An Overview of Follicular Lymphoma

Follicular lymphoma is a common type of non-Hodgkin Lymphoma (NHL). It is usually a slow-growing lymphoma that arises from B-cells (B lymphocytes), a type of white blood cell.

Follicular lymphoma is also called an indolent or low-grade lymphoma for its slow nature, both in terms of its behavior—slower growth—and how it looks under the microscope—less abnormal (more differentiated) than high-grade malignancies.

Checking the Size of a Man's Lymph Nodes
FatCamera / Getty Images

Risk Factors

Follicular may affect anyone of any age, yet it is most common in older adults. That average age at the time of diagnosis is around 60, and it affects men and women equally.


Follicular lymphoma is the most common type of slow-growing lymphoma.

Signs and Symptoms

The appearance of follicular lymphoma is often subtle, with minor warning signs that can go unnoticed for a long time. Symptoms may include:

  • Enlargement of lymph nodes: Swelling of lymph nodes in some region of the body is the most common symptom of follicular lymphoma. These nodes may felt in the neck, the armpit, or the groin, or may be noted on imaging tests in other regions of the body (such as with mediastinal lymph nodes in the chest or retroperitoneal lymph nodes in the abdomen). (The lymph node learning center discusses the function of lymph nodes and locations in greater depth.)
  • Fever of unknown origin (FUO): An elevated temperature (over 100.4 degrees F or 38 degrees C) which is present for three or more consecutive days without any obvious cause may be a symptom of lymphoma. Rather than being related to an undiagnosed infection, it's thought that an FUO is caused by chemical signaling pathways related to cancer itself which increases core body temperature.
  • Unintentional weight loss: Unexplained weight loss is defined as the loss of 5 to 10 percent of body weight (for example, 7.5 to 15 pounds in a 150-pound person) over a period of 6 months or less.
  • Night sweats: Night sweats differ from hot flashes and sweating in that many times they are literally drenching and people need to change their bedclothes and bedding, sometimes several times during the night.
  • Fatigue: Cancer fatigue often differs from "ordinary fatigue" in that it does not improve with a good night of sleep or a cup of coffee.
  • Shortness of breath
  • Generalized Itching: Itching tends to occur all of the body and can be very intense.

The B symptoms of lymphoma include three primary symptoms which may help in predicting how cancer will progress and respond to treatment and include:

  • Fever
  • Unintentional weight loss
  • Drenching night sweats


Follicular lymphoma is usually diagnosed with a lymph node biopsy. This may be done as a surgical biopsy (with nodes that are palpable such as in the neck) or as a core needle biopsy (for nodes deeper in the body).

A small sample of the affected node is taken and examined under the microscope by a pathologist. The features of the affected node suggest the presence of lymphoma. In addition to the appearance under the microscope, immunohistochemistry tests are done to check for lymphoma CD tumor markers and determine the type of non-Hodgkin lymphoma.

Why It's Called 'Follicular' Lymphoma: Like most lymphomas, follicular lymphomas mainly affect lymph nodes. When the lymph nodes affected by this lymphoma are seen under the microscope, they show rounded structures called "follicles." The lymphoma is therefore called follicular lymphoma.

Tests After a Diagnosis: In addition to the biopsy related tests above, a number of other tests are usually required when follicular lymphoma is first diagnosed. These allow the doctor to see the exact extent of the disease and which organs are affected. Blood tests, CT scans and bone marrow tests are usually required.

Research from 2016 has also explored the utility of PET/CT scans to monitor follicular lymphoma, for instance, when results of a CT scan are unclear. In PET-CT, a radioactive tag (18F-fluorodeoxyglucose) is injected into the patient before the CT scan and areas of active disease light up if they take up the radioactive glucose. This helps differentiate active regions of cancer from areas of scar tissue which can appear similar to CT scans.


The stage of follicular lymphoma indicates the extent to which the disease has spread and is important in choosing the best treatments and in estimating the prognosis of the disease. Lymphoma spreads to lymph nodes as well as other organs in the body including the bone marrow. There are four stages of lymphoma which include:

  • Stage I: Only one lymph node (or lymph structure) is involved.
  • Stage II: Two or more lymph nodes (or lymph structures) are involved but only on one side (above or below) the diaphragm.
  • Stage III: Lymph nodes (or structures) on both sides of the diaphragm are involved.
  • Stage IV: The lymphoma is present in the bone marrow and/or tissues or organs other than lymph nodes or lymph structures.

In addition to a number, lymphomas are also given a designation of A or B, with A meaning there are no B symptoms and B indicating the presence of the B symptoms of lymphoma (listed above under symptoms).


Follicular lymphoma is usually a slow-growing disease and often remains unnoticed for a long time in the body before it is diagnosed. As the symptoms are subtle, the disease is often advanced before a diagnosis is made, with most individuals diagnosed when the lymphoma is stage III or IV.

Even in the more advanced stages of the disease, however, there is usually no immediate threat to life at the time of diagnosis. The disease tends to have a "waxing and waning" course, meaning that it flares up and regresses a number of times over several years. Even though none of the treatments are curative in advanced stages, many patients survive for 8 to 10 years or more with treatment.

Transformation: Follicular lymphoma often undergoes a transition at some time, from a smoldering disease to actively progressive disease. This is referred to as transformation. The transformation may occur in all of the cells, or only in one particular part of cancer. The presence of B symptoms increases the chance that the tumor will transform in the near future. After a follicular lymphoma "transforms" it is often treated similarly to a diffuse large B-cell lymphoma.


