Interobserver Variability in Ductal Carcinoma in Situ of the Breast

Mieke R. Van Bockstal, MD, PhD; Martine Berlière, MD, PhD; Francois P. Duhoux, MD, PhD; Christine Galant, MD, PhD


Am J Clin Pathol. 2020;154(5):596-609. 

In This Article

Abstract and Introduction


Objectives: Since most patients with ductal carcinoma in situ (DCIS) of the breast are treated upon diagnosis, evidence on its natural progression to invasive carcinoma is limited. It is estimated that around half of the screen-detected DCIS lesions would have remained indolent if they had never been detected. Many patients with DCIS are therefore probably overtreated. Four ongoing randomized noninferiority trials explore active surveillance as a treatment option. Eligibility for these trials is mainly based on histopathologic features. Hence, the call for reproducible histopathologic assessment has never sounded louder.

Methods: Here, the available classification systems for DCIS are discussed in depth.

Results: This comprehensive review illustrates that histopathologic evaluation of DCIS is characterized by significant interobserver variability. Future digitalization of pathology, combined with development of deep learning algorithms or so-called artificial intelligence, may be an innovative solution to tackle this problem. However, implementation of digital pathology is not within reach for each laboratory worldwide. An alternative classification system could reduce the disagreement among histopathologists who use "conventional" light microscopy: the introduction of dichotomous histopathologic assessment is likely to increase interobserver concordance.

Conclusions: Reproducible histopathologic assessment is a prerequisite for robust risk stratification and adequate clinical decision-making. Two-tier histopathologic assessment might enhance the quality of care.


The incidence of ductal carcinoma in situ (DCIS) of the breast has substantially increased since the introduction of screening mammography. Designated as a nonobligate precursor of invasive breast cancer of no special type, the true progression rate of screen-detected DCIS is increasingly questioned.[1,2] Since almost all patients who are diagnosed with DCIS undergo surgery, evidence on the natural progression of this heterogeneous group of preinvasive lesions is mostly limited to a relatively small series of untreated patients who were initially misdiagnosed as having benign breast disease.[3] Other indirect evidence is provided by autopsy studies and a limited number of reports on untreated (mainly elderly) patients with DCIS who either declined or were unfit to undergo surgery.[4–6] Approximately half of all recurrences after breast-conserving surgery (BCS) for DCIS are invasive cancers.[1] It is assumed that many patients with DCIS are currently overtreated.[7–9] Differentiating indolent from aggressive DCIS lesions remains an important challenge for future research.

In this review, the currently ongoing active surveillance trials for DCIS are discussed. Seven commonly used classification systems for DCIS grading are reviewed. An overview is provided on the available evidence concerning interobserver variability in the histopathologic assessment of DCIS, as well as its clinical consequences. Finally, alternative methods to cope with interobserver variability are discussed.