Cancer starts when cells in the body begin to grow out of control. Cells in nearly any part of the body can become cancer, and can spread to other areas of the body. To learn more about how cancers start and spread, see What Is Cancer?

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

There are two types of lymphoma. They are treated differently, so it’s important to know which one you have. The information here focuses on non-Hodgkin lymphoma in adults.

For information on the other type of lymphoma, see Hodgkin Lymphoma. We also have separate information about non-Hodgkin lymphoma in children and lymphoma of the skin.

The lymph system 

To understand what lymphoma is, it helps to know about the body’s lymph system (also known as the lymphatic system). The lymph system is part of the immune system, which helps fight infections and some other diseases. The lymph system also helps fluids move through the body.

Lymphocytes

The lymph system is made up mainly of immune system cells that help the body fight infections. Most of these cells are lymphocytes, a type of white blood cell. There are 2 main types of lymphocytes:

B lymphocytes (B cells): B cells normally help protect the body against germs (bacteria or viruses) by making proteins called antibodies. The antibodies attach to the germs, marking them for destruction by other parts of the immune system.

T lymphocytes (T cells): There are several types of T cells. Some T cells destroy germs or abnormal cells in the body. Other T cells help boost or slow the activity of other immune system cells.

Non-Hodgkin lymphoma can develop from either type of lymphocyte, but B-cell lymphomas are much more common in the United States than T-cell lymphomas. Different types of lymphoma can develop from each type of lymphocyte, based on how mature the cells are when they become cancerous and other factors. 

Treatment for non-Hodgkin lymphoma depends on which type it is, so it’s important for doctors to find out the exact type of lymphoma you have.

How non-Hodgkin lymphoma starts and spreads

Lymph tissue is found in many places throughout the body, so lymphomas can start almost anywhere.

Research into the causes, prevention, and treatment of non-Hodgkin lymphoma (NHL) is being done in many medical centers throughout the world.

Genetics

Scientists are making a lot of progress in understanding how changes in the DNA inside normal lymphocytes can cause them to develop into lymphoma cells. Once this is understood, drugs may be developed that block these processes. 

Progress in understanding DNA changes in lymphoma cells has already led to improved and highly sensitive tests for detecting this disease. Some of these tests are already in use, and others are being developed. They may be used to:

• Detect lymphoma cells in a biopsy sample
• Determine what type of lymphoma a person has
• Help determine if a lymphoma is likely to grow and spread, even within a certain subtype of lymphoma
• Help figure out if a certain treatment is likely to be helpful
• Help determine if a lymphoma has been destroyed by treatment or if a relapse is likely

For example, in recent years, genetic tests have shown that there are different subtypes of diffuse large B-cell lymphoma (DLBCL), even though they look the same under the microscope. These subtypes seem to have different outcomes (prognoses) and responses to treatment. The hope is that such tests can be used to help guide treatment decisions.

Treatment

Much of the research being done on NHL is focused on looking at new and better ways to treat this disease.

Chemotherapy

Many new chemotherapy drugs are being studied in clinical trials. In recent years, these studies have led to the approval of drugs such as bendamustine (Treanda) and pralatrexate (Folotyn) for use against certain types of lymphoma. Other studies are looking at new ways to combine drugs using different doses or different sequences of drugs.

Stem cell transplants

Researchers continue to improve stem cell transplant methods, including new ways to collect the stem cells before the transplant.

Autologous transplants (which use stem cells from the patient rather than from another person) have the risk of reintroducing lymphoma cells back into the patient after treatment. Researchers are testing new and improved ways to separate out the last traces of lymphoma cells from the stem cells before they are returned to the patient. Some of the new monoclonal antibodies developed for treating lymphoma may help remove these remaining cells.

Researchers are also studying the effectiveness of non-myeloablative (reduced-intensity) stem cell transplants in people with lymphoma. This approach may allow more people to benefit from stem cell transplants, especially those who are older or otherwise in poor health.

Targeted therapies

As researchers have learned more about lymphoma cells, they have developed newer drugs that target specific parts of these cells. These targeted drugs are different from standard chemotherapy drugs, which work by attacking rapidly growing cells. Targeted drugs may work in some cases where chemotherapy doesn’t, and they often have different side effects.

Some targeted drugs, such as ibrutinib (Imbruvica) and idelalisib (Zydelig), are already being used to treat some types of NHL, and are being studied for use against other types. 

Some other targeted drugs that have shown promise against lymphoma in early studies include:

• Phosphatidyl-inositide 3 kinase (PI3K) inhibitors, such as duvelisib and copanlisib
• BCL-2 inhibitors, such as venetoclax (Venclexta)
• Janus kinase (JAK) inhibitors, such as ruxolitinib
• Tyrosine kinase inhibitors, such as crizotinib, for lymphomas that express the ALK protein.

These and many other targeted drugs are now being studied in clinical trials.

Immunotherapy

Doctors have known for some time that people’s immune systems may help fight their cancer. Scientists are now trying to develop ways to encourage this immune reaction. Some types of immunotherapy are already being used to treat lymphoma, as discussed in Immunotherapy for Non-Hodgkin Lymphoma.

Monoclonal antibodies: Lymphoma cells have certain proteins on their surface. Monoclonal antibodies can be made to target these proteins and destroy the lymphoma cells while causing little damage to normal body tissues. This treatment strategy has already proven effective. Several such drugs, including rituximab (Rituxan), are already used to treat lymphoma.

