The Journal of Experimental Medicine
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© The Rockefeller University Press, 0022-1007/2000/1/387/ $5.00
The Journal of Experimental Medicine, Volume 191, Number 2, January 17, 2000 387-394

Brief Definitive Report

Rare Occurrence of Classical Hodgkin's Disease as a T Cell Lymphoma

Markus Müschena,b, Klaus Rajewskya, Andreas Bräuningerc, Audrey Sylvia Baurc,d, Joost J. Oudejanse, Axel Roersa, Martin-Leo Hansmannc, and Ralf Küppersa,b
a Institute for Genetics, Department of Immunology,
b Department of Internal Medicine, Universität zu Köln, 50931 Köln, Germany
c Department of Pathology, University of Frankfurt, 60596 Frankfurt, Germany
d University Institute of Pathology, University Hospital CHUV, 1011 Lausanne, Switzerland
e Department of Pathology, Free University Hospital, 1081 HV Amsterdam, The Netherlands

Correspondence to: Markus Müschen, Universität zu Köln, Medizinische Klinik I, LFI E4 R705, Joseph-Stelzmann-Strasse 9, 50931 Köln, Germany. Tel:49-221-478-4490 Fax:49-221-478-6383 E-mail:markus.mueschen{at}uni-koeln.de.

Recent work identified Hodgkin and Reed-Sternberg (H/RS) cells in classical Hodgkin's disease (cHD) as clonal progeny of mature B cells. Therefore, it is generally assumed that cHD homogenously represents a B cell lymphoma. In a subset of cHD, however, H/RS cells expressing T cell–associated proteins may be candidates for alternative lineage derivation. Single H/RS cells with cytotoxic T cell phenotype were micromanipulated from three cases of cHD and analyzed by single cell polymerase chain reaction for immunoglobulin heavy (IgH) and light chain (IgL) gene rearrangements, T cell receptor (TCR)-ß gene rearrangements, and germline configuration of the IgH and TCR-ß loci. H/RS cells from two cases of cHD harbored clonal, somatically mutated Ig gene rearrangements, whereas TCR-ß loci were in germline configuration. In contrast, H/RS cells from an additional case harbored clonal TCR-ß variable/diversity/joining (VDJ) and DJ gene rearrangements, whereas the IgH locus was in germline configuration on both alleles. Thus, in two cases of cHD with H/RS cells expressing cytotoxic T cell molecules, the tumor cells are derived from mature B cells that aberrantly express T cell markers. In a third case, however, H/RS cells were derived from a T cell, demonstrating that cHD can also occur as a T cell lymphoma.

Key Words: Hodgkin's disease, T cell receptor genes, immunoglobulin genes, somatic hypermutation, Epstein-Barr virus


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