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Non-Hodgkin Lymphomas

(Non-Hodgkin's Lymphomas)


Peter Martin

, MD, Weill Cornell Medicine;

John P. Leonard

, MD, Weill Cornell Medicine

Last full review/revision Jul 2020| Content last modified Jul 2020
Click here for the Professional Version
Topic Resources

Non-Hodgkin lymphomas are a diverse group of cancers that develop in B or T cells (lymphocytes).

  • Often, lymph nodes in the neck, under the arms, or in the groin enlarge rapidly and painlessly.

  • People may have pain or shortness of breath or other symptoms when enlarged lymph nodes press on organs.

  • A lymph node and/or bone marrow biopsy are needed for diagnosis.

  • Treatment may involve radiation therapy, chemotherapy, immunotherapy with monoclonal antibodies, or a combination.

  • Most people are cured or survive for many years.

  • People who relapse are treated with stem cell transplantation.

Lymphomas are cancers of a specific type of white blood cells known as lymphocytes. These cells help fight infections. Lymphomas can develop from either B or T lymphocytes. T lymphocytes are important in regulating the immune system and in fighting viral infections. B lymphocytes produce antibodies, which are essential in fighting off some infections.

This group of cancers is actually more than 50 different diseases that involve B cells or T cells (lymphocytes), which are types of white blood cells. Each of these lymphomas has a distinct appearance under the microscope, a different cell pattern, and a different pattern of symptoms and progression. Most non-Hodgkin lymphomas (80 to 85%) are from B cells. Less than 15 to 20% develop from T cells.

Non-Hodgkin lymphoma is more common than Hodgkin lymphoma. It is the 6th most common cancer in the United States and causes 4% of all cancer deaths. It is more common as people get older.

In the United States, over 70,000 new cases are diagnosed every year, and the number of new cases is increasing, especially among older people and people whose immune system is not functioning normally. People who have had organ transplants and some people who have been infected with hepatitis C or the human immunodeficiency virus (HIV) are at risk of developing non-Hodgkin lymphoma.

Leukemias also are cancers that involve white blood cells. In leukemias, most of the cancerous white blood cells are in the bloodstream and bone marrow. In lymphomas, most of the cancerous white blood cells are within lymph nodes and organs such as the spleen and liver. However, leukemia and non-Hodgkin lymphoma sometimes overlap because people with lymphoma may have cancerous white blood cells in their bloodstream and people with leukemia may have cancer cells in their lymph nodes and organs.

Did You Know...

  • Non-Hodgkin lymphomas are actually a group of more than 50 different diseases.

Causes of Non-Hodgkin Lymphomas

Although the cause of most non-Hodgkin lymphomas is not known, evidence strongly supports a role for viruses in some of the less common types. A rare type of rapidly progressive non-Hodgkin lymphoma, which occurs in southern Japan and the Caribbean, may result from infection with human T-cell lymphotropic virus 1 (HTLV-1), a retrovirus similar to human immunodeficiency virus (HIV). The Epstein-Barr virus is associated with Burkitt lymphoma, another type of non-Hodgkin lymphoma. Other suspected viral causes include hepatitis C virus, Kaposi sarcoma, and herpes virus. People with HIV are at increased risk of developing some subtypes of non-Hodgkin lymphoma. Bacteria such as Helicobacter pylori also increase lymphoma risk, especially in the stomach.

Other people at risk for non-Hodgkin lymphoma include those with

Symptoms of Non-Hodgkin Lymphomas

The first symptom is often rapid and usually painless enlargement of lymph nodes in the neck, under the arms, or in the groin. Enlarged lymph nodes within the chest may press against airways, causing cough and difficulty breathing, or press against blood vessels in the chest, causing swelling of the face, neck, and arms (superior vena cava syndrome). Deep lymph nodes within the abdomen may press against various organs, causing loss of appetite, constipation, abdominal pain, or progressive swelling of the legs.

Some lymphomas can appear in the bloodstream and bone marrow, so people can develop symptoms related to too few red blood cells, white blood cells, or platelets. Too few red blood cells can cause anemia, leading to fatigue, shortness of breath, and pale skin. Too few white blood cells can lead to infections. Too few platelets may lead to increased bruising or bleeding. Non-Hodgkin lymphomas can also invade the digestive tract, skin, and occasionally the nervous system, causing various symptoms. Some people have persistent fever without an evident cause, the so-called fever of unknown origin. This type of fever commonly reflects an advanced stage of disease.

In children, the first symptoms—anemia, rashes, and neurologic symptoms, such as weakness and abnormal sensation—are likely to be caused by infiltration of lymphoma cells into the bone marrow, blood, skin, intestine, brain, and spinal cord. Lymph nodes that become enlarged are usually deep ones, leading to the following:

  • Accumulation of fluid around the lungs, which causes difficulty in breathing

  • Pressure on the intestine, which causes loss of appetite or vomiting

  • Blocked lymph vessels, which causes fluid retention called lymphedema, most noticeably in the arms and legs


Symptoms of Non-Hodgkin Lymphoma



Difficulty breathing

Swelling of the face

Lymph nodes in the chest are enlarged.

