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Watch the Cancer.Net Video: Subtyping of Non-Hodgkin Lymphoma in Adults, with John Sweetenham, MD for an overview of this topic.
There are different types and many subtypes of NHL, and it is very important to know which type and subtype has been diagnosed. Below are the most common types and subtypes, including information on how each may be treated. For more information on the treatment information described here, please read the Treatment section.
First, NHL is generally described by how quickly the cancer is growing: indolent or aggressive. Indolent and aggressive NHL are equally common in adults. In children, aggressive NHL is more common.
Indolent (low-grade) NHL. These types of lymphoma grow very slowly and often have spread by the time they are diagnosed. Most patients with indolent NHL have advanced disease when they first visit an oncologist (a doctor who specializes in treating cancer). Several different types of treatment usually work well for this type of lymphoma, but it may come back months or years after treatment is complete. Patients with indolent NHL may not need to start treatment when it is first diagnosed. They may be followed closely and start treatment only when they develop symptoms or the disease begins to change; this is called watchful waiting. When indolent lymphoma is located only in one area (called localized disease, stages I and II; see Staging), radiation therapy may cure the NHL.
Aggressive (high-grade) NHL. These types of lymphoma usually need more intensive chemotherapy. Treatment is usually started immediately, and radiation therapy may be recommended in addition to chemotherapy. These lymphomas are often curable.
Some subtypes of lymphoma cannot easily be classified as indolent or aggressive. For example, mantle cell lymphoma (see below) has features of both indolent and aggressive NHL.
In addition, the doctor will determine what type of cell the lymphoma started in and classify the disease within two major groups:
B-cell lymphoma. About 90% of people with lymphoma have B-cell lymphoma.
T-cell lymphoma. About 10% of people with lymphoma have T-cell lymphoma.
In addition to determining if the NHL is indolent or aggressive and whether it is B-cell or T-cell lymphoma, it is very important to determine the subtype of NHL because each subtype can behave differently and may require different treatments. There are about 35 subtypes of NHL; the most common subtypes are described below.
Distinguishing between the different subtypes of NHL can be difficult and requires pathologists (doctors who specialize in interpreting laboratory tests and evaluating cells, tissues, and organs to diagnose disease) who are experts in the diagnosis of lymphoma. Such specialists will use sophisticated techniques and work closely with experienced oncologists. The diagnosis is based on how the lymphoma looks under the microscope and confirmed by additional information from other tests, including tests of genetic material within the lymphoma cells. For more information on this process, see Diagnosis.
Subtypes of B-cell lymphoma
The most common subtypes of B-cell lymphoma are described below.
Diffuse large B-cell lymphoma (DLBCL). This is the most common form of lymphoma; about 30% of people with NHL have this type. It is an aggressive form of NHL that often (about 40% of the time) involves organs other than the lymph nodes. DLBCL is often curable with chemotherapy given in combination with rituximab (Rituxan); see the Treatment section. Radiation therapy is also used for some patients, especially if the lymphoma is localized (in a small area). Treatments to prevent the lymphoma from spreading to the brain, called central nervous system (CNS) prophylaxis, may be given, but most patients do not need this type of treatment. Recent research has shown that there are different types of DLBCL, known as germinal center and non-germinal center. Clinical trials (research studies) to find out whether different types of treatment should be used for these different types of DLBCL are ongoing.
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 type. 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 about 80% of patients live at least five years after being diagnosed with follicular lymphoma. Patients with follicular lymphoma may receive a combination of chemotherapy, monoclonal antibodies, and/or radiation therapy, or they may be followed closely with watchful waiting (see Treatment).
Recent clinical trials have suggested that the survival for patients with follicular lymphoma has improved over the last few years, although more research is needed to confirm this. Newer drugs such as bendamustine (Treanda) and lenalidomide (Revlimid) have been shown to be effective for this subtype and are being studied in clinical trials as part of first-line treatment (initial treatment given after diagnosis)
Over time, follicular lymphoma may turn into DLBCL (see above), which will then require more aggressive treatment. Stem cell transplantation, tumor vaccines, and monoclonal antibody treatments may also be available in 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 as well.
