Follicular lymphoma is a type of slow-growing blood cancer that affects the lymphatic system, often appearing first as painless swellings in the neck, armpit, or groin. Many people live with this condition for years, sometimes without needing immediate treatment, and research continues to improve how we understand and manage it.
Understanding Follicle Centre Lymphoma Follicular Grade I, II – III
Follicle centre lymphoma, also known as follicular lymphoma, develops when white blood cells called B lymphocytes (or B cells) grow out of control. These cells are part of your body’s immune system and normally help fight infections by making antibodies. When they become cancerous, they don’t work properly and instead multiply and gather in clusters.
The name “follicular” refers to the way these abnormal cells typically group together in clumps called follicles inside lymph nodes. Lymph nodes are small, bean-shaped structures scattered throughout your body that act as filtering stations for your lymphatic system. The lymphatic system is like a network of tubes and tissues that helps your body fight disease and maintain fluid balance.
Follicular lymphoma is considered a type of non-Hodgkin lymphoma, which is one of two main categories of lymphoma. The other category is Hodgkin lymphoma, and they’re classified differently based on the types of cells involved and how they look under a microscope.
Epidemiology: Who Gets Follicular Lymphoma
Follicular lymphoma is the second most common type of non-Hodgkin lymphoma, accounting for approximately 20 to 30 percent of all lymphoma cases. In the United States, it represents about 20 percent of all non-Hodgkin lymphomas, with approximately 15,000 to 20,000 new diagnoses each year. The estimated incidence is about 6 new cases per 100,000 people annually.
In the United Kingdom, around 2,300 people are diagnosed with follicular lymphoma each year, making it the most common type of slow-growing lymphoma. The disease is more commonly found in the United States and Europe compared to other parts of the world, and it occurs at lower rates in Asia.
This condition primarily affects older adults. The median age at diagnosis is between 55 and 60 years, meaning that half of all people diagnosed are older than this age and half are younger. It is quite rare in children and young people, with very few cases diagnosed in patients under 20 years old.
There are some differences across demographic groups. The disease affects men and women roughly equally, with no clear sex preponderance. However, follicular lymphoma is more common in people who are white compared to those of Asian or African American descent.
Causes and Origins of Follicular Lymphoma
Researchers don’t know exactly what causes follicular lymphoma, but they have identified some important changes that happen in the cells of most people with this disease. The cancer originates from germinal centre B cells, which are B cells that develop in specific areas of lymph nodes called germinal centres.
In about 85 percent of cases, scientists have found a specific change in the chromosomes of the cancer cells. Chromosomes are structures in your cells that contain your genetic information, organized in 23 pairs. In follicular lymphoma, there’s a translocation, which means that a piece of one chromosome breaks off and attaches to another chromosome. Specifically, genetic material from chromosome 14 moves to chromosome 18, written as t(14;18).
This translocation leads to overproduction of a protein called BCL2, which is an antiapoptotic protein. Apoptosis is the process of programmed cell death that normally happens to old or damaged cells. BCL2 prevents this natural death, giving the affected cells a survival advantage. Instead of dying when they should, these cells continue to live and multiply, eventually leading to lymphoma.
However, this genetic change alone doesn’t fully explain follicular lymphoma. Interestingly, cells with the t(14;18) translocation can be found in some healthy people who never develop lymphoma. Research suggests that having a high frequency of t(14;18)-positive cells in the blood may be a warning sign that appears years before lymphoma is diagnosed.
About 5 percent of follicular lymphomas involve mutations in a gene called BCL-6, which plays a role in the formation of germinal centres. Scientists have also identified other genetic changes involving proteins and genes that control cell growth and interaction, though the full picture of how these changes work together to cause lymphoma is still being studied.
It’s important to understand that these genetic changes happen sometime during a person’s lifetime. Follicular lymphoma is not an inherited disease, meaning it doesn’t pass directly from parents to children through genes.
Risk Factors
While the exact cause of follicular lymphoma remains unknown, certain factors may increase a person’s risk of developing this condition. Age is one of the most significant risk factors. People aged 65 and older are more likely to develop follicular lymphoma compared to younger individuals.
Race also plays a role in risk. White individuals receive this diagnosis more often than people of other racial backgrounds, including those of Asian and African American descent. This pattern holds true across different geographic regions where the disease has been studied.
Some environmental and occupational exposures have been associated with lymphoma in general. Exposure to certain chemicals, such as pesticides and herbicides, has been linked to increased lymphoma risk. Substances like defoliants (including Agent Orange) and even some hair dyes have been studied for their potential connection to lymphoma development.
Certain medical conditions and their treatments may also increase risk. People with autoimmune diseases and those taking medications for these conditions (such as methotrexate) have been associated with an increased risk of developing lymphoma. Additionally, individuals who have received immunosuppressant drugs after organ transplantation may be at higher risk.
Viral infections have been implicated in some types of lymphoma, though they’re mostly linked to high-grade rather than slow-growing lymphomas like follicular lymphoma. These viruses include Epstein-Barr virus, hepatitis B and C viruses, and HIV. Most lymphomas associated with HIV and with immunodeficiency states following organ transplantation tend to be more aggressive types.
Symptoms of Follicular Lymphoma
Many people with follicular lymphoma don’t have any symptoms at all, especially in the early stages. In some cases, the disease is discovered accidentally during routine blood work or imaging tests done for another reason. Because it grows slowly, symptoms may develop gradually over time, which can make them easy to overlook initially.
