CD56: Definition

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CD56 is a protein found on the surface of nerve cells, neuroendocrine cells, and a type of immune cell called natural killer cells. It helps cells stick together. Pathologists test for CD56 to help identify neuroendocrine tumors, some lymphomas, and abnormal plasma cells. CD56 is also known as NCAM, which stands for neural cell adhesion molecule.

CD56 is a test result, not a diagnosis. It is one of the stains a pathologist uses to work out what type of cells are present. This article explains why pathologists test for CD56 and what a positive or negative result means in your pathology report.

Where is CD56 normally found?

In normal tissue, CD56 is found on nerve cells and their supporting cells, on neuroendocrine cells, and on natural killer cells. It is also found on some T cells and on muscle cells that are developing or repairing themselves.

Normal plasma cells usually do not contain CD56. This difference helps pathologists identify abnormal plasma cells.

How do pathologists test for CD56?

Pathologists test for CD56 using immunohistochemistry (IHC). In this test, a thin slice of tissue on a glass slide is treated with an antibody that sticks to CD56. A chemical reaction then colors any cell containing CD56 brown so that it can be seen under the microscope.

Pathologists can also measure CD56 by flow cytometry, which is often used for blood and bone marrow samples.

Why do pathologists test for CD56?

Pathologists use CD56 to confirm what cell types are present. Pathologists test for CD56 in the following situations:

To identify neuroendocrine tumors. Most neuroendocrine tumors and neuroendocrine carcinomas, including small cell carcinoma, are CD56 positive. It is usually tested together with synaptophysin, chromogranin, and INSM1, which are more specific.
To identify natural killer cell lymphomas. Extranodal NK/T-cell lymphoma is usually CD56 positive.
To identify abnormal plasma cells. In multiple myeloma, the plasma cells are often positive for CD56, while normal plasma cells are not. This helps show that the plasma cells are abnormal.
To identify other tumors. CD56 is also positive in some leukemias, neuroblastoma, and some other childhood tumors.

Because CD56 is found in so many different cell types, it is never used on its own to make a diagnosis.

What does a positive CD56 result mean?

A positive result means the tested cells contain CD56. Your report may describe the result as “positive” or say that CD56 “is expressed.” The meaning depends on the tumor type being considered. In a tumor that looks neuroendocrine, a positive result supports that diagnosis. In plasma cells, a positive result suggests that the plasma cells are abnormal.

What does a negative CD56 result mean?

A negative result means the cells being tested do not contain CD56. Your report may describe the result as “negative” or “not expressed.” A negative result makes some diagnoses less likely, but it does not rule them out. For example, some neuroendocrine tumors and some cases of multiple myeloma are negative for CD56.

Questions to ask your doctor

Why was CD56 tested on my sample?
Was the CD56 result positive or negative?
What other stains were done along with CD56?
Does the result support a neuroendocrine tumor or a lymphoma?
If my plasma cells were tested, are they normal or abnormal?
What is the final diagnosis in my report?