eMedicine Specialties > Hematology > Stem Cells and Disorders

Hodgkin Disease

Author: Scott K Dessain, MD, PhD, Associate Professor, Lankenau Institute for Medical Research
Coauthor(s): James L Spears, MD, Fellow, Department of Medicine, Division of Hematology/Oncology, Lankenau Hospital; Athanassios Argiris, MD, Associate Professor, Department of Medicine, Division of Hematology-Oncology, University of Pittsburgh
Contributor Information and Disclosures

Updated: Oct 31, 2008

Introduction

Background

Hodgkin disease (Hodgkin's lymphoma) is a potentially curable malignant lymphoma with distinct histology, biologic behavior, and clinical characteristics. Thomas Hodgkin first described Hodgkin disease (Hodgkin's lymphoma) in 1832. The disease is defined in terms of its microscopic appearance (histology) and the expression of cell surface markers (immunophenotype).

For excellent patient education resources, visit eMedicine's Blood and Lymphatic System Center. Also, see eMedicine's patient education article Lymphoma.

Related eMedicine topics:
Hodgkin Disease [in the Pediatrics: General Medicine section]
Lymphoma, B-Cell
Lymphoma, Diffuse Large Cell
Lymphoma, Malignant Anaplastic (Ki 1+)
Lymphoma, Mantle Cell
Lymphoma, Non-Hodgkin

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Resource Center Cancer: Biologic Therapies
Resource Center Stem Cell Research & Therapy
Specialty Site Hematology-Oncology
High-Dose Therapy and Stem Cell Transplant Useful for Resistant Hodgkin Disease
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Pathophysiology

Histology and classification

As classified by the World Health Organization (WHO), Hodgkin disease (Hodgkin's lymphoma) exists in 5 types.1  Four of these, nodular sclerosis, mixed cellularity, lymphocyte depleted, and lymphocyte rich, are referred to as classic Hodgkin disease (Hodgkin's 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 disease (Hodgkin's lymphoma), the neoplastic cell is the Reed-Sternberg (RS) cell.2,3  Reed-Sternberg cells compose 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 express antibodies. 

Some Hodgkin disease (Hodgkin's 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 disease (Hodgkin's 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 B-lineage cells. 

  • Nodular sclerosis Hodgkin disease (NSHD) (60-80% of all cases): 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 and usually involves the mediastinum and other supradiaphragmatic sites.
  • Mixed-cellularity Hodgkin disease (MCHD) (15-30% of cases): Histologically, 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 (LDHD) (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. It 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 (LRHD) (5% of cases): In this type of Hodgkin disease (Hodgkin's lymphoma), 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 (NLPHD) (5% of cases): In contrast to the other histologic subtypes, the typical Reed-Sternberg cells in NLPHD are either infrequent or absent. 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.

Frequency

United States

Information regarding the incidence and mortality of Hodgkin disease (Hodgkin's 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).4

The NCI estimates 8,220 new cases and 1,350 deaths from Hodgkin disease (Hodgkin's lymphoma)in 2008. The age-adjusted incidence of Hodgkin disease (Hodgkin's lymphoma) is 2.8 cases per 100,000 individuals.

International

Hodgkin disease (Hodgkin's lymphoma) had a worldwide incidence of 62,000 cases in 2002. Compared with North America and Europe, Hodgkin disease (Hodgkin's 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.

Mortality/Morbidity

The 5-year disease-specific survival for patients with stages I and II Hodgkin disease (Hodgkin's lymphoma) is 90%; III, 84%; and IV, 65%.

Race

Hodgkin disease (Hodgkin's lymphoma) incidence rates in the United States vary by race and sex. The incidence in cases per 100,000 individuals is 3.3 for white males, 2.7 for white females, 2.9 for black males, 2.3 for black females, 1.4 for Asian/Pacific Islander males, and 1.0 for Asian/Pacific Islander females.

Sex

Overall, Hodgkin disease (Hodgkin's 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

Age-specific incidence rates of Hodgkin disease (Hodgkin's 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.

Clinical

History

Clinical history features of Hodgkin disease (Hodgkin's lymphoma)

  • Asymptomatic lymphadenopathy may be present (above the diaphragm in 80% of patients).
  • Constitutional symptoms (eg, unexplained weight loss, fever, night sweats) are present in 40% of patients. Collectively, these are known as "B symptoms."
  • Intermittent fever is observed in approximately 35% of cases. Infrequently, the classic Pel-Ebstein fever is observed (high fever for 1-2 wk followed by an afebrile period of 1-2 wk).
  • Chest pain, cough, shortness of breath, or a combination of these things may be present due to a large mediastinal mass or lung involvement. Rarely, hemoptysis is observed.
  • Patients may present with pruritus.
  • Alcohol-induced pain at sites of nodal disease is specific for Hodgkin disease (Hodgkin's lymphoma) and occurs in less than 10% of patients.
  • Back or bone pain occurs rarely.