Many new monoclonal antibodies are being developed as well. One example is epratuzumab, which targets the CD22 antigen on certain lymphoma cells.

Some newer antibodies are attached to substances that can poison cancer cells, and are known as antibody-drug conjugates (ADCs) or immunotoxins. They act as homing devices to deliver the toxins directly to the cancer cells. For example: 

• Brentuximab vedotin (Adcetris) is made up of an antibody to CD30 that is attached to a cell poison. It has been shown to help treat patients with anaplastic large cell lymphoma (ALCL), and is now being studied for use against other types of lymphoma. 
• CAT-8015 (moxetumomab pasudotox) targets the CD22 antigen on certain lymphoma cells, bringing along a toxin known as PE38. An earlier version of this drug showed a great deal of promise in treating hairy cell leukemia (HCL) in early clinical trials. 

Several other ADCs are now being studied as well, including pinatuzumab vedotin and IMG529.

Immune checkpoint inhibitors: Immune system cells normally have substances that act as checkpoints to keep them from attacking other healthy cells in the body. Cancer cells sometimes take advantage of these checkpoints to avoid being attacked by the immune system. Some newer drugs, such as pembrolizumab (Keytruda) and nivolumab (Opdivo), work by blocking these checkpoints, which can boost the immune response against cancer cells. These drugs have shown promise in treating several types of cancer, and are now being studied for use against some types of lymphoma.

Chimeric antigen receptor (CAR) T-cell therapy: In this treatment, immune cells called T cells are removed from the patient’s blood and altered in the lab to have specific receptors (called chimeric antigen receptors, or CARs) on their surface. These receptors can attach to proteins on the surface of lymphoma cells. The T cells are then multiplied in the lab and given back into the patient’s blood, where they can seek out the lymphoma cells and launch a precise immune attack against them.

This technique has shown encouraging results in early clinical trials against some hard-to-treat lymphomas. Doctors are still improving how they make the T cells and are learning the best ways to use them. There is one FDA approved CAR T-cell therapy for certain kinds of advanced or recurrent large B-cell lymphoma.  CAR T-cell therapy for other types of non-Hodgkin lymphoma is only available in clinical trials at this time.

Lymphoma vaccines: Unlike vaccines against infections like measles or mumps, these vaccines are designed to help treat, not prevent, lymphomas. The goal is to create an immune reaction against lymphoma cells in patients who have very early disease or in patients whose disease is in remission. One possible advantage of these types of treatments is that they seem to have very limited side effects. So far, there have been a few successes with this approach, and it’s a major area of research in lymphoma treatment. At this time, lymphoma vaccines are only available in clinical trials. 

Antibiotics

Some types of lymphoma are strongly linked to infections. Researchers are finding that in some cases, treating the infection actually helps treat the lymphoma. For example, gastric MALT lymphoma, which is linked to infection by the bacteria Helicobacter pylori, can often be treated with antibiotics. MALT lymphoma of the tissues around the eye (called ocular adnexal marginal zone lymphoma) has been linked to infection with the bacterium Chlamydophila psittaci. Some research has shown that treating this infection with an antibiotic (doxycycline) might make this lymphoma get better or even go away. More studies may be needed before antibiotics become part of the standard treatment for this type of lymphoma. 

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, or they just don’t feel well and go in for a check-up.

If you have signs or symptoms that suggest you might have lymphoma, exams and tests will be done to find out for sure and, if so, to determine the exact type of lymphoma.

Medical history and physical exam

Your doctor will want to get a thorough medical history, including information about your symptoms, possible risk factors, and other medical conditions. 

Next, the doctor will examine you, paying special attention to the lymph nodes and other areas of the body that might be affected, including the spleen and liver. Because infections are the most common cause of enlarged lymph nodes, the doctor will look for an infection in the part of the body near the swollen lymph nodes. 

The doctor also might order blood tests to look for signs of infection or other problems. If the doctor suspects that lymphoma might be causing your symptoms, he or she might recommend a biopsy of a swollen lymph node or other affected area.

Biopsy

Many symptoms of NHL can also be caused by other problems, like an infection, or by other kinds of cancer. 

For example, enlarged lymph nodes are more often caused by infections than by lymphoma. Because of this, doctors often prescribe antibiotics and wait a few weeks to see if the nodes shrink. If the nodes stay the same or continue to grow, the doctor might order a biopsy. Either a small piece of a node or, more commonly, the entire node is removed for viewing under the microscope and for other lab tests.

A biopsy might be needed right away if the size, texture, or location of a lymph node or the presence of other symptoms strongly suggests lymphoma.

Biopsies to diagnose non-Hodgkin lymphoma

A biopsy is the only way to confirm a person has NHL. There are several types of biopsies. Doctors choose which one to use based on each person’s situation.

Excisional or incisional biopsy: This is the preferred and most common type of biopsy if lymphoma is suspected. In this procedure, a surgeon cuts through the skin to remove the lymph node. 

• If the doctor removes the entire lymph node, it is called an excisional biopsy. 
• If a small part of a larger tumor or node is removed, it is called an incisional biopsy. 

