Mieke Van Bockstal1,2, Marcella Baldewijns3, Cécile Colpaert4, Hélène Dano5, Giuseppe Floris6,7, Christine Galant5, Kathleen Lambein8,9, Dieter Peeters3, Sofie Van Renterghem2, Anne-Sophie Van Rompuy6, Sofie Verbeke2, Stephanie Verschuere10, Jo Van Dorpe2. 1. Department of Pathology, Erasmus Medical Centre, Rotterdam, The Netherlands. 2. Department of Pathology, Ghent University Hospital, Ghent, Belgium. 3. Department of Pathology, Antwerp University Hospital, Antwerp, Belgium. 4. Department of Pathology, GZA, Antwerp, Belgium. 5. Department of Pathology, University Clinics St Luc, Brussels, Belgium. 6. Department of Pathology, University Hospitals Leuven, Leuven, Belgium. 7. Department of Imaging and Pathology, Laboratory of Translational Cell & Tissue Research, KU Leuven, Leuven, Belgium. 8. Department of Pathology, AZ St Lucas Hospital, Ghent, Belgium. 9. Department of Surgical Oncology, University Hospitals Leuven, Leuven, Belgium. 10. Department of Pathology, AZ Delta, Roeselare, Belgium.
Abstract
AIMS: Robust prognostic markers for ductal carcinoma in situ (DCIS) of the breast require high reproducibility and thus low interobserver variability. The aim of this study was to compare interobserver variability among 13 pathologists, in order to enable the identification of robust histopathological characteristics. METHODS AND RESULTS: One representative haematoxylin and eosin-stained slide was selected for 153 DCIS cases. All pathologists independently assessed nuclear grade, intraductal calcifications, necrosis, solid growth, stromal changes, stromal inflammation, and apocrine differentiation. All characteristics were assessed categorically. Krippendorff's alpha was calculated to assess overall interobserver concordance. Cohen's kappa was calculated for every observer duo to further explore interobserver variability. The highest concordance was observed for necrosis, calcifications, and stromal inflammation. Assessment of solid growth, nuclear grade and stromal changes resulted in lower concordance. Poor concordance was observed for apocrine differentiation. Kappa values for each observer duo identified the 'ideal' cut-off for dichotomisation of multicategory variables. For instance, concordance was higher for 'non-high versus high' nuclear grade than for 'low versus non-low' nuclear grade. 'Absent/mild' versus 'moderate/extensive' stromal inflammation resulted in substantially higher concordance than other dichotomous cut-offs. CONCLUSIONS: Dichotomous assessment of the histopathological features of DCIS resulted in moderate to substantial agreement among pathologists. Future studies on prognostic markers in DCIS should take into account this degree of interobserver variability to define cut-offs for categorically assessed histopathological features, as reproducibility is paramount for robust prognostic markers in daily clinical practice. A new prognostic index for DCIS might be considered, based on two-tier grading of histopathological features. Future research should explore the prognostic potential of such two-tier assessment.
AIMS: Robust prognostic markers for ductal carcinoma in situ (DCIS) of the breast require high reproducibility and thus low interobserver variability. The aim of this study was to compare interobserver variability among 13 pathologists, in order to enable the identification of robust histopathological characteristics. METHODS AND RESULTS: One representative haematoxylin and eosin-stained slide was selected for 153 DCIS cases. All pathologists independently assessed nuclear grade, intraductal calcifications, necrosis, solid growth, stromal changes, stromal inflammation, and apocrine differentiation. All characteristics were assessed categorically. Krippendorff's alpha was calculated to assess overall interobserver concordance. Cohen's kappa was calculated for every observer duo to further explore interobserver variability. The highest concordance was observed for necrosis, calcifications, and stromal inflammation. Assessment of solid growth, nuclear grade and stromal changes resulted in lower concordance. Poor concordance was observed for apocrine differentiation. Kappa values for each observer duo identified the 'ideal' cut-off for dichotomisation of multicategory variables. For instance, concordance was higher for 'non-high versus high' nuclear grade than for 'low versus non-low' nuclear grade. 'Absent/mild' versus 'moderate/extensive' stromal inflammation resulted in substantially higher concordance than other dichotomous cut-offs. CONCLUSIONS: Dichotomous assessment of the histopathological features of DCIS resulted in moderate to substantial agreement among pathologists. Future studies on prognostic markers in DCIS should take into account this degree of interobserver variability to define cut-offs for categorically assessed histopathological features, as reproducibility is paramount for robust prognostic markers in daily clinical practice. A new prognostic index for DCIS might be considered, based on two-tier grading of histopathological features. Future research should explore the prognostic potential of such two-tier assessment.
