Lymphoma - Non-Hodgkin: Subtypes

Approved by the Lineagotica Editorial Board, 12/2016

A full-text transcript is available.

ON THIS PAGE: You will find descriptions of the most common types and subtypes of NHL, as well as information about how each may be treated. To see other pages, use the menu.

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 information 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.

    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 may eliminate the NHL. 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 immediately. These types of lymphoma usually need more intensive chemotherapy. The doctor may recommend radiation treatment in addition to chemotherapy, especially in patients with limited stage disease (stage I or II). Many 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 a number of them 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

The most common subtypes of B-cell lymphoma are:

  • 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, known as 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. There is no known cure. However, recent studies show that more than 85% of patients live for at least 5 years after being diagnosed with follicular lymphoma. In addition, 50% of patients are estimated to live longer than 12 years. 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 starting 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 drugs such as bendamustine (Treanda) and lenalidomide (Revlimid), usually in combination with rituximab, are effective for this subtype. There are many new drugs being tested for use as part of first-line treatment for follicular lymphoma.

    Over time, follicular lymphoma may turn into DLBCL (see above), which will then require more aggressive treatment. This is called transformation. Stem cell transplantation, chimeric antigen receptor T-cells (CAR T-cells), and monoclonal antibody treatments may also be available treatment options, usually as part of clinical trials.

    Localized radiation therapy is often a common treatment choice for early-stage disease (stages I and II), but it may be combined with other treatments.

  • 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 that may be managed like follicular lymphoma (see above).

    The first approach to treating mantle cell lymphoma is to use a combination of chemotherapy and a monoclonal antibody. Most people with mantle cell lymphoma will have the disease return after finishing chemotherapy. As a result, doctors offer some patients high-dose chemotherapy followed by autologous stem cell transplantation at the end of their initial chemotherapy treatment, with the transplant often followed by maintenance therapy with the monoclonal antibody rituximab. Doctors may offer patients who do not have a stem cell transplant maintenance therapy with rituximab or other monoclonal antibody. Patients may also need radiation therapy to manage local symptoms.

    If chemotherapy does not work, there are differing opinions on the best way to treat mantle cell lymphoma. Research shows that drugs such as bortezomib (Velcade), 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 very closely related to a disease called B-cell chronic lymphocytic leukemia (CLL). About 5% of people with NHL have this subtype, which is considered indolent lymphoma. Patients with small lymphocytic lymphoma may receive a combination of chemotherapy and/or a monoclonal antibody. Or, they may be followed closely with watchful waiting. Stem cell transplantation, tumor vaccines, monoclonal antibody, or CAR T-cell treatments may also be available in clinical trials. Ibrutinib is now approved for patients who have had their disease return after initial treatment. Some patients can use ibrutinib as part of initial treatment, although this is still being studied.

  • 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 anthracycline-based chemotherapy plus rituximab. Depending on the chemotherapy regimen used, some patients also receive radiation therapy to the chest. Newer chemotherapy treatments may eliminate the need for radiation therapy in most patients. A closely related lymphoma called mediastinal grey-zone lymphoma (MGZL) may also occur in the same age group. It is approached 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 can also involve 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 similarly to follicular lymphoma. Sometimes, the doctor may recommend surgical removal of the spleen.

  • 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 and adjacent to the eye. 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 often successfully treated with antibiotics to treat an infection with Helicobacter pylori. This bacterium is causally related to the development of this lymphoma subtype. Other times, radiation therapy, surgery, chemotherapy, monoclonal antibodies, or a combination of these is the most common treatment plan. For disease in only 1 part of the body, radiation therapy can often cure MALT.

  • 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, lymph nodes, and spleen. In many patients, this lymphoma produces proteins, called “M proteins,” that are found at high levels in the blood. When this occurs, the condition is called Waldenstrom’s macroglobulinemia (WM). Patients with WM sometimes have thickened blood, which may cause symptoms such as headache, blurry vision, dizziness, and shortness of breath. Treatment is similar to that for chronic lymphocytic leukemia or follicular lymphoma (see above). Treatment may include:

    • Watchful waiting

    • Chemotherapy

    • Targeted therapy with monoclonal antibodies

    • Combinations of chemotherapy and monoclonal antibodies

    • Ibrutinib

    Clinical trial researchers are studying using chemotherapy followed by stem cell transplantation as 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

    It begins 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 usually appears with a mass in the abdomen. Because this type of lymphoma spreads quickly, it needs immediate treatment. That treatment includes intensive chemotherapy, usually with treatment for the CNS to prevent it from spreading to the brain. This type of NHL is often curable with immediate treatment.

Subtypes of T-cell and NK-cell lymphoma

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

  • 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 have this subtype without the ALK-1 protein in the cell. It 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, especially for the subtype without the ALK-1 protein.

  • 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 as with DLBCL (see above) or using other drugs. 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 systems, 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. Some patients experience remission, which is when symptoms go away for a period of time. Allogenic (ALLO) stem cell transplantation is the best approach for treatment of this type.

  • Extranodal NK/T-cell lymphoma, nasal type. This is an aggressive type of lymphoma that is very rare in the United States and Europe 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 windpipe, gastrointestinal tract, skin, or a man’s testicles. Standard chemotherapy does not always work well for this type of NHL. That’s why combining radiation therapy with chemotherapy is an important addition to treatment when the disease is localized. Compared to other T-cell lymphomas, this subtype responds better to asparaginase (Elspar). This drug is now a standard part of initial treatment and is also used when this subtype of lymphoma comes back after treatment. Researchers are also studying stem cell transplantation for this type of lymphoma in clinical trials.

  • 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 who 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. Radiation therapy, chemotherapy, or targeted therapy can help treat this form of NHL. Scientists have developed new drugs for the treatment of cutaneous lymphomas, some of which can be taken orally as a pill.

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. Or, use the menu to choose another section to continue reading this guide.