CLINICAL VIGNETTE

A Case of Vulvar Extramammary Pagets Disease

Angela Ruman, M.D.

Case Report A 56-year-old postmenopausal woman presented with complaints of vulvar itching, and she noticed a welldemarcated reddish lesion on her vulva. She had been seen three to four months before and had initially been treated for an eczematous lesion with topical steroids. She denied any vaginal discharge or history of recurrent yeast infections. She reported no change in the lesion or her symptoms with use of the topical steroids. On the genital exam she had a macular, solitary reddish circular lesion on her right labia. She had no other gross abnormalities. She was sent to dermatology clinic where she had a vulvar biopsy which established the pathologic diagnosis of extramammary Paget's disease. She was sent to OB/Gyn for further evaluation and treatment. Discussion In 1874 Sir James Paget first described mammary Paget's disease. It was not until 1889 that Crocker described the first case of extramammary Paget's disease affecting the scrotum and penis. In 1901 Dubreiuhl reported the first case of vulvar extramammary Paget's disease. 1 Vulvar extramammary Paget's disease is a rare condition that comprises only 1-2% of vulvar malignancies.2 In 1998 only 200 cases of vulvar extramammary Paget's disease were reported in the literature. 1 Due to the disease's relatively low incidence, and since many cases are unreported, its true incidence remains unknown. 3 Extrammammary Paget's disease occurs most commonly in the sixth and seventh decades, with an average age of 63 years. 3 It can be found in both men and women; however, it is most commonly seen in postmenopausal Caucasian females.2 Typically involved sites are the vulvar, perianal, scrotal and penile regions; rare sites include the thighs, buttocks, axilla, eyelids and external ear canal.4 Grossly, the lesions can appear well defined, moist and reddish. 3 The lesions can be white to red, scaling or macerated. The lesions can appear infiltrated, eroded or look like an ulcerated plaque. 5 19

Patients can present with complaints of vulvar pruritus, vulvar irritation, vulvar burning or they may notice a vulvar lesion. 3 The differential diagnosis for extramammary Paget's disease includes psoriasis, contact dermatitis, fungal infections, lichen sclerosis, intraepithelial neoplasia, and melanoma. The nonspecific clinical findings often lead to misdiagnoses. Many patients do not seek medical care immediately, and those who do are often treated for other diseases with extended periods of topical steroids. An average of one year can pass before a biopsy is taken and definitive diagnosis is made. 4 Histologically, Paget's disease resembles Bowen's disease and superficial spreading melanoma.5 It is characterized microscopically by the presence of specific tumor cells called Paget's cells. Paget cells are large cells with pale clear cytoplasm, large round hyperchromatic nuclei which tend to form clusters or solid nests. Paget cells can be found at all levels of the epidermis. They can migrate within the epidermis in a horizontal as well as vertical manner. Because of this type of migratory pattern, there is a high local recurrence rate (40%) of vulvar extramammary Paget's disease after local excision.1 The pathogenesis of extramammary Paget's disease remains controversial. An unusual feature of extramammary Paget's disease and one that spurred controversy regarding its histiogenesis is its association with underlying invasive apocrine gland carcinoma. While mammary Paget's disease is almost always associated with an underlying invasive ductal carcinoma and is generally accepted as being of underlying apocrine gland and/or ductal origin, vulvar extramammary Paget's disease is associated with an underlying invasive apocrine gland carcinoma in only about 25% of cases.1 Genitourinary, gastrointestinal and breast carcinomas comprise the majority of the coexisting cancers.2 Some authors believe that Paget's cells of extramammary Paget's disease originate in the epidermis and should be viewed as a form of abnormal differentiation of epidermal stem cells. The underlying apocrine gland invasive carcinoma found in 25% of cases should be viewed as a second synchronous primary malignancy. Other authors believe that, with regard to pathogenesis, extramammary Paget's disease should not be differentiated from mammary Paget's disease. The Paget's cells in both extramammary Paget's disease and mammary Paget's disease are likely to be of apocrine gland and/or duct origin and extend into the epidermis by migration or metastasis from the underlying apocrine glands and/or

