Chronic Lymphocytic Leukemia (CLL) is a cancer of white blood cells, specifically lymphocytes. These abnormal lymphocytes accumulate in the blood and bone marrow, potentially interfering with normal blood cell production. This article outlines the methods used to identify and confirm a CLL diagnosis.
When Testing Becomes Necessary
Many individuals with chronic lymphocytic leukemia do not experience symptoms early on, with the condition often discovered incidentally during routine blood tests performed for other reasons. However, when symptoms do arise, they can be vague and mimic other common illnesses. People might experience persistent fatigue, unexplained weight loss, night sweats, or recurrent infections due to a compromised immune system. Swollen lymph nodes, particularly in the neck, armpits, or groin, are also a common indicator. Abdominal discomfort from an enlarged spleen can occur as well, prompting a visit to the doctor.
Key Diagnostic Tests
Complete Blood Count (CBC) with Differential
A complete blood count with differential is often the initial test performed when CLL is suspected. This blood test measures the quantities of red blood cells, white blood cells, and platelets in your blood. In individuals with CLL, this test typically reveals an elevated number of lymphocytes, a condition known as lymphocytosis. A lymphocyte count exceeding 5,000 cells per cubic millimeter of blood strongly suggests CLL, although further tests are needed to confirm the diagnosis.
The peripheral blood smear, which is part of the CBC, involves examining a blood sample under a microscope. This can reveal the presence of abnormal-looking lymphocytes, sometimes referred to as smudge cells, which are characteristic of CLL. Additionally, the CBC might show lower levels of red blood cells (anemia) or platelets (thrombocytopenia) as the disease progresses and abnormal lymphocytes crowd out healthy cells in the bone marrow.
Flow Cytometry
Flow cytometry is considered the definitive test for confirming a CLL diagnosis. This laboratory technique analyzes cells by passing them through a laser beam, detecting specific proteins, or “markers,” on their surface. For CLL, flow cytometry identifies a characteristic pattern of markers on the abnormal B-lymphocytes, such as the co-expression of CD5, CD19, CD20 (dim), and CD23.
This test is performed on peripheral blood samples and confirms the presence of clonal B-lymphocytes. Flow cytometry also helps distinguish CLL from other blood disorders and can provide insights into the aggressiveness of the leukemia cells.
Genetic and Cytogenetic Testing
Genetic and cytogenetic tests, while not solely diagnostic, provide important prognostic information about CLL. Fluorescence In Situ Hybridization (FISH) is a common cytogenetic test that examines chromosomes inside the cancerous lymphocytes for specific changes. This test can identify chromosomal abnormalities such as deletions on chromosome 17p (del(17p)), which includes the TP53 gene, deletion on chromosome 11q (del(11q)), and trisomy 12.
Additional genetic tests include assessing the immunoglobulin heavy chain variable region (IgVH) mutation status and TP53 gene sequencing. An unmutated IgVH gene and the presence of a TP53 mutation or 17p deletion are associated with a less favorable prognosis. These genetic insights help guide treatment decisions and predict how the disease might behave over time.
Bone Marrow Biopsy
A bone marrow biopsy is not always necessary for the initial diagnosis of CLL, as blood tests often provide sufficient information. However, it may be performed in specific situations, such as when blood test results are inconclusive or to assess the extent of bone marrow involvement. This procedure involves taking a small sample of bone marrow fluid and solid tissue, typically from the back of the hip bone.
The biopsy can help determine if low blood cell counts, such as anemia or thrombocytopenia, are due to bone marrow infiltration by leukemia cells or other conditions. In some cases, a bone marrow biopsy is used to evaluate the effectiveness of treatment or if there is a suspicion that the CLL has transformed into a more aggressive form of lymphoma.
Understanding Your Diagnosis
Confirming a CLL diagnosis involves a comprehensive evaluation of all test results by medical professionals. The presence of a persistently high number of abnormal lymphocytes in the blood, exceeding 5,000 B-cells per microliter, is a primary indicator. Flow cytometry then confirms that these lymphocytes are clonal B-cells and display the specific surface markers characteristic of CLL, such as CD5, CD19, and CD23.
Medical professionals integrate these laboratory findings with the individual’s clinical presentation, including any reported symptoms and findings from a physical examination. This holistic approach ensures an accurate diagnosis and helps differentiate CLL from other conditions that might present with similar blood count abnormalities.
Initial Steps After Diagnosis
Once a diagnosis of chronic lymphocytic leukemia is confirmed, the immediate next step involves consulting with a hematologist or oncologist, a doctor specializing in blood disorders and cancer. These specialists will discuss the diagnosis in detail and outline the path forward. Disease staging is performed after diagnosis to understand the extent of the cancer.
CLL is commonly staged using systems like the Rai or Binet classifications, which consider factors such as lymphocyte count, the presence of enlarged lymph nodes, spleen, or liver, and whether anemia or thrombocytopenia are present. These staging systems help determine the disease’s progression and guide subsequent management. The decision to monitor the disease through regular check-ups or to initiate treatment is individualized, based on the stage and other prognostic factors.