Non-Hodgkin Lymphoma


Non-Hodgkin lymphoma (NHL) is cancer that begins in lymphocytes, white blood cells that are an important part of the body’s infection-fighting immune system. 

Seattle Cancer Care Alliance (SCCA) offers comprehensive treatment from a team of experts for all types of non-Hodgkin as well as Hodgkin lymphoma.

What is non-Hodgkin lymphoma?

In people with lymphoma, something goes wrong inside the lymphocytes.

  • Lymphocytes are a type of white blood cell made in the bone marrow and found in the blood and lymph tissue.
  • In lymphoma, the lymphocytes don’t mature and can’t carry out their normal immune functions defending against infection. 
  • The lymphoma cells don’t die off like they should but instead collect in the lymph nodes. 
  • NHL can spread through the lymph system to other lymph nodes and outside the lymph nodes to the bone marrow, lungs or liver.
  • NHL can be cured or controlled for many years in many people who have the disease.
How common is NHL?

NHL is one of the most common cancers in the United States, with about 72,000 people newly diagnosed each year.

What causes NHL?

Doctors do not know what causes NHL. It is more common in men than in women, and the risk increases with age. 

You may be at higher risk if any of these is true:

  • Your immune system is weakened by an inherited disease, autoimmune disease, human immunodeficiency virus (HIV) or drugs given because you had an organ transplant.
  • You have been infected with human T-lymphotropic virus type I (HTLV-1), Epstein-Barr virus (which causes mononucleosis), Helicobacter pylori (a bacterium that causes ulcers) or hepatitis C virus.
  • You were exposed to certain chemicals, such as ingredients in pesticides, herbicides, solvents or fertilizers.

Keep in mind that many people who get the disease have none of these risk factors, and most people with these risk factors do not develop the disease.

Your lymph system

To understand lymphoma, it helps to have a basic knowledge of the lymph system. 

What is the lymph system?

The lymph system is a network of tubes (lymphatic vessels) that slowly carry fluid from your tissues into your bloodstream to be recycled. The fluid (lymph) contains waste products from body tissues as well as immune system cells.

What are lymph nodes?

Lymph nodes are small bean-shaped organs linked by your lymphatic vessels. They are part of your immune system. They store lymphocytes and act as filters to trap foreign particles. 

Where are these nodes?

Lymph nodes are located throughout your body in your neck, underarms and groin and behind your knees. They are also deeper inside your body in your chest, abdomen and pelvic area.

What else makes up the lymph system?

Along with lymph nodes, you have other lymph tissue, including organs related to your immune and blood-forming systems, such as your spleen, thymus and bone marrow.

How do lymphocytes protect the body?

There are several types of lymphocytes. 

  • B lymphocytes, or B cells. These make antibodies. Antibodies attach to bacteria and to cells infected with a virus or bacteria so that other immune cells recognize them and know to destroy them.
  • T lymphocytes, or T cells. These are involved in destroying invaders or tumor cells or in attracting or stimulating other immune cells to do this.
  • Natural killer cells. These scout for abnormal cells and destroy them.


It’s important to correctly identify the type and subtype of your lymphoma to determine which treatments are most likely to be effective. 

There are two main types of lymphoma: 

  • Hodgkin lymphoma, which involves Reed-Sternberg cells, abnormal B cells
  • Non-Hodgkin lymphoma, in which there are no Reed-Sternberg cells

Within NHL, there are about 60 types and subtypes based on: 

  • Whether the disease originates from B cells or T cells
  • Whether it is fast or slow growing
  • How and where the cells grow in the body
  • The genetic characteristics and other molecular features of the cells affected
  • Their appearance under a microscope
B-cell lymphoma or T-cell lymphoma?

Most NHLs — about 90 percent — begin in the B cells. The most common subtype of B-cell lymphoma is diffuse large B-cell lymphoma, but there are several other NHL B-cell subtypes.

About 10 percent of NHLs begin in the T cells. In some of these, natural killer cells are also involved. These are called NK/T-cell lymphomas. Read more about NHL T-cell subtypes.

Cutaneous lymphoma, a rare NHL, may be either B-cell or T-cell type. It occurs mainly in the skin but may involve lymph nodes, blood and other organs.

Indolent lymphoma or aggressive lymphoma?

NHLs are often described by how quickly they grow. 

  • Indolent (low-grade) NHL tends to grow slowly and cause fewer symptoms. The most common indolent subtype is follicular lymphoma. Over time, indolent NHL may transform into aggressive NHL.
  • Aggressive (high-grade) NHL tends to grow and spread quickly and cause severe symptoms. The most common aggressive subtype is diffuse large B-cell lymphoma.