If the enlarged node is just under the skin, this is a fairly simple operation that can often be done with local anesthesia (numbing medicine). But if the node is inside the chest or abdomen, the patient will be sedated or given general anesthesia (drugs are used to put the patient into a deep sleep). This method almost always provides enough of a sample to diagnose the exact type of non-Hodgkin lymphoma.

Needle biopsy: Needle biopsies are less invasive than excisional or incisional biopsies, but the drawback is that they might not remove enough of a sample to diagnose lymphoma (or to determine which type it is). There are 2 main types of needle biopsies:

• In a fine needle aspiration (FNA) biopsy, the doctor uses a very thin, hollow needle attached to a syringe to withdraw (aspirate) a small amount of tissue from an enlarged lymph node or a tumor mass. 
• For a core needle biopsy, the doctor uses a larger needle to remove a slightly larger piece of tissue.

To biopsy an enlarged node just under the skin, the doctor can aim the needle while feeling the node. If the node or tumor is deep inside the body, the doctor can guide the needle using a computed tomography (CT) scan or ultrasound (see descriptions of imaging tests later in this section).

Most doctors do not use needle biopsies to diagnose lymphoma. But if the doctor suspects that your lymph node is enlarged because of an infection or by the spread of cancer from another organ (such as the breast, lungs, or thyroid), a needle biopsy may be the first type of biopsy done. An excisional biopsy might still be needed to diagnose and classify lymphoma, even after a needle biopsy has been done.

If lymphoma has already been diagnosed, needle biopsies are sometimes used to check abnormal areas in other parts of the body that might be from the lymphoma spreading or coming back after treatment.

Other types of biopsies

These procedures are not normally done to diagnose lymphoma, but they might be used to help determine the stage (extent) of a lymphoma that has already been diagnosed. 

Bone marrow aspiration and biopsy: These procedures are often done after lymphoma has been diagnosed to help determine if it has reached the bone marrow. The 2 tests are often done at the same time. The samples are usually taken from the back of the pelvic (hip) bone, although in some cases they may be taken from other bones.

For a bone marrow aspiration, you lie on a table (either on your side or on your belly). After cleaning the skin over the hip, the doctor numbs the area and the surface of the bone with local anesthetic, which can cause a brief stinging or burning sensation. A thin, hollow needle is then inserted into the bone and a syringe is used to suck out a small amount of liquid bone marrow. Even with the anesthetic, most patients still have some brief pain when the marrow is removed.

A bone marrow biopsy is usually done just after the aspiration. A small piece of bone and marrow is removed with a slightly larger needle that is pushed into the bone. The biopsy can also cause some brief pain.

Lumbar puncture (spinal tap): This test looks for lymphoma cells in the cerebrospinal fluid (CSF), which is the liquid that bathes the brain and spinal cord. Most people with lymphoma will not need this test. But doctors may order it for certain types of lymphoma or if a person has symptoms that suggest the lymphoma may have reached the brain.

For this test, you may lie on your side or sit up. The doctor first numbs an area in the lower part of your back over the spine. A small, hollow needle is then placed between the bones of the spine to withdraw some of the fluid. 

Pleural or peritoneal fluid sampling: Lymphoma that has spread to the chest or abdomen can cause fluid to build up. Pleural fluid (inside the chest) or peritoneal fluid (inside the abdomen) can be removed by placing a hollow needle through the skin into the chest or abdomen.

• When this procedure is used to remove fluid from the area around the lung, it’s called a thoracentesis. 
• When it is used to collect fluid from inside the abdomen, it’s known as a paracentesis. 

The doctor uses a local anesthetic to numb the skin before inserting the needle. The fluid is then withdrawn and looked at under the microscope to check for lymphoma cells. 

Lab tests on biopsy samples

All biopsy samples and fluids are looked at under a microscope by a pathologist (a doctor specially trained to recognize cancer cells). The size and shape of the cells and how they are arranged may show not only if the person has a lymphoma, but also what type of lymphoma it is. But usually other types of lab tests are needed as well. 

Flow cytometry and immunohistochemistry: For both flow cytometry and immunohistochemistry, samples of cells are treated with antibodies that stick to certain proteins on cells. For imunohistochemistry, the cells are then looked at under a microscope to see if the antibodies stuck to them (meaning they have these proteins), For flow cytometry, a special machine is used to look for the antibodies.

These tests can help determine whether a lymph node is swollen because of lymphoma, some other cancer, or a non-cancerous disease. The tests can also be used for immunophenotyping – determining which type of lymphoma a person has, based on certain proteins in or on the cells. Different types of lymphocytes have different proteins on their surface, which correspond to the type of lymphocyte and how mature it is.

Chromosome tests: Normal human cells have 23 pairs of chromosomes (strands of DNA), each of which is a certain size and looks a certain way under the microscope. But in some types of lymphoma, the cells have changes in their chromosomes, such as having too many, too few, or abnormal chromosomes. These changes can often help identify the type of lymphoma.

• Cytogenetics: In this lab test, the cells are looked at under a microscope to see if the chromosomes have any abnormalities. A drawback of this test is that it usually takes about 2 to 3 weeks because the cells must grow in lab dishes for a couple of weeks before their chromosomes are ready to be viewed under the microscope. 
• Fluorescent in situ hybridization (FISH): This test looks more closely at lymphoma cell DNA using special fluorescent dyes that only attach to specific genes or parts of chromosomes. FISH can find most chromosome changes that can be seen in standard cytogenetic tests, as well as some gene changes too small to be seen with cytogenetic testing. FISH is very accurate and can usually provide results within a couple of days, which is why this test is now used in many medical centers.
• Polymerase chain reaction (PCR): PCR is a very sensitive DNA test that can find gene changes and certain chromosome changes too small to be seen with a microscope, even if very few lymphoma cells are present in a sample.

