Spatial associations among Reed sternberg, Hodgkin and immune cells in Hodgkin lymphoma

The majority of malignant cells in classic Hodgkin lymphoma, a B-cell lymphoma, are large bi- or multi-nucleated Reed Sternberg cells as opposed to smaller mono-nucleated Hodgkin cells. Together, Reed Sternberg and Hodgkin Cells (HRS cells) constitute a small fraction of cell types with normal T- and B-lymphocytes forming the majority. We used concepts and spatial statistics from landscape ecology to infer process from the histologies of six patients. Multiple immune stains for CD3, CD20, CD30, PAX5 antibodies and H&E (Hematoxylin and Eosin) stained sections permitted spatial mapping of HRS, T, and B cells. Combining over 6 patients, 85.9% of HRS cells were polyploid Reed Sternberg cells. Based on 22 subsamples, HRS, T-, and B-cells constituted 0.7% (ranging from 0.16 to 1.77%), 59% (57.6–63.0%) and 40% (36.0–42.2%) of the three cell types, respectively. HRS cells exhibited a significantly clumped distribution with small clusters of cells scattered throughout the tumor. Across subsamples T-cells showed no consistent patterns of association with HRS cells. In most subsamples, HRS and B cells showed a negative association with HRS cells. HRS cells were more abundant in areas with lower B-cell densities. From these results we offer the hypothesis that B-cells inhibit rather than facilitate HRS cells.