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Office gynecology frequently involves the diagnosis and management of preinvasive lower genital tract disease, most often involving the uterine cervix. Since widespread introduction of the Papanicolaou (Pap) test in the 1950s, cervical cancer screening has reduced the incidence of and mortality rate from invasive cervical cancer by more than 70 percent (Howlader, 2014). This is true despite a continued rise in the incidence of preinvasive lesions (Kurdgelashvili, 2013). Approximately 7 percent of U.S. women who undergo Pap testing will have an abnormal result (Wright, 2012). An abnormal screening test prompts further patient evaluation, usually with colposcopy and biopsy. Histologic results are more definitive and inform appropriate management.


In the lower genital tract (LGT), the term intraepithelial neoplasia refers to squamous epithelial lesions that are potential precursors of invasive cancer. These lesions demonstrate a range of histologic abnormality from mild to severe based on cytoplasmic, nuclear, and histologic changes. The severity of a squamous intraepithelial lesion is graded by the proportion of epithelium with abnormal cells from the basement membrane upward toward the surface. In the case of cervical intraepithelial neoplasia (CIN), abnormal cells confined to the lower third of the squamous epithelium are referred to as mild dysplasia or CIN 1, extending into the middle third as moderate dysplasia or CIN 2, into the upper third as severe dysplasia or CIN 3, and full-thickness involvement as carcinoma in situ (CIS) (Fig. 29-1). Squamous neoplasia of the vagina, vulva, perianal, and anal squamous epithelia (VaIN, VIN, PAIN, and AIN, respectively) are graded similarly with the caveat that VIN 1 is no longer recognized. The natural history of these extracervical lesions is less understood than for CIN. In contrast, the cervical columnar epithelium does not demonstrate an analogous neoplastic disease spectrum because it is only one cell-layer thick. Histologic abnormalities are therefore limited to either adenocarcinoma in situ (AIS) or adenocarcinoma.


A. Normal ectocervical epithelium is a nonkeratinizing, stratified squamous epithelium. Mitoses are normally confined to the lower layers, namely, the basal and parabasal epithelial layers. B. Low-grade squamous intraepithelial lesion (LSIL). This biopsy’s location at the transformation zone is indicated by the presence of both columnar epithelium (asterisk) and squamous epithelium. Low-grade SIL has a disordered proliferation of squamous cells and increased mitotic activity confined to the basal one third of the epithelium. Koilocytotic atypia, which is indicative of proliferative HPV infection, involves the more superficial epithelium. Koilocytosis is typified by nuclear enlargement, coarse chromatin, nuclear “wrinkling,” and perinuclear halos. C. This high-grade SIL shows disordered, highly atypical squamous cells and increased mitotic activity involving the full thickness of the epithelium. Note the mitotic figure located close to epithelial surface (yellow arrow). (Used with permission from Dr. Kelley Carrick.)

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