Loss of appetite

Abdominal pain or distention from a blocked bowel or fluid in the abdomen

Lymph nodes in the abdomen are enlarged.

Lymphoma cells are blocking the flow of bile from the liver.

Decreased urine production

Lymph nodes are blocking the flow of urine from the kidney to the bladder

Progressive swelling of the legs

Lymph vessels in the groin or abdomen are blocked producing lymphedema.

Weight loss



Bloating and cramping (indicating malabsorption—nutrients are not absorbed normally into the blood)

Lymphoma cells are growing in or around the small intestine.

Shortness of breath

Chest pain

Cough (indicating fluid accumulation around the lungs, called pleural effusion)

Lymph vessels in the chest are blocked.

Swelling of the face and neck

Blood vessels in the chest are blocked.

Thickened, dark, itchy areas of skin

Lymphoma cells are infiltrating the skin.

Weight loss


Night sweats

The disease is spreading throughout the body.


Shortness of breath

Pale skin (indicating anemia, or too few red blood cells)

One or more of the following occurs:

  • Bleeding into the digestive tract

  • Destruction of red blood cells by an enlarged spleen or by abnormal antibodies

  • Invasion and destruction of bone marrow by lymphoma cells

  • Inability of the bone marrow to produce enough red blood cells because it is damaged by treatment (drugs or radiation therapy)

Susceptibility to severe bacterial infections

Lymphoma cells are invading the bone marrow and lymph nodes, reducing antibody production.

Diagnosis and Classification

  • Lymph node biopsy

Doctors suspect non-Hodgkin lymphoma when a person with no apparent infection develops persistent and painless enlargement of lymph nodes that lasts for several weeks. Sometimes enlarged lymph nodes deep within the chest or abdomen are found unexpectedly when a chest x-ray or computed tomography (CT) is done for another reason.

Doctors do a biopsy of an enlarged lymph node to diagnose non-Hodgkin lymphomas and to distinguish them from Hodgkin lymphoma and other disorders that cause enlarged lymph nodes.

The type of biopsy depends on which node is enlarged and how much tissue is needed. Doctors must remove enough tissue to be able to distinguish non-Hodgkin lymphoma from other disorders that can cause lymph node enlargement, including Hodgkin lymphomas, infections, inflammation, or other cancers. The best way to obtain enough tissue is with an excisional biopsy (a small incision made to remove a piece of the lymph node). Occasionally, when an enlarged lymph node is close to the body's surface, a sufficient amount of tissue can be obtained by inserting a hollow needle (usually under ultrasound or CT guidance) through the skin and into the lymph node (core needle biopsy). When an enlarged lymph node is deep inside the abdomen or chest, surgery may be needed to obtain a piece of tissue.

Although more than 50 different disorders can be called non-Hodgkin lymphomas, doctors sometimes group them into two broad categories.

Indolent lymphomas are characterized by

  • A long survival period (many years)

  • Rapid response to many treatments

  • Variable periods of remission but lack of cure with current standard therapies

Aggressive lymphomas are characterized by

  • Rapid progression without therapy

  • High rates of cure with standard chemotherapy but short survival when cure is not achieved

Although non-Hodgkin lymphomas are usually diseases of middle-aged and older people, children and young adults may develop lymphomas. Lymphomas that develop in children and young adults are commonly aggressive subtypes.

Staging of Non-Hodgkin Lymphomas

  • Imaging studies

  • Bone marrow biopsy

  • Blood tests (including liver and kidney function tests)

Many people with non-Hodgkin lymphomas have disease that has spread at the time of diagnosis. In only 10 to 30% of people, the disease is limited to one region. People with these lymphomas undergo similar staging procedures as people with Hodgkin lymphoma. In addition, a bone marrow biopsy is occasionally done.

The disease is classified into four stages based on the extent of its spread (I, II, III, IV). The higher the number, the more the lymphoma has spread.

Limited stage disease includes stages I and II; advanced stage disease includes stages III and IV. In stages I and II, if non-Hodgkin lymphoma is present in an organ outside the lymph system, it is classified as stage IE or IIE. Bulky disease is the term used when there is a tumor mass in the chest, the size of which may be different for different types of lymphomas.

The choice of treatment and the prognosis are based on the stage. Several procedures are used to stage or assess non-Hodgkin lymphoma. Basic blood tests, including a complete blood count and tests of liver and kidney function, are done.

Positron emission tomography (PET) combined with computed tomography (combined PET-CT) is the most sensitive technique for determining the location and size of cancerous lesions and how active the cancer cells are. If combined PET-CT scan is not available, a contrast CT scan of the chest, abdomen, and pelvis is done. Other tests such as magnetic resonance imaging (MRI) of the brain or spinal cord are done if symptoms of the nervous system are present.

Bone marrow biopsy may be done, particularly when the blood tests show anemia or low platelet counts. In some types of non-Hodgkin lymphoma, the PET-CT can reliably detect bone marrow involvement, so a bone marrow biopsy may not always be necessary. In other types of non-Hodgkin lymphoma, the PET-CT cannot reliably detect bone marrow involvement and a bone marrow biopsy may be needed if staging would change the choice of treatment.


