Non-Hodgkin lymphoma (also known as non-Hodgkin’s lymphoma, NHL, or sometimes just lymphoma) is a cancer that starts in cells called lymphocytes, which are part of the body’s immune system.

Lymphocytes are in the lymph nodes and other lymphoid tissues (such as the spleen and bone marrow).

Some other types of cancer – lung or colon cancers, for example – can spread to lymph tissue such as the lymph nodes. But cancers that start in these places and then spread to the lymph tissue are not lymphomas.

The main types of lymphomas are:

  • Hodgkin lymphoma (also known as Hodgkin’s lymphoma, Hodgkin disease, or Hodgkin’s disease), which is named after Dr. Thomas Hodgkin, who first described it
  • Non-Hodgkin lymphoma

These different types of lymphomas behave, spread, and respond to treatment differently.

Doctors can usually tell the difference between them by looking at the cancer cells under a microscope. In some cases, sensitive lab tests may be needed to tell them apart.

Types of non-Hodgkin lymphoma

Classifying non-Hodgkin lymphoma (NHL) can be quite confusing (even for doctors) because there are so many types and because several different systems have been used. The most recent system is the World Health Organization (WHO) classification. The WHO system groups lymphomas based on how they look under a microscope, the chromosome features of the lymphoma cells, and the presence of certain proteins on the surface of the cells. (Older systems classified lymphomas only by how the cells looked under a microscope.)

The more common types of lymphoma are B-cell or T-cell lymphomas. Some rarer forms of non-Hodgkin lymphoma are not discussed here.

Risk factors for non-Hodgkin lymphoma

A risk factor is something that affects your chance of getting a disease such as cancer. Different cancers have different risk factors. Some risk factors, like smoking, can be changed; others, like a person’s age or family history, can’t.

But risk factors don’t tell us everything. Having a risk factor, or even many risk factors, does not mean that you will get the disease. And many people who get the disease may have few or no known risk factors. Even if a person with non-Hodgkin lymphoma has a risk factor, it’s often very hard to know how much that risk factor may have contributed that person developing lymphoma.

Researchers have found several factors that may affect a person’s chance of getting non-Hodgkin lymphoma. There are many types of lymphoma, and some of these factors have been linked only to certain types.

Age

Getting older is a strong risk factor for lymphoma overall, with most cases occurring in people in their 60s or older. But some types of lymphoma are more common in younger people.

Gender

Overall, the risk of non-Hodgkin lymphoma is higher in men than in women, but there are certain types of non-Hodgkin lymphoma that are more common in women. The reasons for this are not known.

Race, ethnicity, and geography

In the United States, whites are more likely than African Americans and Asian Americans to develop non-Hodgkin lymphoma.

Worldwide, non-Hodgkin lymphoma is more common in developed countries, with the United States and Europe having the highest rates. Some types of lymphoma that have been linked to specific infections (described further on) are more common in certain parts of the world.

Exposure to certain chemicals

Some studies have suggested that chemicals such as benzene and certain herbicides and insecticides (weed- and insect-killing substances) may be linked with an increased risk of non-Hodgkin lymphoma. Research to clarify these possible links is still in progress.

Some chemotherapy drugs used to treat other cancers may increase the risk of developing non-Hodgkin lymphoma many years later. For example, patients who have been treated for Hodgkin disease have an increased risk of later developing non-Hodgkin lymphoma. But it’s not totally clear if this is related to the disease itself or if it is an effect of the treatment.

Radiation exposure

Studies of survivors of atomic bombs and nuclear reactor accidents have shown they have an increased risk of developing several types of cancer, including leukemia, thyroid cancer, and non-Hodgkin lymphoma.

Patients treated with radiation therapy for some other cancers, such as Hodgkin disease, have a slightly increased risk of developing non-Hodgkin lymphoma later in life. This risk is greater for patients treated with both radiation therapy and chemotherapy.

Immune system deficiency

People with weakened immune systems have an increased risk for non-Hodgkin lymphoma. For example, people who receive organ transplants (kidney, heart, liver) are treated with drugs that suppress their immune system to prevent it from attacking the new organ. These people have a higher risk of developing non-Hodgkin lymphoma.

