Lymphoma is a cancer of a part of the immune system called the lymph system. There are many types of lymphoma. One type is Hodgkin disease. The rest are called non-Hodgkin lymphomas.

Non-Hodgkin lymphomas begin when a type of white blood cell, called a T cell or B cell, becomes abnormal. The cell divides again and again, making more and more abnormal cells. These abnormal cells can spread to almost any other part of the body. Most of the time, doctors don't know why a person gets non-Hodgkin lymphoma. You are at increased risk if you have a weakened immune system or have certain types of infections.

Non-Hodgkin lymphoma can cause many symptoms, such as

• Swollen, painless lymph nodes in the neck, armpits or groin
• Unexplained weight loss
• Fever
• Soaking night sweats
• Coughing, trouble breathing or chest pain
• Weakness and tiredness that don't go away
• Pain, swelling or a feeling of fullness in the abdomen

Your doctor will diagnose lymphoma with a physical exam, blood tests, a chest x-ray, and a biopsy. Treatments include chemotherapy, radiation therapy, targeted therapy, biological therapy, or therapy to remove proteins from the blood. Targeted therapy uses substances that attack cancer cells without harming normal cells. Biologic therapy boosts your body's own ability to fight cancer. If you don't have symptoms, you may not need treatment right away. This is called watchful waiting.

Lymphoma, or lymphatic cancer, is a broad term encompassing a variety of cancers of the lymphatic system. The two main groups of lymphoma in humans are Hodgkin lymphoma (HL), also known as Hodgkin disease, and the non-Hodgkin lymphoma (NHL).

Hodgkin lymphoma, named for Thomas Hodgkin, a British physician who identified it in 1832, is a rare cancer and accounts for only about 14 percent of all lymphomas and less than 1 percent of all cases of cancer in this country.

In Hodgkin lymphoma, cells in the lymphatic system become abnormal. They divide too rapidly and grow without any order or control. Because lymphatic tissue is present in many parts of the body, Hodgkin lymphoma can start almost anywhere. Hodgkin lymphoma may occur in a single lymph node, a group of lymph nodes, or, sometimes, in other parts of the lymphatic system such as the bone marrow and spleen. This type of cancer tends to spread in a fairly orderly way from one group of lymph nodes to the next group. For example, Hodgkin lymphoma that arises in the lymph nodes in the neck spreads first to the nodes above the collarbones, and then to the lymph nodes under the arms and within the chest. Eventually, it can spread to almost any other part of the body (contiguous spread).

The other group, non-Hodgkin lymphoma, accounts for about 3 percent of all malignancies. In non-Hodgkin lymphoma, cells in the lymphatic system become abnormal. They divide and grow without any order or control, or old cells do not die as cells normally do. Because lymphatic tissue is present in many parts of the body, non-Hodgkin lymphoma can start almost anywhere in the body. Non-Hodgkin lymphoma may occur in a single lymph node, a group of lymph nodes, or in another organ. This type of cancer can spread to almost any part of the body, including the liver, bone marrow, and spleen (non-contiguous spread).

The major components of the lymphatic system are lymphatic vessels, lymph, lymph nodes, and some other lymphatic organs.

Lymphatic vessels carry lymph, a colorless liquid, throughout the body. Along lymph vessels are small bean-shaped glandular nodules called lymph nodes.

Other lymphatic organs are:

• Tonsil: clusters of lymphatic tissues just under the mucous membranes that line the nose, mouth, and pharynx.
• Spleen: it is similar to a lymph node in shape and structure but it is much larger.
• Thymus: a soft organ with two lobes that is located anterior to the ascending aorta and posterior to the sternum.
• Peyer patch: lymphoid tissue on the visceral surface of the small intestine.

Lymphoma is a general term for cancers that start in the lymph system (the tissues and organs that produce, store, and carry white blood cells that fight infections). The two main kinds of lymphoma are—

• Hodgkin lymphoma, which spreads in an orderly manner from one group of lymph nodes to another.
• Non-Hodgkin lymphoma, which spreads through the lymphatic system in a non-orderly manner.

Hodgkin lymphoma and non-Hodgkin lymphoma can occur in children, teens, and adults.

What Causes Lymphoma?

Non-Hodgkin lymphoma becomes more common as people get older. Unlike most cancers, rates of Hodgkin lymphoma are highest among teens and young adults (ages 15 to 39 years) and again among older adults (ages 75 years or older). White people are more likely than black people to develop non-Hodgkin lymphoma, and men are more likely than women to develop lymphoma.

Scientists do not fully understand all of the causes of lymphoma, but research has found many links. For example—

• Research has shown that people who are infected with the human immunodeficiency virus (HIV) are at much higher risk of developing lymphoma.
• Other viruses, such as human T-cell lymphotrophic virus and Epstein Barr virus, also have been linked with certain kinds of lymphoma.
• People exposed to high levels of ionizing radiation have a higher risk of developing non-Hodgkin lymphoma.
• Family history has been linked with a higher risk of Hodgkin lymphoma.
• Some studies suggest that specific ingredients in herbicides and pesticides may be linked with lymphoma, but scientists don’t know how much is needed to raise the risk of developing lymphoma.

Symptoms of Lymphoma

Symptoms of Hodgkin lymphoma and non-Hodgkin lymphoma include swollen lymph nodes, especially in the part of the body where the lymphoma starts to grow. Other symptoms include fever, night sweats, feeling tired, and weight loss.

