Follicular Lymphoma (FL) is a type of cancer classified as a Non-Hodgkin Lymphoma (NHL). It is a malignancy that originates in the body’s lymphatic system, specifically affecting B-lymphocytes, a type of white blood cell. FL is considered the most common of the indolent, or slow-growing, lymphomas. This slow progression significantly influences how the disease is managed from the time of diagnosis.
Defining Follicular Lymphoma
FL develops from B-lymphocytes and is categorized as a B-cell NHL. The term “follicular” describes the growth pattern where malignant cells cluster in a nodular formation within the lymph nodes. This organization mimics the normal structure of germinal centers, but the cells are abnormal.
The biological signature of FL involves the \(t(14;18)\) chromosomal translocation, found in 85% to 90% of cases. This rearrangement moves the \(BCL2\) gene, resulting in the overexpression of the \(BCL2\) protein. Since \(BCL2\) is an anti-apoptotic protein, it prevents the cancerous B-cells from undergoing programmed cell death, giving them a survival advantage.
FL is grouped with indolent lymphomas, contrasting with aggressive types like Diffuse Large B-cell Lymphoma (DLBCL). Although FL is slow to progress, it carries a risk of “transformation” into a faster-growing, more aggressive lymphoma, most often DLBCL. This transformation is a clinical event requiring immediate therapeutic intervention.
Diagnosis and Classification
FL is often detected incidentally during routine exams or when a patient notices painless swelling in the lymph nodes (neck, armpit, or groin). A biopsy is mandatory to confirm the diagnosis and analyze cellular structure, typically using an excisional or core needle biopsy. Pathologists examine the tissue for the characteristic follicular growth pattern and perform molecular tests for the \(t(14;18)\) translocation and \(CD20\) and \(BCL2\) proteins.
After diagnosis, the disease is staged and graded to determine its extent and growth rate. Staging uses the Ann Arbor system, ranging from Stage I (single lymph node region) to Stage IV (widespread disease, including non-lymphatic organs). Most patients are diagnosed with advanced-stage disease (Stage III or IV), but immediate treatment is not always necessary due to the indolent nature of FL.
Grading predicts disease behavior by counting centroblasts within the follicular clusters. Grades 1, 2, and 3a are low-grade or indolent. Grade 3b contains a high concentration of centroblasts and is treated like an aggressive lymphoma. Further workup includes a Positron Emission Tomography-Computed Tomography (PET/CT) scan to map disease spread and a bone marrow biopsy to check for marrow involvement. Blood tests often check for Lactate Dehydrogenase (LDH) levels, as elevated LDH can indicate a higher risk of transformation.
Management Strategies
Management is highly individualized, shaped by FL’s indolent nature and the patient’s characteristics. For individuals with low-grade, asymptomatic FL and a low tumor burden, the initial approach is often “Watchful Waiting” or active surveillance. This strategy involves regular monitoring without immediate treatment. Delaying therapy until symptoms develop does not negatively impact overall survival, allowing patients to avoid treatment side effects for years.
Active treatment is necessary when the disease causes symptoms (fever, weight loss, night sweats), or when there is bulky disease or rapid progression. Effective treatments incorporate targeted therapy using the monoclonal antibody rituximab, which targets the \(CD20\) protein on B-cells. Rituximab can be used alone for low-tumor-burden intervention or in combination with chemotherapy.
Chemotherapy regimens are combined with rituximab, such as R-CHOP or the combination of bendamustine and rituximab (BR). The BR regimen is often preferred as a first-line option due to longer progression-free survival and fewer toxicities compared to R-CHOP. For patients with localized (Stage I or II) disease, radiation therapy to the affected areas is often the preferred, potentially curative, treatment.
Long-Term Prognosis and Follow-Up
FL is considered a chronic, relapsing condition; it is highly treatable but generally not curable. Despite this, the long-term outlook is favorable, with a 5-year overall survival rate around 90% in the modern era. Many individuals live for years, often dying from unrelated causes, which underscores the slow growth pattern.
Following initial treatment, patients enter a surveillance phase, monitored for recurrence or relapse. The disease can return at any time, requiring a new course of therapy and re-evaluation of the management approach. A persistent risk exists for “histologic transformation,” where the indolent FL converts into a more aggressive form, such as DLBCL.
The risk of transformation is estimated at approximately 3% per year, often signaled by new, rapidly growing masses or severe B-symptoms. Although transformation is associated with a worse prognosis than non-transformed FL, outcomes have improved with modern protocols. Regular follow-up appointments and imaging are necessary to monitor the disease, detect relapses, and identify transformation early for timely intervention.