Reproductive Pathology I Case Studies


CASE 6: Squamous cell carcinoma in situ of vulva


Clinical History:

A 30 year-old woman noted a white plaque on the vulva. She had been sexually active for the past 16 years, with multiple sexual partners. She had no medical problems. Following a punch biopsy, an excisional biopsy was performed.

Image 6.1 to 6.2:

Sections of the lesion show vulvar intraepithelial neoplasia (VIN) that involves the full thickness of the epithelium (VIN III).

Answers:

  1. Does the tissue represent labia minora or labia majora?

    2. The tissue is from the labia minora, since no hair follicles are noted.

  2. Why did the lesion appear white?

    3. Vulvar carcinoma in situ with associated areas of dysplasia is present with areas of hyperkeratosis. The thickened stratum corneum appears white when moist.

  3. Is there stromal invasion?

    4. Dermal (stromal) invasion is not seen.

  4. Should any additional examinations be performed?

    5. Vulvar CIS may be associated with vaginal or cervical squamous cell carcinoma (lower genital tract neoplasia) because of similar risk factors--especially human papillomavirus (HPV) infection. The patient should be followed carefully.

    HPV testing by PCR for high risk types such as 16 may be a useful adjunct to the Pap smear. HPV positivity is significantly associated with cytologic diagnoses of a high grade squamous intraepithelial lesion (HSIL) or worse. In addition, cases of Pap smears with atypical squamous cells of uncertain significance (ASCUS) that are HPV positive are found to be associated with histological abnormalities on biopsy.

  5. Explain the pathophysiology of this disease.

    6. Human papillomavirus (HPV) has many different types, some of which infect the lower genital tract, and a few of them, particularly type 16, are associated with progression to carcinoma. Transformation to cancer from normal epithelium is a multistep process. Most HPV infections regress spontaneously over time, but some CIN lesions progress to cancer. If HPV is integrated into the squamous epithelial cell genome, the viral E2 gene may become inactivated, leading to overexpression of the viral E6 and E7 proteins, which bind and inactivate host cell tumor suppressor proteins of the Rb and p53 genes.