Differential cell counts were made on nine lymph nodes whose structure was replaced by diffuse Hodgkin's disease; two of these nodes had the classical histological appearance of the lymphocytic predominance subtype, four of the mixed cellularity subtype, and three of the lymphocytic depletion subtype. Our attempts to achieve valid sampling methods are recorded. The counts, in general, confirm the postulated histological basis of the Rye classification of the subtypes of the diffuse disease. The major discrepancy is that, contrary to the histological descriptions, our direct counts have shown that lymphocytes, are, in general, more numerous in the lymphocytic depletion than in the mixed cellularity subtypes. The cell counts also show that normal mononuclear cells (mainly fibroblasts and macrophage-type cells) are much more numerous in the mixed cellularity subtype than in the other forms of diffuse Hodgkin's disease; this feature has not been emphasised in the Rye classification. On the basis of our differential counts, a hypothesis is proposed that could explain the natural history of the different subtypes of diffuse Hodgkin's disease as the resultant of three processes: (a) tumour aggressiveness, (b) specific cell-mediated immunological reactions, and (c) non-immunological stromal responses.
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