Background
Hodgkin lymphoma (formerly, Hodgkin disease) is a potentially curable lymphoma with distinct histology, biologic behavior, and clinical characteristics. Thomas Hodgkin first described the disorder in 1832; in the 20th century, realization that the disease is a lymphoid malignancy led to it being renamed Hodgkin lymphoma. The disease is defined in terms of its microscopic appearance (histology) and the expression of cell surface markers (immunophenotype). (See Pathophysiology.)
To diagnose Hodgkin lymphoma a histologic evaluation is always required, and an excisional lymph node biopsy is recommended for this purpose (see Workup). Various imaging studies are used to stage the patient.
Treatment for Hodgkin lymphoma is with multiagent chemotherapy, with or without radiation therapy. Treatment seeks to balance the risk of treatment failure with the risk of treatment side effects (see Treatment).
See also the Medscape Reference topic Pediatric Hodgkin Disease.
Pathophysiology
As classified by the World Health Organization (WHO), Hodgkin lymphoma exists in 5 types.[1] Four of these—nodular sclerosis, mixed cellularity, lymphocyte depleted, and lymphocyte rich—are referred to as classic Hodgkin lymphoma. The fifth type, nodular lymphocyte predominant Hodgkin disease (NLPHD), is a distinct entity with unique clinical features and a different treatment paradigm.
In classic Hodgkin lymphoma, the neoplastic cell is the Reed-Sternberg (RS) cell.[2, 3] Reed-Sternberg cells comprise only 1-2% of the total tumor cell mass. The remainder is composed of a variety of reactive, mixed inflammatory cells consisting of lymphocytes, plasma cells, neutrophils, eosinophils, and histiocytes.
Most Reed-Sternberg cells are of B-cell origin, derived from lymph node germinal centers but no longer able to produce antibodies. Some Hodgkin lymphoma cases have been identified in which the Reed-Sternberg cell is of T-cell origin but these are rare, accounting for 1-2% of classic Hodgkin lymphoma.
The Reed-Sternberg cells consistently express the CD30 (Ki-1) and CD15 (Leu-M1) antigens. CD30 is a marker of lymphocyte activation that is expressed by reactive and malignant lymphoid cells and was originally identified as a cell surface antigen on Reed-Sternberg cells. CD15 is a marker of late granulocytes, monocytes, and activated T cells that is not normally expressed by cells of B lineage.
Nodular sclerosis Hodgkin disease
In nodular sclerosis Hodgkin disease (NSHD), which constitutes 60-80% of all cases of Hodgkin lymphoma, the morphology shows a nodular pattern. Broad bands of fibrosis divide the node into nodules. The capsule is thickened. The characteristic cell is the lacunar-type Reed-Sternberg cell, which has a monolobated or multilobated nucleus, a small nucleolus, and abundant pale cytoplasm.
NSHD is frequently observed in adolescents and young adults. It usually involves the mediastinum and other supradiaphragmatic sites.
Mixed-cellularity Hodgkin disease
In mixed-cellularity Hodgkin disease (MCHD), which constitutes 15-30% of cases, the infiltrate is usually diffuse. Reed-Sternberg cells are of the classic type (large, with bilobate, double or multiple nuclei, and a large, eosinophilic nucleolus). MCHD commonly affects the abdominal lymph nodes and spleen. Patients with this histology typically have advanced-stage disease with systemic symptoms. MCHD is the histologic type most commonly observed in patients with human immunodeficiency virus (HIV) infection.
Lymphocyte-depleted Hodgkin disease
Lymphocyte-depleted Hodgkin disease (LDHD) constitutes less than 1% of cases. The infiltrate in LDHD is diffuse and often appears hypocellular. Large numbers of Reed-Sternberg cells and bizarre sarcomatous variants are present.
LDHD is associated with older age and HIV-positive status. Patients usually present with advanced-stage disease. Epstein-Barr virus (EBV) proteins are expressed in many of these tumors. Many cases of LDHD diagnosed in the past were actually were non-Hodgkin lymphomas, often of the anaplastic large-cell type.
Lymphocyte-rich classic Hodgkin disease
Lymphocyte-rich classic Hodgkin disease (LRHD) constitutes 5% of cases. In LRHD, Reed-Sternberg cells of the classic or lacunar type are observed, with a background infiltrate of lymphocytes. It requires immunohistochemical diagnosis. Some cases may have a nodular pattern. Clinically, the presentation and survival patterns are similar to those for MCHD.
