Pathology of healing: what else might we look at?

Several aspects of the article by Morita et al. (Cancer Medicine 5:1607-18, 2016), examining the spontaneous healing phenomenon with reference to tumor infiltrating lymphocytes (TILs), require clarification. The concept of "healing", which can perhaps be more accurately termed "regressive change", remains controversial due to a lack of concrete evidence. Since regressive change is characterized by fibrosis and lymphocytes, a cancer nest that appears to lack a distinct basement membrane, surrounded only by lymphocytes, as in Morita et al's Figure 2F, should be meticulously examined because the appearance may correspond to a tumor having just completed the process of invasion. In our experience, a layer of myoepithelial cells in such foci is often difficult to detect even with immunohistochemistry. Thus, we suggest evaluating the viability of cancer cells within the nest by employing several markers, such as Ki67 and apoptotic markers, to judge whether the tumor is intraductal. It might also be useful to compare cases with versus without regressive change to elucidate the biology of such tumors. For these reasons, a tumor, floating within a pool of TILs and lacking obvious fibrous bands, might be an interesting material to examine in future studies.