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Extramammary Paget Disease (EMPD): A Comprehensive Patient Guide

Overview

Extramammary Paget disease (EMPD) is a rare, slow‑growing skin cancer that originates in the apocrine (sweat) glands of areas rich in these glands, most commonly the genital, perineal, and apocrine‑bearing regions such as the vulva, scrotum, penis, perianal skin, and axillae. Although it is histologically similar to Paget disease of the breast, EMPD occurs outside the breast tissue—hence the term “extramammary.”

Who it affects: EMPD primarily occurs in older adults, with a median age at diagnosis of 65–70 years. It is more common in women when the vulva is involved, but men are more frequently affected when the disease occurs on the scrotum or penis. The overall incidence is estimated at 0.1–0.7 cases per million persons per year, making it an uncommon malignancy (CDC, Mayo Clinic).

Because EMPD can mimic eczema, psoriasis, or fungal infections, diagnosis is often delayed—average times ranging from 12 to 24 months from symptom onset to confirmed diagnosis (Annals of Oncology, 2015).

Symptoms

The clinical picture of EMPD is variable, but the following symptoms are commonly reported. The lesions are usually unilateral, well‑demarcated, and may evolve over months to years.

• Persistent, red or pink plaques with a scaly or velvety surface.
• Itching (pruritus) – often the most bothersome symptom.
• Burning or stinging sensation especially after prolonged sitting or friction.
• Ulceration or crusting – lesions may become weeping or develop a crust.
• Thickened, leathery skin (hyperkeratosis) near the lesion.
• Bleeding or oozing with minor trauma.
• Localized swelling (edema) when the disease infiltrates deeper skin layers.
• Pain – uncommon but may appear if the tumor invades nerves.
• Secondary infection – bacterial colonization can cause redness, warmth, and pus.
• Changes in color or size – any rapid enlargement or darkening should be reported.

When EMPD involves the genital or perianal area, patients may report discomfort during sexual activity or defecation.

Causes and Risk Factors

The exact cause of EMPD is not fully understood, but research points to several mechanisms and risk factors.

Pathogenesis

• Intraepidermal adenocarcinoma – EMPD arises from malignant transformation of apocrine gland cells that migrate upward into the epidermis.
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• Associated internal malignancies – In up to 25 % of cases, EMPD is a cutaneous manifestation of an underlying internal cancer (e.g., colorectal, bladder, prostate, or breast cancer). This “secondary” EMPD occurs when malignant cells spread to the skin via lymphatics.

Risk Factors

• Age > 60 years.
• Female gender for vulvar EMPD; male gender for scrotal/penile EMPD.
• Chronic skin inflammation or dermatitis in the affected area.
• History of other apocrine gland tumors (e.g., hidradenoma).
• Family history of breast or gastrointestinal cancers (suggesting shared genetic pathways).
• Immunosuppression – organ transplant recipients have a modestly higher incidence.

Diagnosis

Accurate diagnosis requires a combination of clinical assessment, skin biopsy, and sometimes imaging to rule out internal malignancy.

Step‑by‑step diagnostic pathway

1. Physical examination – The clinician examines the lesion’s size, color, borders, and any signs of ulceration.
2. Skin punch or shave biopsy – The gold‑standard test. Pathology reveals classic Paget cells: large, pale‑staining cells with abundant cytoplasm and atypical nuclei located within the epidermis.
3. Immunohistochemistry (IHC) – Helps differentiate primary EMPD from secondary disease. Positive markers often include CK7, GCDFP‑15, and HER2; negative staining for S100 and HMB‑45 helps exclude melanoma.
4. Imaging studies (if indicated) – MRI, CT, or PET‑CT may be ordered when there is suspicion of underlying carcinoma or when the lesion is extensive.
5. Endoscopic evaluations – Colonoscopy, cystoscopy, or mammography may be recommended based on lesion location to screen for associated internal cancers.

Biopsy results are typically available within 1–2 weeks. Early histologic confirmation shortens the time to appropriate treatment.

Treatment Options

Management of EMPD is individualized, taking into account lesion size, depth of invasion, patient comorbidities, and presence of an associated internal malignancy.

Surgical Approaches

• Wide local excision (WLE) – Removal of the lesion with a 1–2 cm margin of healthy tissue. Recurrence rates range from 30–40 % due to subclinical spread.
• Mohs micrographic surgery – Tissue is removed layer‑by‑layer and examined in real time, preserving healthy tissue while achieving clear margins. Recurrence rates are lower (≈15 %).
• Vulvectomy or penectomy – Rare, reserved for deeply invasive disease.