Nodular lymphocyte-predominant Hodgkin disease
Nodular lymphocyte-predominant Hodgkin disease (NLPHD) constitutes 5% of cases. In contrast to the other histologic subtypes, the typical Reed-Sternberg cells are either infrequent or absent in NLPHD. Instead, lymphocytic and histiocytic (L&H) cells, or "popcorn cells" (their nuclei resemble an exploded kernel of corn), are seen within a background of inflammatory cells, which are predominantly benign lymphocytes. Unlike Reed-Sternberg cells, L&H cells are positive for B-cell antigens, such as CD19 and CD20, and are negative for CD15 and CD30.
A diagnosis of NLPHD needs to be supported by immunohistochemical studies, because it can appear similar to LRHD or even some non-Hodgkin lymphomas.
Etiology
The etiology of Hodgkin lymphoma is unknown. Infectious agents, particularly EBV, may be involved in the pathogenesis. In as many as 50% of cases, the tumor cells are EBV-positive; EBV positivity is higher with MCHD (60-70%) than with NSHD (15-30%). Almost 100% of HIV-associated cases are EBV-positive.
An epidemiologic study from Denmark and Sweden showed an increased risk of EBV-positive Hodgkin lymphoma in patients with a self-reported history of infectious mononucleosis (IM) in adolescence.[4] The average incubation time from IM to symptoms of Hodgkin lymphoma was 2.9 years.
Patients with HIV infection have a higher incidence of Hodgkin lymphoma compared with the population without HIV infection. However, Hodgkin lymphoma is not considered an acquired immunodeficiency syndrome (AIDS)-defining neoplasm.
Genetic predisposition may play a role in the pathogenesis of Hodgkin lymphoma. Approximately 1% of patients with Hodgkin lymphoma have a family history of the disease. Siblings of an affected individual have a 3- to 7-fold increased risk for developing Hodgkin lymphoma. This risk is higher in monozygotic twins. Human leukocyte antigen (HLA)-DP alleles are more common in Hodgkin lymphoma.
A study by Chang et al found that routine residential UV radiation exposure may have a protective effect against lymphomagenesis through mechanisms that may be independent of vitamin D.[5]
Epidemiology
United States statistics
Information regarding the incidence and mortality of Hodgkin lymphoma in the United States can be found at the National Cancer Institute (NCI) Surveillance Epidemiology and End Results (SEER) database Website (www.seer.cancer.gov). Data are also collected by the American Cancer Society (ACS).[6] The NCI estimated that 8,830 new cases and 1,300 deaths from Hodgkin lymphoma would occur in 2011. The age-adjusted incidence of Hodgkin lymphoma is 2.8 cases per 100,000 individuals.
International statistics
Hodgkin lymphoma had a worldwide incidence of 62,000 cases in 2002. Compared with North America and Europe, Hodgkin lymphoma is relatively rare in Japan (age-adjusted incidence of 0.3 per 100,000 males) and China (age-adjusted incidence of 0.2 per 100,000 males). In developing countries, the incidence of the mixed-cellularity (MCHD) and lymphocyte-depleted (LDHD) subtypes is higher. In contrast, the nodular-sclerosis (NSHD) subtype is most frequent in developed countries.
Race-, sex-, and age-related differences in incidence
Hodgkin lymphoma incidence rates in the United States vary by race and sex. The US incidence in cases per 100,000 individuals is 3.3 for white males, 2.8 for white females, 3.2 for black males, 2.4 for black females, 1.5 for Asian/Pacific Islander males, and 1.0 for Asian/Pacific Islander females. Overall, Hodgkin lymphoma is somewhat more common in males than in females. The observed male predominance is particularly evident in children, in whom 85% of the cases are in males.
Age-specific incidence rates of Hodgkin lymphoma have a bimodal distribution in both sexes, peaking in young adults (aged 15-34 y) and older individuals (>55 y). In the United States, young adults typically have NSHD, whereas children (aged 0-14 y) and older individuals more commonly have the MCHD subtype.
Prognosis
The 5-year disease-specific survival rates for patients with Hodgkin lymphoma are as follows[7] :
- Stages I and II - 90%
- Stage III - 84%
- Stage IV - 65%
In addition to the stage of the disease, many factors contribute to the likelihood of survival from Hodgkin lymphoma (see Staging). These are considered in order to best match each patient to the correct type and intensity of therapy.
Survivors of Hodgkin lymphoma may have long-term sequelae from their therapy, including cardiac disease, pulmonary disease, secondary cancers, infertility, and infectious complications.[8] With the current widespread use of nonleukemogenic chemotherapy (ABVD) and the use of smaller radiation fields and doses, the rate of treatment-related deaths is expected to decrease. See Complications of Therapy in Treatment.
Patient Education
Before the initiation of treatment, patients with Hodgkin lymphoma should be counseled about the potential complications of Hodgkin lymphoma therapy, including the risk of cardiac disease, lung toxicity, and secondary cancers. Patients should also be apprised of the potential loss of fertility that may arise from MOPP chemotherapy, escalated BEACOPP chemotherapy, pelvic irradiation, or HDC, so that they may explore fertility-preserving options such as sperm banking, oral contraceptive use, or oophoropexy.
