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A number of different examinations and tests are usually required to diagnose non-Hodgkin's lymphoma, as well as to assess how far the disease has spread and how well your body systems are working. Depending on your situation, the physician may use some or all of these tests to determine the best way to treat your disease.
The information from a patient's history, physical examinations, x-rays, scans, laboratory tests and biopsies is analyzed to allow the physician to determine the extent of disease and recommend the treatment (or treatments) that have the best chance of producing either a remission or cure.
The signs and symptoms of non-Hodgkin’s lymphoma
A sign or symptom is anything out of the ordinary the patient is experiencing that could be caused by a disease.
Signs are physical findings. The most common one that people with NHL experience is swelling of the lymph nodes, which may or may not be painful. This often occurs in the neck or under the arms, but some people may also experience swelling of lymph nodes in other parts of the body. For example, enlarged lymph nodes in the groin can cause swelling in the legs or ankles, while enlarged lymph nodes in the abdomen can cause abdominal discomfort, swelling, back pain or a feeling of bloating. Signs of NHL presenting in an extra-nodal site vary with the specific site. For example, NHL presenting in the stomach often causes ulcer-like symptoms, such as pain, and internal bleeding. Less commonly, patients with NHL may have no swollen lymph nodes.
Symptoms are the patient’s reported experiences that may indicate the presence of disease. For NHL, these may include chills, fever, sweating (often at night) unexplained weight loss, lack of energy, itching or symptoms produced by enlarged lymph nodes.
Most people who have these non-specific complaints do not have lymphoma. However, it is important that anyone who has persistent symptoms be seen by a doctor to make sure that lymphoma is not present. Serious illnesses do not simply come and go, they persist.
What the doctor looks for during a physical examination
If you have symptoms suggesting NHL, a complete physical examination will be performed. During this examination, the doctor will look for swollen lymph nodes under the chin, in the neck and tonsil area, above the shoulders, on the elbows, in the armpits, and in the groin. The doctor will also examine other parts of the body to see whether there is swelling or fluid in your chest or abdomen that could be caused by swollen lymph nodes. Your abdomen will also be examined to see whether any internal organs are enlarged. You will be asked about pain and examined for any weakness or paralysis that could be caused by an enlarged lymph node pressing against nerves or the spinal cord.
If the doctor suspects lymphoma after reviewing your symptoms and performing a physical examination, he or she may order other tests to help confirm the diagnosis. These tests should include a biopsy, and may also include blood tests, x-rays and other imaging tests, scans, a bone marrow evaluation, and perhaps an examination of the cerebrospinal fluid.
Biopsies and how they are performed
A biopsy: is a procedure in which a piece of tissue from an area of suspected cancer is removed from the body and examined under a microscope. The information provided by this tissue sample is crucial to diagnosing and treating NHL.
There are several types of biopsies. One is called a core, or needle biopsy, in which a needle is inserted into a lymph node suspected of being cancerous and a small tissue sample is removed. This type of biopsy can be done under local anesthesia and stitches are usually not required. It is more often used to confirm a relapse rather than an initial diagnosis.
Core biopsies often do not provide sufficient tissue to establish a diagnosis. Consequently, if a lymph node is readily accessible, many physicians recommend an open biopsy (also called a surgical biopsy), in which an entire swollen lymph node is usually removed. This procedure can usually be done under local anesthesia, but a general (whole body) anesthetic is sometimes needed, and a few stitches are often required. When the only signs of lymphoma are in the abdomen or the pelvis, core needle biopsies are often performed. Laparoscopy (inserting a tube) or even abdominal surgery may be necessary to obtain a sample of the tumor for examination.
After a tissue sample has been removed, it is examined by a Pathologist (a doctor who studies tissues and cells to identify diseases). Pathologists look at the tissue under a microscope and then provide the oncologist with a detailed report. Information obtained from a biopsy indicates the type of NHL. If the pathologist’s interpretation of the biopsy is uncertain, it should be reviewed by another pathologist who is expert in lymphoma (a hematopathologist).
Imaging tests and how they help evaluate the cancer
Physicians often will order imaging tests that provide pictures of the inside of the body. Most of these tests are painless, and no anesthetic is required. Several types of imaging procedures may be needed, and the necessary tests will be chosen to help best evaluate your cancer, including:
X-rays: X-rays use radiation to take pictures of areas inside the body. The amount of radiation used in most diagnostic tests are so small that it poses little risk to the patient.
CT or CAT (computerized axial tomography) scan: A CT scan takes x-rays from different angles around the body. The pictures that are obtained are then combined using a computer to give a detailed image. People with NHL often have CT scans of the neck, chest, abdomen and pelvis. These tests are useful in determining how many nodes are involved, how large they are and whether internal organs are affected by NHL.
