Hodgkin Lymphoma Differential Diagnoses

Sections

DDx

Diagnostic Considerations

Other conditions to consider in the differential diagnosis of Hodgkin lymphoma include the following:

Any disease presenting with lymphadenopathy and constitutional symptoms
Infection with human immunodeficiency virus (HIV)
Hypersensitivity reaction
Other solid tumors
Non-Hodgkin lymphoma, particularly diffuse large B cell lymphoma and anaplastic large cell lymphoma, both of which may have CD30 expression^[34]

Because Hodgkin lymphoma is considered a curable malignancy and the differential diagnosis is broad, medicolegal problems may arise from failure to diagnose the disease in a timely manner, possibly due to the following factors:

The misinterpretation of B symptoms
A lack of follow-up for abnormal chest radiographs or physical examination findings
A missed pathologic diagnosis because a needle biopsy was obtained rather than an excisional lymph node biopsy

Occasionally, Hodgkin lymphoma can present as hemophagocytic syndrome (hemophagocytic lymphohistiocytosis).^[35]The hemophagocytic syndrome may be more prevalent in patients with Epstein-Barr virus (EBV) antigen expression and has the following characteristics:

Pancytopenia
Fever
Hepatosplenomegaly with liver function test abnormalities
Elevated serum levels of ferritin and triglycerides
Phagocytosis of hematopoietic lineage cells by benign macrophages

