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Advances in Hematology
Volume 2011 (2011), Article ID 920898, 18 pages
http://dx.doi.org/10.1155/2011/920898
Review Article

Pathobiology of Hodgkin Lymphoma

1Hematopathology Section, Department of Hematology and Oncological Sciences “L. and A. Seràgnoli”, S. Orsola-Malpighi Hospital, University of Bologna, 40126 Bologna, Italy
2Molecular Pathology Laboratory, Haematopathology Unit, Department of Haematology and Oncology “L. and A. Seràgnoli”, S. Orsola-Malpighi Hospital, University of Bologna, Via Massarenti, 9 - 40138 Bologna, Italy
3Department of Human Pathology, University of Palermo, 90133 Palermo, Italy

Received 30 August 2010; Accepted 11 November 2010

Academic Editor: Kensei Tobinai

Copyright © 2011 Pier Paolo Piccaluga et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. H. Stein, G. Delsol, S. Pileri, L. Weiss, S. Poppema, and E. Jaffe, “Classical Hodgkin lymphoma, introduction,” in WHO Classification of Tumors of the Hematopoietic and Lymphoid Tissue, S. Swerdlow, E. Campo, N. L. Harris et al., Eds., pp. 326–329, IARC, Lyon, France, 2008. View at Google Scholar
  2. M. Hummel, T. Marafioti, K. Ziemann, and H. Stein, “Ig rearrangements in isolated Reed-Sternberg cells: conclusions from four different studies,” Annals of Oncology, vol. 7, supplement 4, pp. S31–S33, 1996. View at Google Scholar · View at Scopus
  3. T. Marafioti, M. Hummel, and M. Hummel, “Origin of nodular lymphocyte-predominant Hodgkin's disease from a clonal expansion of highly mutated germinal-center B cells,” New England Journal of Medicine, vol. 337, no. 7, pp. 453–458, 1997. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  4. K. F. Izban, J. F. Nawrocki, S. Alkan, and E. D. Hsi, “Monoclonal IgH gene rearrangement in microdissected nodules from nodular sclerosis Hodgkin disease,” American Journal of Clinical Pathology, vol. 110, no. 5, pp. 599–606, 1998. View at Google Scholar · View at Scopus
  5. A. Bräuninger, M. L. Hansmann, J. G. Strickler, R. Dummer, G. Burg, K. Rajewsky, and R. Küppers, “Identification of common germinal-center B-cell precursors in two patients with both Hodgkin's disease and non-Hodgkin's lymphoma,” New England Journal of Medicine, vol. 340, no. 16, pp. 1239–1247, 1999. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  6. R. Küppers, U. Klein, M. L. Hansmann, and K. Rajewsky, “Cellular origin of human B-cell lymphomas,” New England Journal of Medicine, vol. 341, no. 20, pp. 1520–1529, 1999. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  7. T. Marafioti, M. Hummel, and M. Hummel, “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, vol. 95, no. 4, pp. 1443–1450, 2000. View at Google Scholar · View at Scopus
  8. V. Seitz, M. Hummel, T. Marafioti, I. Anagnostopoulos, C. Assaf, and H. Stein, “Detection of clonal T-cell receptor gamma-chain gene rearrangements Reed-Sternberg cells of classic Hodgkin disease,” Blood, vol. 95, no. 10, pp. 3020–3024, 2000. View at Google Scholar · View at Scopus
  9. S. Poppema, G. Delsol, S. Pileri et al., “Nodular lymphocyte predominant Hodgkin lymphoma,” in WHO Classification of Tumors of the Hematopoietic and Lymphoid Tissue, S. Swerdlow, E. Campo, N. L. Harris et al., Eds., pp. 323–325, IARC, Lyon, France, 2008. View at Google Scholar
  10. N. L. Harris, “Hodgkin's disease: classification and differential diagnosis,” Modern Pathology, vol. 12, no. 2, pp. 159–176, 1999. View at Google Scholar · View at Scopus
  11. E. S. Jaffe, “Introduction: Hodgkin's lymphoma—pathology, pathogenesis, and treatment,” Seminars in Hematology, vol. 36, no. 3, pp. 217–219, 1999. View at Google Scholar · View at Scopus
  12. N. L. Harris, E. S. Jaffe, and E. S. Jaffe, “The World Health Organization classification of neoplastic diseases of the haematopoietic and lymphoid tissues: report of the Clinical Advisory Committee Meeting, Airlie House, Virginia, November 1997,” Histopathology, vol. 36, no. 1, pp. 69–86, 2000. View at Publisher · View at Google Scholar · View at Scopus
  13. R. J. Jones, C. D. Gocke, and C. D. Gocke, “Circulating clonotypic B cells in classic Hodgkin lymphoma,” Blood, vol. 113, no. 23, pp. 5920–5926, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  14. B. Falini, S. Pileri, and S. Pileri, “CD30 (Ki-1) molecule: a new cytokine receptor of the tumor necrosis factor receptor superfamily as a tool for diagnosis and immunotherapy,” Blood, vol. 85, no. 1, pp. 1–14, 1995. View at Google Scholar · View at Scopus
