Microglandular adenosis: a non-obligate precursor of triple-negative breast cancer?

Microglandular adenosis is a rare glandular lesion of the breast, which can mimic well-differentiated invasive carcinoma, and is characterized by a haphazard proliferation of uniform small round glands with open lumina and lacking a myoepithelial cell layer. This lesion has a rather unique immunohistochemical profile characterized by expression of cytokeratins and S-100, and lack of estrogen receptor (ER) and progesterone receptor (PR). The role of microglandular adenosis as a potential precursor of invasive breast cancer has long been a matter of controversy; however, recent molecular analyses have demonstrated that these lesions are heterogeneous at the genetic level, and that at least a subset of microglandular adenosis are clonal and display gene copy number alterations. Importantly, the pattern of genetic aberrations found in microglandular adenosis differs from that of other non-obligate precursors of ER-positive breast cancer. Carcinomas arising in microglandular adenosis are mostly of triple-negative phenotype (i.e. lack of ER, PR and HER2) and express S100, similar to microglandular adenosis. Genetic alterations found in microglandular adenosis have been shown to be similar to those found in synchronous invasive carcinomas. Here we review the clinical, morphological, and molecular features of microglandular adenosis, with an emphasis on its role as a non-obligate precursor of triple-negative breast cancer, and discuss areas for future research endeavors to clarify the clinical and biological significance of these fascinating lesions.