Differential Diagnoses

Workup

Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Vardiman JW, eds. World Health Organization Classification of Tumours: Pathology and Genetics of Tumours of Haematopoietic and Lymphoid Tissues. 4th ed. Lyon, France: IARC Press; 2008.
Swerdlow SH, Campo E, Pileri SA, Harris NL, Stein H, Siebert R, et al. The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood. 2016 May 19. 127 (20):2375-90. [Medline]. [Full Text].
Hentrich M, Maretta L, Chow KU, et al. Highly active antiretroviral therapy (HAART) improves survival in HIV-associated Hodgkin's disease: results of a multicenter study. Ann Oncol. 2006 Jun. 17(6):914-9. [Medline]. [Full Text].
[Guideline] NCCN Clinical Practice Guidelines in Oncology: Hodgkin Lymphoma. National Comprehensive Cancer Network. Available at http://www.nccn.org/professionals/physician_gls/pdf/hodgkins.pdf. Version 1.2018 — December 20, 2017; Accessed: March 22, 2018.
[Guideline] Eichenauer DA, Aleman BMP, André M, Federico M, Hutchings M, Illidge T, et al. Hodgkin lymphoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2018 May 23. 25 Suppl 3:iii70-5. [Medline]. [Full Text].
Cheson BD, Pfistner B, Juweid ME, et al. Revised response criteria for malignant lymphoma. J Clin Oncol. 2007 Feb 10. 25(5):579-86. [Medline]. [Full Text].
Schmitz N, Pfistner B, Sextro M, et al. Aggressive conventional chemotherapy compared with high-dose chemotherapy with autologous haemopoietic stem-cell transplantation for relapsed chemosensitive Hodgkin's disease: a randomised trial. Lancet. 2002 Jun 15. 359(9323):2065-71. [Medline].
Thomas RK, Re D, Wolf J, Diehl V. Part I: Hodgkin's lymphoma--molecular biology of Hodgkin and Reed-Sternberg cells. Lancet Oncol. 2004 Jan. 5(1):11-8. [Medline].
Re D, Kuppers R, Diehl V. Molecular pathogenesis of Hodgkin's lymphoma. J Clin Oncol. 2005 Sep 10. 23(26):6379-86. [Medline].
Gutensohn N, Cole P. Childhood social environment and Hodgkin's disease. N Engl J Med. 1981 Jan 15. 304(3):135-40. [Medline].
Hjalgrim H, Smedby KE, Rostgaard K, et al. Infectious mononucleosis, childhood social environment, and risk of Hodgkin lymphoma. Cancer Res. 2007 Mar 1. 67(5):2382-8. [Medline].
Staal SP, Ambinder R, Beschorner WE, Hayward GS, Mann R. A survey of Epstein-Barr virus DNA in lymphoid tissue. Frequent detection in Hodgkin's disease. Am J Clin Pathol. 1989 Jan. 91(1):1-5. [Medline].
Hjalgrim H, Askling J, Rostgaard K, Hamilton-Dutoit S, Frisch M, Zhang JS, et al. Characteristics of Hodgkin's lymphoma after infectious mononucleosis. N Engl J Med. 2003 Oct 2. 349(14):1324-32. [Medline].
Weiss LM, Chen YY, Liu XF, Shibata D. Epstein-Barr virus and Hodgkin's disease. A correlative in situ hybridization and polymerase chain reaction study. Am J Pathol. 1991 Dec. 139(6):1259-65. [Medline]. [Full Text].
Pallesen G, Hamilton-Dutoit SJ, Rowe M, Young LS. Expression of Epstein-Barr virus latent gene products in tumour cells of Hodgkin's disease. Lancet. 1991 Feb 9. 337(8737):320-2. [Medline].
Goldin LR, Pfeiffer RM, Gridley G, Gail MH, Li X, Mellemkjaer L, et al. Familial aggregation of Hodgkin lymphoma and related tumors. Cancer. 2004 May 1. 100(9):1902-8. [Medline].
Harty LC, Lin AY, Goldstein AM, Jaffe ES, Carrington M, Tucker MA, et al. HLA-DR, HLA-DQ, and TAP genes in familial Hodgkin disease. Blood. 2002 Jan 15. 99(2):690-3. [Medline].
Mack TM, Cozen W, Shibata DK, Weiss LM, Nathwani BN, Hernandez AM, 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 Feb 16. 332(7):413-8. [Medline].
Mueller NE, Grufferman S. Hodgkin lymphoma. Schottenfeld D, Fraumeni JF Jr , eds. Cancer Epidemiology and Prevention. New York, NY: Oxford University Press; 2006. 872-97.
Enciso-Mora V, Broderick P, Ma Y, Jarrett RF, Hjalgrim H, Hemminki K, et al. A genome-wide association study of Hodgkin's lymphoma identifies new susceptibility loci at 2p16.1 (REL), 8q24.21 and 10p14 (GATA3). Nat Genet. 2010 Dec. 42(12):1126-30. [Medline].
Cozen W, Li D, Best T, Van Den Berg DJ, Gourraud PA, Cortessis VK, et al. A genome-wide meta-analysis of nodular sclerosing Hodgkin lymphoma identifies risk loci at 6p21.32. Blood. 2012 Jan 12. 119(2):469-75. [Medline]. [Full Text].
National Cancer Institute. SEER stat fact sheets: Hodgkin lymphoma. Available at http://www.seer.cancer.gov/statfacts/html/hodg.html. Accessed: March 17, 2017.
Siegel RL, Miller KD, Jemal A. Cancer statistics, 2018. CA Cancer J Clin. 2018 Jan. 68 (1):7-30. [Medline]. [Full Text].
Sant M, Allemani C, Tereanu C, De Angelis R, Capocaccia R, Visser O, et al. Incidence of hematologic malignancies in Europe by morphologic subtype: results of the HAEMACARE project. Blood. 2010 Nov 11. 116(19):3724-34. [Medline].
Correa P, O'Conor GT. Epidemiologic patterns of Hodgkin's disease. Int J Cancer. 1971 Sep 15. 8(2):192-201. [Medline].
Cancer Research UK. Hodgkin lymphoma - UK incidence statistics. Available at http://www.cancerresearchuk.org/cancer-info/cancerstats/types/hodgkinslymphoma/incidence/#Overall. Accessed: March 17, 2017.
Ries LAG, Kosary CL, Hankey BF, Miller BA, Harras A, Edwards BK, et al. SEER Cancer Statistics Review, 1973-1994. Available at http://seer.cancer.gov/csr/1973_1994/. Accessed: March 22, 2018.
Howlader N, Noone AM, Krapcho M, et al, eds. Bethesda, Md: National Cancer Institute. Bethesda, et al. SEER Cancer Statistics Review, 1975-2008. (Based on November 2010 SEER data submission, posted to the SEER Website, 2011.). Available at http://seer.cancer.gov/csr/1975_2008/. Accessed: September 27, 2012.
Das P, Ng A, Constine LS, Hodgson DC, Mendenhall NP, Morris DE, et al. ACR Appropriateness Criteria on Hodgkin's lymphoma: favorable prognosis stage I and II. J Am Coll Radiol. 2008 Oct. 5(10):1054-66. [Medline]. [Full Text].
