Extramammary Paget disease of skin

Extramammary Paget disease (EMPD) of skin is an uncommon malignant intraepithelial adenocarcinoma usually of the anogenital skin, and rarely the axilla. EMPD is classified into primary and secondary disease:

• Primary EMPD is of cutaneous origin, and although classified as intraepithelial, significant numbers are associated with a cutaneous adnexal carcinoma 
• Secondary EMPD is associated with a primary adenocarcinoma elsewhere in the body, usually in organs with a contiguous epithelial lining e.g. perianal EMPD is associated with adenocarcinoma of the gastrointestinal tract, and genital EMPD is associated with genitourinary malignancy

Extramammary Paget disease of skin is differentiated from mammary Paget disease, which has a similar appearance involving the nipple or areola, but is a manifestation of an underlying breast cancer.

• The tumour cells of primary EMPD originate either from the intraepidermal cells of apocrine gland ducts or from pluripotent keratinocyte stem cells
• Secondary EMPD results from direct extension or metastasis from another sites (as described in the introduction) 

• EMPD is seen more frequently in women than in men, except in Asian populations 
• Age - arises in the fifth decade or after, with a peak at 65 years
• It is more common in Caucasians
• The most common symptom is of a mild to moderate itch or burning sensation
• Bleeding may occur secondary to scratching

• Distribution
• Affects anywhere on the ano-genital skin
• In women it has a predominantly vulvar distribution
• Rarely, it can arise in the axillae 

• Morphology
  • Usually presents as a unilateral well-defined pink-red patch or plaque; sometimes with erosions, crusts, or scale
  • It tends to progress slowly over a number of years; failing to respond to topical treatments 

• Histology is required
• The differentiation between primary and secondary disease is not always straightforward clinically and sometimes relies on immunohistological investigations
• In secondary EMPD, further investigation is directed to looking for an associated malignancy 

• Management 
• Surgical treatment with wide-local excision of visible disease is often recommended for treatment; primary EMPD lesions can become invasive and metastasize, and can be associated underlying appendageal adenocarcinoma
• Given the high rates of local recurrence (30-50%), margin-controlled surgical excision (Mohs micrographic surgery) is the treatment of choice (not available in all centres) 
• Non-surgical options are less successful but are sometimes used e.g. in the very elderly, with extensive disease or recurrence after vulvectomy
  
• In secondary EMPD the treatment is directed predominantly at the associated carcinoma

• Prognosis
  • Given the high rate of local recurrence, patients need regular follow-up and further surgery may be needed
  • Although the 5-year survival rate is 75–95%, quality of life can be significantly impacted after radical surgery
  • Outcome is also affected by the presence of any underlying carcinoma