Stromal tumour infiltrating lymphocytes (sTILs) are a strong prognostic marker in triple negative breast cancer (TNBC). Consistency scoring sTILs is good and was excellent when an internet-based scoring aid developed by the TIL-WG was used to score cases in a reproducibility study. This study aimed to evaluate the reproducibility of sTILs assessment using this scoring aid in cases from routine practice and to explore the potential of the tool to overcome variability in scoring. Twenty-three breast pathologists scored sTILs in digitized slides of 49 TNBC biopsies using the scoring aid. Subsequently, fields of view (FOV) from each case were selected by one pathologist and scored by the group using the tool. Inter-observer agreement was good for absolute sTILs (ICC 0.634, 95% CI 0.539-0.735, p < 0.001) but was poor to fair using binary cutpoints. sTILs heterogeneity was the main contributor to disagreement. When pathologists scored the same FOV from each case, inter-observer agreement was excellent for absolute sTILs (ICC 0.798, 95% CI 0.727-0.864, p < 0.001) and good for the 20% (ICC 0.657, 95% CI 0.561-0.756, p < 0.001) and 40% (ICC 0.644, 95% CI 0.546-0.745, p < 0.001) cutpoints. However, there was a wide range of scores for many cases. Reproducibility scoring sTILs is good when the scoring aid is used. Heterogeneity is the main contributor to variance and will need to be overcome for analytic validity to be achieved.

2nd Department of Pathology Semmelweis University Budapest Üllői út 93 1091 Budapest Hungary

Department of Clinical Pathology Sahlgrenska University Hospital 41345 Gothenburg Sweden

Department of Histopathology Cambridge University Hospitals National Health Service Foundation Trust Cambridge CB2 0QQ UK

Department of Medical Sciences University of Turin 10126 Turin Italy

Department of Pathology Bács Kiskun County Teaching Hospital 6000 Kecskemét Hungary

Department of Pathology Helsinki University Central Hospital 00029 Helsinki Finland

Department of Pathology Klinikum Donaustadt 1090 Vienna Austria

Department of Pathology Medical University of Vienna Währinger Gürtel 18 20 1090 Vienna Austria

Department of Pathology Riga Stradins University LV 1007 Riga Latvia

Department of Pathology School of Medicine University of Patras 26504 Rion Greece

Department of Surgical Pathology Zealand University Hospital 4000 Roskilde Denmark

Diagnostic and Research Institute of Pathology Medical University of Graz 8010 Graz Austria

Discipline of Pathology Lambe Institute for Translational Research School of Medicine National University of Ireland Galway H91 TK33 Galway Ireland

Division of Pathological Anatomy Department of Health Sciences University of Florence 50134 Florence Italy

Irish National Breast Screening Programme BreastCheck St Vincent's University Hospital D04 T6F4 Dublin Ireland

Laboratório de Anatomia Patológica Instituto Politécnico de Coimbra 3000 075 Coimbra Portugal

Laboratory of Translational Cell and Tissue Research Department of Imaging and Pathology University Hospitals Leuven 3000 Leuven Belgium

National Institute for Health Research Cambridge Biomedical Research Centre Cambridge CB2 0QQ UK

Pathology Department Herlev University Hospital DK 2730 Herlev Denmark

School of Mathematics Statistics and Applied Mathematics National University of Ireland Galway H91 TK33 Galway Ireland

School of Medicine University College Dublin D04 V1W8 Dublin Ireland

The Fingerland Department of Pathology Charles University Medical Faculty and University Hospital 50003 Hradec Kralove Czech Republic

Tumor Pathology Department Maria Sklodowska Curie National Research Institute of Oncology Gliwice Branch 44 102 Gliwice Poland

UDIAT Centre Diagnòstic Pathology Department Institut Universitari Parc Taulí UAB Parc Taulí 1 08205 Sabadell Spain

Unit of Anatomic Pathology Department of Biomedical and Neuromotor Sciences University of Bologna Bellaria Hospital 40139 Bologna Italy

Unit of Pathology Candiolo Cancer Institute FPO IRCCS 10060 Candiolo Italy

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ONEST (Observers Needed to Evaluate Subjective Tests) Analysis of Stromal Tumour-Infiltrating Lymphocytes (sTILs) in Breast Cancer and Its Limitations