Correspondence

Correction

Clonality of Reed–Sternberg Cells in Hodgkin's Disease

N Engl J Med 1999; 340:394-395February 4, 1999

Article

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

3 References

1. 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
   Full Text | Web of Science | Medline

2. 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 | Web of Science | Medline

3. 3

   Kanzler H, Kuppers 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
   CrossRef | Web of Science | Medline

Citing Articles (4)

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   Cheng Liu, Frida Schain, Hongya Han, Dawei Xu, Hillevi Andersson-Sand, Pontus Forsell, Hans-Erik Claesson, Magnus Björkholm, Jan Sjöberg. (2011) Epigenetic and transcriptional control of the 15-lipoxygenase-1 gene in a Hodgkin lymphoma cell line. Experimental Cell Research
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   Alessia Caleo, Abel S??nchez-Aguilera, Sandra Rodr??guez, Ana M. Dotor, Luis Beltr??n, Aitor F. de Larrinoa, Francisco J. Men??rguez, Miguel A. Piris, Juan F. Garc??a. (2003) Composite Hodgkin Lymphoma and Mantle Cell Lymphoma. The American Journal of Surgical Pathology 27:12, 1577-1580
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   Lian-hua Kim, Suat-cheng Peh, Sibrand Poppema. (2003) Dual variant of Epstein-Barr virus in Hodgkin/Reed-Sternberg cells: Single-cell PCR study onlatent membrane protein-1 gene. International Journal of Cancer 107:2, 250-255
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4. 4

   Hsiao-Wen Chang, Siew-Meng Chong, Suat-Cheng Peh, Szu-Hee Lee. (1999) X-chromosome inactivation analysis of isolated Reed-Sternberg cells in nodular sclerosing Hodgkin's disease. British Journal of Haematology 107:3, 641-647
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