Hodgkin lymphoma

2010-09-01   Ralf Küppers  

1.Institut of Cell Biology (Cancer Research) University of Duisburg-Essen, Medical School, Virchowstrasse 173, 45122 Essen, Germany
2.Department of Cancer Research, Mount Vernon Hospital, Northwood, Middlesex, UK

Clinics and Pathology

Noted

t(2;5)

Disease

Hodgkin lymphoma (HL) involves a clonal expansion of neoplastic B lymphocytes. A very small subset of cases of classical HL may derive from T cells.

Epidemiology

A distinguishing feature with non-Hodgkins lymphomas (NHLs) is its relative frequency in patients under 20 years.

Pathology

About 95% of HL belong to the subgroup of classical HL, the remaining 5% are lymphocyte predominant HL. Most classical HL can be classified as nodular sclerotic (NS) or mixed cellularity (MS) subtypes; two uncommon subtypes, lymphocyte-rich classical and lymphocyte depletion, present less typical pictures and examples of the former have sometimes been reclassified as low-grade B-cell NHLs. In classical HL, the tumor cells are called Hodgkin and Reed-Sternberg (HRS) cells, in lymphocyte predominant HL they are nowadays called LP cells (previously L&H, lymphocytic and histiocytic, cells).

Prognosis

Unlike NHLs, the prognosis of HD has improved in recent decades with a five-year survival rate of over 80%.

Note

  • Several recurrent genetic lesions have been identified in HRS cells of classical HL. The most frequently found lesions affect members of the NF-kappaB or JAK/STAT signaling pathways: inactivating mutation in NFKBIA (10-20% of cases), NFKBIE (ca. 10% of cases), TNFAIP3 (40%), SOCS1 (40%), genomic gains of REL (30%) and JAK2 (30%) and rare BCL3 translocations. TNFAIP3 mutations are mainly found in Epstein-Barr virus-negative cases of HL, suggesting that TNFAIP3 mutations and EBV infection are alternative pathogenetic mechanisms in HL. In very rare instances, mutations have been found in the tumor suppressor genes CD95 and TP53. Four or six cases analysed were found to harbor gains of MDM2. Further genomic imbalances have been identified by comparative genomic hybridization studies; these include gains of IKBKB, CD40 and MAP3K14, i.e. further regulators of NF-kappaB signalling.
  • Few genetic lesions are known for LP cells of lymphocyte predominant HL: mutations in SOCS1 and translocations involving the BCL6 protooncogene. Mutations in TNFAIP3 or NFKBIA seem to play no role in LP cells, although they also show strong NF-kappaB activity.
  • Both HRS and LP cells show aberrant somatic hypermutation of several proto-oncogenes (PIM1, Rho/TTF, MYC, PAX5) in a considerable fraction of cases. However, as most mutations are in the 5 untranslated regions of the genes, it is unclear whether or which fractions of these mutations have a pathogenetic relevance.

    • Genes Involved and Proteins

    Article Bibliography

    Pubmed IDLast YearTitleAuthors
    96783291998Cytogenetics of Hodgkin's disease.Atkin NB et al
    186410272008Detection of genomic imbalances in microdissected Hodgkin and Reed-Sternberg cells of classical Hodgkin's lymphoma by array-based comparative genomic hybridization.Hartmann S et al
    97133401998Chromosomal abnormalities in Hodgkin's disease are not restricted to Hodgkin/Reed-Sternberg cells.Jansen MP et al
    102107141999Precursors of Hodgkin's disease and B-cell lymphomas.Manis JP et al
    193806392009TNFAIP3 (A20) is a tumor suppressor gene in Hodgkin lymphoma and primary mediastinal B cell lymphoma.Schmitz R et al
    194006912009Pathogenesis of classical and lymphocyte-predominant Hodgkin lymphoma.Schmitz R et al
    92508551997Hodgkin's disease--time for a change.Schwartz RS et al
    203390892010Genome-wide copy number analysis of Hodgkin Reed-Sternberg cells identifies recurrent imbalances with correlations to treatment outcome.Steidl C et al
    76329541995Numerical chromosome aberrations are present within the CD30+ Hodgkin and Reed-Sternberg cells in 100% of analyzed cases of Hodgkin's disease.Weber-Matthiesen K et al

    Citation

    Ralf Küppers

    Hodgkin lymphoma

    Atlas Genet Cytogenet Oncol Haematol. 2010-09-01

    Online version: http://atlasgeneticsoncology.org/haematological/2068/hodgkin-lymphoma

    Historical Card

    1999-05-01 Hodgkin lymphoma by  Niels B Atkin 

    Department of Cancer Research, Mount Vernon Hospital, Northwood, Middlesex, UK