General Considerations
Paget’s disease of the skin is an intraepithelial neoplasia, or adenocarcinoma in situ, and accounts for less than 1% of all vulvar malignancies. Reports of long-term survivals suggest that the in situ stage of the disease persists for a long time or that invasive disease is a different clinicopathologic entity. It appears that there are two separate lesions: (a) intraepithelial extramammary Paget’s disease and (b) pagetoid changes in the skin associated with an underlying adenocarcinoma.

Experts believe that an adenocarcinoma associated with Paget’s disease arises as a primary adenocarcinoma of an underlying apocrine gland, Bartholin’s gland, or anorectum, and represents two separate disease entities, not a spectrum. Unlike mammary Paget’s disease, less than 20% of vulvar Paget’s disease is associated with an underlying adenocarcinoma. Paget’s disease with an underlying adenocarcinoma metastasizes frequently to regional lymph nodes and distally. Paget’s disease without an underlying adenocarcinoma behaves like an intraepithelial neoplasia and can be treated as such. However, patients with Paget’s disease should be carefully examined for the presence of synchronous primaries elsewhere; 20-30% of these patients will be found to have carcinomas at other sites, including the breast, rectum, bladder, cervix, ovary, and urethra.

Pathology
The initial lesion may be confused with a number of benign forms of chronic vulvar pruritus. It is a pruritic, slowly spreading, velvety-red discoloration of the skin that eventually becomes eczematoid in appearance with secondary maceration and development of white plaques; it may spread to involve the skin of the perineum, the perianal area, and the adjacent skin of the thigh. Grossly, the lesion gives the impression of “cake icing.” Because of the serpiginous growth pattern of Paget cells in the basal layer of the epidermis, the true extent of disease is difficult to assess.

Paget’s disease of the vulvar skin is an intraepithelial disease. The typical Paget cell, pathognomonic of the disease process, apparently arises from abnormal differentiation of the cells of the basal layer of the epithelium (

Fig 49-4). The appearance of malignant cells varies from that of the clear cell of the apocrine gland epithelium to a totally undifferentiated basal cell. It has been suggested that there may be both an intraepithelial and an invasive variety of the disease. The intraepithelial stage of the disease persists for years without evidence of an underlying adenocarcinoma.

Diagnosis
Paget’s disease primarily affects postmenopausal white women in the seventh decade of life, but can be seen in younger patients. Pruritus and vulvar soreness are the most frequent symptoms. These symptoms may persist for years before the patient seeks medical attention. The lesion may be localized to one labium or involve the entire vulvar area. The lesion usually has an eczematoid appearance macroscopically and usually begins on the hair-bearing portions of the vulva. It is not unusual for the disease process to extend beyond the vulva to involve the perirectal area, buttocks, thighs, inguinal area, and mons. Intraepithelial extramammary Paget’s disease presents as a lesion with hyperemic areas associated with a superficial white coating to give the impression of “cake icing.” Although these lesions can be very extensive, most are confined to the epithelial layer. The diagnosis is made by vulvar biopsy. It is important to palpate the lesion in its entirety. A generous biopsy should be taken of any area that appears to be thickened to rule out an underlying adenocarcinoma.

Treatment
Because extramammary Paget’s disease is an intraepithelial neoplasia it can be treated as such. Wide local excision is the primary treatment modality for this disease process. The lesion needs to be excised in its entirety; however, wide margins need to be removed around the primary lesion as disease often extends beyond the clinically visible erythematous area. The underlying dermis should be removed for adequate histologic evaluation. Often such a resection involves a complete vulvectomy. Careful histologic examination of the entire operative specimen is necessary to delineate the true extent of disease, ensure free surgical margins, and detect the remote possibility of underlying adenocarcinoma. For this reason, laser therapy is unsatisfactory. Patients who have Paget’s disease with underlying adenocarcinoma should be treated with radical local excision of the vulva and bilateral inguinal lymph node dissection as they would for any other invasive tumor involving the vulvar area.

Prognosis
Paget’s disease of the vulva has a great propensity for local recurrence, which may represent persistence of the disease or development of new disease in the remaining vulvar skin. Extramammary Paget’s disease characteristically requires repeated local excisions of recurrent disease after treatment of the primary disease by total vulvectomy. Invasive disease without evidence of lymph node metastases has a favorable prognosis; however, with nodal metastases, the disease is almost invariably fatal.

Rowley KC, Gallion HH, Donalson ES, et al. Prognostic factors in early vulvar cancer. Gynecol Oncol 1988;31:43.