Origin of histiocyte‐like cells and multinucleated giant cells in malignant fibrous histiocytoma: Neoplastic or reactive?

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Abstract
The origin of histiocyte‐like cells in malignant fibrous histiocytoma (MFH) remains controversial. To determine whether histiocyte‐like cells and multinucleated giant cells show reactive or neoplastic proliferation, we transplanted human storiform‐pleomorphic MFH to nude mice and investigated the origin of histiocyte‐like cells using the DNA in situ hybridization (ISH) system. In addition, we analyzed the mRNA expression of mouse c‐fms and human colony stimulating factor‐1 (CSF‐1); immunohistochemical expression of markers detectable in cells of monocyte/macrophage lineage. The DNA ISH revealed neoplastic proliferation of fibroblastic cells and bizarre multinucleated giant cells of human origin. Monocyte/macrophage lineage cells were seen in parental tumors, whereas they did not participate in neoplastic proliferation in transplanted tumors. The parental tumors expressed human CSF‐1 mRNA and the histiocyte‐like cells in transplanted tumors expressed ‘mouse’c‐fms mRNA. These results suggest that MFH induce infiltration of monocyte/macrophage and CSF‐1 is one of the mediators involved in this phenomenon, because the human CSF‐1 can act as a ligand to the mouse c‐fms. Histiocyte‐like cells in MFH should be considered as a reactive monocyte/macrophage lineage rather than as an element of neoplasm.