The diagnostic challenge of low-grade ductal carcinoma in situ.

BACKGROUND: Diagnostic agreement among pathologists is 84% for ductal carcinoma in situ (DCIS). Studies of interpretive variation according to grade are limited. METHODS: A national sample of 115 pathologists interpreted 240 breast pathology test set cases in the Breast Pathology Study and their interpretations were compared to expert consensus interpretations. We assessed agreement of pathologists\u27 interpretations with a consensus reference diagnosis of DCIS dichotomised into low- and high-grade lesions. Generalised estimating equations were used in logistic regression models of rates of under- and over-interpretation of DCIS by grade. RESULTS: We evaluated 2097 independent interpretations of DCIS (512 low-grade DCIS and 1585 high-grade DCIS). Agreement with reference diagnoses was 46% (95% confidence interval [CI] 42-51) for low-grade DCIS and 83% (95% CI 81-86) for high-grade DCIS. The proportion of reference low-grade DCIS interpretations over-interpreted by pathologists (i.e. categorised as either high-grade DCIS or invasive cancer) was 23% (95% CI 19-28); 30% (95% CI 26-34) were interpreted as a lower diagnostic category (atypia or benign proliferative). Reference high-grade DCIS was under-interpreted in 14% (95% CI 12-16) of observations and only over-interpreted 3% (95% CI 2-4). CONCLUSION: Grade is a major factor when examining pathologists\u27 variability in diagnosing DCIS, with much lower agreement for low-grade DCIS cases compared to high-grade. These findings support the hypothesis that low-grade DCIS poses a greater interpretive challenge than high-grade DCIS, which should be considered when developing DCIS management strategies