  15. L. Teofili, A. L. Di Febo, and A. L. Di Febo, “Expression of the c-met proto-oncogene and its ligand, hepatocyte growth factor, in Hodgkin disease,” Blood, vol. 97, no. 4, pp. 1063–1069, 2001. View at Publisher · View at Google Scholar · View at Scopus
  16. N. L. Harris, E. S. Jaffe, and E. S. Jaffe, “A revised European-American classification of lymphoid neoplasms: a proposal from the International Lymphoma Study Group,” Blood, vol. 84, no. 5, pp. 1361–1392, 1994. View at Google Scholar · View at Scopus
  17. H. Stein, R. Von Wasielewski, S. Poppema, K. MacLennan, and M. Guenova, “Nodular sclerosis classical Hodgkin lymphoma,” in WHO Classification of Tumors of the Hematopoietic and Lymphoid Tissue, S. Swerdlow, E. Campo, N. L. Harris et al., Eds., p. 330, IARC, Lyon, France, 2008. View at Google Scholar
  18. L. Weiss, R. Von Wasielewski, G. Delsol, S. Poppema, and H. Stein, “Mixed cellularity classical Hodgkin lymphoma,” in WHO Classification of Tumors of the Hematopoietic and Lymphoid Tissue, S. Swerdlow, E. Campo, N. L. Harris et al., Eds., p. 331, IARC, Lyon, France, 2008. View at Google Scholar
  19. I. Anagnostopoulos, P. Isaacson, and H. Stein, “Lymphocyte-rich classical Hodgkin lymphoma,” in WHO Classification of Tumors of the Hematopoietic and Lymphoid Tissue, S. Swerdlow, E. Campo, and N. L. Harris, Eds., pp. 332–333, IARC, Lyon, France, 2008. View at Google Scholar
  20. D. Benharroch, H. Stein, and S. Peh, “Lymphocyte-depleted classical Hodgkin lymphoma,” in WHO Classification of Tumors of the Hematopoietic and Lymphoid Tissue, S. Swerdlow, E. Campo, N. L. Harris et al., Eds., p. 334, IARC, Lyon, France, 2008. View at Google Scholar
  21. N. L. Harris, E. S. Jaffe, and E. S. Jaffe, “World health organization classification of neoplastic diseases of the hematopoietic and lymphoid tissues: report of the clinical advisory committee meeting - Airlie house, Virginia, November 1997,” Journal of Clinical Oncology, vol. 17, no. 12, pp. 3835–3849, 1999. View at Google Scholar · View at Scopus
  22. I. Anagnostopoulos, M. L. Hansmann, and M. L. Hansmann, “European Task Force on Lymphoma project on lymphocyte predominance Hodgkin disease: histologic and immunohistologic analysis of submitted cases reveals 2 types of Hodgkin disease with a nodular growth pattern and abundant lymphocytes,” Blood, vol. 96, no. 5, pp. 1889–1899, 2000. View at Google Scholar · View at Scopus
  23. S. Poppema, E. Kaiserling, and K. Lennert, “Hodgkin's disease with lymphocytic predominance, nodular type (nodular paragranuloma) and progressively transformed germinal centres—a cytohistological study,” Histopathology, vol. 3, no. 4, pp. 295–308, 1979. View at Google Scholar · View at Scopus
  24. D. Y. Mason, P. M. Banks, and P. M. Banks, “Nodular lymphocyte predominance Hodgkin's disease. A distinct clinicopathological entity,” American Journal of Surgical Pathology, vol. 18, no. 5, pp. 526–530, 1994. View at Google Scholar · View at Scopus
  25. S. A. Rosenberg and H. S. Kaplan, “Evidence for an orderly progression in the spread of Hodgkin's disease,” Cancer Research, vol. 26, no. 6, pp. 1225–1231, 1966. View at Google Scholar · View at Scopus
  26. D. P. Regula Jr., R. T. Hoppe, and L. M. Weiss, “Nodular and diffuse types of lymphocyte predominance Hodgkin's disease,” New England Journal of Medicine, vol. 318, no. 4, pp. 214–219, 1988. View at Google Scholar · View at Scopus
  27. H. Kim, “Composite lymphoma and related disorders,” American Journal of Clinical Pathology, vol. 99, no. 4, pp. 445–451, 1993. View at Google Scholar · View at Scopus
  28. R. Von Wasielewski, M. Werner, and M. Werner, “Lymphocyte-predominant Hodgkin's disease: an immunohistochemical analysis of 208 reviewed Hodgkin's disease cases from the German Hodgkin study group,” American Journal of Pathology, vol. 150, no. 3, pp. 793–803, 1997. View at Google Scholar · View at Scopus
  29. J. Delabie, E. Vandenberghe, and E. Vandenberghe, “Histiocyte-rich B-cell lymphoma: a distinct clinicopathologic entity possibly related to lymphocyte predominant Hodgkin's disease, paragranuloma subtype,” American Journal of Surgical Pathology, vol. 16, no. 1, pp. 37–48, 1992. View at Google Scholar · View at Scopus
