What is Follicular Lymphoma?
Follicular lymphoma, often abbreviated as FL, is a type of cancer called non-Hodgkin lymphoma, or NHL. It’s the second most common type of this cancer, making up nearly 30% of all lymphomas. FL is categorized as a type of “indolent” NHL, meaning it’s a slower-growing cancer. This type of lymphoma involves B-cells, which are a type of white blood cell that play a key role in our immune system.
When doctors look at FL under a microscope, they rate it from 1 to 3, with 1 being “low grade” or relatively slow-growing, and 3 being “high grade” or more aggressive. Despite its slow growth, it’s important to remember that FL is a serious condition, and people with it will typically need to be monitored and treated over a number of years.
What Causes Follicular Lymphoma?
Follicular lymphoma (FL) comes from a type of white blood cells known as B-cells, which are important for your body’s immune response. Most people diagnosed with FL have a genetic rearrangement, specifically at the locations 14 and 18 (q32;q21) in the chromosomes. This rearrangement leads to an increased production of a protein known as B-cell lymphoma 2 (BCL2), which stops cells from dying naturally. About 5% of FL cases have certain mutations that mess up BCL-6, a specific protein necessary for germinal center formation (the germinal center is a type of lymph node where B cells mature). BCL-6–related protein is largely responsible for controlling gene expression and modulating how B-cells respond to a substance called interleukin-4 (IL-4).
Researchers believe certain upregulated (over active) genes associated with p21, p16, and G1 arrest may also have a role in FL. Regulatory proteins (p120, p16, CKD10, p21), transcription factors (proteins that help turn on certain genes, such as the Id2 and PAX5), and genes related to cell interaction like tumor necrosis factor (TNF), interleukin-4 receptor α (IL4RA), and interleukin-2 receptor subunit gamma (IL2RG) are also more active. In contrast, genes associated with adhesion, such as MRP14 and MRP8, are less active in people with FL.
Risk Factors and Frequency for Follicular Lymphoma
Follicular lymphoma (FL), a type of Non-Hodgkin Lymphoma (NHL), is the second most prevalent in the United States. About six new cases surface for every 100,000 people every year. The condition is more common among Caucasians than Asians and African Americans.
FL is more often found in the United States and Europe than in other parts of the globe. It is primarily an ailment of older adults, with a median age of 55. It’s relatively rare to see this in children and is almost never seen in individuals under 20 years old. Getting exposed to pesticides and herbicides increases one’s risk of developing FL.
- Follicular lymphoma (FL) is a common type of Non-Hodgkin Lymphoma (NHL) in the US.
- Annually, about six new cases appear for every 100,000 people.
- FL is more common among Caucasians than Asians or African Americans.
- FL is common in the US and Europe, but less so elsewhere in the world.
- It typically affects older adults, with the median age being 55.
- FL is not common in children and rarely occurs in people under 20.
- Exposure to pesticides and herbicides can increase the risk of FL.
Signs and Symptoms of Follicular Lymphoma
Follicular Lymphoma (FL) is a disease that often presents as swelling of painless lymph nodes, which tends to grow and shrink over time. The lymph nodes affected can be in the armpit, neck, thigh, or groin areas. Occasionally, it can present as a large, symptomless mass in the mediastinum, the area in the chest between the lungs. Only about 20% of people with this condition experience symptoms like night sweats, fever, and weight loss. A similar proportion has increased levels of a chemical in the bloodstream called lactate dehydrogenase (LDH). Most of the time, FL just affects bone marrow and parts of the body involved in lymph production. In children, it primarily impacts the tonsils and lymph nodes in the head and neck.
FL is ordinarily slow progressing with a mainly favorable prognosis. In over half of cases, the disease involves the bone marrow. Infiltration in marrow is most commonly identified by a particular spread pattern. Some cases show identifiers like deeply grooved nuclei in certain blood cells. In the spleen, it can look like groups of lymphocytes in the white pulp area.
There are subtypes of FL, such as double-hit follicular lymphoma and low-grade FL with a high proliferation index, that display low-grade appearance but may have a comparatively more aggressive progression. Scientists are conducting extensive research on these and other uncommon subtypes for more insights.
In some cases, FL can transform into different aggressive forms of Non-Hodgkin Lymphoma (NHL), like DLBCL, Burkitt and Burkitt-like lymphoma, and high-grade B-cell lymphoma. This change can also occur in B-cell acute lymphoblastic leukemia (B-ALL). These transformations undertake a worse prognosis. Suspicions of transformation might surface when observing rapid growth of certain masses, the occurrence of B symptoms, and abnormal test results, including elevated levels of serum LDH or calcium.
Testing for Follicular Lymphoma
To evaluate follicular lymphoma (FL), which is a type of blood cancer that develops in your lymphatic system, doctors will look at your medical history and perform a physical examination. They will also order laboratory tests, which include a complete blood count to check the number and types of blood cells in your blood, routine chemistries like blood tests that measure how well your organs are functioning, and lactate dehydrogenase (LDH), a type of enzyme found in many body tissues. Imaging tests may also be performed. These can include CT scans, MRI scans, and whole-body combined fluorodeoxyglucose positron emission tomography with computed tomography (FDG PET/CT), which can help create detailed images of your body’s tissues and cells.
A definitive diagnosis of FL typically needs an assessment of a lymph node, taken from a biopsy, and flow cytometry, a technique that is used to measure the physical and chemical characteristics of cells. In some cases, genetic testing may also be needed to confirm the diagnosis.