The human immunodeficiency virus (HIV) can also weaken the immune system, and people infected with HIV are at increased risk of non-Hodgkin lymphoma.

Some genetic (inherited) syndromes can cause children to be born with a deficient immune system. Along with an increased risk of serious infections, these children also have a higher risk of developing non-Hodgkin lymphoma. These inherited immune deficiency diseases can be passed on to children, but people with non-Hodgkin lymphoma who don’t have these inherited diseases do not pass an increased risk of lymphoma on to their children.

Autoimmune diseases

Some autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus (SLE or lupus), Sjogren (Sjögren) disease, celiac sprue (gluten-sensitive enteropathy), and others have been linked with an increased rate of non-Hodgkin lymphoma.

In autoimmune diseases, the immune system sees the body’s own tissues as foreign and attacks them, as it would a germ. Lymphocytes (the cells from which lymphomas start) are part of the body’s immune system. The overactive immune system in autoimmune diseases may make lymphocytes grow and divide more often than normal. This might increase the risk of them developing into lymphoma cells.

Certain infections

Some types of infections may raise the risk of non-Hodgkin lymphoma in different ways.

Causes non-Hodgkin lymphoma

Researchers have found that non-Hodgkin lymphoma is linked with a number of risk factors, but the causes of most lymphomas are unknown. This is complicated by the fact that lymphomas are actually a diverse group of cancers.

Still, scientists have made a lot of progress in understanding how certain changes in DNA can cause normal lymphocytes to become lymphoma cells. Normal human cells grow and function mainly based on the information contained in each cell’s chromosomes. Human DNA is packaged in 23 pairs of chromosomes, which are long molecules of DNA in each cell. DNA is the chemical that makes up our genes – the instructions for how our cells function. We look like our parents because they are the source of our DNA. But DNA affects more than how we look.

Some genes control when cells grow and divide. Genes that speed up cell division or help cells live longer are called oncogenes. Others that slow down cell division or make cells die at the right time are called tumor suppressor genes.

Each time a cell prepares to divide into 2 new cells, it must make a new copy of the DNA in its chromosomes. This process is not perfect, and errors can occur that may affect genes within the DNA. Cancers can be caused by DNA mutations (changes) that turn on oncogenes or turn off tumor suppressor genes.

Some people inherit DNA mutations from a parent that increase their risk for some types of cancer. But non-Hodgkin lymphoma is not one of the cancer types often caused by these inherited mutations. In other words, there’s no increased risk of lymphoma in the children of patients with lymphoma.

DNA changes related to non-Hodgkin lymphoma are usually acquired after birth, rather than being inherited. Acquired changes may result from exposure to radiation, cancer-causing chemicals, or infections, but often these changes occur for no apparent reason. They seem to happen more often as we age, and lymphomas for the most part are a cancer of older people.

Translocations are a type of DNA change that can cause non-Hodgkin lymphoma to develop. A translocation means that DNA from one chromosome breaks off and becomes attached to a different chromosome. When this happens, oncogenes can be turned on or tumor suppressor genes can be turned off. Some lymphomas tend to have specific chromosome defects. For example, most cases of follicular lymphoma have a translocation between chromosomes 14 and 18, which turns on the bcl-2 oncogene. This stops the cell from dying at the right time, which can lead to lymphoma.

Scientists are learning much about the exact gene changes involved in lymphoma. This information is being used to develop more accurate tests to detect and classify certain types of lymphoma. Hopefully, these discoveries can be used to develop new treatments as well.

Researchers are beginning to understand how these gene changes develop in people with certain risk factors, but they still do not know why most lymphomas develop in people with no apparent risk factors.

Lymphocytes (the cells from which lymphomas start) are immune system cells, so it’s not surprising that changes in the immune system seem to play an important role in many cases of lymphoma.

