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, the disease 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. About 85% to 90% of patients with indolent NHL have advanced disease when they first visit an oncologist (a doctor who specializes in cancer). This type of lymphoma usually responds well to several different types of treatment, but it may also come back after treatment. In some cases, patients with indolent NHL may also be able to be followed closely and start treatment only when necessary; this approach is called watchful waiting. In cases of localized disease (stage I-II), treatment to cure the NHL with radiation therapy is sometimes possible.
Aggressive (high-grade) NHL. These types of lymphoma usually require chemotherapy that may be very intensive. 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.
Second, the doctor will determine what type of cell the lymphoma started in and classify the disease within two major groups:
B-cell lymphoma. B-cell lymphoma makes up about 90% of all cases of lymphoma.
T-cell lymphoma. T-cell lymphoma makes up about 10% of all lymphoma cases.
Subtyping
In addition to determining if the NHL is indolent or aggressive, and whether it is B-cell or T-cell, 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 recognized subtypes of NHL; the most common subtypes are described below. Distinguishing between the different subtypes of NHL can be difficult and requires specialized pathologists (doctors who specialize in interpreting laboratory tests and evaluating cells, tissues, and organs to diagnose disease) who are experienced 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, 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 all cases of NHL). This subtype is an aggressive form of NHL and involves organs outside the lymph nodes in about 40% of cases at the time of diagnosis. This type of lymphoma can often be cured with chemotherapy based on anthracycline drugs (doxorubicin [Adriamycin]) and the monoclonal antibody rituximab (Rituxan), see the Treatment section, sometimes combined with radiation therapy. Treatments involving the central nervous system (CNS) may be included to prevent the lymphoma from spreading to the brain (called CNS prophylaxis). Recent genetic studies show that there may be different subtypes of DLBCL, called germinal center and non-germinal center.
Follicular lymphoma. This is the second most common form of lymphoma in the United States and Europe, accounting for about 20% of all cases of NHL. It usually begins in the lymph nodes, is most often indolent, and grows very slowly. There is no known cure; about 50% of people survive at least eight to 10 years after diagnosis. Patients with follicular lymphoma may be treated with combination chemotherapy, monoclonal antibodies, radiation therapy, or may be followed closely with watchful waiting. Over time, follicular lymphoma may transform into a diffuse large B-cell lymphoma (see above), which will then require more aggressive therapy. Stem cell transplantation, tumor vaccines, interferon, and monoclonal antibody treatments may also be available in clinical trials. Recent clinical trials have suggested that the survival for patients with follicular lymphoma has improved over the last few years, although this needs more research to confirm. Localized radiation therapy may cure early-stage (stage I-II) disease.
Mantle cell lymphoma. This is an aggressive subtype that makes up 7% of all NHL cases. It most often appears in people over age 60. It usually involves the bone marrow, lymph nodes, spleen, and gastrointestinal system (esophagus, stomach, intestines) and is identified by its expression of a protein called the cyclin D1 protein. Mantle cell lymphoma often does not respond, or stops responding, to chemotherapy. At this time, there is substantial debate about the best way to treat mantle cell lymphoma. A drug called bortezomib (Velcade) has been shown to be effective for this disease and is now being studied in clinical trials as part of the first-line chemotherapy. Clinical trials using high-dose chemotherapy followed by stem cell transplantation or monoclonal antibodies after anthracycline-containing chemotherapy regimens are in progress. Several new drugs are also under investigation 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) and represents about 5% of all NHL cases. It is considered an indolent lymphoma. Patients with small lymphocytic lymphoma may be treated with a combination of chemotherapy, monoclonal antibodies, radiation therapy, or may be followed closely with watchful waiting. Stem cell transplantation, tumor vaccines, interferon, and monoclonal antibody treatments may also be available in clinical trials.
Mediastinal large B-cell lymphoma. This is an aggressive form of diffuse large B-cell lymphoma (see above). It appears as a large mass in the chest area, which may cause respiratory symptoms 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 the ages of 30 and 40 and represents about 2.5% of all NHL cases. It is treated most often with anthracycline-based chemotherapy, and most patients also receive rituximab and radiation therapy to the chest. Although radiation therapy has traditionally been considered a particularly important part of treatment for mediastinal large B-cell lymphoma for some patients, this is no longer certain.
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. When MALT occurs in the stomach, it is often successfully treated with antibiotics to treat a bacterium called Helicobacter pylori, which is thought to cause the lymphoma. In other cases, radiation treatment, surgery, chemotherapy, monoclonal antibodies, or a combination of these is the most common treatment.
