Table 1.

Key Features of the breast lesions of limited metastatic potential

Entity	Key features
Encapsulated papillary carcinoma (EPC)	Characterised by fibrovascular cores covered by proliferating malignant epithelial cells forming well-circumscribed/dilated ductal profile pattern and surrounded by a thick fibrous capsule. Cystic with focal solid areas and may be multinodular. Low to intermediate grade nuclei. Typically strongly positive for nuclear ER and negative for HER2. Cases maintaining myoepithelial cells at the periphery can be considered as DCIS. However, >80% completely lack myoepithelial cells throughout and behave in an indolent invasive pattern with reported lymphovascular invasion (3%), nodal metastasis (3%) and local in-breast or chest wall recurrence (7%) occurring in cases lacking coexisting conventional-type invasive carcinomas. Current consensus is to be managed as in situ disease but rare invasive behaviour may be expected. Recurrence is associated with aggressive behaviour. Occasional cases featuring high grade nuclei or focal micropapillary pattern can be considered as invasive disease.
Solid papillary carcinoma (SPC)	Similar to EPC but features solid growth pattern and frequent neuroendocrine and mucinous differentiation, nuclear palisading and cell spindling and more often multinodular, lack peripheral fibrous capsule and associated with coexisting invasive carcinoma. Definition of invasion in SPC completely lacking myoepithelial cells and show multinodularity with closely apposed clusters/duct-like structures is often problematic. Although current consensus is to consider SPC as an in situ disease, the WHO working group define invasive SPC by the presence of geographical jigsaw pattern with more ragged and irregular margins coupled with complete lack of myoepithelial cells. As the growth pattern of SPC is variable and distinction of cases with complex architecture from those without is subjective, Controversy regarding categorisation of individual cases exists and should be acknowledged.
Low-grade adenosquamous carcinoma (LG-ASC)	A rare variant of MBC featuring glandular and tubular structures and solid nests of squamous cells in a spindle cell background and commonly arises in association with benign proliferative complex sclerosing and papillary breast lesions. It is often difficult to be differentiated from the proliferative phase of these benign fibrosclerosing lesions. Their entrapped, compressed glandular elements imitate the syringoid glands of LG-ASC and their radiating configuration may appear infiltrative at the periphery in addition to squamous metaplasia. Features favouring malignancy include extension into surrounding breast tissue, ER-negativity, lack of myoepithelial cells around some glandular/tubular structures that show dual expression of low and high molecular weight CKs, and scattered squamous (p63+) islands in the dense spindle cell background with peripheral prominent inflammatory component. However, immunoreactivity for myoepithelial cells at the edge of some tumour islands can be seen and that adenosquamous proliferation is morphologically and immunohistochemically indistinguishable from those seen in the reactive-looking fibrosclerosing breast lesions. Pure LG-ASC has a favourable prognosis with very rare incidence of lymph node or distant metastasis and it needs to be differentiated from the aggressive high-grade adenosquamous MBC. LG-ASC and syringomatous adenoma of the nipple are locally aggressive lesions, sharing morphological and molecular features as well as the propensity for local recurrence, differing only in their location and designation.
Low grade fibromatosis-like metaplastic carcinoma	Infiltrative tumour with entrapped normal breast structures. Low grade spindle cell proliferation with pale eosinophilic cytoplasm and slender nuclei with tapered edges and finely distributed chromatin but with focal plump fusiform and polygonal tumour cells, with more rounded nuclei arranged in “epithelioid” clumps mainly seen centrally in the tumour. Variable cellularity and collagenisation, DCIS rarely present (10–15%). Scattered inflammatory infiltrate comprised of lymphocytes and plasma cells with occasional lymphoid follicles at the edges of the tumours. Often difficult to be differentiated from other BSCT including fibromatosis, nodular fasciitis, myofibroblastoma, solitary fibrous tumour and scar. IHC: typically expression of cytokeratins including low and high molecular weight and p63. CKs+ cells usually appear as cords or sheets of polygonal cells; rarely as isolated positive cells. SMA is often positive particularly in CK negative cells. Typically negative for CD34, hormone receptor, HER2 and desmin. They are characterised by low genomic instability, and do not share CNAs with other metaplastic carcinomas. These tumours can be locally aggressive with an increased incidence of local recurrence, but the potential for lymph node or distant metastasis is very low. Events are associated with higher grade lesions which are often large in size.
Borderline Phyllodes Tumour	Although features of benign and malignant phyllodes are largely defined and it is often easy to be differentiated in most cases, some cases of phyllodes tumour (7%–34%) show overlapping features and exhibit some but not all featuring characteristics of malignant phyllodes tumours and lack frank sarcomatous stroma. Although these tumours not labelled as malignant and are associated with a lower rate of local recurrence than malignant tumours (14%–25%), they exhibit the ability to recur at distant sites despite being a rare event. The subjective diagnostic features of these tumours coupled with the ability to metastasise make predicting behaviour of these tumours in routine practice problematic.
Atypical adenomyoepithelioma	Similar to phyllodes tumours, features and behaviour of benign and malignant adenomyoepitheliomas are largely defined. However, some cases show features of benign adenomyoepithelioma with focal or slight to moderate increase of mitotic figures and cytonuclear atypia in the proliferating myoepithelial cell population. The behaviour of these cases is difficult to predict and lymph node metastasis has been reported in such cases lacking overt features of malignancy. Therefore it should be acknowledged that a diagnosis of atypical adenomyoepithelioma should not exclude the possibility of invasive behaviour in a small proportion of cases which is not expected in benign cases and not sufficient for managing the case as an invasive tumour.

MBC= metaplastic breast carcinoma. BSCL=breast spindle cell lesion, CAN=copy number alteration