Follicular lymphoma

by Philip Berardi, MD PhD FRCPC
March 19, 2022

What is follicular lymphoma?

Follicular lymphoma is a type of cancer that comes from specialized immune cells called lymphocytes. Follicular lymphoma is the second most common lymphoma to affect adults.

Where in the body is follicular lymphoma found?

Follicular lymphoma can start anywhere in the body where lymphocytes gather in large numbers. The most common locations include lymph nodes, the gastrointestinal tract (in particular the stomach and small bowel), the skin, and the breast.

What are the symptoms of follicular lymphoma?

Patients with follicular lymphoma may notice a painless lump or swelling that slowly increases in size over time. Other symptoms of follicular lymphoma include fatigue, unintentional weight loss, loss of appetite, night sweats, and fever.

How do pathologists make the diagnosis of follicular lymphoma?

The diagnosis of follicular lymphoma is usually made after a small piece of tissue is removed in a procedure called a biopsy. Depending on the features of the cancer, patients are then typically either followed (‘watch and wait’) or treated by chemotherapy and/or radiation therapy. Occasionally and only in specific situations is the tumour removed by surgery.

What does follicular lymphoma look like under the microscope?

Most follicular lymphomas are made up of small, dark cells that look similar to normal lymphocytes. However, some tumours contain larger, more abnormal-looking cells. Pathologists use the term pattern of growth to describe the way the cancer cells are arranged. When the cancer cells are arranged in small round groups the pattern is called follicular. When the cancer cells grow in very large shapeless groups and there is no space between the groups, the pattern is called diffuse. The diffuse pattern is important because it can be associated with a worse prognosis. In particular, if a grade 3B tumour (see Grade below) shows a diffuse pattern of growth, the diagnosis changes from follicular lymphoma to diffuse large B-cell lymphoma (DLBCL).​

What other tests are performed to confirm the diagnosis of follicular lymphoma?

Immunohistochemistry is a test that allows pathologists to learn more about the types of proteins made by specific cells. Cells that produce a protein are called positive or reactive. Cells that do not produce a protein are called negative or non-reactive. Immunohistochemistry is commonly performed on cases of follicular lymphoma to confirm the diagnosis and to exclude other diseases that can look similar under the microscope.

Follicular lymphoma commonly shows the following immunohistochemistry results:

• CD20 – Positive.
• CD10 – Positive.
• BCL2 – Positive.
• BCL6 – Positive.
• CD23 – Negative.
• CD3 – Negative.
• CD5 – Negative.
• Cyclin D1 – Negative.

The Ki-67 labelling index is a way of estimating how quickly cells are dividing. Generally, the quicker the cancer cells divide (the higher the Ki-67 labelling index), the more concerned your doctor will be that your lymphoma will behave aggressively.

How do pathologists grade follicular lymphoma and why is the grade important?

Pathologists use the term grade to describe the difference between the cancer cells in follicular lymphoma and normal lymphocytes. After examining the tumour under the microscope, follicular lymphoma is given a grade from 1 through 3. Grade 3 follicular lymphoma can be further subdivided into grades 3A and 3B.

Pathologists determine the tumour grade by counting the number of large cancer cells called centroblasts in a given area. Tumours with more large cells are given a higher grade.

Grade 1 and grade 2 tumours are grouped together and are referred to as low-grade or grade 1-2 because they tend to grow and spread very slowly. Tumours that behave in this manner are also referred to as indolent. Grade 3 tumours are referred to as high-grade because they tend to behave in a more aggressive manner and are associated with a poorer overall outcome.

Over time, low-grade (grade 1 or grade 2) tumours can change into high-grade (grade 3) tumours. If you develop new symptoms and were initially diagnosed with low-grade follicular lymphoma, your doctor may perform another biopsy to see if the tumour has changed to a higher grade.

What does it mean if my report says the follicular lymphoma shows transformation?

Over time, some follicular lymphomas will increase in grade (become more aggressive) and the final step in this change is the development of a more serious form of lymphoma called diffuse large B-cell lymphoma (DLBCL). Pathologists call the development of diffuse large B-cell lymphoma from follicular lymphoma transformation. Your pathologist will carefully examine your tissue for any evidence of diffuse large B-cell lymphoma.