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Lymphomas (Non-Hodgkin's)


An in-depth report on the causes, diagnosis, and treatment of lymphomas.


The physician will take a medical history and perform a physical examination to detect any node enlargements. If these simple procedures point to lymphomas, additional tests will be needed either to rule out other diseases or to confirm the diagnosis of lymphomas and determine the extent of the disease. It is sometimes reasonable to wait a period of time for the swelling and symptoms to recede before deciding that additional testing is necessary, since the swelling may be due to a temporary infection. However, it should be noted that in some cases, particularly in follicular, small cleaved cell lymphoma (the most common NHL), that the lymphoma waxes and wanes, so lymph nodes should still be checked periodically to be sure there is no recurrence of swelling.

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 strep or other throat infections.
  • In young people, infectious mononucleosis (caused by the Epstein Barr virus) is a common cause of swollen lymph nodes.
  • The patient should report any recent travel, particularly to countries with a high incidence of tropical diseases, which 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.

Hodgkin's Disease. 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 Hodgkins disease under some circumstances. [For more information, seeWell-Connected Report #83 Hodgkin's Disease.]

Comparison Between Hodgkin's Disease and Non-Hodgkin's Lymphomas


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.


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% to 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.


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.


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. [SeeWell-Connected Report #83 Hodgkin's Diseaseor 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, which may resemble Hodgkin's disease.

Physical Examination

The physician 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. Soft nodes suggest infection or inflammatory conditions.

Blood Tests

Blood tests help rule out infection and other diseases. Such tests include those blood counts and blood chemistries for kidney and liver function, uric acid, calcium, and phosphate levels. In a patient already diagnosed with lymphoma, blood tests that measure the enzyme lactate dehydrogenase are important in determining the prognosis; elevated levels indicate bulkier tumors. The presence of anemia may indicate specific NHLs, such as diffuse, small lymphocytic lymphoma.


A biopsy is the most important test for diagnosing lymphomas and can be used to tell the difference between non-Hodgkin's versus Hodgkin's disease. A biopsy has risks, some serious, and should only be performed by a qualified and experienced physician. Sometimes a physician 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. (It should be noted, however, that some lymphomas may regress and appear to be benign, only to reappear at a later time.)

The Procedure. The physician removes the node and checks the surrounding areas. The tissue in the node is then examined under a microscope for signs of infection and abnormalities indicating cancer or other conditions.

Results. Even if biopsies do not turn up cellular abnormalities, disease may still be present in some cases. The physician should continue to observe the patient until swelling or other signs of disease are gone. Biopsied tissue samples should be frozen in case special tests are later required. Such tests may include detection of particular antibodies, genetic and immune factors, and certain markers (substances that are indicative of disease) located on the surface of the cells. If lymphoma has been diagnosed, the tissue will be examined for its histology, the cellular structures that will determine the lymphoma type.

Bone Marrow Aspirate and Biopsy

Bone marrow aspirate and biopsy are routinely performed to determine whether the disease has spread. With bone marrow aspirate, bone marrow cells are sucked out through a special needle. A biopsy may be performed before or after the aspiration. In this procedure, a special needle removes a core of the marrow that is structurally intact.

Click the icon to see an image of bone marrow aspiration.

Imaging Techniques

Chest X-Ray. A chest X-ray allows a view of the lymph nodes in the chest and neck area. It is particularly useful in detecting Hodgkin's disease and is 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 than X-rays 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 important in detecting lymphomas in the abdominal and pelvic areas if a chest X-ray is normal and lymphomas are still suspected.

Click the icon to see an image of a CT machine.

Lymphangiography. Lymphangiography is an X-ray of the lymph glands and vessels after injection of a dye. It provides additional information on lower parts of the body and is a good complement to CT scans if the latter does not reveal abnormal lymph nodes but they are still suspected. On its own, however, lymphangiography misses cancer in 20% of cases. There is a slight risk that the dye will affect the lungs, so this test should not be used in patients with severe lung disease. Lymphangiography is not commonly used for staging non-Hodgkin's lymphomas.

Click the icon to see an image of a lymphangiogram.

Other Advanced Imaging Techniques. A number of advanced imaging techniques, including gallium scintigraphy and positron emission tomography (PET) are proving to be very helpful. Special PET imaging techniques known as FDG/PET scans may be more accurate than CT scans for staging lymphomas and more accurate than gallium scintigraphy in identifying the disease in the bone. They are also very accurate for evaluating the success of chemotherapy in patients who have been treated for lymphomas and for detecting relapsing lymphoma. Gallium scans are also useful for evaluating the success of chemotherapy.

Magnetic resonance imaging (MRI) may be used to detect the spread of the disease to the brain, spine, chest, pelvic, and abdomen. How additional tests such as MRI and PET scanning will impact the management of patients with lymphomas, however, is still unknown.

Click the icon to see an image of a MRI machine.

DNA Tests

Tests of lymphoma's DNA are in use or are being developed to detect particular genetic abnormalities that help determine outlook and may eventually lead to new treatments. Examples of such abnormal genetic arrangements are those that affect normal cell death, resist chemotherapy, or trigger aggressive cancer growth.

An advanced approach called the microarray technique uses chips that contain up to thousands of DNA sequences that represent specific normal and abnormal genes. Such sequences have been compiled for lymphomas and eventually experts may be able to match a patient's DNA to these patterns and identify specific subtypes.

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.
  • BCL-6 is a cancer gene implicated in diffuse large B-cell lymphoma. High levels of this gene in these patients indicate a better outlook after treatment.

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