V. Hodgkin Lymphoma
hematopathologists, oncologists, and molecular biologists came together to create the Revised European-American Classification of Lymphoid Neoplasms (REAL). Of importance, this
classification scheme incorporated objective criteria, such as immunophenotype and genetic aberrations, together with morphologic and clinical features, to define distinct clinicopathologic
entities. Experience has shown that most entities in the REAL classification can be diagnosed reproducibly by experienced pathologists and stratify patients into good and bad prognosis
groups.  More recently, an international group of hematopathologists and oncologists convened by the World Health Organization (WHO) reviewed and updated the REAL
classification, resulting in the inclusion of a number of additional rare entities. Presented here is the WHO classification ( Table 14-2 ), which sorts the lymphoid neoplasms into five
broad categories, based on their cell of origin:
1. Precursor B-cell neoplasms (neoplasms of immature B cells)
2. Peripheral B-cell neoplasms (neoplasms of mature B cells)
3. Precursor T-cell neoplasms (neoplasms of immature T cells)
4. Peripheral T-cell and NK-cell neoplasms (neoplasms of mature T cells and natural killer cells)
5. Hodgkin lymphoma (neoplasms of Reed-Sternberg cells and variants).
Before we discuss the specific entities described in the WHO classification, some important principles relevant to the lymphoid neoplasms need to be emphasized.
• Lymphoid neoplasia can be suspected from the clinical features, but histologic examination of lymph nodes or other involved tissues is required for diagnosis.
• As will be recalled from Chapter 6 , antigen receptor genes rearrange during normal B- and T-cell differentiation through a mechanism that ensures that each developing
lymphocyte makes a single, unique antigen receptor. In most lymphoid neoplasms, antigen receptor gene rearrangement
precedes transformation; hence, the daughter cells derived from the malignant progenitor share the same antigen receptor gene configuration and sequence and synthesize identical
antigen receptor proteins(either immunoglobulins or T-cell receptors). In contrast, normal immune responses are polyclonal and thus comprise populations of lymphocytes expressing
many different antigen receptors. As a result, analyses of antigen receptor genes and/or their protein products can be used to distinguish reactive and malignant lymphoid proliferations. In
addition, each antigen receptor gene rearrangement produces a unique DNA sequence that constitutes a highly specific clonal marker that can be used to detect small numbers of residual
malignant cells after therapy.
• The vast majority of lymphoid neoplasms (80% to 85%) are of B-cell origin, most of the remainder being T-cell tumors; only rarely are tumors of NK origin encountered. Most
lymphoid neoplasms resemble some recognizable stage of B- or T-cell differentiation ( Fig. 14-4 ), a feature that is used in their classification. Markers recognized by antibodies
that are helpful in the characterization of lymphomas and leukemias are listed in Table 14-3 .
• As tumors of the immune system, lymphoid neoplasms often disrupt normal architecture and function of the immune system, leading to immune abnormalities. Both a loss of
vigilance (as evidenced by susceptibility to infection) and breakdown of tolerance (manifested by autoimmunity) can be seen, sometimes in the same patient. In a further, ironic
twist, patients with inherited or acquired immunodeficiency are themselves at high risk of developing certain lymphoid neoplasms, particularly those caused by oncogenic viruses
• Neoplastic B and T cells tend to recapitulate the behavior of their normal counterparts. Like normal lymphocytes, transformed B and T cells tend to home to particular tissue
sites, leading to characteristic patterns of involvement. For example, follicular lymphomas proliferate in the B-cell areas of the lymph node, producing a nodular or follicular
pattern of growth, whereas T-cell lymphomas typically grow in paracortical T-cell zones. As is true of their normal
counterparts, lymph node homing of neoplastic lymphocytes is likely regulated by expression of particular chemokine receptors. Variable numbers of neoplastic B and T lymphoid cells
also recirculate periodically through the lymphatics and peripheral blood to distant sites. Sensitive molecular techniques have shown that most lymphoid tumors are widely disseminated at
the time of diagnosis. The most notable exception to this rule is Hodgkin lymphoma, which is sometimes restricted to one group of lymph nodes.
• Hodgkin lymphoma spreads in an orderly fashion, and as a result staging is of importance in determining therapy. In contrast, the spread of NHL is less predictable, and as was
noted above, most patients are assumed to have systemic disease at the time of diagnosis. Hence, staging in particular NHLs provides useful prognostic information but is generally
not as important in guiding therapy as is the case in Hodgkin lymphoma.
Figure 14-4Origin of lymphoid neoplasms. Stages of B- and T-cell differentiation from which specific lymphoid tumors emerge are shown. Key: CLP, common lymphoid precursor; BLB,
pre-B lymphoblast; NBC, naive B cell; MC, mantle B cell; GC, germinal center B cell; MZ, marginal zone B cell; DN, CD4/CD8 double negative pre-T cell; DP, CD4/CD8 double positive
pre-T cell; PTC, peripheral T cell.
TABLE 14-3-- Some Immune Cell Antigens Detected by Monoclonal Antibodies
Date: 2016-04-22; view: 457