Comprehensive Characterization of Invasive Mammary Carcinoma with Lobular Features: Integrating Morphology and E-cadherin Immunohistochemistry Patterns

Background Breast cancer treatment prioritizes molecular subtypes over histologic types. However, considering the unique biological behavior of invasive lobular carcinoma (ILC), its diagnosis is crucial for patient management. Therefore, this study aimed to review breast cancer cases, focusing on the E-cadherin patterns and lobular morphology of cases misclassified in the original reports. Methods A comprehensive review was conducted on 481 breast cancer biopsy cases diagnosed as invasive breast carcinoma of no special type (IBC-NST) or ILC with E-cadherin staining. These cases were categorized into six groups based on tumor morphology (ductal/lobular) and E-cadherin expression pattern (membranous/loss/aberrant): 1) ductal/membranous, 2) lobular/loss, 3) lobular/aberrant, 4) Mixed, 5) ductal/loss or aberrant, and 6) lobular/membranous. Results In 211 cases (43.8%), an E-cadherin pattern indicating ILC (loss and aberrant) was observed alongside lobular morphology, representing 5.52% of all breast cancer biopsies during the relevant period. Moreover, 181 cases (37.6%) showed a membranous pattern with ductal morphology, four (0.8%) were mixed IBC-NST and ILC, and 85 (17.7%) exhibited discordance between morphology and E-cadherin expression. Notably, only 15 of 58 cases (25.9%) identified as ILC based on aberrant patterns were initially diagnosed as ILC. Among 58 cases showing membranous pattern with lobular morphology, only two were diagnosed as ILC in the original reports. Similarly, of 27 cases with loss or aberrant pattern with ductal morphology, only nine (33.3%) were initially diagnosed as IBC-NST. Conclusions In real-world practice, diagnosing ILC often heavily depends on E-cadherin results. This study emphasizes the need for diagnostic clarification in cases with discordance between morphology and E-cadherin patterns.