Rare occurrence of classical Hodgkin's disease as a T cell lymphoma - PubMed (original) (raw)

Rare occurrence of classical Hodgkin's disease as a T cell lymphoma

M Müschen et al. J Exp Med. 2000.

Abstract

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)-beta gene rearrangements, and germline configuration of the IgH and TCR-beta loci. H/RS cells from two cases of cHD harbored clonal, somatically mutated Ig gene rearrangements, whereas TCR-beta loci were in germline configuration. In contrast, H/RS cells from an additional case harbored clonal TCR-beta 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.

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Figures

Figure 1

Figure 1

Immunostaining of cHD, case III. Histological stainings were as follows: (A) the tissue is stained for CD30 with the use of alkaline phosphatase (4-fold magnification); (B) hemalaun-eosin staining of some multinucleated Reed-Sternberg cells at 60-fold magnification; (C) staining for CD15 at 40-fold magnification. Staining of this case for expression of perforin is shown on the cover illustration of this issue.

Figure 2

Figure 2

Amplification of IgH gene and TCR-β gene rearrangements from H/RS cells. PCR strategies for amplification of PCR products which are specific for IgH (A) or TCR-β (B) germline configuration (i), DJ gene rearrangements (ii), and VDJ gene rearrangements (iii) are depicted. VH1-VH7 and Vβ1-Vβ24 represent the seven Ig VH gene families and the 24 TCR Vβ gene families; and JH1-JH6 and Jβ1.1-1.6 and Jβ2.1-2.7 indicate the Ig JH and the TCR Jβ genes, respectively. The IgH DJ (A, ii) and IgH VDJ (A, iii) rearrangements and TCR-β DJ (B, ii) and TCR-β VDJ (B, iii) rearrangements depict those amplified from cases I and III, respectively. Arrows indicate the PCR primers used (not to scale). (C) A fragment (codons 95–115) of the sequence alignment of the clonal TCR Vβ7.1–Dβ1–Jβ1.6 rearrangement amplified from single H/RS cells of case III is given. The germline sequence of Vβ7.1, Dβ1, and Jβ1.6 genes (top) is compared with the clonal sequence variants (A, B, and C) obtained from eight, two, and four H/RS cells of case III, respectively. The three sequence variants (A, B, and C) differ by single nucleotide substitutions in codons 98, 105, and 108 (complete sequence data are available from GenBank/EMBL/DDBJ under accession nos. AJ243645–AJ243647). (D) Sequence alignment of the clonal TCR Dβ1–Jβ1.4 rearrangement amplified from 14 H/RS cells of case III is given. In contrast to the clonal Vβ7.1 gene rearrangement (C), the Dβ1–Jβ1.4 gene rearrangement does not exhibit intraclonal diversity (complete sequence data is available from GenBank/EMBL/DDBJ under accession no. AJ243648).

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