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      Drugs & Diseases > Hematology

      Hodgkin Lymphoma Workup

      Updated: Sep 22, 2023
      • Author: Bradley W Lash, MD; Chief Editor: Emmanuel C Besa, MD  more...
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      Workup

      Approach Considerations

      The patient’s history and physical examination are important for diagnosis, but the foundation for determining the ideal Hodgkin lymphoma treatment is accurate staging. Imaging, sampling (biopsy), and an assessment of prognostic factors are required for staging. Hematologic (complete blood cell [CBC] count) and blood chemistry studies may reveal nonspecific findings in patients with Hodgkin lymphoma that may be associated with disease extent. Several of these findings have been used as prognostic factors.

      Formerly, staging laparotomy and laparoscopy were the standard of care in Hodgkin lymphoma, but with modern imaging and treatment paradigms these procedures are no longer needed.

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      Laboratory Tests

      Complete blood cell (CBC) count studies for anemia (low red blood cell [RBC] count), lymphopenia (low white blood cell [WBC] count), excess neutrophils (neutrophilia), or eosinophils (eosinophilia) should be performed. Some of these factors have prognostic implications, as noted under Prognosis. Hodgkin lymphoma–associated anemia is most commonly the anemia of chronic disease. However, it may result from bone marrow involvement by tumor or, rarely, from the presence of an autoantibody (as indicated by a positive warm-agglutinin on a Coombs test). Platelet counts may be increased or decreased.

      The erythrocyte sedimentation rate (ESR)—a general marker of inflammation—may be elevated in Hodgkin lymphoma. An elevated ESR has been associated with worse prognosis. However, the ESR is a nonspecific test that should not be used for Hodgkin lymphoma screening.

      Lactate dehydrogenase (LDH) may be increased. LDH levels may correlate with the bulk of disease.

      Serum creatinine may be elevated in the rare cases of nephrotic syndrome associated with Hodgkin lymphoma. Levels of 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).

      A test for human immunodeficiency virus (HIV) is important in the workup of Hodgkin lymphoma, because antiretroviral therapies can improve disease outcomes in HIV-positive patients. [3] Screening for hepatitis B and C should also be considered.

      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.

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      Imaging Studies

      Imaging studies are important for accurate staging of Hodgkin lymphoma. These studies include plain x-rays, computed tomography (CT) scans, and positron emission tomography (PET) scans. In addition, imaging studies can help to define disease bulk, which has prognostic implications. The definition of bulky disease varies, but in general is defined as any nodal mass greater than 10 cm (>5 cm in some studies) and a mediastinal mass greater than one third the thoracic diameter as measured at T5/6.

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      CT Scanning

      Historically, posteroanterior (PA) and lateral chest x-rays have been used to measure mediastinal mass in relationship to thoracic diameter. This approach remains the gold standard, but with the availability of cross-sectional imaging in CT scanning, chest radiography has been largely replaced by CT. See the image below.

      A computed tomography (CT) scan showing bulk disea A computed tomography (CT) scan showing bulk disease in a patient with Hodgkin lymphoma.
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      On 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 (see the image below).

      This computed tomography scan is from a 46-year pa 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).
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      PET scanning

      PET scanning is now considered essential to the initial staging of Hodgkin lymphoma, because of its ability to distinguish between viable tumor and necrosis or fibrosis in residual masses that are often present after treatment in patients who have no other clinical or biochemical evidence of disease. [36] This imaging study is often performed in conjunction with CT scanning (see the images below). [37] A mediastinal mass, representing mediastinal lymphadenopathy, is a very common finding in classical Hodgkin lymphoma, although it is uncommon in nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL).

      The American College of Radiology does not recommend changing chemotherapy or omitting radiation therapy based on PET scan response for early-stage patients. [29, 30]

      A positron emission tomography (PET) scan obtained A positron emission tomography (PET) scan obtained with fluorodeoxyglucose (FDG) that shows increased FDG uptake in a mediastinal lymph node.
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      This image depicts a computed tomography (CT) scan 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.
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      Biopsy and Histologic Findings

      A histologic diagnosis of Hodgkin lymphoma is always required. An excisional lymph node biopsy is recommended because the lymph node architecture is important for histologic classification (see the image below). When a patient presents with neck lymphadenopathy and risk factors for a head and neck cancer, a fine-needle aspiration is usually advised as the initial diagnostic step, followed by excisional biopsy if squamous cell histology is excluded.

      Mixed cellularity Hodgkin lymphoma showing both mo Mixed cellularity Hodgkin lymphoma showing both mononucleate and binucleate Reed-Sternberg cells in a background of inflammatory cells (hematoxylin and eosin, original magnification x200).
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      Bone marrow biopsies are indicated in some cases. Bone marrow involvement is more common in elderly patients and those with advanced-stage disease, systemic symptoms, or a high-risk histology. However, given the low incidence of bone marrow involvement, some experts and expert groups feel that bone marrow biopsy can be omitted, particularly in early-stage disease. There is a bone marrow risk calculator available to help determine need for bone marrow biopsy. [38]

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

      Central nervous system (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 lymphoma is exceedingly rare, but it has been reported.

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      Staging

       

      Clinical staging involves assessment of disease extent by clinical examination, history, and imaging techniques. The Ann Arbor classification (1971) is used most often for Hodgkin lymphoma. It classifies cases into the following four stages, principally on the basis of lymph node involvement:

      • Stage I - A single lymph node area or single extranodal site
      • Stage II - Two or more lymph node areas on the same side of the diaphragm
      • Stage III - Lymph node areas on both sides of the diaphragm
      • Stage IV - 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 one 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 (ie, bulk >10 cm).

      Spread of Hodgkin 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 Hodgkin lymphoma are discussed in Overview/Prognosis.

      See also Hodgkin Lymphoma Staging.

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