Diagnosis
The doctor will take a medical history and perform a physical examination. If these simple procedures point to Hodgkin's disease, a number of additional tests may be needed to either rule out other diseases or to confirm HD and determine the extent of the cancer.
Ruling Out Other Conditions
Many patients seek medical help for abnormally swollen lymph nodes (commonly referred to as “swollen glands”). Swollen glands can be caused by many conditions, most often infections, and are rarely serious.
Infections. In the great majority of cases, swollen glands are caused by an infection:
- For example, although Hodgkin's often first appears in the neck, enlarged lymph nodes in that location are much more likely to be a sign of a strep or other throat infections.
- Infectious mononucleosis (caused by the Epstein Barr virus) is a common cause of swollen lymph nodes in young people.
- Recent travel, particularly to countries with a high incidence of tropical diseases, can trigger similar symptoms.
- Other infections that cause similar symptoms include cat scratch fever, Lyme or other tick-borne disease, HIV, tularemia, tuberculosis, syphilis, herpes simplex virus, cytomegalovirus, and hepatitis.
Non-Hodgkin's Lymphomas. Although both Hodgkin's disease and non-Hodgkin's lymphomas are malignancies of the lymph nodes, they can usually be distinguished by certain characteristics. It is extremely important to differentiate between Hodgkin's lymphomas and non-Hodgkin's lymphomas, since the treatments for these two conditions differ. In particular, a subtype of lymphoma called anaplastic large-cell lymphoma (ALCL) might be confused with Hodgkin’s disease under some circumstances. [For more information, see In-Depth Report #84: Non-Hodgkin's lymphomas.]
Comparison Between Hodgkin's Disease and Non-Hodgkin's Lymphomas | ||
Characteristics | Hodgkin's Disease | Non-Hodgkin's Lymphomas |
Age and Prevalence | Average age is 27.7 with two age peaks, the major one between 15 and 24 with a lesser peak after age 55. It is less common than NHL. | Average age is about 67. It is more common than HD. |
Location | In both malignancies, the disease occurs most often in lymph nodes above the collarbone. However, in HD it is also more likely to appear in the chest cavity between the lungs (the mediastinum), particularly in younger patients. Only about 15 - 20% of cases are found in areas below the diaphragm. Disease occurs outside the nodes in about 4% of cases. | In both malignancies, the disease occurs most often in lymph nodes above the collarbone. In NHL, however, it is also more likely to appear in the nodes in the abdomen (called the mesenteric nodes). The disease occurs in the chest cavity in less than 40% of patients. (An exception, lymphoblastic lymphoma, which is seen most often in young people, is likely to first appear in the chest.) Disease occurs outside the nodes in about 23% of patients. Slow-growing lymphomas are common in the liver and bone marrow. |
Symptoms | More likely than NHL (40%) to have systemic symptoms (such as fever and night sweats) at the time of diagnosis. | Less likely to have systemic symptoms (27%) at the time of diagnosis. |
Progression | Less likely than NHL to be diagnosed in stage IV (10%). Hodgkin's disease usually progresses in an orderly way from one lymph node region to the next. This process may be slow, particularly in younger people, or very aggressive. The disease typically spreads downward from the initial site. If it spreads below the diaphragm, it usually reaches the spleen first; the disease then may spread to the liver and bone marrow. If the disease starts in the nodes in the middle of the chest, it may spread outward to the chest wall and areas around the heart and lungs. | More likely than HD to be diagnosed in stage IV (36%). The lymphomas are less predictable in their course than Hodgkin's disease and they are more apt to spread. |
Other Cancers or Serious Conditions in the Lymphatic System. Other cancers that can travel to lymph nodes include breast cancer and leukemia.
Very serious causes of enlarged lymph nodes include disorders of the lymph system that include Castleman's disease, lymphomatoid granulomatosis, and angioimmunoblastic lymphadenopathy. These lymph system disorders, although noncancerous, involve abnormal lymph cells. They are often fatal and can be very difficult to distinguish from lymphomas. Many of the other serious illnesses involving diseased lymph nodes develop simultaneously at multiple sites, while Hodgkin's nearly always starts at one location before spreading to nearby nodes. [See In-Depth Report #84: Non-Hodgkin's lymphomas or Report #86: Acute lymphocytic leukemia.]
Exposure to Chemicals. Exposure to industrial chemicals or certain medications, such as phenytoin (Dilantin), may cause enlarged nodes. In addition, other drugs, such as cephalosporins, penicillins, or sulfonamides, can cause enlarged nodes and other symptoms, including fever and rash that may resemble Hodgkin's disease.
Physical Examination
The doctor will examine not only the affected lymph nodes but also the surrounding tissues and other lymph node areas for signs of infection, skin injuries, or tumors. The consistency of the node is sometimes indicative of certain conditions. For example, a stony, hard node is often a sign of cancer, usually one that has metastasized (spread to another part of the body). A firm, rubbery node may indicate lymphoma (including Hodgkin's). Soft nodes suggest infection or inflammatory conditions.
