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Since the introduction of the Papanicolaou (Pap) test in the 1950s, cytology screening has been associated with a significant reduction in both the incidence of and mortality rate from invasive cervical cancer (Saslow, 2002). Annually, approximately 7 percent of U.S. women who undergo screening will have abnormal cervical cytologic results requiring a clinical response (Jones, 2000). Accordingly, office gynecology frequently involves the diagnosis and management of preinvasive lower genital tract disease.


The term intraepithelial neoplasia refers to squamous epithelial lesions of the lower genital tract that are considered to be precursors of invasive cancer. Lesions are diagnosed by biopsy and histologic evaluation. Cervical, vaginal, vulvar, perianal, and anal intraepithelial neoplasia (CIN, VaIN, VIN, PAIN, and AIN, respectively) demonstrate a disease spectrum ranging from mildly dysplastic cytoplasmic and nuclear changes to those of severe dysplasia. There is no invasion through the basement membrane, which would then characterize an invasive cancer.


The severity of an intraepithelial lesion is graded by the proportion of epithelium affected from the basement membrane upward toward the surface. In the case of 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 lesions of the vagina, vulva, perianal, and anal epithelia are graded similarly with the caveat that VIN 1 is no longer recognized. The natural history of these extracervical lesions is less well understood than for CIN.

Figure 29-1
Graphic Jump Location

A. Normal ectocervical mucosa. The ectocervical epithelium is a nonkeratinizing, stratified squamous epithelium that matures in response to estrogen stimulation. Mitoses are normally confined to the deeper layers, that is, the basal and parabasal epithelial layers. B. Cervical biopsy taken from the transformation zone with mild squamous dysplasia (CIN I). The transformation zone is indicated by the presence of both squamous epithelium and endocervical glands (yellow asterisk). CIN 1 is characterized by a disordered proliferation of squamous cells and increased mitotic activity confined to the basal one third of the epithelium, with koilocytotic atypia involving the more superficial epithelium. Koilocytosis is typified by nuclear enlargement, coarse chromatin, nuclear “wrinkling,” and perinuclear halos. C. Severe squamous dysplasia (CIN 3/squamous cell carcinoma in situ) is characterized by disordered proliferation of atypical squamous cells and increased mitotic activity involving the full thickness of the epithelium. Note the mitotic figure located close to epithelial surface (arrow). Abnormal mitoses are sometimes present. (Photographs contributed by Dr. Kelley Carrick.)


In contrast, because it is only one cell-layer thick, the cervical columnar epithelium does not demonstrate an analogous neoplastic disease spectrum. Histologic abnormalities are therefore limited to either adenocarcinoma in situ(AIS) or ...

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