Lymphoma refers to a varied group of cancers of the blood that develop from white blood cells in the lymphatic system. The lymphatic system is a group of organs and tissues that are part of the immune system and also help to form new blood cells. It includes lymph nodes, small organs composed of lymphoid tissue located at various points throughout the body that are joined by lymphatic vessels; the spleen, a small organ on the left side of the abdomen that produces lymphocytes and stores red blood cells; the bone marrow, which produces new red and white blood cells; and the thymus gland just below the neck, which produces one type of lymphocyte, the T cell.
Two major types of lymphoma were defined in the early 1980s—Hodgkin disease, sometimes called Hodgkin lymphoma or HL; and non-Hodgkin lymphoma or NHL. HL was named for Thomas Hodgkin (1798–1866), a British doctor who first described it in 1832, and was the first form of lymphoma to be officially defined, in 1963. Researchers focused on Hodgkin disease relatively early because it can be treated effectively by radiation therapy. Other forms of lymphoma were then grouped under the general heading of non-Hodgkin lymphoma or NHL in 1982. This entry will focus on non-Hodgkin lymphoma or NHL.
Like Hodgkin disease, non-Hodgkin lymphoma begins in the lymphocytes, or white blood cells in the immune system. About 85 percent of
NHLs originate in B cells, which are lymphocytes produced in the bone marrow. Most of the remaining 15 percent develop from T cells produced in the thymus gland. What happens is that the abnormal B or T cells start to multiply uncontrollably, often within the lymph nodes, causing swelling and pain. The lymphoma can spread from the lymph nodes to the lymphatic vessels, tonsils, adenoids, spleen, thymus, and bone marrow. A non-Hodgkin lymphoma can also spread outside the lymphatic system to such other organs as the liver.
Non-Hodgkin lymphomas vary considerably in their speed of development and danger to survival. The 1982 classification categorized NHLs as low-grade, intermediate-grade, or high-grade depending on their aggressiveness and the organs affected by the cancer. Low-grade lymphomas are sometimes called indolent lymphomas because they grow slowly and cause relatively few symptoms. Intermediate-grade and high-grade lymphomas grow and spread more rapidly and cause severe symptoms.
Non-Hodgkin lymphoma accounts for about 4 percent of all cancer diagnoses in the United States. It is seventh in frequency among all cancers and is five times more common than Hodgkin disease. About 64,000 Americans are diagnosed with NHLs each year, and 18,700 die from this form of cancer. The five-year survival rate for non-Hodgkin lymphomas is 63 percent.
Non-Hodgkin lymphomas usually affect older adults; they are most likely to occur in people over sixty. Low-grade lymphomas account for 37 percent of NHLs in patients aged thirty-five to sixty-four but account for only 16 percent of cases in patients younger than thirty-five. Low-grade lymphomas are extremely rare in children.
Risk factors (other than age) for non-Hodgkin lymphoma include:
- Exposure to certain chemicals, particularly benzene and certain weed-killing chemicals
- Exposure to radiation, including nuclear reactor accidents as well as radiation treatment for cancer
- Taking drugs that suppress the immune system, including chemotherapy for cancer as well as drugs given to prevent rejection of a transplanted organ
- Certain infections, including AIDS and infection with a bacterium associated with stomach ulcers
- Autoimmune diseases, including lupus and rheumatoid arthritis
- Extreme obesity
Non-Hodgkin lymphomas are caused by the uncontrolled multiplication of abnormal B or T cells. What triggers the formation of the abnormal cells is not completely understood but is thought to be related to the activation of abnormal genes called oncogenes. Oncogenes are genes that have the potential to trigger normal cells into becoming cancerous.
The most common symptoms of NHLs are:
- Swollen but painless lymph nodes in the neck, groin, or armpit areas
- Unexplained or unintended weight loss
- Soaking night sweats
- Coughing or difficulty breathing
- Chest pain
- Fatigue that does not go away
- Itchy skin
- Pain, swelling, or a feeling of fullness in the abdomen
A few patients may have no symptoms at all in the early stages of the disease other than swollen lymph nodes.
The diagnosis of NHLs can be complicated because none of the symptoms of lymphomas are unique to this type of cancer. The first step in diagnosing non-Hodgkin lymphoma is to rule out other
diseases that can cause swollen lymph nodes. In addition to examining the patient's lymph nodes as part of a physical examination, the doctor will order blood and urine tests to see whether an infection might be the cause of thepatient's symptoms. The doctor will also ask how long the symptoms have been present; while the flu can cause fever and fatigue, for example, those symptoms should go away after a week or two.
