High-resolution microCT to assess breast microcalcification morphometry by histologic lesion subtype and radiologic classification.

Purpose: To assess associations of 3D morphometry of breast calcifications, determined using high-resolution microCT, with underlying histopathology and evaluate the potential for classifying tissue calcifications as an aid in optimizing identification and diagnosis of the most severe pathology in a biopsy.

Methods: We compared morphometry of calcifications in tissue blocks (n = 156) of benign breast disease (n = 74), ductal carcinoma in situ (n = 39), and ductal carcinoma in situ with invasive breast cancer (n = 43) using (10 µm) microCT. Matched sections were reviewed microscopically to define lesion(s) in which calcifications were embedded. 3D reconstructions of calcifications were reviewed independently by two masked radiologists to assess the need for biopsy and calcification morphology. Calcification morphometry was compared to pathologic diagnosis using linear mixed models.

Results: A total of 12,216 calcifications (IQR 9-66 per specimen) were analyzed. Individual breast cancer-associated calcifications were significantly larger than benign breast disease-associated calcifications (p_adjusted = 0.012) and calcification volume was positively associated with grade of ductal carcinoma in situ (P_trend = 0.009). Structure model index revealed more cylindrical shape in breast cancer calcifications versus benign breast disease calcifications (p_adjusted = 0.008). Re-analysis by the specific microscopic lesion containing the calcification, rather than the most severe diagnosis per biopsy, strengthened associations. Radiologists agreed on biopsy recommendation in 92% of microCT images, while achieving sensitivities of 53.1% and 54.3%. and specificities of 50.0% and 54.1%.

Conclusion: Our analysis provides proof-of-concept that morphometry of tissue calcifications varies by lesion type, suggesting that future studies may enable development of a pathologic classification linked to diagnosis and mammographic findings.