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HPV and Anal Squamous Intraepithelial Neoplasia: The Lower Anogenital Squamous Terminology (LAST) project undertaken in 2012 by the College of American Pathologists (CAP) and American Society for Colposcopy and Cervical Pathology (ASCCP) recommended that HPV-induced anal squamous dysplasias be divided into low-grade and high-grade.

Low-grade squamous intraepithelial lesions (LGSIL) are usually associated with low-risk HPV genotypes 6 and 11. High-grade squamous intraepithelial lesions (HGSIL) are mostly caused by high-risk HPV genotypes 16 and 18. Some LGSIL may be associated with high-risk genotypes, and conversely HGSIL may show low-risk genotypes. Immunocompromised patients (especially HIV+) are at increased risk of progression of LGSIL to HGSIL and from HGSIL to invasive squamous cell carcinomas.

The older terminology was a three-tier system and included anal intraepithelial neoplasia (AIN) 1, 2, and 3. LGSIL encompasses AIN1 and HGSIL includes AIN2 and AIN3. Anogenital condylomas generally have low-grade dysplasia and are included in the LGSIL category. LGSILs show minimal cytologic atypia and scant mitotic figures confined to the basal third of the epithelium. There is orderly maturation to the surface.

In HGSIL (shown here), the cytologic abnormalities involve lower two-thirds or full thickness of the epithelium and include nuclear enlargement and hyperchromasia, nuclear membrane irregularity, pleomorphism, and increased mitotic activity. Abnormal mitoses are frequently present well above the basal zone. Atypical parakeratosis is commonly seen on the surface. These changes can occur on a flat mucosa (shown here) or in the context of a condyloma.

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