Follicular Lymphoma
Follicular lymphoma is a slow-growing cancer that affects white blood cells and is the second most common type of non-Hodgkin lymphoma. While there is currently no cure, many people live for years with this condition, and advances in treatment are helping patients live longer, healthier lives.
Table of contents
- What is Follicular Lymphoma?
- Signs and Symptoms
- Causes and Risk Factors
- How Doctors Diagnose This Condition
- Stages of Follicular Lymphoma
- Treatment Options
- Living with Follicular Lymphoma
- Outlook and Prognosis
What is Follicular Lymphoma?
Follicular lymphoma is a type of cancer that affects white blood cells called lymphocytes, which are cells that help your body fight infections. It is a form of non-Hodgkin lymphoma, which means it is a cancer of the lymphatic system that is different from Hodgkin lymphoma[1]. The lymphatic system is made up of organs, glands, vessels, and clusters of cells called lymph nodes. It’s part of the body’s immune system that helps fight germs and disease[1].
Follicular lymphoma gets its name from the fact that the cancer starts in the follicles of the lymph nodes. These follicles are groups of germ-fighting white blood cells inside each lymph node. When these white blood cells become cancer cells, they may build up in the lymph nodes and continue to gather in groups that look like follicles[1].
This type of lymphoma is considered indolent, meaning it is slow-growing[2][3]. Follicular lymphoma is the second most common type of non-Hodgkin lymphoma, with about 15,000 to 20,000 new cases diagnosed in the United States each year[2]. It accounts for 20 to 30 percent of all non-Hodgkin lymphoma cases[3][6].
Follicular lymphoma can affect the lymph nodes, bone marrow, and other organs[1][2]. Although it usually cannot be cured, people can live for many years with this condition, and it is often treated as more of a chronic disease[3]. Most people with this condition die with it, not from it[2].
Signs and Symptoms
Follicular lymphoma grows slowly and may never cause symptoms[1]. Many people do not notice symptoms right away, and in some cases, it is discovered during routine bloodwork or imaging for another issue[3]. You can have follicular lymphoma without having any symptoms[2].
When symptoms do appear, the most common one is painless swelling in the neck, armpit, or groin. This is a sign of enlarged lymph nodes[1][2][3]. These swellings are usually painless and persistent[3].
Other symptoms that may develop include:
- Fatigue or feeling very tired[1][3]
- Fever[1][3]
- Night sweats[1][3]
- Losing weight without trying (especially losing 10% or more of your weight within the past six months)[1][2]
- Feeling full quickly[1]
- Shortness of breath[4]
- Recurring infections due to weakened immune function[3]
If follicular lymphoma affects your spleen or bone marrow, it may lead to low red blood cells and anemia, which is a condition where you don’t have enough healthy red blood cells[21]. Signs of anemia may include skin that looks paler than usual, muscle weakness, feeling lightheaded, and shortness of breath[21].
If you have any of these symptoms, it’s important to see your doctor. However, remember that these symptoms can also be caused by other conditions that are not cancer[3].
Causes and Risk Factors
Doctors don’t know exactly what causes follicular lymphoma[1][4]. Researchers do know that changes in people’s chromosomes happen in about 85% of cases. These changes transform normal B cells into cancer cells[2]. B cells are white blood cells that make antibodies to fight infections. But cancer cells don’t function in this normal way. Instead, they multiply and grow[2].
Most cases of follicular lymphoma show a translocation (a rearrangement) in the chromosomes called t(14;18). This leads to an overexpression of a protein called BCL2, which is an antiapoptotic protein that helps cells avoid dying when they should[6]. These genetic changes happen at some point during your lifetime. Follicular lymphoma is not inherited[2].
Several factors may increase your risk of developing follicular lymphoma:
- Age: People age 65 and older are more likely to have this condition. The median age at diagnosis is around 60 years[2][4].
- Race: People who are white receive this diagnosis more often than people of other races[2][6].
- Family history: If you have a family history of lymphoma, this may increase your risk[4].
- Immune system disorders: You may be at increased risk if you have HIV, rheumatoid arthritis, lupus, or celiac disease, which are all immune system disorders[4].
- Exposure to certain chemicals: Chemicals such as pesticides and herbicides have been associated with lymphoma[4].
It’s important to note that children can develop follicular lymphoma, but it’s so different from the adult form that researchers consider it a different type of cancer. Unlike the adult type, pediatric follicular lymphoma is often curable[2].
How Doctors Diagnose This Condition
Follicular lymphoma diagnosis often begins with a physical exam. Your doctor will check for swollen lymph nodes in the neck, underarms, and groin, and check for a swollen spleen or liver[9]. Your doctor will also ask you questions about your symptoms and medical history[4].
If your doctor notices that you have enlarged lymph nodes, it doesn’t necessarily mean you have cancer. Enlarged lymph nodes are most often caused by infections or other problems. Your doctor may give you an antibiotic to see if the swelling goes down in a few weeks[4].