Some subtypes have features of both indolent and aggressive disease, making them difficult to classify into either group.

Where did the lymphoma start?

Names of some NHL subtypes relate to the area where the disease originates. 

  • Nodal lymphomas originate in the lymph nodes.
  • Extranodal lymphomas start in places other than the lymph nodes.
  • Follicular lymphoma usually starts in the follicle cells in the lymph, and it grows in a follicular pattern, meaning the cells clump together.
  • Mantle cell lymphoma originates in the mantle zone, or outer layer, of the lymph node.
  • Marginal lymphomas start in the interface (margin) between lymphoid and non-lymphoid pulp in the spleen and lymph nodes.

Learn about subtypes

With each subtype of NHL, there are small nuances that matter for your treatment. Over time, physicians who specialize in NHL gain deep knowledge of these subtleties. Things like knowing which therapies to use and when to use them. How to tell whether your treatment is working. Or if you’re likely to get unusual side effects. 

Physicians develop this expertise in part by treating many people each year with the same disease. It’s nearly impossible for an oncologist who treats many kinds of cancer to know every detail about a rare NHL subtype. They might see only one patient with that subtype every five years. Here, our NHL specialists see many every year, year after year, building a wealth of experience.

This disease affects NK cells and causes skin lesions. It is rare in the United States and more common in Asia and parts of Latin America. It usually strikes older adults and is linked with Epstein-Barr virus. The main treatment is chemotherapy. Because this subtype of NHL is severe and hard to treat, patients should get care at an academic center that can transition them to a bone marrow transplant.

There are three types of this rare, aggressive T-cell lymphoma.

  • Primary cutaneous ALCL, one of several types of cutaneous lymphoma.
  • ALK-positive (ALK+) ALCL, body-wide disease which expresses a protein called anaplastic lymphoma kinase (ALK). It usually affects children.
  • ALK-negative (ALK-) ALCL, body-wide disease which doesn’t express ALK. It is typically found in adults over age 60.

Both ALK+ and ALK- are treated as aggressive lymphomas. Patients with ALK+ ALCL tend to have excellent outcomes with the standard chemotherapy known as CHOP (cyclophosphamide, doxorubicin hydrochloride, vincristine and prednisone). In 2011, the drug brentuximab vedotin (Adcetris) was approved for patients with both ALK+ and ALK- relapsed or refractory systemic ALCL.

AITL is an aggressive subtype. It is typically diagnosed at stage III or IV. People with AITL usually have fever, night sweats, weight loss, skin rashes and autoimmune disorders, and they often develop infections. Physicians don’t know what causes AITL, but it has been linked with Epstein-Barr virus. To start, treatment usually involves steroids. It often progresses and may be treated with the typical T-cell NHL treatments — chemotherapy or other medicine-based options  — as well as radiation therapy.

This is an aggressive subtype of B-cell NHL found mostly in young men. The average age is 30. In the United States, the disease usually starts as a large tumor in the belly. It can also start in the testicles, ovaries or other organs. Patients are usually treated with chemotherapy. More than half enter complete remission.

CLL and SLL are closely related and are a subtype of B-cell NHL. 

  • In CLL, the cancer cells are mainly in the blood and bone marrow. 
  • In SLL, the cancer cells are mainly in the lymph nodes and spleen. 

Along with common NHL symptoms, CLL/SLL may cause shortness of breath, anemia, bruising and frequent infections.

Both are slow growing. You and your physician may decide to monitor the disease rather than treat it. This is called watchful waiting.If you do need active treatment, it could include chemotherapy and antibody therapy. If the disease does not respond to therapy or it becomes fast growing form, your physician may recommend a bone marrow transplant.

This is also known as lymphoma of the skin and is a subtype of . It mainly affects lymphocytes in the skin but may involve lymph nodes, blood and other organs.

It is nearly always slow growing. The chance of recovery is usually very good. Many people have a relapse after responding to treatment at first.

Treatment may be:

  • Directed at the skin. This includes surgery, radiation therapy, phototherapy (using ultraviolet light) and medicines put on the skin.

Directed at the whole body (systemic treatments). This includes photopheresis, interferon, targeted therapies, chemotherapy or other medicines and bone marrow transplant.

DLBCL is the most common subtype of NHL. It is also a subtype of B-cell NHL. DLBCL makes up about 30 percent of NHLs in the United States. 

There are several subtypes:

  • Primary mediastinal B-cell lymphoma. This is typically only in the space in the chest between the lungs.
  • Intravascular large B-cell lymphoma. This is typically throughout the body.
  • Primary effusion lymphoma. This is a rare subtype linked with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS).

