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Blood, Vol. 95 No. 10 (May 15), 2000:
pp. 3020-3024
PLENARY PAPER
Detection of clonal T-cell receptor gamma-chain gene
rearrangements in Reed-Sternberg cells of classic Hodgkin disease
Volkhard Seitz,
Michael Hummel,
Theresa Marafioti,
Ioannis Anagnostopoulos,
Chalid Assaf, and
Harald Stein
Institute of Pathology, Consultation and Reference Center for Lymph
Node Pathology and Haematopathology, University Hospital Benjamin
Franklin, Free University Berlin, Berlin, Germany.
Recent molecular single-cell studies have shown that in
approximately 95% of cases, Reed-Sternberg cells of classic Hodgkin disease (HD) are derived from B cells of germinal center origin. Attempts to determine the cellular nature of the remaining cases have
so far failed. To clarify whether they are derived from T cells, this
study examined 791 single CD30+ Hodgkin and
Reed-Sternberg (HRS) cells from 13 T-cell marker-positive cases and
from 6 cases with null-cell phenotype for rearranged T-cell
receptor-gamma (TCR- ) genes by single copy polymerase chain
reaction. Monoclonally rearranged TCR- genes were detectable in 2 of
the 13 classic HD cases with T-cell marker-positive HRS cells, with
none detectable in the null-cell cases. Eight of the T-cell
marker-positive cases and all 6 null-cell cases were also studied for
rearrangements of immunoglobulin genes. Six of the 8 T-cell
marker-positive cases harbored clonal immunoglobulin gene
rearrangements. The 2 cases without rearranged immunoglobulin genes
were those that contained clonal TCR- rearrangements and lacked
expression of the B-cell-specific activator protein. From these
findings we conclude that cases of classic HD with T-cell-derived HRS
cells definitely exist, although their overall incidence at 1% to 2%
is very low. Even within the T-cell marker-positive cases only a
minority (15%) were derived from T cells. The majority (85%)
originated from B cells, indicating that the T-cell antigens expressed
by HRS cells are, in contrast to those expressed in non-Hodgkin
lymphoma, not lineage specific.
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