Imaging tests

Imaging tests use x-rays, sound waves, magnetic fields, or radioactive particles to produce pictures of the inside of the body. These tests might be done for a number of reasons, including:

• To look for possible causes of certain symptoms (such as enlarged lymph nodes in the chest in someone having chest pain or trouble breathing)
• To help determine the stage (extent) of the lymphoma
• To help show if treatment is working
• To look for possible signs of lymphoma coming back after treatment

Chest x-ray

The chest might be x-rayed to look for enlarged lymph nodes in this area.

Computed tomography (CT) scan

A CT scan combines many x-rays to make detailed, cross-sectional images of your body. This scan can help tell if any lymph nodes or organs in your body are enlarged. CT scans are useful for looking for lymphoma in the abdomen, pelvis, chest, head, and neck.

CT-guided needle biopsy: A CT can also be used to guide a biopsy needle into a suspicious area. For this procedure, you lie on the CT scanning table while the doctor moves a biopsy needle through the skin and toward the area. CT scans are repeated until the needle is in the right place. A biopsy sample is then removed to be looked at under a microscope.

Magnetic resonance imaging (MRI) scan

Like CT scans, MRI scans show detailed images of soft tissues in the body. But MRI scans use radio waves and strong magnets instead of x-rays. This test is not used as often as CT scans for lymphoma, but if your doctor is concerned about spread to the spinal cord or brain, MRI is very useful for looking at these areas.

Ultrasound

Ultrasound uses sound waves and their echoes to create pictures of internal organs or masses. In the most common type of ultrasound, a small, microphone-like instrument called a transducer is placed on the skin (which is first lubricated with a gel). It gives off sound waves and picks up the echoes as they bounce off the organs. The echoes are converted by a computer into an image on a computer screen. 

Ultrasound can be used to look at lymph nodes near the surface of the body or to look inside your abdomen for enlarged lymph nodes or organs such as the liver and spleen. It can also detect kidneys that have become swollen because the outflow of urine has been blocked by enlarged lymph nodes. (It can’t be used to look at lymph nodes in the chest because the ribs block the sound waves.)

Positron emission tomography (PET) scan

For a PET scan, you are injected with a slightly radioactive form of sugar, which collects mainly in cancer cells. A special camera is then used to create a picture of areas of radioactivity in the body. The picture is not detailed like a CT or MRI scan, but it can provide helpful information about your whole body.

PET scans can be used for many reasons in a person with lymphoma:

• They can help tell if an enlarged lymph node contains lymphoma. 
• They can help spot small areas in the body that might be lymphoma, even if the area looks normal on a CT scan.
• They can help tell if a lymphoma is responding to treatment. Some doctors will repeat the PET scan after 1 or 2 courses of chemotherapy. If the chemotherapy is working, the lymph nodes will no longer take up the radioactive sugar.
• They can be used after treatment in helping decide whether an enlarged lymph node still contains lymphoma or is just scar tissue.

PET/CT scan: Some machines can do both a PET scan and a CT scan at the same time. This lets the doctor compare areas of higher radioactivity on the PET scan with the more detailed appearance of that area on the CT scan. PET/CT scans can often help pinpoint the areas of lymphoma better than a CT scan alone.

Bone scan

This test is not usually done unless a person is having bone pain or has lab test results that suggest the lymphoma may have reached the bones.

For bone scans, a radioactive substance called technetium is injected into a vein. It travels to damaged areas of bone, and a special camera can then detect the radioactivity. Lymphoma often causes bone damage, which may be picked up on a bone scan. But bone scans can’t show the difference between cancers and non-cancerous problems, such as arthritis and fractures, so further tests might be needed. 

Other tests

Blood tests

Blood tests measure the amounts of certain types of cells and chemicals in the blood. They are not used to diagnose lymphoma, but they can sometimes help determine how advanced the lymphoma is. 

• A complete blood count (CBC) measures the levels of different cells in the blood. For a person already known to have lymphoma, low blood cell counts might mean that the lymphoma is growing in the bone marrow and affecting new blood cell formation. 
• Blood chemistry tests are often done to look at kidney and liver function. 
• If lymphoma has been diagnosed, the lactate dehydrogenase (LDH) level may be checked. LDH levels are often increased in patients with lymphomas. 
• For some types of lymphoma or if certain treatments might be used, your doctor may also advise you to have tests to see if you’ve been infected with certain viruses, such as hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV). Infections with these viruses may affect your treatment.

Tests of heart and lung function

These tests are not used to diagnose lymphoma, but they might be done if you are going to get certain chemotherapy drugs commonly used to treat lymphoma that could affect the heart or the lungs. 

• Your heart function may be checked with an echocardiogram (an ultrasound of the heart) or a MUGA scan.
• Your lung function may be checked with pulmonary function tests, in which you breathe into a tube connected to a machine.