  • People with immune deficiencies (due to inherited conditions, drug treatment, organ transplants, or HIV infection) have a much higher chance of developing lymphoma than people without an immune deficiency.
  • People with certain autoimmune diseases (where the immune system constantly attacks a certain part of the body) have an increased risk of getting lymphoma.
  • People with certain chronic infections are also at increased risk, probably because the immune system is constantly making new lymphocytes to fight the infection, which increases the chances for mistakes in their DNA.

Prevention of non-Hodgkin lymphoma

Most people with non-Hodgkin lymphoma have no risk factors that can be changed, so there is no way to protect against these lymphomas. For now, the best way to reduce the risk for non-Hodgkin lymphoma is to try to prevent known risk factors such as immune deficiency.

Infection with the human immunodeficiency virus (HIV) is a preventable cause of immune deficiency. HIV is spread among adults mostly through unprotected sex and by injection drug users sharing contaminated needles. Blood transfusions are now an extremely rare source of HIV infection. Curbing the spread of HIV would prevent many deaths from non-Hodgkin lymphoma. Treating HIV with anti-HIV drugs also lowers the chance of developing non-Hodgkin lymphoma.

Preventing the spread of the human T-cell leukemia/lymphoma virus (HTLV-1) could have a great impact on non-Hodgkin lymphoma in areas of the world where this virus is common, such as Japan and the Caribbean region. The virus is rare in the United States but seems to be increasing in some areas. The same strategies used to prevent HIV spread could also help control HTLV-1.

Helicobacter pylori infection has been linked to some lymphomas of the stomach. Treating H. pylori infections with antibiotics and antacids may lower this risk, but the benefit of this strategy has not been proven yet. Most people withH. pylori infection have no symptoms, and some have only mild heartburn. More research is needed to find the best way to detect and treat this infection in people without symptoms.

Another risk factor for non-Hodgkin lymphoma is infection with the Epstein-Barr virus (the cause of infectious mononucleosis, or mono), but there is no known way of preventing this infection.

Some lymphomas are caused by treatment of cancers with radiation and chemotherapy or by the use of immune-suppressing drugs to avoid rejection of transplanted organs. Doctors are trying to find better ways to treat cancer and organ transplant patients without increasing the risk of lymphoma as much. But for now, the benefits of these treatments still usually outweigh the small risk of developing lymphoma many years later.

Some studies have suggested that being overweight or obese may increase your risk of non-Hodgkin lymphoma. Other studies have suggested that a diet high in fat and meats may raise your risk. Staying at a healthy weight and eating a healthy diet may help protect against lymphoma, but more research is needed to confirm this.

Early detection of non-Hodgkin lymphoma

At this time, there are no widely recommended screening tests for this cancer. (Screening is testing for cancer in people without any symptoms.) Still, in some cases lymphoma can be found early.

The best way to find this cancer early is prompt attention to the signs and symptoms of this disease, which are discussed in the section “How is non-Hodgkin lymphoma diagnosed?”

Careful, regular medical check-ups are important for people with known risk factors for non-Hodgkin lymphoma (such as HIV infections, organ transplants, autoimmune disease, or prior cancer treatment). These people do not commonly develop lymphoma, but they and their doctors should be aware of possible symptoms and signs of lymphoma.

Signs and symptoms of non-Hodgkin lymphoma

Non-Hodgkin lymphoma can cause many different signs and symptoms, depending on where it is in the body. In some cases it might not cause any symptoms until it grows quite large. Common signs and symptoms include:

  • Enlarged lymph nodes
  • Swollen abdomen (belly)
  • Feeling full after only a small amount of food
  • Chest pain or pressure
  • Shortness of breath or cough
  • Fever
  • Weight loss
  • Night sweats
  • Fatigue (extreme tiredness)
  • Low red blood cell counts (anemia)

Swollen lymph nodes

Non-Hodgkin lymphoma can cause lymph nodes to become enlarged. When this occurs in lymph nodes close to the surface of the body (such as on the sides of the neck, in the groin or underarm areas, or above the collar bone), they may be seen or felt as lumps under the skin. These are often found by the patient, a family member, or a health care professional. Although enlarged lymph nodes are a common symptom of lymphoma, they are much more often caused by infections.

