Follicular lymphoma is a slow-growing cancer that affects the lymphatic system, and understanding how it is diagnosed is essential for anyone facing this condition. Diagnosis involves several steps, from recognizing symptoms to confirming the disease through specialized tests, and even determining whether someone is eligible for clinical trials.

Introduction: Who Should Undergo Diagnostics

Many people with follicular lymphoma do not experience symptoms in the early stages of the disease. Because this cancer grows slowly, it can be present in the body for some time before causing noticeable problems. This makes it important to know when to seek medical attention.^[1]

You should consider seeing a doctor if you notice painless swelling in your neck, armpit, or groin that does not go away. These swellings are often the first sign of enlarged lymph nodes, which are small glands that play a role in fighting infections. Lymph nodes can become swollen for many reasons, including common infections, but when they remain enlarged for weeks or return after initially shrinking, it is time to get checked.^[3]

Other symptoms that should prompt a visit to your healthcare provider include persistent tiredness that does not improve with rest, unexplained weight loss (especially losing more than 10% of your body weight over six months), night sweats that soak your clothing or bedding, and fevers that come and go without an obvious cause. Some people also experience shortness of breath or a feeling of fullness in the abdomen if lymph nodes or organs like the spleen become enlarged.^[1][4]

Because follicular lymphoma is slow-growing, it is sometimes discovered during routine blood tests or imaging scans performed for other health concerns. If your doctor notices abnormal results or finds enlarged lymph nodes during a physical examination, they will likely recommend further tests to determine the cause.^[4]

It is also important to remember that follicular lymphoma mainly affects older adults, with most people diagnosed around age 60 or older. However, it can occur at any age. People who are white are more likely to be diagnosed with this condition compared to people of other races. If you have a family history of lymphoma or have been exposed to certain chemicals or have certain immune system disorders, you may be at higher risk and should discuss this with your doctor.^[1][2]

Diagnostic Methods Used to Identify Follicular Lymphoma

The process of diagnosing follicular lymphoma begins with a visit to your doctor, who will perform a physical examination and ask about your symptoms and medical history. Your doctor will check for swollen lymph nodes in your neck, armpits, and groin, and may also examine your abdomen to see if your spleen or liver is enlarged.^[1]

If your doctor finds enlarged lymph nodes or suspects lymphoma based on your symptoms, the next step is usually a biopsy. A biopsy is the only way to confirm whether you have follicular lymphoma. During this procedure, a doctor removes all or part of a swollen lymph node so that it can be examined under a microscope by specialists.^[1][3]

There are different types of biopsies. In most cases, doctors perform an excisional biopsy, which means removing the entire lymph node. If the lymph node is in a location that is difficult to reach, doctors may use a thin needle to remove a small amount of tissue. This is called a fine-needle aspiration biopsy. The biopsy is usually an outpatient procedure, meaning you can go home the same day. The area may be numbed with a local anesthetic to minimize discomfort.^[1]

Once the tissue sample is obtained, laboratory specialists examine it closely under a microscope. They look for abnormal B cells, which are white blood cells that normally help fight infections. In follicular lymphoma, these B cells become cancerous and grow in a pattern that looks like follicles, or small clusters. This is why the disease is called “follicular” lymphoma.^[3]

The specialists also perform tests to understand more about the cancer cells. One common test checks for a specific change in the chromosomes of the cancer cells, called the t(14;18) translocation. This chromosomal change is found in about 85% of people with follicular lymphoma and helps confirm the diagnosis. The translocation causes the cancer cells to produce too much of a protein called BCL2, which allows the cells to survive longer than normal.^[2][7]

In addition to the biopsy, your doctor will order blood tests to check your overall health and look for signs that the lymphoma is affecting your blood cell counts. Blood tests can show whether you have anemia (low red blood cells), which can cause tiredness, or low levels of other blood cells, such as white blood cells or platelets. These tests help doctors understand how the disease is affecting your body.^[1][6]

