Vulvar and Vaginal Cancer

Clinical Features

Itching is the most common symptom, although some patients present with palpable or visible abnormalities of the vulva. About half of patients are asymptomatic. There is no absolutely diagnostic appearance. Most lesions are elevated, but the color may be white, red, pink, gray, or brown (Figure 40-1). About 20% of the lesions have a “warty” appearance, and the lesions are multicentric in about two thirds of cases.

FIGURE 40-1 Vulvar intraepithelial neoplasia type III: carcinoma in situ of the vulva. Note the pigmented and multicentric nature of the lesions and the extensive perianal involvement in this patient.

Diagnosis

Careful inspection of the vulva in a bright light, with the aid of a magnifying glass if necessary, is the most useful technique for detecting abnormal areas. Colposcopic examination of the entire vulva after the application of 5% acetic acid will sometimes highlight additional acetowhite areas.

Management

The mainstay of treatment is local superficial surgical excision, with primary closure. The microscopic disease seldom extends significantly beyond the colposcopic lesion, so margins of about 5 mm are usually adequate. For extensive lesions involving most of the vulva, a “skinning” vulvectomy, in which the vulvar skin is removed and replaced by a split-thickness skin graft, may be used. Because the subcutaneous tissues are not excised, the cosmetic result is superior to that obtained with vulvectomy.

Laser therapy is also effective, particularly for multiple small lesions, or for lesions involving the clitoris, labia minora, or perianal area. No specimen is available for histologic study after laser ablation, so a liberal number of biopsies must be taken before treatment to exclude invasive cancer.

Clinical Features

Itching and tenderness are common and may be long-standing. The affected area is usually well demarcated and eczematoid in appearance, with the presence of white plaquelike lesions. As growth progresses, extension beyond the vulva to the mons pubis, thighs, and buttocks may occur; rarely, it may extend to involve the mucosa of the rectum, vagina, or urinary tract. In 10% to 20% of cases, Paget’s disease is associated with an underlying adenocarcinoma.

Histologic Features

The disease is an adenocarcinoma in situ and is characterized by large, pale, pathognomonic Paget’s cells, which are seen within the epidermis and skin adnexa. They are rich in mucopolysaccharide, a diastase-resistant substance that stains positive with periodic acid–Schiff stain. The intracytoplasmic mucin may also be demonstrated by Mayer’s mucicarmine stain. The Paget’s cells are typically located adjacent to the basal layer, both in the epidermis and in the adnexal structures.

Management

The histologic extent of Paget’s disease is frequently far beyond the visible lesion. Local superficial excision with 5- to 10-mm margins is required to clear the gross lesion, exclude underlying invasive cancer, and relieve symptoms. Recurrences are common and may be treated by further excision or laser therapy. If an underlying invasive carcinoma is present, the treatment should be the same as for other invasive vulvar cancers.

Clinical Features

Patients generally present with a vulvar lump, although long-standing pruritus is common. The lesions may be raised, ulcerated, pigmented, or warty in appearance, and definitive diagnosis requires biopsy under local anesthesia. Most lesions occur on the labia majora; the labia minora are the next most common sites. Less commonly, the clitoris or the perineum is involved (Figure 40-2). About 5% of cases are multifocal.

FIGURE 40-2 A small perineal carcinoma. Note that the remainder of the vulva is normal.

Methods of Spread

Vulvar cancer spreads by direct extension to adjacent structures, such as the vagina, urethra, and anus; by lymphatic embolization to regional lymph nodes; and by hematogenous spread to distant sites, including the lungs, liver, and bone. In most cases, the initial lymphatic metastases are to the inguinal lymph nodes, located between Camper’s fascia and the fascia lata. From these superficial nodes, spread occurs to the femoral nodes located medial to the femoral vein. Cloquet’s node, which is situated beneath the inguinal ligament, is the most cephalad of the femoral node group. From the inguinofemoral nodes, spread occurs to the pelvic nodes, particularly the external iliac group (Figure 40-3).

FIGURE 40-3 Lymphatic drainage of the vulva. Inguinal nodes are displayed on the right side of the groin, and femoral nodes are seen on the left side of the groin.

The incidence of lymph node metastases in vulvar cancer is about 30%. It is related to the size of the lesion (Table 40-1). About 5% of patients have metastases to pelvic lymph nodes. Such patients usually have three or more positive unilateral inguinofemoral lymph nodes. Hematogenous spread usually occurs late in the disease and rarely occurs in the absence of lymphatic metastases.

