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Follicular Lymphoma Stages and Grades: What To Expect With Progression

Medically reviewed by Leonora Valdez Rojas, M.D.
Written by Maureen McNulty
Updated on August 12, 2024

When you receive a diagnosis of follicular lymphoma, your doctor will usually determine the grade and stage of your cancer. The cancer’s grade provides information about your B cells, a type of white blood cell important in the immune system for protecting against infections. The stage explains where in your body the lymphoma is located and how far it has spread.

Together, the grade and stage of the cancer help your doctor figure out which treatment options are best for you. Furthermore, your doctor may use a prognostic score to help predict your outlook. Although all this information is crucial for your doctor to analyze, it’s also important for you to know what it means for you and your future.

Read on to learn more about the grades and stages of follicular lymphoma and what to expect with progression.

Grades of Follicular Lymphoma

To determine the grade of your follicular lymphoma, a doctor will perform a lymph node biopsy, in which all or part of a lymph node is removed. (Lymph nodes are small, bean-shaped structures, located throughout the body, that play a role in the body’s immune system.) Samples of the lymph node are carefully studied under a microscope. The doctor will count the number of cancerous cells, some of which may appear larger than the other healthy B cells. The doctor will then assign your lymphoma a grade depending on how many large cells the doctor sees and how they are arranged.

Follicular lymphomas grades include grade 1, 2, 3A, and 3B. Grades 1 and 2 are usually grouped together and called “follicular lymphoma grade 1-2.” It can be useful to know what to expect from each grade.

The stage of follicular lymphoma is based on how cancer has spread and whether it is causing noticeable symptoms.

Most cases of follicular lymphoma are diagnosed at grade 1, 2, or 3A, meaning they’re low-grade lymphomas. Low-grade follicular lymphomas usually grow slowly and don’t cause many symptoms. Grade 3B, on the other hand, is considered high-grade lymphoma. It grows quickly and may require more aggressive treatment.

In some cases, follicular lymphoma may transform into a different type of lymphoma that is high-grade and grows faster. It may develop into diffuse large B-cell lymphoma (DLBCL), Burkitt lymphoma, high-grade B-cell lymphoma, or B-cell acute lymphoblastic leukemia.

Stages of Follicular Lymphoma

To see where cancer cells are located and whether they have spread, your doctor will usually use imaging tests such as a computed tomography scan (CT scan) or positron emission tomography scan (PET scan). These tests help your doctor see whether and where the cancer has spread so they can assign a stage to your lymphoma. You’ll also need to have a bone marrow biopsy to determine if there are cancer cells in your bone marrow, where blood cells develop.

Follicular lymphoma stages are based on how many lymph nodes are affected, where these lymph nodes are located, and whether cancer cells can be found in other organs inside or outside the lymphatic system. The higher the stage, the more advanced the lymphoma.

Follicular lymphoma staging can help your doctor predict your outlook and determine which treatment plan may be best for you. Knowing what to expect from each stage may help you feel better prepared if and when the cancer progresses.

Stage 1 Follicular Lymphoma

Stage 1 lymphoma indicates early disease that has not yet spread. It affects just one lymph node, a single group of lymph nodes, or a single organ outside the lymphatic system without nodal involvement. Stage 1 lymphoma is slow growing and may cause very few symptoms — or none at all. The symptom that often develops first is a swollen lymph node, which may appear as a lump in your armpit, neck, or groin.

If your lymphoma is at stage 1, you may receive radiation therapy. Stage 1 follicular lymphoma is often treated with radiation if the lymphoma is grade 1, 2, or 3A. If your lymphoma is grade 3B, it may require more aggressive treatment, including targeted therapy such as rituximab (Rituxan) or chemotherapy.

If your stage 1 follicular lymphoma consists of a small tumor, radiation may be enough to eliminate the cancer. In one study, 40 people with stage 1 or 2, grade 1 or 2 follicular lymphoma were treated with radiation. Most of the trial participants had good outcomes, and after five years, two-thirds remained disease-free.

Stage 2 Follicular Lymphoma

In stage 2, lymphoma has begun to spread but only to nearby areas. In this stage, lymphoma cells can be found in two or more groups of lymph nodes located on the same side of the diaphragm (the muscle that separates your chest from your abdomen). Alternatively, a stage 2 follicular lymphoma diagnosis can mean that cancer cells are found in one organ plus a nearby group of lymph nodes.

Like stage 1 lymphoma, stage 2 lymphoma may be curable with radiation treatments if the tumor is small. Some people will also benefit from treatment with targeted therapy such as rituximab or chemotherapy.

Stage 3 Follicular Lymphoma

In stage 3 follicular lymphoma, cancer cells have spread further, and lymphoma can be found either on both sides of the diaphragm or above it but with involvement of the spleen. Most cases of follicular lymphoma are diagnosed at advanced stages — stages 3 and 4.

