Your pathology report for chronic lymphocytic leukemia (CLL)

By Rosemarie Tremblay-LeMay MD FRCPC
August 19, 2025

Chronic lymphocytic leukemia (CLL) is a type of cancer that affects the blood and bone marrow. It starts in lymphocytes, a type of white blood cell that helps protect the body against infections. In CLL, the bone marrow produces too many abnormal lymphocytes. These cells do not work properly and crowd out normal blood cells. Over time, this can cause problems such as anemia, frequent infections, and an increased risk of bleeding.

CLL usually progresses slowly, and many people live with the disease for years before requiring treatment. It is the most common type of leukemia in adults, especially in older individuals.

What are the symptoms of chronic lymphocytic leukemia?

Many people with CLL do not have symptoms when they are first diagnosed, and the disease may only be discovered during routine blood work. When symptoms do appear, they may include:

  • Swollen lymph nodes in the neck, armpits, or groin.

  • An enlarged spleen, which can cause a feeling of fullness or discomfort in the abdomen.

  • Fatigue, fever, night sweats, or unexplained weight loss.

  • Frequent or long-lasting infections.

  • Easy bruising or bleeding.

Some people with CLL develop autoantibodies, which are proteins made by the immune system that mistakenly attack the body’s own cells.

This can lead to conditions such as:

  • Hemolytic anemia, where red blood cells are destroyed.

  • Immune thrombocytopenia, where platelets are destroyed, increasing the risk of bleeding.

Because CLL affects the immune system, people with this disease are also more vulnerable to infections.

What causes chronic lymphocytic leukemia?

The exact cause of CLL is not fully known. It likely results from a combination of genetic changes and environmental exposures.

  • Genetic changes: CLL begins when mutations (mistakes) occur in the DNA of lymphocytes. These changes cause the cells to grow and divide abnormally instead of maturing normally. The abnormal lymphocytes build up in the blood, bone marrow, and lymph nodes.

  • Family history: People with close relatives who have CLL or other blood cancers have a higher risk of developing CLL themselves, suggesting an inherited component.

  • Environmental exposures: Chemicals such as pesticides or herbicides may slightly increase the risk. Some studies suggest a possible link with Agent Orange, a chemical used during the Vietnam War.

  • Age and gender: CLL is more common in adults over the age of 60 and occurs more often in men than women.

  • Immune system factors: A weakened immune system or certain immune disorders may also increase risk.

It is important to know that most people who develop CLL do not have any clear risk factors, and the disease is not caused by lifestyle choices.

What is the difference between chronic lymphocytic leukemia and small lymphocytic lymphoma?

CLL and small lymphocytic lymphoma (SLL) are essentially the same disease. The difference is where the cancer cells are found:

  • If the abnormal lymphocytes are mostly in the blood and bone marrow, the disease is called CLL.

  • If they are mostly in lymph nodes or other tissues and not in the blood, it is called SLL.

Because the same type of cell is involved, doctors often describe the disease as CLL/SLL.

How is the diagnosis of chronic lymphocytic leukemia made?

The diagnosis usually starts with a blood test. If the blood shows an increased number of lymphocytes (a finding called lymphocytosis), additional tests are performed to see if the lymphocytes are abnormal.

Other tests that may be used include:

  • Biopsy: A small tissue sample may be taken from the bone marrow or an enlarged lymph node.

  • Flow cytometry: This test examines proteins on the surface of the lymphocytes to confirm that they are cancer cells.

  • Immunohistochemistry: A staining technique that shows which proteins are made by the cancer cells.

What does chronic lymphocytic leukemia look like under the microscope?

When pathologists examine the blood under a microscope, the cancer cells appear small with very little cytoplasm (the body of the cell). They have a round nucleus (the part that holds genetic material) with clumpy chromatin, giving the nucleus a “soccer ball” appearance.

The cells are fragile and often break during the preparation of the slide, creating smudge cells, which are a common finding in CLL.

What other tests are performed to confirm the diagnosis?

Immunohistochemistry

Immunohistochemistry (IHC) uses special dyes to highlight proteins made by the cancer cells. CLL cells usually produce proteins such as CD20, CD19, PAX5, and CD79a, although CD20 is often weaker than in normal B cells. They also usually produce CD5, CD23, CD43, and LEF1. Proteins such as CD10 and Cyclin D1 are not typically produced in CLL, which helps rule out other lymphomas.

Flow cytometry

Flow cytometry examines thousands of cells very quickly and records the proteins found on each cell. CLL cells usually show strong expression of CD200. Expression of CD38 in more than 30% of cancer cells may suggest a more aggressive disease.

Molecular tests

Pathologists also look for genetic changes using tests such as fluorescence in situ hybridization (FISH). These tests can find missing or extra pieces of chromosomes.

Common findings in CLL include:

  • Trisomy 12 – An extra copy of chromosome 12.

  • 13q deletion – Part of chromosome 13 is missing.

  • 11q deletion (ATM) – Part of chromosome 11 is missing.

  • 17p deletion (TP53) – Part of chromosome 17 is missing, including the TP53 gene, which normally helps prevent cancer.

Tumors with 11q or 17p deletions, or with multiple abnormalities, often behave more aggressively.

Mutations in the immunoglobulin heavy chain gene (IGHV) may also be found. Tumors with this mutation tend to be less aggressive and are associated with a better prognosis.

What are prolymphocytes, and why are they important?

Prolymphocytes are larger, more immature lymphocytes that may be seen in small numbers in CLL.

  • If they make up less than 15% of the cancer cells, the diagnosis remains typical CLL.

  • If they make up 15–55%, the disease is called atypical CLL, which may behave more aggressively.

  • If more than 55% of the cells are prolymphocytes, the diagnosis changes to B-cell prolymphocytic leukemia, which is a different and more aggressive disease.

What does transformation mean, and why is it important?

Over time, CLL can sometimes change, or transform, into a more aggressive lymphoma. This is called Richter transformation.

In CLL, Richter transformation can lead to one of three types of lymphoma:

  • Prolymphocytoid transformation.

  • Diffuse large B-cell lymphoma.

  • Classic Hodgkin lymphoma.

Transformation is important because it means the disease is more aggressive and requires different treatment.

Questions to ask your doctor

If you have been diagnosed with chronic lymphocytic leukemia, you may wish to ask your doctor the following questions:

  • Do I have CLL, SLL, or both?

  • What genetic changes were found in my cancer, and how do they affect my prognosis?

  • What stage is my disease, and what does that mean for treatment?

  • Do I need treatment now, or is watchful waiting a safe option?

  • What symptoms should I look for that might mean the disease is progressing?

A+ A A-