The lymphatic system is part of the body's defense against infections. The system is a network of vessels throughout the body that collect invading organisms, such as viruses, and abnormal cells. The invaders are moved into lymph nodes where they are destroyed by white blood cells, including cells called lymphocytes. In general, there are two major types of lymphocytes, so-called T and B cells. B Lymphocytes are responsible for the body’s manufacturing of chemicals called antibodies, while T lymphocytes are involved in the body’s fighting off infections and cancers with specially immunized cells.

Lymphoma is a cancer of the lymphocytes, which means these cells grow abnormally and out of control. Lymphoma usually begins in a lymph node, but it also can begin in the stomach, intestines, skin or any other organ, since lymphocytes are found in all of these organs. The two main types of lymphoma are Hodgkin disease and non-Hodgkin lymphoma. Over the past decade, there have been important advances in understanding the derivation of lymphocytes that come from different areas of the lymph node (e.g., the inside portion, outside portion) as well as lymphocytes that populate specific organs in the body. Consequently, many lymphomas of the non-Hodgkin variety are further subclassified and this information is taken into account when a diagnosis is made.

Hodgkin Disease
In Hodgkin disease, the abnormal cells are called the Reed-Sternberg cells. This type of cancer can spread throughout the lymphatic system, affecting any organ or lymph tissue in the body. Hodgkin disease usually affects people in their late 20s or older than 50. Males get the disease more often than females, and whites are affected more often than people of other races. The disorder strikes about 5 in every 100,000 people.

Non-Hodgkin Lymphoma
Most lymphoma is non-Hodgkin lymphoma. In adults, non-Hodgkin lymphoma affects males more than females and often occurs between the ages of 60 and 70. Whites are affected more often than people of other races. The disorder affects about 16 in every 100,000 people — or about 45,000 people in the United States.

This cancer has become more common. This may be related to the rise in the number of people who have suppressed immune systems, such as people infected with human immunodeficiency virus (HIV) and people who have undergone an organ transplant that requires long-term treatment with drugs that alter the immune system.

Different types of lymphoma occur in different age groups.

• In adulthood — Adult non-Hodgkin lymphoma is classified by the size, type and distribution of cancer cells in the lymph nodes. The three types are low grade (slower growing), intermediate grade and high grade (aggressive).
  • Low-grade lymphomas include small-lymphocytic lymphoma, follicular small-cleaved-cell lymphoma and follicular mixed-cell lymphoma.
  • Intermediate-grade lymphomas include follicular large-cell lymphoma, diffuse small-cleaved-cell lymphoma, diffuse mixed lymphoma and diffuse large-cell lymphoma.
  • High-grade lymphomas include immunoblastic lymphoma, lymphoblastic lymphoma and small noncleaved (Burkitt's and non-Burkitt's) lymphoma.
  • There are also more refined molecular classifications of these types of non-Hodgkin lymphoma based upon specific chemicals and genes of the cell.



• In childhood — Childhood non-Hodgkin lymphomas include lymphoblastic lymphoma, large-cell lymphoma and small-noncleaved-cell lymphoma (including Burkitt's and non-Burkitt's lymphomas). Note that high-grade (aggressive) non-Hodgkin lymphomas usually affect children and young adults.

Several factors may contribute to the development of lymphoma:

• Environmental factors — Recent studies show a possible link between lymphoma and exposure to certain chemicals, herbicides and insecticides. Further study is needed.



• Genetic factors — Studies indicate that patients with certain genetic (inherited) immunodeficiency disorders, such as Wiskott-Aldrich syndrome, may have an increased risk of developing lymphoma.



• Viral infections — Research suggests links between lymphoma and certain viruses, such as the Epstein-Barr virus and HIV. For example, one study found that Burkitt's disease was related to Epstein-Barr virus in nearly all cases in Africa and in 15% of U.S. cases. Patients infected with HIV, especially those with AIDS, also are more likely to get both Hodgkin and non-Hodgkin lymphoma.

The main symptom of both Hodgkin and non-Hodgkin lymphomas is swelling of lymph nodes in the neck, under the arms or in the groin. Other symptoms can include:

• Fever
• Night sweats
• Fatigue
• Abdominal pain
• Unexplained weight loss
• Itchy skin
• Rash
• Difficulty swallowing

Because swollen lymph nodes caused by lymphoma usually are painless, lymph nodes may get larger slowly over a long time before the patient notices. Also, the fever commonly associated with lymphoma may appear and disappear for several weeks before the patient sees a doctor. Even the unexplained weight loss caused by certain lymphomas may continue for months before the patient seeks medical help.

If your doctor suspects lymphoma based on your medical history and the results of a physical examination, he or she will order blood tests and do a test called a lymph node biopsy.

In lymph node biopsy, your doctor will inject a local anesthetic beneath your skin to numb the area around a swollen lymph node. After the area is numb, a sterile needle is used to remove a small piece of tissue. The tissue is then examined in a laboratory for evidence of lymphoma. Occasionally, a whole lymph node is removed surgically instead of a small piece of tissue because this can help the pathologist be more certain of the diagnosis. Because lymphoma can also involve the bone marrow, frequently patients will have an evaluation of the bone marrow cells as well.

You may also need other tests, including X-rays to look at the chest, bones, liver and spleen; a bone marrow biopsy; a gallium scan or a positron emission tomography (PET) scan ; and a computed tomography (CT) scan of your abdomen. For a gallium or a PET scan, a radiologist will inject you with a harmless amount of a radioactive material that collects in sites where there is lymphoma. A scanner then creates images of these sites.

