Diagnosing Anal Squamous Intraepithelial Lesions With and Without p16: An Interobserver Variability Study
Uma Krishnamurti1, Mohammad Mohammad2, Ashley Monsrud3
1Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA.
Journal of Lower Genital Tract Disease
|December 21, 2019
Summary
Accurate grading of anal squamous intraepithelial lesions (ASIL) is challenging. A two-tiered diagnosis (high-grade SIL vs. no high-grade SIL) with p16 testing significantly improves interobserver agreement for ASIL grading.
Area of Science:
- Pathology
- Oncology
- Gastroenterology
Background:
- Accurate morphologic diagnosis and grading of anal squamous intraepithelial lesions (ASIL) present diagnostic challenges.
- Interobserver variability can impact the reliability of ASIL grading.
- The utility of p16 immunostaining in improving diagnostic accuracy requires further investigation.
Purpose of the Study:
- To investigate interobserver variability in ASIL grading.
- To evaluate the utility of p16 in enhancing the accuracy of ASIL grading.
- To determine optimal diagnostic criteria for ASIL.
Main Methods:
- Six pathologists reviewed hematoxylin and eosin (H&E) stained slides from 146 anal biopsies.
- p16 immunostaining results were reviewed in conjunction with H&E slides where available.
- Interobserver agreement was calculated using Cohen's kappa (κ) for various diagnostic tiers.
Main Results:
- Moderate agreement was observed for a 4-tiered ASIL diagnosis (κ = 0.48-0.57).
- Substantial agreement was achieved when pooling AIN 2 and AIN 3 as high-grade SIL (HSIL) (κ = 0.71-0.78).
- Almost perfect agreement was found for a 2-tiered diagnosis (HSIL vs. no HSIL), particularly with concurrent p16 review.
Conclusions:
- Judicious use of p16 is crucial for accurate ASIL diagnosis.
- A 2-tiered diagnostic approach (HSIL vs. no HSIL) demonstrates substantial to almost perfect interobserver agreement, especially when p16 is not indicated per guidelines.
- When p16 is indicated but not performed or reviewed, diagnostic agreement decreases significantly, underscoring the importance of rational p16 utilization for optimal patient care.
