HODGKINS-DISEASE WITH MONOCLONAL AND POLYCLONAL POPULATIONS OF REED-STERNBERG CELLS

Background. There is strong evidence that Reed-Sternberg cells have a lymphoid phenotype, but clonally rearranged genes for B-cell and T-cel l antigen receptors have not been demonstrable in tumor tissue from mo st patients with Hodgkin's disease. To elucidate this issue, we assaye d single Reed-Sternberg cells from 12 patients with classic Hodgkin's disease of a B-cell immunophenotype to detect rearranged immunoglobuli n variable-region heavy-chain (V-H) genes. Methods. We isolated single Reed-Sternberg cells from frozen sections that had been immunostained for CD30. The rearranged V-H genes of these cells were amplified by t he polymerase chain reaction and analyzed by gel electrophoresis and n ucleotide sequencing. Results. In all 12 patients, the Reed-Sternberg cells studied contained rearranged V-H genes. Three patterns were obse rved: in three patients the rearrangements in each patient were identi cal, in six patients all the rearrangements were unrelated and unique, and in three patients both identical and unrelated rearrangements wer e detected. Apparently somatic mutations of V-H genes were present in some Reed-Sternberg cells but absent in others. Conclusions. Reed-Ster nberg cells with B-cell phenotypes have rearranged V-H genes; therefor e, these cells arise from B cells. The pattern of V-H gene mutations s uggests that Reed-Sternberg cells can correspond to either immunologic ally naive or memory B cells. In half our patients the population of R eed-Sternberg cells was polyclonal; in the other half, monoclonal or m ixed cell populations were found. Correlation with the clinical stage suggests that polyclonal Hodgkin's disease can present as a widespread lymphoma.