Female patients who have received chest radiation therapy should be encouraged to perform regular breast self-examinations. All patients should be counseled on health habits that may help reduce the risk of cancer and cardiovascular disease, including avoidance of smoking, control of lipids, and the use of sunscreen.
Patients should also be advised about the long-term risk of infection after undergoing splenectomy and the importance of calling their physician if they experience a fever.
Patients should understand the risk of psychosocial problems that may affect survivors of Hodgkin lymphoma. Consultations with social workers, psychologists, and psychiatrists may be helpful to manage some of these issues.
For patient education information, see the Blood and Lymphatic System Center, as well as Lymphoma.
Jaffe ES, Harris NL, Stein H, Vardiman JW, eds. World Health Organization Classification of Tumours: Pathology and Genetics of Tumours of Haematopoietic and Lymphoid Tissues. Lyon, France: IARC Press; 2001.
Thomas RK, Re D, Wolf J, Diehl V. Part I: Hodgkin's lymphoma--molecular biology of Hodgkin and Reed-Sternberg cells. Lancet Oncol. Jan 2004;5(1):11-8. [Medline].
Re D, Küppers R, Diehl V. Molecular pathogenesis of Hodgkin's lymphoma. J Clin Oncol. Sep 10 2005;23(26):6379-86. [Medline].
Hjalgrim H, Smedby KE, Rostgaard K, et al. Infectious mononucleosis, childhood social environment, and risk of Hodgkin lymphoma. Cancer Res. Mar 1 2007;67(5):2382-8. [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. Aug 11 2011;118(6):1591-9. [Medline]. [Full Text].
Jemal A, Siegel R, Ward E, et al. Cancer statistics, 2006. CA Cancer J Clin. Mar-Apr 2006;56(2):106-30. [Medline]. [Full Text].
Keegan TH, Clarke CA, Chang ET, Shema SJ, Glaser SL. Disparities in survival after Hodgkin lymphoma: a population-based study. Cancer Causes Control. Jun 26 2009;[Medline].
Ng AK, Mauch PM. Late complications of therapy of Hodgkin's disease: prevention and management. Curr Hematol Rep. Jan 2004;3(1):27-33. [Medline].
Ménard F, Besson C, Rincé P, et al. Hodgkin lymphoma-associated hemophagocytic syndrome: a disorder strongly correlated with Epstein-Barr virus. Clin Infect Dis. Aug 15 2008;47(4):531-4. [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. Feb 10 2007;25(5):571-8. [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. Jun 2006;17(6):914-9. [Medline]. [Full Text].
Mani H, Jaffe ES. Hodgkin lymphoma: an update on its biology with new insights into classification. Clin Lymphoma Myeloma. Jun 2009;9(3):206-16. [Medline].
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. Nov 19 1998;339(21):1506-14. [Medline]. [Full Text].
Hoppe RT, Advani RH, Ai WZ, Ambinder RF, Bello CM, Bierman PJ, et al. Hodgkin lymphoma. J Natl Compr Canc Netw. Sep 1 2011;9(9):1020-58. [Medline].
Eichenauer DA, Engert A, Dreyling M. Hodgkin's lymphoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. Sep 2011;22 Suppl 6:vi55-8. [Medline].
Cheson BD, Pfistner B, Juweid ME, et al. Revised response criteria for malignant lymphoma. J Clin Oncol. Feb 10 2007;25(5):579-86. [Medline]. [Full Text].
Fermé C, Eghbali H, Meerwaldt JH, et al. Chemotherapy plus involved-field radiation in early-stage Hodgkin's disease. N Engl J Med. Nov 8 2007;357(19):1916-27. [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. Jun 15 2002;359(9323):2065-71. [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. May 1999;10(5):527-32. [Medline]. [Full Text].
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. Sep 1 2007;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. Aug 20 2007;25(24):3746-52. [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. Nov 2006;28(11):711-4. [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. Nov 19 1992;327(21):1478-84. [Medline].
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. Feb 1 2002;20(3):630-7. [Medline]. [Full Text].
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. Jun 12 2003;348(24):2386-95. [Medline]. [Full Text].
[Best Evidence] Engert A, Diehl V, Franklin J, et al. Escalated-dose BEACOPP in the treatment of patients with advanced-stage Hodgkin's lymphoma: 10 years of follow-up of the GHSG HD9 study. J Clin Oncol. Sep 20 2009;27(27):4548-54. [Medline].
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. Jul 21 2011;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. Aug 10 2011;CD007941. [Medline].
