Pseudoepitheliomatous Hyperplasia: Definition

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Pseudoepitheliomatous hyperplasia (PEH) is a noncancerous change in which the surface lining of the skin or a mucosal surface becomes thicker and grows downward into the tissue below. It is a reaction to something else happening in the tissue, such as a long-standing wound, an infection, or a tumor sitting underneath. Your report may also call it pseudocarcinomatous hyperplasia, which means the same thing.

The name describes what the change looks like. Hyperplasia means an increase in the number of cells. “Epithelioma” is an old word for a skin cancer, and “pseudo” means false. Together, the name means the lining has grown in a way that looks like cancer but is not cancer.

Pseudoepitheliomatous hyperplasia describes what the pathologist saw under the microscope, not a diagnosis on its own. It is usually reported together with the condition that caused it. This article explains what pseudoepitheliomatous hyperplasia means, what causes it, and how pathologists tell it apart from squamous cell carcinoma.

Where is pseudoepitheliomatous hyperplasia found?

Pseudoepitheliomatous hyperplasia develops in tissues covered by squamous epithelium, a lining made of flat cells stacked in layers. The skin is the most common location. In the skin, the change affects the epidermis, the outermost layer.

It can also develop in the mucosa that lines the mouth and tongue, the voice box, the food pipe (esophagus), and the genital area. These surfaces have the same type of squamous lining as the skin.

What causes pseudoepitheliomatous hyperplasia?

Pseudoepitheliomatous hyperplasia is caused by long-lasting irritation or stimulation of the squamous lining. The lining responds by making more cells, and those cells push down into the tissue beneath. Common causes include:

Chronic wounds and ulcers. The edge of an ulcer, burn, or wound that has been healing for a long time often shows this change.
Infections. Some deep fungal infections, certain bacterial infections such as those caused by mycobacteria, and some parasitic infections produce this change in the overlying skin.
Granular cell tumor. A granular cell tumor is a noncancerous tumor that often causes the overlying lining to thicken. It is one of the best-known causes in the mouth and on the tongue.
Other tumors under the surface. Some lymphomas and other skin growths can cause the surface above them to react the same way.
Long-term scratching or rubbing. Itchy skin conditions that are scratched repeatedly over months or years can produce thick, raised areas with this change.
Reactions to foreign material. Tattoo ink and other material in the skin can trigger a reaction that includes this change.
Irritation in the mouth. Constant rubbing from a sharp tooth or a poorly fitting denture can cause it in the mouth lining.

In some cases, the tissue sample shows no cause. This is more likely when the biopsy is small or does not include the deeper tissue where the cause may be.

What does pseudoepitheliomatous hyperplasia look like under the microscope?

Under the microscope, pseudoepitheliomatous hyperplasia appears as a thickened squamous lining with irregular strands and tongues of cells reaching down into the tissue below. Normally, the bottom edge of the lining is fairly smooth. In pseudoepitheliomatous hyperplasia, it becomes jagged and uneven.

Some of the downward strands are cut across when the tissue is sliced for the glass slide. These cut strands can look like small islands of squamous cells sitting alone in the deeper tissue. This appearance is the main reason the change can be mistaken for cancer.

The cells themselves usually look normal. They mature in an orderly way from the bottom of the lining to the top, as healthy squamous cells do. The pathologist often sees a nearby cause of the change, such as inflammation, an ulcer, organisms, or tumor cells.

How is pseudoepitheliomatous hyperplasia different from squamous cell carcinoma?

Pseudoepitheliomatous hyperplasia can closely resemble squamous cell carcinoma, a type of cancer that also starts from squamous cells. Both show squamous cells extending below the surface. Pathologists rely on several features to tell them apart:

How the cells look. In pseudoepitheliomatous hyperplasia, the cells look normal or only slightly changed. In squamous cell carcinoma, the cells usually look abnormal, with large, dark, or irregular nuclei.
How deep the cells go. Pseudoepitheliomatous hyperplasia stays fairly close to the surface. Squamous cell carcinoma tends to grow deeper and spread irregularly into surrounding tissue.
Whether a cause is present, finding an infection, an ulcer, or a tumor such as a granular cell tumor supports pseudoepitheliomatous hyperplasia.
How the tissue reacts. Cancer cell invasion often causes scarring around it. This reaction is usually absent in pseudoepitheliomatous hyperplasia.

The distinction can be difficult on a small or shallow biopsy, because the features that separate the two are often at the base of the lesion. A keratoacanthoma, a fast-growing skin growth closely related to squamous cell carcinoma, can be particularly hard to separate from both.

A long-standing wound or scar is also a setting where squamous cell carcinoma can occasionally develop. For this reason, the pathologist examines the tissue carefully even when pseudoepitheliomatous hyperplasia is the most likely explanation.

How is pseudoepitheliomatous hyperplasia identified?

A pathologist identifies pseudoepitheliomatous hyperplasia by examining a tissue sample under a microscope. The sample may come from a biopsy or from the complete removal of a lesion, called an excision. Once the pathologist identifies the change, they look for its cause.

Additional tests may be performed on the same tissue to find the cause of pseudoepitheliomatous hyperplasia. These include:

Special stains for organisms. Special stains such as PAS and Grocott (GMS) make fungi easier to see. An acid-fast stain highlights mycobacteria. A negative stain makes an infection less likely but does not always rule it out.
Immunohistochemistry. Immunohistochemistry can show the type of cells under the surface. For example, S100 and SOX10 are positive in a granular cell tumor.
Deeper sections. The pathologist may cut more slices from the tissue block to look for the cause or for any sign of cancer.

Not every case needs these tests. The pathologist chooses them based on the location, what the lesion looked like to your doctor, and what is seen under the microscope.

Your report may describe the change as “florid,” meaning it is very prominent. When the pathologist cannot confidently separate the change from cancer, the report may say that squamous cell carcinoma “cannot be excluded” and suggest a larger sample.

What happens after pseudoepitheliomatous hyperplasia is found?

Because pseudoepitheliomatous hyperplasia is a reaction, the next steps depend on what caused it. The change usually settles once the underlying cause is treated or removed. Possibilities include:

A cause was found. Your care team focuses on that condition, such as an infection, a granular cell tumor, or a chronic wound.
An infection is suspected. A fresh tissue sample may be sent for culture, a test that grows the organism so it can be identified.
Cancer could not be ruled out. A deeper biopsy or removal of the whole lesion may be considered so the pathologist can examine its base.
No cause was found. Your doctor may watch the area or take another sample if it does not heal or continues to grow.

Your doctor will combine the pathology report with how the lesion looks and how long it has been present to decide on the next step.

Questions to ask your doctor

What caused the pseudoepitheliomatous hyperplasia in my sample?
Did the pathologist find an infection, a tumor, or another condition underneath?
Were special stains or other tests done, and what did they show?
Was the biopsy deep enough to rule out squamous cell carcinoma?
My report says cancer “cannot be excluded.” Do I need another biopsy or surgery?
Was the whole lesion removed?
Should a sample be sent for culture?
How will we know if the area is healing?
What changes should prompt me to come back sooner?