Follicular lymphoma histology refers to the detailed microscopic examination of tissue samples to diagnose and understand follicular lymphoma. This process involves pathologists analyzing thin slices of tissue, typically from a lymph node, under a microscope. It is an important step in determining the presence and characteristics of this specific type of cancer. The insights gained from histology guide further diagnostic and treatment decisions.
Understanding Follicular Lymphoma and Histology
Follicular lymphoma (FL) is a common non-Hodgkin lymphoma, a cancer originating in lymphocytes. FL arises from B-cells, part of the immune system that produces antibodies. These cancerous B-cells develop within the germinal centers of lymph nodes. The disease tends to be slow-growing, or indolent, often affecting older adults.
Histology is the study of the minute structure of biological tissues. In the context of disease, it is called histopathology and involves preparing tissue samples by slicing and staining them, then examining them under a microscope. This microscopic view allows pathologists to observe cellular arrangements and abnormalities, providing a visual assessment of diseases like follicular lymphoma at a cellular level.
Key Microscopic Characteristics
Under the microscope, pathologists identify distinct features of follicular lymphoma. The most defining characteristic is the “follicular pattern” of growth, where lymphoma cells form abnormal, densely packed clusters or nodules. These neoplastic follicles often efface the normal architecture of the lymph node, appearing in a “back-to-back” arrangement.
Within these abnormal follicles, two primary types of cancerous B-cells are observed: centrocytes and centroblasts. Centrocytes are generally smaller cells with irregular, often cleaved or indented nuclei, inconspicuous nucleoli, and minimal cytoplasm. Centroblasts, conversely, are larger cells with round or oval, vesicular nuclei and one to three prominent nucleoli typically located near the nuclear membrane.
Follicular lymphoma presents with a mixture of centrocytes and centroblasts, though their proportions can vary. Unlike normal germinal centers, which contain tingible body macrophages, these macrophages are absent or scarce in follicular lymphoma. While most commonly seen in lymph node biopsies, these characteristic features can also be found in other affected sites, such as the bone marrow or spleen.
Grading and Its Significance
Follicular lymphoma is graded based on the number of centroblasts observed within cancerous follicles, which influences prognosis and treatment. The World Health Organization (WHO) classification system categorizes FL into three grades. Pathologists count centroblasts in high-power microscopic fields (HPF) to determine the grade. An HPF is defined as the area visible under a microscope at 400 times magnification.
Grade 1 follicular lymphoma features 0 to 5 centroblasts per high-power field, while Grade 2 contains 6 to 15 centroblasts per HPF. These are considered low-grade, slow-growing lymphomas.
Grade 3 follicular lymphoma is diagnosed when more than 15 centroblasts are present per HPF and is further subdivided. Grade 3A includes cases where centrocytes are still present alongside numerous centroblasts, and its clinical behavior can resemble lower-grade lymphomas. In contrast, Grade 3B consists almost entirely of sheets of centroblasts, behaving more aggressively, similar to diffuse large B-cell lymphoma. This histological grading guides decisions on whether to pursue watchful waiting or more intensive therapies.
Beyond the Microscope: Immunophenotyping and Molecular Tests
While microscopic examination is important for diagnosing follicular lymphoma, additional tests complement histological findings by providing more specific information. Immunophenotyping, performed through techniques like immunohistochemistry (IHC) or flow cytometry, identifies specific proteins or markers on the surface of lymphoma cells. For follicular lymphoma, cells express pan-B-cell markers such as CD20, and germinal center markers like CD10 and BCL6. They are negative for CD5 and CD23. These markers help confirm the B-cell origin and follicular nature of the lymphoma.
Molecular and genetic tests further enhance the diagnostic picture by detecting specific chromosomal abnormalities. The most common genetic change in follicular lymphoma is the t(14;18) translocation, found in 80% to 90% of cases. This translocation results in the overexpression of the BCL2 gene, an anti-apoptotic protein that helps cancer cells survive by preventing programmed cell death. While the t(14;18) translocation is a hallmark, its presence alone is not sufficient for diagnosis, as it can be found in healthy individuals. These advanced tests are performed with initial histological analysis, offering a comprehensive understanding for accurate diagnosis and tailored patient management.