Nonfibroblastic origin of foreign body sarcomas implicated by histological and electron microscopic studies.

Abstract

Twenty foreign body sarcomas induced in CBA/H, CBA/H-T6, or AKR mice by s.c. implantation of foreign body material were investigated histologically and by electron microscopy in search of morphological characteristics which would indicate the cell of origin. Eighteen of these sarcomas generally conformed to classes of anaplasticity defined earlier in our laboratory. Myxoid areas were apparent in two of these sarcomas. In addition, a hemangiosarcoma and a bone-forming sarcoma were studied. In spite of the heterogeneity of sarcoma types obtained in this study, all sarcomas were characterized by ( a ) pericellular, periodic acid-Schiff-positive, argyrophilic, and filamentous substance resembling basal lamina; ( b ) a sparsity of collagen production; and ( c ) prominent cytoplasmic accumulations of 60-A microfilaments in 60 to 100% of the cells from each sarcoma. Sarcomas from six mice with leiomyomatous cells, containing extensive concentrations of microfilaments ultrastructurally, also had many acid fuchsin-positive cells when examined with the light microscope. The consistent presence of these morphological characteristics despite variability of histological sarcoma types suggests that a pluriopotential mesenchymal cell type other than the fibroblast is the common progenitor cell. This cell must be presumed to be derived from the local tissue at the implantation site since chimera studies have already excluded radiosensitive stem cells of the bone marrow as the source. The pericyte, besides closely related cell types that are a fixed structural part of the microvascular bed ( i.e. , endothelial cells and smooth muscle cells), was considered to be the most likely progenitor cell because ( a ) it possesses mesenchymal pluripotentiality to account for the histological variety within and between sarcomas and ( b ) it possesses subcellular morphological features compatible with those seen in the tumor cells. Virus particles were present in 15 of 20 sarcomas studied. Intracisternal type A particles were demonstrated in 12 of 17 sarcomas of CBA/H and CBA/H-T6 animals (or their hybrids) while 3 of 3 sarcomas induced in ARK mice contained immature type C particles. The significance of virus particles associated with foreign body sarcomas remains to be determined.