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Previous Volume 340:394-395 February 4, 1999 Number 5 Next

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To the Editor: In 1995 we reported in the Journal the results of a molecular analysis of single Reed–Sternberg cells in biopsy specimens from patients with Hodgkin's disease.¹ Amplified immunoglobulin heavy-chain gene sequences bore the hallmarks of B cells, and in 6 of the 12 cases we studied, there was evidence of the presence of monoclonal Reed–Sternberg cells — that is, identical immunoglobulin-gene rearrangements in several different Reed–Sternberg cells. Unexpectedly, we also found polyclonal Reed–Sternberg cells (i.e., cells with unrelated immunoglobulin-gene rearrangements). Other groups have also found polyclonal Reed–Sternberg cells,² but some investigators indicated that the cells in individual cases were derived from a single precursor.³

We have continued to study the clonal nature of Reed–Sternberg cells, and we believe that we can now satisfactorily account for these conflicting data. First, it is clear that Reed–Sternberg cells show a high degree of immunoglobulin-gene somatic mutations, which means that family-specific V_H primers rather than consensus primers are required for the polymerase chain reaction that allows identification of clonal immunoglobulin-gene rearrangements. Second, when Reed–Sternberg cells (or other cells) are isolated, precautions must be taken to avoid aspirating medium that contains DNA leached from the polyclonal reactive B cells present in the tissue sample.

Unless scrupulous attention is paid to these technical aspects of the method, there is a risk that artifactual results may suggest a polyclonal proliferative process in Hodgkin's disease. In our original cases, and in 25 cases analyzed more recently, we did not find polyclonal immunoglobulin sequences in Reed–Sternberg cells, and we are therefore persuaded that these cells are of monoclonal origin.

Michael Hummel, Ph.D.
Theresa Marafioti, M.D.
Harald Stein, M.D.
Freie Universität Berlin
D-12200 Berlin, Germany

References

1. Hummel M, Ziemann K, Lammert H, Pileri S, Sabattini E, Stein H. Hodgkin's disease with monoclonal and polyclonal populations of Reed-Sternberg cells. N Engl J Med 1995;333:901-906. [Free Full Text]
2. Delabie J, Tierens A, Gavrill T, Wu G, Weisenburger DD, Chan WC. Phenotype, genotype and clonality of Reed-Sternberg cells in nodular sclerosis Hodgkin's disease: results of a single-cell study. Br J Haematol 1996;94:198-205. [CrossRef][Medline]
3. Kanzler H, Küppers R, Hansmann ML, Rajewsky K. Hodgkin and Reed-Sternberg cells in Hodgkin's disease represent the outgrowth of a dominant tumor clone derived from (crippled) germinal center B cells. J Exp Med 1996;184:1495-1505. [Free Full Text]

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