Table 2.

Key Features of the breast lesions of uncertain malignant nature

Entity	Key features
Infiltrating epitheliosis (IE)	IE is a rare lesion characterized by infiltrating epithelial islands, solid clusters, ducts and duct-like structures immersed in a scleroelastotic stroma. Proliferating cells feature architectural and cytological patterns and immunohistochemical profile reminiscent of those of usual ductal hyperplasia. The infiltrative nature and the lack of peripheral myoepithelial cells raise the concern that IE is a form of invasive low-grade malignant neoplasm, with some similarities to LG-ASC exist. However, the immunoprofile, benign cytonuclear features, the absence of an in situ carcinoma and focal preservation of peripheral myoepithelial cells support the current view that IE is a form of benign exaggerated hyperplastic process. No events related to a malignant behaviour have been reported in cases diagnosed as IE and the evidence to describe its nature and predict its behaviour compared to benign hyperplastic or low-grade malignant process remains lacking. Therefore the uncertain nature and behaviour of such lesions should be acknowledged.
Mammary Pleomorphic Adenoma (PA)	Breast PA is often associated with a papillary lesion similar to other low-grade MBC and adenomyoepithelioma. Despite the perceived indolent benign clinical behaviour of breast PA, local recurrences have been reported in the few published cases and cytologically malignant features characteristic of conventional mammary-type carcinomas have been demonstrated in PA and categorised as “carcinoma ex pleomorphic adenoma”. In the more common PA in the salivary gland, lymphovascular invasion and distant metastasis have been reported in histologically benign cases. Absence of peripheral myoepithelial cells is a feature of breast PA. These tumours may represent a form of low-grade indolent breast tumour that resides at the lower end of a spectrum of matrix-producing MBC featuring prominent stromal metaplastic differentiation and low-grade cytological features. These tumours are best regarded as PA-like tumours of the breast to reflect the uncertainty of their nature and behaviour
Mammary Cylindroma	These tumours may represent a variant of low grade adenoid cystic carcinomas of the breast with prominent cylindromatous differentiation. The behaviour and origin of breast cylindroma may not be the same as the dermal counterparts and breast tumours show infiltration of the surrounding tissue. Both adenoid cystic carcinoma and breast cylindroma share the same immunoprofile with triple negative phenotype, p63 and strong c-kit expression. These tumours can be considered as lesions of uncertain malignant nature to reflect the current uncertainty regarding the nature and behaviour of these tumours.
Microglandular adenosis (MGA) and atypical microglandular adenosis	Despite the infiltrative nature and the lack of peripheral myoepithelial cells around the proliferating glands of MGA, the indolent clinical behaviour in the limited number published in literature and the bland cytological features render the benign nature of MGA. However, some cases show cytonuclear atypia, frequently associated with ER-negative carcinomas, and the diffuse strong nuclear S100 positivity together with recent molecular evidence suggest that MGA is a neoplastic process. The nature and behaviour of MGA particularly when associated with atypia remain unknown and such uncertainty needs to be acknowledged.

MBC=metaplastic breast carcinoma