ducts.1 This theory seems to be the more popular one. Four histologic forms of vulvar extramammary Paget's disease have been recognized.(Table 1) 1 The treatment of noninvasive extramammary Paget's disease is wide surgical excision as the disease usually extends well beyond the gross lesion. 6 Frozen sections are obtained to ensure adequate excision. Paget's disease of the vulva is almost always noninvasive and can oftentimes be managed by simple vulvectomy or wide local excision. Mohs micrographic surgery has also been used as treatment. Among treatments for noninvasive vulvar extramammary Paget's disease, vulvectomy has a 15% recurrence rate, Mohs micrographic surgery has a 27% recurrence rate and wide local excision has a 43% recurrence rate.4 The role of laser ablation in Paget's disease is controversial.7 It is best used for treatment of recurrent disease. Other modalities that are currently being investigated for treatment of noninvasive extramammary Paget's disease are radiotherapy, topical chemotherapy and CO2 laser vaporization and photodynamic therapy. These treatment modalities are not well suited, however, for treatment of extramammary Paget's disease that is invasive, poorly defined and multicentric.4 For invasive lesions,
Table 1: Forms of Vulvar Extramammary Pagets Disease Intra-epidermal vulvar extramammary Paget's disease The basement membrane is intact and the Paget cells are located and confined to the epidermis only. This form accounts for approximately 75% of vulvar extramammary Paget's disease. Minimally invasive vulvar extramammary Paget's disease The Paget cells break through the basement membrane and invade the underlying dermis less than 1 mm. This form is rare. Invasive vulvar extramammary Paget's disease The Paget cells break through the basement membrane and invade the underlying dermis more than 1 mm. This form is very rare. Vulvar extramammary Paget's disease with an underlying apocrine gland adenocarcinoma This form accounts for 25% of vulvar extramammary Paget's disease. One study looked at histologic appearance as one possible means of identifying patients with a poorer prognosis. Patients with extramammary Paget's disease confined to the epidermis had better outcomes than patients whose extramammary Paget's disease invaded the dermis and those who had an underlying adenocarcinoma. 2

radical vulvectomy and bilateral groin dissection have been used.1 Conclusion It is important to recognize that not all vulvar lesions are benign nor do they all respond to topical steroids. While the incidence of vulvar extramammary Paget's disease is extremely low, if a lesion is not responding to a current treatment a biopsy is necessary to make the diagnosis. If vulvar extramammary Paget's disease is diagnosed surgical treatment is the current standard. Long-term follow up is required to exclude recurrence of the disease and development of associated cancer. REFERENCES
1. Piura B, Rabinovich A, Dgani R. Extramammary Paget's disease of the vulva: report of five cases and review of the literature. Eur J Gynaecol Oncol. 1999;20(2):98-101. 2. Parker LP, Parker JR, Bodurka-Bevers D, et al. Paget's disease of the vulva: pathology, pattern of involvement, and prognosis. Gynecol Oncol. 2000 Apr;77(1):183-189. 3. Pliskow S. Vulvar Paget's disease. Clinicopathological review of 14 cases. J Fla Med Assoc. 1990 Jul;77(7):667-671. 4. Zollo JD, Zeitouni NC. The Roswell Park Cancer Institute experience with extramammary Paget's disease. Br J Dermatol. 2000 Jan;142(1):59-65. 5. Habif TP. Clinical Dermatology: a Color Guide to Diagnosis and Therapy, 3rd ed. St. Louis (MO): Mosby;1996. 6. Mehta NJ, Torno R, Sorra T. Extramammary Paget's disease. South Med J. 2000 Jul;93(7):713-715. 7. Ryan KJ, editor. Kistner's Gynecology and Women's Health, 7th ed. St. Louis (MO): Mosby;1999.

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