We aren't certain what causes lymphomas, though there are some risk factors associated with an increased risk. Some risk factors associated with lymphoma, and follicular lymphoma (FL) specifically, include:

  • A diet lower in fruits and vegetables
  • Lower levels of physical activity
  • Smoking: Unlike other non-Hodgkin's lymphoma, the risk of FL is increased in people who smoke.
  • Alcohol intake: Alcohol use may affect risk in either direction; small amounts of wine are associated with slightly lower risk and higher daily amounts of alcohol are associated with an increased risk.
  • Age (as noted above, FL increases with age)
  • Obesity
  • Immunosuppression
  • Environmental exposures to pesticides, industrial solvents, and hydrocarbons
  • Genetic susceptibility may contribute to some cases.
  • Unlike other types of non-Hodgkin's lymphoma, FL is not linked with Epstein-Barr virus infections, H.pylori.
  • UV light exposure is associated with a decreased risk. (Vitamin D may play a protective role against FL).


There are several treatments options available for follicular lymphoma, with the best choices having to do with the stage of cancer, its aggressiveness (the grade), other medical conditions you have, your general health, and what treatments you have had in the past. For early-stage disease, radiation alone may be all that is needed. With advanced-stage disease, the drugs below are often used in combination (see combination therapy below).

Wait and Watch

If a follicular lymphoma is not causing symptoms, watchful waiting may be the "treatment" of choice. With watchful waiting, you will be closely monitored with exams and imaging tests so that treatment can be initiated when cancer begins to progress. This can sound frightening, though it has been found that the survival rate does not change when this approach is used.

Radiation Therapy

For stage I follicular lymphomas, radiation therapy may be the only therapy needed, and may cure the disease. Involved field radiation therapy (IFRT) is often the radiation method used. In contrast to extended field radiation therapy, IFRT delivers radiation to only the affected tissues, sparing healthy tissue. (Radiation therapy carries a risk of secondary cancers and this decreases that risk.)


Chemotherapy is often used with good responses. It is often used as part of a combination therapy (see below).

Targeted Therapy

Targeted therapy uses medication which directly targets cancer cells or the signaling pathways involved in tumor growth.

The monoclonal antibody Rituxan (rituximab) is often used (see combination therapies) along with chemotherapy and has made a significant difference in survival rates. Monoclonal antibodies such as rituximab are man-made antibodies designed to attach to specific markers present on lymphoma cells (CD markers). Both rituximab and Gazyva (obinutuzumab) attack the CD 20 tumor marker.

Tazverik was approved to treat adult patients with relapsed or refractory disease whose tumors are positive for an EZH2 mutation, after having tried at least two other therapies. It can also be used as a treatment for adult patients with relapsed or refractory disease who have no satisfactory alternative treatment options.

Treanda (bendamustine) has also been found to increase progression-free survival but has a greater incidence of side effects. Gazyva (obinutuzumab) plus bendamustine may work for those who do not respond to rituximab.


Radioimmunotherapy is a treatment in which a drug (usually a monoclonal antibody) is combined with particles of radiation allowing the drug to deliver the radiation precisely to cancer cells. An example is Zevalin (yttrium-90 ibritumomab tiuxetan).

Clinical Trials

Many drugs and procedures are currently being studied in clinical trials, including the immunotherapy drug Keytruda (pembrolizumab), stem cell transplants, and more. Here are some of the latest discoveries in research on lymphoma.

Combination Therapies

There are several combination therapies that may be used both initially or when a follicular lymphoma progresses. These include:

  • R-Bendamustine (rituximab and bendamustine): This combination appears to have fewer side effects (less peripheral neuropathy and hair loss).
  • Treanda (bendamustine) alone
  • Rituximab alone
  • R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone)
  • R-CVP (rituximab, cyclophosphamide, vincristine, and prednisone)
  • Fludara (fludarabine) and rituximab
  • Zydelig (idelalisib) with or without rituximab
  • Revlimid (lenalidomide) with or without rituximab

Maintenance Therapy

When follicular lymphoma responds, targeted therapy such as rituximab may be continued for a few years to help prolong remission.

Side Effects

The side effects of your treatment will depend on the specific treatment you receive. With targeted therapy such as rituximab, the most common side effect is allergic reactions during rituximab infusions. Other side effects may include low blood counts and a cough or nasal discharge.


If follicular lymphoma is found in the early stages, it may be curable with radiation therapy. Yet even with the more advanced stages of the disease, people can often survive many years with treatment. A tool called the Follicular Lymphoma International Prognostic Index or FLIPI is sometimes used to get an idea about your specific prognosis. This index considers several different factors and provides a number that estimates the 10-year survival rate of the disease.

Keep in mind that there are many different factors that affect prognosis with cancer, and sometimes people live much longer than expected, or vice versa. We do know that tobacco use, obesity, and alcohol use are associated with poorer survival, and therefore a healthy lifestyle is very important.


The treatment of lymphoma is changing rapidly. It's important to learn all you can about your cancer. Studies tell us that people who are educated about their cancer not only feel more in control and empowered, but may have better outcomes as well.

Ask for help and let others help you. Consider becoming involved in a support group and/or online lymphoma support community. No matter how loving your friends and family, it can be priceless to talk with others who are facing the same challenges you are.

Most of all, remember that significant advances are taking place in the treatment of cancers such as follicular lymphoma. Be your own advocate as a cancer patient and learn about these discoveries. There is much hope.

A Word From Verywell

If you're wondering what your loved one may be going through, you may wish to check out what cancer survivors have said when asked the question: what is it really like to live with cancer? Follicular lymphoma, in being slow-growing cancer, is often present for many years. In other words, it is a marathon and not a sprint. Take a moment to learn how to take care of yourself as you care for a loved one with cancer.

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