Physicians perform an array of tests to diagnose CLL and determine both its type and subtype. Diagnostic tests can reveal abnormalities in the appearance of cells and in the amounts of different types of blood cells in circulation, changes in the bone marrow, specific alterations in the genetic and molecular makeup of the diseased cells, and other factors that are helpful in deciding on the most effective course of treatment.

A physical exam will be performed, during which the doctor will check the lymph nodes, spleen, and liver because lymphocytes can accumulate in these spots and cause swelling. In some cases, the first sign of CLL is an enlarged spleen or liver.

One key test used to diagnose CLL is a complete blood count, a test that can show whether the amounts of various components of the blood are within normal ranges. People with CLL may have low numbers of red blood cells, which causes anemia; platelet levels may be low, leading to bleeding and bruising; and normal white blood cell levels may be diminished, which might lead to infections. Blood tests can also show the blood levels of proteins called immunoglobulins and whether the gene responsible for producing a specific immunoglobulin called IgVH has changed, or mutated. (CLL patients with a mutation in this gene generally have a less aggressive form of the disease.)

In a bone marrow biopsy, physicians insert a hollow needle into the hip bone to remove a small piece of bone and marrow for examination. In a bone marrow aspirate, they withdraw a small sample of liquid bone marrow through a syringe.

Doctors perform a bone marrow evaluation when symptoms of the disease appear. Treatment usually becomes necessary at this point. (For more information about treating CLL, visit the Treatment section of this overview.)

In addition, physicians use a number of tests that help them determine specific features of the cells in biopsied tissue. These tests can identify genetic abnormalities such as chromosomal rearrangements — which are common in leukemias — and specific proteins called antigens on the surfaces of the cells. This information helps the doctor identify the cells’ origins and determine the patient’s prognosis. Commonly performed tests include:

  • cytogenetic studies to identify chromosomal changes in cells
  • immunohistochemistry studies, tests that determine which specific proteins, called antibodies, are found on the surface of a patient’s cancer cells
  • flow cytometry, in which prepared cells are passed through a laser beam for analysis
  • molecular genetic studies, which are highly sensitive DNA and RNA tests used to determine specific genetic traits of cancer cells

One important cytogenetic test now in use is called fluorescent in situ hybridization, or FISH. This test looks for several chromosomal changes that signal whether a patient’s CLL will progress quickly and aggressively. For example, patients with mutations such as deletions of genetic material from chromosomes 17 and 11 are much more likely to need treatment for the disease within one to five years following diagnosis than people without these abnormalities.

New diagnostic tests and procedures are emerging from work on the human genome and gene expression analysis, a technique that allows researchers to identify which genes are “turned on” in cancer cells and other cells in the body. These are likely to be important in the future but are currently experimental.