Follicular lymphoma is a slow-growing blood cancer that develops when abnormal white blood cells called B cells accumulate in the body’s lymph nodes and other organs. This type of cancer often doesn’t cause symptoms for years, and many people are diagnosed during routine health checks. While it typically cannot be cured, people with follicular lymphoma can often live for many years, and newer treatments continue to improve outcomes.
What is Follicular Lymphoma?
Follicular lymphoma is the second most common type of non-Hodgkin lymphoma, which is cancer that affects the lymphatic system. The lymphatic system is part of your immune system and includes organs, glands, tubes, and clusters of cells called lymph nodes that help your body fight infections. This cancer specifically develops from B lymphocytes, which are white blood cells that normally produce antibodies to protect you from infections.[1]
The name “follicular” comes from the way cancer cells group together. When B cells become cancerous, they often gather in clumps called follicles inside lymph nodes, mimicking the normal structures where healthy B cells mature. These cancer cells don’t work properly to fight infections. Instead, they multiply slowly and can spread to lymph nodes throughout the body, as well as to the bone marrow and other organs.[3]
Follicular lymphoma is considered an indolent or slow-growing cancer. Unlike aggressive cancers that develop quickly, this type may take years to cause noticeable problems. Most people with follicular lymphoma live for many years with the condition, and the phrase doctors often use is that people “die with it, not from it.” However, in a small number of cases, follicular lymphoma can transform into a more aggressive type of cancer called diffuse large B-cell lymphoma.[1]
How Common is Follicular Lymphoma?
In the United States, approximately 15,000 to 20,000 new cases of follicular lymphoma are diagnosed each year. This accounts for about 20 to 30 percent of all non-Hodgkin lymphomas, making it a relatively common blood cancer. The disease primarily affects older adults, with most people receiving their diagnosis around age 60 or 65. It’s rarely seen in people under 20 years of age.[1][2]
The condition is more common in certain populations. People who are white receive this diagnosis more often than people of other races, particularly compared to Asians and African Americans. There doesn’t appear to be a significant difference between men and women in terms of who develops follicular lymphoma. The disease is more frequently found in the United States and Europe compared to other parts of the world.[2][8]
Interestingly, children can develop a form of follicular lymphoma, but it behaves very differently from the adult type. Pediatric follicular lymphoma is considered a separate disease by researchers and, unlike the adult form, can often be cured with treatment.[1]
What Causes Follicular Lymphoma?
Doctors and researchers don’t fully understand what causes follicular lymphoma. However, they have identified specific changes that occur in the cells of people with this condition. In about 85 to 90 percent of cases, there is a chromosomal change called a translocation. Specifically, this is known as the t(14;18) translocation, where pieces of two different chromosomes swap places.[1][2]
This chromosomal swap causes a gene called BCL2 to become overactive. The BCL2 gene normally helps control cell death, a natural process that removes old or damaged cells from the body. When BCL2 is overexpressed due to the translocation, it prevents B cells from dying when they should. This gives these cells a survival advantage, allowing them to accumulate over time instead of being naturally cleared away.[2]
The t(14;18) translocation by itself is not enough to cause follicular lymphoma. Researchers have found these abnormal cells in healthy people who never develop the disease. It appears that additional genetic changes must occur over time for the cells to become truly cancerous. These changes happen gradually, which is why follicular lymphoma develops slowly and often isn’t discovered until later in life.[8]
Who is at Higher Risk?
Age is the most significant risk factor for developing follicular lymphoma. The disease primarily affects people who are 55 years or older, with many cases diagnosed in people in their 60s. It’s extremely rare in young adults and children, though when it does occur in younger people, it often behaves differently.[2]
Certain immune system problems may increase the risk of developing lymphomas, including follicular lymphoma. People with conditions that weaken the immune system are at higher risk. This includes people with congenital immunodeficiencies (immune problems present from birth), those infected with HIV, and people who have received organ transplants and must take immunosuppressant medications to prevent rejection.[8]
Autoimmune diseases, where the immune system mistakenly attacks the body’s own tissues, have also been linked to an increased risk of lymphoma. Examples include rheumatoid arthritis, lupus, and celiac disease. Some of the medications used to treat these conditions, such as methotrexate, may also play a role in increasing lymphoma risk, though it’s difficult to separate the effects of the disease from the effects of the treatment.[8]
Exposure to certain environmental factors has been associated with lymphoma risk. These include chemicals such as pesticides and herbicides, and hair dyes. A defoliant called Agent Orange, used during the Vietnam War, has also been linked to lymphoma. Additionally, some viruses have been implicated in causing various types of lymphomas, though these are more commonly associated with aggressive forms rather than follicular lymphoma.[2][8]
Recognizing the Symptoms
One of the challenging aspects of follicular lymphoma is that many people have no symptoms at all when they are first diagnosed. The cancer can grow quietly for years without causing any noticeable problems. In fact, it’s not uncommon for the disease to be discovered accidentally during routine blood work or imaging tests performed for other reasons.[4]
When symptoms do appear, the most common sign is painless swelling in one or more areas of the body. This typically occurs in the neck, armpit, or groin, where lymph nodes are located close to the surface of the skin. The swelling represents enlarged lymph nodes filled with cancer cells. Unlike swollen lymph nodes caused by infections, which are often tender and go away after a few weeks, lymph nodes affected by follicular lymphoma remain swollen and continue to grow slowly over time.[1][3]
Some people experience what doctors call “B symptoms,” which are general symptoms that can occur with lymphomas. These include heavy night sweats that soak through your clothes and bedding, fevers that come and go without an obvious cause like an infection, and significant weight loss—particularly losing 10 percent or more of your body weight within six months without trying. Fatigue, or a persistent feeling of tiredness that doesn’t improve with rest, is another common complaint.[1][4]
When follicular lymphoma affects the bone marrow, where blood cells are made, it can cause additional symptoms related to low blood cell counts. Low red blood cells, called anemia, can make you feel tired and short of breath. Low platelet counts can lead to easy bruising or bleeding problems. Low white blood cell counts can make you more susceptible to infections. Some people may feel full quickly when eating or experience abdominal discomfort if lymph nodes or the spleen become enlarged inside the abdomen.[4]
Can Follicular Lymphoma Be Prevented?