After someone is diagnosed with Non-Hodgkin Lymphoma, doctors will try to figure out if it has spread, and if so, how far. This process is called staging. The stage of a cancer describes how much cancer is in the body. It helps determine how serious the cancer is and how best to treat it. Doctors also use a cancer's stage when talking about survival statistics.

Tests used to gather information for staging can include:

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

In general, the results of imaging tests such as PET or CT scans are the most important when determining the stage of the lymphoma. 

Lugano classification

A staging system is a way for members of a cancer care team to sum up the extent of a cancer’s spread. The current staging system for NHL in adults is known as the Lugano classification, which is based on the older Ann Arbor system.

The stages are described by Roman numerals I through IV (1-4). Limited stage (I or II) lymphomas that affect an organ outside the lymph system (an extranodal organ) have an E added (for example, stage IIE).

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 tonsils (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 is in a group of lymph node(s) and in one area of 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 in lymph node areas on both sides of (above and below) the diaphragm.
• The lymphoma is in lymph nodes above the diaphragm, as well as in the spleen.

Stage IV

The lymphoma has spread widely into at least one organ outside the lymph system, such as the bone marrow, liver, or lung.

Bulky disease

This term is often used to describe large tumors in the chest. It is especially important for stage II lymphomas, as bulky disease might need more intensive treatment.

Staging small lymphocytic lymphoma (SLL)/chronic lymphocytic leukemia (CLL)

The system above 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. See Chronic Lymphocytic Leukemia Stages.

How staging might affect treatment

The stage of a lymphoma is often important when determining a person’s treatment options, but it is more important for some types of lymphoma than for others. For many of the more common types of NHL, treatment is based in part on whether the lymphoma is “limited” (stage I or stage II non-bulky) or “advanced” (stage III or IV). For stage II bulky lymphomas, certain other factors (known as prognostic factors) are used to help determine if the lymphoma should be treated as limited or advanced. 

For some other types of NHL, such as fast-growing lymphomas like Burkitt lymphoma, the stage is less important when deciding on treatment. 

See Treating B-cell Non-Hodgkin Lymphomas and Treating T-cell Non-Hodgkin Lymphomas for more on this.

Non-Hodgkin lymphoma (NHL) can cause many different signs and symptoms, depending on the type of lymphoma and where it is in the body. Sometimes it might not cause any symptoms until it grows quite large. Some common signs and symptoms include:

• Enlarged lymph nodes
• Fever
• Sweating and chills
• Weight loss
• Fatigue (extreme tiredness)
• Swollen abdomen (belly)
• Feeling full after only a small amount of food
• Chest pain or pressure
• Shortness of breath or cough

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 usually not painful. 

Although enlarged lymph nodes are a common symptom of lymphoma, they are much more often caused by infections. Lymph nodes that grow in reaction to infection are called reactive nodes or hyperplastic nodes and are often tender to the touch.

General symptoms

Non-Hodgkin lymphoma often causes general symptoms, such as:

• Fever
• Sweating and chills, especially at night
• Unexplained weight loss
• Feeling very tired
• Severe or frequent infections
• Easy bruising or bleeding

Symptoms from lymphoma in the abdomen

Lymphomas that start or grow in the abdomen (belly) can cause swelling or pain in the abdomen. This could be from lymph nodes or organs such as the spleen or liver enlarging, but it can also be caused by the build-up of large amounts of fluid. 

An enlarged spleen might press on the stomach, which can cause a loss of appetite and feeling full after only a small meal.

Lymphomas in the stomach or intestines can cause abdominal pain, nausea, or vomiting. 

Symptoms from 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, trouble breathing, or 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 is called SVC syndrome. It can be life-threatening and must be treated right away.

Symptoms from 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.

Symptoms from lymphoma in the skin 

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

Having one or more of the symptoms above doesn’t mean you definitely have lymphoma. In fact, many of these symptoms are more likely to be caused by other conditions, such as an infection. Still, if you have any of these symptoms, have them checked by a doctor so that the cause can be found and treated, if needed.

Cancer survivors can be affected by a number of health problems, but often a major concern is facing cancer again. If a cancer comes back after treatment it is called a recurrence. But some cancer survivors may develop a new, unrelated cancer later. This is called a second cancer. 

People who have had non-Hodgkin lymphoma (NHL) can get any type of second cancer, but they have an increased risk of certain cancers, including:

• Melanoma skin cancer
• Lung cancer
• Kidney cancer
• Kaposi sarcoma
• Cancers of the head/neck area (includes the lip, tongue, floor of the mouth, throat, salivary glands, and voice box)
• Colon cancer
• Thyroid cancer
• Bone and soft tissue cancer
• Bladder cancer
• Leukemia and myelodysplastic syndrome
• Hodgkin disease

Radiation therapy to the chest increases the risk of breast cancer in women who were treated before age 30. Mesothelioma, a rare cancer of the outer lining of the lung, is also increased in those who were treated with chest radiation.

Follow-up after treatment

After completing treatment for NHL, you should still see your doctor regularly and may have tests to look for signs that the cancer has come back. Let your doctors know if you have any new symptoms or problems, as they could be due to the lymphoma coming back or from a new disease or cancer.

Women who were treated with chest radiation prior to the age of 30 have an increased risk of breast cancer. The American Cancer Society recommends yearly breast MRIs in addition to mammograms and clinical breast exams beginning at age 30 for these women.

