific lymphoma is pre-GC, GC, or post-GC. Pre-GC lymphomas include most cases of CLL and mantle-cell lymphoma. GC or post-GC lymphomas include most cases of diffuse large B-cell lymphomas (DLBCLs), mucosa-associated lymphoid-tissue (MALT) lymphomas, lymphoplasmacytic lymphomas [associated with Waldenstrom's macroglobulinemia (WM)], and follicular lymphoma. Extramedullary plasmacytomas are derived from a clone of pathologic plasmablasts that migrate from the bone marrow and become established in soft tissue with the assistance of adhesion molecules.

Gene microarrays are currently being evaluated to allow further discrimination within otherwise relatively homogeneous subtypes. This is best established for DLBCL, the most common lymphoma subtype seen in practice. DLBCL can be characterized into GC or activated subtypes (3). The GC subtype is associated with a better prognosis. It is expected that this technology will be more extensively adopted in general clinical practice to allow appropriate risk-adapted therapy. Currently, gene arrays are not widely available outside of clinical trials.

The latest comprehensive categorization of lymphomas is the WHO classification (Table 1), which evolved from the "working formulation" (WF) (4) and its successor, the Revised European-American Lymphoma (REAL) classification (5). Knowledge of the WF and its relationship to the WHO classification is helpful, because it can provide insight into both the nature and the expectations of treatment. Essentially, the WF categorized lymphomas according to the expected outcome with therapy and was thus a convenient tool for making therapeutic decisions. It grouped entities as low, intermediate, or high grade. The current, more precise WHO classification allows the inclusion of more homogeneous disease entities in clinical trials, which will lead to improved treatment outcomes.

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