Staging

In 1989, the International Federation of Gynecology and Obstetrics (FIGO) Cancer Committee introduced a surgical staging system for vulvar cancer. This system was revised in 1994, and the present FIGO staging system is shown in Table 40-2.

TABLE 40-2 INTERNATIONAL FEDERATION OF GYNECOLOGY AND OBSTETRICS (FIGO) STAGING OF VULVAR CARCINOMA (1994)

Management

In the past, en bloc radical vulvectomy and bilateral inguinofemoral lymphadenectomy, with or without pelvic lymphadenectomy, had been considered the standard treatment for invasive vulvar cancer. During the past 30 years, a more conservative approach has been used for the primary lesion, and the groin dissection has frequently been performed through a separate groin incision.

Using the separate incision technique, major wound breakdown is significantly reduced, so hospital stays are shorter. Groin seromas and cellulitis are common acute complications, whereas deep venous thrombosis and pulmonary embolism are uncommon. Chronic complications include lower leg lymphedema, genital prolapse, and urinary stress incontinence. Rarely, introital stenosis, pubic osteomyelitis, a femoral hernia, or a rectoperineal fistula may occur.

To decrease the morbidity associated with groin dissection, current research is focusing on identification of a sentinel node (or nodes). After the injection of a blue dye and a radiocolloid around the primary tumor, the sentinel nodes are identified and resected. They are subjected to thorough histopathologic analysis to detect any small micrometastases. Theoretically, patients with negative sentinel nodes should be at very low risk for disease in other nodes, so full groin dissection could be avoided. At the time of writing, this approach remains experimental.

Prognosis

The overall survival rate for vulvar carcinoma is about 70%. Survival by FIGO stage is shown in Table 40-3. Survival also correlates significantly with lymph node status because patients with positive nodes have a 5-year survival rate of about 50%, whereas those with negative nodes have a 5-year survival rate of about 90%. Patients with one involved node have a good prognosis, regardless of stage, whereas those with three or more involved nodes do poorly, regardless of stage.

TABLE 40-3 SURVIVAL FOR VULVAR CANCER BY FIGO STAGE (EPIDERMOID INVASIVE CANCER ONLY)

Data from the Annual Report on the Results of Treatment in Gynecological Cancer. Patients treated 1996-1998. J Epidemiol Biostat 83:7-26, 2003.

Diagnosis and Staging

Any pigmented lesion on the vulva requires excisional biopsy for histologic diagnosis. The FIGO staging of vulvar cancer does not apply well to melanomas, which are usually smaller lesions and tend to metastasize early. The prognosis correlates more closely with the depth of penetration into the dermis. Those lesions that penetrate to a depth of 1 mm or less from the granular layer of the epidermis rarely metastasize. Clark’s levels are not readily applicable to vulvar melanomas.

Management

For the superficial lesions referred to previously, radical local excision alone, with margins of at least 1 cm, is adequate therapy. For lesions with 1 mm or deeper invasion, radical local excision of the primary tumor is usually combined with at least ipsilateral inguinal-femoral lymphadenectomy. Adjuvant therapy with nonspecific immunostimulants or chemotherapeutic agents has been disappointing, although vaccines prepared from the patient’s own tumor have shown some promise.

Prognosis

The overall 5-year survival rate for vulvar melanomas is about 30%, which is comparable to that for cutaneous melanomas of nongenital origin.

Vulvar Sarcoma

Vulvar sarcomas represent 1% to 2% of vulvar malignancies. Many histologic types have been reported, including leiomyosarcomas, fibrosarcomas, neurofibrosarcomas, liposarcomas, rhabdomyosarcomas, angiosarcomas, and epithelioid sarcomas. Leiomyosarcomas are the most common, and recurrences are most likely with lesions larger than 5 cm, with infiltrating margins, and with five or more mitotic figures per 10 high-power fields.

Etiology

VAIN appears to be related to infection with the wart virus in many cases, and vaccination against HPV should decrease the incidence of VAIN and vaginal cancer in the future. Patients with a past history of in situ or invasive carcinoma of the cervix or vulva are at increased risk. Some lesions may occur after irradiation for cervical cancer.