Unfortunately, there are no known ways to prevent follicular lymphoma because the exact cause is not fully understood. The chromosomal changes that lead to the disease occur spontaneously during a person’s life, and there is no way to predict or prevent them from happening.[1]
However, reducing exposure to known risk factors may help lower the overall risk of developing lymphomas. This could include minimizing contact with pesticides and other potentially harmful chemicals when possible, especially in occupational settings. People who work with such substances should use appropriate protective equipment and follow safety guidelines.[8]
For people with conditions that affect the immune system, working closely with healthcare providers to manage these conditions appropriately is important. While some medications that suppress the immune system may increase lymphoma risk, the benefits of treating serious conditions like autoimmune diseases or preventing organ transplant rejection typically outweigh these risks. The decision about treatment should always be made in consultation with your doctor.[8]
Because follicular lymphoma often doesn’t cause symptoms until it has progressed, there is currently no routine screening test recommended for the general population. If you have risk factors or are concerned about symptoms, speaking with your doctor is the best approach. They can assess your individual situation and determine whether any tests are warranted.
Understanding What Happens in the Body
In follicular lymphoma, the disease process begins in the bone marrow, where all blood cells are made. Normally, B cells develop in the bone marrow and then travel to lymph nodes to complete their maturation in special areas called germinal centers. These germinal centers contain structures called follicles, which are essentially training grounds where B cells learn to recognize and fight specific infections.[2][7]
In people who develop follicular lymphoma, the disease is believed to start when early B cells in the bone marrow acquire the t(14;18) translocation. These cells then migrate to the lymph nodes to continue their development. In the germinal centers, they pick up additional genetic and epigenetic changes—modifications that affect how genes work without changing the DNA sequence itself. These cumulative changes transform the cells into cancer cells that keep multiplying instead of maturing normally or dying when they should.[7]
The cancer cells in follicular lymphoma tend to grow in a pattern that mimics normal lymph node structures. They cluster together in groups that look like follicles, which is why the disease gets its name. These abnormal follicles can be seen under a microscope when a lymph node biopsy is examined by a pathologist. The cells within these follicles include a mix of smaller cells called centrocytes and larger cells called centroblasts, both of which are types of B cells normally found in germinal centers.[2][7]
Over time, the cancer cells can spread from the initial lymph nodes to other lymph nodes throughout the body. They can also leave the lymph nodes and travel through the bloodstream to the bone marrow and other organs such as the spleen or liver. Despite this spread, the cancer typically continues to grow slowly, which is characteristic of indolent lymphomas. The slow growth rate means that many people can live for years with the disease, sometimes without needing treatment.[1]
In a small percentage of cases, follicular lymphoma can transform into a more aggressive type of cancer. This process, called transformation, most commonly results in diffuse large B-cell lymphoma, a fast-growing cancer that requires immediate and intensive treatment. The risk of transformation varies among patients, and doctors monitor for signs of this change during follow-up care.[1][9]
When Follicular Lymphoma Returns
Because follicular lymphoma is generally considered incurable, it often returns after treatment. This is called relapsed or recurrent follicular lymphoma. The pattern of this disease is typically one of repeated cycles: periods of remission (when the cancer is controlled and symptoms are minimal or absent) followed by periods when the cancer becomes active again.[9]
Most people with follicular lymphoma will experience multiple relapses over the course of their lives. The time between relapses can vary widely from person to person. Some people may go many years before the cancer returns, while others may relapse more quickly. Research shows that people who relapse within two years of initial chemotherapy treatment tend to have a more challenging course of disease, with lower five-year survival rates compared to those who relapse later.[9]
When follicular lymphoma relapses, it doesn’t always require immediate treatment. Just as with newly diagnosed disease, if the relapse is not causing symptoms, doctors may recommend a period of active surveillance or “watch and wait.” During this time, patients are monitored closely with regular check-ups and tests, but treatment is held until symptoms develop or the disease begins to cause problems.[9]
When relapsed follicular lymphoma does need treatment, doctors have several options available. The choice depends on many factors, including how long it has been since the last treatment, what treatments were used previously, the extent of disease, the patient’s overall health, and their personal preferences. Treatment options may include different chemotherapy regimens, targeted therapies that attack specific features of cancer cells, immunotherapy drugs that help the immune system fight the cancer, or newer approaches such as CAR-T cell therapy.[9]
The term refractory follicular lymphoma refers to cases where the cancer doesn’t respond to treatment or progresses while someone is receiving treatment. Refractory disease can be more challenging to treat and may require novel therapies or participation in clinical trials testing new drugs. Despite these challenges, many treatment options continue to emerge, offering hope for people with difficult-to-treat disease.[9]