Pathogenesis of classical and lymphocyte-predominant Hodgkin lymphoma

Annu Rev Pathol. 2009;4:151-74. doi: 10.1146/annurev.pathol.4.110807.092209.


Hodgkin and Reed-Sternberg (HRS) cells in classical Hodgkin lymphoma (HL) and lymphocytic and histiocytic (L&H) cells in nodular lymphocyte-predominant HL (NLPHL) are derived from germinal-center B cells. HRS cells have, however, largely lost their B cell phenotype and aberrantly express markers and transcriptional regulators of other hematolymphoid cell types. Deregulation of multiple signaling pathways and downstream transcription factors, including receptor tyrosine kinases, nuclear factor-kappa B (NF-kappaB), and Janus kinase/signal transducer and activator of transcription (JAK/STAT), is a further hallmark of HRS cells. These cells harbor genetic lesions that contribute to or cause increases in the activity of transcription factors of the NF-kappaB and STAT families. HRS cells are found within a mixed reactive cellular infiltrate and interact with these nonmalignant cells in a complex fashion that appears to be essential for HRS cell survival and proliferation. Less is known about the pathogenesis of L&H cells in NLPHL, but increases in the activity of receptor tyrosine kinases, NF-kappaB, and JAK/STAT have also been detected.

Publication types

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

MeSH terms

  • Cell Differentiation
  • Cell Lineage
  • Gene Expression Regulation, Neoplastic
  • Gene Regulatory Networks
  • Histiocytes / immunology
  • Histiocytes / metabolism
  • Histiocytes / pathology*
  • Hodgkin Disease / genetics
  • Hodgkin Disease / immunology
  • Hodgkin Disease / metabolism
  • Hodgkin Disease / pathology*
  • Humans
  • Janus Kinases / metabolism
  • Lymphocytes / immunology
  • Lymphocytes / metabolism
  • Lymphocytes / pathology*
  • Lymphoma, B-Cell / pathology
  • Mediastinal Neoplasms / pathology
  • NF-kappa B / metabolism
  • Phenotype
  • Receptor Protein-Tyrosine Kinases / metabolism
  • Reed-Sternberg Cells / immunology
  • Reed-Sternberg Cells / metabolism
  • Reed-Sternberg Cells / pathology*
  • STAT Transcription Factors / metabolism
  • Signal Transduction / genetics


  • NF-kappa B
  • STAT Transcription Factors
  • Receptor Protein-Tyrosine Kinases
  • Janus Kinases