Lymphocytosis and smudge cells are characteristic signs of chronic lymphocytic leukemia. They can also be signs of conditions such as other cancers, infections, and autoimmune diseases.

Lymphocytosis is an elevated lymphocyte count. Lymphocytes are a group of white blood cells that help your body fight off disease. Most laboratories define lymphocytosis as a lymphocyte count of over 3 to 4 billion cells per liter of blood.

Smudge cells, or basket cells, are white blood cells that are partially destroyed during the preparation of a blood smear. The presence of smudge cells suggests that your lymphocytes are abnormally fragile.

Lymphocytosis and the presence of smudge cells are common findings in people with chronic lymphocytic leukemia (CLL). These findings can also have other causes, such as infectious diseases, other types of blood cancer, and medication side effects.

Read on to learn more about what it means to have lymphocytosis and smudge cells.

Smudge cells are broken remnants of white blood cells in your blood that primarily form when a blood smear is prepared.

A blood smear is a sample of your blood placed on a glass slide so healthcare professionals can examine the shape and number of blood cells in your sample.

Doctors use blood smears to help diagnose conditions such as:

Smudge cells get their name from their appearance under a microscope, where they appear as smudges without a well-defined border.

Finding smudge cells in your blood sample suggests that your blood cells are more fragile than normal. The formation of smudge cells has been linked to reduced expression of the protein vimentin.

A high lymphocyte count combined with the presence of smudge cells is often a sign of a type of cancer called CLL. Almost everybody with CLL has smudge cells in their sample.

Do smudge cells always mean you have CLL?

Having lymphocytosis and smudge cells in your blood sample doesn’t necessarily mean you have CLL. Smudge cells can form due to infectious disease and other causes, such as medication side effects.

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Lymphocytosis with smudge cells is a hallmark feature of CLL. Most people with CLL have smudge cells in their blood samples. Nearly all the smudge cells in people with CLL are lymphocytes.

Smudge cells typically make up 20–30% of the total lymphocytes in the blood of people with CLL, but this percentage has been reported as high as 75%.

Many other types of blood cancer can also cause lymphocytosis and smudge cells to appear in your blood sample. They include the following conditions:

Lymphocytosis with smudge cells can also be a sign of monoclonal B-cell lymphocytosis, which is not considered a type of cancer.

Some viral, parasitic, and bacterial infections can cause your white blood cells to become more fragile, which can lead to the development of smudge cells. They can also cause your body to produce a higher number of lymphocytes.

Infections are the leading cause of lymphocytosis not caused by cancer. Many types of infections can cause lymphocytosis or smudge cells to form in your blood sample.

In a 2021 study, researchers reported a case of a boy with infectious mononucleosis with an elevated lymphocyte count. About half of his white blood cells were smudge cells.

In a 2020 study, researchers reported a case of a 55-year-old man who developed COVID-19 and a high lymphocyte count. A total of 63% of the lymphocytes in his blood sample were smudge cells.

Other infections linked to lymphocytosis include:

Lymphocytosis with smudge cells has also been linked to some noncancerous or infectious causes that include:

These causes usually heal within 3 months. If your lymphocytosis lasts longer than this, doctors may suspect an underlying blood cancer.

Smudge cells may also form simply because your blood sample is old.

Lymphocytosis is a higher-than-usual count of a type of white blood cell called lymphocytes. Smudge cells are damaged white blood cells that suggest your blood cells are more fragile.

Lymphocytosis and smudge cells are common signs of CLL. Other conditions that can cause lymphocytosis and smudge cells to form in your blood sample are other blood cancers, infections, and medication side effects.