Atlas of Genetics and Cytogenetics in Oncology and Haematology

Home   Genes   Leukemias   Solid Tumors   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

X Y 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 NA

Hodgkin lymphoma

Written2010-09Ralf Küppers
Institut of Cell Biology (Cancer Research) University of Duisburg-Essen, Medical School, Virchowstrasse 173, 45122 Essen, Germany
This article is an update of :
1999-05Niels B Atkin
Department of Cancer Research, Mount Vernon Hospital, Northwood, Middlesex, UK

(Note : for Links provided by Atlas : click)


ICD-Morpho 9650/3 Classical Hodgkin lymphoma
Atlas_Id 2068
Other namesHodgkin's disease (HD)

Clinics and Pathology

Note 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-Hodgkin's 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%.


  • 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.
  • Cytogenetics

    Cytogenetics Morphological
  • The neoplastic cells in typical HL lymph nodes comprise mononuclear Hodgkin and multilobate, binucleate or multinucleate Reed-Sternberg cells, and that these are clonal with modal chromosome numbers varying from case to case is indicated from direct chromosome analysis and DNA measurements and directly shown by the detection of clonal immunoglobulin V gene rearrangements in isolated HRS cells.
  • The modes are about twice as frequently in the triploid-tetraploid (particularly 65-80 chromosomes) as neardiploid region; the clonal aneuploidy has been demonstrated by simultaneous fluorescence immunophenotyping and interphase chromosomal analysis to occur in the Hodgkin and Reed-Sternberg cells.
  • Unlike NHLs, where a number of chromosomal translocations specific for histopathological types of tumor have been discovered, similarly specific changes have unfortunately not been reported for HD; occasionally, translocations such as t(14;18) that are common in specific types of NHL have been found; translocations involving the immunoglobulin loci have been found in about 20% of classical HL, but the partner genes are mostly still unknown; deletions and duplications, common in other types of tumor, including NHLs, have been described in HL, such as del(1p), dup(1q), del(6q) and del(7q); a nonrandom change involving chromosome 4, with breakpoints in the region 4q25-28, has been found on several occasions and merits further investigation.
  • In chromosome studies, both direct and after culturing, diploid as well as aneuploid metaphases are commonly found in HD, not unexpectedly since histopathological studies usually reveal a considerable excess of lymphocytes and other cells with normal morphology compared to the aneuploid Hodgkin and Reed-Sternberg cells; a recent intriguing finding using FISH, however, has been that 1-12% of "normal" nuclei in HD have abnormalities, most commonly trisomies for various chromosomes.
  • The multinucleated Reed-Sternberg cells most likely derive from mononucleated Hodgkin cells through a process similar to endomitosis, i.e. nuclear division without cell division.
  • Bibliography

    Cytogenetics of Hodgkin's disease.
    Atkin NB.
    Cytogenet Cell Genet. 1998;80(1-4):23-7.
    PMID 9678329
    Detection of genomic imbalances in microdissected Hodgkin and Reed-Sternberg cells of classical Hodgkin's lymphoma by array-based comparative genomic hybridization.
    Hartmann S, Martin-Subero JI, Gesk S, Husken J, Giefing M, Nagel I, Riemke J, Chott A, Klapper W, Parrens M, Merlio JP, Kuppers R, Brauninger A, Siebert R, Hansmann ML.
    Haematologica. 2008 Sep;93(9):1318-26. Epub 2008 Jul 18.
    PMID 18641027
    Hodgkin lymphoma.
    Hoppe RT, Mauich PT, Armitage JO, Dielh V, Weiss LM (editors).
    Lippincott Williams & Wilkins, Philadelphia 2nd edition, 2007.
    Chromosomal abnormalities in Hodgkin's disease are not restricted to Hodgkin/Reed-Sternberg cells.
    Jansen MP, Hopman AH, Haesevoets AM, Gennotte IA, Bot FJ, Arends JW, Ramaekers FC, Schouten HC.
    J Pathol. 1998 Jun;185(2):145-52.
    PMID 9713340
    Hodgkin's disease.
    Kaplan HS.
    Kaplan HS: Second Edition. Harvard University Press, Massachusetts 1980.
    Precursors of Hodgkin's disease and B-cell lymphomas.
    Manis JP.
    N Engl J Med. 1999 Apr 22;340(16):1280-2.
    PMID 10210714
    TNFAIP3 (A20) is a tumor suppressor gene in Hodgkin lymphoma and primary mediastinal B cell lymphoma.
    Schmitz R, Hansmann ML, Bohle V, Martin-Subero JI, Hartmann S, Mechtersheimer G, Klapper W, Vater I, Giefing M, Gesk S, Stanelle J, Siebert R, Kuppers R.
    J Exp Med. 2009 May 11;206(5):981-9. Epub 2009 Apr 20.
    PMID 19380639
    Pathogenesis of classical and lymphocyte-predominant Hodgkin lymphoma.
    Schmitz R, Stanelle J, Hansmann ML, Kuppers R.
    Annu Rev Pathol. 2009;4:151-74. (Review)
    PMID 19400691
    Hodgkin's disease--time for a change.
    Schwartz RS.
    N Engl J Med. 1997 Aug 14;337(7):495-6.
    PMID 9250855
    Genome-wide copy number analysis of Hodgkin Reed-Sternberg cells identifies recurrent imbalances with correlations to treatment outcome.
    Steidl C, Telenius A, Shah SP, Farinha P, Barclay L, Boyle M, Connors JM, Horsman DE, Gascoyne RD.
    Blood. 2010 Jul 22;116(3):418-27. Epub 2010 Mar 25.
    PMID 20339089
    Numerical chromosome aberrations are present within the CD30+ Hodgkin and Reed-Sternberg cells in 100% of analyzed cases of Hodgkin's disease.
    Weber-Matthiesen K, Deerberg J, Poetsch M, Grote W, Schlegelberger B.
    Blood. 1995 Aug 15;86(4):1464-8.
    PMID 7632954


    This paper should be referenced as such :
    Köppers, R
    Hodgkin lymphoma
    Atlas Genet Cytogenet Oncol Haematol. 2011;15(6):527-528.
    Free journal version : [ pdf ]   [ DOI ]
    On line version :
    History of this paper:
    Atkin, NB. Hodgkin's disease. Atlas Genet Cytogenet Oncol Haematol. 1999;3(2):87-88.

    Other genes implicated (Data extracted from papers in the Atlas) [ 37 ]


    External links

    COSMICHisto = - Site = haematopoietic_and_lymphoid_tissue (COSMIC)
    arrayMap (UZH-SIB Zurich)Topo ( C42) Morph ( 9650/3) -   [auto + random 100 samples .. if exist ]   [tabulated segments]
    Other databaseLeukemia Society of America
    Other databaseHodgkin lymphomas&subsettype=CLINICALGROUP Lymphomas: Hodgkin lymphomas (Clinical group) - ArrayMap (UHZ-SIB)
    REVIEW articlesautomatic search in PubMed
    Last year articlesautomatic search in PubMed
    All articlesautomatic search in PubMed

    © Atlas of Genetics and Cytogenetics in Oncology and Haematology
    indexed on : Fri Oct 8 16:35:32 CEST 2021

    Home   Genes   Leukemias   Solid Tumors   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

    For comments and suggestions or contributions, please contact us