Related Medscape topic:
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Physical

Physical examination findings in Hodgkin disease (Hodgkin's lymphoma) 

  • Palpable painless lymphadenopathy occurs in the cervical area (60-80%), axilla (6-20%), and, less commonly, in the inguinal area (6-20%). It is described as rubbery adenopathy.
  • Involvement of the Waldeyer ring or occipital or epitrochlear areas is infrequently observed.
  • Splenomegaly may be present.
  • Patients may have hepatomegaly.
  • Superior vena cava syndrome resulting from massive mediastinal lymphadenopathy can also be seen.
  • Central nervous system (CNS) symptoms or signs may be due to paraneoplastic syndromes, including cerebellar degeneration, neuropathy, Guillain-Barré syndrome, or multifocal leukoencephalopathy.

Related Medscape topic:
 Specialty Site Neurology & Neurosurgery

Causes

The etiology of Hodgkin disease (Hodgkin's lymphoma) is unknown.

  • Infectious agents, particularly EBV, may be involved in the pathogenesis of Hodgkin disease (Hodgkin's lymphoma).
  • In as many as 50% of Hodgkin disease (Hodgkin's lymphoma) 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 Hodgkin disease (Hodgkin's lymphoma) cases are EBV-positive.
  • An epidemiologic study from Denmark and Sweden showed an increased risk of EBV-positive Hodgkin disease (Hodgkin's lymphoma) in patients with a self-reported history of infectious mononucleosis (IM) in adolescence.5 The average incubation time from IM to symptoms of Hodgkin disease (Hodgkin's lymphoma) was 2.9 years.
  • Patients with HIV infection have a higher incidence of Hodgkin disease (Hodgkin's lymphoma) compared with the population without HIV infection. However, Hodgkin disease (Hodgkin's lymphoma) is not considered an acquired immunodeficiency syndrome (AIDS)-defining neoplasm.
  • Genetic predisposition may play a role in the pathogenesis of Hodgkin disease (Hodgkin's lymphoma). Approximately 1% of patients with Hodgkin disease (Hodgkin's lymphoma) have a family history of the disease. Siblings of an affected individual have a 3- to 7-fold increased risk for developing Hodgkin disease (Hodgkin's lymphoma). This risk is higher in monozygotic twins.
  • Human leukocyte antigen (HLA)-DP alleles are more common in Hodgkin disease (Hodgkin's lymphoma).

More on Hodgkin Disease

Overview: Hodgkin Disease
Differential Diagnoses & Workup: Hodgkin Disease
Treatment & Medication: Hodgkin Disease
Follow-up: Hodgkin Disease
References
Further Reading
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Further Reading

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Keywords

Hodgkin disease, Hodgkin's lymphoma, Hodgkin's disease, Hodgkin lymphoma, HD, malignant lymphoma, malignant lymphogranuloma, Reed-Sternberg cells, lymph cancer, Epstein-Barr virus, EBV, nodular sclerosis Hodgkin disease, NSHD, mixed-cellularity Hodgkin disease, MCHD, lymphocyte-depleted Hodgkin disease, LDHD, lymphocyte-depleted Hodgkin's disease, lymphocyte-rich Hodgkin disease, nodular Hodgkin disease, NHD, nodular lymphocyte-predominant Hodgkin disease, NLPHD, lymph node cancer

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Contributor Information and Disclosures

Author

Scott K Dessain, MD, PhD, Associate Professor, Lankenau Institute for Medical Research
Scott K Dessain, MD, PhD is a member of the following medical societies: American Society of Hematology
Disclosure: Nothing to disclose.

Coauthor(s)

James L Spears, MD, Fellow, Department of Medicine, Division of Hematology/Oncology, Lankenau Hospital
James L Spears, MD is a member of the following medical societies: American Society of Clinical Oncology
Disclosure: Nothing to disclose.

Athanassios Argiris, MD, Associate Professor, Department of Medicine, Division of Hematology-Oncology, University of Pittsburgh
Athanassios Argiris, MD is a member of the following medical societies: American Association for Cancer Research, American College of Physicians, and American Medical Association
Disclosure: Nothing to disclose.

Medical Editor

Koyamangalath Krishnan, MD, FRCP, FACP, Dishner Endowed Chair of Excellence in Medicine, Professor of Medicine and Chief of Hematology-Oncology, Program Director, Hematology-Oncology Fellowship, 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.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

Wendy Hu, MD, Consulting Staff, Department of Hematology/Oncology and Bone Marrow Transplantation, Huntington Memorial Medical Center
Wendy Hu, MD is a member of the following medical societies: American Association for the Advancement of Science, American College of Physicians, American Society for Blood and Marrow Transplantation, American Society of Hematology, and Physicians for Social Responsibility
Disclosure: Nothing to disclose.

CME Editor

Rajalaxmi McKenna, MD, FACP, Consulting Staff, Department of Medicine, Southwest Medical Consultants, SC, Good Samaritan Hospital, Advocate Health Systems
Rajalaxmi McKenna, MD, FACP is a member of the following medical societies: American Society of Clinical Oncology, American Society of Hematology, and International Society on Thrombosis and Haemostasis
Disclosure: Nothing to disclose.

Chief Editor

Emmanuel C Besa, MD, Professor, Department of Medicine, Division of Hematologic Malignancies, Kimmel Cancer Center, Thomas Jefferson University
Emmanuel C Besa, MD is a member of the following medical societies: American Association for Cancer Education, American College of Clinical Pharmacology, American Federation for Medical Research, American Society of Hematology, and New York Academy of Sciences
Disclosure: Nothing to disclose.

 
 
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