Das P, Ng A, Constine LS, Advani R, Flowers C, Friedberg J, et al. ACR Appropriateness Criteria(R) on Hodgkin's lymphoma-unfavorable clinical stage I and II. J Am Coll Radiol. 2011 May. 8(5):302-8. [Medline]. [Full Text].
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 Nov 19. 339(21):1506-14. [Medline]. [Full Text].
Steidl C, Lee T, Shah SP, Farinha P, Han G, Nayar T, et al. Tumor-associated macrophages and survival in classic Hodgkin's lymphoma. N Engl J Med. 2010 Mar 11. 362(10):875-85. [Medline]. [Full Text].
Bierman PJ, Lynch JC, Bociek RG, Whalen VL, Kessinger A, Vose JM, et al. The International Prognostic Factors Project score for advanced Hodgkin's disease is useful for predicting outcome of autologous hematopoietic stem cell transplantation. Ann Oncol. 2002 Sep. 13(9):1370-7. [Medline].
Swerdlow SH, Campo E, Harris NL, et al, eds. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. 4th ed. Lyon, France: IARC Press; 2008.
Menard F, Besson C, Rince P, et al. Hodgkin lymphoma-associated hemophagocytic syndrome: a disorder strongly correlated with Epstein-Barr virus. Clin Infect Dis. 2008 Aug 15. 47(4):531-4. [Medline].
Juweid ME, Stroobants S, Hoekstra OS, Mottaghy FM, Dietlein M, Guermazi A, et al. Use of positron emission tomography for response assessment of lymphoma: consensus of the Imaging Subcommittee of International Harmonization Project in Lymphoma. J Clin Oncol. 2007 Feb 10. 25(5):571-8. [Medline].
Juweid ME, Stroobants S, Hoekstra OS, et al. Use of positron emission tomography for response assessment of lymphoma: consensus of the Imaging Subcommittee of International Harmonization Project in Lymphoma. J Clin Oncol. 2007 Feb 10. 25(5):571-8. [Medline]. [Full Text].
Vassilakopoulos TP, Angelopoulou MK, Constantinou N, Karmiris T, Repoussis P, Roussou P, et al. Development and validation of a clinical prediction rule for bone marrow involvement in patients with Hodgkin lymphoma. Blood. 2005 Mar 1. 105(5):1875-80. [Medline].
Cosset JM, Henry-Amar M, Meerwaldt JH, Carde P, Noordijk EM, Thomas J, et al. The EORTC trials for limited stage Hodgkin's disease. The EORTC Lymphoma Cooperative Group. Eur J Cancer. 1992. 28A(11):1847-50. [Medline].
Engert A, Plütschow A, Eich HT, Lohri A, Dörken B, Borchmann P, et al. Reduced treatment intensity in patients with early-stage Hodgkin's lymphoma. N Engl J Med. 2010 Aug 12. 363(7):640-52. [Medline].
DeVita VT Jr. A selective history of the therapy of Hodgkin's disease. Br J Haematol. 2003 Sep. 122(5):718-27. [Medline].
Connors JM. State-of-the-art therapeutics: Hodgkin's lymphoma. J Clin Oncol. 2005 Sep 10. 23(26):6400-8. [Medline].
Advani R, Maeda L, Lavori P, et al. Impact of positive positron emission tomography on prediction of freedom from progression after Stanford V chemotherapy in Hodgkin's disease. J Clin Oncol. 2007 Sep 1. 25(25):3902-7. [Medline]. [Full Text].
Gallamini A, Hutchings M, Rigacci L, et al. Early interim 2-[18F]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. J Clin Oncol. 2007 Aug 20. 25(24):3746-52. [Medline]. [Full Text].
Johnson P, Federico M, Kirkwood A, Fosså A, Berkahn L, Carella A, et al. Adapted Treatment Guided by Interim PET-CT Scan in Advanced Hodgkin's Lymphoma. N Engl J Med. 2016 Jun 23. 374 (25):2419-29. [Medline]. [Full Text].
Levine JM, Weiner M, Kelly KM. Routine use of PET scans after completion of therapy in pediatric Hodgkin disease results in a high false positive rate. J Pediatr Hematol Oncol. 2006 Nov. 28(11):711-4. [Medline].
Wilder RB, Ng A, Constine LS, et al, for the Expert Panel on Radiation Oncology-Hodgkin's Lymphoma. ACR Appropriateness Criteria(R) Hodgkin's lymphoma--stage III and IV [online publication]. Reston, Va: American College of Radiology; 2010. [Full Text].
Koeck J, Abo-Madyan Y, Lohr F, Stieler F, Kriz J, Mueller RP, et al. Radiotherapy for early mediastinal Hodgkin lymphoma according to the German Hodgkin Study Group (GHSG): the roles of intensity-modulated radiotherapy and involved-node radiotherapy. Int J Radiat Oncol Biol Phys. 2012 May 1. 83(1):268-76. [Medline].
Specht L, Yahalom J, Illidge T, Berthelsen AK, Constine LS, Eich HT, et al. Modern radiation therapy for Hodgkin lymphoma: field and dose guidelines from the international lymphoma radiation oncology group (ILROG). Int J Radiat Oncol Biol Phys. 2014 Jul 15. 89 (4):854-62. [Medline].
Noordijk EM, Carde P, Dupouy N, Hagenbeek A, Krol AD, Kluin-Nelemans JC, et al. Combined-modality therapy for clinical stage I or II Hodgkin's lymphoma: long-term results of the European Organisation for Research and Treatment of Cancer H7 randomized controlled trials. J Clin Oncol. 2006 Jul 1. 24(19):3128-35. [Medline].
Engert A, Schiller P, Josting A, Herrmann R, et al. Involved-field radiotherapy is equally effective and less toxic compared with extended-field radiotherapy after four cycles of chemotherapy in patients with early-stage unfavorable Hodgkin's lymphoma... J Clin Oncol. 2003 Oct 1. 21(19):3601-8. [Medline].
Arakelyan N, Jais JP, Delwail V, Briere J, Moles-Moreau MP, Senecal D, et al. Reduced versus full doses of irradiation after 3 cycles of combined doxorubicin, bleomycin, vinblastine, and dacarbazine in early stage Hodgkin lymphomas: results of a randomized trial. Cancer. 2010 Sep 1. 116(17):4054-62. [Medline].
Canellos GP, Anderson JR, Propert KJ, et al. Chemotherapy of advanced Hodgkin's disease with MOPP, ABVD, or MOPP alternating with ABVD. N Engl J Med. 1992 Nov 19. 327(21):1478-84. [Medline].
Connors JM, et al; ECHELON-1 Study Group. Brentuximab Vedotin with Chemotherapy for Stage III or IV Hodgkin's Lymphoma. N Engl J Med. 2018 Jan 25. 378 (4):331-344. [Medline]. [Full Text].