  30. K. Lennert, Malignant Lymphomas Other than Hodgkin's Disease, Springer, New York, NY, USA, 1978.
  31. P. L. Nguyen, J. A. Ferry, and N. L. Harris, “Progressive transformation of germinal centers and nodular lymphocyte predominance Hodgkin's disease: a comparative immunohistochemical study,” American Journal of Surgical Pathology, vol. 23, no. 1, pp. 27–33, 1999. View at Publisher · View at Google Scholar · View at Scopus
  32. H. Stein, T. Marafioti, and T. Marafioti, “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, vol. 97, no. 2, pp. 496–501, 2001. View at Publisher · View at Google Scholar · View at Scopus
  33. H. Laumen, P. J. Nielsen, and T. Wirth, “The BOB.1/OBF.1 co-activator is essential for octamer-dependent transcription in B cells,” European Journal of Immunology, vol. 30, no. 2, pp. 458–469, 2000. View at Publisher · View at Google Scholar · View at Scopus
  34. S. Tedoldi, A. Mottok, and A. Mottok, “Selective loss of B-cell phenotype in lymphocyte predominant Hodgkin lymphoma,” Journal of Pathology, vol. 213, no. 4, pp. 429–440, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  35. J. M. Munro, A. S. Freedman, and A. S. Freedman, “In vivo expression of the B7 costimulatory molecule by subsets of antigen- presenting cells and the malignant cells of Hodgkin's disease,” Blood, vol. 83, no. 3, pp. 793–798, 1994. View at Google Scholar · View at Scopus
  36. A. Carbone, A. Gloghini, and A. Gloghini, “Expression of functional CD40 antigen on Reed-Sternberg cells and Hodgkin's disease cell lines,” Blood, vol. 85, no. 3, pp. 780–789, 1995. View at Google Scholar · View at Scopus
  37. W. Timens, L. Visser, and S. Poppema, “Nodular lymphocyte predominance type of Hodgkin's disease is a germinal center lymphoma,” Laboratory Investigation, vol. 54, no. 4, pp. 457–461, 1986. View at Google Scholar · View at Scopus
  38. M. L. Hansmann, H. Stein, F. Dallenbach, and C. Fellbaum, “Diffuse lymphocyte-predominant Hodgkin's disease (diffuse paragranuloma). A variant of the B-cell-derived nodular type,” American Journal of Pathology, vol. 138, no. 1, pp. 29–36, 1991. View at Google Scholar · View at Scopus
  39. V. Brune, E. Tiacci, and E. Tiacci, “Origin and pathogenesis of nodular lymphocyte-predominant Hodgkin lymphoma as revealed by global gene expression analysis,” Journal of Experimental Medicine, vol. 205, no. 10, pp. 2251–2268, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  40. T. Marafioti, C. Mancini, and C. Mancini, “Leukocyte-specific phosphoprotein-1 and PU.1: two useful markers for distinguishing T-cell-rich B-cell lymphoma from lymphocyte-predominant Hodgkin's disease,” Haematologica, vol. 89, no. 8, pp. 957–964, 2004. View at Google Scholar · View at Scopus
  41. S. Prakash, T. Fountaine, M. Raffeld, E. S. Jaffe, and S. Pittaluga, “IgD positive L&H cells identify a unique subset of nodular lymphocyte predominant Hodgkin lymphoma,” American Journal of Surgical Pathology, vol. 30, no. 5, pp. 585–592, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  42. A. Liso, D. Capello, and D. Capello, “Aberrant somatic hypermutation in tumor cells of nodular-lymphocyte-predominant and classic Hodgkin lymphoma,” Blood, vol. 108, no. 3, pp. 1013–1020, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  43. G. Delsol, P. Brousset, S. Chittal, and F. Rigal-Huguet, “Correlation of the expression of Epstein-Barr virus latent membrane protein and in situ hybridization with biotinylated BamHI-W probes in Hodgkin's disease,” American Journal of Pathology, vol. 140, no. 2, pp. 247–253, 1992. View at Google Scholar · View at Scopus
  44. G. Niedobitek, L. S. Young, and H. Herbst, “Epstein-barr virus infection and the pathogenesis of malignant lymphomas,” Cancer Surveys, vol. 30, pp. 143–162, 1997. View at Google Scholar · View at Scopus
  45. J. Yahalom, “Role of radiation therapy in Hodgkin's lymphoma,” Cancer Journal, vol. 15, no. 2, pp. 155–160, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  46. P. Seam, J. E. Janik, D. L. Longo, and V. T. DeVita, “Role of chemotherapy in Hodgkin's lymphoma,” Cancer Journal, vol. 15, no. 2, pp. 150–154, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  47. B. Klimm and A. Engert, “Combined modality treatment of Hodgkin's lymphoma,” Cancer Journal, vol. 15, no. 2, pp. 143–149, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  48. F. Quddus and J. O. Armitage, “Salvage therapy for Hodgkin's lymphoma,” Cancer Journal, vol. 15, no. 2, pp. 161–163, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  49. B. Sarina, L. Castagna, and L. Castagna, “Allogeneic transplantation improves the overall and progression-free survival of Hodgkin lymphoma patients relapsing after autologous transplantation: a retrospective study based on the time of HLA typing and donor availability,” Blood, vol. 115, no. 18, pp. 3671–3677, 2010. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  50. H. Stein, D. Y. Mason, and J. Gerdes, “The expression of the Hodgkin's disease associated antigen Ki-1 in reactive and neoplastic lymphoid tissue: evidence that Reed-Sternberg cells and histiocytic malignancies are derived from activated lymphoid cells,” Blood, vol. 66, no. 4, pp. 848–858, 1985. View at Google Scholar · View at Scopus
