Invasion in breast lesions: the role of the epithelial–stroma barrier

Abstract

Despite the significant biological, behavioural and management differences between ductal carcinoma in situ (DCIS) and invasive carcinoma of the breast, they share many morphological and molecular similarities. Differentiation of these two different lesions in breast pathological diagnosis is based typically on the presence of an intact barrier between the malignant epithelial cells and stroma; namely, the myoepithelial cell (MEC) layer and surrounding basement membrane (BM). Despite being robust diagnostic criteria, the identification of MECs and BM to differentiate in-situ from invasive carcinoma is not always straightforward. The MEC layer around DCIS may be interrupted and/or show an altered immunoprofile. MECs may be absent in some benign locally infiltrative lesions such as microglandular adenosis and infiltrating epitheliosis, and occasionally in non-infiltrative conditions such as apocrine lesions, and in these contexts this does not denote malignancy or invasive disease with metastatic potential. MECs may also be absent around some malignant lesions such as some forms of papillary carcinoma, yet these behave in an indolent fashion akin to some DCIS. In Paget's disease, malignant mammary epithelial cells extend anteriorly from the ducts to infiltrate the epidermis of the nipple but do not typically infiltrate through the BM into the dermis. Conversely, BM-like material can be seen around invasive carcinoma cells and around metastatic tumour cell deposits. Here, we review the role of MECs and BM in breast pathology and highlight potential clinical implications. We advise caution in interpretation of MEC features in breast pathology and mindfulness of the substantive evidence base in the literature associated with behaviour and clinical outcome of lesions classified as benign on conventional morphological examination before changing classification to an invasive lesion on the sole basis of MEC characteristics.

Breaking through to the Other Side: Microenvironment Contributions to DCIS Initiation and Progression

“…The critical diagnostic consideration is exclusion of micro-invasive carcinoma (defined as invasive foci no larger than 1 mm; Figure 1E, 1F) admixed within the in situ tumor. Several immunohistochemical stains for myoepithelial cells can be used to assist in the clinical diagnosis of DCIS vs. invasive carcinoma, although diagnostic pitfalls exist with any one specific marker and therefore utilization of several stains is advised to most accurately assess for the presence of a myoepithelial cell layer [4]. Further, as described later in this review, decreased or variable expression of particular myoepithelial markers may in fact contribute to altered myoepithelial cell function leading to invasive progression.…”

Morphologic and immunohistochemical features of carcinoma involving microglandular adenosis of the breast following neoadjuvant chemotherapy

“…Invasion is fundamentally defined as the breach of the basement membrane, and not just loss of myoepithelial cells. 19 While some invasive carcinomas such as well differentiated cutaneous squamous cell carcinoma and basal cell carcinomas have been reported to display a continuous basement membrane, 20 studies of breast neoplasia have repeatedly observed a gradual loss of basement membrane, as demonstrated by IHC studies, with increasing degree of tumor dedifferentiation. Thin, but often fragmented and discontinuous, basement membrane has been seen in well differentiated tumors, including tubular carcinomas, in contrast to its consistent absence of staining in poorly differentiated tumors.…”

Comparison of the Magnetic Resonance Imaging Findings of Paget’s Disease of the Breast and Malignant Tumor Invasion of the Nipple-Areola Complex

“…These findings are consistent with those of Moon et al (12), although the difference between the two groups in their study was smaller compared to that in our study. Patients with MTION may exhibit more edema and areolar-periareolar skin thickening because MTION involves all layers of the skin or areolar lymphatics, whereas PDB is located within the epidermis of the NAC (2,14,15).…”