Rakha, Emad A.Badve, SunilEusebi, VincenzoReis-Filho, Jorge S.Fox, Stephen B.Dabbs, David J.Decker, ThomasHodi, ZsoltIchihara, ShuLee, Andrew HS.Palacios, JoséRichardson, Andrea L.Vincent-Salomon, AnneSchmitt, Fernando C.Tan, Puay-HoonTse, Gary M.Ellis, Ian O.2017-06-052017-06-052016-08-16Rakha, E. A., Badve, S., Eusebi, V., Reis-Filho, J. S., Fox, S. B., Dabbs, D. J., … Ellis, I. O. (2016). Breast lesions of uncertain malignant nature and limited metastatic potential: Proposals to improve their recognition and clinical management. Histopathology, 68(1), 45–56. http://doi.org/10.1111/his.12861https://hdl.handle.net/1805/12850Breast lesions comprise a family of heterogeneous entities with variable patterns of presentation, morphology and clinical behaviour. The majority of breast lesions are classified traditionally into benign and malignant conditions and their behaviour can, in the vast majority of cases, be predicted with a reasonable degree of accuracy. However, there remain lesions which show borderline features and lie in a grey zone between benign and malignant, as their behaviour cannot be predicted reliably. Defined pathological categorization of such lesions is challenging, and for some entities is recognized to be subjective and include a range of diagnoses, and forms of terminology, which may trigger over- or undertreatment. The rarity of these lesions makes the acquisition of clinical evidence problematic and limits the development of a sufficient evidence base to support informed decision-making by clinicians and patients. Emerging molecular evidence is providing a greater understanding of the biology of these lesions, but this may or may not be reflected in their clinical behaviour. Herein we discuss some breast lesions that are associated with uncertainty regarding classification and behaviour, and hence management. These include biologically invasive malignant lesions associated with uncertain metastatic potential, such as low-grade adenosquamous carcinoma, low-grade fibromatosis-like spindle cell carcinoma and encapsulated papillary carcinoma. Other lesions of uncertain malignant nature remain, such as mammary cylindroma, atypical microglandular adenosis, mammary pleomorphic adenoma and infiltrating epitheliosis. The concept of categories of (1) breast lesions of uncertain malignant nature and (2) breast lesions of limited metastatic potential are proposed with details of which histological entities could be included in each category, and their management implications are discussed.en-USPublisher PolicyBreast lesionsDifferentiationBehaviorTerminologyLesions of uncertain malignant potentialLesions of uncertain metastatic potentialBreast lesions of uncertain malignant nature and limited metastatic potential: proposals to improve their recognition and clinical managementArticle