  51. S. Pileri, E. Sabattini, and E. Sabattini, “Hodgkin's disease: update of findings,” Haematologica, vol. 76, no. 3, pp. 175–182, 1991. View at Google Scholar · View at Scopus
  52. H. Stein, H. Herbst, I. Anagnostopoulos, G. Niedobitek, F. Dallenbach, and H. C. Kratzsch, “The nature of Hodgkin and Reed-Sternberg cells, their association with EBV, and their relationship to anaplastic large-cell lymphoma,” Annals of Oncology, vol. 2, no. 2, pp. 33–38, 1991. View at Google Scholar · View at Scopus
  53. C. Millward, “CD30 (Ber-H2) expression in nonhematopoietic tumors,” Applied Immunohistochemistry, vol. 6, no. 3, pp. 164–168, 1998. View at Publisher · View at Google Scholar · View at Scopus
  54. R. Schwarting, J. Gerdes, H. Durkop, B. Falini, S. Pileri, and H. Stein, “Ber-H2: a new anti-Ki-1 (CD30) monoclonal antibody directed at a formol-resistant epitope,” Blood, vol. 74, no. 5, pp. 1678–1689, 1989. View at Google Scholar · View at Scopus
  55. S. A. Pileri, G. Roncador, and G. Roncador, “Antigen retrieval techniques in immunohistochemistry: comparison of different methods,” Journal of Pathology, vol. 183, no. 1, pp. 116–123, 1997. View at Publisher · View at Google Scholar · View at Scopus
  56. B. Falini, A. Bolognesi, and A. Bolognesi, “Response of refractory Hodgkin's disease to monoclonal anti-CD30 immunotoxin,” Lancet, vol. 339, no. 8803, pp. 1195–1196, 1992. View at Publisher · View at Google Scholar · View at Scopus
  57. P. L. Tazzari, A. Bolognesi, and A. Bolognesi, “Ber-H2 (anti-CD30)-saporin immunotoxin: a new tool for the treatment of Hodgkin's disease and CD30+ lymphoma: in vitro evaluation,” British Journal of Haematology, vol. 81, no. 2, pp. 203–211, 1992. View at Google Scholar · View at Scopus
  58. K. V. Foyil and N. L. Bartlett, “Anti-CD30 antibodies for Hodgkin lymphoma,” Current Hematologic Malignancy Reports, vol. 5, no. 3, pp. 140–147, 2010. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  59. S. A. Pileri, S. Poggi, E. Sabattini, A. De Vivo, B. Falini, and H. Stein, “Is Hodgkin's disease a unique entity?” Leukemia and Lymphoma, vol. 15, no. 1, pp. 3–6, 1995. View at Google Scholar · View at Scopus
  60. S. Ascani, P. L. Zinzani, and P. L. Zinzani, “Peripheral T-cell lymphomas. Clinico-pathologic study of 168 cases diagnosed according to the R.E.A.L. classification,” Annals of Oncology, vol. 8, no. 6, pp. 583–592, 1997. View at Publisher · View at Google Scholar · View at Scopus
  61. B. Falini, S. Pileri, and S. Pileri, “Variable expression of leucocyte-common (CD45) antigen in CD30 (Ki1)-positive anaplastic large-cell lymphoma: implications for the differential diagnosis between lymphoid and nonlymphoid malignancies,” Human Pathology, vol. 21, no. 6, pp. 624–629, 1990. View at Publisher · View at Google Scholar · View at Scopus
  62. P. Korkolopoulou, J. Cordell, M. Jones, L. Kaklamanis, A. Tsenga, K. C. Gatter, and D. Y. Mason, “The expression of the B-cell marker mb-1 (CD79a) in hodgkin's disease,” Histopathology, vol. 24, no. 6, pp. 511–515, 1994. View at Google Scholar · View at Scopus
  63. D. A. Filippa, M. Ladanyi, and M. Ladanyi, “CD30 (Ki-1)-positive malignant lymphomas: clinical, immunophenotypic, histologie, and genetic characteristics and differences with Hodgkin's disease,” Blood, vol. 87, no. 7, pp. 2905–2917, 1996. View at Google Scholar · View at Scopus
  64. S. Chittal, “Epithelial membrane antigen in hematolymphoid neoplasms: a review,” Applied Immunohistochemistry and Molecular Morphology, vol. 5, no. 4, pp. 203–215, 1997. View at Google Scholar · View at Scopus
  65. K. Watanabe, Y. Yamashita, A. Nakayama, Y. Hasegawa, H. Kojima, T. Nagasawa, and N. Mori, “Varied B-cell immunophenotypes of Hodgkin/Reed-Sternberg cells in classic Hodgkin's disease,” Histopathology, vol. 36, no. 4, pp. 353–361, 2000. View at Publisher · View at Google Scholar · View at Scopus
  66. A. Tzankov, J. Krugmann, F. Fend, M. Fischhofer, R. Greil, and S. Dirnhofer, “Prognostic significance of CD20 expression in classical Hodgkin lymphoma: a clinicopathological study of 119 cases,” Clinical Cancer Research, vol. 9, no. 4, pp. 1381–1386, 2003. View at Google Scholar · View at Scopus