Nodal marginal zone B-cell lymphoma. This type of indolent lymphoma involves the lymph nodes. It is rare, accounting for about 1% of all lymphomas. In general, this type of lymphoma is treated similarly to follicular lymphoma (see above).
Lymphoplasmacytic lymphoma. This is an indolent form of lymphoma that accounts for 1% of all NHL cases. This form of lymphoma most often involves the bone marrow, lymph nodes, and spleen. In many patients, this lymphoma produces protein which is found at high levels in the blood. When this occurs, the condition is known as Waldenstrom’s macroglobulinemia (WM). Patients with WM often have hyperviscosity (thickened blood) that 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, combination chemotherapy, monoclonal antibodies, or combinations of chemotherapy and monoclonal antibodies. Chemotherapy followed by stem cell transplantation is being explored in clinical trials.
Primary effusion lymphoma. This very aggressive form of lymphoma most often occurs in people with the human immunodeficiency virus (HIV, the virus that causes autoimmune deficiency syndrome or AIDS), otherwise immunocompromised, or elderly. It appears in the lung, heart, or abdominal cavities; often, there is not one identifiable 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 infectious mononucleosis, also known as "mono"). In the United States, it appears most often in a child’s abdomen. It is often curable with doxorubicin-based chemotherapy. Stem cell transplantation for Burkitt lymphoma may be helpful.
Subtypes of T-cell lymphoma
The most common subtypes of T cell and natural killer (NK) lymphoma follow.
Anaplastic large cell lymphoma, T/null-cell, primary cutaneous lymphoma. This lymphoma involves the skin only. It is often indolent, although aggressive subtypes of the disease are possible. When the cancer is localized, radiation therapy is often effective. If there is spread, doxorubicin-based chemotherapy is the usual treatment.
Peripheral T-cell lymphoma. This is an aggressive form of lymphoma that is most often discovered at an advanced stage. It is most common in people over 60 and makes up about 6% of all lymphoma in the United States and Europe. The cells of this lymphoma are variable in size, and they express certain types of proteins (CD4 or CD8) on their surface. It is treated like diffuse large B-cell lymphoma (see above), with doxorubicin-based chemotherapy. Stem cell transplantation may be considered in some cases.
Angioimmunoblastic T-cell lymphoma. This is an aggressive form of lymphoma marked by the symptoms it produces: 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 specific genetic changes found on the T-cell receptors. It is treated like other diffuse large cell lymphomas.
Anaplastic large cell lymphoma, T/null-cell, primary systemic type. This form makes up about 2% of all lymphoma and about 10% of all childhood lymphoma. An increased amount of the ALK-1 protein in the cancer cells is characteristic of this subtype of lymphoma. It occurs in both adults and children. It is an aggressive form of lymphoma that often responds well to treatment.
Precursor T-lymphoblastic lymphoma/leukemia (precursor T-cell acute lymphoblastic leukemia). This type of lymphoma makes up about 15% of all childhood cases of acute lymphocytic lymphoma (ALL) and about 25% of all adult cases of ALL. It is most common in late childhood, adolescence, and early adulthood, and is more common in males. It is called leukemia if there are more than 25% bone marrow blasts (immature white blood cells); it is called lymphoma if there are fewer than 25% bone marrow blasts and a mediastinal mass (a mass forming in the chest area) or there is a mass elsewhere. Lymphoblastic lymphoma most often begins as a large mass in the chest area that moves quickly to the bone marrow. This is considered a very aggressive form of lymphoma. It is treated with intensive chemotherapy, sometimes including stem cell transplantation and may include radiation therapy.
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. This form of lymphoma usually does not respond well to chemotherapy, though some success has been seen with ziduvidine (Retrovir) and interferon. About two-thirds of patients experience remission (temporary or permanent absence of 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 but more common in Asian and Hispanic communities. It can occur in children or adults, most often involving the nasal area and sinuses. But, it can also involve the trachea, gastrointestinal tract, testicles (in men), or skin. It often does not respond well to standard chemotherapy, but it may be treated with radiation therapy followed by chemotherapy. Stem cell transplantation for this type of lymphoma is being studied in clinical trials.
Enteropathy type T-cell lymphoma. This type of lymphoma is rare in the United States and Europe. This is an aggressive form of T-cell lymphoma that involves the intestines of patients who have celiac disease (gluten intolerance). If left untreated, it can damage the intestines severely. 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 male adolescents 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.
More information on the specific treatment options described above can be found under the Treatment section.
Last Updated: September 22, 2008
