Types of Non-Hodgkin Lymphoma

July 13, 2024

This page was reviewed under our medical and editorial policy by Alex Herrera, M.D., associate professor, division of lymphoma, Department of Hematology & Hematopoietic Cell Transplantation, City of Hope^® Cancer Center Duarte

Non-Hodgkin lymphoma (NHL) has many different forms, and knowing the specific type and subtype a patient has will help the care team develop an appropriate treatment plan. Doctors classify NHL by looking at several factors, including the type of white blood cell involved, how quickly the cancer is growing and the specific genetic abnormalities in the lymphoma cells.

Non-Hodgkin Lymphoma Cell Types

First, doctors determine which type of white blood cell (lymphocyte) is affected, then classify the lymphoma type within one of three broad groups:

B cell lymphoma begins in B lymphocytes, which help the immune system fight infection by churning out antibodies against viruses and other germs. Of the roughly 85,600 Americans diagnosed with NHL each year, approximately 90% have the B cell form.

T cell lymphoma begins in T lymphocytes, which directly destroy foreign invaders or help regulate other immune system cells. In the United States, T cell lymphoma accounts for about 10% of all NHL cases.

NK cell lymphoma begins in the immune system’s natural killer (NK) cells, which attack tumors and viruses. It is very rare, making up less than 1% of NHL diagnoses.

Aggressive and Indolent

NHL may be grouped into one of two categories: indolent or aggressive.

• Indolent NHL tends to progress slowly, may cause few signs or symptoms, and may not require immediate treatment.
• Aggressive NHL forms grow and spread quickly, sometimes with severe symptoms, which usually need prompt treatment.

B Cell Lymphoma Types

B cell lymphomas have numerous subtypes, ranging from relatively common to very rare, and from indolent to aggressive. They also vary in where they arise in the body and in which groups of people they most often affect.

Diffuse Large B Cell Lymphoma (DLBCL)

Diffuse large B cell lymphoma is the most common form of lymphoma among Americans, accounting for about 30% of all NHL diagnoses. It largely affects older adults, and sometimes involves body tissues and organs other than the lymph nodes. DLBCL is considered an aggressive form of NHL, but it tends to respond well to treatment. According to the American Cancer Society (ACS), about three-quarters of patients show no signs of the cancer after their initial treatment, which most commonly includes a combination of chemotherapy drugs and Rituxan^® (rituximab), a monoclonal antibody.

Double-Hit/Triple-Hit Lymphoma

This is a further subtype of diffuse large B cell lymphoma, accounting for about 5% of DLBCL cases. It is highly aggressive and involves changes in either two particular genes (double-hit) or three (triple-hit). In rare cases, double-hit lymphoma begins as follicular lymphoma that transforms at some point. These are fairly new lymphoma classifications, so researchers are still sorting out the appropriate treatment plans. In general, patients receive various combinations of chemotherapy and rituximab.

Primary Mediastinal Large B-Cell Lymphoma

This is another aggressive subtype of diffuse large B cell lymphoma. It appears as a large mass in the middle of the chest, and it may cause breathing problems or swelling in the face, neck and arms. About 2.5% of people with NHL have this subtype, and it most commonly affects women in their 30s. Most often, the disease is treated with combinations of chemotherapy drugs and rituximab.

Follicular Lymphoma

Follicular lymphoma accounts for about 20% of all NHL cases among Americans, and it is the most common form of indolent lymphoma. People with this subtype are usually diagnosed in their 60s; it is rare in younger adults. If a patient has few or no symptoms, patient monitoring may be the initial approach. When treatment is necessary, it may involve chemotherapy, radiation therapy, targeted therapies and/or rituximab or other immunotherapies.

Follicular lymphoma is generally considered a chronic disease that may go into remission for many years with treatment.

Mantle Cell Lymphoma (MCL)

Mantle cell lymphoma accounts for about 5% to 7% of all cases, and it is another subtype that largely affects people older than 60. It is also much more common in men than in women. The cancer often starts off as indolent, but it may become more aggressive over time. At the time of diagnosis, it is usually widespread — affecting lymph nodes, bone marrow, the spleen and the digestive tract. MCL treatment varies, but may include rituximab plus high-dose chemotherapy, often followed by a stem cell transplant using a patient’s own cells to rebuild the immune system damaged by the chemotherapy. Other options include targeted therapies, immunotherapies or less-intensive chemotherapy, with or without rituximab. MCL may be challenging to treat, but new therapies are under study in clinical trials.

MALT Lymphoma

This cancer most often begins in the stomach, in which case it is known as gastric MALT lymphoma. In some cases, MALT lymphoma may begin elsewhere in the body, including the lungs, skin, thyroid or salivary glands. Gastric MALT lymphoma accounts for roughly 8% of NHL cases, according to the Leukemia and Lymphoma Society. MALT lymphoma is typically diagnosed around the age of 60, and some patients have a history of autoimmune disease, such as lupus or rheumatoid arthritis. Gastric MALT lymphoma is sometimes caused by infection with H. pylori, a type of bacteria that commonly causes stomach ulcers. In those cases, antibiotics are often prescribed to treat the infection, which may also treat the lymphoma. MALT lymphomas may be treated with chemotherapy, radiation therapy, targeted therapies and/or rituximab.

Chronic Lymphocytic Leukemia/Small-Cell Lymphocytic Lymphoma (CLL/SLL)

These are two closely related forms of NHL that together make up roughly 5% of all NHL cases. Many doctors consider CLL and SLL two variants of the same cancer. The only difference is where they arise in the body: the blood and bone marrow (CLL) or lymph nodes and/or the spleen (SLL). Both are usually indolent, and people may live many years after diagnosis. Many people have few symptoms initially, and treatment may be delayed. When it is needed, several treatment options are available, including newer targeted drugs that zero in on specific molecules that help cancer cells survive and grow.

