Advertisement

Current Hematologic Malignancy Reports

, Volume 4, Issue 3, pp 125–128 | Cite as

Is Hodgkin lymphoma just another B-cell lymphoma?

  • Harald SteinEmail author
  • Roshanak Bob
Article

Abstract

Hodgkin disease was the first defined lymphoid neoplasm. For many decades it was regarded as a disease separate from non-Hodgkin lymphoma. However, recent studies have shown that the dysplastic cells of Hodgkin lymphoma (HL) are monoclonal B cells. This finding raised again the question “Is HL just another B-cell lymphoma?” This article reviews the different aspects of HL and B-cell non-Hodgkin lymphoma (B-NHL), concluding that—despite the same cell of origin—fundamental differences exist in morphology, cellular composition, immunophenotype, activation or inhibition of transcription factors, epigenetics, and clinical behavior. These findings lead us to conclude that HL and B-NHLs should stay as two separate categories.

Keywords

Hodgkin Lymphoma Hodgkin Disease Classic Hodgkin Lymphoma Dysplastic Cell Nodular Lymphocyte Predominant Hodgkin Lymphoma 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References and Recommended Reading

  1. 1.
    Jaffe ES, Harris NL, Stein H, Issacson P: Classification of lymphoid neoplasms: the microscope as a tool for disease discovery. Blood 2008, 112:4384–4399.PubMedCrossRefGoogle Scholar
  2. 2.
    Mason DY, Banks PM, Chan J, et al.: Nodular lymphocyte predominance Hodgkin’s disease. A distinct clinicopathological entity. Am J Surg Pathol 1994, 18:526–530.PubMedCrossRefGoogle Scholar
  3. 3.
    Küppers R, Rajewsky K, Zhao M, et al.: 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 1994, 91:10962–10966.PubMedCrossRefGoogle Scholar
  4. 4.
    Marafioti T, Hummel M, Foss HD, et al.: 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 2000, 95:1443–1450.PubMedGoogle Scholar
  5. 5.
    Schwering I, Bräuninger A, Klein U, et al.: Loss of the B-lineage-specific gene expression program in Hodgkin and Reed-Sternberg cells of Hodgkin lymphoma. Blood 2003, 101:1505–1512.PubMedCrossRefGoogle Scholar
  6. 6.
    Marafioti T, Pozzobon M, Hansmann ML, et al.: Expression of intracellular signaling molecules in classical and lymphocyte predominance Hodgkin disease. Blood 2004, 103:188–193.PubMedCrossRefGoogle Scholar
  7. 7.
    Stein H, Marafioti T, Foss HD, et al.: 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 2001, 97:496–501.PubMedCrossRefGoogle Scholar
  8. 8.
    Loddenkemper C, Anagnostopoulos I, Hummel M, et al.: Differential Emu enhancer activity and expression of BOB.1/OBF.1, Oct2, PU.1, and immunoglobulin in reactive B-cell populations, B-cell non-Hodgkin lymphomas, and Hodgkin lymphomas. J Pathol 2004, 202:60–69.PubMedCrossRefGoogle Scholar
  9. 9.
    Dallenbach FE, Stein H: Expression of T-cell-receptor beta chain in Reed-Sternberg cells. Lancet 1989, 2(8667):828–830.PubMedCrossRefGoogle Scholar
  10. 10.
    Ehlers A, Oker E, Bentink S, et al.: Histone acetylation and DNA demethylation of B cells result in a Hodgkin-like phenotype. Leukemia 2008, 22:835–841.PubMedCrossRefGoogle Scholar
  11. 11.
    Mathas S, Hinz M, Anagnostopoulos I, et al.: Aberrantly expressed c-Jun and JunB are a hallmark of Hodgkin lymphoma cells, stimulate proliferation and synergize with NF-kappa B. EMBO J 2002, 21:4104–4113.PubMedCrossRefGoogle Scholar
  12. 12.
    Mathas S, Janz M, Hummel F, et al.: Intrinsic inhibition of transcription factor E2A by HLH proteins ABF-1 and Id2 mediates reprogramming of neoplastic B cells in Hodgkin lymphoma. Nat Immunol 2006, 7:207–215.PubMedCrossRefGoogle Scholar
  13. 13.
    Ushmorov A, Ritz O, Hummel M, et al.: Epigenetic silencing of the immunoglobulin heavy-chain gene in classical Hodgkin lymphoma-derived cell lines contributes to the loss of immunoglobulin expression. Blood 2004, 104:3326–3334.PubMedCrossRefGoogle Scholar
  14. 14.
    Collins GP, Paterson JC, May GE, et al.: Dysregulation of Pax5 activity contributes to the extinction of the B-cell phenotype in Reed-Sternberg cells[abstract 517]. Presented at the 50th American Society of Hematology Annual Meeting and Exposition. San Francisco; December 6–9, 2008.Google Scholar
  15. 15.
    Ushmorov A, Leithäuser F, Sakk O, et al.: Epigenetic processes play a major role in B-cell-specific gene silencing in classical Hodgkin lymphoma. Blood 2006, 107:2493–2500.PubMedCrossRefGoogle Scholar
  16. 16.
    Jundt F, Acikgöz O, Kwon SH, et al.: Aberrant expression of Notch1 interferes with the B-lymphoid phenotype of neoplastic B cells in classical Hodgkin lymphoma. Leukemia 2008, 22:1587–1594.PubMedCrossRefGoogle Scholar
  17. 17.
    Stein H, Delsol G, Pileri SA, et al.: Hodgkin lymphoma. In WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues, edn 4. Edited by Swerdlow SH, Campo E, Harris NL, et al.: Lyon, France: International Agency for Research on Cancer; 2008:321–334.Google Scholar
