Introduction
The vulva is the external part of the female reproductive system that acts as a sensory tissue during sexual intercourse, protects the internal genital organs from infection, and assists in micturition. It is a part of both the urinary and genital systems that consist of the vaginal opening, inner and outer labia, clitoris, mons pubis, vestibular bulbs, Bartholin's glands, urethral opening, and other organs. Extramammary Paget disease (EMPD) is a rare skin condition in areas with abundant apocrine sweat glands, such as the vulva. However, scrotal, penile, perineal, and perianal skin may also be affected. It is predominantly seen in females and mostly occurs during the sixth to eighth decades of life. It appears as reddish, ulcerated, well-demarcated scaly lesions, and the exact cause of primary EMPD has been debated. The first case of extramammary Paget’s disease affecting the penis and scrotum was reported by Dr. Crocker in 1889. EMPD represents about 6.5 percent of all cutaneous Paget diseases, and only a few hundred cases have been reported in the global medical literature.
What Is Vulvar Paget’s Disease?
Vulvar Paget’s disease (VPD) is an extremely rare malignant condition that affects the top layers of the skin of the vulva. It mostly resembles mammary Paget’s disease (a rare type of breast cancer) of the nipple and areola and mainly affects women after menopause (stopping of menstrual periods). However, this disease is often limited to the epidermal layer and mucosa without invasion. A French dermatologist first reported Paget’s disease of the vulva, Dr. Dubreuil, in 1901. It has a high local recurrence and low mortality rate and is often misdiagnosed with eczematous skin lesions due to its non-specific symptoms and lack of clinical evidence. VPD is a rare form of cutaneous adenocarcinoma (a rare type of skin cancer) of the vulva but the most common extramammary Paget's disease (60 to 80 percent) that accounts for approximately one to two percent of all vulvar neoplasms.
What Are the Symptoms of Vulvar Paget’s Disease?
Vulvar Paget’s disease is very slow spreading, symptoms are vague, and around ten percent of the women may be asymptomatic. The clinical presentation of this condition is usually non-specific and mimics chronic skin lesions or eczema (a common skin disorder characterized by dry and itchy patches). Therefore, it is often initially delayed or misdiagnosed. The symptoms of vulvar Paget’s disease include:
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Thickened red-colored skin presenting a velvety appearance.
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Skin irritation and itchy rash.
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Moist areas of the skin that bleed easily.
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Patches of red and white scaly or crusty appearance.
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Burning sensation and persistent pain or tenderness.
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Vaginal discharge.
How Is Vulvar Paget’s Disease Diagnosed?
Diagnosing vulvar Paget’s disease can be challenging as the condition is rare and resembles various chronic skin lesions. In most cases, the symptoms are present almost two years before the diagnosis is confirmed. Physical examination is performed initially, followed by imaging diagnostic tests such as a pelvic ultrasound, computed tomography (CT) scan, and magnetic resonance imaging (MRI). However, it may be confirmed by a skin biopsy (removing a small piece of tissue and examining it under a microscope) or a vulvar excisional biopsy. Though this condition may be noninvasive, some patients may be diagnosed with bladder cancer years after the diagnosis of vulvar Paget's disease. Therefore, if vulvar Paget’s disease is suspected, colonoscopy (a small flexible camera is inserted to check the rectum and large intestine) or cystoscopy (a tiny camera is inserted to check the bladder), urine examinations and other tests are recommended to rule out cancers of the colon or bladder.
Vulvar Paget’s disease is generally a slow-growing tumor; however, occasionally, the Paget cells may extend from the epidermis to the dermis and cause metastasis to the regional lymph nodes. Some of the other potential sites of metastasis of VPD include the liver, adrenal glands, bones, and lungs. Immunohistochemistry techniques are usually recommended to differentiate vulvar Paget’s disease from other primary or metastatic tumors.
How Is Vulvar Paget’s Disease Managed?
In patients with anogenital Paget’s disease, radiotherapy is the definitive treatment, especially to avoid recurrence, and generally, surgery is the treatment of choice when the patient is first diagnosed with vulvar Paget’s disease. However, the results may not be encouraging as this condition has high recurrence rates. Some of the non-surgical treatment options include:
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Topical chemotherapy with intralesional interferon alfa-2b.
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Radiotherapy.
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Photodynamic therapy with topical aminolevulinic acid, 5 percent Imiquimod cream, and topical Fluorouracil.
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Carbon dioxide (CO2) laser ablation.
Five percent Imiquimod cream is a promising treatment option. Studies have demonstrated that many patients experienced reduced symptoms, no clinical evidence of residual Paget’s disease, and complete remission within eight weeks. Though noninvasive treatment methods are not associated with any severe adverse effects, a combination of surgical and non-surgical options are usually recommended in patients with vulvar Paget’s disease.
Vulvar Paget’s disease is a chronic and relapsing condition, and surgery is recommended in most cases. The type of surgical intervention depends on the size and location of the condition and hence varies among patients. However, studies have not reported evidence to conclude the best or least effective treatment to minimize the toxic effects, delay the progression, prolong the survival, prevent relapse, or improve patients' quality of life.
Surgery requires a hospital stay for a few days, followed by several weeks of recovery at home. Follow-up examinations are performed every four to six months for up to ten years after the surgery. Some of the surgical techniques used to treat vulvar Paget’s disease include:
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Local Excision: A wide local excision is recommended to remove the affected tissue and some normal tissue. The disease usually extends into tissues that look similar to normal skin, and it can be hard for surgeons to decide on the extent of tissue removal, as it may cause severe morbidity. However, biopsies can guide surgery, and skin grafting may be required in some cases.
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Vulvectomy: It is a partial or complete removal of the vulva. If the entire vulva, along with inner and outer labia, clitoris, and some tissue under the skin, is removed, it is called a simple vulvectomy. If the entire vulva, deep tissues, and surrounding lymph nodes are removed, it is called radical vulvectomy. Vulvectomy may be associated with complications such as swelling, bleeding, scarring, infections, and disturbances in sexual function.
Conclusion
Vulvar Paget’s disease is a slow-spreading, rare malignant condition of the vulva and the most common extramammary Paget’s disease seen in postmenopausal women. It may be often misdiagnosed due to its non-specific symptoms and lack of clinical evidence. Though surgery is the treatment of choice, it has a high rate of local recurrence or near the surgical site. Imiquimod cream (five percent) is also known to be beneficial for some patients with VPD. Patients with vulvar Paget’s disease are at a high risk of developing bladder cancer and other malignancies; hence, routine screening tests such as mammograms and Pap smear tests are necessary. However, multidisciplinary collaborations and further research are needed to understand this complex condition.