Lymphoma in the abdomen

Lymphomas in the abdomen can cause it to become swollen and tender. This could be because of lymph nodes in the abdomen enlarging, but it can also be caused by the build-up of large amounts of fluid.

Lymphoma can enlarge the spleen so that it presses on the stomach. This can make a person feel full after eating only a small amount of food.

When lymphoma is in the intestines or causes swelling near the intestines, bowel movements may be blocked, which may lead to abdominal pain, nausea, or vomiting. Lymphoma in the intestines can also cause holes to develop in the intestine wall (called perforations). This allows the contents of the intestines to leak out into the abdominal cavity, leading to serious infection and severe pain with nausea and vomiting.

Lymphomas of the stomach often cause stomach pain, nausea, and reduced appetite.

Lymphoma in the chest

When lymphoma starts in the thymus or lymph nodes in the chest, it may press on the nearby trachea (windpipe), which can cause coughing or trouble breathing. Lymphomas in this area can also cause a feeling of chest pain or pressure.

The superior vena cava (SVC) is the large vein that carries blood from the head and arms back to the heart. It passes near the thymus and lymph nodes inside the chest. Lymphomas in this area may push on the SVC, which can cause the blood to back up in the veins. This can lead to swelling (and sometimes a bluish-red color) in the head, arms, and upper chest. It can also cause trouble breathing and a change in consciousness if it affects the brain. This condition, known as SVC syndrome, can be life-threatening and must be treated right away.

Lymphoma affecting the brain

Lymphomas of the brain, called primary brain lymphomas, can cause headache, trouble thinking, weakness in parts of the body, personality changes, and sometimes seizures.

Other types of lymphoma can spread to the area around the brain and spinal cord. This can cause problems such as double vision, facial numbness, and trouble speaking.

Lymphoma in the skin

Lymphomas of the skin may be seen or felt. They often appear as extremely itchy, red or purple lumps or nodules under the skin. (For more details, see our document Lymphoma of the Skin.)

General symptoms

B symptoms

Along with causing symptoms and signs in the part of the body where it starts, non-Hodgkin lymphoma can also cause general symptoms, such as:

  • Unexplained weight loss
  • Fever
  • Drenching night sweats (enough to soak clothing and sheets)

When talking about lymphoma, doctors call these B symptoms. B symptoms are most common in more rapidly growing lymphomas. These symptoms are important not only in helping diagnose non-Hodgkin lymphoma, but also in determining the stage and prognosis (outlook) if lymphoma is found (see “How is non-Hodgkin lymphoma staged?”).

Symptoms caused by low blood cell counts

If lymphoma cells are in the bone marrow they can crowd out the normal, healthy cells that make new blood cells. This can lead to problems like:

  • Severe or frequent infections (from low white blood cell counts)
  • Easy bruising or bleeding (from low blood platelet counts)
  • Fatigue (from low red blood cell counts: anemia)

Anemia can also occur if the lymphoma cells cause the body to destroy red blood cells (this is called hemolytic anemia).

Many symptoms of lymphoma can be caused by things other than cancer. Still, if you are having symptoms, you should see your doctor so the cause can be found.

How is non-Hodgkin lymphoma diagnosed?

Most people with non-Hodgkin lymphoma (NHL) see their doctor because they have felt a lump that hasn’t gone away, they develop some of the other symptoms of NHL (see the previous section), or they just don’t feel well and go in for a check-up.

If signs or symptoms suggest that a person might have non-Hodgkin lymphoma, exams and tests will be done to find out for certain if they do and, if so, to determine the exact type of lymphoma.

Stages of non-Hodgkin lymphoma

Once non-Hodgkin lymphoma is diagnosed, tests are done to determine the stage (extent of spread) of the disease. The treatment and prognosis (outlook) for a patient with non-Hodgkin lymphoma depend in part on the stage of the lymphoma.