The main test to diagnose follicular lymphoma is a lymph node biopsy. This is a procedure to remove a sample of tissue for testing in a lab. A biopsy is the only way to know for sure if you have follicular lymphoma[2][9]. Your doctor may remove all or part of a lymph node. If a node is hard to reach, they may use a very thin needle to remove a little bit of lymph node tissue through your skin. This is usually an outpatient procedure, which means you don’t need to stay overnight in a hospital[4].
After confirming your diagnosis, your healthcare provider will order additional tests to stage the cancer and determine how far it has spread. These tests may include[2][9]:
- Blood tests to check your overall health and to measure levels of certain substances
- PET scans (positron emission tomography scans) to create pictures of organs and tissues inside the body
- CT scans (computed tomography scans) to make detailed pictures of areas inside the body
- MRI (magnetic resonance imaging) to make pictures using magnets and radio waves
- Bone marrow aspiration and biopsy to collect cells from the bone marrow for testing
In the lab, experts will look at the tissue from the biopsy under a microscope. Testing lymphoma cells in the lab helps doctors understand the type and grade of follicular lymphoma[9].
Stages of Follicular Lymphoma
After diagnosis, doctors stage the lymphoma to find out how many places in your body are affected and where they are. Staging helps your doctor plan the best treatment for you[8].
Follicular lymphoma stages range from I to IV[2]:
- Stage I: Cancer is in one or more lymph nodes[2]
- Stage II: Cancer is in lymph nodes above or below your diaphragm. Your diaphragm is a band of muscle that separates your chest from your abdomen[2]
- Stage III: Cancer is in lymph nodes on both sides of your diaphragm[2]
- Stage IV: Cancer has spread beyond your lymph nodes to other organs[2]
Since follicular lymphoma doesn’t cause symptoms right away, most people have Stage III or IV disease by the time they’re diagnosed[2]. Despite the advanced stage at diagnosis, many patients do not require treatment for prolonged periods of time[14].
Doctors also grade follicular lymphoma based on how the cells look under a microscope. The grade tells the doctor how quickly the lymphoma is likely to grow and spread. Follicular lymphoma is usually divided into three grades[8]:
- Grade 1: Slow growing
- Grade 2: Slow growing
- Grade 3: This is divided into 3A (slow growing) and 3B (faster growing)
Grades 1, 2, and 3A are considered low grade or slow growing, and doctors treat them the same way. Grade 3B is faster growing and doctors usually treat it similar to high grade lymphoma[8].
Treatment Options
Treatment for follicular lymphoma depends on the stage of the disease, the grade, how severe your symptoms are, and your overall health. Because follicular lymphoma is slow-growing, you may not need treatment right away if you don’t have symptoms[1][2].
Active Surveillance (Watch and Wait)
If you have no symptoms or very few symptoms, your doctor may recommend not treating the disease right away. This approach is called active surveillance or “watch and wait”[3][10]. Research shows that early treatment of asymptomatic follicular lymphoma doesn’t improve survival[2]. Studies have shown that patients who are managed with active surveillance have survival outcomes similar to those who are treated early in the course of their disease[10].
With this strategy, your doctor will check on your condition regularly through checkup visits and various tests, such as blood tests and imaging scans. You’ll only get treatment if you begin to develop symptoms or if there are signs that the disease is progressing[2][10].
Radiation Therapy
For Stage I follicular lymphoma (limited disease), doctors often use radiation therapy. Radiation therapy uses high-energy rays to kill cancer cells. In about half of people with limited disease, radiation alone can provide a long-lasting remission[2][10].
Chemotherapy and Immunotherapy
For more advanced stages of follicular lymphoma, treatment may involve chemotherapy, which uses drugs to kill cancer cells. Follicular lymphoma is generally very responsive to chemotherapy[10].
Doctors often combine chemotherapy with immunotherapy, which helps your immune system fight cancer. A common immunotherapy drug is rituximab (Rituxan), which is a monoclonal antibody. Monoclonal antibodies target specific markers found on cancer cells and help recruit immune cells to destroy tumors[10].
Common combination regimens include[10]:
- R-Bendamustine (rituximab and bendamustine)
- R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone)
- R-CVP (rituximab, cyclophosphamide, vincristine, and prednisone)
After initial treatment, some patients may receive maintenance therapy for up to two years. This involves continued use of monoclonal antibodies to help prolong remission for patients with no signs of lymphoma[10].
Other Treatment Options
Other treatments that may be used include[1][2]:
- Targeted therapy: Drugs that target specific proteins or genes in cancer cells
- CAR-T cell therapy: A treatment that uses your own immune cells, which are modified in a lab to fight cancer
- Radioimmunotherapy: Treatment that uses a radioactive particle connected to an antibody that targets cancer cells
- Stem cell transplant: In some cases, particularly for relapsed disease
Treatment for Relapsed Disease
Follicular lymphoma is a continually relapsing disease. After treatment, the cancer often comes back, and each time it returns, the interval from initial therapy to relapse becomes an important factor[11]. When the disease relapses, management is based on the initial treatment, the interval from prior therapies, and the toxicity of available therapies. Multiple agents are available for patients after two or more lines of therapy[11].
