Lymphoma - Non-Hodgkin: Subtypes

Approved by the Lineagotica Editorial Board, 02/2018

ON THIS PAGE: You will find descriptions of the most common types and subtypes of NHL. You will also find information about how each subtype may be treated. Use the menu to see other pages.

There are different types and subtypes of NHL. It is very important to know which type and subtype has been diagnosed. Below are the most common types and subtypes, including information about how each may be treated. For more information about the treatment options described here, see the Treatment Options section.

Types of NHL

First, the doctor will determine what type of cell the lymphoma started in and classify the disease within 1 of the 3 major groups:

  • B-cell lymphoma. About 90% of people in western countries with lymphoma have B-cell lymphoma.

  • T-cell lymphoma. About 10% of people with lymphoma have T-cell lymphoma. These lymphomas are more frequent in Asian countries.

  • NK-cell lymphoma. Less than 1% of people with lymphoma have NK-cell lymphoma.

NHL is also described by how quickly the cancer is growing, either “indolent” or “aggressive.” Indolent and aggressive NHL are equally common in adults. In children, aggressive NHL is more common.

  • Indolent NHL. These types of lymphoma grow slowly. As a result, people with indolent NHL may not need to start treatment when it is first diagnosed. They are followed closely, and treatment is only started when they develop symptoms or the disease begins to change. This is called watchful waiting or active surveillance.

    When indolent lymphoma is located only in 1 or 2 adjacent areas, it is called localized disease (stages I and II, see the Stages section). For people with localized disease, radiation therapy is often used. However, most patients with indolent NHL have stage III or IV disease at the time of diagnosis. There are many effective treatments for these stages of indolent NHL. However, it may come back months or years after treatment has finished and require more treatment.

  • Aggressive NHL. These types of lymphoma may develop rapidly, and treatment is usually started within weeks. These types of lymphoma usually need more intensive chemotherapy. The doctor may recommend radiation therapy to treat stage I or II disease and to treat lymphoma where the site of the disease is large, sometimes called “bulky” disease. Some forms of aggressive lymphoma may be cured with effective treatment.

Some subtypes of lymphoma cannot easily be classified as indolent or aggressive. For example, mantle cell lymphoma (see below) has both indolent and aggressive NHL features.

Subtypes of NHL

In addition to determining if the NHL is indolent or aggressive and whether it is B-cell, T-cell, or NK-cell lymphoma, it is very important to determine the subtype of NHL. This is because each subtype can behave differently and may require different treatments. There are more than 60 NHL subtypes, although some are quite rare. The most common subtypes are described below, along with some basic information about different treatments. Learn more in the Treatment Options section.

Distinguishing among the different subtypes of NHL can be difficult and requires pathologists or hematopathologists who are experts in the diagnosis of lymphoma. These specialists use sophisticated techniques and work closely with experienced oncologists. The diagnosis is based on how the lymphoma looks under the microscope. The doctors confirm the diagnosis with additional information from other tests, including tests of genetic material within the lymphoma cells. For more information on this process, see the Diagnosis section.

Subtypes of B-cell lymphoma

These are the most common subtypes of B-cell lymphoma.

  • Diffuse large B-cell lymphoma (DLBCL).This is the most common form of lymphoma. About 30% of NHL in the United States is this type. It is an aggressive form of NHL that involves organs other than the lymph nodes about 40% of the time. About 2 out of 3 people with DLBCL are cured with chemotherapy given in combination with rituximab (Rituxan). Radiation therapy is also used for some patients, especially if the lymphoma is found in a limited area. Your doctor may check the fluid around the brain, called cerebrospinal fluid (CSF), in certain cases at diagnosis and recommend treatments to prevent the lymphoma from spreading to the brain, called central nervous system (CNS) prophylaxis. However, most patients do not need this type of treatment.

    Recent research shows that there are different types of DLBCL, including germinal center and non-germinal center. Research studies, called clinical trials, continue to look at whether patients should receive different types of treatment for these different types of DLBCL.

