What is Transformed Follicular Lymphoma?

Follicular lymphoma (FL) is a type of slow-growing blood cancer that affects a type of white blood cell called B lymphocytes. The average survival for people with follicular lymphoma is about 8 to 10 years, but the disease has a pattern of relapsing and becoming less responsive to treatment over time.

Follicular lymphoma can also transform into a more aggressive lymphoma type, most commonly diffuse large B-cell lymphoma (DLBCL). This process is called transformed follicular lymphoma (tFL). 

What Happens During Follicular Lymphoma Transformation?

Transformation means that the follicular lymphoma cells change into a different type, usually a rapidly growing and more difficult to treat type (that’s why they are called aggressive). This happens when the cancerous B cells lose their original follicular growth pattern and a new, more aggressive type of cancer cells arise. This new type can be more resistant to treatment and it needs to be adjusted to this more rapidly growing lymphoma.

The exact reasons why this happens are not fully understood. However, there are some factors linked:

• The accumulation of genetic mutations in the cancer cells over time.
• Changes in the immune system allow more aggressive cancer cells to grow.
• Treatment-related factors, but transformation can also occur in untreated patients.

How is tFL Diagnosed?

The best way to confirm follicular lymphoma transformation is through a biopsy of an affected lymph node or other involved tissue. This involves removing a small sample of tissue and analyzing it under a microscope to see if the follicular lymphoma cells have changed into a more aggressive form. The gold standard for diagnosing transformation is finding:

• A large number of large, aggressive B cells (called centroblasts) in the sample
• The loss of the original cell structure of the lymphoma
• Genetic markers confirm that the transformed cells are related to the original follicular lymphoma cells

Sometimes, follicular lymphoma and DLBCL can be found in the same tissue sample at diagnosis. This is called composite histology, and while it suggests that transformation is occurring, it does not always confirm it. Doctors generally consider transformation to have occurred if a biopsy shows aggressive lymphoma at least six months after the initial follicular lymphoma diagnosis.

What Are the Signs of Transformed Follicular Lymphoma?

After monitoring for symptoms and lab tests, doctors may suspect transformation. These signs can include:

• A sudden increase in tumor size or a rapidly growing lymph node.
• A significant rise in lactate dehydrogenase (LDH)
• The appearance of lymphoma in new, unusual sites such as bones, skin, or soft tissues can sometimes be discovered in physical examination, but in others, only with imaging tests.
• B-symptoms: unexplained fevers, night sweats, and weight loss.
• High levels of calcium in the blood (hypercalcemia).

However, not all of these symptoms automatically mean that follicular lymphoma has transformed. Some patients with worsening follicular lymphoma may experience similar symptoms without an actual transformation. That’s why a biopsy is crucial for a definitive diagnosis.

Am I at Risk of FL Transformation?

The risk of transformation varies widely due to differences in how transformation is defined, how often biopsies are performed, and the follow-up time in studies. Based on current information, the transformation risk tends to increase over time. In 2020, a study reported that 14.3% of patients experienced transformation with 6.8 years of median follow-up.

What Are Treatments for tFL? 

Adapted from: ashpublications.org What should I know about tFL? 

Final Thoughts 

Transformed follicular lymphoma (tFL) is a serious progression of follicular lymphoma that significantly affects treatment and survival. While researchers continue to study ways to predict and prevent transformation, early detection through biopsy and close monitoring remains essential. Patients diagnosed with follicular lymphoma should work closely with their healthcare team to watch for signs of transformation and discuss treatment options if it occurs.

Learn more about follicular lymphoma with HealthTree’s updates and conference news! 

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Sources:

• What should I know about tFL?
• Transformation of Follicular Lymphoma