Paget’s Disease of the Vulva

Paget’s disease of the vulva is a rare skin condition affecting the external female genital area. Although it accounts for only about 1% of vulvar cancers, it requires careful diagnosis and treatment because it often extends beyond visible borders and has a tendency to recur.

Table of contents

• What is Paget’s Disease of the Vulva?
• Who is Most Affected?
• Common Symptoms and Signs
• How is it Diagnosed?
• Association with Other Cancers
• Treatment Options
• Disease Recurrence and Long-Term Monitoring
• Outlook and Survival

What is Paget’s Disease of the Vulva?

Paget’s disease of the vulva, also known as extramammary Paget’s disease (EMPD) of the vulva, is a rare type of skin condition that may be associated with cancer. The term “extramammary” means “outside the breast,” which helps distinguish it from Paget’s disease of the breast.^[3] This condition typically causes red, scaly or crusty areas of skin that grow slowly, often resembling common skin conditions like eczema.^[3]

The disease was named after Sir James Paget, a British physician who first described a similar condition affecting the nipple and areola in 1874. The characteristic appearance of the vulvar form was later described as having a “cake-icing scaling” or “cupcake frosting” appearance.^[5][4]

There are two main types of this disease. Primary Paget’s disease develops in the skin on its own, while secondary Paget’s disease develops due to an underlying cancer in nearby organs.^[3] About 7% to 40% of cases are associated with an underlying cancer, though the exact cause of primary disease remains unknown.^[3]

extramammary Paget’s disease, EMPD, vulvar Paget’s disease, PDV

• Vulva
• Labia majora (outer lips)
• Labia minora (inner lips)
• Perianal area

Who is Most Affected?

Paget’s disease of the vulva predominantly affects postmenopausal Caucasian women.^[5][4] The disease is most commonly seen in people between 50 and 80 years old, with studies showing it peaks around age 65.^[8] Research indicates that vulvar Paget’s disease is more prevalent among those with higher body mass index and in those who have used hormone replacement therapy.^[4]

Although the disease is more common in women, men can also develop extramammary Paget’s disease in other areas. The disease is particularly more common among male Asian populations when it occurs.^[3]

Common Symptoms and Signs

Many people with Paget’s disease of the vulva experience symptoms for a long time before diagnosis is made. Typically, symptoms are present for 2 years or even more before a diagnosis, and diagnosis is often delayed because both patients and healthcare providers may initially attribute the symptoms to more common, benign conditions.^[5][4]

The most common symptoms include:

• Long-standing itching in the vulvar area
• Burning sensation
• Pain or tenderness
• Irritation

On physical examination, the affected skin typically appears red with a scaly or crusty surface. The rash may have irregular borders and can resemble eczema or other dermatological conditions.^[3][6] In some cases, the red skin is partially covered with a thin white coating, which has been classically described as having a “cupcake frosting” appearance.^[4]

As the disease progresses, the skin may become thickened with white raised areas. In more advanced cases, deep sores called ulcers or raised lumps called nodules may develop, and there may be bleeding or discharge from the affected area.^[3][6] The skin may also appear swollen.

About 10% of people with Paget’s disease of the vulva do not experience any symptoms at all.^[3] The lesions may be painful at times, but some individuals remain asymptomatic even at the time of diagnosis.^[5]

How is it Diagnosed?

Diagnosis begins with a physical examination by a healthcare provider who will ask about symptoms and examine the affected area. If Paget’s disease is suspected, the definitive diagnosis is made through a skin biopsy.^[3][5] During this simple procedure performed under local anesthesia, a small sample of the affected skin is removed and examined under a microscope.

Under the microscope, a pathologist looks for characteristic abnormal cells called Paget cells. These cells are larger than normal skin cells, have clear cytoplasm, and a prominent nucleus. They may appear vacuolated with standard staining.^[4][11] The diagnosis is confirmed by identifying these vacuolated Paget cells through a punch biopsy.^[4]

Because the appearance of Paget cells can be similar to other types of skin cancer, special laboratory staining techniques called immunohistochemical stains may be needed to confirm the diagnosis. These special stains, such as cytokeratin 7, help differentiate Paget’s disease from other similar-appearing conditions.^[4][5]

Association with Other Cancers

An important aspect of Paget’s disease of the vulva is its association with other cancers. Approximately 10-30% of patients with this disease have associated invasive adenocarcinomas (a type of cancer that begins in gland cells).^[5] When underlying cancer is present, the disease tends to be more aggressive with higher recurrence rates.^[5]

Secondary Paget’s disease results from an underlying cancer in nearby or distant organs. One-third of secondary cases result from rectal cancer. Other cancers that may cause secondary disease include:^[3]

