Immunohistochemical Staining for Extramammary Paget's Disease (EMPD)



Why is Immunohistochemical Staining Useful?


Immunohistochemical staining allows a pathologist to view both healthy and abnormal cells through the use of protein markers. This helps with tumor classification and diagnosis. The presence of Paget’s disease cells can be confirmed through the use of histochemical stains. Typically, extramammary Paget’s disease (EMPD) cells stain for low molecular weight cytokeratins (such as CK-7 or CK-20), and GCDFP-15, periodic acid-Schiff (PAS), and CEA.

CK-7 (Cytokeratin 7) stain is the most common for determining EMPD. It is also used for testing for other cancers including: lung, breast, thyroid, endometrium, cervix, ovary, salivary gland and upper GI tract, urothelial carcinoma, and papillary renal cell carcinoma. Under a microscope, a positive CK-7 test for EMPD will typically demonstrate large, pale staining to clear intraepidermal neoplastic cells containing abundant mucin, arranged singly or occasionally in nests or gland-like formations. Associated changes include squamous hyperplasia, fibroepithelioma-like hyperplasia and papillomatous hyperplasia.

CK-20 (Cytokeratin 20) stain is sometimes used to determine secondary cancers which may be associated with EMPD. The combination of CK-7 and CK-20 can help distinguish primary EMPD from cancer that may have spread. Gross cystic disease fluid protein 15 (GCDFP-15) is also sometimes used.

It can be challenging to distinguish between secondary and primary EMPD, especially if the primary EMPD invades the epidermis or if other cancers are not apparent. Immunohistochemical staining with CK-7, CK-20, and GCDFP-15 may be useful to distinguish them. In secondary EMPD, tumor cells are positive for CK7 and CK20, but negative for GCDFP-15, whereas primary EMPD is commonly positive for CK-7 and GCDFP-15 but negative for CK-20.