  67. A. Tzankov, A. Zimpfer, and A. Zimpfer, “Expression of B-cell markers in classical Hodgkin lymphoma: a tissue microarray analysis of 330 cases,” Modern Pathology, vol. 16, no. 11, pp. 1141–1147, 2003. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  68. B. Falini, H. Stein, and H. Stein, “Expression of lymphoid-associated antigens on Hodgkin's and Reed-Sternberg cells of Hodgkin's disease. An immunocytochemical study on lymph node cytospins using monoclonal antibodies,” Histopathology, vol. 11, no. 12, pp. 1229–1242, 1987. View at Google Scholar · View at Scopus
  69. T. T. Casey, S. J. Olson, J. B. Cousar, and R. D. Collins, “Immunophenotypes of Reed-Sternberg cells: a study of 19 cases of Hodgkin's disease in plastic-embedded sections,” Blood, vol. 74, no. 8, pp. 2624–2628, 1989. View at Google Scholar · View at Scopus
  70. M. Müschen, K. Rajewsky, and K. Rajewsky, “Rare occurrence of classical Hodgkin's disease as a T cell lymphoma,” Journal of Experimental Medicine, vol. 191, no. 2, pp. 387–394, 2000. View at Publisher · View at Google Scholar · View at Scopus
  71. B. Falini, M. Fizzotti, and M. Fizzotti, “A monoclonal antibody (MUM1p) detects expression of the MUM1/IRF4 protein in a subset of germinal center B cells, plasma cells, and activated T cells,” Blood, vol. 95, no. 6, pp. 2084–2092, 2000. View at Google Scholar · View at Scopus
  72. J. Gerdes, J. Van Baarlen, S. Pileri, R. Schwarting, J. A. Van Unnik, and H. Stein, “Tumor cell growth fraction in Hodgkin's disease,” American Journal of Pathology, vol. 128, no. 3, pp. 390–393, 1987. View at Google Scholar · View at Scopus
  73. E. Sabattini, J. Gerdes, and J. Gerdes, “Comparison between the monoclonal antibodies Ki-67 and PC10 in 125 malignant lymphomas,” Journal of Pathology, vol. 169, no. 4, pp. 397–403, 1993. View at Google Scholar · View at Scopus
  74. Leoncini, “Apoptosis in Hodgkin's disease: an in situ endlabelling study correlated with proliferation indices and expression of cell death gene, p53 and BCL2,” Current Diagnostic Pathology, vol. 2, pp. 51–52, 1995. View at Google Scholar
  75. K. N. Naresh, G. T. O'Conor, C. S. Soman, J. Johnson, S. H. Advani, I. T. Magrath, and K. G. Bhatia, “A study of p53 protein, proliferating cell nuclear antigen, and p21 in Hodgkin's disease at presentation and relapse,” Human Pathology, vol. 28, no. 5, pp. 549–555, 1997. View at Publisher · View at Google Scholar · View at Scopus
  76. P. Smolewski, T. Robak, and T. Robak, “Prognostic factors in Hodgkin's disease: multivariate analysis of 327 patients from a single institution,” Clinical Cancer Research, vol. 6, no. 3, pp. 1150–1160, 2000. View at Google Scholar · View at Scopus
  77. D. Aldinucci, A. Gloghini, A. Pinto, R. De Filippi, and A. Carbone, “The classical Hodgkin's lymphoma microenvironment and its role in promoting tumour growth and immune escape,” Journal of Pathology, vol. 221, no. 3, pp. 248–263, 2010. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  78. D. Aldinucci, A. Pinto, A. Gloghini, and A. Carbone, “Chemokine receptors as therapeutic tools in Hodgkin lymphoma: CCR4 and beyond,” Blood, vol. 115, no. 3, pp. 746–747, 2010. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  79. S. Poppema, “Immunobiology and pathophysiology of Hodgkin lymphomas,” Hematology American Society of Hematology Education Program, pp. 231–238, 2005. View at Google Scholar
  80. S. Merluzzi, B. Frossi, G. Gri, S. Parusso, C. Tripodo, and C. Pucillo, “Mast cells enhance proliferation of B lymphocytes and drive their differentiation toward IgA-secreting plasma cells,” Blood, vol. 115, no. 14, pp. 2810–2817, 2010. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  81. D. Molin, M. Fischer, and M. Fischer, “Mast cells express functional CD30 ligand and are the predominant CD30L-positive cells in Hodgkin's disease,” British Journal of Haematology, vol. 114, no. 3, pp. 616–623, 2001. View at Publisher · View at Google Scholar · View at Scopus
  82. R. Küppers, “Molecular biology of Hodgkin lymphoma,” Hematology/the Education Program of the American Society of Hematology. American Society of Hematology, pp. 491–496, 2009. View at Google Scholar · View at Scopus
  83. N. Fazilleau, L. Mark, L. J. McHeyzer-Williams, and M. G. McHeyzer-Williams, “Follicular helper T cells: lineage and location,” Immunity, vol. 30, no. 3, pp. 324–335, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  84. D. Molin, A. Edström, I. Glimelius, B. Glimelius, G. Nilsson, C. Sundström, and G. Enblad, “Mast cell infiltration correlates with poor prognosis in Hodgkin's lymphoma,” British Journal of Haematology, vol. 119, no. 1, pp. 122–124, 2002. View at Publisher · View at Google Scholar · View at Scopus
