Official reprint from UpToDate®
www.uptodate.com ©2017 UpToDate, Inc. and/or its affiliates. All Rights Reserved.

Epidemiology, pathologic features, and diagnosis of classical Hodgkin lymphoma

Jon C Aster, MD
Olga Pozdnyakova, MD
Section Editor
Arnold S Freedman, MD
Deputy Editor
Alan G Rosmarin, MD


Hodgkin lymphoma (HL), formerly called Hodgkin's disease, arises from germinal center or post-germinal center B cells. HL has a unique cellular composition, containing a minority of neoplastic cells (Reed-Sternberg cells and their variants) in an inflammatory background. It is separated from the other B cell lymphomas based on its unique clinicopathologic features, and can be divided into two major sub-groups, based on the appearance and immunophenotype of the tumor cells (table 1):

Classical HL – The tumor cells in this group are derived from germinal center B cells, but typically fail to express many of the genes and gene products that define normal germinal center B cells. Based on differences in the appearance of the tumor cells and the composition of the reactive background, classical HL is further divided into the following subtypes:

Nodular sclerosis classical HL (NSHL)

Mixed cellularity classical HL (MCHL)

Lymphocyte rich classical HL (LRHL)

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:

Subscribers log in here

Literature review current through: Nov 2017. | This topic last updated: May 31, 2017.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2017 UpToDate, Inc.
  1. Siegel RL, Miller KD, Jemal A. Cancer Statistics, 2017. CA Cancer J Clin 2017; 67:7.
  2. Sant M, Allemani C, Tereanu C, et al. Incidence of hematologic malignancies in Europe by morphologic subtype: results of the HAEMACARE project. Blood 2010; 116:3724.
  3. Smith A, Howell D, Patmore R, et al. Incidence of haematological malignancy by sub-type: a report from the Haematological Malignancy Research Network. Br J Cancer 2011; 105:1684.
  4. Ries LA, Kosary CL, Hankey BF, et al. (Eds). SEER cancer statistics review: 1973-1994, NIH publ no. 97-2789, National Cancer Institute, Bethesda 1997.
  5. Evens AM, Antillón M, Aschebrook-Kilfoy B, Chiu BC. Racial disparities in Hodgkin's lymphoma: a comprehensive population-based analysis. Ann Oncol 2012; 23:2128.
  6. Correa P, O'Conor GT. Epidemiologic patterns of Hodgkin's disease. Int J Cancer 1971; 8:192.
  7. Correa P, O'Conor GT. Geographic pathology of lymphoreticular tumors: summary of survey from the geographic pathology committee of the international union against cancer. J Natl Cancer Inst 1973; 50:1609.
  8. Gutensohn N, Cole P. Childhood social environment and Hodgkin's disease. N Engl J Med 1981; 304:135.
  9. World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues, Swerdlow SH, Campo E, Harris NL, et al. (Eds), IARC Press, Lyon 2008.
  10. Cozen W, Katz J, Mack TM. Risk patterns of Hodgkin's disease in Los Angeles vary by cell type. Cancer Epidemiol Biomarkers Prev 1992; 1:261.
  11. Glaser SL. Regional variation in Hodgkin's disease incidence by histologic subtype in the US. Cancer 1987; 60:2841.
  12. McNally RJ, Alston RD, Cairns DP, et al. Geographical and ecological analyses of childhood acute leukaemias and lymphomas in north-west England. Br J Haematol 2003; 123:60.
  13. Hu E, Hufford S, Lukes R, et al. Third-World Hodgkin's disease at Los Angeles County-University of Southern California Medical Center. J Clin Oncol 1988; 6:1285.
  14. Jarrett RF, MacKenzie J. Epstein-Barr virus and other candidate viruses in the pathogenesis of Hodgkin's disease. Semin Hematol 1999; 36:260.
  15. Flavell KJ, Biddulph JP, Powell JE, et al. South Asian ethnicity and material deprivation increase the risk of Epstein-Barr virus infection in childhood Hodgkin's disease. Br J Cancer 2001; 85:350.
  16. Vianna NJ, Greenwald P, Brady J, et al. Hodgkin's disease: cases with features of a community outbreak. Ann Intern Med 1972; 77:169.