• Anal cancer
• Bladder cancer
• Cervical cancer
• Ovarian cancer
• Uterine cancer
• Colorectal cancer
• Breast cancer

Because of this association, when Paget’s disease of the vulva is diagnosed, additional screening is often recommended. It is advisable to conduct further evaluation of the breast, genitourinary tract, and gastrointestinal tract to exclude concurrent malignancy, especially if lesions are found on the urethra and perianal areas.^[4] Recommended screening tests may include colonoscopy, cystoscopy (camera examination of the bladder), Pap smear test, and mammogram.^[7]

In some cases, patients may be diagnosed with bladder cancer many years after the diagnosis of Paget’s disease of the vulva.^[5] Although the disease is generally slow-growing, Paget cells may occasionally extend into deeper layers of skin and cause metastases (spread of cancer), usually to regional lymph nodes. Less commonly, the disease can spread to the lungs, bones, adrenal glands, and liver.^[5]

Treatment Options

The standard treatment for Paget’s disease of the vulva is surgery. Surgery has been the treatment of choice by default, though it presents significant challenges.^[2][4] The main difficulty is that the disease often extends beyond the visible edges of the lesion, making it challenging to remove all affected tissue adequately.^[2]

Surgical options include wide local excision (removing the lesion with a margin of healthy tissue), partial vulvectomy (removal of part of the vulva), or complete vulvectomy (removal of all of the vulva).^[4][6] The standard approach is wide local excision with lateral margins extending from 2 to 3 cm beyond the clinically affected area.^[7] Subsequent vulvar or perineal reconstruction often requires a multidisciplinary effort involving gynecologic oncology and plastic surgery teams.^[4]

In some cases, a specialized surgical technique called Mohs micrographic surgery may be used. This technique involves removing thin layers of tissue and examining them under a microscope until no abnormal cells are detected. It may be particularly useful for lesions in areas where tissue preservation is important, and has been shown to reduce recurrence rates.^[6][8]

Removal of inguinal lymph nodes (glands in the groin) is not necessary unless the final pathology shows invasion into deeper tissue layers.^[4]

Several non-surgical treatment options are also available:^[4][8]

• Topical medications: Creams such as imiquimod (which stimulates the immune system to destroy abnormal cells), fluorouracil, or bleomycin can be applied directly to the affected area. Imiquimod can be safely used for treatment, including for micro-invasive disease, with studies noting a 43% response rate.^[4]
• Laser therapy: Carbon dioxide laser treatment can be used to destroy affected tissue
• Photodynamic therapy: A form of light treatment that uses light-sensitive compounds to target diseased cells
• Radiotherapy: Radiation therapy may be used in combination with surgery or as an alternative treatment in elderly patients or those unfit for surgery^[6][8]

Skin complications including pain, skin peeling, and ulceration are common among all such treatments.^[4]

Disease Recurrence and Long-Term Monitoring

One of the major challenges with Paget’s disease of the vulva is its high recurrence rate. Recurrence is common despite negative surgical margins, meaning that even when the edges of the removed tissue appear free of disease, the condition often comes back.^[4] Studies report recurrence rates of 33%-60% following wide local excision.^[7] Research has found no significant differences in recurrence rates between patients who underwent surgery and those who did not, and no association between positive margins following primary surgery and recurrence.^[19]

The majority of patients experience multiple recurrences over time, with 18% having four or more recurrences.^[19] Multiple local excisional procedures are often required over a 10-20 year period, resulting in the risk of subsequent vulvar disfigurement and impacted quality of life.^[4]

Because of the chronic nature of the disease and its tendency to recur, regular follow-up is essential. After treatment, regular follow-up appointments with a healthcare provider are necessary to check the response to treatment and to detect any areas of disease that may come back.^[6][8] Because of the increased risk of malignancy, patients should be monitored indefinitely.^[3]

Outlook and Survival

Despite the challenges of treatment and the high recurrence rate, the overall prognosis for Paget’s disease of the vulva is favorable. The disease is generally slow-growing and, when not associated with invasive cancer, has a good outlook.^[5]

Although the disease is typically diagnosed at a locally-advanced stage and has a high recurrence rate, the prognosis is overall favorable with a 5-year survival rate of nearly 90%.^[4] People without underlying cancer typically recover fully.^[3] However, the risk of death can increase if there is also an associated cancer.^[3]

The prognosis depends on several factors including the extent of the disease, presence of underlying malignancies, and response to treatment. Early detection and appropriate management are key to improving outcomes and reducing the risk of complications.^[6]

It is important for individuals with Paget’s disease of the vulva to work closely with a multidisciplinary healthcare team, including gynecologists, dermatologists, and oncologists, to develop a personalized treatment plan tailored to their specific needs and circumstances.^[6] Open communication with healthcare providers and adherence to treatment recommendations are essential for managing the condition effectively.