Interobserver variability in upfront dichotomous histopathological assessment of ductal carcinoma in situ of the breast: the DCISion study

Abstract

Histopathological assessment of ductal carcinoma in situ (DCIS), a non-obligate precursor of invasive breast cancer, is characterized by considerable inter-observer variability. Previously, post hoc dichotomization of multi-categorical variables was used to determine the 'ideal' cut-offs for dichotomous assessment. The present international multi-center study evaluated inter-observer variability among 39 pathologists who performed upfront dichotomous evaluation of 149 consecutive DCIS.All pathologists independently assessed nuclear atypia, necrosis, solid DCIS architecture, calcifications, stromal architecture and lobular cancerization in one digital slide per lesion. Stromal inflammation was assessed semi-quantitatively. Tumor-infiltrating lymphocytes (TILs) were quantified as percentages and dichotomously assessed with a cut-off 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 inter-observer variability. Stromal inflammation (KA = 0,564), dichotomously assessed TILs (KA = 0,520) and comedonecrosis (KA = 0,539) showed slightly lower inter-observer disagreement. Solid DCIS architecture (KA = 0,602) and calcifications (KA = 0,676) presented with the lowest inter-observer variability. Semi-quantitative assessment of stromal inflammation resulted in a slightly higher inter-observer concordance than upfront dichotomous TILs assessment (KA = 0,564 versus KA = 0,520). High stromal inflammation corresponded best with dichotomously assessed TILs when the cut-off was set at 10% (kappa = 0,881). Nevertheless, a post hoc TILs cut-off set at 20% resulted in the highest inter-observer agreement (KA = 0,669).Despite upfront dichotomous evaluation, the inter-observer variability remains considerable and is at most acceptable, although it varies among the different histopathological features. Future studies should investigate its impact on DCIS prognostication. Forthcoming machine learning algorithms may be useful to tackle this substantial diagnostic challenge.

Pathological features of 11,337 patients with primary ductal carcinoma in situ (DCIS) and subsequent events: results from the UK Sloane Project

“…21 An alternative two-tier grading system (high vs non-high grade) has been proposed; 22 however, one recent international study of 149 DCIS cases assessed by 39 breast pathologists using such a dichotomous grading system still showed only moderate agreement (kappa = 0.422). 23 As several worldwide trials are presently being undertaken of active surveillance vs surgical intervention for low-risk DCIS, 12 including the LORIS, 9 LORD 10 and the COMET trials 11 , the reproducible grading of DCIS is increasingly important for clinical management and methods for improving reproducibility require further exploration.…”

Prognostic value of histopathological DCIS features in a large-scale international interrater reliability study

“…We therefore firstly would suggest to objectify histological grading by using a numerical semi-quantitative scoring system which separately evaluates each of these features, analogous to the modified Bloom and Richardson grading system for IBC [ 42 , 43 ]. Dichotomous scoring systems may further improve reliability and prognostic value and should be further explored evaluating different cut-offs [ 44 , 45 ].…”

Grading variation in 2,934 patients with ductal carcinoma in situ of the breast: the effect of laboratory- and pathologist-specific feedback reports

“…Furthermore, in comparison to grading of invasive breast cancer, which is performed according to the modified Bloom and Richardson grading classification (Elston-Ellis modification) [33,34], with scoring of the three subcategories (tubular differentiation, nuclear polymorphism and mitotic count) grading of DCIS is less standardized. Recently, dichotomous histopathological assessment of ductal carcinoma was studied as an alternative with (better) acceptable degrees of interobserver variability, however, interobserver variation remained considerable and at best acceptable [35]. In addition, other recent data showed that even among 35 expert breast pathologists, the threshold for comedonecrosis is highly variable [36].…”