Skip to main content
Log in

Pathologie des Hodgkin-Lymphoms

Pathology of Hodgkin’s lymphoma

Der Onkologe Aims and scope

Zusammenfassung

Hodgkin-Lymphome sind die häufigsten bösartigen Erkrankungen des Lymphknotens in Westeuropa. Anhand der Ausprägung von CD20 und CD30 durch die Tumorzellen unterscheidet man das lymphozytenreiche Hodgkin-Lymphom von den Subtypen des klassischen Hodgkin-Lymphoms. Die L&H-Zellen des lymphozytenreichen Hodgkin-Lymphom sind ebenso wie die Hodgkin- und Reed-Sternberg-Zellen des klassischen Hodgkin-Lymphoms klonale Proliferate. Sie stammen in der Regel von B-Zellen ab und stellen die eigentliche Tumorzellpopulation dar. Genexpressionsanalysen konnten zeigen, dass die Hodgkin- und Reed-Sternberg-Zellen des klassischen Hodgkin-Lymphoms einen globalen Verlust von typischen B-Zell-Genen zeigen und 6 verschiedene Rezeptortyrosinkinasen aberrant ausprägen. Die gleichzeitige Ausprägung verschiedener Rezeptortyrosinkinasen ist wahrscheinlich ein Transformationsmechanismus im Hodgkin-Lymphom. Die spezifische Hemmung dieser Kinasen ist ein möglicher Ansatz für eine neue Therapiestrategie.

Abstract

Hodgkin’s lymphoma is the most frequent malignant process of the lymph node in Western Europe. On the basis of the expression of CD20 and CD30 in the tumor cells, one can differentiate lymphocyte predominant Hodgkin’s lymphoma from classical Hodgkin’s lymphoma with its sub-types. L&H cells of lymphocyte predominant, and the Hodgkin and Reed-Sternberg cells of classical Hodgkin’s lymphoma are clonal proliferates. These usually descend from B cells and represent the actual tumor cell population. Gene expression analyses have demonstrated that the Hodgkin and Reed-Sternberg cells of classical Hodgkin’s lymphoma show a global loss of typical B cell genes and have an aberrant expression of six different receptor tyrosine kinases. Specific blocking of these kinases may be a new therapeutic option.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Abb. 1
Abb. 2
Abb. 3
Abbildung 4

Literatur

  1. Stein H, Delsol G, Pileri S et al. (2001) Hodgkin Lymphoma. In: Jaffe ES, Harris NL, Stein H, Vardiman JW (eds) World Health Organization Classification of Tumours. Pathology and Genetics of Tumours of Haematopoietic and Lymphoid Tissues. IARC Press, Lyon, pp 237–252

  2. van den Berg A, Visser L, Poppema S (1999) High Expression of the CC Chemokine TARC in Reed-Sternberg Cells. A Possible Explanation for the Characteristic T-Cell Infiltrate in Hodgkin‚s Lymphoma. Am J Pathol 154:1685–1691

    PubMed  Google Scholar 

  3. Küppers R, Rajewsky K, Zhao M, Simons G, Laumann R, Fischer R, Hansmann ML (1994) Hodgkin disease: Hodgkin and Reed-Sternberg cells picked from histological sections show clonal immunoglobulin gene rearrangements and appear to be derived from B cells at various stages of development. Proc Natl Acad Sci U S A 91:10962–10966

    PubMed  Google Scholar 

  4. Kanzler H, Küppers R, Hansmann ML, Rajewsky K (1996) Hodgkin and Reed-Sternberg cells in Hodgkin’s disease represent the outgrowth of a dominant tumor clone derived from (crippled) germinal center B cells. J Exp Med 184:1495–1505

    Article  PubMed  Google Scholar 

  5. Marafioti T, Hummel M, Foss HD et al. (2000) Hodgkin and Reed-Sternberg cells represent an expansion of a single clone originating from a germinal center B-cell with functional immunoglobulin gene rearrangements but defective immunoglobulin transcription. Blood 95:1443–1450

