Epithelioid Cells: Definition

Epithelioid cells

Epithelioid cells look like epithelial cells under a microscope. They are usually round or many-sided, with plenty of cytoplasm and a round or oval nucleus. The word “epithelioid” means “resembling epithelium,” so it describes how the cells look rather than what they are. Many different cell types can take on an epithelioid appearance, including immune cells, pigment cells, and the cells that line blood vessels.

Epithelioid cells are a description of what the pathologist observed, not a diagnosis on their own. They can appear in harmless conditions such as inflammation, as well as in both noncancerous and cancerous tumors. This article explains what epithelioid cells look like, which cells can appear epithelioid, and how pathologists determine what they really are.

What do epithelioid cells look like under the microscope?

Pathologists use the word epithelioid when cells share several features with epithelial cells. The cells are round or polygonal, not long and thin. They have abundant cytoplasm, which often stains pink on routine staining. The nucleus is usually round or oval and sits near the center of the cell.

Epithelioid cells often sit close together in sheets, nests, or small clusters. This crowded arrangement is another reason they resemble epithelial tissue. Pathologists often contrast epithelioid cells with spindle cells, which are long and thin. A tumor may be made of epithelioid cells, spindle cells, or a mixture of both.

Which cells can look epithelioid?

Epithelioid cells can come from several different tissues, so the term alone does not tell the pathologist what the cells are. The cell types that most often take on an epithelioid appearance include:

Epithelial cells. Cancers that start from epithelial cells, called carcinomas, are often made of epithelioid cells. This is especially true in poorly differentiated carcinomas that have lost their normal structure.
Histiocytes. Histiocytes are immune cells that clean up debris and fight infection. When they gather together to wall off something the body cannot remove, they often become epithelioid.
Melanocytes. Melanoma, a cancer that starts in pigment-producing cells, often forms large epithelioid cells. Some melanomas look so much like carcinoma that special tests are needed to tell them apart.
Endothelial cells. The endothelial cells that line blood vessels can become epithelioid in some vascular tumors.
Mesothelial cells. The mesothelial cells that line the chest and abdomen are naturally epithelioid. The most common type of mesothelioma is called epithelioid mesothelioma for this reason.
Other connective tissue cells. Some sarcomas and related tumors are made partly or entirely of epithelioid cells, even though they do not start from epithelium.

What are epithelioid histiocytes?

Epithelioid histiocytes are immune cells that have changed shape to look like epithelial cells. They are the main building block of a granuloma. A granuloma is a small, tightly packed cluster of these cells that forms when the body tries to wall off something it cannot easily destroy. Some epithelioid histiocytes fuse together to form very large cells called multinucleated giant cells.

Epithelioid histiocytes and granulomas are a form of inflammation, not cancer. Infections such as tuberculosis and some fungal infections can cause them. They also occur in conditions such as Crohn’s disease and sarcoidosis, and as a reaction to foreign material in tissue. Your report may describe the granulomas as necrotizing or non-necrotizing, which helps your doctor narrow down the cause.

Which tumors are described as epithelioid?

Some tumors include the word epithelioid in their name because their cells look epithelioid under the microscope. Despite the name, most of these tumors do not start from epithelial cells. Examples include:

Epithelioid sarcoma. Epithelioid sarcoma is a rare cancer that usually starts in the soft tissue of the arms or legs in young adults.
Epithelioid hemangioendothelioma. Epithelioid hemangioendothelioma is a rare cancer that starts from the cells lining blood vessels.
Epithelioid mesothelioma. This is the most common type of mesothelioma, a cancer of the lining of the chest or abdomen.
PEComa. A perivascular epithelioid cell tumor (PEComa) is made of unusual cells that grow around blood vessels. Many are noncancerous, but some behave like cancer.
Epithelioid angiomyolipoma. Epithelioid angiomyolipoma is a related tumor that usually starts in the kidney.

Other tumors may contain epithelioid cells without the word appearing in their name. Examples include some gastrointestinal stromal tumors (GIST) and some angiosarcomas. In these cases, your report may describe the tumor as having an “epithelioid pattern” or “epithelioid features.”

How do pathologists identify what epithelioid cells are?

Because epithelioid cells can come from many different tissues, pathologists often need more than their appearance to identify them. The most common additional test is immunohistochemistry, which uses antibodies to detect proteins made by particular cell types. Pathologists usually use a panel of stains because no single stain answers the question on its own. Common examples include:

Epithelial cells. Cytokeratin stains, such as pancytokeratin and EMA, are usually positive in carcinoma.
Histiocytes. Histiocytes stain positive for CD68 and CD163.
Melanocytes. Stains such as S100, SOX10, and Melan-A support melanoma.
Endothelial cells. Stains such as CD31 and ERG support a tumor that started from blood vessel cells.

Results are always interpreted together. For example, epithelioid sarcoma is usually cytokeratin-positive even though it is not a carcinoma. Most epithelioid sarcomas also lose a protein called INI1 (SMARCB1), and this loss helps distinguish them from carcinoma. Depending on the case, the pathologist may also use molecular tests that look for specific genetic changes.

Are epithelioid cells cancerous?

Epithelioid cells are not cancerous by definition. The word describes only the shape and appearance of the cells. Epithelioid cells are found in inflammation, in noncancerous tumors, and in cancers.

When epithelioid cells are found in a tumor, the pathologist looks at other features to decide whether it is noncancerous or cancerous. These features include how abnormal the cells look, called nuclear atypia, and how many dividing cells, or mitotic figures, are present. The pathologist also looks for areas of dead tissue, called necrosis, and for invasion into the surrounding tissue. The pathologist also considers where the tumor started and the results of any special tests.

Questions to ask your doctor

What type of cells did the epithelioid cells turn out to be?
Are the epithelioid cells part of inflammation or part of a tumor?
If granulomas were found, what is the most likely cause?
Were tests for infection done on my sample?
Which immunohistochemistry stains were used, and what did they show?
Is the tumor noncancerous or cancerous?
Were any molecular or genetic tests done on my sample?
Do I need any further tests or follow-up?