Horning SJ, Hoppe RT, Breslin S, et al. Stanford V and radiotherapy for locally extensive and advanced Hodgkin's disease: mature results of a prospective clinical trial. J Clin Oncol. 2002 Feb 1. 20(3):630-7. [Medline]. [Full Text].
Advani RH, Hong F, Fisher RI, Bartlett NL, Robinson KS, Gascoyne RD, et al. Randomized Phase III Trial Comparing ABVD Plus Radiotherapy With the Stanford V Regimen in Patients With Stages I or II Locally Extensive, Bulky Mediastinal Hodgkin Lymphoma: A Subset Analysis of the North American Intergroup E2496 Trial. J Clin Oncol. 2015 Jun 10. 33 (17):1936-42. [Medline].
Diehl V, Franklin J, Pfreundschuh M, et al. Standard and increased-dose BEACOPP chemotherapy compared with COPP-ABVD for advanced Hodgkin's disease. N Engl J Med. 2003 Jun 12. 348(24):2386-95. [Medline]. [Full Text].
Viviani S, Zinzani PL, Rambaldi A, et al. ABVD versus BEACOPP for Hodgkin's lymphoma when high-dose salvage is planned. N Engl J Med. 2011 Jul 21. 365(3):203-12. [Medline].
Bauer K, Skoetz N, Monsef I, Engert A, Brillant C. Comparison of chemotherapy including escalated BEACOPP versus chemotherapy including ABVD for patients with early unfavourable or advanced stage Hodgkin lymphoma. Cochrane Database Syst Rev. 2011 Aug 10. CD007941. [Medline].
Mounier N, Brice P, Bologna S, Briere J, Gaillard I, Heczko M, et al. ABVD (8 cycles) versus BEACOPP (4 escalated cycles ≥ 4 baseline): final results in stage III-IV low-risk Hodgkin lymphoma (IPS 0-2) of the LYSA H34 randomized trial. Ann Oncol. 2014 Aug. 25 (8):1622-8. [Medline].
Carde P, Karrasch M, Fortpied C, Brice P, Khaled H, Casasnovas O, et al. Eight Cycles of ABVD Versus Four Cycles of BEACOPPescalated Plus Four Cycles of BEACOPPbaseline in Stage III to IV, International Prognostic Score ≥ 3, High-Risk Hodgkin Lymphoma: First Results of the Phase III EORTC 20012 Intergroup Trial. J Clin Oncol. 2016 Apr 25. [Medline].
Edwards-Bennett SM, Jacks LM, Moskowitz CH, et al. Stanford V program for locally extensive and advanced Hodgkin lymphoma: the Memorial Sloan-Kettering Cancer Center experience. Ann Oncol. 2010 Mar. 21(3):574-81. [Medline].
Gayoso J, Balsalobre P, Pascual MJ, Castilla-Llorente C, López-Corral L, Kwon M, et al. Busulfan-based reduced intensity conditioning regimens for haploidentical transplantation in relapsed/refractory Hodgkin lymphoma: Spanish multicenter experience. Bone Marrow Transplant. 2016 May 9. [Medline].
Moskowitz CH, Nademanee A, Masszi T, Agura E, Holowiecki J, Abidi MH, et al. Brentuximab vedotin as consolidation therapy after autologous stem-cell transplantation in patients with Hodgkin's lymphoma at risk of relapse or progression (AETHERA): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2015 May 9. 385 (9980):1853-62. [Medline].
Ferme C, Eghbali H, Meerwaldt JH, et al. Chemotherapy plus involved-field radiation in early-stage Hodgkin's disease. N Engl J Med. 2007 Nov 8. 357(19):1916-27. [Medline]. [Full Text].
Engert A, Franklin J, Eich HT, et al. Two cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine plus extended-field radiotherapy is superior to radiotherapy alone in early favorable Hodgkin's lymphoma: final results of the GHSG HD7 trial. J Clin Oncol. 2007 Aug 10. 25(23):3495-502. [Medline]. [Full Text].
Herbst C, Rehan FA, Brillant C, Bohlius J, Skoetz N, Schulz H, et al. Combined modality treatment improves tumor control and overall survival in patients with early stage Hodgkin's lymphoma: a systematic review. Haematologica. 2010 Mar. 95(3):494-500. [Medline]. [Full Text].
Meyer RM, Gospodarowicz MK, Connors JM, Pearcey RG, Wells WA, Winter JN, et al. ABVD alone versus radiation-based therapy in limited-stage Hodgkin's lymphoma. N Engl J Med. 2012 Feb 2. 366(5):399-408. [Medline].
Hutchings M, Mikhaeel NG, Fields PA, Nunan T, Timothy AR. Prognostic value of interim FDG-PET after two or three cycles of chemotherapy in Hodgkin lymphoma. Ann Oncol. 2005 Jul. 16(7):1160-8. [Medline].
Hutchings M, Loft A, Hansen M, Pedersen LM, Buhl T, Jurlander J, et al. FDG-PET after two cycles of chemotherapy predicts treatment failure and progression-free survival in Hodgkin lymphoma. Blood. 2006 Jan 1. 107(1):52-9. [Medline].
Advani RH, Horning SJ. Treatment of early-stage Hodgkin's disease. Semin Hematol. 1999 Jul. 36(3):270-81. [Medline].
von Tresckow B, Plutschow A, Fuchs M, Klimm B, Markova J, Lohri A, et al. Dose-intensification in early unfavorable Hodgkin's lymphoma: final analysis of the German Hodgkin Study Group HD14 trial. J Clin Oncol. 2012 Mar 20. 30(9):907-13. [Medline].
Armitage JO. Early-stage Hodgkin's lymphoma. N Engl J Med. 2010 Aug 12. 363(7):653-62. [Medline].
Duggan DB, Petroni GR, Johnson JL, Glick JH, Fisher RI, Connors JM, et al. Randomized comparison of ABVD and MOPP/ABV hybrid for the treatment of advanced Hodgkin's disease: report of an intergroup trial. J Clin Oncol. 2003 Feb 15. 21(4):607-14. [Medline].
Johnson PW, Radford JA, Cullen MH, Sydes MR, Walewski J, Jack AS, et al. Comparison of ABVD and alternating or hybrid multidrug regimens for the treatment of advanced Hodgkin's lymphoma: results of the United Kingdom Lymphoma Group LY09 Trial (ISRCTN97144519). J Clin Oncol. 2005 Dec 20. 23(36):9208-18. [Medline].
Boleti E, Mead GM. ABVD for Hodgkin's lymphoma: full-dose chemotherapy without dose reductions or growth factors. Ann Oncol. 2007 Feb. 18(2):376-80. [Medline].
Wedgwood A, Younes A. Prophylactic use of filgrastim with ABVD and BEACOPP chemotherapy regimens for Hodgkin lymphoma. Clin Lymphoma Myeloma. 2007 Dec. 8 Suppl 2:S63-6. [Medline].
