Comparative ultrastructure of atypical ductal hyperplasia, intraductal carcinoma, and infiltrating ductal carcinoma of the breast

Abstract

Atypical ductal hyperplasia, intraductal carcinoma, and frankly infiltrating ductal carcinoma of the breast were studied by electron microscopy. Atypical ductal hyperplasia was characterized by the presence of very abundant, irregular and frequently giant, polypoid microvilli. Intraductal carcinoma cells displayed very complex cell interdigitations. Conspicuous intracytoplasmic lumina were exclusively observed in infiltrating carcinoma cells. Anomalies in the cell membrane and its derivatives appear to be a common denominator of all these lesions. Both loosely arranged and tightly packed cytoplasmic filaments were much more abundant in infiltrating carcinoma cells than in either atypical hyperplasia or intraductal carcinoma. Phagocytosed leukocytes were often found within carcinomatous breast cells. The possible connection of this observation with immunologic phenomena remains obscure. Further ultrastructural studies may conceivably develop some of these features into more accurate diagnostic criteria for doubtful breast lesions.

Plasticity of Mammary Cell Boundaries Governed by EGF and Actin Remodeling

“…During early embryonic development and puberty, the elongated tips of mammary buds form multilayered epithelia, and cells within the interior layers show prominent interdigitation and high levels of desmosomes (Ewald et al, 2012;Nazario et al, 1994). Interdigitated structures are also prominent in intraductal carcinomas, suggesting that they may have acquired characteristics of the normal developmental program (Goldenberg et al, 1969). In keratinocyte and endothelial cell cultures, interdigitated structures are observed as intermediates in the formation of stable cell-cell contacts (Hoelzle and Svitkina, 2012;Vasioukhin et al, 2000).…”

Mammary collective cell migration involves transient loss of epithelial features and individual cell migration within the epithelium

“…A previous ultrastructural study has examined ductal hyperplasias, ductal carcinoma in situ and infiltrating ductal carcinomas from human patients to determine the basis of the invasive switch in human breast cancer (Goldenberg et al, 1969). Importantly, the authors reported that: ''The most notable finding in our ultrastructural study of various types of breast lesions was an increased degree of cell membrane anomaly paralleling the increased degree of aggressiveness among these lesions… atypical ductal hyperplasia was characterized by abundant microvilli… [i]ntraductal carcinomas were recognizable by extremely complex cell interdigitations.…”

“…Importantly, the authors reported that: ''The most notable finding in our ultrastructural study of various types of breast lesions was an increased degree of cell membrane anomaly paralleling the increased degree of aggressiveness among these lesions… atypical ductal hyperplasia was characterized by abundant microvilli… [i]ntraductal carcinomas were recognizable by extremely complex cell interdigitations. Infiltrating ductal carcinomas were detectable by an overabundance of cellular microvilli'' (Goldenberg et al, 1969). The morphological similarity between the complex interdigitations in the intraductal carcinomas in that study and in the normal mammary cells undergoing morphogenesis in our study is striking and suggests that at least some human breast cancers might recapitulate aspects of a normal developmental migration program.…”

Lymphoreticular infiltration in human tumours: prognostic and biological implications: a review

“…Goldenberg, Goldenberg and Sommers (1969) an ingenious attempt to equate lack of infiltration with poor survival.…”