Paget's Disease of the Vulva

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By Jeyashree Sundaram, MB

The vulva, consisting of the outer lips (labia majora), and inner lips (labia minora), is the visible outer portion of the female genitalia. The vulva gives access to the sexual organs, vestibule, urinary opening, and the vagina in women.

Paget's disease of the vulva (PDV), a rare disease, accounts for about 1% of all the neoplasms of the vulva. Approximately 10–30% of patients with PDV have associated invasive adenocarcinomas. In these patients, PDV is mostly aggressive with higher recurrence rates. In general, invasive cancer originates in the vulva; however, it may arise in other organs such as the urethra, rectum, or bladder.

History

The description of this disease involving the areola and nipple was first published by Sir James Paget in 1874 (in honor of whom it is known as mammary Paget disease). In 1889, extramammary Paget’s disease was reported by Crocker, involving the penis and scrotum.

William Dubreuilh’s description was reported in 1901. The French dermatologist described for the first time the characteristic appearance of PDV as cake-icing scaling.

There are controversies about the pathogenesis, optimal treatment methods, recurrence, and prevalence of underlying adenocarcinoma or related malignancies in this disease. Due to the rarity of PDV, characterization is difficult. Angiogenesis has an important role to play in disease pathogenesis.

In a study on the role of p53—a tumor suppressor protein—in PDV, it was found that p53 affects the progression of PDV. The study also concluded that neither p53 nor Ki67—a proliferation marker—have any prognostic role.

Symptoms and Diagnosis

Caucasian postmenopausal women are found to be more prone to Paget’s disease of the vulva. Symptoms include long-standing tenderness and itching, irritation, and burning sensation. Usually, symptoms are present for 2 years or even more before a diagnosis made. The lesions may be painful at times; however, some individuals are asymptomatic during diagnosis.

Though the appearance of the rash can create confusion with other similar vulvar rashes, biopsy typically provides a confirmation of the diagnosis. When Paget’s disease of the vulva is suspected, colonoscopy or cystoscopy is done as an additional diagnostic measure to look for cancers in the colon or bladder, respectively, if urinary or bowel symptoms are present.

Many years after the diagnosis of PDV, patients may be diagnosed with cancer of the bladder. Though vulvar Paget disease may be noninvasive, most of these patients have invasive bladder disease.

Paget's disease of the vulva is generally a slow-growing tumor. The Paget cells may extend from the epidermis into the dermis occasionally and can cause metastases, usually to the regional lymph nodes. The lungs, bones, adrenal glands, and liver are other potential metastasis sites, although metastasis to the urinary bladder is rare. Immunohistochemistry stain techniques are found to be useful to differentiate Paget’s disease from other bladder tumors (both primary and metastatic).

Treatment

Generally, surgical treatment is provided for PDV. However, the results are not encouraging as the recurrence rates are high. Wide local resection causes major functional defects in the anogenital-vulvar area. In some cases, multiple excisions have been necessary over many years. If not treated, on the other hand, the disease can spread to the thighs, mons pubis, vagina, urinary tract, or rectum.

If an underlying cancer is associated with PDV, the malignancy may spread to the lymph nodes of the groin. In such a situation it is important to treat the disease similarly to squamous cell cancer of the vulva, namely, by radical local excision and groin lymph node resection.

Nonsurgical treatments such as photodynamic therapy, topical chemotherapy, radiotherapy, and CO2 laser ablation are also used in certain situations.

In the case of patients with anogenital Paget's disease, radiotherapy is the definitive method of treatment, especially to prevent recurrence. Dosages ranging from 40 to 50 Gy or even lower have resulted in low recurrence rates. For patients with recurrent disease, imiquimod cream is used for treatment with a high rate of success.

Studies have found no evidence to conclude on the best or least effective treatment method with respect to bringing about a delay in disease progression or relapse, prolonging survival, minimizing toxic effects, or improving the quality of life.

Although noninvasive methods have the advantage of not being associated with severe side effects, a combination of surgical and nonsurgical methods is usually recommended.