These symptoms can also come from other conditions. If you have any of them, talk to your doctor.

• Men develop NHL 30 percent more often than women. Eighty-five percent of childhood Hodgkin lymphoma cases are in males, as are all lymphoma histologies in adults except nodular sclerosing.
• HL (Hodgkin Lymphoma) peaks in the 20-29 age range and again in the 50+ range. The histologies for these two peaks are different.
• Caucasian children are at slightly greater risk than African-American children.

Others at risk are:

• People with immune deficiency diseases, such as chronic immunosuppression (for organ transplants), acquired immunosuppression, Klinefelter syndrome, Chediak-Higashi syndrome, lymphocytopenia, lymphoid infiltrates in the skin; malignant lymphoma, mycosis fungoides, Sezary's disease, malignant histiocytosis, Letter-Siwe's disease, multiple myeloma, plasmacytoma, any leukemia, Waldenstrom's macroglobulinemia.
• People with autoimmune disease, such as rheumatoid arthritis or systemic lupus erythematosus.
• People infected with HIV (particularly primary lymphoma of the brain).
• People taking immunosuppressant drugs following organ transplant.
• People who have received radiation therapy and/or chemotherapy.
• People who work extensively with or are otherwise exposed to chemicals, such as pesticides or some fertilizers.
• People who have persistent generalized lymphadenopathy, lymphatic disorders, including frequent lymphoid hyperplasia, chronic lymphadenopathy, infectious mononucleosis, exposure to Epstein-Barr virus.

Hodgkin Lymphoma

Often there are no symptoms, but about 40% of people will have some vague signs of the disease. If symptoms do occur, they may include:

• Persistent, painless swelling of lymph nodes, especially in the neck, underarm, or groin
• Unexplained fevers, tiredness, night sweats, weight loss, and itching
• Cough, shortness of breath, chest discomfort
• Enlarged spleen
• Alcohol-induced pain

Non-Hodgkin Lymphoma

Often the first sign of NHL is swelling of the lymph nodes, usually in the neck, underarm, or groin. However, because the enlargement is painless, the symptom is easily ignored. Only about 20% of those with NHL have systemic symptoms. When they do occur, symptoms include:

• Fever that doesn't go away
• Night sweats
• Constant tiredness
• Unexplained weight loss
• Itching

Because there are so many forms of NHL involving different organs, signs and symptoms vary, often depending on the areas of the body or systems affected.

Advanced Lymphoma

• Enlarged liver
• Enlarged spleen, resulting in abdominal distension

Lymphoma Involving the Gastrointestinal Tract

• Palpable abdominal mass
• Abdominal pain
• Nausea
• Vomiting
• Intestinal obstruction
• Gastrointestinal bleeding

Lymphoma Involving the Bone Marrow

• Symptoms of anemia, such as pallor, difficulty breathing, fatigue, and rapid heart beat
• Recurrent infections
• Increased bruising
• Petechiae

Lymphoma Involving the Urinary Tract

• Fatigue
• Loss of appetite
• Anemia
• Renal failure

Cutaneous T-Cell Lymphoma (CTCL)

• Redness
• Itching
• Flat, raised patches on the skin (plaques)
• Skin tumors of various types (for example, isolated dark patches, raised thick nodules, or oozing ulcerated lesions), depending on the exact type of CTCL and the stage of growth

Current therapy for Hodgkin lymphoma cures over 75% of patients. Standards of treatment are radiation therapy and combination chemotherapy.

Treatment for non-Hodgkin lymphoma depends on the cell type and stage at diagnosis. Treatment for both Hodgkin lymphoma and non-Hodgkin lymphoma is usually radiation therapy (for early stage disease, Stage I and II) and/or chemotherapy (for stage III and IV cases), but this may vary by cell type. For example, low grade, low stage non-Hodgkin lymphoma may be treated with radiation only, whereas intermediate grade, low stage NHL should receive radiation and chemotherapy, and high-grade, low stage NHL would probably receive chemotherapy only.

Lymphomas, particularly NHL can convert to a more aggressive form after initial treatment.

Low grade non-Hodgkin lymphomas respond to chemotherapy and irradiation, but continue to relapse for a long period of time.

Key:
X = complete
* = partial
o = optional

Surgery for extranodal lymphomas should be described according to the surgical codes for that site.

Hodgkin Lymphoma (Adult)

Prognostic factors

Cell type (in order from most favorable to least favorable)—Lymphocyte predominant, Nodular sclerosis, Mixed cellularity, Lymphocyte depletion.

Presence or absence of "B" symptoms is an important prognostic indicator as are the presence of large masses, involvement of the spleen, and the absolute number of nodal sites of involvement.

Hodgkin lymphoma may be cured with chemotherapy, but the incidence of secondary acute nonlymphocytic leukemia within 10 years is more than 3%. The risk of subsequent solid tumor primaries is about 13% at 15 years.

Five year Disease Free Survival Rates

(from the National Cancer Institute's Physician Data Query System, July 2003)

Non-Hodgkin Lymphoma (Adult)

Five Year Disease Free Survival Rates for Working Formulation Cell Types (all stages)

from Manual for Clinical Oncology, second edition, DA Casciato and BB Lowitz, Little Brown and Co., 1990)