Edwards-Bennett SM, Jacks LM, Moskowitz CH, Wu EJ, Zhang Z, Noy A, et al. Stanford V program for locally extensive and advanced Hodgkin lymphoma: the Memorial Sloan-Kettering Cancer Center experience. Ann Oncol. Sep 16 2009;[Medline].
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. Aug 10 2007;25(23):3495-502. [Medline]. [Full Text].
Engert A, Plutschow A, Eich HT, et al. Reduced treatment intensity in patients with early-stage Hodgkin's lymphoma. N Engl J Med. Aug 12 2010;363:640-652.
Eich HT, Diehl V, Görgen H, Pabst T, Markova J, Debus J, 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. Sep 20 2010;28(27):4199-206. [Medline].
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. Jul 21 2011;365(3):203-12. [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. Jan 1 2008;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. Oct 20 2011;118(16):4363-5. [Medline].
Savage KJ, Skinnider B, Al-Mansour M, et al. Treating limited-stage nodular lymphocyte predominant Hodgkin lymphoma similarly to classical Hodgkin lymphoma with ABVD may improve outcome. Blood. Oct 27 2011;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. Aug 15 2005;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. Sep 15 2008;113(6):1344-50. [Medline].
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. Feb 2008;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. Nov 4 2010;363(19):1812-21. [Medline]. [Full Text].
Chen R, Gopal AK, Smith SE, Ansell SM, Rosenblatt JD, Klasa R, et al. Results of a Pivotal Phase 2 Study of Brentuximab Vedotin (SGN-35) in Patients with Relapsed or Refractory Hodgkin Lymphoma. American Society of Hematology (ASH) 52nd Annual Meeting: Abstract 283, presented December 6, 2010. American Society of Hematology. Available at http://ash.confex.com/ash/2010/webprogram/Paper30260.html. Accessed August 22, 2011.
Witzig TE, Tang H, Micallef IN, et al. Multi-institutional phase 2 study of the farnesyltransferase inhibitor tipifarnib (R115777) in patients with relapsed and refractory lymphomas. Blood. Nov 3 2011;118(18):4882-9. [Medline]. [Full Text].
Ansell SM, Horwitz SM, Engert A, et al. Phase I/II study of an anti-CD30 monoclonal antibody (MDX-060) in Hodgkin's lymphoma and anaplastic large-cell lymphoma. J Clin Oncol. Jul 1 2007;25(19):2764-9. [Medline]. [Full Text].
Bartlett NL, Younes A, Carabasi MH, et al. A phase 1 multidose study of SGN-30 immunotherapy in patients with refractory or recurrent CD30+ hematologic malignancies. Blood. Feb 15 2008;111(4):1848-54. [Medline].
Takach S, Yang L, Ho J, Sabri E, Martin L, Halpenny M, et al. Monoclonal B cells detected in autologous PBSC grafts from patients with classical Hodgkin lymphoma: impact on relapse and survival following transplantation. Bone Marrow Transplant. Sep 21 2009;[Medline].
Chen R, Gopal AK, Smith SE, et al. Results of a pivotal phase 2 study of brentuximab vedotin (SGN-35) in patients with relapsed or refractory Hodgkin lymphoma. Presented at: American Society of Hematology Annual Meeting; December 4-7, 2010; Orlando, Fla. Blood. 2010;116(21):Abstract 283.
Aleman BM, van den Belt-Dusebout AW, De Bruin ML, et al. Late cardiotoxicity after treatment for Hodgkin lymphoma. Blood. Mar 1 2007;109(5):1878-86. [Medline]. [Full Text].
Wethal T, Lund MB, Edvardsen T, Fosså SD, Pripp AH, Holte H, et al. Valvular dysfunction and left ventricular changes in Hodgkin's lymphoma survivors. A longitudinal study. Br J Cancer. Aug 18 2009;101(4):575-81. [Medline].
Heidenreich PA, Schnittger I, Strauss HW, et al. Screening for coronary artery disease after mediastinal irradiation for Hodgkin's disease. J Clin Oncol. Jan 1 2007;25(1):43-9. [Medline]. [Full Text].
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. Nov 1 2011;29(31):4096-104. [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. Oct 20 2005;23(30):7555-64. [Medline]. [Full Text].
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. Oct 2008;19(10):1795-801. [Medline].
Hodgson DC, Pintilie M, Gitterman L, et al. Fertility among female hodgkin lymphoma survivors attempting pregnancy following ABVD chemotherapy. Hematol Oncol. Mar 2007;25(1):11-5. [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. Mar 1998;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. Feb 2000;19(2):91-9. [Medline].
Canioni D, Deau-Fischer B, Taupin P, Ribrag V, Delarue R, Bosq J, et al. Prognostic significance of new immunohistochemical markers in refractory classical Hodgkin lymphoma: a study of 59 cases. PLoS One. Jul 22 2009;4(7):e6341. [Medline].
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