Nuclear morphology in breast lesions: refining its assessment to improve diagnostic concordance.

BACKGROUND Although evaluation of nuclear morphology plays a crucial role in the diagnosis and categorisation of breast lesions, the criteria used to assess nuclear atypia rely on the subjective evaluation of several features that may result in inter- and intra-observer variation. This study aims to refine the definitions of cytonuclear features in various breast lesions. METHODS ImageJ was used to assess the nuclear morphological features including nuclear diameter, axis length, perimeter, area, circularity, and roundness in 160 breast lesions comprising ductal carcinoma in situ (DCIS), invasive breast carcinoma of no special type (IBC-NST), tubular carcinoma, usual ductal hyperplasia (UDH), columnar cell change (CCC) and flat epithelial atypia (FEA). Reference cells included normal epithelial cells, red blood cells (RBCs) and lymphocytes. RESULTS Reference cells showed size differences not only between normal epithelial cells and RBCs but also between RBCs in varied-sized blood vessels. Nottingham grade nuclear pleomorphism scores 1 and 3 cut-offs in IBC, compared to normal epithelial cells, were 1.4x that of mean maximum Feret's diameter and 2.4x that of mean nuclear area, respectively. Nuclear morphometrics were significantly different in low-grade IBC-NST vs. tubular carcinoma, low-grade DCIS vs. UDH, and in CCC vs. FEA. No differences in the nuclear features between grade matched DCIS and IBC were identified. CONCLUSION This study provides a guide for the assessment of nuclear atypia in breast lesions, refines the comparison with reference cells and highlights the potential diagnostic value of image analysis tools in the era of digital pathology.