Lymphoplasmacytic Lymphoma

This is an indolent form of lymphoma that accounts for about 1% of NHL diagnoses. It often involves the bone marrow, and sometimes the lymph nodes and/or spleen. In most patients, the lymphoma churns out an abundance of so-called M protein. When that protein builds up in the blood, it may cause symptoms such as headaches, blurry vision, dizziness and breathing problems. As with other slow-growing lymphomas, this form may not need immediate treatment. The main treatment options are chemotherapy, targeted therapy and immunotherapy.

Splenic Marginal Zone B Cell Lymphoma

This is a very rare lymphoma that begins in the spleen and usually spreads to the bone marrow and blood. It is considered an indolent lymphoma, and treatment is not always needed right away. When it is, options may include surgically removing the spleen, and rituximab with or without chemotherapy.

Nodal Marginal Zone B Cell Lymphoma

Another rare, indolent lymphoma, this subtype usually begins and remains in the lymph nodes. Since it is slow-growing, doctors sometimes recommend monitoring it. When treatment is needed, the options may include radiation therapy, chemotherapy, targeted therapy and immunotherapy.

Burkitt Lymphoma

This is an aggressive and very rare lymphoma that may affect both adults and children. It has a few subtypes, but the one most commonly seen in the United States is the sporadic form. It usually arises as a large tumor in the abdomen, but may spread to other parts of the body, including the brain. Because of this, Burkitt lymphoma requires prompt treatment — the standard being high-dose chemotherapy with rituximab.

T Cell and NK Cell Lymphoma Types

Although T cell lymphomas are uncommon, there are numerous subtypes, most of which are quite rare. They may be aggressive or indolent and may form within the lymphatic system or outside of it in places like the liver, skin or digestive tract. NK cell lymphomas are generally grouped with T cell forms.

Peripheral T Cell Lymphoma, Not Otherwise Specified (NOS)

This is an aggressive form of lymphoma that makes up about 6% of all lymphomas diagnosed among Americans. It is most common in people older than 60 and is often in an advanced stage when it is diagnosed. It usually requires immediate treatment, most often with chemotherapy.

Angioimmunoblastic T Cell Lymphoma

This subtype accounts for about 4% of all lymphomas, according to the ACS, and is most often diagnosed in older adults. It tends to involve lymph nodes and bone marrow, as well as the spleen or liver. The disease is aggressive, commonly causing symptoms such as high fever and night sweats, skin rash and joint swelling. Treatment usually includes combinations of chemotherapy drugs; while the cancer may go into remission for a long period, it commonly comes back.

Anaplastic Large Cell Lymphoma (ALCL)

This subtype makes up about 2% of lymphomas, according to ACS, and is more common in younger people, including children. While ALCL does tend to grow quickly, it is also treatable in many cases. There are three forms:

Systemic ALCL, which may occur in the lymph system or other tissues and organs

Primary cutaneous ALCL, which is limited to the skin and generally less aggressive than the systemic form

Breast implant-associated ALCL, a rare cancer that may form around breast implants. It is also less aggressive than systemic ALCL

Adult T Cell Lymphoma/Leukemia

A rare and often aggressive disease, this cancer may be found in the lymph system, the blood (in which case it is considered leukemia) or elsewhere in the body. It is specifically caused by infection with a virus called HTLV-1. Treatment often involves different combinations of chemotherapy drugs.

Extranodal NK/T Cell Lymphoma, Nasal Type

This subtype develops from NK cells and usually begins in the inner tissues of the nose or the back of the throat, but it may invade the skin, digestive tract and other organs. It is an aggressive lymphoma that is very rare in the United States, but common in Asia and parts of Latin America. Treatment usually involves a combination of radiation therapy and chemotherapy.

Enteropathy-Associated T Cell Lymphoma

This lymphoma arises in the lining of the intestines and may cause severe abdominal pain, nausea, vomiting and intestinal bleeding. It is a very rare cancer that is diagnosed in some people with celiac disease, an autoimmune condition in which eating gluten triggers the immune system to attack the intestinal lining. It generally requires aggressive treatment, which may include surgery, chemotherapy with multiple drugs and sometimes a stem cell transplant.

Hepatosplenic T Cell Lymphoma (HSTCL)

Another rare and highly aggressive subtype, HSTCL develops from T cells in the liver and spleen. It is more common in teenage boys and young men. Symptoms may include fever, weight loss, fatigue, swollen lymph nodes and abdominal swelling. The disease requires intensive treatment, usually high-dose chemotherapy followed by a stem cell transplant.

Subcutaneous Panniculitis-like T Cell Lymphoma

This subtype also largely affects younger adults, with half of patients 35 or younger when they are diagnosed, according to the Lymphoma Research Foundation. The cancer invades the tissue under the skin, and it is sometimes first diagnosed as panniculitis, an inflammation of fatty tissues. Patients typically develop skin lesions on the limbs and torso, and they may also have fevers, night sweats and weight loss. Chemotherapy is the main treatment.

Mycosis Fungoides

Some T cell lymphomas mainly affect the skin. As a group, they are called cutaneous T cell lymphomas, and mycosis fungoides is the most common. It may arise at any age, but most people are in their 50s or 60s at the time of diagnosis. Typically, the first signs are scaly, red patches on the skin that may be intensely itchy. Treatments may be applied to the skin only, especially in earlier stages. Treatment options may include topical drugs, radiation therapy or ultraviolet (UV) light therapy. Patients with more advanced cancer may need systemic treatments such as chemotherapy, targeted drugs or immunotherapy.