    PubMed  Google Scholar 

  6. Bräuninger A, Küppers R, Strickler JG, Wacker HH, Rajewsky K, Hansmann ML (1997) Hodgkin and Reed-Sternberg cells in lymphocyte predominant Hodgkin disease represent clonal populations of germinal center-derived tumor B cells. Proc Natl Acad Sci U S A 94:9337–9342

    Article  PubMed  Google Scholar 

  7. Marafioti T, Hummel M, Anagnostopoulos I et al. (1997) Origin of nodular lymphocyte-predominant Hodgkin’s disease from a clonal expansion of highly mutated germinal-center B cells. N Engl J Med 337:453–458

    Article  PubMed  Google Scholar 

  8. Bräuninger A, Wacker HH, Rajewsky K, Küppers R, Hansmann ML (2003) Typing the histogenetic origin of the tumor cells of lymphocyte-rich classical Hodgkin’s lymphoma in relation to tumor cells of classical and lymphocyte-predominance Hodgkin’s lymphoma. Cancer Res 63:1644–1651

    PubMed  Google Scholar 

  9. Küppers R, Schwering I, Bräuninger A, Rajewsky K, Hansmann ML (2002) Biology of Hodgkin’s lymphoma. Ann Oncol 13 Suppl 1:11–18

    Google Scholar 

  10. Bräuninger A, Hansmann ML, Strickler JG, Dummer R, Burg G, Rajewsky K, Küppers R (1999) 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 340:1239–1247

    Article  PubMed  Google Scholar 

  11. Marafioti T, Hummel M, Anagnostopoulos I, Foss HD, Huhn D, Stein H (1999) Classical Hodgkin’s disease and follicular lymphoma originating from the same germinal center B cell. J Clin Oncol 17:3804–3809

    PubMed  Google Scholar 

  12. Ohno T, Huang JZ, Wu G, Park KH, Weisenburger DD, Chan WC (2001) The tumor cells in nodular lymphocyte-predominant Hodgkin disease are clonally related to the large cell lymphoma occurring in the same individual. Direct demonstration by single cell analysis. Am J Clin Pathol 116:506–511

    Article  PubMed  Google Scholar 

  13. Bargou RC, Emmerich F, Krappmann D et al. (1997) Constitutive nuclear factor-kappaB-RelA activation is required for proliferation and survival of Hodgkin’s disease tumor cells. J Clin Invest 100:2961–2969

    PubMed  Google Scholar 

  14. Küppers R (2002) Molecular biology of Hodgkin’s lymphoma. Adv Cancer Res 84:277–312

    PubMed  Google Scholar 

  15. Cabannes E, Khan G, Aillet F, Jarrett RF, Hay RT (1999) Mutations in the IkBa gene in Hodgkin’s disease suggest a tumour suppressor role for IkappaBalpha. Oncogene 18:3063–3070

    Article  PubMed  Google Scholar 

  16. Jungnickel B, Staratscheck-Jox A, Bräuninger A et al. (2000) Clonal Deleterious Mutations in the IκBα Gene in the Malignant Cells in Hodgkin‚s Lymphoma. J Exp Med 191:395–402

    Article  PubMed  Google Scholar 

  17. Emmerich F, Meiser M, Hummel M et al. (1999) Overexpression of I Kappa B Alpha Without Inhibition of NF-kappa B Activity and Mutations in the I Kappa B Alpha Gene in Reed-Sternberg Cells. Blood 94:3129–3134

    PubMed  Google Scholar 

  18. Joos S, Granzow M, Holtgreve-Grez H et al. (2003) Hodgkin’s lymphoma cell lines are characterized by frequent aberrations on chromosomes 2p and 9p including REL and JAK2. Int J Cancer 103:489–495

    Article  PubMed  Google Scholar 

  19. Müschen M, Re D, Bräuninger A et al. (2000) Somatic mutations of the CD95 gene in Hodgkin and Reed-Sternberg cells. Cancer Res 60:5640–5643

