Bridging The Gap: Assessing Interobserver Variability in Tumour-Infiltrating Lymphocyte (TIL) Scoring for Triple-Negative Breast Cancer

Background: Tumour-infiltrating lymphocytes (TILs) are emerging as a crucial prog-nostic biomarker in triple-negative breast cancer (TNBC). However, their clinical utility remains constrained by the subjectivity and interobserver variability of manual scoring, despite standardization efforts by the International TILs Working Group (TIL-WG). This study aimed to evaluate the interobserver agreement among pathologists in scoring stromal and intratumoral TILs from H&E-stained TNBC slides and to identify contrib-uting histological factors. Methods: Two consultant pathologists at Hospital Canselor Tuanku Muhriz, Kuala Lumpur independently assessed 64 TNBC cases using TIL-WG guidelines. Interobserver agreement was quantified using intraclass correlation coeffi-cient (ICC) and Cohen's Kappa coefficient. Cases with over 10% scoring discrepancies underwent review by a third pathologist and a consensus discussion was held to explore the underlying confounders. Results: Our results showed moderate interobserver agreement for stromal TILs (ICC = 0.58) and strong agreement for intratumoral TILs (ICC = 0.71). Significant variability was attributed to three main confounding variables: heterogeneous TIL distribution, poorly-defined tumor-stroma interface and focal dense lymphoid infiltrates. Conclusions: These findings underscore the critical need for standardized TILs assessment criteria advocating for the adoption of AI-based scoring method to overcome interobserver variability and enhance the reproducibility of eval-uations.