Why Is Immunohistochemical Staining Useful in Diagnosing Extramammary Paget Disease (EMPD)?

Immunohistochemical (IHC) staining is a valuable laboratory technique used by pathologists to examine tissue samples under a microscope. This method helps identify specific proteins in cells using antibodies that attach to those proteins. By highlighting protein patterns, IHC staining allows doctors to distinguish between normal and abnormal cells and plays a crucial role in confirming a diagnosis of extramammary Paget’s Disease (EMPD), especially when the condition resembles other skin disorders.

EMPD often presents as a red, itchy, or scaly rash that closely resembles other common skin conditions, making a biopsy essential for an accurate diagnosis. IHC staining provides deeper insight beyond what the eye can see on a surface-level skin exam, helping doctors tell the difference between primary EMPD (originating in the skin) and secondary EMPD (caused by a cancer from another part of the body spreading to the skin).

To confirm EMPD and understand its nature, pathologists use a panel of stains that highlight the presence or absence of certain protein markers:

• Cytokeratin 7 (CK7) is the most commonly used marker and is typically positive in primary EMPD. When stained, EMPD cells often appear as large, pale cells in the upper layers of the skin.

• Cytokeratin 20 (CK20) is sometimes used alongside CK7. While CK20 is generally negative in primary EMPD, it may be positive in secondary EMPD, which can suggest the cancer has spread from organs such as the colon or bladder.

• GCDFP-15 (Gross Cystic Disease Fluid Protein 15) and GATA3 may also be positive in primary EMPD and help confirm an apocrine (sweat gland) origin.

• CDX2 and CK20 positivity together may suggest a colorectal origin, which is helpful in identifying secondary EMPD.

• CEA (Carcinoembryonic Antigen) is another marker that can support the diagnosis of EMPD by ruling out other conditions that mimic it.

A typical pattern seen in primary EMPD is CK7-positive, CK20-negative, and CEA-positive. This combination supports the diagnosis and helps exclude other skin conditions or cancers such as melanoma (which is SOX10-positive) or squamous cell carcinoma (which is p63-positive).

These stains also help pathologists assess whether EMPD has invaded deeper skin layers, which can affect treatment decisions. In more advanced or invasive cases, staining might show additional features like involvement of sweat glands, hair follicles, or even lymphatic and blood vessels.

Some EMPD tumors may also express PD-L1, a protein involved in immune response. This finding is more common in invasive EMPD than in non-invasive forms and may offer opportunities for newer treatments like immunotherapy.

Because EMPD can vary significantly from one person to another, the use of IHC staining is an important step in creating an accurate, personalized diagnosis. It not only helps confirm the presence of EMPD but also guides physicians in choosing the most effective treatment options.

If you have been diagnosed with EMPD or suspect you might have it, it’s important to discuss biopsy results and staining outcomes with your healthcare team. These results provide critical information that helps determine whether the disease is limited to the skin or linked to other cancers, and whether it is likely to spread. Your care team will use this information to build a treatment and follow-up plan tailored to your specific needs.

This explanation is intended to help you better understand the diagnostic process and is not a substitute for medical advice from your doctor.