Mantle cell lymphoma. About 7% of people with NHL have mantle cell lymphoma. It most often appears in people older than 60. It usually involves the bone marrow, lymph nodes, spleen, and gastrointestinal system (esophagus, stomach, intestines). Mantle cell lymphoma is usually identified by a protein called the cyclin D1 protein. Chemotherapy often does not work to treat mantle cell lymphoma, or it stops working often. When chemotherapy does not work, there are differing opinions on the best way to treat mantle cell lymphoma. Newer drugs such as bortezomib (Velcade), bendamustine, and lenalidomide have been shown to be effective for this subtype and are being studied in clinical trials as part of first-line treatment. Clinical trials using high-dose chemotherapy followed by stem cell transplantation or monoclonal antibodies after chemotherapy are in progress. Other new drugs are also being studied for mantle cell lymphoma. Some patients may have a slower growing form of the disease that may be managed like follicular lymphoma (see above).
Small lymphocytic lymphoma. This type of lymphoma is very closely related to a disease called B-cell chronic lymphocytic leukemia (CLL), and about 5% of people with NHL have this subtype. It is considered an indolent lymphoma. Patients with small lymphocytic lymphoma may receive a combination of chemotherapy, monoclonal antibodies, and/or radiation therapy, or they may be followed closely with watchful waiting. Stem cell transplantation, tumor vaccines, and monoclonal antibody treatments may also be available in clinical trials.
Mediastinal large B-cell lymphoma. This is an aggressive form of DLBCL (see above). It appears as a large mass in the chest area, which may cause breathing problems or superior vena cava syndrome (SVCS), a collection of symptoms caused by the partial blockage or compression of the superior vena cava, 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, and about 2.5% of people with NHL have this subtype. It is treated most often with anthracycline-based chemotherapy, and most patients also receive rituximab and radiation therapy to the chest.
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. Sometimes, surgical removal of the spleen is recommended.
Extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT). This type of lymphoma most commonly occurs in the stomach, but it may also occur in the lung, skin, thyroid, salivary gland, or eye. Patients with this type of lymphoma often have a history of autoimmune disease, such as lupus, rheumatoid arthritis, or Sjögren’s syndrome. When MALT occurs in the stomach, it is often successfully treated with antibiotics to treat an infection with Helicobacter pylori bacteria, which is thought to cause the lymphoma. Other times, radiation therapy, surgery, chemotherapy, monoclonal antibodies, or a combination of these is the most common treatment plan. For disease in only one part of the body, radiation therapy can often cure the NHL.
Nodal marginal zone B-cell lymphoma. This type of indolent lymphoma involves the lymph nodes. It is rare; about 1% of people with lymphoma have this subtype. In general, this subtype of lymphoma is treated 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 most often involves the bone marrow, lymph nodes, and spleen. In many patients, this lymphoma produces 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 chronic lymphocytic lymphoma/leukemia and may include watchful waiting, chemotherapy, monoclonal antibodies, or combinations of chemotherapy and monoclonal antibodies. Chemotherapy followed by stem cell transplantation is being studied in clinical trials.
Primary effusion lymphoma. This very aggressive form of lymphoma most often occurs in people who have the human immunodeficiency virus (HIV, the virus that causes autoimmune deficiency syndrome or AIDS), people whose immune system does not work well for other reasons, or people who are elderly. It begins in the lung, heart, or abdominal cavities; often, there is not one tumor. It is treated the same as other diffuse large cell lymphoma (see above).
Burkitt lymphoma/Burkitt cell leukemia. This is a very rare and aggressive form of lymphoma. There are three forms of Burkitt lymphoma: endemic, sporadic, and immunodeficiency-related lymphoma. It occurs most commonly in Africa, appears most often in the jawbones of children, and is usually associated with the Epstein-Barr virus (EBV, the virus that causes mononucleosis, also known as "mono"). It can also be associated with HIV. In the United States, Burkitt lymphoma appears most commonly with a mass in the abdomen. Because this type of lymphoma spreads quickly, it needs immediate treatment that includes intensive chemotherapy, usually with some treatment for the central nervous system to prevent it from spreading to the brain. This type of NHL is often curable.