After confirming the diagnosis, your doctor will want to find out how far the lymphoma has spread in your body. This process is called staging. To determine the stage, doctors use imaging tests such as CT scans (computed tomography scans) and PET scans (positron emission tomography scans). These scans create detailed pictures of the inside of your body and show whether lymphoma is present in different lymph nodes or organs.^[1][3]

Another important test is a bone marrow biopsy. This test checks whether the lymphoma has spread to the bone marrow, which is the spongy tissue inside your bones where blood cells are made. During this procedure, a doctor uses a needle to remove a small sample of bone marrow, usually from the hip bone. The sample is then examined under a microscope. If lymphoma cells are found in the bone marrow, it may affect your treatment plan.^[3][6]

Follicular lymphoma is staged from I to IV, with higher numbers indicating more advanced disease. In Stage I, the cancer is found in one or more lymph nodes in a single area. In Stage II, it is in lymph nodes above or below the diaphragm, which is the muscle that separates your chest from your abdomen. In Stage III, lymph nodes on both sides of the diaphragm are affected. In Stage IV, the cancer has spread beyond the lymph nodes to other organs, such as the bone marrow, liver, or spleen. Most people are diagnosed at Stage III or IV because the disease often does not cause symptoms until it is more widespread.^[1][6]

Doctors also look at the grade of the lymphoma, which describes how the cancer cells look under a microscope and how quickly they are likely to grow. Follicular lymphoma is graded from 1 to 3. Grades 1 and 2 are considered low-grade, meaning the cancer grows slowly. Grade 3 is divided into 3A and 3B. Grade 3A is still considered low-grade, but Grade 3B grows faster and is treated more like a high-grade lymphoma. Understanding the grade helps doctors predict how the disease will behave and choose the right treatment.^[6][12]

Diagnostics for Clinical Trial Qualification

Clinical trials are research studies that test new treatments or combinations of treatments to see if they work better than current options. For people with follicular lymphoma, participating in a clinical trial can provide access to cutting-edge therapies that are not yet widely available. However, to be eligible for a clinical trial, you must meet certain criteria, and this requires specific diagnostic tests.^[4]

The first step in qualifying for a clinical trial is having a confirmed diagnosis of follicular lymphoma. This means you need to have had a biopsy that shows the presence of lymphoma cells. The biopsy results must also include information about the type of lymphoma, the grade, and whether certain genetic changes, such as the t(14;18) translocation, are present. Many clinical trials are designed for specific grades or stages of follicular lymphoma, so having this detailed information is essential.^[2][7]

Once the diagnosis is confirmed, you will need to undergo staging tests, including CT scans, PET scans, and a bone marrow biopsy, to determine how far the disease has spread. Clinical trials often have strict requirements about the stage of the disease. For example, some trials may only accept people with early-stage disease, while others are designed for people with advanced or recurrent lymphoma.^[1][3]

Blood tests are also an important part of the qualification process. These tests check your overall health and make sure your organs, such as your liver and kidneys, are functioning well enough to handle the treatment being tested in the trial. Blood tests also measure your blood cell counts to ensure they are within a safe range. If your blood counts are too low, you may not be able to participate in the trial, or you may need treatment to improve them first.^[1]

Some clinical trials require additional tests to look for specific markers on the lymphoma cells. For example, a trial testing a new drug that targets a particular protein on cancer cells may require a test to confirm that your lymphoma cells have that protein. These tests are usually done on the tissue sample from your biopsy.^[2]

Your doctor will also review your medical history and any previous treatments you have received. Some trials are designed for people who have never been treated before, while others are for people whose lymphoma has come back after treatment or has not responded to standard therapies. This is called relapsed or refractory follicular lymphoma. For these trials, doctors need detailed records of your past treatments and how the disease responded.^[9]

Finally, your performance status, which is a measure of how well you can carry out daily activities, may be assessed. Clinical trials often use standardized scales to determine whether you are well enough to participate. This is important because some treatments in trials can have significant side effects, and doctors want to make sure you can tolerate them.^[9]