Page 443 - Robbins Basic Pathology by Vinay Kumar, Abul K. Abbas, Jon C. Aster
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blood elements leads to elevated blood cell counts; Neoplastic Proliferations of White Cells 429
and myelodysplastic syndromes, which are characteristi-
cally associated with ineffective hematopoiesis and • The most common lymphomas are derived from germi-
cytopenias. nal center or post–germinal center B cells. This conclu-
• Histiocytic neoplasms include proliferative lesions of mac- sion is drawn from molecular analyses showing that
rophages and dendritic cells. Of special interest is a spec- most B cell lymphomas have undergone somatic hyper-
trum of proliferations of Langerhans cells (Langerhans mutation, an event confined to germinal center B cells.
cell histiocytoses). Normal germinal center B cells also undergo immuno-
globulin class switching, an event that allows B cells to
Lymphoid Neoplasms express immunoglobulins other than IgM. Class switch-
ing and somatic hypermutation are mistake-prone forms
The numerous lymphoid neoplasms vary widely in their of regulated genomic instability, which places germinal
clinical presentation and behavior, and thus present chal- center B cells at high risk for potentially transforming
lenges to students and clinicians alike. Some characteristi- mutations. In fact, many of the recurrent chromosomal
cally manifest as leukemias, with involvement of the bone translocations found in mature B cell malignancies
marrow and the peripheral blood. Others tend to manifest involve the immunoglobulin loci and appear to stem
as lymphomas, tumors that produce masses in lymph nodes from “accidents” during attempted diversification of the
or other tissues. Plasma cell tumors usually arise within the immunoglobulin genes. In this regard, it is interesting
bones and manifest as discrete masses, causing systemic that mature T cells, which are genomically stable, give
symptoms related to the production of a complete or partial rise to lymphomas infrequently and only very rarely
monoclonal immunoglobulin. While these tendencies are have chromosomal translocations involving the T cell
reflected in the names given to these entities, in reality all receptor loci.
lymphoid neoplasms have the potential to spread to lymph
nodes and various tissues throughout the body, especially • All lymphoid neoplasms are derived from a single trans-
the liver, spleen, bone marrow, and peripheral blood. formed cell and are therefore clonal. As described in
Because of their overlapping clinical behavior, the various lym- Chapter 4, differentiating precursor B and T cells rear-
phoid neoplasms can be distinguished with certainty only by the range their antigen receptor genes, thereby ensuring that
morphologic and molecular characteristics of the tumor cells. each lymphocyte makes a single, unique antigen recep-
Stated another way, for purposes of diagnosis and prog- tor. Because antigen receptor gene rearrangement virtu-
nostication, it is most important to focus on what the tumor ally always precedes transformation, the daughter cells
cell is, not where it resides in the patient. derived from a given malignant progenitor share the
same antigen receptor gene configuration and synthe-
Two groups of lymphomas are recognized: Hodgkin lym- size identical antigen receptor proteins (either immuno-
phomas and non-Hodgkin lymphomas. Although both arise globulins or T cell receptors). Thus, analyses of antigen
most commonly in lymphoid tissues, Hodgkin lymphoma receptor genes and their protein products can be used
is set apart by the presence of distinctive neoplastic Reed- to differentiate clonal neoplasms from polyclonal, reac-
Sternberg giant cells (see later), which usually are greatly tive processes.
outnumbered by non-neoplastic inflammatory cells. The
biologic behavior and clinical treatment of Hodgkin lym- • Lymphoid neoplasms often disrupt normal immune
phoma also are different from those of NHLs, making the function. Both immunodeficiency (as evident by
distinction of practical importance. increased susceptibility to infection) and autoimmunity
may be seen, sometimes in the same patient. Ironically,
Historically, few areas of pathology evoked as much patients with inherited or acquired immunodeficiency
controversy and confusion as the classification of lymphoid are themselves at high risk for the development of
neoplasms, which is perhaps inevitable in view of the certain lymphoid neoplasms, particularly those associ-
intrinsic complexity of the immune system, from which ated with EBV infection.
they arise. Great progress has been made over the past
several decades, however, and an international working • Although NHLs often manifest at a particular tissue site,
group of pathologists, molecular biologists, and clinicians sensitive molecular assays usually show the tumor to be
working on behalf of the World Health Organization widely disseminated at diagnosis. As a result, with few
(WHO) has formulated a widely accepted classification exceptions, only systemic therapies are curative. By con-
scheme that relies on a combination of morphologic, phe- trast, Hodgkin lymphoma often arises at a single site
notypic, genotypic, and clinical features. As background and spreads in a predictable fashion to contiguous
for the subsequent discussion of this classification, certain lymph node groups. For this reason, early in its course,
important principles warrant consideration: it is sometimes treated with local therapy alone.
• B and T cell tumors often are composed of cells that are
The WHO classification of lymphoid neoplasms considers
arrested at or derived from a specific stage of their the morphology, cell of origin (determined by immunophe-
normal differentiation (Fig. 11–13). The diagnosis and notyping), clinical features, and genotype (e.g., karyotype,
classification of these tumors rely heavily on tests (either presence of viral genomes) of each entity. It encompasses
immunohistochemistry or flow cytometry) that detect all lymphoid neoplasms, including leukemias and multiple
lineage-specific antigens (e.g., B cell, T cell, and NK cell myeloma, and separates them on the basis of origin into
markers) and markers of maturity. By convention, many three major categories: (1) tumors of B cells, (2) tumors of
such markers are identified by their cluster of differen- T cells and NK cells, and (3) Hodgkin lymphoma.
tiation (CD) number.
An updated version of the WHO classification of lym-
phoid neoplasms is presented in Table 11–7. As is evident,
the diagnostic entities are numerous. The focus here is on
the following subsets of neoplasms:
