Diagnostic Concordance Among Pathologists Interpreting Breast Biopsy Specimens

Abstract

IMPORTANCE A breast pathology diagnosis provides the basis for clinical treatment and management decisions; however, its accuracy is inadequately understood. OBJECTIVES To quantify the magnitude of diagnostic disagreement among pathologists compared with a consensus panel reference diagnosis and to evaluate associated patient and pathologist characteristics. DESIGN, SETTING, AND PARTICIPANTS Study of pathologists who interpret breast biopsies in clinical practices in 8 US states. EXPOSURES Participants independently interpreted slides between November 2011 and May 2014 from test sets of 60 breast biopsies (240 total cases, 1 slide per case), including 23 cases of invasive breast cancer, 73 ductal carcinoma in situ (DCIS), 72 with atypical hyperplasia (atypia), and 72 benign cases without atypia. Participants were blinded to the interpretations of other study pathologists and consensus panel members. Among the 3 consensus panel members, unanimous agreement of their independent diagnoses was 75%, and concordance with the consensus-derived reference diagnoses was 90.3%. MAIN OUTCOMES AND MEASURES The proportions of diagnoses overinterpreted and underinterpreted relative to the consensus-derived reference diagnoses were assessed. RESULTS Sixty-five percent of invited, responding pathologists were eligible and consented to participate. Of these, 91% (N = 115) completed the study, providing 6900 individual case diagnoses. Compared with the consensus-derived reference diagnosis, the overall concordance rate of diagnostic interpretations of participating pathologists was 75.3% (95% CI, 73.4%–77.0%; 5194 of 6900 interpretations). Consensus ReferenceDiagnosis Pathologist Interpretation vs Consensus-Derived Reference Diagnosis, % (95% CI) No. ofInterpretations Overall ConcordanceRate OverinterpretationRate UnderinterpretationRate Benign without atypia 2070 87 (85–89) 13 (11–15) Atypia 2070 48 (44–52) 17 (15–21) 35 (31–39) DCIS 2097 84 (82–86) 3 (2–4) 13 (12–15) Invasive carcinoma 663 96 (94–97) 4 (3–6) Disagreement with the reference diagnosis was statistically significantly higher among biopsies from women with higher (n = 122) vs lower (n = 118) breast density on prior mammograms (overall concordance rate, 73% [95% CI, 71%–75%] for higher vs 77% [95% CI, 75%–80%] for lower, P < .001), and among pathologists who interpreted lower weekly case volumes (P < .001) or worked in smaller practices (P = .034) or nonacademic settings (P = .007). CONCLUSIONS AND RELEVANCE In this study of pathologists, in which diagnostic interpretation was based on a single breast biopsy slide, overall agreement between the individual pathologists’ interpretations and the expert consensus–derived reference diagnoses was 75.3%, with the highest level of concordance for invasive carcinoma and lower levels of concordance for DCIS and atypia. Further research is needed to understand the relationship of these findings with patient management.

Region of interest identification and diagnostic agreement in breast pathology

“…Previous studies have shown that breast atypia is consistently the most challenging diagnostic category for pathologists. 3,[12][13][14] Thus, even if a pathologist reviews a critical image region, recognizing architectural and cytologic features of atypia and accurately assimilating these features into a diagnostic rubric can be challenging.…”

“…The methods for test case identification and the development and recruitment of pathologists have been previously described. 3,7 Briefly, single, representative diagnostic slides from excisional or core breast biopsies of 180 women were included in this pilot study. Each slide was digitally scanned (iScan Coreo, Ventana Medical Systems, Tucson, AZ, USA), and a whole slide image (WSI) was created, allowing the digital virtual slide to be viewed, magnified, and annotated on a computer using a web-based viewer.…”

“…Three experienced breast pathologists, who were involved in the original B-Path study, 3,7 independently interpreted the 180 cases in the digital WSI format using a standardized diagnosis reporting form and a web-based viewer. Each expert recorded an independent diagnosis and digitally marked an ROI that best exemplified the critical features on the slide, supporting the most severe diagnosis.…”

“…Each year, millions of breast biopsies are performed, yet interpreting such specimens is considered to be one of the more challenging areas in pathology. [1][2][3][4][5] While evaluating a breast biopsy slide, it is critical that the pathologist identifies and then analyzes regions of potential diagnostic interest that might support criteria for diagnosing breast cancer or diagnosing risk-associated non-invasive breast lesions. Pathologists use a complex set of skills to establish a histopathological diagnosis when interpreting a biopsy slide.…”

Automated mitosis detection in histopathology based on non-gaussian modeling of complex wavelet coefficients

“…Manual counting of mitosis is a tedious process and often prone to inter-and intra-reader variations. A recent concordance study for quantifying the magnitude of diagnostic disagreement among pathologists on breast biopsy specimens reported 27.7% overall disagreement between the individual pathologists' interpretations and the expert consensus-derived reference diagnoses [5]. A mitosis has four main phases of prophase, metaphase, anaphase and telophase, and exhibits highly variable appearance.…”