Journal Mobile Options
Table of Contents
Vol. 77, No. 6, 2010
Issue release date: January 2011
Section title: Original Paper
Pathobiology 2010;77:301–308

Refined Prognostic Role of CD68-Positive Tumor Macrophages in the Context of the Cellular Micromilieu of Classical Hodgkin Lymphoma

Tzankov A. · Matter M.S. · Dirnhofer S.
Department of Pathology, University of Basel, Basel, Switzerland
email Corresponding Author

Dr. A. Tzankov

Department of Pathology

University of Basel, Schoenbeinstrasse 40

CH–4031 Basel (Switzerland)

Tel. +41 61 328 68 80, Fax +41 61 265 31 94, E-Mail


  1. Tzankov A, Dirnhofer S: Pathobiology of classical Hodgkin lymphoma. Pathobiology 2006;73:107–125.
  2. Diehl V, Engert A, Re D: New strategies for the treatment of advanced-stage Hodgkin’s lymphoma. Hematol Oncol Clin North Am 2007;21:897–914.
  3. David KA, Mauro L, Evens AM: Relapsed and refractory Hodgkin lymphoma: transplantation strategies and novel therapeutic options. Curr Treat Options Oncol 2007;8:352–374.
  4. Landgren O, Caporaso NE: New aspects in descriptive, etiologic, and molecular epidemiology of Hodgkin’s lymphoma. Hematol Oncol Clin North Am 2007;21:825–840.
  5. MacLennan KA, Bennett MH, Tu A, Hudson BV, Easterling MJ, Hudson GV, Jelliffe AM: Relationship of histopathologic features to survival and relapse in nodular sclerosing Hodgkin’s disease. A study of 1659 patients. Cancer 1989;64:1686–1693.
  6. Lukes RJ, Butler JJ, Hicks EB: Natural history of Hodgkin’s disease as related to its pathologic picture. Cancer 1966;19:317–344.
    External Resources
  7. Keller AR, Kaplan HS, Lukes RJ, Rappaport H: Correlation of histopathology with other prognostic indicators in Hodgkin’s disease. Cancer 1968;22:487–499.
  8. Hess JL, Bodis S, Pinkus G, Silver B, Mauch P: Histopathologic grading of nodular sclerosis Hodgkin’s disease. Lack of prognostic significance in 254 surgically staged patients. Cancer 1994;74:708–714.
  9. Hasenclever D, Diehl V: A prognostic score for advanced Hodgkin’s disease. International Prognostic Factors Project on Advanced Hodgkin’s Disease. N Engl J Med 1998;339:1506–1514.
  10. Josting A, Wolf J, Diehl V: Hodgkin disease: prognostic factors and treatment strategies. Curr Opin Oncol 2000;12:403–411.
  11. Tzankov A, Krugmann J, Fend F, Fischhofer M, Greil R, Dirnhofer S: The prognostic value of CD20 expression in classical Hodgkin Lymphoma – a clinico-pathological study of 119 cases. Clin Cancer Res 2003;9:1381–1386.
  12. Krugmann J, Tzankov A, Gschwendtner A, Fischhofer M, Greil R, Fend F, Dirnhofer S: Longer failure-free survival interval of Epstein-Barr virus-associated classical Hodgkin’s lymphoma: a single-institution study. Mod Pathol 2003;16:566–573.
  13. Poppema S, Potters M, Emmens R, Visser L, Van den Berg A: Immune reactions in classical Hodgkin’s lymphoma. Semin Hematol 1999;36:253–259.
  14. Poppema S, Van den Berg A: Interaction between host T cells and Reed-Sternberg cells in Hodgkin lymphomas. Semin Cancer Biol 2000;10:345–350.
  15. Oudejans JJ, Jiwa NM, Kummer JA, Ossenkoppele GJ, van Heerde P, Baars JW, Kluin PM, Kluin-Nelemans JC, van Diest PJ, Middeldorp JM, Meijer CJ: Activated cytotoxic T cells as prognostic marker in Hodgkin’s disease. Blood 1997;89:1376–1382.
