Excerpt from Malignant Vulvar Lesions

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Background

Increasingly data suggest that human papillomavirus (HPV) may be a cause of some vulvar malignancies.

Frequency

Vulvar cancer accounts for approximately 5% of all female genital malignancies. It occurs in about 1.5 per 100,000 women-years in developed countries but is 2-3 times more frequent in underdeveloped countries. With the exception of the rare sarcomas, this cancer appears most frequently in women aged 65-75 years, and, in some series, almost half of the patients are aged 70 years or older. Vulvar cancer can appear in younger patients, and, in some large cancer referral institutions, approximately 15% of all vulvar cancers occur in women younger than 40 years. These young patients tend to have early microcarcinomas, which may be associated with diffuse intraepithelial neoplasia of the vulva.

As the population ages, the incidence of vulvar cancer may be increasing slowly. In a recent annual report, almost 50% of patients reported to have vulvar cancer were aged 70 years or older, with 15% aged 80 years or older. In most series, an extended delay in diagnosis appears to occur mainly because the patient does not seek medical attention for many months or because the lesion is treated medically for months, without biopsy for definitive diagnosis.

Diagnosis

Histological evaluation is a prerequisite before planning definitive therapy for changes in the epithelium of the vulva, whether pigmentation, hypertrophy, or lump or mass occurs. Many techniques can be used in the office setting to obtain adequate tissue for pathological evaluation. A dermal punch biopsy can be used as it is used elsewhere on the skin. If a lesion is small, excision may not only be diagnostic but also therapeutic. A local anesthetic is usually sufficient, and sutures are placed as needed.

Most vulvar cancer is squamous in origin. Because the vulva is covered with skin, any malignancy that appears elsewhere on the skin also can occur on the vulva. Melanoma is the second most frequent histological type, but this represents less than 5% of vulvar cancers.

Squamous vulvar cancer can have many different growth characteristics. It can occur in an area of epithelial neoplasia that develops into a small nodule, which may break down and ulcerate. Small, warty, or cauliflowerlike growths may arise and be confused with condyloma acuminata. Squamous carcinomas can appear in a background of atrophic changes (ie, lichen sclerosis) or in hypertrophic epithelium. Long-term pruritus, lumps, or masses on the vulva are present in most patients with invasive vulvar cancer.

Metastasis

The cancer can appear anywhere on the vulva, although about three fourths arise primarily on the labia. The more rare types, such as Bartholin gland carcinomas, tend to be localized to that specific region. Because the vulva is rich in lymphatics, metastasis to the inguinal lymph node can occur early in the process. Lymph node involvement is directly related to the depth of stromal invasion, as well as to the size of the primary lesion. Fortunately, bilateral inguinal nodal involvement without ipsilateral side involvement is unusual. This has therapeutic indications. The disease is usually localized and well demarcated; however, in advanced disease, determining the exact site of origin is impossible. Multifocal patterns with invasive cancer are unusual, although kissing lesions can occur as isolated lesions. Unilateral lesions appear to be the norm, particularly in postmenopausal patients.

The clinical evaluation of possible inguinal lymph node metastasis is very imprecise. In 1988, the International Federation of Gynecology and Obstetrics (FIGO) adopted a surgical staging system based on the primary tumor, regional lymph node, remote metastases (TNM) classification system. In 1995, FIGO instituted a subclassification of stage I.

Table 1. Carcinoma of the Vulva: FIGO nomenclature

*The depth of invasion is defined as the measurement of the tumor from the epithelial-stromal junction of the adjacent, most superficial dermal papilla to the deepest point of invasion.

Treatment

A small primary lesion on the vulva (ie, <2 cm) with superficial invasion (ie, <1 mm from the epithelial stromal junction of the adjacent, most superficial dermal papillae) has essentially no risk of lymph node metastasis. Consequently, these lesions can be treated with wide local excision, ensuring that adequate surgical margins are present (not only on the skin but also deep margins).

In larger lesions (ie, stage IB or greater or with stromal invasion >1 mm), the incidence of ipsilateral inguinal lymph node involvement increases as the depth of invasion, as well as the gross size, increases. Consequently, inguinal lymphadenectomy is part of the primary surgical procedure. This can be performed through a small separate inguinal incision, removing the lymph nodes above the cribriform fascia and in the opening of the fascia at the fossa ovalis. If the results are negative on frozen section of these lymph nodes, then a modified partial vulvectomy is the only treatment necessary. If the results on frozen section of the ipsilateral lymph nodes are positive, then most physicians suggest removing the lymph nodes on the contralateral inguinal area as well.

The lesion itself can be treated conservatively, with a partial vulvectomy. Performing complete vulvectomy is an outdated treatment unless the cancer is present bilaterally. If clitoral involvement is present, lymphatic drainage can be direct to the pelvic lymph nodes. Studies have demonstrated that, even with clitoral involvement, the deep lymph nodes are not involved unless the inguinal nodes have evidence of metastasis also. Pelvic lymphadenectomy is largely discontinued, even in cases of lymph node involvement. A large, prospective, randomized study conducted by the Gynecologic Oncology Group (GOG) noted that patient survival rates are better if the pelvic and inguinal area is treated with radiation postsurgically, as compared to patients treated with pelvic lymphadenectomies, even when the pelvic nodes are not involved. Incidence of lymph node metastasis seems to be increased if vascular lymphatic space is involved.

Prognosis

Contemporary data suggest that the overall 5-year survival rate of patients with stage I epidermoid invasive cancer is 85-90%. The survival rate decreases with increasing stage; however, an approximate 5-year survival rate of 40% can be obtained, even in patients with lymph node metastasis.

In a review of the National Cancer Data Base, patients with positive inguinal lymph nodes were found to have 5-year survival rates of 64% with 2-cm lesions and 43% with lesions greater than 2 cm. In patients with primary lesions of any size, the survival rate was identical whether 1 lymph node was positive or 2-3 lymph nodes were positive (55% vs 59%). The survival rate in patients with 4 or more positive nodes was only 33% at 5 years. The 5-year survival rate of patients with 1 positive node, without radiation, was 68% and was 56% with radiation. If 2 or more lymph nodes were positive, the survival rate was 46% without radiation therapy and 48% with radiation.

The 2003 Annual Report noted a 5-year survival rate of 82% in patients with negative lymph nodes who were treated with surgery only, compared to 72% for patients treated with surgery and radiation. If lymph nodes were positive, the survival rate was 48% in patients treated with surgery alone, compared to 31% in patients treated with surgery plus radiation. These studies raise the question of whether or not postoperative radiation therapy is as advantageous as the GOG study noted.

Follow-up

More than 80% of recurrences appear within the first 2 years after therapy, and they may be either local or distant. Because many reoccurring lesions appear locally and near the site of the primary lesion, initial close follow-up is necessary. Visual examination provides the best follow-up.

Local recurrences are more common in patients with large primary tumors than in patients with metastatic disease in the lymph nodes, and local occurrences can appear when the margins are clear on the original operative specimen. Local recurrences can be managed successfully in many instances by repeat local excision and/or interstitial radiation.

Recurrent lesions in the lymph node area, as well as in distant sites, are difficult to treat, and survival rates are poor. If recurrences appear in the inguinal area, excision with or without radiation therapy may be beneficial. Distant metastasis are treated most effectively with chemotherapy, with cisplatin as the drug of choice, and 30% response rates have been achieved in reports.

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