Inter- and intra-laboratory variation in grading of ductal carcinoma in situ of the breast: A nationwide study in the Netherlands

Abstract Background: A considerable part of ductal carcinoma in situ (DCIS) lesions may never progress into invasive breast cancer. Yet, standard treatment consists of surgical excision. Trials aim to identify a subgroup of low-risk DCIS that, under active surveillance, can safely forgo surgical treatment. These low-risk subgroups are in all trials solely based on histologic grade, which highlights the importance of accurate, consistent, and reproducible grading by pathologists. To improve standardization, we aimed to gain insight into laboratory-specific variation of DCIS grading in daily clinical practice. Materials and methods: All synoptic pathology reports of pure DCIS resection specimens between 2013-2016 were retrieved from PALGA, the nationwide Dutch Pathology Registry. Absolute differences in proportions of grade I-III between laboratories (inter-laboratory) were visualized using funnel plots, in which the proportions per laboratory are plotted against the number of DCIS per laboratory, with the national proportions per grade as target. Multivariable analysis to correct for case mix was performed by logistic regression, providing odds ratios (ORs) and 95% confidence intervals (CI) for high-grade (III) versus low-grade (I-II) DCIS per laboratory. Absolute differences of proportions of grade I-III between pathologists within laboratories (intra-laboratory) were also analyzed. Lastly, an online questionnaire was send to all pathology laboratories in the Netherlands to identify how pathologists determine histologic grade in daily clinical practice. Results: In total 4,952 DCIS cases from 36 laboratories were included, of which 12.5% were reported as grade I (range 6.1-24.4%), 39.5% as grade II (18.2-57.6%), and 48.0% as grade III (30.2-72.7%). After correction for case mix, 14 laboratories (38.9%) reported a significantly lower (n=4) or higher (n=10) proportion of high-grade DCIS than the reference laboratory. Adjusted ORs (95% CI) ranged from 0.52 (0.31-0.87) to 3.83 (1.42-10.39). Intra-laboratory analysis also showed significant differences between pathologists within 25% of the laboratories. The results of our questionnaire showed that pathologists mentioned numerous different guidelines as a reference for the histologic grading of DCIS, while 20.3% of them even stated that they grade DCIS (partially) based on intuition. Conclusion: We observed substantial inter- and intra-laboratory variation in the histologic grading of DCIS, which was not explained by differences in case mix. Therefore, there is an urgent need for nationwide standardization of grading practices, especially since the future management of DCIS may alter significantly depending on histologic grade. Citation Format: van Dooijeweert C, van Diest PJ, Willems SM, Kuijpers CC, Overbeek LI, Deckers IA. Inter- and intra-laboratory variation in grading of ductal carcinoma in situ of the breast: A nationwide study in the Netherlands [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-02-06.