Diagnosis

The diagnosis is usually considered because of an abnormal Papanicolaou smear in a woman who either has had a hysterectomy or has no demonstrable cervical abnormality. Definitive diagnosis requires vaginal biopsy, which should be directed by colposcopy or Lugol’s iodine staining. Colposcopic findings are similar to those seen with cervical lesions, although thorough colposcopy of all vaginal walls is technically more difficult. In postmenopausal patients, a 4-week course of topical estrogen before colposcopy is indicated to enhance the colposcopic features and eliminate those patients with Papanicolaou smear abnormalities because of inflammatory atypia.

Management

When the lesion involves the vaginal vault, surgical excision is indicated to treat the VAIN and to exclude invasive cancer. For multifocal disease, laser therapy or topical 5-fluorouracil may be used. Extensive disease may require total vaginectomy and creation of a neovagina using a split-thickness skin graft.

Patterns of Spread

Vaginal cancer spreads by direct invasion as well as by lymphatic and hematogenous dissemination. Direct tumor spread may result in involvement of the bladder, urethra, or rectum, or progressive lateral extension to the pelvic side wall. The lymphatic drainage from the upper vagina is to the obturator, hypogastric, and external iliac nodes, whereas the lower third of the vagina drains primarily to the inguinofemoral nodes. Hematogenous spread is uncommon until the disease is advanced.

Staging

The FIGO staging for vaginal cancer is clinical, as shown in Table 40-4. In practice, all patients should have at least a chest radiograph and pelvic and abdominal computed tomography or magnetic resonance imaging to detect evidence of metastatic spread, including bulky pelvic or para-aortic lymph nodes. Positron emission tomography is increasingly used to look for metastatic disease.

TABLE 40-4 INTERNATIONAL FEDERATION OF GYNECOLOGY AND OBSTETRICS (FIGO) STAGING OF VAGINAL CANCER

Management

Radiotherapy or chemoradiation is the main method of treatment for primary vaginal cancer. Initial treatment usually consists of 4500 to 5000 cGy of externalirradiation to the pelvis to shrink the primary tumor and treat the pelvic lymph nodes and paravaginal tissues. Brachytherapy is then given, either with intracavitary vaginal applicators or by interstitial techniques. When the lower third of the vagina is involved, the groin nodes should either be included in the treatment field or surgically removed.

Radical surgery has a limited role in the management of vaginal cancer. Radical hysterectomy, partial vaginectomy, and pelvic lymphadenectomy may be performed for early lesions in the posterior fornix. Surgery should otherwise be reserved for medically fit patients in whom a central recurrence develops after irradiation. Pelvic exenteration with creation of a neovagina may be appropriate in such patients provided there are no lymph node metastases at the time of exploratory laparotomy and adequate surgical margins can be attained.

Prognosis

The overall 5-year survival rate for vaginal cancer is about 50%. When corrected for death from intercurrent disease, 5-year survival rates should be about 85% to 90% for stage I lesions, 55% to 65% for stage II lesions, 30% to 35% for stage III lesions, and 5% to 10% for stage IV lesions.

Adenocarcinoma

Most adenocarcinomas of the vagina are metastatic, usually from the cervix, endometrium, or ovary, but occasionally from more distant sites such as the kidney, breast, or colon. Most primary vaginal adenocarcinomas are clear cell carcinomas in female offspring of women who ingested diethylstilbestrol (DES) during pregnancy (see later in this chapter). Primary adenocarcinomas of the vagina not related to DES are rare but may arise in residual glands of müllerian (paramesonephric) origin, Gartner’s duct (a remnant of the embryonic wolffian or mesonephric duct), or foci of endometriosis.

Malignant Melanoma

Vaginal melanomas account for fewer than 2% of vaginal malignancies. The mean age at diagnosis is 55 years. The carcinoma usually occurs on the distal anterior wall. Radical surgery has been the traditional treatment, but comparable local control and overall survival maybe obtained with conservative tumor resection and postoperative radiation therapy. The use of high-dose fractions (>400 cGy) may be beneficial. The prognosis is poor, with an overall 5-year survival rate of 5% to 10%.

Sarcoma

Vaginal sarcomas are rare. In adults, leiomyosarcomas are most common, whereas in infants and children, sarcoma botryoides predominates. The latter term comes from the Greek botrys (bunch of grapes), which these lesions usually grossly resemble. The mean age at diagnosis of sarcoma botryoides is 2 to 3 years, with a range of 6 months to 16 years. Histologically the tumor is an embryonal rhabdomyosarcoma. Treatment consists of conservative surgical resection followed by adjuvant chemotherapy, with or without radiation therapy.