Follicular lymphoma

This page was reviewed under our medical and editorial policy by

Swetha Kambhampati, MD, Hematologist-Oncologist, City of Hope | Duarte

This page was reviewed on June 12, 2023.

Follicular lymphoma is considered a form of non-Hodgkin lymphoma that typically grows and spreads slowly and doesn’t exhibit many signs or symptoms. However, some follicular lymphomas may grow more rapidly.

Non-Hodgkin lymphoma is a type of cancer that begins in the lymphatic system, which is part of your immune system. The lymphatic system is made up of:

  • Lymph (a clear liquid that carries lymphocytes)
  • Lymphocytes (white blood cells)
  • Lymph nodes
  • Spleen
  • Tonsils
  • Thymus gland
  • Bone marrow

The three types of lymphocytes are:

Follicular lymphoma begins in the B lymphocytes, typically affecting the lymph nodes, although it may also metastasize to the bone marrow and/or spleen. Twenty percent of all lymphomas in the United States are follicular lymphomas, according to the American Cancer Society.

Follicular lymphoma causes and risk factors

The exact cause of follicular lymphoma is unknown, but researchers believe environmental and immunological factors—such as exposure to pesticides and prior use of immunosuppressive therapy—and certain genetic influences may be at play. According to the National Organization for Rare Disorders, the majority of follicular lymphoma patients (about 85 percent) have a genetic abnormality called a translocation in the cancer cells, in which portions of chromosomes 14 and 18 break off and switch places.

Follicular lymphoma affects slightly more women than men, and it’s less likely to occur in people of Asian or African descent. It’s rare in young people—in fact, the median age at diagnosis is 60-65.

Follicular lymphoma symptoms

Though follicular lymphoma doesn’t always cause noticeable symptoms, you may experience enlarged lymph nodes in your:

  • Armpits
  • Neck
  • Groin
  • Abdomen

You may also have:

  • Spleen enlargement
  • Fatigue
  • Drenching night sweats
  • Chills
  • Unexplained weight loss
  • Shortness of breath

Follicular lymphoma diagnosis

Your doctor can work out a diagnosis of follicular lymphoma through specific testing.

First, your doctor will check for outward signs of lymphoma. During a physical examination, the doctor typically palpates any hardened or enlarged lymph node in your body and examines other organs for swelling or an abnormal buildup of fluid. You may also be asked questions about any symptoms you’ve noticed.

If lymphoma is suspected, you’ll likely undergo:

Blood test: Your doctor will order blood work to check your red blood cell, white blood cell, platelet and LDH levels. LDH (lactate dehydrogenase) is an enzyme that’s often elevated in progressed cases of lymphoma.

Biopsy: If your doctor orders a biopsy, a portion of your lymph node or an entire lymph node will be removed under local or general anesthesia to be examined in a laboratory. This can be done with ultrasound or CT guidance, or sometimes may require a surgical excisional biopsy. A biopsy is the only way to confirm a follicular lymphoma diagnosis.

Imaging tests: A positron emission tomography (PET) and computed tomography (CT) scan, which is called a PET/CT scan when combined, may be used to obtain 3D images of your tissues and organs. This procedure uses a radioactive sugar that’s injected into your body (cancer cells tend to absorb more of this substance than normal cells and appear on the scan as brighter images).

Bone marrow testing: Your doctor may suggest a biopsy of your bone marrow to confirm the presence of lymphoma.

FISH test: A fluorescence in situ hybridization (FISH) test attaches probes marked by a bright dye to your chromosomes so that any translocations are visible.

PCR: A polymerase chain reaction (PCR) test identifies and copies small segments of DNA to detect genetic alterations.

Follicular lymphoma stages

The care team uses a PET/CT scan to stage follicular lymphoma. The stages are listed below.

Stage 1 follicular lymphoma

Only one lymph node region is involved, or only one lymph structure is involved. 

Stage 2 follicular lymphoma

Two or more lymph node regions or lymph node structures on the same side of the diaphragm are involved. 

Stage 3 follicular lymphoma

Lymph node regions or structures on both sides of the diaphragm are involved.

Stage 4 follicular lymphoma

Lymphoma has spread outside of the lymph nodes to bone marrow and/or other organ systems.

Follicular lymphoma treatment

If you have mild or no symptoms, your care team may advise a period of watchful waiting, monitoring your follicular lymphoma with regular checkups and laboratory and imaging tests.

If you do have bothersome symptoms (fevers, chills, night sweats, dropping blood counts, growing lymph nodes causing symptoms or enlarging spleen, among others) or the disease is spreading, you may undergo one of the following treatments.

  • Radiation therapy or radioimmunotherapy: Patients with a local, single site of disease may be responsive to radiation alone. When the disease is more advanced, particles of radiation may be attached to monoclonal antibodies made in the lab and engineered to attach to a specific target on the lymphoma cell called CD20, a treatment known as radioimmunotherapy. When this radiation-enhanced monoclonal antibody enters the body, it seeks out and links to its target to deliver the radiation.
  • Monoclonal antibody therapy: These drugs, such as Rituxan® (rituximab) or Gazyva® (obinutuzumab), target the CD20 marker on the surface of B-cells. Once the drug binds to the marker, it triggers cell death and stimulates your immune system to destroy the B-cells.

Common chemoimmunotherapy combinations for follicular lymphoma include:

  • R-Benda (rituximab and bendamustine)
  • R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone)
  • R-CVP (rituximab, cyclophosphamide, vincristine and prednisone)
  • R-Squared (Revlimid® and rituximab)

Newer treatments are emerging for the treatment of follicular lymphoma when the disease comes back (called a recurrence) or doesn't respond to initial treatments. This includes CAR T-cell therapy, which has received U.S. Food and Drug Administration approval after two lines of treatment. These therapies take a patient's T-cells (white blood cells), change the gene coding in them to recognize and attack lymphoma cells and then infuse them back into the patient.

Bispecific antibodies are another emerging novel immunotherapy for relapsed follicular lymphoma. Bispecific antibodies work by attaching to the surface of cancer cells (by binding to the CD20 marker) and also to the body's immune T-cells (by binding to a marker called CD3), thus engaging the T-cells to eliminate the lymphoma.

Risk for follicular lymphoma transformation

Follicular lymphoma, a slow growing "indolent" lymphoma, can sometimes change into a fast-growing lymphoma. This is called transformation.

A transformation occurs when genetic changes in the indolent lymphoma cells cause them to begin growing faster and behaving more aggressively. The risk of transformation is low, estimated to occur at a rate of about 3 percent per year. A biopsy is the only reliable way to diagnose transformation.

Patients with follicular lymphoma presenting with suspicious signs and symptoms and/or findings on imaging should have a biopsy to rule out a transformation of their follicular lymphoma. In most cases of transformation, the biology at the time of transformation is consistent with diffuse large B-cell lymphoma, an aggressive B-cell non-Hodgkin lymphoma. This may impact the treatment used. 

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