The Children’s Oncology Group has guidelines for the follow-up of patients treated for cancer as a child, teen, or young adult, including screening for second cancers. These can be found at www.survivorshipguidelines.org.

Lymphoma survivors should also follow the American Cancer Society recommendations for the early detection of cancer, such as those for colorectal, lung, and breast cancer. Most experts don’t recommend any other testing to look for second cancers unless you have symptoms.

Can I lower my risk of getting a second cancer?

There are steps you can take to lower your risk and stay as healthy as possible. For example, it’s important to stay away from tobacco products. Smoking increases the risk of many cancers, including some of the second cancers seen in people who have had lymphoma.

To help maintain good health, lymphoma survivors should also:

• Get to and stay at a healthy weight
• Stay physically active
• Eat a healthy diet, with an emphasis on plant foods
• Limit alcohol to no more than 1 drink per day for women or 2 per day for men

These steps may also lower the risk of some other health problems.

See Second Cancers in Adults for more information about causes of second cancers.

It’s important to have honest, open discussions with your cancer care team. You should feel free to ask any question, no matter how minor it might seem. For instance, consider these questions:

When you’re told you have non-Hodgkin lymphoma

• What type of non-Hodgkin lymphoma do I have?
• Has my biopsy been reviewed by a pathologist who’s an expert on lymphoma?
• Do I need any other tests before we can decide on treatment?
• Do I need to see any other types of doctors?
• What’s the stage (extent) of the lymphoma? What does that mean in my case?
• Are there other factors that could affect my treatment options?
• If I’m concerned about the costs and insurance coverage for my diagnosis and treatment, who can help me?

When deciding on a treatment plan

• How much experience do you have treating this type of lymphoma?
• What are my treatment options? What do you recommend, and why?
• Do we need to treat the lymphoma right away?
• Should I get a second opinion before starting treatment? Can you suggest a doctor or cancer center?
• What should I do to be ready for treatment?
• How long will treatment last? What will it be like? Where will it be done?
• What risks or side effects are there to the treatments you suggest?
• How might treatment affect my daily activities?
• What’s my outlook for survival?
• What are the chances of the lymphoma coming back with these treatment plans?
• What would we do if the treatment doesn’t work or if the lymphoma comes back?

During treatment

Once treatment begins, you’ll need to know what to expect and what to look for. Not all of these questions may apply to you, but getting answers to the ones that do may be helpful.

• How will we know if the treatment is working?
• Is there anything I can do to help manage side effects?
• What symptoms or side effects should I tell you about right away?
• How can I reach you on nights, holidays, or weekends?
• Are there any limits on what I can do? 
• Can you suggest a mental health professional I can see if I start to feel overwhelmed, depressed, or distressed?

After treatment

• What type of follow-up will I need after treatment?
• What symptoms should I watch for?
• How will we know if the lymphoma has come back? What would my options be if that happens?

Along with these sample questions, be sure to write down some of your own. For instance, you might want more information about recovery times so that you can plan your work or activity schedule. Or you may want to ask about clinical trials for which you qualify. 

Keep in mind that doctors aren’t the only ones who can give you information. Other health care professionals, such as nurses and social workers, can answer some of your questions. To find out more about communicating with your health care team, see The Doctor-Patient Relationship.

Non-Hodgkin lymphoma (NHL) is one of the most common cancers in the United States, accounting for about 4% of all cancers. The American Cancer Society’s most recent estimates for non-Hodgkin’s lymphoma are for 2018:

• About 74,680 people (41,730 males and 32,950 females) will be diagnosed with NHL. This includes both adults and children.
• About 19,910 people will die from this cancer (11,510 males and 8,400 females).

The average American’s risk of developing NHL during his or her lifetime is about 1 in 47. But each person’s risk can be affected by a number of risk factors.

NHL can occur at any age. In fact, it is one of the more common cancers among children, teens, and young adults. Still, the risk of developing NHL increases throughout life, and more than half of patients are 65 or older at the time of diagnosis. The aging of the American population is likely to lead to an increase in NHL cases during the coming years. 

Visit the American Cancer Society’s Cancer Statistics Center for more key statistics.

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 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. 

Researchers have found several factors that can affect a person’s chance of getting non-Hodgkin lymphoma (NHL). 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 NHL is higher in men than in women, but there are certain types of NHL 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 NHL.

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

Exposure to certain chemicals and drugs

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

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

Some studies have suggested that certain drugs used to treat rheumatoid arthritis (RA), such as methotrexate and the tumor necrosis factor (TNF) inhibitors, might increase the risk of NHL. But other studies have not found an increased risk. Determining if these drugs increase risk is complicated by the fact that people with RA, which is an autoimmune disease, already have a higher risk of NHL (see below). 

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 NHL, leukemia,and thyroid cancer.

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

Having a weakened immune system

People with weakened immune systems have an increased risk for NHL. For example: 

• People who receive organ transplants 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 NHL. 
• The human immunodeficiency virus (HIV) can weaken the immune system, and people infected with HIV are at increased risk of NHL. 
• In some genetic (inherited) syndromes, such as ataxia-telangiectasia (AT) and Wiskott-Aldrich syndrome, children are born with a deficient immune system. Along with an increased risk of serious infections, these children also have a higher risk of developing NHL.

Autoimmune diseases

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

In autoimmune diseases, the immune system mistakenly 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 NHL in different ways.