  16. Ten Berge RL, Oudejans JJ, Dukers DF, Meijer JW, Ossenkoppele GJ, Meijer CJ: Percentage of activated cytotoxic T-lymphocytes in anaplastic large cell lymphoma and Hodgkin’s disease: an independent biological prognostic marker. Leukemia 2001;15:458–464.
  17. Alvaro T, Lejeune M, Salvado MT, Bosch R, Garcia JF, Jaen J, Banham AH, Roncador G, Montalban C, Piris MA: Outcome in Hodgkin’s lymphoma can be predicted from the presence of accompanying cytotoxic and regulatory T cells. Clin Cancer Res 2005;11:1467–1473.
  18. Muenst S, Hoeller S, Dirnhofer S, Tzankov A: Increased PD-1+ tumor-infiltrating lymphocytes in classical Hodgkin lymphoma substantiate reduced overall survival. Hum Pathol 2009;40:1715–1722.
  19. Tzankov A, Meier C, Hirschmann P, Went P, Pileri SA, Dirnhofer S: Correlation of high numbers of intratumoral FOXP3+ regulatory T cells with improved survival in germinal center-like diffuse large B-cell lymphoma, follicular lymphoma and classical Hodgkin’s lymphoma. Haematologica 2008;93:193–200.
  20. Van den Berg A, Visser L, Poppema S: 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 1999;154:1685–1691.
  21. Skinnider BF, Mak TW: The role of cytokines in classical Hodgkin lymphoma. Blood 2002;99:4283–4297.
  22. Schiffer CA, Levi JA, Wiernik PH: The significance of abnormal circulating cells in patients with Hodgkin’s disease. Br J Haematol 1975;31:177–183.
  23. Ree HJ, Kadin ME: Macrophage-histiocytes in Hodgkin’s disease. The relation of peanut-agglutinin-binding macrophage-histiocytes to clinicopathologic presentation and course of disease. Cancer 1985;56:333–338.
  24. Coppleson LW, Rappaport H, Strum SB, Rose J: Analysis of the Rye classification of Hodgkin’s disease. The prognostic significance of cellular composition. J Natl Cancer Inst 1973;51:379–390.
  25. Steidl C, Lee T, Shah SP, et al: Tumor-associated macrophages and survival in classic Hodgkin’s lymphoma. N Engl J Med 2010;362:875–885.
  26. Tzankov A, Zimpfer A, Went P, Maurer R, Pileri SA, Geley S, Dirnhofer S: Aberrant expression of cell cycle regulators in Hodgkin and Reed-Sternberg cells of classical Hodgkin lymphoma. Mod Pathol 2005;18:90–96.
  27. Greil R, Holzner B, Kemmler G, et al: Retrospective assessment of quality of life and treatment outcome in patients with Hodgkin’s disease from 1969 to 1994. Eur J Cancer 1999;35:698–706.
  28. Fong D, Steurer M, Greil R, et al: Hodgkin lymphoma in Tyrol – a population-based study. Ann Hematol 2009;88:449–456.
  29. Tzankov A, Zlobec I, Went P, Robl H, Hoeller S, Dirnhofer S: Prognostic immunophenotypic biomarker studies in diffuse large B cell lymphoma with special emphasis on rational determination of cut-off scores. Leuk Lymphoma 2010;51:199–212.
  30. Adams H, Campidelli C, Dirnhofer S, Pileri SA, Tzankov A: Clinical, phenotypic and genetic similarities and disparities between post-transplant and classical Hodgkin lymphomas with respect to therapeutic targets. Expert Opin Ther Targets 2009;13:1137–1145.
  31. Enblad G, Molin D, Glimelius I, Fischer M, Nilsson G: The potential role of innate immunity in the pathogenesis of Hodgkin’s lymphoma. Hematol Oncol Clin North Am 2007;21:805–823.
  32. Cao X, Cai SF, Fehniger TA, et al: Granzyme B and perforin are important for regulatory T cell-mediated suppression of tumor clearance. Immunity 2007;27:635–646.