  85. C. Steidl, T. Lee, and T. Lee, “Tumor-associated macrophages and survival in classic Hodgkin's lymphoma,” New England Journal of Medicine, vol. 362, no. 10, pp. 875–885, 2010. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  86. R. Küppers and K. Rajewsky, “The origin of Hodgkin and Reed/Sternberg cells in Hodgkin's disease,” Annual Review of Immunology, vol. 16, pp. 471–493, 1998. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  87. R. C. Bargou, C. Leng, and C. Leng, “High-level nuclear NF-κB and Oct-2 is a common feature of cultured Hodgkin/Reed-Sternberg cells,” Blood, vol. 87, no. 10, pp. 4340–4347, 1996. View at Google Scholar · View at Scopus
  88. F. Emmerich, M. Meiser, and M. Meiser, “Overexpression of I kappa B alpha without inhibition of NF-κB activity and mutations in the I kappa B alpha gene in Reed-Sternberg cells,” Blood, vol. 94, no. 9, pp. 3129–3134, 1999. View at Google Scholar · View at Scopus
  89. E. Cabannes, G. Khan, F. Aillet, R. F. Jarrett, and R. T. Hay, “Mutations in the IkBa gene in Hodgkin's disease suggest a tumour suppressor role for IκBα,” Oncogene, vol. 18, no. 20, pp. 3063–3070, 1999. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  90. B. Jungnickel, A. Staratschek-Jox, and A. Staratschek-Jox, “Clonal deleterious mutations in the iκbα gene in the malignant cells in Hodgkin's lymphoma,” Journal of Experimental Medicine, vol. 191, no. 2, pp. 395–401, 2000. View at Publisher · View at Google Scholar · View at Scopus
  91. D. Krappmann, F. Emmerich, U. Kordes, E. Scharschmidt, B. Dörken, and C. Scheidereit, “Molecular mechanisms of constitutive NF-κB/Rel activation in Hodgkin/Reed-Sternberg cells,” Oncogene, vol. 18, no. 4, pp. 943–953, 1999. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  92. R. Schmitz, M. L. Hansmann, and M. L. Hansmann, “TNFAIP3 (A20) is a tumor suppressor gene in Hodgkin lymphoma and primary mediastinal B cell lymphoma,” Journal of Experimental Medicine, vol. 206, no. 5, pp. 981–989, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  93. M. A. Schumacher, R. Schmitz, and R. Schmitz, “Mutations in the genes coding for the NF-κB regulating factors IκBα and A20 are uncommon in nodular lymphocyte-predominant Hodgkin's lymphoma,” Haematologica, vol. 95, no. 1, pp. 153–157, 2010. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  94. M. Montesinos-Rongen, A. Roers, R. Küppers, K. Rajewsky, and M. L. Hansmann, “Mutation of the p53 gene is not a typical feature of Hodgkin and Reed-Sternberg cells in Hodgkin's disease,” Blood, vol. 94, no. 5, pp. 1755–1760, 1999. View at Google Scholar · View at Scopus
  95. S. Poppema, J. Kaleta, and B. Hepperle, “Chromosomal abnormalities in patients with Hodgkin's disease: evidence for frequent involvement of the 14q chromosomal region but infrequent bcl-2 gene rearrangement in Reed-Sternberg cells,” Journal of the National Cancer Institute, vol. 84, no. 23, pp. 1789–1793, 1992. View at Google Scholar · View at Scopus
  96. C. Steidl, A. Telenius, and A. Telenius, “Genome-wide copy number analysis of Hodgkin Reed-Sternberg cells identifies recurrent imbalances with correlations to treatment outcome,” Blood, vol. 116, no. 3, pp. 418–427, 2010. View at Publisher · View at Google Scholar · View at PubMed
  97. M. R. Green, S. Monti, and S. Monti, “Integrative analysis reveals selective 9p24.1 amplification, increased PD-1 ligand expression, and further induction via JAK2 in nodular sclerosing Hodgkin lymphoma and primary mediastinal large B-cell lymphoma,” Blood, vol. 116, no. 17, pp. 3268–3277, 2010. View at Publisher · View at Google Scholar · View at PubMed
  98. T. Feys, B. Poppe, and B. Poppe, “A detailed inventory of DNA copy number alterations in four commonly used Hodgkin's lymphoma cell lines,” Haematologica, vol. 92, no. 7, pp. 913–920, 2007. View at Publisher · View at Google Scholar · View at Scopus
  99. S. Hartmann, J. I. Martin-Subero, and J. I. Martin-Subero, “Detection of genomic imbalances in microdissected Hodgkin and Reed-Sternberg cells of classical Hodgkin's lymphoma by array-based comparative genomic hybridization,” Haematologica, vol. 93, no. 9, pp. 1318–1326, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  100. Vassallo, “Detection of Epstein-Barr virus in Hodgkin's disease,” Applied Immunohistochemistry, vol. 1, pp. 213–219, 1993. View at Google Scholar
  101. M. Rowe, D. T. Rowe, C. D. Gregory, L. S. Young, P. J. Farrell, H. Rupani, and A. B. Rickinson, “Differences in B cell growth phenotype reflect novel patterns of Epstein-Barr virus latent gene expression in Burkitt's lymphoma cells,” EMBO Journal, vol. 6, no. 9, pp. 2743–2751, 1987. View at Google Scholar · View at Scopus
  102. L. Leoncini, D. Spina, and D. Spina, “Neoplastic cells of Hodgkin's disease show differences in EBV expression between Kenya and Italy,” International Journal of Cancer, vol. 65, no. 6, pp. 781–784, 1996. View at Publisher · View at Google Scholar · View at Scopus
