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Follicular Lymphoma


Follicular non-Hodgkin lymphomas (NHL) are considered low-grade cancers because they are slow growing compared to the more common, aggressive forms of NHL. Follicular lymphoma affects the B-cells, a type of lymphoma cell. It occurs more commonly in elderly patients; the average age at diagnosis is 60 years. The majority of patients have advanced disease at the time of diagnosis, and patients commonly have cancer cells that have spread outside the lymph system.

Follicular lymphoma cells are characterized by how they look under the microscope; most cases are associated with a specific abnormality in the cell’s DNA. DNA is organized into 23 paired chromosomes. In the case of follicular lymphoma, genetic material from chromosome 14 is moved to chromosome 18, which is called a translocation (t14:18).

Another feature of follicular lymphomas is the presence of the CD20 antigen, a protein that is found on the surface of the cells. This is important because some targeted therapies for the treatment of lymphomas are designed to locate the cancer cells in the body by detecting this protein.

Classifying follicular lymphoma: Follicular lymphomas are classified according to two systems, the Revised European American Lymphoma (REAL) system and the International Working Formulation (IWF). The REAL system is the most current of these systems and classifies NHL based not only on their appearance, but on genetic features and chemistry of the cancer cells.

Patients with follicular large cell or grade 3 lymphomas are typically treated with approaches designed for aggressive lymphomas. Otherwise, patients with the following follicular lymphomas are all treated with the techniques described in this section.

REAL Classification IWF Classification
Follicle center cell (grade 1) Follicular small cleaved cell
Follicle center cell (grade 2) Follicular mixed small & large cell
Follicle center cell (grade 3) Follicular large cell

Lymphoma stage: In addition to the classifying follicular NHL by the cells involved, it is important that the stage of disease be determined. Stage refers to where the cancer has spread in the body, or the extent of disease. The stage of disease indicates whether the cancer is localized or more advanced. Treatments are determined based on the extent of the cancer and the type of lymphoma cells involved.

Determining the extent of the stage of the cancer requires a number of procedures including computed tomography (CT) and/or magnetic resonance imaging (MRI) scans and blood tests.

Prognosis: The probable course and/or outcome of the cancer is called the prognosis. Identifying factors that indicate a better or worse prognosis may help determine an optimal treatment plan. There are many factors that are evaluated to determine prognosis.

Based on the need to identify which patients with follicular lymphoma are likely to have a poor outcome with conventional treatment, a prognostic index, or tool to help doctors identify a patient’s prognosis, was developed through an international clinical trial.

Results indicate that the following five risk factors are associated with a worse outcome:

  • Age 60 or over
  • Ann Arbor stage III-IV disease
  • Abnormally low levels of hemoglobin, the component of red blood cells that transports oxygen (<12 gm/dl)
  • Elevated lactate dehydrogenase (LDH), a protein found in the blood that indicates tissue damage to the heart, liver, or kidney
  • Cancer in more than four lymph nodes

Patients who have three or more of these risk factors are likely to have a worse prognosis and may benefit from more intensive therapy (see table 1). 1

Table 1: Outcomes among patients with low, intermediate, or high-risk follicular lymphoma

Low-risk Intermediate-risk High-risk
Number of risk factors 0-1 2 =3
Average 5-year survival 90.6% 77.6% 52.5%
Average 10-year survival 70.7% 50.9% 35.5%


Cancer Stage

Following a diagnosis of cancer, the most important step toward getting optimal care is to accurately determine the stage of cancer. Stage describes how far the cancer has spread. Follicular lymphoma may be diagnosed as stage I, II, III, IV or relapsed/recurrent (see below). Each stage of cancer may be treated differently. For more detailed information on possible treatment options for follicular lymphoma, click on the stage below:

Stage I: Cancer is found only in a single lymph node, in the area immediately surrounding that node, or in a single organ.

Stage II: Cancer involves more than one lymph node area on one side of the diaphragm (the breathing muscle separating the abdomen from the chest).

Stage III: Cancer involves lymph node regions above and below the diaphragm. For example, there may be swollen lymph nodes under the arm and in the abdomen.

Stage IV: Cancer involves one or more organs outside the lymph system or a single organ and a distant lymph node site.

In some patients, the lymphoma may grow out of the lymph system into adjacent organs. This is referred to as extranodal extension and designated by an “E” following the stage. For example a patient with a stage II lymphoma that extended into the lungs would be referred to as stage IIE.

Patients with non-Hodgkin lymphoma may also experience general symptoms from their disease. Patients with fever, night sweats, or significant weight loss are said to have “B” symptoms. If these specific symptoms are not present, patients are further classified as “A”.

Relapsed/Refractory: Cancer has persisted or returned (recurred/relapsed) following treatment.


1Solal-Celigny P, Roy P, Colombat P, et al. Follicular Lymphoma International Prognostic Index. Blood. 2004;104:1258-1265.

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