Vulvar intraepithelial neoplasia and vulvar carcinoma

Figure 22-6 A, Numerous condylomas of the vulva encircling the introitus. B, Histopathology of condyloma acuminatum showing acanthosis, hyperkeratosis, and koilocytic atypia with enlarged, atypical nuclei and cytoplasmic vacuolation (center of microphotograph). (A, Courtesy of Dr. Alex Ferenczy, McGill University, Montreal, PQ, Canada.)

Carcinoma of the vulva is an uncommon malignant neoplasm (approximately one eighth as frequent as cervical cancer) representing about 3% of all genital cancers in the female; approximately two thirds occur in women older than 60 years. Squamous cell carcinoma is the most common histologic type of vulvar cancer. In terms of etiology, pathogenesis, and histologic features, vulvar squamous cell carcinomas are divided into two groups: basaloid and warty carcinomas related to infection with high oncogenic risk HPVs (30% of cases) and keratinizing squamous cell carcinomas, not related to HPV infection (70% of cases).14

Invasive basaloid and warty carcinomas develop from a precancerous in situ lesion called classic vulvar intraepithelial neoplasia (classic VIN). This form of VIN includes lesions designated formerly as carcinoma in situ or Bowen disease. Classic VIN is characterized by nuclear atypia of the squamous cells, increased mitoses, and lack of cellular maturation (Fig. 22-7A). It is analogous to cervical squamous intraepithelial lesions (SILs, see under "Cervix"). It most commonly occurs in reproductive-age women, and the risk factors are the same as those associated with cervical squamous intraepithelial lesions (e.g., young age at first intercourse, multiple sexual partners, male partner with multiple sexual partners), since both cervical squamous intraepithelial lesions and classic VIN are related to HPV infection. VIN is frequently multicentric in the vulva, and 10% to 30% of patients with VIN also have vaginal or cervical HPV-related lesions. The majority of cases of classic VIN are positive for HPV 16, and less frequently for other high-risk HPV types, like HPV 18 or 31. Spontaneous regression of VIN lesions has been reported, usually in younger women; the risk of progression to invasive carcinoma is higher in women older than 45 years of age or in women with immunosuppression.

Morphology. HPV-associated vulvar squamous cell carcinomas begin as classic VIN lesions, which present as discrete white (hyperkeratotic), flesh-colored or pigmented, slightly raised lesions. Coexisting carcinomas may be exophytic or indurated, frequently with ulceration. On histologic examination, basaloid carcinoma (Fig. 22-8A) shows an infiltrating tumor characterized by nests and cords of small, tightly packed malignant squamous cells lacking maturation that resemble immature cells from the basal layer of the normal epithelium. The tumor may have foci of central necrosis.

Warty carcinoma is characterized by exophytic, papillary architecture and prominent koilocytic atypia (Fig. 22-8B).

Non-HPV-related keratinizing squamous cell carcinomas frequently arise in individuals with long-standing lichen sclerosus or squamous cell hyperplasia. The mean age of the patients is 76 years. The immediate premalignant lesion is referred to as differentiated vulvar intraepithelial neoplasia (differentiated VIN) or VIN simplex (see Fig. 22-7B).14 Differentiated VIN is characterized by marked atypia of the basal layer of the squamous epithelium with apparently normal epithelial maturation and differentiation in the superfical layers, thus the designation "differentiated VIN." The etiology of differentiated VIN is unknown, but it is postulated that chronic epithelial irritation in lichen sclerosus or squamous cell hyperplasia may contribute to a gradual evolution of the malignant phenotype. The putative molecular events leading to malignant transformation in lichen sclerosus, squamous cell hyperplasia, and differentiated VIN are under investigation. A report of allelic imbalance in lichen sclerosus and squamous cell hyperplasia supports the hypothesis that both conditions pose a risk for neoplasia despite the lack of morphologic evidence of atypia. Rare cases of lichen sclerosus, differentiated VIN, and adjacent carcinoma with identical p53 gene mutations have been reported. Overall, however, p53 gene mutation is an infrequent and rather late event in vulvar carcinogenesis.15

Morphology. Carcinomas associated with lichen sclerosus, squamous cell hyperplasia, and differentiated VIN may develop as nodules in a background of vulvar inflammation. The often-subtle emergence of cancer may be misinterpreted as dermatitis, eczema, or leukoplakia for long periods. The clinical manifestations are nonspecific, including local discomfort, itching, and exudation because of superficial secondary infection, and underscore the importance of repeated examination in women with vulvar inflammatory disorders. Histologic examination reveals infiltrating tumor characterized by nests and tongues of malignant squamous epithelium with prominent central keratin pearls (Fig. 22-9A).

Risk of cancer development in VIN is principally a function of age, extent, and immune status.16 Once invasive cancer develops, metastatic spread is linked to the size of tumor, depth of invasion, and involvement of lymphatic vessels. The initial spread is to inguinal, pelvic, iliac, and periaortic lymph nodes. Ultimately, lymphohematogenous dissemination to the lungs, liver, and other internal organs may occur. Patients with lesions less than 2 cm in diameter have a 60% to 80% 5-year survival after treatment with vulvectomy and lymphadenectomy; however, larger lesions with lymph node involvement have a 5-year survival rate of less than 10%.

Rare variants of squamous cell carcinoma include verrucous carcinomas (Fig. 22-9B), which are fungating tumors resembling condyloma acuminatum, and basal cell carcinomas, which are identical to their counterparts in the skin. Neither tumor is associated with papillomaviruses. Both tumors rarely metastasize and are successfully cured by wide excision.

Glandular Neoplastic Lesions

Дата добавления: 2015-11-13