  103. M. Weinreb, P. J. R. Day, and P. J. R. Day, “The consistent association between Epstein-Barr virus and Hodgkin's disease in children in Kenya,” Blood, vol. 87, no. 9, pp. 3828–3836, 1996. View at Google Scholar · View at Scopus
  104. P. Brousset, D. Schlaifer, and D. Schlaifer, “Persistence of the same viral strain in early and late relapses of Epstein-Barr virus-associated Hodgkin's disease,” Blood, vol. 84, no. 8, pp. 2447–2451, 1994. View at Google Scholar · View at Scopus
  105. A. Sánchez-Aguilera, C. Montalbán, and C. Montalbán, “Tumor microenvironment and mitotic checkpoint are key factors in the outcome of classic Hodgkin lymphoma,” Blood, vol. 108, no. 2, pp. 662–668, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  106. A. Gallamini, M. Hutchings, and M. Hutchings, “Early interim 2-[F]fluoro-2-deoxy-D-glucose positron emission tomography is prognostically superior to international prognostic score in advanced-stage Hodgkin's lymphoma: a report from a joint Italian-Danish study,” Journal of Clinical Oncology, vol. 25, no. 24, pp. 3746–3752, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  107. K. Lennert and N. Mohri, “Histological classification and occurrence of Hodgkin's disease,” Der Internist, vol. 15, no. 2, pp. 57–65, 1974. View at Google Scholar
  108. J. Diebold, P. Jungman, T. Molina, and J. Audouin, “Recent advances in Hodgkin's disease: an overview and review of the literature,” Current Diagnostic Pathology, vol. 2, no. 3, pp. 153–162, 1995. View at Google Scholar · View at Scopus
  109. K. A. MacLennan, M. H. Bennett, A. Tu, B. Vaughan Hudson, M. J. Easterling, G. Vaughan Hudson, and A. M. Jelliffe, “Relationship of histopathologic features to survival and relapse in nodular sclerosing Hodgkin's disease: a study of 1659 patients,” Cancer, vol. 64, no. 8, pp. 1686–1693, 1989. View at Google Scholar · View at Scopus
  110. Grogan, Hodgkin's Disease, Saunders, Philadelphia, Pa, USA, 1995.
  111. P. M. Banks, “The distinction of Hodgkin's disease from T cell lymphoma,” Seminars in Diagnostic Pathology, vol. 9, no. 4, pp. 279–283, 1992. View at Google Scholar · View at Scopus
  112. M. J. Alavaikko, G. Blanco, and G. Blanco, “Follicular dendritic cells have prognostic relevance in Hodgkin's disease,” American Journal of Clinical Pathology, vol. 101, no. 6, pp. 761–767, 1994. View at Google Scholar · View at Scopus
  113. A. S. Baur, C. Meugé-Moraw, G. Michel, and F. Delacrétaz, “Prognostic value of follicular dendritic cells in nodular sclerosing Hodgkin's disease,” Histopathology, vol. 32, no. 6, pp. 512–520, 1998. View at Publisher · View at Google Scholar · View at Scopus
  114. J. G. Strickler, S. A. Michie, R. A. Warnke, and R. F. Dorfman, “The 'syncytial variant' of nodular sclerosing Hodgkin's disease,” American Journal of Surgical Pathology, vol. 10, no. 7, pp. 470–477, 1986. View at Google Scholar · View at Scopus
  115. D. Ben-Yehuda-Salz, A. Ben-Yehuda, A. Polliack, N. Ron, and E. Okon, “Syncytial variant of nodular sclerosing Hodgkin's Disease. A new clinicopathologic entity,” Cancer, vol. 65, no. 5, pp. 1167–1172, 1990. View at Google Scholar · View at Scopus
  116. M. H. Bennett, K. A. MacLennan, and M. J. Easterling, “The prognostic significance of cellular subtypes in nodular sclerosing Hodgkin's disease: an analysis of 271 non-laparotomised cases (BNLI report no. 22),” Clinical Radiology, vol. 34, no. 5, pp. 497–501, 1983. View at Google Scholar
  117. J. A. Ferry, R. M. Linggood, K. M. Convery, J. T. Efird, R. Eliseo, and N. L. Harris, “Hodgkin disease, nodular sclerosis type: implications of histologic subclassification,” Cancer, vol. 71, no. 2, pp. 457–463, 1993. View at Publisher · View at Google Scholar · View at Scopus
  118. E. S. G. D'Amore, C. K. K. Lee, D. M. Aeppli, S. H. Levitt, and G. Frizzera, “Lack of prognostic value of histopathologic parameters in Hodgkin's disease, nodular sclerosis type: a study of 123 patients with limited stage disease who had undergone laparotomy and were treated with radiation therapy,” Archives of Pathology and Laboratory Medicine, vol. 116, no. 8, pp. 856–861, 1992. View at Google Scholar · View at Scopus
  119. J. L. Hess, S. Bodis, G. Pinkus, B. Silver, and P. Mauch, “Histopathologic grading of nodular sclerosis Hodgkin's disease: lack of prognostic significance in 254 surgically staged patients,” Cancer, vol. 74, no. 2, pp. 708–714, 1994. View at Publisher · View at Google Scholar · View at Scopus
  120. R. S. Doggett, T. V. Colby, and R. F. Dorfman, “Interfollicular Hodgkin's disease,” American Journal of Surgical Pathology, vol. 7, no. 2, pp. 145–149, 1983. View at Google Scholar · View at Scopus
  121. P. R. Maheswaran, A. D. Ramsay, A. J. Norton, and W. R. Roche, “Hodgkin's disease presenting with the histological features of Castleman's disease,” Histopathology, vol. 18, no. 3, pp. 249–253, 1991. View at Google Scholar · View at Scopus