Infections that directly transform lymphocytes

Some viruses can directly affect the DNA of lymphocytes, helping to transform them into cancer cells:

• Infection with human T-cell lymphotropic virus (HTLV-1) increases a person’s risk of certain types of T-cell lymphoma. This virus is most common in some parts of Japan and in the Caribbean region, but it’s found throughout the world. In the United States, it causes less than 1% of lymphomas. HTLV-1 spreads through sex and contaminated blood and can be passed to children through breast milk from an infected mother.
• Infection with the Epstein-Barr virus (EBV) is an important risk factor for Burkitt lymphoma in some parts of Africa. In developed countries such as the United States, EBV is more often linked with lymphomas in people also infected with HIV, the virus that causes AIDS. EBV has also been linked with some less common types of lymphoma.
• Human herpes virus 8 (HHV-8) can also infect lymphocytes, leading to a rare type of lymphoma called primary effusion lymphoma. This lymphoma is most often seen in patients who are infected with HIV. HHV-8 infection is also linked to another cancer, Kaposi sarcoma. For this reason, another name for this virus is Kaposi sarcoma-associated herpes virus (KSHV).

Infections that weaken the immune system

Infection with human immunodeficiency virus (HIV), also known as the AIDS virus, can weaken the immune system. HIV infection is a risk factor for developing certain types of NHL, such as primary CNS lymphoma, Burkitt lymphoma, and diffuse large B-cell lymphoma.

Infections that cause chronic immune stimulation

Some long-term infections may increase a person’s risk of lymphoma by forcing their immune system to be constantly active. As more lymphocytes are made to fight the infection, there is a greater chance for mutations in key genes to occur, which might eventually lead to lymphoma. Some of the lymphomas linked with these infections actually get better when the infection is treated.

• Helicobacter pylori, a type of bacteria known to cause stomach ulcers, has also been linked to mucosa-associated lymphoid tissue (MALT) lymphoma of the stomach. 
• Chlamydophila psittaci (formerly known as Chlamydia psittaci) is a type of bacteria that can cause a lung infection called psittacosis. It has been linked to MALT lymphoma in the tissues around the eye (called ocular adnexal marginal zone lymphoma).
• Infection with the bacterium Campylobacter jejuni has been linked to a type of MALT lymphoma called immunoproliferative small intestinal disease. This type of lymphoma, which is also sometimes called Mediterranean abdominal lymphoma, typically occurs in young adults in eastern Mediterranean countries.
• Long-term infection with the hepatitis C virus (HCV) seems to be a risk factor for certain types of lymphoma, such as splenic marginal zone lymphoma.

Body weight and diet

Some studies have suggested that being overweight or obese may increase your risk of NHL. Other studies have suggested that a diet high in fat and meats may raise your risk. More research is needed to confirm these findings. In any event, staying at a healthy weight and eating a healthy diet have many known health benefits outside of the possible effect on lymphoma risk.

Breast implants

Although it is rare, some women with breast implants develop a type of anaplastic large cell lymphoma (ALCL) in their breast. This seems to be more likely with implants that have textured surfaces (as opposed to smooth surfaces).

Researchers have found that non-Hodgkin lymphoma (NHL) is linked with a number of risk factors, but the cause of most lymphomas is not known. 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. DNA is the chemical in our cells that makes up our genes, which control how our cells function. We look like our parents because they are the source of our DNA. But DNA affects more than just how we look. 

Some genes control when cells grow, divide, and die:

• Genes that help cells grow, divide, and stay alive are called oncogenes. 
• Genes that help keep cell division under control or make cells die at the right time are called tumor suppressor genes. 

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 NHL is not one of the cancer types often caused by these inherited mutations. In other words, having a family history of lymphoma does not seem to increase your risk of lymphoma.

Gene changes related to NHL are usually acquired during life, rather than being inherited. Acquired gene changes can 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, which might help explain why most lymphomas are seen in older people.

For some types of lymphoma, some of the gene changes that led to the lymphoma are now known. For example, in follicular lymphoma, the cells often have an exchange of DNA (known as a translocation) between chromosomes 14 and 18, which turns on the BCL-2 oncogene. (Chromosomes are long strands of DNA in each cell.) This oncogene 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 the different types of NHL. 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.

While researchers are beginning to understand some of the gene changes that can lead to NHL, they still do not know why many of these gene changes develop, especially 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, treatment with certain drugs, organ transplants, or HIV infection) have a much higher chance of developing lymphoma than people without a weakened immune system.
• People with certain autoimmune diseases (where the immune system constantly attacks a certain part of the body) have an increased risk of 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.

There is no sure way to prevent non-Hodgkin lymphoma (NHL). Most people with NHL 
have no risk factors that can be changed, so there is no way to protect against these lymphomas. But there are some things you can do that might lower your risk for NHL, such as limiting your risk of certain infections and doing what you can to maintain a healthy immune system.

Infection with HIV, the virus that causes AIDS, is known to increase the risk NHL, so one way to limit your risk is to avoid known risk factors for HIV, such as intravenous drug use or unprotected sex with many partners. You can read more about HIV infection in HIV, AIDS, and Cancer.

Preventing the spread of the human T-cell lymphotropic 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 with H. 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.

Some lymphomas are caused by treatment of other 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.