  • Follicular lymphoma.This is the second most common form of lymphoma in the United States and Europe. About 20% of people with NHL have this subtype. It usually begins in the lymph nodes, is most often indolent, and grows very slowly. People with early, stage I follicular lymphoma may be cured with radiation therapy. For some, bone marrow/stem cell transplantation may cure the disease. Patients with follicular lymphoma may receive a combination of chemotherapy; monoclonal antibodies, a type of targeted therapy; and/or radiation therapy. Or, they may be followed closely with watchful waiting and start treatment only when symptoms appear.

    Recent clinical trials suggest that patients with follicular lymphoma have lived longer over the last few decades. Research shows that rituximab alone or in combination with  drugs such as bendamustine (Treanda) and lenalidomide (Revlimid) are effective for this subtype. There are many new drugs being tested for the treatment of follicular lymphoma

    Over time, follicular lymphoma may turn into DLBCL (see above), which will then require more aggressive treatment. This is called transformation. If follicular lymphoma transforms, it can be treated the same way as DLBCL.

    Localized radiation therapy is often a common treatment choice for people with stage I NHL and for some people with stage II NHL.

  • Mantle cell lymphoma.About 5% to 7% of people with NHL have mantle cell lymphoma. It most often appears in people older than 60 and is much more common in men than in women. It usually involves the bone marrow, lymph nodes, spleen, and gastrointestinal system, which includes the esophagus, stomach, and intestines. Mantle cell lymphoma is identified by a protein called cyclin D1 or by a genetic change within the lymphoma cells involving chromosomes 11 and 14. Some patients have a slower-growing form of the disease and if patients do not have symptoms or a significant amount of disease, some may be prescribed watchful waiting.

    Treatment of mantle cell lymphoma often uses a combination of chemotherapy and a monoclonal antibody. For younger patients who are otherwise healthy, high-dose chemotherapy with autologous stem cell transplantation results in the longest remission, and they may receive maintenance therapy with the monoclonal antibody rituximab. For older patients or those who are not able to receive autologous stem cell transplant, maintenance therapy with rituximab is a standard treatment approach.

    If chemotherapy does not work or the disease comes back, called recurrence, there are differing opinions on the best way to treat mantle cell lymphoma. Research shows that drugs such as acalabrutinib (Calquence), ibrutinib (Imbruvica), and lenalidomide (Revlimid) may be effective treatments for this subtype. Researchers are studying these drugs as part of first-line treatment. Researchers are also studying new drugs for mantle cell lymphoma.

  • Small lymphocytic lymphoma. This type of lymphoma is the same disease as B-cell chronic lymphocytic leukemia (CLL) without a significant amount of disease in the blood. About 5% of people with NHL have this subtype, which is considered indolent lymphoma. People with small lymphocytic lymphoma may not require treatment, but instead receive watchful waiting. Some patients receive a combination of chemotherapy and a monoclonal antibody. Ibrutinib is now approved for patients when the disease returns after initial treatment. Some patients can use ibrutinib as part of initial treatment, although this is still being studied.

  • Double hit lymphoma. This is a highly aggressive subtype of DLBCL, accounting for about 5% of cases. Rarely, low-grade follicular lymphoma may also transform into double hit lymphoma. Double hit lymphomas have changes in the MYC gene and in either the BCL2 or BCL6 gene. Double hit lymphoma is often diagnosed in older adults and there is currently no established treatment regimen, although combinations of chemotherapy and rituximab are the most common options.

  • Primary mediastinal large B-cell lymphoma. This is an aggressive form of DLBCL (see above). It appears as a large mass in the chest area. The mass may cause breathing problems or superior vena cava (SVC) syndrome, a collection of symptoms caused by the partial blockage or compression of the superior vena cava. The superior vena cava is the major vein that carries blood from the head, neck, upper chest, and arms to the heart. Mediastinal large B-cell lymphoma is most common in women between 30 and 40 years old. About 2.5% of people with NHL have this subtype. Most often, doctors treat it with combination chemotherapy plus rituximab. Radiation therapy to the chest may be used in patients for whom chemotherapy did not work. For lymphoma that has not responded to chemotherapy and radiation, CAR T-cell therapy may be an option. A closely related lymphoma called mediastinal grey-zone lymphoma (MGZL) may also occur in the same age group. It is treated in a manner similar to that of primary mediastinal large B-cell lymphoma.

