What is Follicular Lymphoma?
Follicular lymphoma is a type of non-Hodgkin lymphoma characterized by the malignant transformation of B lymphocytes within the lymphoid follicle. It is the second most common subtype of non-Hodgkin lymphoma, accounting for approximately 20-30% of all cases. The disease is typically indolent but can progress to a more aggressive form.
Histological Features
The hallmark of follicular lymphoma in histology is the presence of abnormal, closely packed follicles that replace the normal lymph node architecture. These follicles are typically composed of a mixture of small cleaved cells and larger centroblasts. The follicles lack the usual polarization seen in normal germinal centers and often exhibit a "back-to-back" arrangement.Cellular Composition
The neoplastic follicles in follicular lymphoma predominantly consist of two types of cells: centrocytes and centroblasts. Centrocytes are small to medium-sized cells with irregular, cleaved nuclei and scant cytoplasm. Centroblasts are larger cells with prominent nucleoli and more abundant cytoplasm. The ratio of centrocytes to centroblasts can vary and is used to grade the lymphoma.Grading and Classification
Follicular lymphoma is graded based on the number of centroblasts per high-power field (HPF). The World Health Organization (WHO) classification system includes three grades:
- Grade 1: 0-5 centroblasts per HPF
- Grade 2: 6-15 centroblasts per HPF
- Grade 3: >15 centroblasts per HPFGrade 3 is further subdivided into 3A (with residual centrocytes) and 3B (predominantly centroblasts). Higher-grade follicular lymphomas have a higher propensity for transformation into diffuse large B-cell lymphoma.
Immunohistochemistry and Molecular Markers
Immunohistochemistry (IHC) is crucial for the diagnosis of follicular lymphoma. Key markers include:
- CD20: A pan-B cell marker that is positive in the neoplastic B cells.
- CD10: Often positive, indicating a germinal center origin.
- BCL2: Overexpressed in most cases due to the t(14;18) translocation, which is a hallmark of follicular lymphoma.
- BCL6: Another germinal center marker that is usually positive.The t(14;18) translocation results in the juxtaposition of the BCL2 gene to the IgH locus, leading to overexpression of BCL2 protein and inhibition of apoptosis.
Clinical Presentation
Patients with follicular lymphoma often present with painless, generalized lymphadenopathy. The disease can also involve the bone marrow and spleen. Systemic symptoms such as fever, night sweats, and weight loss (B symptoms) are less common in the early stages but may occur as the disease progresses.Prognosis and Treatment
The prognosis of follicular lymphoma varies based on the grade and stage at diagnosis. Indolent forms of the disease may not require immediate treatment and can be managed with a "watch and wait" approach. Treatment options include:
- Chemotherapy: Common regimens include CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) or bendamustine.
- Immunotherapy: Rituximab, an anti-CD20 monoclonal antibody, is often used in combination with chemotherapy.
- Radiation Therapy: Used for localized disease.
- Stem Cell Transplant: Considered in cases of relapse or transformation to a more aggressive lymphoma.Conclusion
Follicular lymphoma is a distinct type of non-Hodgkin lymphoma with unique histological and molecular features. Understanding its histological appearance, immunophenotype, and clinical behavior is essential for accurate diagnosis and management. Advances in molecular genetics and targeted therapies continue to improve outcomes for patients with this disease.