  17. Vianna NJ, Polan AK. Epidemiologic evidence for transmission of Hodgkin's disease. N Engl J Med 1973; 289:499.
  18. Grufferman S, Cole P, Levitan TR. Evidence against transmission of Hodgkin's disease in high schools. N Engl J Med 1979; 300:1006.
  19. Linabery AM, Erhardt EB, Fonstad RK, et al. Infectious, autoimmune and allergic diseases and risk of Hodgkin lymphoma in children and adolescents: a Children's Oncology Group study. Int J Cancer 2014; 135:1454.
  20. Mueller N, Evans A, Harris NL, et al. Hodgkin's disease and Epstein-Barr virus. Altered antibody pattern before diagnosis. N Engl J Med 1989; 320:689.
  21. Lehtinen T, Lumio J, Dillner J, et al. Increased risk of malignant lymphoma indicated by elevated Epstein-Barr virus antibodies--a prospective study. Cancer Causes Control 1993; 4:187.
  22. Alexander FE, Jarrett RF, Lawrence D, et al. Risk factors for Hodgkin's disease by Epstein-Barr virus (EBV) status: prior infection by EBV and other agents. Br J Cancer 2000; 82:1117.
  23. Hjalgrim H, Askling J, Sørensen P, et al. Risk of Hodgkin's disease and other cancers after infectious mononucleosis. J Natl Cancer Inst 2000; 92:1522.
  24. Armstrong AA, Shield L, Gallagher A, Jarrett RF. Lack of involvement of known oncogenic DNA viruses in Epstein-Barr virus-negative Hodgkin's disease. Br J Cancer 1998; 77:1045.
  25. Siddon A, Lozovatsky L, Mohamed A, Hudnall SD. Human herpesvirus 6 positive Reed-Sternberg cells in nodular sclerosis Hodgkin lymphoma. Br J Haematol 2012; 158:635.
  26. Lacroix A, Collot-Teixeira S, Mardivirin L, et al. Involvement of human herpesvirus-6 variant B in classic Hodgkin's lymphoma via DR7 oncoprotein. Clin Cancer Res 2010; 16:4711.
  27. Grufferman S, Davis MK, Ambinder RF, et al. A protective effect of breast-feeding on risk of Hodgkin's disease in children. Paediatr Perinat Epidemiol 1998; 12:13.
  28. Davis MK, Savitz DA, Graubard BI. Infant feeding and childhood cancer. Lancet 1988; 2:365.
  29. Chang ET, Zheng T, Weir EG, et al. Aspirin and the risk of Hodgkin's lymphoma in a population-based case-control study. J Natl Cancer Inst 2004; 96:305.
  30. Nieters A, Rohrmann S, Becker N, et al. Smoking and lymphoma risk in the European prospective investigation into cancer and nutrition. Am J Epidemiol 2008; 167:1081.
  31. Castillo JJ, Dalia S, Shum H. Meta-analysis of the association between cigarette smoking and incidence of Hodgkin's Lymphoma. J Clin Oncol 2011; 29:3900.
  32. Kroll ME, Murphy F, Pirie K, et al. Alcohol drinking, tobacco smoking and subtypes of haematological malignancy in the UK Million Women Study. Br J Cancer 2012; 107:879.
  33. Kamper-Jørgensen M, Rostgaard K, Glaser SL, et al. Cigarette smoking and risk of Hodgkin lymphoma and its subtypes: a pooled analysis from the International Lymphoma Epidemiology Consortium (InterLymph). Ann Oncol 2013; 24:2245.
  34. Goedert JJ, Coté TR, Virgo P, et al. Spectrum of AIDS-associated malignant disorders. Lancet 1998; 351:1833.
  35. Tinguely M, Vonlanthen R, Müller E, et al. Hodgkin's disease-like lymphoproliferative disorders in patients with different underlying immunodeficiency states. Mod Pathol 1998; 11:307.
  36. Glaser SL, Clarke CA, Gulley ML, et al. Population-based patterns of human immunodeficiency virus-related Hodgkin lymphoma in the Greater San Francisco Bay Area, 1988-1998. Cancer 2003; 98:300.
  37. Garnier JL, Lebranchu Y, Dantal J, et al. Hodgkin's disease after transplantation. Transplantation 1996; 61:71.
  38. Patel P, Hanson DL, Sullivan PS, et al. Incidence of types of cancer among HIV-infected persons compared with the general population in the United States, 1992-2003. Ann Intern Med 2008; 148:728.
