eMedicine Specialties > Hematology > Stem Cells and Disorders

Hodgkin Disease: Differential Diagnoses & Workup

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

Updated: Oct 4, 2009

Differential Diagnoses

Cytomegalovirus
Syphilis
Infectious Mononucleosis
Systemic Lupus Erythematosus
Lung Cancer, Oat Cell (Small Cell)
Toxoplasmosis
Lymphoma, Non-Hodgkin
Tuberculosis
Rheumatoid Arthritis
Sarcoidosis
Serum Sickness

Other Problems to Be Considered

  • Any disease presenting with lymphadenopathy and constitutional symptoms
  • HIV infection
  • Hypersensitivity reaction
  • Other solid tumors

Occasionally, Hodgkin disease (Hodgkin's lymphoma) can present with hemophagocytic syndrome (hemophagocytic lymphohistiocytosis).7 Hemophagocytic syndrome is associated with EBV antigen expression by Reed-Sternberg cells and is clinically characterized by pancytopenia; fever; hepatosplenomegaly with liver function test abnormalities; elevated serum levels of ferritin and triglycerides; and phagocytosis of hematopoietic lineage cells by benign macrophages. 

Workup

Laboratory Studies

  • Erythrocyte sedimentation rate (ESR) (a general marker of inflammation) measurements may be elevated in Hodgkin disease (Hodgkin's lymphoma). An elevated ESR has been associated with worse prognosis. However, the ESR is a nonspecific test that should not be used for Hodgkin disease (Hodgkin's lymphoma) screening.
  • Lactate dehydrogenase (LDH) may be increased. LDH may correlate with the bulk of disease.
  • Complete blood cell (CBC) count studies (for anemia, lymphopenia, neutrophilia, or eosinophilia) should be performed. Hodgkin disease (Hodgkin's lymphoma)–associated anemia is most commonly the anemia of chronic disease. However, it may result from bone marrow involvement by tumor or from the presence of an autoantibody (positive findings on a warm Coombs test). Cytopenias are common in advanced Hodgkin disease (Hodgkin's lymphoma) disease. Platelet counts may be increased or decreased.
  • Serum creatinine in Hodgkin disease (Hodgkin's lymphoma) has a rare association with nephrotic syndrome.
  • Alkaline phosphatase (ALP) may be increased due to the presence of liver or bone involvement. Other uncommon laboratory findings include hypercalcemia, hypernatremia, and hypoglycemia (due to the presence of insulin autoantibodies).
  • An HIV test is important in the workup of Hodgkin disease (Hodgkin's lymphoma) and non-Hodgkin lymphomas, because antiviral therapies can improve disease outcomes in HIV-positive patients.8
  • Serum levels of cytokines (interleukin [IL]-6, IL-10) and soluble CD25 (IL-2 receptor) correlate with tumor burden, systemic symptoms, and prognosis, but these studies are generally obtained only in special situations or in the context of a clinical trial.

Imaging Studies

Imaging studies for Hodgkin disease (Hodgkin's lymphoma) 

  • Computed tomography (CT) scans of the chest, abdomen, and pelvis
    • Possible abnormal findings include enlarged lymph nodes, hepatomegaly and/or splenomegaly (with or without focal parenchymal abnormalities), lung nodules or infiltrates, and pleural effusions.
    • A mediastinal mass, representing mediastinal lymphadenopathy, is a very common finding in classic Hodgkin disease (Hodgkin's lymphoma), although it is uncommon in NLPHD.
  • Positron emission tomography (PET) scanning is now considered to be essential to the initial staging of Hodgkin disease (Hodgkin's lymphoma).9

Other Tests

Sampling of a pleural effusion by thoracentesis and examination of the cells obtained may be useful in the evaluation of Hodgkin disease (Hodgkin's lymphoma). The pleural fluid may be an exudate or transudate, or it may be chylous.

CNS evaluation by lumbar puncture and magnetic resonance imaging (MRI) should be performed if symptoms or signs of CNS involvement are present. CNS involvement with Hodgkin disease (Hodgkin's lymphoma) is exceedingly rare, but it has been reported.

Procedures

  • A histologic diagnosis of Hodgkin disease (Hodgkin's lymphoma) is always required.
    • An excisional lymph node biopsy is recommended, because the lymph node architecture is important for histologic classification.
    • When a patient presents with neck lymphadenopathy that may be due to a head and neck cancer, a fine-needle aspiration (FNA) is usually advised as the initial diagnostic step, followed by excisional biopsy if squamous cell histology is excluded.
  • Bone marrow biopsies
    • Because Hodgkin disease (Hodgkin's lymphoma) in the bone marrow is often patchy, bilateral bone marrow biopsies are advised to improve the identification of advanced disease (stage IV).
    • Bone marrow involvement is more common in elderly individuals, in patients with advanced-stage disease, in the presence of systemic symptoms, and in patients with a high-risk histology.
    • A bone marrow biopsy can be omitted in patients with stage I Hodgkin disease (Hodgkin's lymphoma) and some patients with stage II disease without hematologic abnormalities. 
  • A staging laparotomy is a surgical procedure that includes splenectomy with biopsies of the liver and lymph nodes in the para-aortic, mesenteric, portal, and splenic hilar regions. At present, a staging laparotomy procedure is very rarely indicated, because even early-stage Hodgkin disease (Hodgkin's lymphoma) is most often treated with combination chemotherapy. The procedure can be helpful in rare cases in which radiation therapy is under consideration as the sole treatment of early-stage Hodgkin disease (Hodgkin's lymphoma).

