Paget’s disease of the vulva (PDV) is a rare, slow-growing superficial cancer affecting the external female genitalia, accounting for about 1% to 2% of all vulvar neoplasms. This condition is a form of extramammary Paget’s disease, characterized by the presence of abnormal glandular cells in the skin. Because its presentation often mimics common, non-cancerous skin conditions, diagnosis is frequently delayed. PDV is typically localized at diagnosis, but it has the potential to become invasive or may be associated with other internal cancers.
Defining Paget’s Disease of the Vulva
Paget’s disease of the vulva is classified as an intraepithelial adenocarcinoma, meaning the cancer cells originate from glandular cells and remain confined to the outermost layer of the skin, the epidermis. These distinct cancer cells, known as Paget cells, are large, pale, and scattered among normal skin cells. The disease most commonly affects post-menopausal women, with the average age of diagnosis being around 71 years.
PDV is categorized into two types. Primary PDV arises directly from glandular cells within the vulvar skin (e.g., apocrine glands) and represents the majority of cases. Secondary PDV is less common, occurring when cancer cells from an underlying internal malignancy spread to the vulvar skin.
Cancers leading to secondary PDV often originate in the genitourinary or gastrointestinal tracts (e.g., the bladder, urethra, or rectum). The presence of Paget cells necessitates investigation to rule out an associated internal cancer, which is found in 4% to 25% of cases. In rare instances, the disease can transition to an invasive form, where Paget cells penetrate the dermis, carrying a higher risk of spreading to the lymph nodes.
Recognizing the Clinical Signs
The clinical presentation of Paget’s disease of the vulva is often non-specific and subtle, leading to frequent diagnostic delays. The most common complaint is persistent vulvar itching (pruritus), which affects nearly all patients. Patients also report a burning sensation, tenderness, and general irritation.
Visible skin lesions typically manifest as well-demarcated patches that can be red, pink, or white and scaly, often mimicking chronic eczema or dermatitis. The affected skin may have a velvety or eczematous texture, sometimes appearing as red plaques dotted with small, white islands of tissue (occasionally described as having a “cupcake frosting” appearance). The lesions are chronic and slow-growing, but they can become painful, crusted, or ulcerated, leading to minor bleeding or discharge.
Because the appearance is similar to benign conditions, initial treatments for fungal infections or common skin inflammation often fail, raising suspicion for PDV. The lesions are frequently multifocal, appearing in multiple spots, and are most often found on the labia majora, but can spread to the perineum or perianal area. A definitive tissue diagnosis is necessary when persistent vulvar symptoms do not resolve with standard topical therapies.
Diagnostic Confirmation
Definitive confirmation of Paget’s disease of the vulva requires a tissue sample, usually obtained via a punch biopsy, when clinical suspicion is raised. This procedure involves removing a small core of affected skin for examination by a pathologist, confirming the diagnosis by the presence of characteristic Paget cells within the epidermis. To differentiate PDV from other similar vulvar conditions, such as melanoma or squamous cell carcinoma, specialized staining techniques are utilized. Immunohistochemical staining provides molecular markers that help identify the cellular origin of the abnormal cells, with Paget cells typically staining positive for markers like Cytokeratin 7 (CK7).
If PDV is confirmed, further diagnostic workup is necessary to investigate potential associated internal cancers. This investigation may involve imaging tests, such as MRI or CT scans, to assess the extent of the disease and look for malignancies. Internal examinations, like colonoscopy or cystoscopy, may also be performed if the patient presents with corresponding bowel or urinary symptoms.
Comprehensive Treatment Approaches
Surgical resection remains the standard of care for treating Paget’s disease of the vulva, aiming to completely remove the affected area. The most common approach is Wide Local Excision, which removes the visible lesion along with a margin of surrounding normal tissue. However, the disease often spreads subclinically, meaning Paget cells extend into healthy-looking skin, making it difficult to achieve clean surgical margins.
Positive margins, where cancer cells remain at the edge of the removed tissue, are a common challenge, occurring in up to 50% of cases. Specialized techniques like Mohs micrographic surgery or frozen section analysis can help maximize the chance of achieving clear margins while preserving healthy tissue. If extensive tissue removal is required, a skin graft or reconstructive flap surgery may be necessary to close the wound and restore function.
Due to high rates of local recurrence, alternative and adjunctive therapies are often considered. Topical treatments offer a non-surgical option, with imiquimod 5% cream being the most commonly utilized agent. Imiquimod is an immunomodulator that stimulates the immune response to attack cancer cells, showing promising results for localized or recurrent disease.
Other non-surgical options include laser ablation, which uses focused light energy to destroy abnormal cells, and photodynamic therapy, which involves applying a light-sensitizing compound followed by light exposure. Radiation therapy may be used for recurrent disease, when surgery is contraindicated, or in patients with lymph node involvement. Long-term surveillance with frequent physical examinations and biopsies of suspicious lesions is necessary due to the chronic nature of PDV and the high risk of recurrence.