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. I
n a subset of cHD, however, H/RS cells expressing T cell-associated protein
s may be candidates for alternative lineage derivation. Single H/RS cells w
ith cytotoxic T cell, phenotype were micromanipulated from three cases of c
HD and analyzed by single cell polymerase chain reaction for immunoglobulin
heavy (IgH) and light chain (IgL) gene rearrangements, T cell receptor (TC
R)-beta gene rearrangements, and germline configuration of the ISH and TCR-
beta loci. H/RS cells from two cases of cHD harbored clonal, somatically mu
tated Ig gene rearrangements, whereas TCR-beta loci were in germline config
uration. In contrast, H/RS cells from an additional case harbored clonal TC
R-beta variable/diversity/joining (VDJ) and DJ gene rearrangements whereas
the IgH locus was in germline configuration on both alleles. Thus, in two c
ases of cHD with H/RS cells expressing cytotoxic T cell molecules, the tumo
r cells are derived from mature B cells that aberrantly express T cell mark
ers. In a third case, however, H/RS cells were derived from a T cell, demon
strating that cHD can also occur as a T cell lymphoma.