MRI (magnetic resonance imaging): An MRI is similar to a CT scan but uses magnets and radio frequency waves instead of x-rays. An MRI can provide important information about tissues and organs, particularly the nervous system, that is not available from other imaging techniques. An MRI may be ordered when the physician wants to get clear images of the bones, brain and spinal cord to see whether the cancer has spread to these areas.
Gallium (radioisotope) scan: Radioactive gallium is a chemical that collects in some tumors. Gallium scans are sometimes used when a patient is diagnosed with NHL. This scan is performed by injecting a small amount of radioactive gallium into the body. The small amount of chemical used is not harmful. The body is then scanned from several angles to see whether the gallium has collected in a tumor. If the tumor attracts this chemical, the scan can be repeated after treatment is completed to help determine if the tumor has completely disappeared or become inactive.
PET (positron emission tomography) scan: PET scans now often replace gallium scans in many cancer centers, because the technique is more convenient and more sensitive, particularly in the abdomen. This test evaluates non-Hodgkin's lymphoma activity in different parts of the body. To perform the test, a radioactive glucose (sugar) tracer substance is first injected. A positron camera is then used to detect the radioactivity and produce cross-sectional images of the body. Like gallium scans, PET scans are very useful in determining response to treatment. While CAT scans shows the size of a lymph node, gallium and PET scans show if the lymph node is active (still has disease).
Blood tests
Blood tests are performed to determine whether different types of blood cells are normal in number and appearance when viewed under the microscope. These include red blood cells, white blood cells, and platelets. Abnormalities in these blood cells may sometimes be the first sign of lymphoma. Certain blood tests can be used to determine whether a tumor is affecting the liver, kidneys, or other parts of the body. Blood abnormalities can also help doctors determine potential treatment choices and predict outcomes. For example, in patients with NHL, levels of lactate dehydrogenase (LDH) and/or beta (2) microglobulin (B2M) are commonly measured because higher levels of either or both of these proteins suggests that the lymphoma may be more aggressive and that more intensive treatment may be needed.
If the lymphoma is circulating in the blood, tests can also be used to classify the tumors according to molecular markers (or antigens) on the surface of cancer cells. This process is called immunophenotyping and is also performed on tissue samples removed by biopsy or bone marrow extraction. This information can help distinguish among different types of lymphoma.
Bone marrow examination
Bone marrow is the spongy material found inside our bones. Bone marrow contains immature cells called stem cells, which develop into three main types of cells found in the body: red blood cells that deliver oxygen to all parts of the body and take away the waste product carbon dioxide; white blood cells that protect the body from infection; and platelets that help blood clot. NHL can spread to the bone marrow or start in the bone marrow; therefore doctors may examine part of the marrow to see whether cancer is present. Bone marrow is obtained by numbing the skin, tissue, and surface of the bone with a local anesthetic, inserting a thin needle into the pelvis or another large bone and withdrawing a small sample. The procedure can be painful at the moment when the marrow is withdrawn. Patients should talk with their doctor and nurse if they would like a calming medication before the procedure.
Cerebrospinal fluid examination
In a small number of patients, NHL can spread to the nervous system. When this occurs, the fluid present around the spinal cord and the brain (cerebrospinal fluid) may be abnormal and contain cancer cells. To determine whether this has occurred, the physician may recommend a test called a spinal tap or a lumbar puncture in which a thin needle is inserted into the lower back under local anesthetic. A small sample of fluid is then removed. Cerebrospinal fluid is examined for chemical content and abnormal cells.
Molecular diagnostic tests
Over the past decade, scientists have gained a deeper understanding of how disease works at the level of molecules such as genes and proteins. This understanding has led to powerful new diagnostic tools and treatments. These tools include PCR, which can detect small amounts of genetic material (DNA), and a variety of immunological techniques that detect the expression of specific proteins (antigens) on the surface of tumor cells. Using these tests, doctors can sometimes detect cancer earlier, and they can more accurately classify tumor types. This information may help the physician choose the most appropriate treatment for the disease. Immunological and genetic tests can find evidence of cancer unseen by a pathologist's microscope. An advantage of molecular diagnostic tests is that they are usually highly accurate and require only very small amounts of tissue obtained from biopsies, fine-needle aspirates, or sometimes blood.
Researchers are currently developing ways to measure the activity of genes within the cells of a lymphoma sample. This technique, microarray analysis, may lead to even more accurate diagnoses based on a tumor's individual genetic characteristics and behavior. Currently, the method is being used in an experimental setting for assessing non-Hodgkin's lymphoma tumors, but in the future the technique may be useful for the routine diagnosis and treatment of lymphoma.
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