Screening tests or exams are used to look for a disease in people who have no symptoms. At this time, there are no widely recommended screening tests for non-Hodgkin lymphoma (NHL). This is because no screening test has been shown to lower the risk of dying from this cancer. Still, in some cases lymphoma can be found early. 

The best way to find lymphoma early is to pay attention to possible signs and symptoms. One of the most common symptoms is enlargement of one or more lymph nodes, causing a lump or bump under the skin which is usually not painful. This is most often on the side of the neck, in the armpit, or in the groin. 

Other symptoms can include fever, night sweats, weight loss, feeling tired, and swelling in the abdomen. More often these symptoms are caused by something other than lymphoma, but it’s important to have them checked by a doctor, especially if they don’t go away or get worse.

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

For many people with non-Hodgkin lymphoma, treatment can destroy the lymphoma. Completing treatment can be both stressful and exciting. You may be relieved to finish treatment, but find it hard not to worry about the lymphoma coming back. (When cancer comes back after treatment, it is called recurrence.) This is a very common worry if you’ve had cancer.

For some people, the lymphoma may never go away completely. These people may get regular treatments with chemo, radiation, or other therapies to help keep the lymphoma in check for as long as possible and to help relieve symptoms. Learning to live with lymphoma that doesn’t go away can be difficult and very stressful.

Follow-up care

There are many types of non-Hodgkin lymphomas, which can require different treatments and can have very different outlooks. Your care after treatment will depend on the type of lymphoma you have, what type of treatment you receive, and how well treatment works.

Even if you’ve completed treatment, your doctors will still want to watch you closely. It’s very important to go to all of your follow-up appointments, because lymphoma can sometimes come back even many years after treatment.

Some treatment side effects might last a long time or might not even show up until years after you have finished treatment. Your doctor visits are a good time to ask questions and talk about any changes or problems you notice or concerns you have.

Exams and tests

During your follow-up visits, your doctor will ask you about any symptoms you are having, examine you, and may order blood or imaging tests. Your doctor will probably want to see you regularly, usually every few months for the first year or so and gradually less often after that.

Imaging tests may be done, based on the type, location, and stage of lymphoma. For example, CT scans or PET/CT scans may be used to monitor the size of any remaining tumors, or to look for possible new tumors.

You may need frequent blood tests to check that you have recovered from treatment and to look for possible signs of problems such as lymphoma recurrence. Blood counts can also sometimes become abnormal because of a disease of the bone marrow called myelodysplasia, which can sometimes lead to leukemia. Some chemotherapy drugs can cause this disease. For more on this, see Myelodysplastic Syndromes. It’s also possible for a person to develop leukemia a few years after being treated for lymphoma.

Ask your doctor for a survivorship care plan

Talk with your doctor about developing a survivorship care plan for you. This plan might include:

• A suggested schedule for follow-up exams and tests
• A schedule for other tests you might need in the future, such as early detection (screening) tests for other types of cancer, or tests to look for long-term health effects from your cancer or its treatment
• A list of possible late- or long-term side effects from your treatment, including what to watch for and when you should contact your doctor
• Diet and physical activity suggestions

Keeping health insurance and copies of your medical records

Even after treatment, it’s very important to keep health insurance. Tests and doctor visits cost a lot, and even though no one wants to think of their cancer coming back, this could happen.

At some point after your treatment, you might find yourself seeing a new doctor who doesn’t know about your medical history. It’s important to keep copies of your medical records to give your new doctor the details of your diagnosis and treatment. Learn more in Keeping Copies of Important Medical Records.

Can I lower my risk of the lymphoma progressing or coming back?

If you have (or have had) lymphoma, you probably want to know if there are things you can do that might lower your risk of the lymphoma growing or coming back, such as exercising, eating a certain type of diet, or taking nutritional supplements. Unfortunately, it’s not yet clear if there are things you can do that will help.

Adopting healthy behaviors such as not smoking, eating well, getting regular physical activity, and staying at a healthy weight might help, but no one knows for sure. However, we do know that these types of changes can have positive effects on your health that can extend beyond your risk of lymphoma or other cancers.

About dietary supplements

So far, no dietary supplements (including vitamins, minerals, and herbal products) have been shown to clearly help lower the risk of lymphoma progressing or coming back. This doesn’t mean that no supplements will help, but it’s important to know that none have been proven to do so.

Dietary supplements are not regulated like medicines in the United States – they do not have to be proven effective (or even safe) before being sold, although there are limits on what they’re allowed to claim they can do. If you’re thinking about taking any type of nutritional supplement, talk to your health care team. They can help you decide which ones you can use safely while avoiding those that might be harmful.

If the lymphoma comes back

If the lymphoma does come back at some point, your treatment options will depend on the type of lymphoma, where it is, what treatments you’ve had before, how long it’s been since treatment, and your current health and preferences.

For more general information on dealing with a recurrence, see Coping With Cancer Recurrence.

Could I get a second cancer after treatment?

People who’ve had non-Hodgkin lymphoma can still get other cancers. In fact, lymphoma survivors are at higher risk for getting some other types of cancer. Learn more in Second Cancers After Non-Hodgkin Lymphoma.

Getting emotional support

Some amount of feeling depressed, anxious, or worried is normal when lymphoma is a part of your life. Some people are affected more than others. But everyone can benefit from help and support from other people, whether friends and family, religious groups, support groups, professional counselors, or others. Learn more in Life After Cancer.