The true identity of Hodgkiri's mononuclear cells and Reed-Sternberg (H-RS)cells has been a subject of controversy for decades. Those who believe that Hodgkin's disease (HD) is a heterogeneous discase may consider it to constitute lymphomas of various origins. However, this theory seems incompatible with the finding of similar phenotypic, biologic, and immunologic properties among most HD. We believe that, in the majority of cases, HD, except for LP and some LD-type HD, is a homogeneous disease despite differences in the degree of fibrosis and/or cellular reaction. The heterogeneity in cellular reactions is a result of secrction of various cytokines by H-RS cells, which may or may not be influenced by the presence of EBV. H-RS cells, and anaplastic!arge cell lymphoma (ALCL) cells as well, can express a combination of cytokines and cytokine receptors that is not seen in other types oflymphomas. The unique cytokine/receptor profile ( e.g. the expression of c-kit-RICD 117), along with various properties associated with H-RS/ ALCL cells, leads to a hypothesis that H-RS/ ALCL cells are related to similar lymphohematopoietic progenitor cells with different etiologies and somewhat limited differentiation capacity. A number of H-RS cells may differentiate with limited capacity along the B-cell pathway and may be infected by EBV, which further complicates the biologic and immunologic properties ofthese cells. The majority of H-RS cells may also, however, differentiate along the antigen-presenting dendritic cell pathway, as indicated by the abundant expression of restin, CD 15, CD40,CD54, CD58, CD80, and CD86. The majority of ALCL cells clearly differentiate to T cells, but some may acquire B-cell or histiocyte phenotypes. The progenitor cell hypothesis may explain ( 1) the variable expression of CD 117,CD43, and CD34 as weil as the absence of CD27, CD45 and CD45RA in H-RS cells; (2) the inconsistent and irregular pattems of phenotype and genotype and the various, often very limited, degrees of differentiation among these two types oflymphoma cells; (3) the existence of secondary HD or ALCL associated with rare types of lymphomas or leukemias, or vice versa; (4) the absence of recombinase and of the B-specific transcription factors BSAP; and(5) the frequent expression ofIL- 7 and IL-9 in H-RS cells.

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