  39. Grulich AE, Li Y, McDonald A, et al. Rates of non-AIDS-defining cancers in people with HIV infection before and after AIDS diagnosis. AIDS 2002; 16:1155.
  40. Dal Maso L, Franceschi S, Polesel J, et al. Risk of cancer in persons with AIDS in Italy, 1985-1998. Br J Cancer 2003; 89:94.
  41. Herida M, Mary-Krause M, Kaphan R, et al. Incidence of non-AIDS-defining cancers before and during the highly active antiretroviral therapy era in a cohort of human immunodeficiency virus-infected patients. J Clin Oncol 2003; 21:3447.
  42. Clifford GM, Polesel J, Rickenbach M, et al. Cancer risk in the Swiss HIV Cohort Study: associations with immunodeficiency, smoking, and highly active antiretroviral therapy. J Natl Cancer Inst 2005; 97:425.
  43. Spina M, Berretta M, Tirelli U. Hodgkin's disease in HIV. Hematol Oncol Clin North Am 2003; 17:843.
  44. Landgren O, Pfeiffer RM, Kristinsson SY, Björkholm M. Survival patterns in patients with Hodgkin's lymphoma with a pre-existing hospital discharge diagnosis of autoimmune disease. J Clin Oncol 2010; 28:5081.
  45. Hollander P, Rostgaard K, Smedby KE, et al. Autoimmune and Atopic Disorders and Risk of Classical Hodgkin Lymphoma. Am J Epidemiol 2015; 182:624.
  46. Landgren O, Engels EA, Pfeiffer RM, et al. Autoimmunity and susceptibility to Hodgkin lymphoma: a population-based case-control study in Scandinavia. J Natl Cancer Inst 2006; 98:1321.
  47. Goldin LR, Pfeiffer RM, Gridley G, et al. Familial aggregation of Hodgkin lymphoma and related tumors. Cancer 2004; 100:1902.
  48. Goldin LR, Björkholm M, Kristinsson SY, et al. Highly increased familial risks for specific lymphoma subtypes. Br J Haematol 2009; 146:91.
  49. Hjalgrim H, Rasmussen S, Rostgaard K, et al. Familial clustering of Hodgkin lymphoma and multiple sclerosis. J Natl Cancer Inst 2004; 96:780.
  50. Kharazmi E, Fallah M, Pukkala E, et al. Risk of familial classical Hodgkin lymphoma by relationship, histology, age, and sex: a joint study from five Nordic countries. Blood 2015; 126:1990.
  51. Grufferman S, Cole P, Smith PG, Lukes RJ. Hodgkin's disease in siblings. N Engl J Med 1977; 296:248.
  52. Mack TM, Cozen W, Shibata DK, et al. Concordance for Hodgkin's disease in identical twins suggesting genetic susceptibility to the young-adult form of the disease. N Engl J Med 1995; 332:413.
  53. Oza AM, Tonks S, Lim J, et al. A clinical and epidemiological study of human leukocyte antigen-DPB alleles in Hodgkin's disease. Cancer Res 1994; 54:5101.
  54. Harty LC, Lin AY, Goldstein AM, et al. HLA-DR, HLA-DQ, and TAP genes in familial Hodgkin disease. Blood 2002; 99:690.
  55. Kamper PM, Kjeldsen E, Clausen N, et al. Epstein-Barr virus-associated familial Hodgkin lymphoma: paediatric onset in three of five siblings. Br J Haematol 2005; 129:615.
  56. Diepstra A, Niens M, Vellenga E, et al. Association with HLA class I in Epstein-Barr-virus-positive and with HLA class III in Epstein-Barr-virus-negative Hodgkin's lymphoma. Lancet 2005; 365:2216.
  57. Huang X, Kushekhar K, Nolte I, et al. Multiple HLA class I and II associations in classical Hodgkin lymphoma and EBV status defined subgroups. Blood 2011; 118:5211.
  58. Cozen W, Li D, Best T, et al. A genome-wide meta-analysis of nodular sclerosing Hodgkin lymphoma identifies risk loci at 6p21.32. Blood 2012; 119:469.
  59. Huang X, Kushekhar K, Nolte I, et al. HLA associations in classical Hodgkin lymphoma: EBV status matters. PLoS One 2012; 7:e39986.