  • Splenic marginal zone B-cell lymphoma. This type of lymphoma begins in the spleen and usually involes the bone marrow and the blood. It is usually slow growing, and the treatment approach is often watchful waiting. If a patient needs treatment, this type of lymphoma is often treated with rituximab, although some patients may also need chemotherapy. In some circumstances, surgical removal of the spleen may be needed.

  • Extranodal marginal zone B-cell lymphoma of MALT. This type of lymphoma most commonly occurs in the stomach. However, it may also occur in the lung, skin, thyroid, salivary gland, or in the orbit, adjacent to the eye or in the bowel. Patients with this type of lymphoma sometimes have a history of autoimmune disease, such as lupus, rheumatoid arthritis, or Sjögren syndrome. When MALT occurs in the stomach, it is sometimes caused by a bacteria called Helicobacter pylori. When MALT is caused by this bacteria, antibiotics can sometimes effectively treat the disease. For disease only affecting only one area, radiation therapy can sometimes cure MALT. Rituximab with or without chemotherapy is also used to treat MALT in some cases.

  • Nodal marginal zone B-cell lymphoma. This rare type of indolent lymphoma involves the lymph nodes. About 1% of people with lymphoma have this subtype. In general, doctors treat this subtype of lymphoma similarly to follicular lymphoma (see above).

  • Lymphoplasmacytic lymphoma. This is an indolent form of lymphoma, and 1% of people with NHL have this subtype. This form of lymphoma often involves the bone marrow, and sometimes lymph nodes, and spleen. In many patients, this lymphoma produces a protein, called an “M protein,” that is found in the blood. When this occurs, the condition is called Waldenstrom’s macroglobulinemia (WM). Patients with WM sometimes have elevated serum viscosity, or “thickened” blood, which may cause symptoms such as headache, blurry vision, dizziness, and shortness of breath. Treatment may include:

    • Watchful waiting

    • Chemotherapy

    • Targeted therapy with monoclonal antibodies

    • Combinations of chemotherapy and monoclonal antibodies

Clinical trial researchers are studying using chemotherapy followed by stem cell transplantation as a treatment option, which may be useful if the lymphoma returns after initial treatment.

  • Primary effusion lymphoma. This rare and very aggressive form of lymphoma most often occurs in people:

    • Who have the human immunodeficiency virus (HIV), which causes autoimmune deficiency syndrome (AIDS)

    • Whose immune system does not work well for other reasons

    • Are elderly

This lymphoma often shows up as fluid around the lung, heart, or abdominal cavity. Often, there are no tumor masses. It is treated the same way as other diffuse large-cell lymphomas (see above).

  • Burkitt lymphoma/Burkitt cell leukemia. This is a very rare and aggressive form of lymphoma. There are 3 forms of Burkitt lymphoma:

    • Endemic

    • Sporadic

    • Immunodeficiency-related lymphoma

The endemic subtype occurs most commonly in Africa, appears most often in the jawbones of children, and is usually associated with infection with EBV. It can also be associated with HIV. In the United States, Burkitt lymphoma sometimes appears with a mass in the abdomen, but it can affect many other parts of the body. Because this type of lymphoma spreads quickly, it needs immediate treatment.

Burkitt lymphoma is often curable. A series of treatment with chemotherapy, each usually given over several days in a hospital, can lead to long-term remission in more than 80% of patients.

Subtypes of T-cell and NK-cell lymphoma

These are the most common subtypes of T-cell and NK-cell lymphoma:

  • Anaplastic large cell lymphoma, primary cutaneous type. This subtype of lymphoma only involves the skin. It is often indolent, although aggressive subtypes of the disease are possible. When the cancer is localized, radiation therapy is often effective. If it has spread, chemotherapy is the usual treatment. New drugs have recently been developed for the treatment of cutaneous lymphomas.

