Classifying Anal Intraepithelial Neoplasia 2 Based on LAST Recommendations

Area of Science:

• Pathology
• Oncology
• Immunohistochemistry

Background:

• The Lower Anogenital Squamous Terminology (LAST) guidelines classify human papillomavirus-associated lesions.
• Accurate classification of anal intraepithelial neoplasia (AIN) is crucial for patient management.
• Interobserver variability in diagnosing AIN 2 can impact treatment decisions.

Purpose of the Study:

• To evaluate interobserver agreement among pathologists in classifying anal lesions as high-grade squamous intraepithelial lesions (HSIL) or non-HSIL.
• To assess the impact of p16 immunohistochemistry on diagnostic agreement.

Main Methods:

• Six experienced pathologists reviewed 40 anal lesions previously diagnosed as AIN 2.
• Diagnoses were made based on H&E staining alone and H&E plus p16 immunohistochemistry.
• Interobserver agreement was quantified using κ coefficients.

Main Results:

• Fair agreement (κ = 0.42) was observed with H&E alone, improving to moderate (κ = 0.55) with p16.
• Excellent agreement (κ = 0.92) was achieved when assessing p16 positivity/negativity.
• p16 staining of basal/parabasal layers was a consistent feature in positive consensus cases.
• Adding p16 led to modifications in 48% of diagnoses with conflicting p16 results.

Conclusions:

• p16 immunohistochemistry enhances interobserver agreement in classifying anal squamous lesions.
• Disagreement persists for intermediate lesions, highlighting diagnostic challenges.
• Negative p16 results may help reduce overdiagnosis of HSIL and subsequent unnecessary treatments.