Hemosiderin-Laden Macrophages in Canine Mammary Carcinomas

Simple Summary Macrophages play a key role in cancer. The aim of this study was to identify hemosiderin-laden macrophages (HLMs) and speculate their possible role in canine mammary carcinoma. HLMs, which were variously localized in cancer peritumoral and stromal areas, expressed CD204, an M2 macrophagic marker. In addition, they showed positivity for angiogenic and protumoral molecules, such as VEGF or TGF-alpha. Therefore, HLMs need to be considered for a possible role in cancer progression and survival in canine mammary tumors, protecting cells from hypoxia.Abstract Macrophages are among the main actors in cancer immunoediting, with several functions, including recycling iron and packaging it in hemosiderin. Even though TAMs are widely studied in breast cancer and canine mammary tumors, hemosiderin-laden macrophages (HLMs) have not received as much attention. Considering the growing interest in iron metabolism in cancer, this study aims to evaluate the presence of HLMs in canine mammary tumors. Fifty cases of canine mammary carcinomas presenting aggregates of pigmented macrophages were chosen. Prussian blue and Meguro staining were performed to assess the presence of iron. Immunohistochemistry was carried out to try to identify macrophagic phenotypes and hypothesize their role. Evaluation of the H&E sections showed that pigmented macrophages were variously localized in peritumoral and stromal areas. These pigmented cells were variably stained with Prussian blue and reacted strongly with DAB in the Meguro staining method, thus confirming the presence of iron within them. In their immunohistochemistry, the HLMs were negative for the MAC387 but positive for CD 204 and VEGF. Considering their positivity for CD 204, HLMs could be M2 macrophages that supply iron to both the neoplastic cells and the tumor inflammatory microenvironment, promoting angiogenesis and protecting cancer cells from hypoxia.