Extramammary Paget’s Disease

Extramammary Paget’s Disease


Vulval extramammary Paget’s disease (EMPD) is a nonsquamous intraepithelial lesion of the vulva. It is an uncommon premalignant skin disorder with invasive potential. All areas that contain apocrine glands can be affected, such as the vulva, perianal region, penis, scrotum, perineum and axilla, but it most commonly occurs on the vulva. Extramammary Paget’s disease of the vulva is defined by the presence of so‐called Paget cells in the epithelium. Vulval EMPD spreads in an occult manner, often with more unseen lesions extending beyond the apparent edges. Vulval EMPD can be subclassified into primary or secondary disease. Primary disease originates on the vulva and secondary EMPD is due to a noncutaneous neoplasm, often of adjacent sites, such as the bladder or rectum. Interventions can be surgical, or noninvasive techniques may be applied. The purpose of the treatment is to remove the disease but also to reduce side effects from radical surgery. There is hardly any consensus on treatment.


Even in a vulval clinic, EMPD is seen in less than 1% of the cases. It affects mainly white postmenopausal women, with a median age of 72 years. The true incidence and prevalence remains unknown. To date, only a couple of hundred cases are recorded in the literature. There is an uncertain association between vulval EMPD and distant tumours, such as those of the breast, pancreas, endometrium, bladder, stomach and rectum. The association is variable across the literature, ranging from 0–50%.

Histological features

The histogenesis of primary vulval EMPD is still uncertain. There is evidence that vulval EMPD represents a heterogeneous group of epithelial neoplasms that can be similar both clinically and histopathologically. It has been speculated that it originates from eccrine and / or apocrine glands or from pluripotent keratinocyte cells of the epidermis or its adnexae. There is evidence that these glandular cells spread to the overlying epithelium. It has been suggested that at least a proportion of vulval EMPD arises multicentrically within the epidermis from these pluripotent stem cells. The diagnosis is histological with the characteristic changes on skin biopsy. Immunohistochemistry will help to exclude melanoma and vulval intraepithelial neoplasia as these are important histological differential diagnoses. Histopathology shows epidermal acanthosis and elongated rete ridges. Paget’s cells are large intraepidermal cells with a large nucleus that often has a prominent nucleolus and abundant usually clear, mucin positive, pale cytoplasm. The cells may occur singly in small clusters or large nests (Figure 20.1). The squamous epithelium is often hyperplastic with hyper‐ or parakeratosis. The Paget’s cells may extend into the adnexal duct and pilosebaceous units.

Micrograph displaying clusters of Paget’s cells with abundant clear cytoplasm and round nuclei in the basal layer.

Figure 20.1 Clusters of Paget’s cells with abundant clear cytoplasm and round nuclei in the basal layer.


Vulval EMPD can be classified based on the origin of the neoplastic Paget’s cells as either primary (of cutaneous origin), arising within the epithelium of the vulva, or secondary (of noncutaneous origin), resulting from the spread of an internal malignancy, most commonly from an anorectal adenocarcinoma or urothelial carcinoma of the bladder or urethra, to the vulval epithelium. The primary form comprises more than 75% of cases. Primary EMPD can be further subdivided into a primary, intraepithelial cutaneous form with and without invasion or an intraepithelial cutaneous Paget’s disease as a manifestation of underlying skin appendage adenocarcinoma. Secondary EMPD has an anorectal, urothelial or other origin (Box 20.1).

These subtypes can present similarly on the skin and may appear similar on routine hematoxylin and eosin‐stained slides. Immunohistochemical studies can be used to help differentiate them (Table 20.1). Primary vulval EMPD is immunoreactive for CK 7 and GCDFP‐15 but uncommonly for CK 20. Vulval EMPD secondary to anorectal carcinoma demonstrates CK 20 immunoreactivity but is usually nonreactive for CK 7 and consistently nonimmunoreactive for GCDFP‐15. Vulval EMPD secondary to urothelial carcinoma is immunoreactive for CK 7 and CK 20 but nonimmunoreactive for GCDFP‐15. In addition, UP‐III, which is specific for urothelium, is immunoreactive in secondary vulval EMPD of urothelial origin.

Table 20.1 Immunocytochemistry in EMPD.

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Mar 15, 2018 | Posted by in OBSTETRICS | Comments Off on Extramammary Paget’s Disease
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Primary EMPD Secondary EMPD Intraepithelial neoplasia Melanoma
PAS + +
CK7 + +
CK20 Usually − Usually +