The goal of first-line treatment is to eliminate the cancer. Maintenance treatment aims to get rid of remaining cancer cells and keep them from growing. First-line treatment often consists of chemotherapy, such as bendamustine (Bendeka, Treanda) combined with a monoclonal antibody — rituximab or obinutuzumab (Gazyva) — or a combination of chemotherapy drugs that are referred to using the acronym CHOP: cyclophosphamide, doxorubicin (also known as hydroxydaunorubicin), vincristine (formerly sold as Oncovin), and prednisone.

Maintenance treatment often includes the use of rituximab. People following this treatment plan typically take this medication once every few months for up to two years.

Stage 4 Follicular Lymphoma

Stage 4 follicular lymphoma is the most advanced stage of lymphoma — the cancer has spread to multiple organs or regions of the body. If someone has cancer cells in the bone marrow or in the liver, they’ll be diagnosed with stage 4 lymphoma.

As lymphoma spreads to other regions, it may be more likely to cause symptoms. The tumor may press on the organ it has spread to and generate additional symptoms. For example, a tumor compressing the lungs may lead to coughing or breathing problems. Additionally, when lymphoma reaches the spleen or bone marrow, it often causes anemia (low levels of red blood cells). Symptoms of anemia include fatigue, frequent infections, and bleeding problems.

Read more about how follicular lymphoma develops and common symptoms of the disease.

Stage 4 tumors are often treated using a similar plan as stage 3 lymphomas. First-line treatments with chemotherapy and rituximab may be followed by taking rituximab alone for a long period of time.

Other Staging Information

In addition to a number (1 through 4), your stage may include the letter A or B. For example, your diagnosis may be stage 2A or 2B. These letters indicate whether you have symptoms. People with B-stage lymphoma have a specific set of symptoms known as “B symptoms,” which may include fever, night sweats, and weight loss. People with A stage lymphoma don’t have these symptoms.

Other letters may be added to the stage based on what parts of the body are affected. If there are cancer cells in organs outside the lymph nodes, an E for “extranodal” may be added to the stage. If cancer cells are in the spleen, an S may be added.

Letters in your staging may indicate whether you have symptoms or what parts of the body are affected like S for “spleen.”

Treatment for Follicular Lymphoma

When you know your cancer’s grade and stage, you may wonder what to expect from treatment. The need for lymphoma treatment at stages 2, 3, and 4 will depend on the person’s symptoms. People without symptoms may be managed with monitoring only, following a watchful waiting approach, in which a person has frequent checkups to look for signs that the cancer is progressing. If someone has symptoms, they may receive treatments that aim to relieve those specific symptoms.

The U.S. Food and Drug Administration (FDA) has approved several new drugs to treat follicular lymphoma:

  • Tazemetostat (Tazverik), a new targeted therapy, has been tested and approved for people with follicular lymphoma that came back or didn’t shrink after other treatments.
  • Lenalidomide (Revlimid) is an immunomodulating drug that’s approved for previously treated follicular lymphoma in combination with targeted therapies.
  • Axicabtagene ciloleucel (Yescarta) is a chimeric antigen receptor T-cell therapy that’s been approved for people with follicular lymphoma whose cancer progressed after one treatment option.

Several other drugs have recently been approved specifically for treatment of relapsed or refractory follicular lymphoma:

  • Tisagenlecleucel (Kymriah) — Approved in May 2022
  • Mosunetuzumab-axgb (Lunsumio) — Approved in December 2022
  • Zanubrutinib (Brukinsa) — Approved in March 2024
  • Lisocabtagene maraleucel (Breyanzi) – Approved in May 2024
  • Epcoritamab-bysp (Epinkly) — Approved in June 2024

Talk to your oncology team if you have follow-up questions about treatment options based on your grade and stage of follicular lymphoma. That way, you’ll feel better informed about what to expect, such as side effects, and how treatment might change as the cancer changes.

Prognosis Score

When you have follicular lymphoma, it can be helpful to know what to expect in terms of prognosis. Some doctors use a tool such as the Follicular Lymphoma International Prognostic Index (FLIPI) to obtain a prognostic score between zero and 5. This score estimates outlook and survival rates based on prognostic factors that help predict whether the cancer may get worse. These factors include:

  • How far your lymphoma has spread
  • Your lymphoma stage
  • Your age
  • Your level of lactate dehydrogenase (LDH), a protein your body makes more of when you have cancer, which is measured with a blood test
  • Your hemoglobin level, which is measured with a blood test

Read more about how relapsed and refractory follicular lymphoma is treated.

Talk With Others Who Understand

On MyLymphomaTeam, the social network for people with lymphoma and their loved ones, more than 18,000 people come together to ask questions, give advice, and share their stories with other people who understand life with follicular lymphoma.

Have you been diagnosed with follicular lymphoma? What was the grading and staging process like for you? Share your experience in the comments below, or start a conversation by posting on your Activities page.

Leonora Valdez Rojas, M.D. received her medical degree from the Autonomous University of Guadalajara before pursuing a fellowship in internal medicine and subsequently in medical oncology at the National Cancer Institute. Learn more about her here.
Maureen McNulty studied molecular genetics and English at Ohio State University. Learn more about her here.

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