    PubMed  Google Scholar 

  20. Mathas S, Lietz A, Anagnostopoulos I et al.(2004) c-FLIP mediates resistance of Hodgkin/Reed-Sternberg cells to death receptor-induced apoptosis. J Exp Med 199:1041–1052

    Article  PubMed  Google Scholar 

  21. Kashkar H, Haefs C, Shin H, Hamilton-Dutoit SJ, Salvesen GS, Krönke M, Jürgensmeier JM (2003) XIAP-mediated caspase inhibition in Hodgkin’s lymphoma-derived B cells. J Exp Med 198:341–347

    Article  PubMed  Google Scholar 

  22. Stein H, Marafioti T, Foss HD et al. (2001) Down-regulation of BOB.1/OBF.1 and Oct2 in classical Hodgkin disease but not in lymphocyte predominant Hodgkin disease correlates with immunoglobulin transcription. Blood 97:496–501

    Article  PubMed  Google Scholar 

  23. Torlakovic E, Tierens A, Dang HD, Delabie J (2001) The transcription factor PU.1, necessary for B-cell development is expressed in lymphocyte predominance, but not classical Hodgkin’s disease. Am J Pathol 159:1807–1814

    PubMed  Google Scholar 

  24. Schwering I, Bräuninger A, Klein U et al. (2003) Loss of the B-lineage-specific gene expression program in Hodgkin and Reed-Sternberg cells of Hodgkin lymphoma. Blood 101:1505–1512

    Article  PubMed  Google Scholar 

  25. Foss HD, Reusch R, Demel G, Lenz G, Anagnostopoulos I, Hummel M, Stein H (1999) Frequent expression of the B-cell-specific activator protein in Reed- Sternberg cells of classical Hodgkin’s disease provides further evidence for its B-cell origin. Blood 94:3108–3113

    PubMed  Google Scholar 

  26. Willenbrock K, Ichinohasama R, Kadin ME et al. (2002) T-cell variant of classical Hodgkin’s lymphoma with nodal and cutaneous manifestations demonstrated by single-cell polymerase chain reaction. Lab Invest 82:1103–1109

    PubMed  Google Scholar 

  27. Jundt F, Anagnostopoulos I, Förster R, Mathas S, Stein H, Dörken B (2002) Activated Notch1 signaling promotes tumor cell proliferation and survival in Hodgkin and anaplastic large cell lymphoma. Blood 99:3398–3403

    Article  PubMed  Google Scholar 

  28. Rosenwald A, Wright G, Leroy K et al. (2003) Molecular Diagnosis of Primary Mediastinal B Cell Lymphoma Identifies a Clinically Favorable Subgroup of Diffuse Large B Cell Lymphoma Related to Hodgkin Lymphoma. J. Exp. Med. 198:851–862

    Google Scholar 

  29. Savage KJ, Monti S, Kutok JL et al. (2003) The molecular signature of mediastinal large B-cell lymphoma differs from that of other diffuse large B-cell lymphomas and shares features with classical Hodgkin lymphoma. Blood 102:3871–3879

    Article  PubMed  Google Scholar 

  30. Renné C, Willenbrock K, Küppers R, Hansmann ML, Bräuninger A (2005) Autocrine- and paracrine-activated receptor tyrosine kinases in classic Hodgkin lymphoma. Blood 105:4051–4059

    Article  PubMed  Google Scholar 

Download references

Interessenkonflikt:

Der korrespondierende Autor versichert, dass keine Verbindungen mit einer Firma, deren Produkt in dem Artikel genannt ist, oder einer Firma, die ein Konkurrenzprodukt vertreibt, bestehen.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to M.-L. Hansmann.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Willenbrock, K., Renné, C., Bräuninger, A. et al. Pathologie des Hodgkin-Lymphoms. Onkologe 11, 917–923 (2005). https://doi.org/10.1007/s00761-005-0935-0

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00761-005-0935-0

Schlüsselwörter

Keywords

Navigation