  • Anaplastic large cell lymphoma, systemic type. This form makes up about 2% of all lymphomas and about 10% of all childhood lymphomas. In people with this subtype, an increased amount of the ALK-1 protein may be found in the cancer cells. Those who have ALK-1 protein in the cancer cells often have a better prognosis than those who do not have the ALK-1 protein in the cancer cells. This is an aggressive form of lymphoma, but chemotherapy often works well. New treatments, such as the monoclonal antibody brentuximab vedotin (Adcetris) or stem cell transplantation, may sometimes be a treatment option.

  • Peripheral T-cell lymphoma, not otherwise specified (NOS). This is an aggressive form of lymphoma that is often advanced when doctors find it. It is most common in people older than 60 and makes up about 6% of all lymphomas in the United States and Europe. The cells of this lymphoma vary in size, and they have certain types of proteins, called CD4 or CD8, on their surface. It is treated with chemotherapy. Researchers are studying many new drugs in clinical trials to treat this subtype. Stem cell transplantation may sometimes be an option.

  • Angioimmunoblastic T-cell lymphoma. This is an aggressive form of lymphoma with specific symptoms:
    • Enlarged, often tender, lymph nodes

    • Fever

    • Weight loss

    • Rash

    • High levels of immunoglobulins in the blood

      Patients with angioimmunoblastic lymphoma have lowered immune system functions, so infections are also common. Doctors identify this type of lymphoma by what it looks like under a microscope and by certain proteins found in the tumor cells. It is treated like other aggressive lymphomas.

  • Adult T-cell lymphoma/leukemia (human T-cell lymphotropic virus type I positive). This type of lymphoma is caused by a virus called the human T-cell lymphotropic virus type I. It is an aggressive disease that often involves the bone and skin. Often, lymphoma cells are found in the blood, which is why this condition is sometimes also called leukemia. Chemotherapy does not usually work well for this form of lymphoma, although interferon and zidovudine (Retrovir) help some patients. Allogenic (ALLO) stem cell transplantation may be the best approach for treatment of this type lymphoma in patients whose disease is under control after chemotherapy.

  • Extranodal NK/T-cell lymphoma, nasal type. This is an aggressive type of lymphoma that is very rare in the United States and Europe in general, but more common in Asian and Hispanic communities. It can occur in children or adults, most often involving the nasal area and sinuses. It can also involve the gastrointestinal tract, skin, the testicles, or other areas in the body. Radiation therapy in combination with chemotherapy is an important part of the treatment for disease that involves the nasal/sinus area. This subtype responds well to asparaginase (Elspar), and some patients may benefit from stem cell transplant.

  • Enteropathy-associated T-cell lymphoma. This type of lymphoma is rare in the United States but is more common in Europe. It is an aggressive form of T-cell lymphoma that involves the intestines of patients, some of whom have celiac disease or a history of gluten intolerance. Patients may receive high-dose chemotherapy to treat the disease.

  • Gamma/delta hepatosplenic T-cell lymphoma. This is an aggressive form of peripheral T-cell lymphoma that involves the liver and spleen. The disease occurs most often in teenaged and young men. It is usually managed with chemotherapy followed by ALLO stem cell transplantation.

  • Subcutaneous panniculitis-like T-cell lymphoma. This is a form of peripheral T-cell lymphoma that is similar to gamma/delta hepatosplenic T-cell lymphoma (see above). The disease involves the tissue under the skin and is often first diagnosed as panniculitis, which is inflammation of fatty tissues. It is treated as a high-risk aggressive lymphoma.

  • Mycosis fungoides. This is a rare T-cell lymphoma that primarily involves the skin. It often has a very long and indolent course but may become more aggressive and spread to lymph nodes or internal organs. Mycosis fungoides can be managed with topical medications, controlled exposure to specialized radiation in the form of lights or radiation therapy, and systemic treatments, such as chemotherapy or targeted therapy. This type of NHL cannot be cured, but it is often manageable.  

More information on the specific treatment options described above can be found in the Treatment Options section.

The next section in this guide is Stages. It explains the system doctors use to describe the extent of the disease. You may use the menu to choose a different section to read in this guide.