The most common symptom is painless swelling in one or more areas of the body where lymph nodes are located. These swellings typically appear in the neck, armpit, or groin. Unlike swollen lymph nodes from an infection, which are usually tender and get better within a few weeks, lymphoma-related swellings are persistent and don’t go away on their own.
Some people experience a group of symptoms that doctors call B symptoms. These include heavy sweating at night (night sweats), recurring fevers that come and go without an obvious cause, and unexplained weight loss. The weight loss is considered significant if someone loses more than one-tenth of their body weight over six months without trying.
General fatigue, or feeling very tired all the time, is another common symptom. This tiredness isn’t the normal kind that gets better after a good night’s sleep. It’s a persistent exhaustion that can significantly affect daily activities and quality of life.
When follicular lymphoma spreads beyond lymph nodes to other organs, additional symptoms may appear. If the disease affects the bone marrow, where blood cells are made, it can lead to low blood cell counts. Low red blood cells cause anemia, which makes people feel tired and short of breath. Low platelet counts can cause easy bruising or bleeding problems, as platelets help your blood clot properly.
Some people may feel full quickly when eating or experience abdominal discomfort if lymph nodes or the spleen become enlarged. In cases where the lymphoma affects the skin or other organs, symptoms will depend on which part of the body is involved.
It’s worth noting that most people with follicular lymphoma have advanced disease (stage III or IV) by the time they’re diagnosed, simply because the slow growth means symptoms develop late or not at all in the early stages.
Prevention
Currently, there are no proven methods to prevent follicular lymphoma because the exact causes of the disease are not fully understood. Unlike some cancers where lifestyle changes or vaccines can significantly reduce risk, follicular lymphoma doesn’t have clear preventable risk factors that researchers have identified.
However, avoiding known environmental risk factors might be prudent, even though direct links haven’t been definitively established. Limiting exposure to pesticides, herbicides, and other potentially harmful chemicals where possible may be sensible, particularly for those who work in occupations where such exposures are common.
There is no screening test recommended for follicular lymphoma in people without symptoms. The disease develops slowly and often without early warning signs, and there isn’t evidence that early detection through screening would improve outcomes for most people.
The best approach is to be aware of the symptoms, particularly persistent, painless swellings in the neck, armpit, or groin, along with B symptoms like unexplained weight loss, fevers, and night sweats. Seeing a doctor promptly if these symptoms appear is important for getting an accurate diagnosis and, if needed, appropriate care.
Pathophysiology: What Happens in the Body
Follicular lymphoma represents a disruption in the normal life cycle and function of B lymphocytes. To understand what goes wrong, it helps to know what normally happens with these cells.
B lymphocytes develop in the bone marrow and then travel to lymph nodes and other parts of the lymphatic system. When your body encounters a foreign invader like a virus or bacteria, B cells in the germinal centres of lymph nodes become activated. They multiply and mature into cells that produce antibodies, which are proteins designed to attack specific germs. After the infection is cleared, most of these activated B cells die through the process of apoptosis, returning the immune system to its resting state.
In follicular lymphoma, genetic changes prevent this normal cell death. The translocation that causes BCL2 overexpression essentially gives the cells an “off switch” for apoptosis. Instead of dying when they should, these B cells continue to survive and multiply. Over time, they accumulate in the lymph nodes, spleen, bone marrow, and potentially other organs.
The abnormal B cells don’t function properly. While normal B cells produce antibodies to fight infections, lymphoma cells don’t perform this protective role effectively. As they accumulate, they form the characteristic follicular pattern seen under the microscope, creating clusters that mimic the normal architecture of germinal centres but don’t work the way they should.
The grade of follicular lymphoma is determined by counting specific types of cells called centroblasts, which are larger cells within the follicles. Grade 1 has the fewest centroblasts (0 to 5 per high-power field when viewed under a microscope). Grade 2 has a moderate number (6 to 15 centroblasts). Grade 3 has more than 15 centroblasts and is further divided into 3A, where other cells called centrocytes are present, and 3B, where there are solid sheets of centroblasts.
Studies suggest that this grading system helps predict how the disease will behave. Lower grades (1 and 2, as well as 3A) tend to grow more slowly and are treated similarly as slow-growing lymphomas. Grade 3B behaves more aggressively and is often treated more like high-grade lymphoma.
The bone marrow is involved in 40 to 70 percent of patients, meaning that abnormal lymphoma cells can be found there. Most patients also have widespread disease at the time of diagnosis, with lymph nodes affected in multiple areas of the body, both above and below the diaphragm (the muscle that separates the chest from the abdomen). The spleen may also be enlarged.
In some cases, follicular lymphoma can transform into a more aggressive type of lymphoma, most commonly diffuse large B-cell lymphoma. This transformation means the cancer begins growing much faster and typically requires more intensive treatment. The cells take on different characteristics under the microscope, losing the follicular pattern and spreading in a more diffuse way.
The lymphatic system itself becomes disrupted by the accumulation of lymphoma cells. Lymph nodes enlarge as they fill with abnormal cells. When many lymph nodes are affected, the normal flow of lymph fluid can be impaired. If the bone marrow becomes heavily involved, the production of normal blood cells can be reduced, leading to anemia, increased infection risk from low white blood cells, or bleeding problems from low platelets.