By invitation from the American College of Radiology I presented this lecture covering one of the most challenging subtypes of breast malignancy, the diffusely infiltrating breast cancer (a k a diffuse invasive lobular carcinoma).We challenge the conventional histopathology terminology since we have accumulating evidence that this subtypes originates from the mesenchymal stem cells.
Clinical, imaging and outcome observations indicate that the diffusely infiltrating breast cancer, presenting as a large region of architectural distortion on the mammogram and conventionally termed classic infiltrating lobular carcinoma of diffuse type, represents a very unusual breast malignancy. It accounts for 5-8 % of all breast cancers and is characterized by small, discohesive epithelial cells, which are mostly ER positive and HER2 negative, E-cadherin negative and lack tumor infiltrating lymphocytes. The clinical presentation is typically a symptomatically detected, extensive, firm lesion, often appearing as an interval cancer following a previous mammogram which was interpreted as normal. At palpation this malignancy does not have a distinct tumor mass or focal skin retraction but causes an indistinct “thickening” and eventually shrinks the entire breast, a phenomenon not seen with other breast malignancies. A dominant feature of this malignancy is an excess of connective tissue having concave contours with the surrounding adipose tissue, a feature which makes it difficult to detect on mammograms. These features, a 60% long-term survival and its resistance to adjuvant therapy suggest that it has a site of origin quite different from that of other breast cancers. We propose that this subtype originates from the mesenchymal stem cells through a complex process of mesenchymal-epithelial transformation (MET) and suggest the term “breast cancer of mesenchymal origin”, BCMO. This site of origin is consistent with its clinical, imaging and histopathological features. Control of this unusual malignancy requires new approaches to detection, a revision of histopathological diagnostic criteria and new therapeutic innovations.