Department of Pathology, Erasmus Medical Centre, Rotterdam, The Netherlands.
Department of Pathology, Ghent University Hospital, Ghent, Belgium.
Histopathology. 2018 Dec;73(6):923-932. doi: 10.1111/his.13741. Epub 2018 Oct 22.
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.
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.
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.
用于乳腺导管原位癌（DCIS）的稳健预后标志物需要高重现性，因此需要低观察者间变异性。本研究的目的是比较 13 位病理学家之间的观察者间变异性，以便确定稳健的组织病理学特征。
为 153 例 DCIS 病例选择了一个代表性的苏木精和伊红染色载玻片。所有病理学家均独立评估核级、导管内钙化、坏死、实性生长、间质变化、间质炎症和大汗腺分化。所有特征均进行分类评估。Krippendorff's alpha 用于评估总体观察者间一致性。对于每个观察者对，计算 Cohen's kappa 进一步探索观察者间变异性。坏死、钙化和间质炎症的一致性最高。实性生长、核级和间质变化的评估结果一致性较低。大汗腺分化的一致性较差。每个观察者对的kappa 值确定了多类别变量二分法的“理想”截止值。例如，核级的“非高 versus 高”比“低 versus 非低”的一致性更高。“无/轻度”与“中度/广泛”间质炎症的一致性明显高于其他二分截止值。
DCIS 组织病理学特征的二分评估在病理学家之间产生了中等至较大的一致性。未来关于 DCIS 预后标志物的研究应考虑这种观察者间变异性程度，以定义分类评估的组织病理学特征的截止值，因为在日常临床实践中，重现性对于稳健的预后标志物至关重要。可以考虑基于组织病理学特征的两阶段分级为 DCIS 制定新的预后指数。未来的研究应探索这种两阶段评估的预后潜力。