The next step in diagnosis is imaging studies, including a chest x ray and a computed tomography (CT) scan or magnetic resonance imaging (MRI) study of the chest, abdomen, or pelvic area. These tests can identify the location and size of tumors within the lymph nodes in those parts of the body. A newer type of imaging test that may be ordered to detect lymphoma is a positron emission tomography (PET) scan. In a PET scan, a radioactive substance called a tracer is injected into the patient's circulation. The radioactive material tends to concentrate in tissues that show an increased level of metabolic activity, which often means a tumor.
In addition to imaging studies, the doctor will collect a tissue sample called a biopsy to be examined under the microscope in a specialized laboratory. If the swollen lymph node is close to the surface of the skin, the doctor can remove the tissue sample through a hollow needle. If the lymph node lies deeper within the body, a surgeon may be called in to remove the tissue by making an incision.
To determine whether the lymphoma has spread, the doctor may also order a bone marrow biopsy. In this test, the patient is given a local anesthetic and a sample of bone marrow is removed from the hip bone through a hollow needle.
The first step in treating any kind of cancer is called staging. Staging is a description of the location of the cancer, its size, how far it has penetrated into healthy tissue, and whether it has spread to other parts of the body. Non-Hodgkin's lymphoma is classified into four stages:
- Stage I: The disease is limited to one lymph node group or one tissue or organ (such as the spleen or liver).
- Stage II. The disease involves two or more lymph node groups on the same side of the diaphragm, or in one part of an organ and the lymph nodes near that organ.
- Stage III. The disease has spread to lymph node groups on both sides of the diaphragm and may involve a part of an organ or tissue near those groups.
- Stage IV. The disease has spread to several parts of one or more organs in addition to the lymph nodes.
The treatment of non-Hodgkin lymphoma depends on the subtype to which the tumor belongs and its stage of development.
- If the patient has an indolent NHL without symptoms, the doctor may recommend watchful waiting rather than beginning treatment right away, as all forms of cancer therapy have some side effects.
- Early-stage NHLs are treated with either radiation therapy or a combination of radiation and chemotherapy. Chemotherapy for lymphoma usually involves a combination of drugs rather than a single agent. It may be given either intravenously or by mouth.
- Early-stage lymphomas may also be treated with biological therapy, which involves vaccines and other drugs intended to boost the functioning of the patient's immune system. Biological therapy is also given to offset some of the side effects of radiation and chemotherapy.
- Aggressive lymphomas are treated with a combination of chemotherapy and biological therapy.
- Patients whose cancers return after therapy are given high doses of radiation, chemotherapy, or both, followed by stem cell transplantation. This procedure involves giving the patient stem cells after chemotherapy in order to help the patient's bone marrow recover and begin to produce healthy blood cells again.
The prognosis of non-Hodgkin lymphoma depends on the specific tumor type and location; the patient's age; severity of symptoms; the patient's ability to tolerate intensive chemotherapy; and whether the disease has spread beyond the lymph nodes. In general, patients older than sixty, patients with weakened immune systems, and patients with T-cell lymphomas have worse prognoses than younger patients, patients who are otherwise healthy, and patients with B-cell lymphomas.
About 70 percent of patients with intermediate- or high-grade lymphomas at the time of diagnosis either fail to respond to treatment or
have a recurrence of their cancer. About 5 percent of patients with recurrent cancer will survive for two years after the recurrence.
There is no way to prevent non-Hodgkin lymphoma because its causes are still unknown, and some potential risk factors may not yet have been identified.
Researchers are looking for an explanation for the rise in the number of cases of NHLs in the United States since the 1970s. The figure nearly doubled between the 1970s and early 2000s. Although some of the increase can be explained by improved diagnostic techniques, there appear to be other factors involved that have not yet been identified.
Other scientists are studying various innovative treatments for non-Hodgkin lymphoma, including new anticancer drugs, new types of biological therapy, and improved methods of stem cell transplantation.
WORDS TO KNOW
Biological therapy: An approach to cancer treatment that is intended to strengthen the patient's own immune system rather than attack the cancer cells directly.
Diaphragm: A sheet of muscle extending across the bottom of the rib cage that separates the chest from the abdomen.
Indolent: The medical term for a tumor or disease that grows or develops slowly.
Lymph nodes: Small rounded masses of lymphoid tissue found at various points along the lymphatic vessels.
Lymphocyte: A type of white blood cell that fights infection. Lymphocytes are divided into two types, T cells (produced in the thymus gland) and B cells (produced in the bone marrow).
Oncogene: A gene that has the potential to cause a normal cell to become cancerous.
Staging: Measuring the severity or spread of a cancer.
Stem cell: A type of body cell that has the ability to differentiate into various types of specialized cells.
Thymus: A small organ located behind the breastbone that is part of the lymphatic system and produces T cells.
SEE ALSO Hodgkin disease; Leukemia
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