Burkitt Lymphoma is a serious form of cancer affecting the lymphatic system, a network of tissues and organs that help rid the body of toxins, waste, and other unwanted materials. Diagnosis often begins with examining tissue samples under a microscope, a process known as histology. Pathologists identify Burkitt Lymphoma by analyzing these samples for specific cellular characteristics. This article explores how microscopic examinations contribute to diagnosis.
What is Burkitt Lymphoma?
Burkitt Lymphoma is an aggressive type of B-cell non-Hodgkin lymphoma. In Burkitt Lymphoma, these B cells grow and divide uncontrollably.
The disease presents in several forms globally. Endemic Burkitt Lymphoma, often seen in equatorial Africa, typically affects children and frequently manifests as a jaw tumor. Sporadic Burkitt Lymphoma occurs worldwide, affecting both children and adults, and commonly involves the abdomen. A third form is associated with immunodeficiency, particularly in individuals with HIV/AIDS.
Preparing the Tissue for Analysis
Diagnosing Burkitt Lymphoma begins with obtaining a tissue sample, usually through a biopsy from an affected area, such as a lymph node or tumor. Once collected, the tissue undergoes preparation for microscopic examination. The sample is first placed in a fixative, commonly formalin, which preserves the tissue structure.
Following fixation, the tissue is processed to remove water and prepare it for embedding. It is then embedded in paraffin wax. This paraffin block is then thinly sliced, typically to a thickness of 3 to 5 micrometers, using a specialized instrument called a microtome. The slices are then mounted onto glass slides and stained, most commonly with hematoxylin and eosin (H&E), which highlights cellular components for microscopic viewing.
Microscopic Hallmarks of Burkitt Lymphoma
When examining an H&E-stained tissue slide of Burkitt Lymphoma, a characteristic appearance emerges. The most striking feature is the “starry sky” pattern, characterized by scattered, pale-staining macrophages against a dense, uniform background of dark-staining lymphoma cells. These macrophages are benign immune cells that have engulfed dead tumor cells, creating clear spaces that resemble stars in a night sky.
The lymphoma cells themselves display uniformity in size and shape, appearing as medium-sized cells. Each cell possesses a round or oval nucleus containing one to several prominent nucleoli, which are small, dense structures within the nucleus. The cytoplasm is generally basophilic, meaning it stains blue with H&E, and often contains small, clear vacuoles. These cells exhibit a very high mitotic rate, reflecting the tumor’s rapid growth. This high proliferative index, often close to 100%, is a defining feature of Burkitt Lymphoma.
Confirming the Diagnosis with Specialized Tests
While the “starry sky” appearance and cellular morphology provide strong indications, confirming a diagnosis of Burkitt Lymphoma requires additional specialized tests. Immunohistochemistry (IHC) uses antibodies to detect specific proteins on or within the lymphoma cells. For Burkitt Lymphoma, cells typically test positive for B-cell markers such as CD20 and CD10, and often for BCL6.
Conversely, they are usually negative for BCL2, a protein often found in other types of lymphoma, which helps distinguish Burkitt Lymphoma. A very high Ki-67/MIB-1 proliferation index, often exceeding 95%, further supports the diagnosis, reflecting the rapid cell division. The cells are typically negative for CD34, a marker found on some immature blood cells.
Beyond IHC, genetic testing is performed to identify the characteristic chromosomal translocations involving the MYC gene. The most common translocation is t(8;14), where a piece of chromosome 8 (containing MYC) moves to chromosome 14. Less common variants include t(2;8) and t(8;22). These translocations can be detected using techniques like Fluorescence In Situ Hybridization (FISH), which uses fluorescent probes to highlight specific genetic sequences. Identifying this MYC translocation is a definitive diagnostic criterion, helping to differentiate Burkitt Lymphoma from other high-grade B-cell lymphomas that might share some microscopic features.