TY - JOUR
T1 - Interobserver variability in upfront dichotomous histopathological assessment of ductal carcinoma in situ of the breast
T2 - the DCISion study
AU - Dano, Hélène
AU - Altinay, Serdar
AU - Arnould, Laurent
AU - Bletard, Noella
AU - Colpaert, Cecile
AU - Dedeurwaerdere, Franceska
AU - Dessauvagie, Benjamin
AU - Duwel, Valérie
AU - Floris, Giuseppe
AU - Fox, Stephen
AU - Gerosa, Clara
AU - Jaffer, Shabnam
AU - Kurpershoek, Eline
AU - Lacroix-Triki, Magali
AU - Laka, Andoni
AU - Lambein, Kathleen
AU - MacGrogan, Gaëtan Marie
AU - Marchió, Caterina
AU - Martinez, Dolores Martin
AU - Nofech-Mozes, Sharon
AU - Peeters, Dieter
AU - Ravarino, Alberto
AU - Reisenbichler, Emily
AU - Resetkova, Erika
AU - Sanati, Souzan
AU - Schelfhout, Anne Marie
AU - Schelfhout, Vera
AU - Shaaban, Abeer M.
AU - Sinke, Renata
AU - Stanciu-Pop, Claudia Maria
AU - Stobbe, Claudia
AU - van Deurzen, Carolien H.M.
AU - Van de Vijver, Koen
AU - Van Rompuy, Anne Sophie
AU - Verschuere, Stephanie
AU - Vincent-Salomon, Anne
AU - Wen, Hannah
AU - Bouzin, Caroline
AU - Galant, Christine
AU - Van Bockstal, Mieke R.
N1 - Publisher Copyright:
© 2019, The Author(s), under exclusive licence to United States & Canadian Academy of Pathology.
PY - 2020/3/1
Y1 - 2020/3/1
N2 - Histopathological assessment of ductal carcinoma in situ, a nonobligate precursor of invasive breast cancer, is characterized by considerable interobserver variability. Previously, post hoc dichotomization of multicategorical variables was used to determine the “ideal” cutoffs for dichotomous assessment. The present international multicenter study evaluated interobserver variability among 39 pathologists who performed upfront dichotomous evaluation of 149 consecutive ductal carcinomas in situ. All pathologists independently assessed nuclear atypia, necrosis, solid ductal carcinoma in situ architecture, calcifications, stromal architecture, and lobular cancerization in one digital slide per lesion. Stromal inflammation was assessed semiquantitatively. Tumor-infiltrating lymphocytes were quantified as percentages and dichotomously assessed with a cutoff at 50%. Krippendorff’s alpha (KA), Cohen’s kappa and intraclass correlation coefficient were calculated for the appropriate variables. Lobular cancerization (KA = 0.396), nuclear atypia (KA = 0.422), and stromal architecture (KA = 0.450) showed the highest interobserver variability. Stromal inflammation (KA = 0.564), dichotomously assessed tumor-infiltrating lymphocytes (KA = 0.520), and comedonecrosis (KA = 0.539) showed slightly lower interobserver disagreement. Solid ductal carcinoma in situ architecture (KA = 0.602) and calcifications (KA = 0.676) presented with the lowest interobserver variability. Semiquantitative assessment of stromal inflammation resulted in a slightly higher interobserver concordance than upfront dichotomous tumor-infiltrating lymphocytes assessment (KA = 0.564 versus KA = 0.520). High stromal inflammation corresponded best with dichotomously assessed tumor-infiltrating lymphocytes when the cutoff was set at 10% (kappa = 0.881). Nevertheless, a post hoc tumor-infiltrating lymphocytes cutoff set at 20% resulted in the highest interobserver agreement (KA = 0.669). Despite upfront dichotomous evaluation, the interobserver variability remains considerable and is at most acceptable, although it varies among the different histopathological features. Future studies should investigate its impact on ductal carcinoma in situ prognostication. Forthcoming machine learning algorithms may be useful to tackle this substantial diagnostic challenge.
AB - Histopathological assessment of ductal carcinoma in situ, a nonobligate precursor of invasive breast cancer, is characterized by considerable interobserver variability. Previously, post hoc dichotomization of multicategorical variables was used to determine the “ideal” cutoffs for dichotomous assessment. The present international multicenter study evaluated interobserver variability among 39 pathologists who performed upfront dichotomous evaluation of 149 consecutive ductal carcinomas in situ. All pathologists independently assessed nuclear atypia, necrosis, solid ductal carcinoma in situ architecture, calcifications, stromal architecture, and lobular cancerization in one digital slide per lesion. Stromal inflammation was assessed semiquantitatively. Tumor-infiltrating lymphocytes were quantified as percentages and dichotomously assessed with a cutoff at 50%. Krippendorff’s alpha (KA), Cohen’s kappa and intraclass correlation coefficient were calculated for the appropriate variables. Lobular cancerization (KA = 0.396), nuclear atypia (KA = 0.422), and stromal architecture (KA = 0.450) showed the highest interobserver variability. Stromal inflammation (KA = 0.564), dichotomously assessed tumor-infiltrating lymphocytes (KA = 0.520), and comedonecrosis (KA = 0.539) showed slightly lower interobserver disagreement. Solid ductal carcinoma in situ architecture (KA = 0.602) and calcifications (KA = 0.676) presented with the lowest interobserver variability. Semiquantitative assessment of stromal inflammation resulted in a slightly higher interobserver concordance than upfront dichotomous tumor-infiltrating lymphocytes assessment (KA = 0.564 versus KA = 0.520). High stromal inflammation corresponded best with dichotomously assessed tumor-infiltrating lymphocytes when the cutoff was set at 10% (kappa = 0.881). Nevertheless, a post hoc tumor-infiltrating lymphocytes cutoff set at 20% resulted in the highest interobserver agreement (KA = 0.669). Despite upfront dichotomous evaluation, the interobserver variability remains considerable and is at most acceptable, although it varies among the different histopathological features. Future studies should investigate its impact on ductal carcinoma in situ prognostication. Forthcoming machine learning algorithms may be useful to tackle this substantial diagnostic challenge.
UR - http://www.scopus.com/inward/record.url?scp=85073988323&partnerID=8YFLogxK
U2 - 10.1038/s41379-019-0367-9
DO - 10.1038/s41379-019-0367-9
M3 - Article
C2 - 31534203
AN - SCOPUS:85073988323
SN - 0893-3952
VL - 33
SP - 354
EP - 366
JO - Modern Pathology
JF - Modern Pathology
IS - 3
ER -