Saxman SB, Nichols CR, Einhorn LH. Pulmonary toxicity in patients with advanced-stage germ cell tumors receiving bleomycin with and without granulocyte colony stimulating factor. Chest. 1997 Mar. 111(3):657-60. [Medline].
Federico M, Luminari S, Iannitto E, Polimeno G, Marcheselli L, Montanini A, et al. ABVD compared with BEACOPP compared with CEC for the initial treatment of patients with advanced Hodgkin's lymphoma: results from the HD2000 Gruppo Italiano per lo Studio dei Linfomi Trial. J Clin Oncol. 2009 Feb 10. 27(5):805-11. [Medline].
Engert A, Haverkamp H, Kobe C, Markova J, Renner C, Ho A, et al. Reduced-intensity chemotherapy and PET-guided radiotherapy in patients with advanced stage Hodgkin's lymphoma (HD15 trial): a randomised, open-label, phase 3 non-inferiority trial. Lancet. 2012 May 12. 379(9828):1791-9. [Medline].
Horning SJ, Hoppe RT, Advani R, et al. Efficacy and late effects of Stanford V chemotherapy and radiotherapy in untreated Hodgkin's disease: mature data in early and advanced stage patients [abstract 308]. Blood. 2004. 104:92a.
Gordon LI, Hong F, Fisher RI, et al. Randomized phase III trial of ABVD vs. Stanford V /- radiation therapy in locally extensive and advanced stage Hodgkin's lymphoma... Blood (ASH Annual Meeting Abstracts). 2010. 116(21):185; (E2496) [abstract 415].
Hoppe RT. Hodgkin's disease--the role of radiation therapy in advanced disease. Ann Oncol. 1996. 7 Suppl 4:99-103. [Medline].
Loeffler M, Brosteanu O, Hasenclever D, Sextro M, Assouline D, Bartolucci AA, et al. Meta-analysis of chemotherapy versus combined modality treatment trials in Hodgkin's disease. International Database on Hodgkin's Disease Overview Study Group. J Clin Oncol. 1998 Mar. 16(3):818-29. [Medline].
Aleman BM, Raemaekers JM, Tomisic R, Baaijens MH, Bortolus R, Lybeert ML, et al. Involved-field radiotherapy for patients in partial remission after chemotherapy for advanced Hodgkin's lymphoma. Int J Radiat Oncol Biol Phys. 2007 Jan 1. 67(1):19-30. [Medline].
Johnson PW, Sydes MR, Hancock BW, Cullen M, Radford JA, Stenning SP. Consolidation radiotherapy in patients with advanced Hodgkin's lymphoma: survival data from the UKLG LY09 randomized controlled trial (ISRCTN97144519). J Clin Oncol. 2010 Jul 10. 28(20):3352-9. [Medline].
Portlock CS. Nodular lymphocyte predominant Hodgkin's disease. Cancer Treat Res. 2006. 131:353-62. [Medline].
Schulz H, Rehwald U, Morschhauser F, et al. Rituximab in relapsed lymphocyte-predominant Hodgkin lymphoma: long-term results of a phase 2 trial by the German Hodgkin Lymphoma Study Group (GHSG). Blood. 2008 Jan 1. 111(1):109-11. [Medline]. [Full Text].
Eichenauer DA, Fuchs M, Pluetschow A, et al. Phase 2 study of rituximab in newly diagnosed stage IA nodular lymphocyte-predominant Hodgkin lymphoma: a report from the German Hodgkin Study Group. Blood. 2011 Oct 20. 118(16):4363-5. [Medline].
Savage KJ, Skinnider B, Al-Mansour M, Sehn LH, Gascoyne RD, Connors JM. Treating limited-stage nodular lymphocyte predominant Hodgkin lymphoma similarly to classical Hodgkin lymphoma with ABVD may improve outcome. Blood. 2011 Oct 27. 118(17):4585-90. [Medline].
Lavoie JC, Connors JM, Phillips GL, et al. High-dose chemotherapy and autologous stem cell transplantation for primary refractory or relapsed Hodgkin lymphoma: long-term outcome in the first 100 patients treated in Vancouver. Blood. 2005 Aug 15. 106(4):1473-8. [Medline]. [Full Text].
Gopal AK, Metcalfe TL, Gooley TA, et al. High-dose therapy and autologous stem cell transplantation for chemoresistant Hodgkin lymphoma: the Seattle experience. Cancer. 2008 Sep 15. 113(6):1344-50. [Medline].
Przepiorka D, van Besien K, Khouri I, et al. Carmustine, etoposide, cytarabine and melphalan as a preparative regimen for allogeneic transplantation for high-risk malignant lymphoma. Ann Oncol. 1999 May. 10(5):527-32. [Medline]. [Full Text].
Anderlini P, Saliba R, Acholonu S, et al. Fludarabine-melphalan as a preparative regimen for reduced-intensity conditioning allogeneic stem cell transplantation in relapsed and refractory Hodgkin''s lymphoma: the updated M.D. Anderson Cancer Center experience. Haematologica. 2008 Feb. 93(2):257-64. [Medline]. [Full Text].
Younes A, Bartlett NL, Leonard JP, Kennedy DA, Lynch CM, Sievers EL, et al. Brentuximab vedotin (SGN-35) for relapsed CD30-positive lymphomas. N Engl J Med. 2010 Nov 4. 363(19):1812-21. [Medline]. [Full Text].
Younes A, Gopal AK, Smith SE, Ansell SM, Rosenblatt JD, Savage KJ, et al. Results of a pivotal phase II study of brentuximab vedotin for patients with relapsed or refractory Hodgkin's lymphoma. J Clin Oncol. 2012 Jun 20. 30 (18):2183-9. [Medline]. [Full Text].
Ansell SM, Lesokhin AM, Borrello I, Halwani A, Scott EC, Gutierrez M, et al. PD-1 blockade with nivolumab in relapsed or refractory Hodgkin's lymphoma. N Engl J Med. 2015 Jan 22. 372 (4):311-9. [Medline]. [Full Text].
Ansell S, et al. Nivolumab in Patients (Pts) with Relapsed or Refractory Classical Hodgkin Lymphoma (R/R cHL): Clinical Outcomes from Extended Follow-up of a Phase 1 Study (CA209-039). Blood. 2015. 126(23):[Full Text].
Chen R, Zinzani PL, Fanale MA, Armand P, Johnson NA, Brice P, et al. Phase II Study of the Efficacy and Safety of Pembrolizumab for Relapsed/Refractory Classic Hodgkin Lymphoma. J Clin Oncol. 2017 Jul 1. 35 (19):2125-2132. [Medline]. [Full Text].
Aleman BM, van den Belt-Dusebout AW, De Bruin ML, et al. Late cardiotoxicity after treatment for Hodgkin lymphoma. Blood. 2007 Mar 1. 109(5):1878-86. [Medline]. [Full Text].
Wethal T, Lund MB, Edvardsen T, et al. Valvular dysfunction and left ventricular changes in Hodgkin's lymphoma survivors. A longitudinal study. Br J Cancer. 2009 Aug 18. 101(4):575-81. [Medline]. [Full Text].