DLBCL advances quickly. Treatment usually starts right away with chemotherapy and the antibody therapy rituximab (Rituxan). After their initial treatment, most people enter long-term remission. In some people, the disease doesn’t respond to treatment (refractory disease), or it gets better but then gets worse (relapsed disease). Then high-dose chemotherapy and a bone marrow transplant may be an option.

This extremely rare subtype affects the intestines. It happens mainly in middle-aged men who are sensitive to gluten, the main protein in wheat flour. It develops when celiac sprue (gluten-sensitive enteropathy) progresses to cancer. There is no standard treatment. Treatments can include surgery to remove the affected part of the intestine, chemotherapy and bone marrow transplant. A gluten-free diet might prevent this lymphoma.

This subtype is more common in parts of Asia and South America. It is linked with Epstein-Barr virus, which causes mononucleosis (often called mono). It often involves the upper airways, such as the nose and upper throat. It can also invade the skin and gastrointestinal tract. This is the only peripheral T-cell lymphoma subtype for which radiation therapy is the main treatment.

Follicular means the cells tend to grow in a circle. This subtype of B-cell NHL is often slow growing. It makes up about 20 percent of NHLs and affects many lymph nodes throughout the body as well as the bone marrow. About 30 percent of the time, it transforms into aggressive diffuse B-cell lymphoma.

Since it typically grows slowly, you and your physician may decide to monitor the disease rather than treat it. This is known as watchful waiting.

If you do need active treatment, it could include chemotherapy, radiation therapy or immunotherapy. Many patients enter long-term remission after treatment. But in most people the disease gets better but then gets worse (relapsed disease) or doesn’t respond to treatment (refractory disease). Then options include high-dose chemotherapy and a bone marrow transplant or treatments being tested in clinical trials.

This is called leukemia but is sometimes thought of as lymphoma.It is a subtype of B-cell NHL and gets its name from the way the cells look. They have fine structures on their surface that make them look hairy. The disease is rare, with fewer than 1,000 people diagnosed in the United States each year.

It is slow growing. Treatment may not be needed in the early stages. Some patients need a blood transfusion from time to time. If your spleen becomes enlarged or your blood counts drop, your options may include surgery to remove the spleen and chemotherapy.

This extremely rare, aggressive disease starts in the liver or spleen. It can cause fever, abdominal pain, weakness and swelling of the liver and spleen. It happens mainly in children, young men and people whose immune system is suppressed (usually due to an organ transplant). There is no standard treatment. One option is chemotherapy using the medicine anthracycline. This causes a short-term response in most patients. Complete remission is rare. Physicians typically recommend a bone marrow transplant using a donor’s stem cells (allogeneic transplant) the first time a patient goes into remission.

In this subtype of B-cell NHL, abnormal lymphocytes build up, forming nodules around the body, most often the lungs. The nodules damage or destroy blood vessels in the area. This subtype is linked to infection with Epstein-Barr virus, which causes mononucleosis (often called mono).

If the disease has low impact on your health, you and your physician may decide to monitor the disease rather than treat it. This is called watchful waiting. If you do need active treatment, options include interferon, corticosteroids, chemotherapy and the antibody therapy rituximab (Rituxan).

MCL typically affects men between the ages of 50 and 70. It has often spread throughout the body by the time it is diagnosed. It may be in the lymph nodes, bone marrow, blood, digestive tract and spleen.

This B-cell NHL subtype can be hard to label as either slow growing or fast growing. Physicians often approach MCL as fast growing (aggressive) because it is hard to treat.

Treatment may include chemotherapy combined with immunotherapy. Bone marrow transplant is an option for some people. Many treatments are being studied in clinical trials.

Marginal zone lymphomas are slow growing. They are typically diagnosed in people in their 60s. There are three main subtypes.

Extranodal marginal zone B-cell lymphoma (mucosa-associated lymphoid tissue lymphoma, MALT)

This starts outside the lymph nodes. Usually it is only in the area where it began. Gastric MALT develops in the stomach. It may be linked with an infection. Antibiotics for the infection are typically the first treatment. They often put the cancer into complete remission. If the cancer relapses, physicians may use immunotherapy, chemotherapy, radiation therapy or surgery. Non-gastric MALT develops in the lungs, skin, thyroid, salivary glands and tissues near the eye. Treatment depends on where the disease is. It usually involves surgery or radiation therapy.

Nodal marginal zone B-cell lymphoma

This disease, found mainly in women, usually stays in the lymph nodes. Lymphoma cells may also be in the bone marrow. Treatment often begins with watchful waiting. If you need active treatment, options include radiation therapy and chemotherapy.