  60. Tan KL, Scott DW, Hong F, et al. Tumor-associated macrophages predict inferior outcomes in classic Hodgkin lymphoma: a correlative study from the E2496 Intergroup trial. Blood 2012; 120:3280.
  61. Lukes R, Butler J, Hicks E. Natural history of Hodgkin's disease as related to its pathological picture. Cancer 1966; 19:317.
  62. Lukes RJ, Butler JJ. The pathology and nomenclature of Hodgkin's disease. Cancer Res 1966; 26:1063.
  63. Strickler JG, Michie SA, Warnke RA, Dorfman RF. The "syncytial variant" of nodular sclerosing Hodgkin's disease. Am J Surg Pathol 1986; 10:470.
  64. Sextro M, Diehl V, Franklin J, et al. Lymphocyte predominant Hodgkin's disease--a workshop report. European Task Force on Lymphoma. Ann Oncol 1996; 7 Suppl 4:61.
  65. Ashton-Key M, Thorpe PA, Allen JP, Isaacson PG. Follicular Hodgkin's disease. Am J Surg Pathol 1995; 19:1294.
  66. Neiman RS, Rosen PJ, Lukes RJ. Lymphocyte-depletion Hodgkin's disease. A clinicopathological entity. N Engl J Med 1973; 288:751.
  67. Leoncini L, Del Vecchio MT, Kraft R, et al. Hodgkin's disease and CD30-positive anaplastic large cell lymphomas--a continuous spectrum of malignant disorders. A quantitative morphometric and immunohistologic study. Am J Pathol 1990; 137:1047.
  68. Stein H, Herbst H, Anagnostopoulos I, et al. The nature of Hodgkin and Reed-Sternberg cells, their association with EBV, and their relationship to anaplastic large-cell lymphoma. Ann Oncol 1991; 2 Suppl 2:33.
  69. Schmitz R, Stanelle J, Hansmann ML, Küppers R. Pathogenesis of classical and lymphocyte-predominant Hodgkin lymphoma. Annu Rev Pathol 2009; 4:151.
  70. von Wasielewski R, Mengel M, Fischer R, et al. Classical Hodgkin's disease. Clinical impact of the immunophenotype. Am J Pathol 1997; 151:1123.
  71. Zukerberg LR, Collins AB, Ferry JA, Harris NL. Coexpression of CD15 and CD20 by Reed-Sternberg cells in Hodgkin's disease. Am J Pathol 1991; 139:475.
  72. Schmid C, Pan L, Diss T, Isaacson PG. Expression of B-cell antigens by Hodgkin's and Reed-Sternberg cells. Am J Pathol 1991; 139:701.
  73. von Wasielewski R, Werner M, Fischer R, et al. Lymphocyte-predominant Hodgkin's disease. An immunohistochemical analysis of 208 reviewed Hodgkin's disease cases from the German Hodgkin Study Group. Am J Pathol 1997; 150:793.
  74. Venkataraman G, Song JY, Tzankov A, et al. Aberrant T-cell antigen expression in classical Hodgkin lymphoma is associated with decreased event-free survival and overall survival. Blood 2013; 121:1795.
  75. Carbone A, Gloghini A, Gattei V, et al. Expression of functional CD40 antigen on Reed-Sternberg cells and Hodgkin's disease cell lines. Blood 1995; 85:780.
  76. Munro JM, Freedman AS, Aster JC, et al. In vivo expression of the B7 costimulatory molecule by subsets of antigen-presenting cells and the malignant cells of Hodgkin's disease. Blood 1994; 83:793.
  77. Diepstra A, van Imhoff GW, Karim-Kos HE, et al. HLA class II expression by Hodgkin Reed-Sternberg cells is an independent prognostic factor in classical Hodgkin's lymphoma. J Clin Oncol 2007; 25:3101.
  78. Kanzler H, Küppers R, Hansmann ML, Rajewsky K. 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 1996; 184:1495.
  79. Pinkus GS, Pinkus JL, Langhoff E, et al. Fascin, a sensitive new marker for Reed-Sternberg cells of hodgkin's disease. Evidence for a dendritic or B cell derivation? Am J Pathol 1997; 150:543.
  80. Ansell SM, Lesokhin AM, Borrello I, et al. PD-1 blockade with nivolumab in relapsed or refractory Hodgkin's lymphoma. N Engl J Med 2015; 372:311.
