follicular lymphoma

follicular lymphoma
Name	Follicular lymphoma
Caption	Micrograph of follicular lymphoma showing follicular structures
Field	Oncology, Hematology
Symptoms	Painless lymphadenopathy, fatigue, night sweats, fever, weight loss
Complications	Transformation to diffuse large B-cell lymphoma, Bone marrow failure
Onset	Typically older adults
Duration	Chronic
Types	Grade 1, 2, 3A, 3B
Causes	Genetic translocations, particularly t(14;18), involving BCL2
Risks	Family history, certain autoimmune diseases, exposure to pesticides
Diagnosis	Excisional lymph node biopsy, flow cytometry, immunohistochemistry
Differential	Other non-Hodgkin lymphomas, reactive lymphadenopathy
Prevention	Not clearly established
Treatment	Watchful waiting, radiation therapy, immunotherapy, chemotherapy, targeted therapy
Medication	Rituximab, Obinutuzumab, Bendamustine, Lenalidomide
Prognosis	Generally indolent but incurable; median survival >10 years
Frequency	~20% of non-Hodgkin lymphomas in the West
Deaths	Variable, often due to transformation or complications

follicular lymphoma is a common indolent B-cell lymphoma and a major subtype of non-Hodgkin lymphoma. It is characterized by a neoplastic proliferation of germinal center B-cells that typically form follicular structures. The disease has a strong genetic association with the t(14;18) chromosomal translocation, which leads to overexpression of the anti-apoptotic protein BCL2. While often slow-growing, it is considered incurable with standard therapies and can transform into more aggressive lymphomas.

Signs and symptoms

Many patients are asymptomatic at diagnosis, with the disease discovered incidentally during examinations for unrelated issues. The most common presenting sign is painless, persistent lymphadenopathy, often in the neck, axilla, or groin. Systemic **B symptoms** such as night sweats, unexplained fever, and significant weight loss may occur, particularly with more advanced disease. Patients may also report profound fatigue due to anemia or the disease's systemic effects. Less common manifestations include splenomegaly, hepatomegaly, and symptoms from bone marrow involvement, such as increased susceptibility to infection or bleeding.

Causes and pathophysiology

The primary molecular event in most cases is the t(14;18) translocation, which places the BCL2 gene from chromosome 18 under the control of the powerful immunoglobulin heavy chain enhancer on chromosome 14. This translocation is thought to occur during V(D)J recombination in pre-B cells in the bone marrow. The resultant constitutive overexpression of BCL2 inhibits apoptosis, allowing the abnormal B-cell to survive. Subsequent accumulation of additional genetic mutations in genes such as EZH2, CREBBP, and MLL2 drives full lymphomagenesis. Environmental risk factors are poorly defined but may include exposure to certain herbicides and pesticides.

Diagnosis

Definitive diagnosis requires an excisional lymph node biopsy to assess the tissue architecture. Histopathological examination reveals effacement of the normal lymph node structure by neoplastic follicles. Key diagnostic tests include immunohistochemistry, where the tumor cells are positive for B-cell markers like CD20 and CD79a, as well as germinal center markers CD10 and BCL6, while being negative for CD5 and CD23. Flow cytometry on the biopsy specimen or peripheral blood can confirm a clonal B-cell population. The presence of the t(14;18) translocation can be confirmed by fluorescence in situ hybridization or polymerase chain reaction.

Staging and grading

Staging follows the Ann Arbor staging system, incorporating findings from physical examination, computed tomography scans of the chest, abdomen, and pelvis, and bone marrow biopsy. Positron emission tomography is increasingly used to assess metabolic activity. Grading, based on the number of large cells (centroblasts) per high-power field, is critical: Grade 1-2 and Grade 3A are considered indolent, while Grade 3B behaves similarly to diffuse large B-cell lymphoma and is treated aggressively. The Follicular Lymphoma International Prognostic Index is used to stratify risk based on factors like age, stage, hemoglobin level, number of nodal areas, and serum lactate dehydrogenase.

Treatment

Management is highly individualized. For asymptomatic, low-tumor-burden disease, initial watchful waiting is often appropriate. First-line therapy for symptomatic patients typically involves immunotherapy combined with chemotherapy; common regimens include Rituximab plus CHOP or Bendamustine. Radiation therapy can be curative for localized (Stage I-II) disease. For relapsed or refractory cases, options include Lenalidomide plus Rituximab, phosphatidylinositol 3-kinase inhibitors like Copanlisib, stem cell transplantation, and newer CAR-T cell therapy such as Axicabtagene ciloleucel. Radioimmunotherapy with agents like Ibritumomab tiuxetan is also used in some settings.

Prognosis

Follicular lymphoma is characterized by a relapsing and remitting course, with a median overall survival now exceeding 10-12 years due to advances in therapy. However, it is generally considered incurable with conventional treatments. The major cause of mortality is histological transformation to a more aggressive lymphoma, most commonly diffuse large B-cell lymphoma, which occurs at a rate of approximately 2-3% per year. Prognosis is influenced by the FLIPI score, response to initial therapy, and the molecular genetic profile of the tumor. Long-term follow-up is essential to monitor for transformation, treatment-related complications, and the development of secondary malignancies.

Category:Non-Hodgkin lymphoma Category:Lymphomas