Presarcomatous lesions of experimentally induced sarcomas in rats: morphologic, histochemical, and...

Morphological studies have been performed mainly on manifest sarcomas, leading to divergent views of its histogenesis. However, histogenesis requires understanding of the tumor precursor cells and cannot be resolved by static morphologic studies. Defining presarcomatous lesions is made more difficult because they do not possess a basement membrane that serves as biologic and nosologic boundary like in epithelial cancers. The present study, therefore, investigated the early phases of experimentally induced rat sarcoma, which closely resembles human malignant fibrous histiocytoma (MFH). Histological, enzyme- and immunohistochemical methods were used to define the sequential events involved in tumorigenesis. A benzo[a]pyrene-oil mixture was injected intramuscularly into the thighs of rats, producing MFH 120 days later. Groups of animals were sacrificed every 10 days. The injections produced soft tissue lesions characterized by three distinct phases that overlapped or existed simultaneously in one animal: an initial acute inflammatory reaction characterized by an infiltration of lymphocytes, monocytes and macrophages, a second mesenchymal fibromatous phase characterized by the predominance of spindle-shaped, focally atypical fibroblast-like cells and collagen, and a third premalignant neovascularization phase characterized by dominant capillary proliferations. Overt MFH developed 120 days after injection and consisted of spindle-shaped fibroblast- and histiocyte-like cells containing atypical mitoses and arranged in a storiform pattern. Control animals injected with olive oil revealed acute inflammatory reactions after 30 days and no signs of chronic inflammation or malignancy after 60 and 120 days. We concluded that these experimentally-induced rat sarcomas develop in a triphasic pattern that resembles non-healing granulation tissue, with neovascularization preceding the occurrence of overt MFH.