Evaluation and Staging of Non-Hodgkin’s Lymphoma

This content has been reviewed and approved by

James O. Armitage, MD
The Joe Shapiro Professor of Internal Medicine
Section of Oncology/Hematology
University of Nebraska Medical Center

When the diagnosis of non-Hodgkin's lymphoma is confirmed, a series of tests must be performed to determine the best management. These will always begin with a careful patient history and physical examination. Other tests will include measuring and characterizing cells in the blood along with tests that measure the function of specific organs, such as the liver and kidney. Tests also will include measurement of a specific enzyme—called lactate dehydrogenase (LDH)—in the blood.

Many other blood tests might be done, including measurement of the proteins in the blood, thyroid function, a protein called beta-2 microglobulin, level of calcium in the blood, and others. For most patients, a biopsy of the bone marrow will be performed to rule out lymphoma involvement in that organ.

In addition to the previously named studies, images will usually be obtained to look for involvement of internal organs. In most patients, this will include a computed tomogram (CT scan) of the chest, abdomen, and pelvis and a positron emission tomography (PET) scan.

These two tests are complementary with the CAT scan in looking for changes in normal anatomy. However, results of a PET scan are abnormal in sites of abnormal metabolism, which is frequently seen in lymphomas. Thus, a normal CAT scan might not see a very small site of lymphoma that could be seen on a PET scan. Sometimes abnormalities on CAT scan don't represent lymphoma, and the PET scan is normal. Also, not all lymphomas are abnormal on PET scans.

All these tests will be used to determine the stage of the cancer. This is a reflection of the degree of spread of the lymphoma—stage I is localized (confined) to one spot and stage IV is widespread. The stages are as defined below:

• Stage I: Cancer is limited to a single lymph node, in the area immediately surrounding that node, or in a single organ.
• Stage II: Cancer involves more than one lymph node area on one side of the diaphragm (the breathing muscle separating the abdomen from the chest).
• Stage III: The cancer involves lymph node regions above and below the diaphragm. For example, there may be swollen lymph nodes under the arm and in the abdomen.
• Stage IV: Cancer involves one or more organs outside the lymph system or a single organ and a distant lymph node site.

Patients who have disease confined to a site outside the lymph nodes will often be termed as Stage IE. Following the Roman numeral for the stage, there will often be a letter: A or B. A means the absence of fever, night sweats, and weight loss, and B indicates the presence of such symptoms.

For these purposes, fever means an unexplained temperature of 101°F or higher; night sweats mean drenching sweat at night that might cause one to change bed clothes; and weight loss is a loss of 10 percent or more of body weight within the past 6 months.

For non-Hodgkin's lymphomas, it has been apparent for some time that the stage is not an adequate method to predict the outcome of therapy. A number of systems have been devised over the years to try to better predict outcome.

The most widely used of these is a system that was developed by international collaboration—called the International Prognostic Index (IPI). This was developed originally for patients with diffuse large B-cell lymphoma, but is frequently applied to patients with all types of non-Hodgkin's lymphoma. Patients have a score of 0 to 5 depending upon the presence or absence of the following:

• Age greater than 60
• Reduced performance status—that is, the inability to carry out usual tasks or the need to rest part of each day
• LDH elevation in the serum
• Multiple extranodal sites of involvement by lymphoma
• Stage III or IV
  

Patients with none of these abnormalities have a much better outlook than patients with multiple abnormalities. However, patients with diffuse (nonfollicular) large B-cell lymphoma with multiple abnormalities still have some chance for a cure.

For patients under 60, there is a modification of the IPI that is widely used. This involves only the three characteristics noted below and the score ranges from 0 to 3.

• Reduced performance status
• Elevated serum LDH
• Stage III-IV
  

Other prognostic systems have been devised for follicular lymphoma and peripheral T-cell lymphoma, but are not as widely applied.