Attenuated to absent myoepithelial cells in benign and non-invasive breast lesions-potential diagnostic pitfalls

Loss of the myoepithelial cell (MEC) layer at the epithelial-stromal interface is a key histological marker of invasion in malignant breast lesions. However, certain benign and non-invasive entities may exhibit diminished or absent MECs, creating significant diagnostic challenges and occasionally leading to erroneous interpretation as invasive carcinoma. Despite their bland cytology, some of these lesions, such as microglandular adenosis (MGA) and pleomorphic adenoma, display infiltrative-like growth patterns. Loss of MECs around proliferating epithelium-lined clefts accompanied by spindled stroma in malignant phyllodes tumours may mimic metaplastic carcinoma. Atypical MGA lacking MECs may resemble acinic cell carcinoma. Diagnostic clues include the benign or hyperplastic appearance of the lesional cells, their immunoprofile and the absence of a sudden transition between areas with and without peripheral MECs. Awareness of such entities is key to preventing overdiagnosis and inappropriate clinical management. This review discusses these lesions, highlights their differential diagnoses and outlines key diagnostic pitfalls. Practical guidance is also provided on the optimal use and interpretation of myoepithelial markers to improve diagnostic accuracy and reduce the risk of misclassification.