  81. Falini B, Bigerna B, Pasqualucci L, et al. Distinctive expression pattern of the BCL-6 protein in nodular lymphocyte predominance Hodgkin's disease. Blood 1996; 87:465.
  82. Carbone A, Gloghini A, Gaidano G, et al. Expression status of BCL-6 and syndecan-1 identifies distinct histogenetic subtypes of Hodgkin's disease. Blood 1998; 92:2220.
  83. 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.
  84. Browne P, Petrosyan K, Hernandez A, Chan JA. The B-cell transcription factors BSAP, Oct-2, and BOB.1 and the pan-B-cell markers CD20, CD22, and CD79a are useful in the differential diagnosis of classic Hodgkin lymphoma. Am J Clin Pathol 2003; 120:767.
  85. 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.
  86. 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.
  87. Doerr JR, Malone CS, Fike FM, et al. Patterned CpG methylation of silenced B cell gene promoters in classical Hodgkin lymphoma-derived and primary effusion lymphoma cell lines. J Mol Biol 2005; 350:631.
  88. Müschen M, Rajewsky K, Bräuninger A, et al. Rare occurrence of classical Hodgkin's disease as a T cell lymphoma. J Exp Med 2000; 191:387.
  89. Poppema S, Kaleta J, Hepperle B. 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. J Natl Cancer Inst 1992; 84:1789.
  90. M'kacher R, Bennaceur-Griscelli A, Girinsky T, et al. Telomere shortening and associated chromosomal instability in peripheral blood lymphocytes of patients with Hodgkin's lymphoma prior to any treatment are predictive of second cancers. Int J Radiat Oncol Biol Phys 2007; 68:465.
  91. Weber-Matthiesen K, Deerberg J, Poetsch M, et al. Numerical chromosome aberrations are present within the CD30+ Hodgkin and Reed-Sternberg cells in 100% of analyzed cases of Hodgkin's disease. Blood 1995; 86:1464.
  92. Inghirami G, Macri L, Rosati S, et al. The Reed-Sternberg cells of Hodgkin disease are clonal. Proc Natl Acad Sci U S A 1994; 91:9842.
  93. Green MR, Monti S, Rodig SJ, et al. 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 2010; 116:3268.
  94. Roemer MG, Advani RH, Ligon AH, et al. PD-L1 and PD-L2 Genetic Alterations Define Classical Hodgkin Lymphoma and Predict Outcome. J Clin Oncol 2016; 34:2690.
  95. Carbone A, Gloghini A, Larocca LM, et al. Human immunodeficiency virus-associated Hodgkin's disease derives from post-germinal center B cells. Blood 1999; 93:2319.
  96. Levine AM. HIV-associated Hodgkin's disease. Biologic and clinical aspects. Hematol Oncol Clin North Am 1996; 10:1135.
  97. Audouin J, Diebold J, Pallesen G. Frequent expression of Epstein-Barr virus latent membrane protein-1 in tumour cells of Hodgkin's disease in HIV-positive patients. J Pathol 1992; 167:381.
  98. Pelstring RJ, Zellmer RB, Sulak LE, et al. Hodgkin's disease in association with human immunodeficiency virus infection. Pathologic and immunologic features. Cancer 1991; 67:1865.
  99. Opelz G, Henderson R. Incidence of non-Hodgkin lymphoma in kidney and heart transplant recipients. Lancet 1993; 342:1514.
  100. Herndier BG, Sanchez HC, Chang KL, et al. High prevalence of Epstein-Barr virus in the Reed-Sternberg cells of HIV-associated Hodgkin's disease. Am J Pathol 1993; 142:1073.
  101. Schmitz R, Hansmann ML, Bohle V, et al. TNFAIP3 (A20) is a tumor suppressor gene in Hodgkin lymphoma and primary mediastinal B cell lymphoma. J Exp Med 2009; 206:981.
  102. Otto C, Giefing M, Massow A, et al. Genetic lesions of the TRAF3 and MAP3K14 genes in classical Hodgkin lymphoma. Br J Haematol 2012; 157:702.
  103. Reichel J, Chadburn A, Rubinstein PG, et al. Flow sorting and exome sequencing reveal the oncogenome of primary Hodgkin and Reed-Sternberg cells. Blood 2015; 125:1061.
  104. Tiacci E, Döring C, Brune V, et al. Analyzing primary Hodgkin and Reed-Sternberg cells to capture the molecular and cellular pathogenesis of classical Hodgkin lymphoma. Blood 2012; 120:4609.