  18. 18.
    Fan Z, Natkunam Y, Bair E, et al.: Characterization of variant patterns of nodular lymphocyte predominant Hodgkin lymphoma with immunohistologic and clinical correlation. Am J Surg Pathol 2003, 27:1346–1356.PubMedCrossRefGoogle Scholar
  19. 19.
    Alkan S, Ross CW, Hanson CA, Schnitzer B: Epstein-Barr virus and bcl-2 protein overexpression are not detected in the neoplastic cells of nodular lymphocyte predominance Hodgkin’s disease. Mod Pathol 1995, 8:544–547.PubMedGoogle Scholar
  20. 20.
    Wang T, Lasota J, Hanau CA, Miettinen M: Bcl-2 oncoprotein is widespread in lymphoid tissue and lymphomas but its differential expression in benign versus malignant follicles and monocytoid B-cell proliferations is of diagnostic value. APMIS 1995, 103:655–662.PubMedCrossRefGoogle Scholar
  21. 21.
    Torlakovic E, Tierens A, Dang HD, Delabie J: The transcription factor PU.1, necessary for B-cell development is expressed in lymphocyte predominance, but not classical Hodgkin’s disease. Am J Pathol 2001, 159:1807–1814.PubMedGoogle Scholar
  22. 22.
    Prakash S, Fountaine T, Raffeld M, et al.: IgD positive L&H cells identify a unique subset of nodular lymphocyte predominant Hodgkin lymphoma. Am J Surg Pathol 2006, 30:585–592.PubMedCrossRefGoogle Scholar
  23. 23.
    Mottok A, Renné C, Willenbrock K, et al.: Somatic hypermutation of SOCS1 in lymphocyte-predominant Hodgkin lymphoma is accompanied by high JAK2 expression and activation of STAT6. Blood 2007, 110:3387–3390.PubMedCrossRefGoogle Scholar
  24. 24.
    Nogová L, Rudiger T, Engert A: Biology, clinical course and management of nodular lymphocyte-predominant Hodgkin lymphoma. Hematology Am Soc Hematol Educ Program 2006, 266–272.Google Scholar
  25. 25.
    Felgar RE, Steward KR, Coursar JB, Macon WR: Tcell rich large B-cell lymphomas contain non-activated CD8-positive cytoxic T cells, show increased tumor-cell apoptosis, have lower B-cell expression than diffuse large B-cell lymphomas. Am J Pathol 1998, 153:1707–1715.PubMedGoogle Scholar
  26. 26.
    Nam-Cha SH, Roncador G, Sanchez-Verde L, et al.: PD-1, a follicular T-cell marker useful for recognizing nodular lymphocyte-predominant Hodgkin lymphoma. Am J Surg Pathol 2008, 32:1252–1257.PubMedCrossRefGoogle Scholar
  27. 27.
    Marafioti T, Hummel M, Anagnostopoulos I, et al.: Origin of nodular lymphocyte-predominant Hodgkin’s disease from a clonal expansion of highly mutated germinal-center B cells. N Engl J Med 1997, 337:453–458.PubMedCrossRefGoogle Scholar
  28. 28.
    Liso A, Capello D, Marafioti T, et al.: Aberrant somatic hypermutation in tumor cells of nodular-lymphocyte-predominant and classic Hodgkin lymphoma. Blood 2006, 108:1013–1020.PubMedCrossRefGoogle Scholar
  29. 29.
    Pasqualucci L, Neumeister P, Goossens T, et al.: Hypermutation of multiple proto-oncogenes in B-cell diffuse large-cell lymphomas. Nature 2001, 412:341–346.PubMedCrossRefGoogle Scholar
  30. 30.
    Wlodarska I, Nooyen P, Maes B, et al.: Frequent occurrence of BCL6 rearrangements in nodular lymphocyte predominance Hodgkin lymphoma but not in classical Hodgkin lymphoma. Blood 2003, 101:706–710.PubMedCrossRefGoogle Scholar
  31. 31.
    Wlodarska I, Stul M, De Wolf-Peeters C, Hagemeijer A: Heterogeneity of BCL6 rearrangements in nodular lymphocyte predominant Hodgkin’s lymphoma. Haematologica 2004, 89:965–972.PubMedGoogle Scholar
  32. 32.
    Renné C, Martín-Subero JI, Hansmann ML, Siebert R: Molecular cytogenetic analyses of immunoglobulin loci in nodular lymphocyte predominant Hodgkin’s lymphoma reveal a recurrent IGH-BCL6 juxtaposition. J Mol Diagn 2005, 7:352–356.PubMedGoogle Scholar
  33. 33.
    Brune V, Tiacci E, Pfeil I, et al.: Origin and pathogenesis of nodular lymphocyte-predominant Hodgkin lymphoma as revealed by global gene expression analysis. J Exp Med 2008, 205:2251–2268.PubMedCrossRefGoogle Scholar
  34. 34.
    Tsai HK, Mauch PM: Nodular lymphocyte-predominant Hodgkin lymphoma [review]. Semin Radiat Oncol 2007, 17:184–189.PubMedCrossRefGoogle Scholar
  35. 35.
    El Weshi A, Akhtar S, Mourad WA, et al.: T-cell/histiocyterich B-cell lymphoma: clinical presentation, management and prognostic factors: report on 61 patients and review of literature. Leuk Lymphoma 2007, 48:1764–1773.PubMedCrossRefGoogle Scholar
  36. 36.
    Fanale MA, Younes A: Nodular lymphocyte predominant Hodgkin’s lymphoma [review]. Cancer Treat Res 2008, 142:367–381.PubMedGoogle Scholar

Copyright information

© Current Medicine Group, LLC 2009

Authors and Affiliations

  1. 1.Pathology Institute, Campus Benjamin FranklinCharité University of MedicineBerlinGermany

Personalised recommendations