Lymphoma - Non-Hodgkin: Subtypes

Aprobado por la Junta Editorial de Cancer.Net, 03/2021

ON THIS PAGE: You will find descriptions of the most common types and subtypes of NHL. 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 have been diagnosed. Sometimes more than 1 type of lymphoma can be found in the same patient. Below are the most common types and subtypes. For information about treatment options, see the Types of Treatment section.

Cell 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.

Indolent and aggressive NHL

NHL is also described by how quickly the cancer is growing. “Indolent” NHL grows slowly, while “aggressive” NHL may develop rapidly. Indolent and aggressive NHL are equally common in adults. In children, aggressive NHL is more common. Some subtypes of lymphoma cannot easily be classified as indolent or aggressive. For example, mantle cell lymphoma 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. Learn how they are treated in the Types of Treatment 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 and which marker proteins are expressed on the lymphoma cells. 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 common subtypes of B-cell lymphoma.

Diffuse large B-cell lymphoma (DLBCL). DLBCL is the most common form of lymphoma. About 30% of NHL in the United States is DLBCL. It is an aggressive form of NHL that involves organs other than the lymph nodes about 40% of the time. 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. Follicular lymphoma 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. Over time, follicular lymphoma may turn into DLBCL (see above). This is called transformation. Clinical trials suggest that people with follicular lymphoma have lived longer over the last few decades due to treatment advances. Follicular lymphoma sometimes has a genetic change within the lymphoma cells involving chromosomes 14 and 18. This genetic abnormality changes the function of a protein called BCL2.

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 characterized by a genetic change within lymphoma cells involving chromosomes 11 and 14. This genetic change alters the function of a protein called cyclin D1. Some patients have a slower-growing form of the disease, and if they do not have symptoms or a significant amount of disease, they may be monitored using the watchful waiting approach.

Small lymphocytic lymphoma. This type of lymphoma is the same disease as B-cell chronic lymphocytic leukemia (CLL) but without a significant amount of disease circulating in the blood. About 5% of people with NHL have this subtype, which is considered an indolent lymphoma.

Double hit/triple hit lymphoma. This is a highly aggressive subtype of DLBCL, accounting for about 5% of these 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. Triple hit lymphomas have changes in the MYC, BCL2, and BCL6 genes.

Primary mediastinal large B-cell lymphoma. This is an aggressive form of DLBCL (see above). It appears as a large mass in the central chest. 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 to the heart from the head, neck, upper chest, and arms. 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. A closely related lymphoma called mediastinal grey-zone lymphoma (MGZL) may also occur in the same age group.

Splenic marginal zone B-cell lymphoma. This type of lymphoma begins in the spleen and usually involves the bone marrow and the blood. It is usually slow growing.

Extranodal marginal zone B-cell lymphoma of MALT. This type of lymphoma is usually localized at diagnosis. It 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.

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.

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, sometimes lymph nodes, and spleen. In most patients, this lymphoma produces an immunoglobulin (IgM antibody) 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. Changes in the MYD88 gene are detected in more than 90% of cases of lymphoplasmacytic lymphoma and WM. Looking for mutations in this gene may be helpful in diagnosing lymphoplasmacytic lymphoma.

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. This subtype is characterized by genetic changes on chromosome 8 involving the MYC gene, which contributes to rapid cancer growth.

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.

Anaplastic large cell lymphoma, systemic type. This aggressive form of lymphoma makes up about 2% of all lymphomas and about 10% of all childhood lymphomas. Some people with this subtype have genetic changes on chromosome 2, involving the ALK gene. Individuals with cancer cells that have changes in ALK, called ALK-positive, often have a a better prognosis than those without this change, called ALK-negative.

Breast implant-associated anaplastic large cell lymphoma. This is a relatively recently recognized subtype that arises in tissue near breast implants. It is usually less aggressive than the systemic type of anaplastic large cell lymphoma.

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. Researchers are studying many new drugs in clinical trials to treat this subtype.

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

People with angioimmunoblastic lymphoma have a lowered immune system function, so infections are also common.

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.

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.

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. Some people with this subtype have celiac disease or a history of gluten intolerance.

Hepatosplenic T-cell lymphoma. This is an aggressive form of peripheral T-cell lymphoma that involves the liver and spleen. It is more common in males and occurs more frequently in teenagers and young adults, with a median age at diagnosis of 35 years.

Subcutaneous panniculitis-like T-cell lymphoma. This is a form of peripheral T-cell lymphoma that is similar to 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.

Mycosis fungoides. This rare T-cell lymphoma primarily involves the skin, either in patches or with diffuse redness of the skin. It often has a very long and indolent course but may become more aggressive and spread to lymph nodes or internal organs.

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