64 Interobserver Concordance of Tumor Infiltrating Lymphocyte Assessment in Triple Negative Breast Carcinoma; TMA vs Whole Sections

Introduction/Objective Tumor infiltrating lymphocytes (TILs) assessment is recognized as an important prognostic and therapeutic biomarker in several tumor types including triple negative breast cancer (TNBC). The assessment of TILs faces several challenges including low to intermediate interobserver concordance. The use of tissue microarray (TMA) in TILs assessment and its relationship/concordance with whole sections have been rarely studied. The objective of this study is to evaluate the reproducibility of TILS assessment in TNBC among various users and to compare TILS assessment using TMA vs whole tissue sections (WS). Methods/Case Report Hematoxylin and eosin (H&E)-stained sections of the TMAs were prepared and assessed for quality and tumor adequacy. Whole-section H&E-stained slides for all cases were retrieved and independently scored for tumor-infiltrating lymphocytes (TILs) by one junior and two senior pathologists. The assessment followed the guidelines of the International TILs Working Group. TILs scores were categorized into three groups: Low: <20%; Intermediate: 20–49%; and High: ≥50%. A total of 100 cases were collected; however, 76 cases were evaluable after excluding inadequate samples or cases with missing information. Fleiss’ Kappa was used to assess interobserver agreement among the three raters for both WS and TMA datasets. The Intraclass Correlation Coefficient (ICC) was used to assess the degree of agreement among the three raters for continuous variables before categorization and Cohen’s Kappa was applied to both WS and TMA datasets to assess interobserver agreement between any 2 raters. Results The interobserver agreement for WS analysis (Cohen’s Kappa) was fair while for TMA was moderate. The ICC also showed moderate agreement among the three raters. Cohen’s Kappa for TMA vs WS for each of the 3 observers ranged from fair to strong. Fleiss’ Kappa showed fair agreement for WS vs TMA. Conclusion In conclusion interobserver variability in TIL scoring remains a challenge. TMAs improve consistency but at the cost of reduced correlation with full-section assessments.