Tests used to gather information for staging include:

  • Physical exam
  • Biopsies of enlarged lymph nodes or other abnormal areas
  • Blood tests
  • Imaging tests, such as CT scans
  • Bone marrow aspiration and biopsy (often but not always done)
  • Lumbar puncture (spinal tap – this may not need to be done)

These tests are described in the section “How is non-Hodgkin lymphoma diagnosed?”

 

Ann Arbor staging system

A staging system is a way for members of a cancer care team to summarize the extent of a cancer’s spread. The Ann Arbor staging system is most often used to describe the extent of non-Hodgkin lymphoma in adults.

The stages are described by Roman numerals I through IV (1-4). Lymphomas that affect an organ outside the lymph system (an extranodal organ) have E added to their stage (for example, stage IIE), while those affecting the spleen have an S added.

Stage I

Either of the following means the disease is stage I:

  • The lymphoma is in only 1 lymph node area or lymphoid organ such as the thymus (I).
  • The cancer is found only in 1 area of a single organ outside of the lymph system (IE).

Stage II

Either of the following means the disease is stage II:

  • The lymphoma is in 2 or more groups of lymph nodes on the same side of (above or below) the diaphragm (the thin band of muscle that separates the chest and abdomen). For example, this might include nodes in the underarm and neck area but not the combination of underarm and groin nodes (II).
  • The lymphoma extends from a single group of lymph node(s) into a nearby organ (IIE). It may also affect other groups of lymph nodes on the same side of the diaphragm.

Stage III

Either of the following means the disease is stage III:

  • The lymphoma is found in lymph node areas on both sides of (above and below) the diaphragm.
  • The cancer may also have spread into an area or organ next to the lymph nodes (IIIE), into the spleen (IIIS), or both (IIISE).

Stage IV

Either of the following means the disease is stage IV:

  • The lymphoma has spread outside the lymph system into an organ that is not right next to an involved node.
  • The lymphoma has spread to the bone marrow, liver, brain or spinal cord, or the pleura (thin lining of the lungs).

Other modifiers may also be used to describe the lymphoma stage:

Bulky disease

This term is used to describe tumors in the chest that are at least one-third as wide as the chest, or tumors in other areas that are at least 10 centimeters (about 4 inches) across. It is usually designated by adding the letter X to the stage. Bulky disease might need more intensive treatment.

A vs. B

Each stage may also be assigned an A or B. The letter B is added (stage IIIB, for example) if a person has any of the B symptoms listed below:

  • Loss of more than 10% of body weight over the previous 6 months (without dieting)
  • Unexplained fever of at least 101.5°F
  • Drenching night sweats

These symptoms usually mean the disease is more advanced. If a person has any of these, then more intensive treatment is usually recommended. If no B symptoms are present, the letter A is added to the stage.

Small lymphocytic lymphoma (SLL) /chronic lymphocytic leukemia (CLL)

The Ann Arbor system is most often used to stage this lymphoma if it is only in lymph nodes. But if the disease is affecting the blood or bone marrow, it is often staged using the systems for CLL. These systems are described in our document Leukemia – Chronic Lymphocytic, in the section “How is chronic lymphocytic leukemia staged?”

Treatment for non-Hodgkin lymphoma

This information represents the views of the doctors and nurses serving on the American Cancer Society’s Cancer Information Database Editorial Board. These views are based on their interpretation of studies published in medical journals, as well as their own professional experience.

The treatment information in this document is not official policy of the Society and is not intended as medical advice to replace the expertise and judgment of your cancer care team. It is intended to help you and your family make informed decisions, together with your doctor.

General treatment information

Once non-Hodgkin lymphoma has been diagnosed and staged, your cancer care team will discuss treatment options with you. Several different types of treatment can be used against non-Hodgkin lymphoma. The treatment options depend on the type of lymphoma and its stage (extent), as well as the other prognostic factors. Of course, no 2 patients are exactly alike, and standard options are often tailored to each patient’s situation.

The main types of treatment for non-Hodgkin lymphoma are:

  • Chemotherapy
  • Immunotherapy
  • Targeted therapy
  • Radiation
  • Stem cell transplant

In rare cases, surgery is also used.