There is also a small chance (2-3% each year) that follicular lymphoma can progress to a more aggressive form of cancer called diffuse large B-cell lymphoma. This is called transformation[2][7]. When this happens, more intensive treatment is needed.
Living with Follicular Lymphoma
Living with follicular lymphoma can be challenging, not just because of the physical symptoms, but also due to the emotional impact. Although it takes time and may involve making some changes to your everyday life, most people adjust well to life after a diagnosis of follicular lymphoma and find a “new normal”[23].
Managing Fatigue
Cancer-related fatigue is a common and often intense symptom of follicular lymphoma that can significantly affect your daily life and overall well-being[21]. Fatigue is also a potential side effect of cancer treatments like chemotherapy, radiation therapy, or immunotherapy[21].
Here are some ways to help manage fatigue:
- Stay active: It may seem counterintuitive, but physical activity can actually give you energy. Studies show that people with lymphoma can reduce fatigue by being active. Even short bursts of activity, like walking for 5-10 minutes, can help[21].
- Eat well: Focus on iron-rich foods if you have anemia. Foods like fortified cereals, oysters, white beans, beef liver, lentils, cooked spinach, and firm tofu can help[21].
- Rest when needed: Listen to your body and rest when you feel tired.
Healthy Living
A healthy lifestyle has lots of benefits, both physically and emotionally. It can help prepare you for treatment, reduce the risk of side effects, and lower the likelihood of developing other illnesses in the future[23].
Some recommendations include:
- Quit smoking: Studies show that smoking cigarettes puts you at a higher risk for follicular lymphoma and raises your chances of dying from the disease[18].
- Exercise regularly: Physical activity can help during treatment for follicular lymphoma. A couple of studies found that exercise during chemotherapy greatly improved a person’s quality of life. Stick to moderate activities like walking, cycling, dancing, water aerobics, stretching, tai chi, or yoga[18].
- Eat healthy foods: A nutritious diet can help keep you healthy mentally and physically. During treatment, a healthy diet can help you better tolerate treatment. Keep a good balance of carbohydrates, protein, fat, fiber, dairy, vitamins, minerals, fruits, and vegetables[18].
- Stay hydrated: It’s important to drink plenty of liquids during treatment. Experts usually suggest around 6-8 glasses each day[18].
Protecting Yourself from Infection
Your risk of infection is higher with lymphoma. While it isn’t possible to protect yourself completely from infections, there are things you can do to lower your risk[18]:
- Stay away from sick people when possible
- Don’t share cups or other personal items
- Wash your hands frequently, especially after touching animals or before eating
- Keep your household clean
- Wear shoes outside to protect your feet from cuts or wounds
- Keep cooked and uncooked food separate
- Cook and store your food at the proper temperatures
Emotional Support
A follicular lymphoma diagnosis can feel overwhelming. It’s important to find someone to talk to and not to compare your journey to anyone else’s—everyone’s experience is different[19]. Being diagnosed can be hugely scary, and many people describe it as “out of this world” experience[19].
Living with the knowledge that the lymphoma may return can also be challenging. Some patients describe always waiting for it to come back, always waiting to feel ill or for lumps and bumps to appear. This pressure can grow the further on you go without having relapsed[19].
Support resources are available through lymphoma organizations, including helplines, peer support groups, and online communities. These can provide valuable information and emotional support throughout your journey[3].
Outlook and Prognosis
Follicular lymphoma is usually not considered curable, but it is categorized more as a chronic disease. Patients can live for many years with this form of lymphoma[3]. The median survival of patients with follicular lymphoma has historically been approximately 8-10 years, but literature from the rituximab era has shown a further increase in overall survival[14].
Recent advances in treatment have substantially improved patient survival. New treatments, including newer immunotherapy drugs, offer hope that a cure may be on the horizon[2][12]. Most people with follicular lymphoma die with it, not from it[2].
Although most patients have indolent disease and remain asymptomatic for decades, with many dying with lymphoma rather than because of it, some patients have an aggressive clinical course. The clinical heterogeneity of follicular lymphoma poses a challenge to doctors, who need to consider age, comorbidities, likelihood of relapse, and treatment accessibility when deciding on the most appropriate treatment strategy[12].
The prognosis can vary depending on several factors, including:
- The stage and grade of the disease at diagnosis
- Your age and overall health
- How well you respond to treatment
- Whether the disease transforms to a more aggressive type
Regular follow-up with your healthcare team is important. They will monitor your condition and help you manage any symptoms or side effects from treatment. With ongoing medical care and a healthy lifestyle, many people with follicular lymphoma live full and active lives for many years[23].
