Significant inter- and intra-laboratory variation in grading of ductal carcinoma in situ of the breast: a nationwide study of 4901 patients in the Netherlands

van Dooijeweert, C., van Diest, P. J., Willems, S. M., Kuijpers, C. C. H. J., Overbeek, L. I. H. & Deckers, I. A. G., Apr-2019, In : Breast Cancer Research and Treatment. 174, 2, p. 479-488 10 p.

Research output: Contribution to journalArticleAcademicpeer-review

  • Carmen van Dooijeweert
  • Paul J van Diest
  • Stefan M Willems
  • Chantal C H J Kuijpers
  • Lucy I H Overbeek
  • Ivette A G Deckers

PURPOSE: A considerable part of ductal carcinoma in situ (DCIS) lesions may never progress into invasive breast cancer. However, standard treatment consists of surgical excision. Trials aim to identify a subgroup of low-risk DCIS patients that can safely forgo surgical treatment based on histologic grade, which highlights the importance of accurate grading. Using real-life nationwide data, we aimed to create insight and awareness in grading variation of DCIS in daily clinical practice.

METHODS: All synoptic pathology reports of pure DCIS resection specimens between 2013 and 2016 were retrieved from PALGA, the nationwide Dutch Pathology Registry. Absolute differences in proportions of grade I-III were visualized using funnel plots. Multivariable analysis was performed by logistic regression to correct for case-mix, providing odds ratios and 95% confidence intervals for high-grade (III) versus low-grade (I-II) DCIS.

RESULTS: 4952 DCIS reports 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). Significant grading differences were also observed among pathologists within laboratories.

CONCLUSION: In this cohort of 4901 patients, we observed substantial inter- and intra-laboratory variation in DCIS grading, 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.

Original languageEnglish
Pages (from-to)479-488
Number of pages10
JournalBreast Cancer Research and Treatment
Issue number2
Publication statusPublished - Apr-2019
Externally publishedYes


  • Aged, Breast Neoplasms/pathology, Carcinoma, Intraductal, Noninfiltrating/pathology, Female, Humans, Laboratories/standards, Logistic Models, Middle Aged, Neoplasm Grading, Netherlands, Odds Ratio, Registries

ID: 124008832