Chronic Lymphocytic Leukemia (CLL) is a cancer of the blood and bone marrow, characterized by the slow, uncontrolled growth of B-lymphocytes. These abnormal cells accumulate, crowding out healthy blood cells in the bone marrow, blood, and lymph nodes. The diagnostic process uses specialized laboratory tests to definitively identify these cancerous B-cells and distinguish them from other conditions.
Initial Indication and Discovery
The majority of CLL cases are discovered accidentally during routine medical check-ups. A physician may order a standard blood test, a Complete Blood Count (CBC), for an unrelated reason, which then reveals an unusually high number of lymphocytes. This finding, known as lymphocytosis, prompts further investigation into CLL.
In a smaller number of cases, diagnosis begins when a person reports vague symptoms, such as persistent fatigue, night sweats, or unintentional weight loss (B symptoms). A physical examination might also reveal painless swelling in the lymph nodes or an enlargement of the spleen or liver. These findings lead the doctor to order foundational blood tests to look for an underlying blood disorder.
Core Blood Analysis and Confirmation Testing
The Complete Blood Count (CBC) is the foundational test that provides the first concrete data point in the diagnosis process. This test measures the types and numbers of cells in the blood, and in a patient with suspected CLL, it will typically show an abnormally high absolute lymphocyte count. A blood smear is also often examined under a microscope, which may show an abundance of small, mature-looking lymphocytes and characteristic “smudge cells,” which are fragile, ruptured white blood cells.
The definitive confirmation of Chronic Lymphocytic Leukemia relies on a highly specialized laboratory technique called flow cytometry. This test is performed on a blood sample and uses fluorescently tagged antibodies to analyze thousands of individual cells, creating a “fingerprint” of the proteins on the cell surfaces. CLL cells have a unique immunophenotype, which is a specific pattern of surface markers that confirms they are cancerous and not normal lymphocytes.
The characteristic immunophenotype for CLL cells includes the co-expression of T-cell marker CD5 along with B-cell markers CD19 and CD23. The cells also typically show low expression of other B-cell markers, such as CD20 and surface immunoglobulin. This distinct combination of markers allows flow cytometry to distinguish CLL from other types of lymphoma or leukemia.
Interpreting Results and Defining the Diagnosis
The official diagnosis of Chronic Lymphocytic Leukemia is based on a specific numerical threshold derived from the flow cytometry results. A person must have a count of 5,000 or more abnormal, monoclonal B-lymphocytes per cubic millimeter of peripheral blood to be officially diagnosed with CLL. This elevated count must also be sustained for a period of at least three months, ensuring the persistent nature of the condition.
The interpretation of the flow cytometry results is important for distinguishing CLL from a related, non-cancerous condition called Monoclonal B-cell Lymphocytosis (MBL). MBL is considered a pre-cancerous state where the same abnormal B-cells are present and show the identical CLL-like immunophenotype. However, MBL is defined by having a monoclonal B-cell count that is less than 5,000 cells per cubic millimeter.
Individuals with high-count MBL (500 to 5,000 B-cells per cubic millimeter) are monitored closely. They carry an annual risk of about one to two percent of progressing to active CLL.
Tests for Staging and Disease Activity
Once the diagnosis of CLL is confirmed, additional specialized tests are performed to assess the disease’s potential activity and guide future management. One important method is Fluorescent In Situ Hybridization (FISH), which is a cytogenetic test that examines the chromosomes within the CLL cells. FISH testing looks for specific deletions or gains in genetic material that affect the disease’s prognosis.
Certain findings from the FISH test are associated with more aggressive disease behavior, such as the deletion of part of chromosome 17p or 11q. Conversely, a deletion of chromosome 13q is linked to a more favorable disease course. The IgVH mutation status is another key prognostic indicator that determines the aggressiveness of the B-cells; unmutated genes suggest a more rapidly progressing form of the disease.
While not required for the initial diagnosis, imaging tests like CT scans or a bone marrow biopsy may be necessary later to fully assess the extent of the disease (staging), particularly if treatment is being considered. Staging systems, such as the Rai or Binet systems, utilize physical exam findings and blood counts to determine the overall burden of the disease.