Staging

The Ann Arbor classification (1971) is used most often for cases of Hodgkin disease (Hodgkin's lymphoma). Clinical staging involves assessment of disease extent by clinical examination, history, and imaging techniques. When staging laparotomies are used as part of staging, the disease extent is designated as pathologic staging.10

  • Stage I denotes a single lymph node area or single extranodal site.
  • Stage II denotes 2 or more lymph node areas on the same side of the diaphragm.
  • Stage III denotes lymph node areas on both sides of the diaphragm.
  • Stage IV denotes disseminated or multiple involvement of the extranodal organs. Involvement of the liver or the bone marrow is considered stage IV disease. For staging classifications, the spleen is considered to be a lymph node area. Involvement of the spleen is denoted with the S suffix (ie, IIBS).
  • A or B designations denote the absence or presence of B symptoms.
    • A "B" designation includes the presence of 1 or more of the following:
      • Fever (temperature >38°C)
      • Drenching night sweats
      • Unexplained loss of more than 10% of body weight within the preceding 6 months
    • An "A" designation is the absence of the above.
    • An "X" designation is sometimes used to indicate the presence of bulky disease.
  • Approximately one third of new patients have splenic involvement based on laparotomy data. However, this depends on the histologic subtype. Two thirds of patients with the mixed cellularity subtype have splenic involvement, compared with only one third of patients with the lymphocyte-depleted or nodular sclerosis histology. When liver or bone marrow involvement is present, the spleen is likely to be involved.
  • Spread of Hodgkin disease (Hodgkin's lymphoma) takes place via the lymphatics, hematogenous routes, and direct extension.
  • Contiguous involvement of extranodal sites (eg, involvement of the lung parenchyma due to direct extension of large mediastinal lymphadenopathy) is not considered stage IV disease. Rather, it is designated with the E suffix (ie, IIBE).

Unfavorable factors in limited-stage Hodgkin disease (Hodgkin's lymphoma)
Many factors that can be assessed at the time of the disease diagnosis can help to determine whether a patient's Hodgkin disease (Hodgkin's lymphoma) has a high or low risk of proving resistant to therapy. Such an estimate is important for treatment planning. In addition, it can help identify patients who would potentially benefit from participating in clinical trials that seek to either minimize therapy in low-risk patients or intensify therapy in high-risk patients.

In patients with stage I or II disease, the following factors are considered unfavorable and, if present, will increase the intensity of the recommended initial therapy:

  • Bulky disease, defined as a mediastinal mass greater than one third of the intrathoracic diameter (on a chest radiograph) or greater than 35% of the thoracic diameter at vertebral level T5-6. Hodgkin disease (Hodgkin's lymphoma) also qualifies as bulky disease if it is greater than 10 cm in diameter on a CT scan.
  • An ESR result (a general marker of inflammation) 50 mm/h or higher, if the patient is otherwise asymptomatic
  • More than 3 sites of disease involvement
  • The presence of B symptoms
  • The presence of extranodal disease
The International Prognostic Factors Project (IPFP) score for advanced Hodgkin disease (Hodgkin's lymphoma)
The IPFP was a survey of the characteristics at diagnosis and outcomes of 5,141 patients with Hodgkin disease (Hodgkin's lymphoma) with either advanced disease, defined as either stage III or IV disease, or earlier stage disease with systemic symptoms or bulky features. The following characteristics were determined to each contribute independently to an increased relative risk for Hodgkin disease (Hodgkin's lymphoma) progression despite therapy:
  • Serum albumin less than 4 g/dL
  • Hemoglobin less than 10.5 g/dL
  • Male sex
  • Stage IV disease
  • Age 45 years or older
  • White blood cell (WBC) count greater than 15,000/mm3
  • Lymphocyte count less than 600/mm3 or less than 8% of the total WBC count
The International Prognostic Score (IPS) is considered to be the number of features that are present at diagnosis for Hodgkin disease (Hodgkin's lymphoma).11 The IPS correlates with the rate of freedom from disease progression and overall survival. Patients with 0-1 of these factors would be predicted to have a 90% overall survival. In contrast, patients with 4 or more of these factors may have an overall survival rate of only 59%. One limitation of this scoring method is that it was unable to clearly identify the highest risk subgroup of patients with Hodgkin disease (Hodgkin's lymphoma), that is, those who may benefit from up-front high-dose therapy. Analysis of cytokines and other serum markers may help to identify these patients in the future.

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

Additional resources on Hodgkin Disease are available at Medscape’s Hodgkin Disease Resource Center.

Further Resources

Related eMedicine Topics

Clinical Trials

Clinical Guidelines

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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, 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.

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, and American Medical Association
Disclosure: Nothing to disclose.

Medical Editor

Koyamangalath Krishnan, MD, FRCP, FACP, Paul 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: eMedicine Salary Employment

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, Southwest Medical Consultants, SC, Department of Medicine, 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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