Lipogenic stromal cells as members of the foam-cell population in human atherosclerosis: Immunocytochemical and ultrastructural assessment of 6 cases

To identify the nature of foam cells in atherosclerosis, carotid atherosclerotic plaques (CAPs) from six patients were studied. Hematoxylin-and-eosin, Congo Red and Oil Red O staining were used to study histopathologic alterations in CAPs. CD31, alpha-smooth-muscle actin (alpha-SMA), CD68, desmin and S100 were stained immunohistochemically. The ultrastructure of foam cells was analyzed by transmission electron microscopy (TEM). CAPs were shown to be composed of a fibrous cap covering a dome-shaped mass with a peripheral, circumferential fringe merging with a basal band which itself met the tunica media, the latter consisting of smooth-muscle cells (SMCs). The interior of the dome-shaped mass exhibited fibrosis, neovascularization, hemorrhage, necrosis and calcification. Lipid droplets identified by histological stains and TEM were found in the rounded epithelioid foam cells regarded as macrophages, as well as in spindled cells interpreted here as lipoleiomyocytes (lipid-containing SMCs), lipofibroblasts and lipomyofibroblasts; and all these cells were located in different regions of the CAPs. All of these lipid-laden cells were strongly positive for CD68 but negative for desmin. Foam cells were weakly positive for alpha-SMA, CD31 and S100. The results indicate that the light microscopically identifiable population of foam/lipid-laden cells hide a spectrum of diverse differentiation ranging from the expected macrophage phenotype to non-macrophage phenotypes. The origin of these diverse cell phenotypes in terms of multipotential mesenchymal precursors and the origin of the intracellular lipid are discussed.