  122. S. M. Hsu, S. S. Xie, P. L. Hsu, and J. A. Waldron, “Interleukin-6, but not interleukin-4, is expressed by Reed-Sternberg cells in Hodgkin's disease with or without histologic features of Castleman's disease,” American Journal of Pathology, vol. 141, no. 1, pp. 129–138, 1992. View at Google Scholar · View at Scopus
  123. R. J. Lukes, “Criteria for involvement of lymph node, bone marrow, spleen, and liver in Hodgkin's disease,” Cancer Research, vol. 31, no. 11, pp. 1755–1767, 1971. View at Google Scholar · View at Scopus
  124. E. Patsouris, H. Noel, and K. Lennert, “Cytohistologic and immunohistochemical findings in Hodgkin's disease, mixed cellularity type, with a high content of epithelioid cells,” American Journal of Surgical Pathology, vol. 13, no. 12, pp. 1014–1022, 1989. View at Google Scholar · View at Scopus
  125. M. C. Kinney, J. P. Greer, and R. S. Stein, “Lymphocyte-depletion Hodgkin's disease. Histopathologic diagnosis of marrow involvement,” American Journal of Surgical Pathology, vol. 10, no. 3, pp. 219–226, 1986. View at Google Scholar
  126. B. A. Agnarsson and M. E. Kadin, “Ki-1 positive large cell lymphoma. A morphologic and immunologic study of 19 cases,” American Journal of Surgical Pathology, vol. 12, no. 4, pp. 264–274, 1988. View at Google Scholar · View at Scopus
  127. J. J. Butler, “The histologic diagnosis of Hodgkin's disease,” Seminars in Diagnostic Pathology, vol. 9, no. 4, pp. 252–256, 1992. View at Google Scholar · View at Scopus
  128. R. J. Pelstring, R. B. Zellmer, L. E. Sulak, P. M. Banks, and N. Clare, “Hodgkin's disease in association with human immunodeficiency virus infection: pathologic and immunologic features,” Cancer, vol. 67, no. 7, pp. 1865–1873, 1991. View at Google Scholar · View at Scopus
  129. M. L. Hansmann, H. H. Wacker, and H. J. Radzun, “Paragranuloma is a variant of Hodgkin's disease with predominance of B-cells,” Virchows Archiv—A Pathological Anatomy and Histopathology, vol. 409, no. 2, pp. 171–181, 1986. View at Google Scholar · View at Scopus
  130. T. Rüdiger, G. Ott, M. M. Ott, S. M. Müller-Deubert, and H. K. Müller-Hermelink, “Differential diagnosis between classic Hodgkin's lymphoma, T-cell-rich B-cell lymphoma, and paragranuloma by paraffin immunohistochemistry,” American Journal of Surgical Pathology, vol. 22, no. 10, pp. 1184–1191, 1998. View at Publisher · View at Google Scholar
  131. J. A. McBride, J. Rodriguez, R. Luthra, N. G. Ordóñez, F. Cabanillas, and W. C. Pugh, “T-cell-rich B large-cell lymphoma simulating lymphocyte-rich Hodgkin's disease,” American Journal of Surgical Pathology, vol. 20, no. 2, pp. 193–201, 1996. View at Publisher · View at Google Scholar
  132. M. Ashton-Key, P. A. Thorpe, J. P. Allen, and P. G. Isaacson, “Follicular Hodgkin's disease,” American Journal of Surgical Pathology, vol. 19, no. 11, pp. 1294–1299, 1995. View at Google Scholar
  133. V. Diehl and A. Josting, “Hodgkin's disease,” Cancer Journal, vol. 6, supplement 2, pp. S150–S158, 2000. View at Google Scholar
  134. R. Von Wasielewski, M. Mengel, and M. Mengel, “Classical Hodgkin's disease: clinical impact of the immunophenotype,” American Journal of Pathology, vol. 151, no. 4, pp. 1123–1130, 1997. View at Google Scholar
  135. E. Jaffe, H. Stein, S. Swerdlow, E. Campo, S. Pileri, and N. Harris, “B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and classical Hodgkin lymphoma,” in WHO Classification of Tumors of the Hematopoietic and Lymphoid Tissue, S. Swerdlow, E. Campo, N. L. Harris et al., Eds., pp. 267–268, IARC, Lyon, France, 2008. View at Google Scholar
  136. N. Asano, K. Yamamoto, and K. Yamamoto, “Age-related epstein-barr virus (EBV) associated B-cell lymphoproliferative disorders: comparison with EBV-positive classic hodgkin lymphoma in elderly patients,” Blood, vol. 113, no. 12, pp. 2629–2636, 2009. View at Publisher · View at Google Scholar · View at PubMed
  137. J. I. Cohen, H. Kimura, S. Nakamura, Y. H. Ko, and E. S. Jaffe, “Epstein-Barr virus-associated lymphoproliferative disease in non-immunocompromised hosts: a status report and summary of an international meeting, 8-9 September 2008,” Annals of Oncology, vol. 20, no. 9, pp. 1472–1482, 2009. View at Publisher · View at Google Scholar · View at PubMed
  138. A. Younes, “Novel treatment strategies for patients with relapsed classical Hodgkin lymphoma,” Hematology/the Education Program of the American Society of Hematology. American Society of Hematology, pp. 507–519, 2009. View at Google Scholar
  139. G. Corazzelli, R. De Filippi, and R. De Filippi, “Tumor flare reactions and response to lenalidomide in patients with refractory classic Hodgkin lymphoma,” American Journal of Hematology, vol. 85, no. 1, pp. 87–90, 2010. View at Publisher · View at Google Scholar · View at PubMed