Heidenreich PA, Schnittger I, Strauss HW, et al. Screening for coronary artery disease after mediastinal irradiation for Hodgkin's disease. J Clin Oncol. 2007 Jan 1. 25(1):43-9. [Medline]. [Full Text].
Milano MT, Li H, Constine LS, Travis LB. Survival after second primary lung cancer: a population-based study of 187 Hodgkin lymphoma patients. Cancer. 2011 Dec 15. 117(24):5538-47. [Medline].
Swerdlow AJ, Higgins CD, Smith P, et al. Second Cancer Risk After Chemotherapy for Hodgkin's Lymphoma: A Collaborative British Cohort Study. J Clin Oncol. 2011 Nov 1. 29(31):4096-104. [Medline].
Barbaro PM, Johnston K, Dalla-Pozza L, Cohn RJ, Wang YA, Marshall GM, et al. Reduced incidence of second solid tumors in survivors of childhood Hodgkin's lymphoma treated without radiation therapy. Ann Oncol. 2011 Dec. 22(12):2569-74. [Medline].
Behringer K, Breuer K, Reineke T, et al. Secondary amenorrhea after Hodgkin's lymphoma is influenced by age at treatment, stage of disease, chemotherapy regimen, and the use of oral contraceptives during therapy: a report from the German Hodgkin's Lymphoma Study Group. J Clin Oncol. 2005 Oct 20. 23(30):7555-64. [Medline].
Sieniawski M, Reineke T, Josting A, et al. Assessment of male fertility in patients with Hodgkin's lymphoma treated in the German Hodgkin Study Group (GHSG) clinical trials. Ann Oncol. 2008 Oct. 19(10):1795-801. [Medline].
Kornblith AB, Herndon JE 2nd, Zuckerman E, et al. Comparison of psychosocial adaptation of advanced stage Hodgkin's disease and acute leukemia survivors. Cancer and Leukemia Group B. Ann Oncol. 1998 Mar. 9(3):297-306. [Medline].
Loge JH, Abrahamsen AF, Ekeberg, Kaasa S. Fatigue and psychiatric morbidity among Hodgkin's disease survivors. J Pain Symptom Manage. 2000 Feb. 19(2):91-9. [Medline].
Ng A, Constine LS, Advani R, Das P, Flowers C, Friedberg J, et al. ACR Appropriateness Criteria: follow-up of Hodgkin's lymphoma. Curr Probl Cancer. 2010 May-Jun. 34(3):211-27. [Medline]. [Full Text].
Andre M, Bosly A. BEACOPP_escalated versus ABVD in advanced Hodgkin's lymphoma. Lancet Oncol. 2013 Aug 12. [Medline].
Moskowitz AJ, Schöder H, Yahalom J, McCall SJ, Fox SY, et al. PET-adapted sequential salvage therapy with brentuximab vedotin followed by augmented ifosamide, carboplatin, and etoposide for patients with relapsed and refractory Hodgkin's lymphoma: a non-randomised, open-label, single-centre, phase 2 study. Lancet Oncol. 2015 Mar. 16 (3):284-92. [Medline].
Garcia-Sanz R, Sureda A, Alonso-Alvarez S, Gonzalez AP, Rodriguez A, et al. Evaluation of the Regimen Brentuximab Vedotin Plus ESHAP (BRESHAP) in Refractory or Relapsed Hodgkin Lymphoma Patients: Preliminary Results of a Phase I-II Trial from the Spanish Group of Lymphoma and Bone Marrow Transplantation (GELTAMO). Blood. 2015. [Full Text].
Cassaday RD, Fromm J, Cowan AJ, Libby EN III, Philip M, et al. Safety and Activity of Brentuximab Vedotin (BV) Plus Ifosfamide, Carboplatin, and Etoposide (ICE) for Relapsed/Refractory (Rel/Ref) Classical Hodgkin Lymphoma (cHL): Initial Results of a Phase I/II Trial. Blood. 2016. [Full Text].
LaCasce AS, Bociek RG, Sawas A, Caimi P, Agura E, Matous J, et al. Brentuximab vedotin plus bendamustine: a highly active first salvage regimen for relapsed or refractory Hodgkin lymphoma. Blood. 2018 Jul 5. 132 (1):40-48. [Medline]. [Full Text].
Herrera AF, Moskowitz AJ, Bartlett NL, Vose JM, Ramchandren R, Feldman TA, et al. Interim results of brentuximab vedotin in combination with nivolumab in patients with relapsed or refractory Hodgkin lymphoma. Blood. 2018 Mar 15. 131 (11):1183-1194. [Medline]. [Full Text].
Ramchandren R, Fanale M, Rueda A, et al. Nivolumab for Newly Diagnosed Advanced-Stage Classical Hodgkin Lymphoma (cHL): Results from the Phase 2 Checkmate 205 Study. Blood. 2017. 130(Suppl 1):651. [Full Text].
Wang CM, Wu ZQ, Wang Y, Guo YL, Dai HR, Wang XH, et al. Autologous T Cells Expressing CD30 Chimeric Antigen Receptors for Relapsed or Refractory Hodgkin Lymphoma: An Open-Label Phase I Trial. Clin Cancer Res. 2017 Mar 1. 23 (5):1156-1166. [Medline]. [Full Text].
Lister TA, Crowther D, Sutcliffe SB, Glatstein E, Canellos GP, Young RC, et al. Report of a committee convened to discuss the evaluation and staging of patients with Hodgkin's disease: Cotswolds meeting. J Clin Oncol. 1989 Nov. 7 (11):1630-6. [Medline].
[Guideline] Cheson BD, Fisher RI, Barrington SF, et al. Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification. J Clin Oncol. 2014 Sep 20. 32 (27):3059-68. [Medline]. [Full Text].
Federico M, Bellei M, Brice P, Brugiatelli M, Nagler A, Gisselbrecht C, et al. High-dose therapy and autologous stem-cell transplantation versus conventional therapy for patients with advanced Hodgkin's lymphoma responding to front-line therapy. J Clin Oncol. 2003 Jun 15. 21(12):2320-5. [Medline].
Connors JM, et al; ECHELON-1 Study Group. Brentuximab Vedotin with Chemotherapy for Stage III or IV Hodgkin's Lymphoma. N Engl J Med. 2018 Jan 25. 378 (4):331-344. [Medline]. [Full Text].
Canioni D, Deau-Fischer B, Taupin P, et al. Prognostic significance of new immunohistochemical markers in refractory classical Hodgkin lymphoma: a study of 59 cases. PLoS One. 2009 Jul 22. 4(7):e6341. [Medline]. [Full Text].
Chang ET, Canchola AJ, Cockburn M, et al. Adulthood residential ultraviolet radiation, sun sensitivity, dietary vitamin D, and risk of lymphoid malignancies in the California Teachers Study. Blood. 2011 Aug 11. 118(6):1591-9. [Medline]. [Full Text].
Eich HT, Diehl V, Gorgen H, et al. Intensified chemotherapy and dose-reduced involved-field radiotherapy in patients with early unfavorable Hodgkin's lymphoma: final analysis of the German Hodgkin Study Group HD11 trial. J Clin Oncol. 2010 Sep 20. 28(27):4199-206. [Medline].

