Identification of common germinal-center B-cell precursors in two patients with both Hodgkin's disease and non-Hodgkin's lymphoma

N Engl J Med. 1999 Apr 22;340(16):1239-47. doi: 10.1056/NEJM199904223401604.


Background: Hodgkin's disease and non-Hodgkin's B-cell lymphoma occasionally occur in the same patient. The identification of a common precursor of the two types of lymphoma would show definitively that Reed-Sternberg cells originate from B cells.

Methods: We studied lymphomas from two patients, one with a composite lymphoma (classic Hodgkin's disease and a follicular lymphoma in the same lymph node) and the other with a T-cell-rich B-cell lymphoma that was followed by classic Hodgkin's disease. Single Reed-Sternberg cells and non-Hodgkin's lymphoma cells from frozen sections were micromanipulated. The rearranged immunoglobulin variable-region genes (V genes) of the heavy and light chains were amplified by the polymerase chain reaction from genomic DNA and sequenced.

Results: In both patients, the Reed-Sternberg cells were related clonally to the non-Hodgkin's lymphoma B cells. The V genes carried somatic mutations (a hallmark of germinal-center B cells and their descendants). In both patients, some somatic mutations were shared by the Reed-Sternberg and non-Hodgkin's lymphoma cells, whereas other somatic mutations were found exclusively in one or the other cell type.

Conclusions: In two patients with classic Hodgkin's disease and non-Hodgkin's B-cell lymphoma, we identified a common B-cell precursor, probably a germinal-center B-cell, for both lymphomas. This finding suggests that the two types of lymphoma underwent both shared and distinct transforming events and provides proof of the B-cell derivation of Reed-Sternberg cells in classic Hodgkin's disease.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Amino Acid Sequence
  • B-Lymphocytes* / immunology
  • Base Sequence
  • Female
  • Gene Rearrangement*
  • Gene Rearrangement, B-Lymphocyte
  • Genes, Immunoglobulin
  • Hodgkin Disease / genetics
  • Hodgkin Disease / immunology
  • Hodgkin Disease / pathology*
  • Humans
  • Immunoglobulin Variable Region / genetics*
  • Lymphoma, B-Cell / genetics
  • Lymphoma, B-Cell / immunology
  • Lymphoma, B-Cell / pathology*
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Mutation
  • Polymerase Chain Reaction
  • Reed-Sternberg Cells* / immunology


  • Immunoglobulin Variable Region

Associated data

  • GENBANK/AJ011130
  • GENBANK/AJ011131
  • GENBANK/AJ011132
  • GENBANK/AJ011133
  • GENBANK/AJ011134
  • GENBANK/AJ011135
  • GENBANK/AJ011136
  • GENBANK/AJ011137
  • GENBANK/AJ011138
  • GENBANK/AJ011139