Follicular Lymphoma – Causes, Symptoms and Treatment

What is Follicular Lymphoma?

Follicular lymphoma (FL) is a malignant disease of the lymphatic system and belongs to the group of non-Hodgkin lymphomas (NHL). It arises from cancerous B-lymphocytes – a subtype of white blood cells – that multiply uncontrollably and form follicular (nodular) patterns within the lymph nodes. Follicular lymphoma is classified as an indolent lymphoma, meaning it typically grows slowly and may remain asymptomatic for years.

Accounting for approximately 20–25% of all non-Hodgkin lymphomas, follicular lymphoma is one of the most common lymphoma subtypes in adults. It predominantly affects older individuals, with a peak incidence between the 6th and 7th decade of life.

Causes and Risk Factors

The exact causes of follicular lymphoma are not yet fully understood. In most cases, a characteristic chromosomal change is present:

• Translocation t(14;18): This genetic alteration leads to overexpression of the BCL-2 gene, which inhibits programmed cell death (apoptosis) and promotes the survival of malignant cells. This translocation is found in approximately 85% of patients with follicular lymphoma.
• Genetic predisposition: Individuals with a family history of lymphoma have an elevated risk.
• Immunodeficiency: A weakened immune system, such as from immunosuppressive therapy or HIV infection, may increase the risk.
• Environmental factors: Exposure to certain chemicals (e.g., pesticides, organic solvents) has been discussed as a possible contributing factor.

Symptoms

Follicular lymphoma often remains without noticeable symptoms for extended periods and is sometimes discovered incidentally. Possible symptoms include:

• Painless lymph node swelling, most commonly in the neck, armpits, or groin
• Enlarged spleen (splenomegaly) or liver (hepatomegaly)
• Fatigue and general malaise
• Night sweats, fever, and unintentional weight loss (known as B symptoms)
• Rarely: breathing difficulties or abdominal discomfort due to larger lymph node masses

Diagnosis

Diagnosing follicular lymphoma requires several investigative steps:

Histological Examination

Lymph node biopsy followed by histological and immunohistochemical analysis is the diagnostic gold standard. It reveals the characteristic follicular growth pattern and immunophenotype (e.g., CD10+, BCL-2+, CD20+).

Imaging and Staging

To determine the extent of the disease (staging), the following are used:

• CT (computed tomography) of the neck, thorax, abdomen, and pelvis
• PET-CT (positron emission tomography) to assess metabolic activity of lymphoma lesions
• Bone marrow biopsy to detect bone marrow involvement

Laboratory Tests

Complete blood count, LDH (lactate dehydrogenase), beta-2 microglobulin, and other laboratory values assist in risk assessment and monitoring of disease progression.

Grading

Follicular lymphoma is classified into three grades of malignancy (Grade 1, 2, and 3a = indolent; Grade 3b = more aggressive, treated similarly to diffuse large B-cell lymphoma).

Treatment

The treatment of follicular lymphoma depends on the stage, grade, and the overall health status of the patient.

Watch and Wait

In asymptomatic patients at early or advanced stages without a clear treatment indication, active surveillance without immediate therapy may be appropriate, as early treatment does not improve survival in this group.

Immunochemotherapy

When treatment is indicated, immunochemotherapy is the standard approach. It combines:

• Rituximab (anti-CD20 antibody) with chemotherapy regimens such as CHOP, CVP, or Bendamustine
• A subsequent Rituximab maintenance therapy for two years can reduce the risk of relapse.

Radiation Therapy

In early-stage disease (Stage I and II), radiation therapy alone can be used with curative intent for localized involvement.

Novel Therapeutic Approaches

• Obinutuzumab: A newer anti-CD20 antibody that can be used as an alternative to Rituximab.
• PI3K inhibitors (e.g., Idelalisib, Copanlisib): For patients with relapsed or refractory follicular lymphoma.
• CAR T-cell therapy: Possible in selected cases, particularly for heavily pre-treated patients.
• Autologous stem cell transplantation: An option for younger patients with relapsed disease.

Prognosis

Follicular lymphoma is generally not curable, but it is manageable over the long term. Many patients live with the disease for many years. The 10-year survival rate is approximately 60–80%. Risk stratification is performed using the Follicular Lymphoma International Prognostic Index (FLIPI), which considers age, disease stage, number of affected lymph node regions, hemoglobin level, and LDH levels. In rare cases (approximately 3–5% per year), follicular lymphoma can transform into a more aggressive lymphoma (histological transformation).

References

1. Swerdlow SH et al. (eds.) – WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. 4th edition, IARC Press, Lyon, 2017.
2. Dreyling M et al. – Newly diagnosed and relapsed follicular lymphoma: ESMO Clinical Practice Guidelines. Annals of Oncology, 2021; 32(3): 298–308.
3. National Comprehensive Cancer Network (NCCN) – NCCN Clinical Practice Guidelines in Oncology: B-Cell Lymphomas. Version 2025. Available at: www.nccn.org.