A blood test may show atypical lymphocytes, which are a type of white blood cell that have a small amount of cytoplasm, the substance that fills each cell, and a deeply divided nucleus, the core component of a cell. If the lymph node assessment shows small-to-medium-sized cells with CD20+, CD10+, and BCL2+ markers, this supports an FL diagnosis. CD10 and BCL2 are both proteins that can be found in types of lymphoma. It can be difficult to tell FL apart from reactive hyperplasia, a non-cancerous condition where lymph nodes become swollen due to an infection or disease. In these cases, the level of CD10 can be helpful as high levels support an FL diagnosis. Before treatment starts, a bone marrow biopsy is typically done to confirm the stage of the disease.
Genetic testing can be used to evaluate FL as most cases will show changes in immunoglobulin genes, which are part of your immune system’s defenses against infection. Furthermore, most cases show a change known as a “translocation” of genetic material between chromosomes 14 and 18. This change affects the immunoglobulin heavy chain (IgH), an essential part of antibodies, and BCL2, a gene that can control cell death. This leads to too much BCL2, which prevents cells in the follicular centre from dying normally – this is a process called apoptosis. An increased amount of BCL2 is often seen in FL but can also appear in other types of non-Hodgkin lymphoma (a group of blood cancers), such as diffuse large B-cell lymphoma (DLBCL).
After treatment has successfully reduced the disease, patients should have follow-up appointments every three months during the first year and then every three to six months afterwards.
Treatment Options for Follicular Lymphoma
Follicular lymphoma (FL), a type of blood cancer, can be managed in various ways, depending on the stage or severity of the disease. Some treatment options include:
- Radiotherapy: a procedure that uses high-energy rays to destroy cancer cells.
- Immunochemotherapy: a treatment that combines chemotherapy (drugs that kill cancer cells) and immunotherapy (drugs that help the body’s immune system fight cancer).
- Rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (collectively known as R-CHOP) are specific drugs used in chemotherapy.
- Single-agent rituximab: a type of immunotherapy using only one drug.
- Observation: for cases without symptoms, doctors may choose to simply closely monitor the patient.
Choosing a treatment often depends on the stage or severity of the lymphoma, the doctor’s decision, and the patient’s personal preference. For instance, in the early stage (stage I), radiotherapy is often the preferred treatment. However, a stronger treatment like R-CHOP may be utilized for more aggressive types of lymphoma.
For latter stages of follicular lymphoma (stages II, III, and IV), the main concern is improving the patient’s quality of life, reducing symptoms, and correcting abnormalities in blood cell counts. People without symptoms are typically closely observed without any interventions. For those experiencing symptoms, anti-CD20 antibodies (a type of immunotherapy like obinutuzumab and rituximab) may be combined with chemotherapy.
For patients with recurring symptoms or severe progression of the lymphoma, a procedure called autologous hematopoietic stem cell transplantation may be preferred. This procedure involves transplanting the patient’s own healthy stem cells to replace cells damaged by cancer. Patients with advanced disease who do not respond to traditional treatments may also be invited to participate in clinical trials for newer treatments like chimeric antigen receptor (CAR) T-cell therapy, a type of immunotherapy that modifies a patient’s cells to recognize and kill cancer cells.
What else can Follicular Lymphoma be?
Follicular Lymphoma (FL) is distinguished from other types of lymphomas based on a few key features. These include a certain arrangement of cells (nodular pattern), a lack of specific types of immune system cells (tangible body macrophages), the presence of cells that all come from an identical parent cell (monoclonal cells), and a specific combination of markers present on the surface of the cells (immunophenotyping: CD10, BCL-2, BCL-6).
To diagnose FL, doctors need to rule out the following conditions that could show similar symptoms:
- Follicular colonization by other low-grade lymphomas
- Mantle cell lymphoma with a diffuse pattern
- Marginal zone B-cell lymphoma
- Peripheral T-cell lymphoma
- Reactive hyperplasia (increase in cell number due to a reaction to a stimulus)
- Small lymphocytic lymphoma/chronic lymphocytic leukemia (SLL/CLL)
This requires a thorough evaluation and appropriate testing to ensure an accurate diagnosis.
What to expect with Follicular Lymphoma
The chances of recovery and risk associated with follicular lymphoma, a type of blood cancer, are determined using certain factors based on a study called the Follicular Lymphoma International Prognostic Index (FLIPI2). These factors include:
* Higher than normal levels of a protein called Beta 2 microglobulin in your blood
* Involvement of the bone marrow
* Hemoglobin levels less than 12g/dL (which indicates anemia)
* The largest affected lymph node being more than 6 cm
* Being over 60 years old
The 5-year survival rate without the disease progressing, based on these risk factors, is:
* Low risk (if none of these risk factors are present): 80%
* Intermediate risk (if 1-2 of these risk factors are present): 51%
* High risk (if 3-5 of these risk factors are present): 19%
Possible Complications When Diagnosed with Follicular Lymphoma
Follicular lymphoma can lead to several complications, such as the suppression of bone marrow activity, the impairment of organ functioning, and negative side effects caused by intensive chemotherapy treatments.
Here’s a simple list to give you an idea of the common complications:
- Suppression of bone marrow activity
- Impairment of organ functioning
- Negative side effects caused by intensive chemotherapy treatments
Preventing Follicular Lymphoma
Before starting treatment, patients need to be informed about what to expect both in terms of outcomes and potential side effects. This includes the possible harmful effects from chemotherapy and a procedure called hematopoietic stem cell transplantation. Chemotherapy is a method used to kill cancer cells, and hematopoietic stem cell transplantation involves replacing blood-forming cells in the bone marrow that have been destroyed by chemotherapy or radiation. Keeping patients informed can help them to better manage and understand their condition.
