Two groups of lymphomas are recognized: Hodgkin lymphomas and non-Hodgkin lymphomas. Although both arise most commonly in lymphoid tissues, Hodgkin lymphoma is set apart by the presence of distinctive neoplastic RS giant cells (see later), which usually are greatly outnumbered by nonneoplastic inflammatory cells. The biologic behavior and clinical treatment of Hodgkin lymphoma also are different from those of NHLs, making the distinction of practical importance.
An international group of pathologists, molecular biologists, and clinicians working on behalf of the World Health Organization (WHO) has formulated a widely accepted classification scheme for lymphoid neoplasms and myeloid neoplasms (discussed later) that relies on a combination of morphologic, phenotypic, genotypic, and clinical features. As background for the subsequent discussion of this classification, certain important principles warrant consideration:
B and T cell tumors often are composed of cells that are arrested at or derived from a specific stage of normal lymphocyte differentiation (
Fig. 12.13 ). The diagnosis and classification of these tumors rely heavily on tests (either immunohistochemistry or flow cytometry) that detect lineage-specific antigens (e.g., B cell, T cell, and NK cell markers) and markers of maturity. By convention, many such markers are identified by their cluster of differentiation (CD) number.
Class switching and somatic hypermutation are mistake-prone forms of regulated genomic instability that place germinal center B cells at relatively high risk for potentially transforming mutations. The most common lymphomas are derived from B cells that have migrated into germinal centers following antigen stimulation. This conclusion is drawn from analyses showing that most B cell lymphomas have undergone somatic hypermutation, an event confined to germinal center B cells. Normal germinal center B cells also undergo immunoglobulin class switching, which allows B cells to express immunoglobulins other than IgM. Many of the recurrent chromosomal translocations found in mature B cell malignancies involve the immunoglobulin loci and appear to stem from “accidents” during attempted diversification of the immunoglobulin genes. By contrast, mature T cells, which are genomically stable, give rise to lymphoma infrequently and only very rarely have chromosomal translocations involving the T cell receptor loci.
http://ebooksmedicine.net • Like other cancers, lymphoid neoplasms are derived from a single transformed cell and are therefore clonal. As described in Chapter 5, precursor B and T cells rearrange their antigen receptor genes through a mechanism that ensures that each lymphocyte makes a single, unique antigen receptor. Because antigen receptor gene rearrangement virtually always precedes transformation, the daughter cells derived from a given malignant progenitor share the same antigen receptor gene configuration and synthesize identical antigen receptor proteins (either immunoglobulins or T cell receptors). Thus, analyses of antigen receptor genes and their protein products can be used to differentiate lymphoid neoplasms (which are clonal) from immune reactions (which are polyclonal).
• Lymphoid neoplasms often disrupt normal immune function. Both immunodeficiency (made evident by increased susceptibility to infection) and autoimmunity may be seen, sometimes in the same patient. Ironically, patients with inherited or acquired immunodeficiencies are at high risk for the development of certain lymphoid neoplasms, particularly those associated with EBV infection.
• Although NHLs often manifest at a particular tissue site, sensitive molecular assays usually show that the tumor is widely disseminated at diagnosis. As a result, with few exceptions, only systemic therapies are curative for those with NHL. By contrast, Hodgkin lymphoma often arises at a single site and spreads in a predictable fashion to contiguous lymph node groups.