Stages of Non-Hodgkin Lymphoma


Extent of Spread


Limited to one lymphatic tissue site (lymph node, thymus, or spleen), or only one site outside the lymphatic system (IE)*


Involves two or more lymph node regions on the same side of the diaphragm, above or below it (for example, some enlarged nodes in the neck and some in the armpit), or extension outside an involved lymph node area with or without other lymph node areas on the same side of the diaphragm (IIE)*


Involves spleen and lymph node regions above and below the diaphragm (for example, some enlarged nodes in the neck and some in the groin)


Involves other parts of the body (such as the bone marrow, lungs, or liver), as well as lymph nodes

* In stages I and II, if lymphoma is present in an organ outside the lymph system, it is classified as stage IE or IIE.

Treatment of Non-Hodgkin Lymphomas

  • Chemotherapy, radiation therapy, or both

  • Immunotherapy (drugs made up of antibodies that attack cancer cells), with or without chemotherapy

  • Sometimes stem cell transplantation

The treatment of non-Hodgkin lymphoma varies widely based on the subtype.

For some people with indolent lymphomas, treatment is not needed when the lymphoma is first diagnosed. Studies show that waiting does not compromise outcome and prevents the patient from being exposed to side effects of treatment. For people with indolent lymphomas, treatment, when needed, extends life and relieves symptoms for many years. For people with aggressive lymphomas, cure is possible and therefore waiting without treatment is not usually done. The likelihood of a cure or long-term survival depends on the type of non-Hodgkin lymphoma and the stage when treatment starts. It is somewhat of a paradox that indolent lymphomas usually respond readily to treatment by going into remission (in which the disease is under control), often followed by long-term survival, but the disease usually is not cured. In contrast, aggressive non-Hodgkin lymphomas, which usually require very intensive treatment to achieve remission, have a good chance of being cured.

Stage I non-Hodgkin lymphomas: Limited disease

People with indolent lymphomas who have very limited disease (stage I) are often treated with radiation therapy limited to the site of the lymphoma and adjacent areas. With this approach, most people do not have a disease recurrence in the irradiated area, but non-Hodgkin lymphomas can recur elsewhere in the body as long as 10 years after treatment, so people require long-term monitoring. People with aggressive lymphomas at a very early stage need to be treated with combination chemotherapy and sometimes radiation therapy.

Stages II to IV non-Hodgkin lymphomas: Advanced disease

Almost all people with indolent lymphomas have stage II to IV disease. They do not always require treatment initially, but they are monitored for evidence of lymphoma progression, which could signal a need for therapy, sometimes years after the initial diagnosis. There is no evidence that early treatment extends survival in people with indolent lymphomas at more advanced stages. If the disease begins to progress, there are many treatment choices.

Multiple treatment options exist, and the choice of treatment may depend on a variety of factors, including the lymphoma subtype, the extent of spread, and the person’s symptoms, and co-existing medical conditions. Treatment may include therapy with monoclonal antibodies (such as rituximab) alone or combined with chemotherapy. Most treatments are given intravenously. Sometimes, oral drugs are used. Treatment usually produces a remission. The average length of remission depends on the intensity of the treatment. Sometimes treatment may also include maintenance therapy (therapy given after the initial treatment to help prevent relapse).

For people with aggressive stage II to IV non-Hodgkin lymphomas, combinations of chemotherapy drugs are given promptly, often together with rituximab. Many potentially effective combinations of chemotherapy drugs are available. Combinations of chemotherapy drugs are often given names created by using the initial letter of each drug that is included. For example, one of the oldest and still one of the most commonly used combinations is known as CHOP (cyclophosphamide, [hydroxy]doxorubicin, vincristine [Oncovin], and prednisone). Rituximab has been shown to improve the outcome of CHOP and is now routinely added to the combination (R-CHOP). About 60 to 70% of people with aggressive non-Hodgkin lymphomas at an advanced stage are cured with R-CHOP chemotherapy. Newer combinations of drugs are being studied. Chemotherapy, which often causes different types of blood cells to decrease in number, is sometimes better tolerated if special proteins (called growth factors) are also given to stimulate growth and development of blood cells.

Did You Know...

  • Combinations of chemotherapy drugs are often named by combining the initial letter of each drug name.

Posttreatment strategies

After radiation therapy, there is an increased risk of secondary cancers occurring 10 or more years after treatment in organs that were in the radiation field. Leukemias may develop in some people many years after successful treatment for non-Hodgkin lymphoma, regardless of the treatment used.

After treatment has been finished, people should have regular doctor's examinations and tests to look for return of the lymphoma (post-treatment surveillance). The type of tests depends on the patient's risk factors and type of treatment they received.


Most people who have a relapse of an aggressive lymphoma receive high doses of chemotherapy drugs combined with autologous stem cell transplantation, involving the person's own stem cells. With this type of treatment, some people are cured. Sometimes stem cells from a sibling or even an unrelated donor (allogeneic transplant) can be used, but this type of transplantation has a greater risk of complications. Sometimes people are offered treatment with chimeric antigen receptor (CAR) T cells, which are T cells that have been genetically engineered to fight against lymphoma.

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