Authors: Serdar Altinay; Laurent Arnould; Noella Bletard; Cecile Colpaert; Franceska Dedeurwaerdere; Benjamin Dessauvagie; Valérie Duwel; Giuseppe Floris; Stephen Fox; Clara Gerosa; Shabnam Jaffer; Eline Kurpershoek; Magali Lacroix-Triki; Andoni Laka; Kathleen Lambein; Gaëtan Marie MacGrogan; Caterina Marchió; Dolores Martin Martinez; Sharon Nofech-Mozes; Dieter Peeters; Alberto Ravarino; Emily Reisenbichler; Erika Resetkova; Souzan Sanati; Anne-Marie Schelfhout; Vera Schelfhout; Abeer M Shaaban; Renata Sinke; Claudia Maria Stanciu-Pop; Claudia Stobbe; Carolien H M van Deurzen; Koen Van de Vijver; Anne-Sophie Van Rompuy; Stephanie Verschuere; Anne Vincent-Salomon; Hannah Wen; Hélène Dano; Caroline Bouzin; Christine Galant; Mieke R Van Bockstal Journal: Mod Pathol Date: 2019-09-18 Impact factor: 7.842
Authors: Mieke R Van Bockstal; Marie C Agahozo; Linetta B Koppert; Carolien H M van Deurzen Journal: Int J Cancer Date: 2019-05-08 Impact factor: 7.396
Authors: Esther H Lips; Jelle Wesseling; Maartje van Seijen; Katarzyna Jóźwiak; Sarah E Pinder; Allison Hall; Savitri Krishnamurthy; Jeremy Sj Thomas; Laura C Collins; Jonathan Bijron; Joost Bart; Danielle Cohen; Wen Ng; Ihssane Bouybayoune; Hilary Stobart; Jan Hudecek; Michael Schaapveld; Alastair Thompson Journal: J Pathol Clin Res Date: 2021-02-23
Authors: Eiron John Lugtu; Denise Bernadette Ramos; Alliah Jen Agpalza; Erika Antoinette Cabral; Rian Paolo Carandang; Jennica Elia Dee; Angelica Martinez; Julius Eleazar Jose; Abegail Santillan; Ruth Bangaoil; Pia Marie Albano; Rock Christian Tomas Journal: PLoS One Date: 2022-05-12 Impact factor: 3.752
Authors: Avinash Kammardi Shashiprakash; Brendon Lutnick; Brandon Ginley; Darshana Govind; Nicholas Lucarelli; Kuang-Yu Jen; Avi Z Rosenberg; Anatoly Urisman; Vighnesh Walavalkar; Jonathan E Zuckerman; Marco Delsante; Mei Lin Z Bissonnette; John E Tomaszewski; David Manthey; Pinaki Sarder Journal: Proc SPIE Int Soc Opt Eng Date: 2021-02-15
Authors: Emma J Groen; Jan Hudecek; Lennart Mulder; Maartje van Seijen; Mathilde M Almekinders; Stoyan Alexov; Anikó Kovács; Ales Ryska; Zsuzsanna Varga; Francisco-Javier Andreu Navarro; Simonetta Bianchi; Willem Vreuls; Eva Balslev; Max V Boot; Janina Kulka; Ewa Chmielik; Ellis Barbé; Mathilda J de Rooij; Winand Vos; Andrea Farkas; Natalja E Leeuwis-Fedorovich; Peter Regitnig; Pieter J Westenend; Loes F S Kooreman; Cecily Quinn; Giuseppe Floris; Gábor Cserni; Paul J van Diest; Esther H Lips; Michael Schaapveld; Jelle Wesseling Journal: Breast Cancer Res Treat Date: 2020-07-30 Impact factor: 4.872