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Office gynecology includes the diagnosis and management of preinvasive lower anogenital tract (LAGT) disease, most often involving the uterine cervix, but also the vulvar, vaginal, perianal, and anal epithelia. An understanding of human papillomavirus (HPV) as the causative agent of most LAGT neoplasia has greatly advanced screening, diagnosis, management, and prevention efforts. Importantly, in current clinical practice, evidence-based knowledge is ever evolving and translates into rapidly changing patient-care recommendations. Although most study findings and clinical guidelines to date refer to women, these are applicable to the care of some transgender men (Hembree, 2017).


In the LAGT, the term intraepithelial neoplasia refers to 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 squamous intraepithelial lesions is graded by the proportion of epithelium with abnormal cells. These alterations begin at the basement membrane and continue upward toward the epithelium surface. With cervical intraepithelial neoplasia (CIN), abnormal cells solely confined to the lower third of the squamous epithelium are referred to as mild dysplasia or CIN 1. Those that extend into the middle third are moderate dysplasia or CIN 2; into the upper third, severe dysplasia or CIN 3; and full-thickness involvement, carcinoma in situ (CIS) (Fig. 29-1). Preinvasive squamous lesions of the vagina, vulva, perianal, and anal squamous epithelia are graded similarly to CIN. 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 those that are contained in the columnar epithelium, adenocarcinoma in situ (AIS), or those that invade past the epithelial basement membrane, adenocarcinoma.


A. Normal ectocervical epithelium is a nonkeratinizing, stratified, squamous epithelium, which contains basal, parabasal, intermediate, and superficial layers. The epithelium matures and accumulates glycogen in its upper layers. Mitoses are usually confined to the parabasal layer. B. Low-grade squamous intraepithelial lesion (LSIL). This biopsy’s location at the transformation zone is indicated by the presence of both mucinous columnar endocervical epithelium (asterisks) and squamous epithelium. LSIL has disordered squamous cell proliferation and increased mitotic activity confined to the basal one third of the epithelium. Koilocytotic atypia, indicative of proliferative human papillomavirus (HPV) infection, involves the more superficial epithelium. Koilocytosis is typified by nuclear enlargement, coarse chromatin, nuclear “wrinkling,” perinuclear halos, and greater prevalence of binucleation/multinucleation. C. High-grade squamous intraepithelial lesion (HSIL). This example shows disordered, markedly atypical squamous cells and increased mitotic activity that involves the epithelium’s full thickness. Note the mitotic figure located close to the epithelial surface (red arrow). (Reproduced with permission from Dr. Kelley Carrick.)


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