Media Gallery

Micrograph of Hodgkin lymphoma in a fine-needle aspiration lymph node specimen (field stain). Eosinophils, Reed-Sternberg cells, plasma cells, and histocytes can be seen.
Nodular sclerosing Hodgkin lymphoma of the mediastinum. The diagnosis is strongly suggested by the presence of distinct nodules on the cut surface of this lymph node.
A Reed-Sternberg cell in Hodgkin lymphoma. Reed-Sternberg cells are large, abnormal lymphocytes that may contain more than one nucleus. Image courtesy of National Cancer Institute.
Mixed cellularity Hodgkin lymphoma showing both mononucleate and binucleate Reed-Sternberg cells in a background of inflammatory cells (hematoxylin and eosin, original magnification x200).
Very high magnification micrograph of nodular lymphoctye predominant Hodgkin lymphoma (NLPHL), with a popcorn-shaped Reed-Sternberg cell (hematoxylin and eosin).
A positron emission tomography (PET) scan obtained with fluorodeoxyglucose (FDG) that shows increased FDG uptake in a mediastinal lymph node.
A computed tomography (CT) scan showing bulk disease in a patient with Hodgkin lymphoma.
This computed tomography scan is from a 46-year patient with Hodgkin lymphoma at the level of the neck. Enlarged lymph nodes are visible on the left side of the neck (red-shaded region).
This image depicts a computed tomography (CT) scan, positron-emission tomography (PET) scan, and maximum intensity projection (MIP) PET scan from a patient with histologically proven Hodgkin lymphoma.

