Analysis of a clonally related mantle cell and Hodgkin lymphoma indicates Epstein-Barr virus infection of a Hodgkin/Reed-Sternberg cell precursor in a germinal center

Am J Surg Pathol. 2003 Nov;27(11):1483-8. doi: 10.1097/00000478-200311000-00014.


The simultaneous occurrence of a Hodgkin lymphoma (HL) and a non-Hodgkin lymphoma (NHL) is a rare event, and single cell analyses of such composite lymphomas revealed that NHL and Hodgkin/Reed-Sternberg (HRS) tumor cells are frequently descendants of the same tumor clone precursors. Here we present a composite lymphoma consisting of a mantle cell lymphoma (MCL) and an HL with EBV- and EBV+ HRS cells. Analysis of rearranged V genes of single cells revealed a clonal relationship between MCL and HL tumor cells. Although V gene rearrangements of the MCL were unmutated, mutations were observed in HRS cells. Besides mutations shared by all HRS cells, the EBV+ HRS cells carried identical additional mutations. These findings show that both lymphomas derive from a common precursor, most likely a pre germinal center (GC) B cell that already carried some transforming event(s). However, the presence of mutations in the V genes of the HRS cells further corroborates the importance of the GC reaction for the pathogenesis of HL. Importantly, the finding that only a subclone of the HRS clone, defined by a particular mutation pattern, was EBV infected represents a strong indication that EBV infection of the HRS cell precursor happened in the GC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Animals
  • Clone Cells
  • Epstein-Barr Virus Infections / complications
  • Epstein-Barr Virus Infections / pathology*
  • Gene Rearrangement
  • Germinal Center / pathology
  • Germinal Center / virology
  • Herpesvirus 4, Human / genetics
  • Herpesvirus 4, Human / isolation & purification
  • Herpesvirus 4, Human / pathogenicity
  • Hodgkin Disease / pathology*
  • Hodgkin Disease / virology
  • Humans
  • Immunoglobulin Variable Region / genetics
  • Immunohistochemistry
  • Immunophenotyping
  • In Situ Hybridization
  • Lymphoma, Mantle-Cell / pathology*
  • Lymphoma, Mantle-Cell / virology
  • Male
  • Micromanipulation
  • Polymerase Chain Reaction
  • RNA-Binding Proteins / analysis
  • Reed-Sternberg Cells / pathology*
  • Reed-Sternberg Cells / virology
  • Ribosomal Proteins*


  • Immunoglobulin Variable Region
  • RNA-Binding Proteins
  • Ribosomal Proteins
  • RPL22 protein, human