Splenic marginal zone B-cell lymphoma

This subtype of NHL, found in the bone marrow, blood and spleen, is rare. It is typically found in men and has been linked with hepatitis C. Treatment may include watchful waiting unless symptoms become a problem. If you need active treatment, options include surgery to remove the spleen, radiation therapy to the spleen, immunotherapy and chemotherapy.

Physicians use this name for T-cell lymphomas that don’t fit easily into any of the other subtypes of peripheral T-cell lymphoma. These lymphomas tend to be widespread and aggressive. Most people diagnosed are in their 60s. Most are treated with chemotherapy.

This rare B-cell NHL subtype is more common in people with immune system diseases, such as HIV/AIDS. It often involves the brain (primary brain lymphoma) and may be found in and around the spinal cord and eyes (primary intraocular lymphoma).

Over time, it spreads throughout the central nervous system (brain and spinal cord). The symptoms are different than for most lymphomas. Symptoms may include headaches, confusion, vision problems, facial paralysis and seizures.

To start, people with this subtype may receive corticosteroids to control symptoms and reduce swelling. Other treatments include chemotherapy, radiation therapy and occasionally bone marrow transplant.

People with this rare, aggressive disease usually have small bumps or lesions under their skin. It’s most common in people age 30 to 50. Sometimes it is linked with lupus. The typical treatment is chemotherapy with a combination of medicines.

Waldenström macroglobulinemia (WM) cells grow mainly in your bone marrow. There they can crowd out normal, healthy blood cells that your body needs (white blood cells, red blood cells and platelets). WM cells also make large amounts of an antibody called immunoglobulin M. This can build up around your body, causing symptoms of its own.

Treatment for WM differs from treatment for other types of lymphoma, and there’s no single standard treatment. It’s important to be treated at a specialized center with WM expertise, where experienced physicians can tailor treatment to you.

Learn More About Waldenström Macroglobulinemia


Symptoms of NHL can come on very quickly. Some people are diagnosed with the disease within days to weeks of getting symptoms. Some types of NHL come on slowly over several months.

NHL symptoms may be similar to symptoms caused by other conditions that are not related to cancer. Check with your doctor if you feel concerned about any symptoms you have.

Symptoms of NHL include:
  • Painless swollen lymph nodes in your neck, underarm, groin, chest or abdomen
  • Unexplained fever, weight loss or night sweats
  • Ongoing fatigue
  • Itchy skin
  • Red bumps on your skin
  • Swelling in your face, neck or upper chest
  • Feeling of fullness in your abdomen (from an enlarged liver, spleen or lymph nodes)
  • Abdominal problems, such as nausea, vomiting and indigestion


If your doctor suspects you may have lymphoma, they will do a physical exam to look for signs of the disease and ask about your health history.

To confirm the presence of lymphoma, you will need a biopsy. This means removing part or all of a lymph node or a small sample of tissue surgically or with a needle. Experts in identifying blood-related cancers (hematopathologists) look at the cells under a microscope to diagnose the disease and accurately identify the type.

You might also have any or all of these tests:
  • Imaging tests — such as a chest X-ray, ultrasound, magnetic resonance imaging (MRI), computed tomography (CT) scan or positron emission tomography (PET) scan to see pictures of the inside of your body and look for enlarged lymph nodes, tumors or other cancer activity
  • Blood tests — to check the types and numbers of blood cells (complete blood count) and look for chemicals that signal disease in certain organs or tissues (blood chemistry analysis)
  • Lumbar puncture — taking a sample of cerebrospinal fluid from your spine with a needle to check for cancer cells
  • Bone marrow tests — taking samples of bone marrow and a small piece of bone from your pelvis using a needle (bone marrow aspiration and biopsy) to check for cancer cells

If you have lymphoma, you may need more tests to identify the type or subtype. These include an immunohistochemistry study; immunophenotyping, or flow cytometry; and cytogenetic analysis.


Staging means finding out how far lymphoma has spread in your lymph system or other parts of your body. Accurate staging allows your doctors to choose the most appropriate therapy for you — and help you avoid therapy that is not likely to be effective in your situation.

NHLs range from stage I to stage IV, with I being the least advanced and IV being the most advanced.

Doctors may add a letter after your stage to describe more about your disease.

  • E (such as “stage IIIE”) means your cancer is outside your lymph nodes (extranodal).
  • S (such as “stage IIIS”) means the cancer is in your spleen.

If your lymphoma comes back after treatment, it is called recurrent or relapsed. Your doctor will order imaging or other tests to restage it.