  105. Bennett MH, MacLennan KA, Easterling MJ, et al. The prognostic significance of cellular subtypes in nodular sclerosing Hodgkin's disease: an analysis of 271 non-laparotomised cases (BNLI report no. 22). Clin Radiol 1983; 34:497.
  106. MacLennan KA, Bennett MH, Tu A, et al. Relationship of histopathologic features to survival and relapse in nodular sclerosing Hodgkin's disease. A study of 1659 patients. Cancer 1989; 64:1686.
  107. Haybittle JL, Hayhoe FG, Easterling MJ, et al. Review of British National Lymphoma Investigation studies of Hodgkin's disease and development of prognostic index. Lancet 1985; 1:967.
  108. Michel G, Bouzourene H, Delacretaz F, et al. Histologic grade of nodular sclerosing Hodgkin's disease: Is it a prognostic factor? Third International Symposium on Hodgkin's lymphoma, Kolne, Germany 1995.
  109. van Spronsen DJ, Vrints LW, Hofstra G, et al. Disappearance of prognostic significance of histopathological grading of nodular sclerosing Hodgkin's disease for unselected patients, 1972-92. Br J Haematol 1997; 96:322.
  110. Ferry JA, Linggood RM, Convery KM, et al. Hodgkin disease, nodular sclerosis type. Implications of histologic subclassification. Cancer 1993; 71:457.
  111. Wijlhuizen TJ, Vrints LW, Jairam R, et al. Grades of nodular sclerosis (NSI-NSII) in Hodgkin's disease. Are they of independent prognostic value? Cancer 1989; 63:1150.
  112. Hess JL, Bodis S, Pinkus G, et al. Histopathologic grading of nodular sclerosis Hodgkin's disease. Lack of prognostic significance in 254 surgically staged patients. Cancer 1994; 74:708.
  113. Georgii A, Hasenclever D, Fischer R, et al. Histopathological grading of nodular sclerosing Hodgkin's reveals significant differences in survival and relapse rather under protocOl-therapy. Third International Symposuim on Hodgkin's lymphoma, September, Kolne, Germany 1995.
  114. von Wasielewski R, Seth S, Franklin J, et al. Tissue eosinophilia correlates strongly with poor prognosis in nodular sclerosing Hodgkin's disease, allowing for known prognostic factors. Blood 2000; 95:1207.
  115. von Wasielewski S, Franklin J, Fischer R, et al. Nodular sclerosing Hodgkin disease: new grading predicts prognosis in intermediate and advanced stages. Blood 2003; 101:4063.
  116. Connors JM. Risk assessment in the management of newly diagnosed classical Hodgkin lymphoma. Blood 2015; 125:1693.
  117. Touati M, Delage-Corre M, Monteil J, et al. CD68-positive tumor-associated macrophages predict unfavorable treatment outcomes in classical Hodgkin lymphoma in correlation with interim fluorodeoxyglucose-positron emission tomography assessment. Leuk Lymphoma 2015; 56:332.
  118. Koh YW, Park CS, Yoon DH, et al. CD163 expression was associated with angiogenesis and shortened survival in patients with uniformly treated classical Hodgkin lymphoma. PLoS One 2014; 9:e87066.
  119. Wu D, Thomas A, Fromm JR. Reactive T cells by flow cytometry distinguish Hodgkin lymphomas from T cell/histiocyte-rich large B cell lymphoma. Cytometry B Clin Cytom 2016; 90:424.
  120. David JA, Huang JZ. Diagnostic Utility of Flow Cytometry Analysis of Reactive T Cells in Nodular Lymphocyte-Predominant Hodgkin Lymphoma. Am J Clin Pathol 2016; 145:107.
  121. Bakshi NA, Finn WG, Schnitzer B, et al. Fascin expression in diffuse large B-cell lymphoma, anaplastic large cell lymphoma, and classical Hodgkin lymphoma. Arch Pathol Lab Med 2007; 131:742.
  122. Dojcinov SD, Venkataraman G, Raffeld M, et al. EBV positive mucocutaneous ulcer--a study of 26 cases associated with various sources of immunosuppression. Am J Surg Pathol 2010; 34:405.
  123. Swerdlow SH, Campo E, Pileri SA, et al. The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood 2016; 127:2375.