of 9

Table 1. Stage Distribution and 5-Year Relative Survival by Stage at Diagnosis for All Races and Both Sexes: 2011-2015

Stage at Diagnosis	Stage Distribution, %	5-year Relative Survival, %
Stage I (only in originating layer of cells)	15	92.3
Stage II (confined to primary site)	40	93.4
Stage III (spread to regional lymph nodes)	21	83.0
Stage IV (cancer has metastasized)	20	72.9
Unstaged	4	82.7
Source: National Cancer Institute. SEER stat fact sheets: Hodgkin lymphoma. Available at: http://www.seer.cancer.gov/statfacts/html/hodg.html. Accessed: September 12, 2018

Table 1. Cotswold Modification of Ann Arbor Staging System

Stage	Area of Involvement
I	Single lymph node group
II	Multiple lymph node groups on same side of diaphragm
III	Multiple lymph node groups on both sides of diaphragm

Table 2. International Conference on Malignant Lymphomas Modification of Ann Arbor Staging

Stage		Area of Involvement	Extranodal (E) Status
I	Single node or adjacent group of nodes		Single extranodal lesions without nodal involvement
II	Multiple lymph node groups on same side of diaphragm		Stage I or II by nodal extent with limited contiguous extranodal involvement
II bulky*	Multiple lymph node groups on same side of diaphragm with bulk >10 cm		N/A
III	Multiple lymph node groups on both sides of diaphragm; nodes above the diaphragm with spleen involvement		N/A
IV	Multiple noncontiguous extranodal sites		N/A
A/B	B symptoms: weight loss >10%, fever, drenching night sweats		N/A
*Stage II bulky disease is defined as limited or advanced on the basis of histology and a number of prognostic factors.

Table 3. Unfavorable Risk Factors for Stages I and II Hodgkin Lymphoma

Risk Factor	GSHG	EORTC/LSA
Age	–	≥50 y
Histology	–	MC or LD
ESR or B symptoms	>50 mm/hr if A or >30 if B	>50 mm/hr if A or > 30 if B
Mediastinal mass*	MMR >0.33	MMR >0.35
Number of nodal sites	>2	>3
Extranodal lesions	Any	–
* Mediastinal mass is measured on chest x-ray by the mediastinal mass ratio (MMR), which is the maximum width of the mass/maximum intrathoracic diameter.ESR = erythrocyte sedimentation rate; LD = lymphocyte depletion; MC = mixed cellularity.

Back to List

Author

Bradley W Lash, MD Attending Physician, Lehigh Valley Cancer Institute

Bradley W Lash, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American Society of Clinical Oncology, American Society of Hematology

Disclosure: Nothing to disclose.

Coauthor(s)

Zachary Wolfe, MD Fellow in Hematology/Oncology, Lehigh Valley Health Network

Zachary Wolfe, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American Society of Clinical Oncology, American Society of Hematology, International Society on Thrombosis and Haemostasis

Disclosure: Nothing to disclose.

Athanassios Argiris, MD Professor, Division of Hematology-Oncology, Department of Medicine, University of Pittsburgh School of Medicine

Athanassios Argiris, MD is a member of the following medical societies: American Association for Cancer Research, American College of Physicians, American Medical Association

Disclosure: Nothing to disclose.

Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Chief Editor

Emmanuel C Besa, MD Professor Emeritus, Department of Medicine, Division of Hematologic Malignancies and Hematopoietic Stem Cell Transplantation, Kimmel Cancer Center, Jefferson Medical College of Thomas Jefferson University

Emmanuel C Besa, MD is a member of the following medical societies: American Association for Cancer Education, American Society of Clinical Oncology, American College of Clinical Pharmacology, American Federation for Medical Research, American Society of Hematology, New York Academy of Sciences

Disclosure: Nothing to disclose.

Acknowledgements

Scott K Dessain, MD, PhD Associate Professor, Lankenau Institute for Medical Research

Disclosure: Genentech Speaker's bureau.

Virginia Kaklamani, MD, Fellow, Department of Internal Medicine, Division of Hematology-Oncology, Northwestern University Medical School

Disclosure: Nothing to disclose.

Koyamangalath Krishnan, MD, FRCP, FACP Paul Dishner Endowed Chair of Excellence in Medicine, Professor of Medicine and Chief of Hematology-Oncology, James H Quillen College of Medicine at East Tennessee State University

Koyamangalath Krishnan, MD, FRCP, FACP is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians-American Society of Internal Medicine, American Society of Hematology, and Royal College of Physicians

Disclosure: Nothing to disclose.

James L Spears, MD Consulting Staff, Bux-Mont Hematology Oncology Medical Associates

James L Spears, MD is a member of the following medical societies: American Society of Clinical Oncology

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Christine Wasilewski, MD, MPH, Fellow, Department of Medicine, Division of Hematology-Oncology, Thomas Jefferson University Hospital

Disclosure: Nothing to disclose.

Hodgkin Lymphoma Differential Diagnoses

Diagnostic Considerations

Differential Diagnoses

About

Membership

Apps

WebMD Network

Editions

What to Read Next on Medscape

Hodgkin Lymphoma Differential Diagnoses

Diagnostic Considerations

Differential Diagnoses

References

Tables

Contributor Information and Disclosures

What would you like to print?

Find Us On

About

Membership

Apps

WebMD Network

Editions

What to Read Next on Medscape

Related Conditions and Diseases

Medscape Consult

News & Perspective

Tools

Slideshow

Most Popular Articles

Recommended