Subtypes of T-cell and natural killer (NK) lymphoma
The most common subtypes of T cell and a cell called natural killer (NK; cells that fight microbes and cancer cells) lymphoma are described below.
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, some of which can be given orally (by mouth) as a pill.
Peripheral T-cell lymphoma, NOS. This is an aggressive form of lymphoma that is most often found when it is advanced. 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 are variable in size, and they have certain types of proteins (called CD4 or CD8) on their surface. It is treated with chemotherapy like DLBCL (see above). Stem cell transplantation may sometimes be an option.
Angioimmunoblastic T-cell lymphoma. This is an aggressive form of lymphoma with specific symptoms: swollen lymph nodes, fever, weight loss, rash, and high levels of antibodies called gamma globulin in the blood. Since patients with angioimmunoblastic lymphoma have lowered immune systems, infections are also common. This type of lymphoma is identified by what it looks like under a microscope and by certain proteins found in the tumor cells. It is treated like other diffuse large cell lymphomas.
Anaplastic large cell lymphoma, systemic type. This form makes up about 2% of all lymphomas and about 10% of all childhood lymphomas. An increased amount of the ALK-1 protein may be found in the cancer cells of this subtype for some people. Those who have this subtype of lymphoma with the ALK-1 protein in the cells often have a better prognosis (chance of recovery) than those who have this subtype without the ALK-1 protein in the cell. It is an aggressive form of lymphoma, but treatment often works well, including new treatments such as the recently approved drug brentuximab vendotin (Adcetris).
Precursor T-lymphoblastic lymphoma/leukemia (precursor T-cell acute lymphoblastic leukemia). This is a rare type of lymphoma that makes up about 2% of all NHL. It is most common for young adults and is more common for men than women. This type of lymphoma is the same as a form of leukemia called acute lymphoblastic leukemia (ALL). When it is mainly located in the lymph nodes it is called lymphoblastic lymphoma, and when it is mainly found in the blood or bone marrow it is called ALL. When it is mainly in the lymph nodes, it most commonly involves the lymph nodes in the center of the chest. Both lymphoblastic lymphoma and ALL are aggressive diseases that require intensive chemotherapy, including treatment for the central nervous system to prevent it from spreading to the brain. Stem cell transplantation is sometimes used. It is often cured with these treatments.
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 most 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 zidovudine (Retrovir) and interferon have helped some patients. About two-thirds of patients experience remission (temporary or permanent absence of cancer symptoms).
Extranodal NK/T-cell lymphoma, nasal type. This is an aggressive type of lymphoma that is very rare in the United States and Europe overall 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 trachea (windpipe), gastrointestinal tract, testicles (in men), or skin. Standard chemotherapy does not often work well for this type of NHL, but radiation therapy followed by chemotherapy can help treat the disease. Recently, a drug used for acute lymphoblastic leukemia called asparaginase (Elspar) has helped treat this subtype of lymphoma for patients who have been newly diagnosed or had the disease come back after treatment. Stem cell transplantation for this type of lymphoma is being studied in clinical trials.
Enteropathy-associated T-cell lymphoma. This type of lymphoma is rare in the United States but more common in Europe. It is an aggressive form of T-cell lymphoma that involves the intestines of patients who have celiac disease (gluten intolerance). High-dose chemotherapy may be used to treat enteropathy type T-cell lymphoma.
Gamma/delta hepatosplenic T-cell lymphoma. This is an aggressive form of peripheral T-cell lymphoma that involves the liver and spleen. It occurs most often in adolescent and young men. It is treated as a high-risk diffuse large cell lymphoma (see above).
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). It involves the tissue under the skin and is often first diagnosed as panniculitis (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 immunotherapy can help treat this form of NHL. New drugs have been developed 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 section.