Hodgkin's Disease with Monoclonal and Polyclonal Populations of Reed–Sternberg Cells

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Abstract
There is strong evidence that Reed–Sternberg cells have a lymphoid phenotype, but clonally rearranged genes for B-cell and T-cell antigen receptors have not been demonstrable in tumor tissue from most patients with Hodgkin's disease. To elucidate this issue, we assayed single Reed–Sternberg cells from 12 patients with classic Hodgkin's disease of a B-cell immunophenotype to detect rearranged immunoglobulin variable-region heavy-chain (Vh) genes. We isolated single Reed–Sternberg cells from frozen sections that had been immunostained for CD30. The rearranged Vh genes of these cells were amplified by the polymerase chain reaction and analyzed by gel electrophoresis and nucleotide sequencing. In all 12 patients, the Reed–Sternberg cells studied contained rearranged Vh genes. Three patterns were observed: in three patients the rearrangements in each patient were identical, in six patients all the rearrangements were unrelated and unique, and in three patients both identical and unrelated rearrangements were detected. Apparently somatic mutations of Vh genes were present in some Reed–sternberg cells but absent in others. Reed–Sternberg cells with B-cell phenotypes have rearranged Vh genes; therefore, these cells arise from B cells. The pattern of Vh gene mutations suggests that Reed–Sternberg cells can correspond to either immunologically naive or memory B cells. In half our patients the population of Reed–Sternberg cells was polyclonal; in the other half, monoclonal or mixed cell populations were found. Correlation with the clinical stage suggests that polyclonal Hodgkin's disease can present as a widespread lymphoma.