Contextual interpretation of luminal phenotype in low-grade breast epithelial proliferations

Diagnosing low-grade intraductal epithelial proliferations and distinguishing hyperplasia from neoplasia has traditionally relied on well-established morphological and immunophenotypic criteria. However, in routine practice, differentiating luminal epithelial proliferations that are not necessarily clonal from bona fide neoplastic precursor lesions remains challenging. In specific clinical scenarios, such as gynaecomastia, adolescent breast tissue and fibroepithelial lesions, epithelial proliferations may appear morphologically and immunophenotypically worrisome for neoplasia, yet the clinical context supports a non-neoplastic process. Rather than representing conventional clonal neoplasia, these changes may reflect hormonally driven or stromal-induced luminal differentiation and often lack the sharp demarcation typical of conventional neoplasia. This narrative review delineates these context-dependent diagnostic pitfalls and proposes an integrated framework that emphasises architectural features, clonal demarcation and the clinical setting. By positioning these borderline lesions within a biological continuum and refining diagnostic thresholds in context, this approach aims to improve diagnostic reproducibility, mitigate the risk of overdiagnosis and support appropriate, risk-adapted patient management.