If you are diagnosed with lymphoma, the next step is to determine the cancer's stage. To do this, your doctor will take into account whether you have any of the so-called "B symptoms," including fever, weight loss and night sweats. The stages range from Stage I, in which the cancer is limited to one area, such as only one lymph node, to Stage IV, in which the cancer has spread extensively outside the lymph system and possibly to the bone marrow or other organs.

Occasionally, a procedure called laparoscopic surgery is done to help to determine the cancer's stage. In this procedure, a small incision is made in the abdomen, and a thin, lighted tube called a laparoscope is used to see if cancer has spread to any of the internal organs. During the procedure, small pieces of tissue also may be removed and examined under a microscope for signs of cancer.

Like other cancers, lymphoma will continue to worsen unless it is treated.

There is no definitive way to prevent Hodgkin or non-Hodgkin lymphomas. You may be able to lower your risk of lymphoma by taking precautions to avoid becoming infected with HIV. It is not known whether avoiding certain chemicals will prevent lymphoma.

Radiation is the traditional treatment for early stages of Hodgkin disease. Chemotherapy, possibly with radiation, is used in later stages of the illness. Whether chemotherapy may be used instead of radiation for early stage disease is being investigated. Treatment for non-Hodgkin lymphoma depends on the grade of lymphoma (low, intermediate or high), the stage of the disease, and the age and health of the patient.

• In very early stages, low-grade (slow-growing) lymphomas sometimes can be cured with a combination of radiation and chemotherapy. Otherwise, treatment is based on when symptoms develop and how bad they are. Early, aggressive therapy is not thought to improve survival for most low-grade lymphomas. In some cases of early stage, low-grade lymphoma, the disease will be monitored, but no treatment will be given unless the disease gets worse. If a patient with early stage, low-grade (slow-growing) lymphoma has symptoms, or if the disease has spread significantly, it can be treated with radiation therapy.



• Advanced-stage, low-grade lymphoma may be treated in a variety of ways, ranging from chemotherapy with or without radiation therapy to a bone marrow transplant. In a bone marrow transplant, the patient's bone marrow cells are killed and then cancer-free bone marrow cells are injected.



• For higher-grade lymphomas, cure is possible in 40% to 50% of cases. The main treatment is chemotherapy. Radiation also is used sometimes. Intermediate-grade lymphoma may be treated with a combination of chemotherapy drugs. More advanced stages may require higher-dose chemotherapy and possibly a bone marrow transplant or stem cell transplant. In a bone marrow transplant, the patient's bone marrow cells are killed and then cancer-free bone marrow cells are injected. Stem cells are immature cells that grow into blood cells. In a stem cell transplant, the patient's stem cells are removed and treated to kill the cancer before being injected back into the patient. Burkitt's lymphoma, a high-grade lymphoma, can be cured in 80% of cases with a combination of chemotherapy drugs.

If cancer returns in a person who has been treated for intermediate and high-grade lymphomas, he or she may be a candidate for a bone marrow or stem cell transplant.

In recent clinical trials, radioimmunotherapy has been used to treat advanced, higher-grade or lymphomas that keep returning after treatment. This therapy involves injecting antibodies with added radioactive iodine. The antibodies are proteins that are part of the immune system and attack cancer cells. The added radiation helps to kill the cells. Researchers are studying other biological therapies that use the immune system to fight cancer.

Immunotherapy: Specific chemicals on the surface of lymphoma cells have been characterized. Proteins called antibodies that react with these chemicals have been developed. When these antibodies are given to patients with certain types of lymphomas, dramatic improvements have occurred in both the shrinkage of the lymphoma tumors and in improving overall survival. When a lymph node containing lymphoma cells is sampled and studied by a pathologist, tests for the presence or absence of these chemicals are done. If the chemicals are present, many patients will receive the specific antibodies in addition to chemotherapy or radiation, with greater expectations for cure.

See your doctor if you experience any symptoms of lymphoma for more than two weeks.

Hodgkin Disease

This is considered to be the most curable of all the blood cancers. With proper treatment, about 80% of patients survive 5 years or longer. Patients diagnosed with Stage I disease have more than a 90% chance of living 10 years or more. Those diagnosed in Stage IV have a 50% chance of living 10 years or more.

Non-Hodgkin Lymphoma

For patients with non-Hodgkin lymphoma, the chance of survival depends on the grade and stage of cancer, overall health, and response to treatment. Between 50% and 80% of patients survive 5 years or more. The higher-grade aggressive types of lymphoma are more likely to be cured with chemotherapy, but this form of cancer can be fatal. Lower-grade lymphomas, while usually not curable, often have longer average survival times, with mean survival reaching 10 years in some cases.

Most children respond well to treatment, even though children tend to have the higher-grade, aggressive types of non-Hodgkin lymphoma. As many as 70% to 90% of children survive 5 years or more.

With both types of lymphomas, it is important for the patient to be monitored life-long for the development of second cancers, which may occur either as a result of the initial lymphoma, or as a consequence of the treatment provided for the initial lymphoma.

Leukemia & Lymphoma Society, The
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Phone: 914-949-5213
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E-Mail: infocenter@leukemia-lymphoma.org
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National Cancer Institute (NCI)
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Bethesda, MD 20892-2580
Phone: 301-435-3848
Toll-Free: 1-800-422-6237
http://www.nci.nih.gov/

American Cancer Society (ACS)
1599 Clifton Rd., NE
Atlanta, GA 30329-4251
Toll-Free: 1-800-227-2345
http://www.cancer.org/