Blood Tests
Blood tests are performed to measure white and red blood cells, blood protein levels, the uric acid level, blood proteins, and the liver's function. Another blood test is the erythrocyte sedimentation rate (ESR), which is sometimes elevated in Hodgkin's disease (although it is not specific for this condition).
Click the icon to see an image of the formed elements of blood.
Imaging Techniques
Chest X-Ray. A chest x-ray shows the lymph nodes in the chest and neck area, where Hodgkin's disease usually starts. It a useful step for detection of enlarged lymph nodes.
Click the icon to see an image of an x-ray machine.
Computer Tomography. Computed tomography (CT) scans are more accurate and can detect abnormalities in the chest and neck area, as well as revealing the extent of the cancer and whether it has spread outside the nodes. In one study, CT scans provided evidence of disease in 15% of sites that were considered normal on chest x-ray. A CT scan also is useful in detecting cancer below the diaphragm in the abdomen and pelvic areas.
Click the icon to see an image of a CT machine.
Other Advanced Imaging Techniques. Other newer advanced imaging techniques, including positron emission tomography (PET) and gallium-67 scintigraphy, are proving to be very helpful. Gallium scintigraphy has also been proven to detect the presence of HD, relapse, progression, and helps doctors to predict outcome. A specific PET scan technique called FDG-PET may be even more useful, because it can detect more disease sites both above and below the diaphragm. These imaging techniques can be used for staging the disease, often reducing the need for invasive procedures, which are required for examining areas undetectable using standard imaging techniques. Magnetic resonance imaging (MRI) has been used but has not yet proven to be very useful beyond the evaluation of the chest wall.
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Lymphangiography. Lymphangiography is an x-ray of the lymph glands and vessels after an injection of a dye. It might provide additional information on lower parts of the body, but it is generally not performed routinely. By itself, lymphangiography misses cancer in 20% of cases. It may be used after a diagnosis of stage I or II Hodgkin's disease to pinpoint the location of lymph nodes that are scheduled to be treated. There is a small risk that the dye will affect the lungs, so this test should not be used in patients with severe lung disease. The test is usually not necessary in patients who are receiving multidrug chemotherapy. It is also not usually performed on children.
Click the icon to see an image of a lymphangiogram.
Biopsy
A biopsy of the suspicious lymph node is the most definitive way to diagnose Hodgkin's disease. A biopsy has risks, and should only be performed by a qualified and experienced doctor. Sometimes a doctor may choose to wait and observe the involved lymph nodes, which will usually regress on their own if a temporary infection is causing the enlargement. However, some lymphomas may regress and appear to be benign, only to reappear at a later time.
The Procedure. During a biopsy, the doctor usually removes the node and checks the surrounding areas. The tissue in the node is then examined for signs of infection and blood cell or other abnormalities. Biopsies of bone marrow may also be performed in patients with existing Hodgkin's disease if the doctor suspects that it may have spread to the marrow.
Laparotomy and Laparoscopy
Laparotomy and laparoscopy are abdominal surgeries that have been used to examine internal organs and stage the disease in patients who were candidates for radiation. The goal was to determine whether the disease had spread or not. They play a more limited role in HD management now than previously, since many patients receive a combination of chemotherapy, (which fights cancer throughout the body), and radiation for local disease, making this procedure unnecessary.
Click the icon to see an illustrated series detailing spleen removal surgery.
Laparotomy. Laparotomy is abdominal surgery used to examine the internal organs, particularly the liver, spleen, and any nodes not detectable using noninvasive imaging techniques. During this procedure, the spleen is removed (splenectomy) and tissue samples in the abdominal area are taken for biopsy. Because removal of the spleen affects the body's resistance to infection, after laparotomy some patients are susceptible to infection, which can be life-threatening. This risk has been greatly minimized with use of preoperative vaccinations and chemotherapy treatments that have less of a negative effect on the immune system. Children are at higher risk for infection than adults. It is advisable to be vaccinated against Hemophilus influenzae type b, meningococcal, and pneumococcal organisms at least one week before splenectomy. Some investigators recommend re-immunization with all three vaccines 2 years after completion of treatment and pneumococcal vaccine every 6 years thereafter.
Laparoscopy. A less-invasive technique called laparoscopy is sometimes considered to avoid the invasive laparotomy. This procedure uses small abdominal incisions and the insertion of fiberoptic tubes and tiny cameras for viewing the internal areas. The laparoscopy has a high incidence of missing cancers, but if cancer is observed and confirmed with a biopsy, then the patient does not need a laparotomy.
Click the icon to see an image of laparoscopy.
Biologic Markers
Biologic markers, called biomarkers for short, are high levels of substances that are released by tumors and indicate the level of cancer activity. Biomarkers can be found in sputum, blood, and tissue samples. Biomarkers can be enzymes, hormones, amino-acid compounds, antigens (identified by antibodies that specifically target them), growth factors, and other chemicals. Some under investigation include the following:
- CD44 is a molecule that binds to the surface of cells and may be involved in metastasis. High levels of this molecule may suggest a more aggressive disease.
- Interleukin (IL) 10 is another immune factor that may indicate a poor outlook when it occurs in high levels.
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