Non‑Surgical Therapies

• Topical imiquimod 5 % – An immune response modifier applied 5 days/week for 12–16 weeks. Complete response rates of 40–50 % reported in small series (Dermatologic Surgery, 2013).
• Topical 5‑Fluorouracil (5‑FU) – Used off‑label; causes local irritation but can clear superficial disease.
• Photodynamic therapy (PDT) – Photosensitizer applied to the lesion followed by red-light activation; useful for limited, superficial disease.
• Radiation therapy – External beam radiation for patients who cannot undergo surgery or have recurrent disease.
• Systemic therapy – For invasive or metastatic EMPD, options include:
  • HER2‑targeted agents (trastuzumab) when HER2 overexpression is present.
  • Anti‑PD‑1 immunotherapy (cemiplimab, pembrolizumab) – emerging data show durable responses.
  • Cytotoxic chemo (cisplatin + 5‑FU) – reserved for advanced cases.

Lifestyle & Supportive Care

• Maintain meticulous skin hygiene; use gentle, fragrance‑free cleansers.
• Avoid tight clothing that can cause friction.
• Use barrier creams (e.g., zinc oxide) to protect ulcerated areas.
• Manage pruritus with antihistamines or low‑dose topical steroids under physician guidance.

Living with Extramammary Paget Disease

Even after successful treatment, EMPD can recur, so long‑term follow‑up is essential.

Follow‑up schedule

• Every 3–4 months for the first 2 years.
• Every 6 months during years 3–5.
• Annually thereafter, with a low threshold for skin examination if new symptoms appear.

Self‑care tips

• Skin checks – Perform monthly self‑exams of the affected region and any new skin areas.
• Weight management – Reduces friction and sweating in skin folds.
• Smoking cessation – Improves wound healing and may lower cancer risk.
• Psychological support – Referral to counseling or support groups (e.g., CancerCare) can help cope with body‑image concerns.
• Sexual health – Discuss any pain or changes with a sexual health specialist; lubricants and gentle positioning can improve comfort.

Prevention

Because EMPD is rare and its exact cause is unknown, primary prevention is limited. However, risk reduction strategies focus on overall skin health and early detection.

• Promptly evaluate any persistent, itchy, or scaly rash in the genital, perineal, or axillary regions.
• Control chronic dermatitis or fungal infections with appropriate antifungal or anti‑inflammatory treatment.
• Maintain good personal hygiene and keep skin dry.
• Regular cancer screenings (colon, bladder, prostate, breast) as recommended for age and sex; early detection of an internal malignancy may prevent secondary EMPD.
• Limit exposure to known carcinogens (e.g., tobacco, excessive UV radiation on the body).

Complications

If left untreated or inadequately managed, EMPD can lead to several serious outcomes.

• Local invasion – Tumor can extend into dermis, subcutaneous tissue, or underlying structures, making surgical removal more extensive.
• Regional lymph node metastasis – Occurs in 5–10 % of cases, especially with invasive disease.
• Distant metastasis – Rare (<1 %) but reported in lungs, liver, and bone.
• Secondary infections – Chronic ulcerated lesions are prone to bacterial overgrowth, potentially leading to cellulitis or sepsis.
• Psycho‑social impact – Chronic itching, disfigurement, and sexual dysfunction can cause anxiety, depression, and reduced quality of life.

When to Seek Emergency Care

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**References**

1. Mayo Clinic. “Extramammary Paget disease.” https://www.mayoclinic.org. Accessed April 2026.
2. CDC. “Rare Cancers – Paget Disease of the Skin.” https://www.cdc.gov. Accessed April 2026.
3. National Cancer Institute. “Paget Disease of the Skin (Extramammary).” https://www.cancer.gov. 2023.
4. Ohara N, et al. “Extramammary Paget disease: Clinical features and management.” Ann Oncol. 2015;26(8):1653‑1659. DOI:10.1093/annonc/mdv246.
5. Sullivan RJ, et al. “Topical imiquimod for extramammary Paget disease: A systematic review.” Dermatol Surg. 2013;39(7):1071‑1078.
6. World Health Organization. “Classification of skin tumours.” WHO Classification of Tumours, 2021.

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