Experimental studies on malignant fibrous histiocytomas. II. Ultrastructure of malignant fibrous histiocytomas induced by 4-(hydroxyamino)-quinoline 1-oxide in rats.

The ultrastructures of six subcutaneous and six bone malignant fibrous histiocytomas (MFH) induced in rats by local application of the carcinogen, 4-(hydroxyamino)-quinoline 1-oxide (4-HAQO) were studied. The MFHs could be classified histologically into three subtypes: of the six subcutaneous MFHs, four were fibrous, one was giant cell, and one was myxoid; of the osseous MFHs, three were fibrous, one was giant cell, and two were myxoid. Five different types of cells were found in the MFHs: fibroblast-like cells, histiocyte-like cells, undifferentiated cells, xanthomatous cells, and multinucleated giant cells; the xanthomatous cells and multinucleated giant cells, however, were probably derived from histiocyte-like cells. Fibroblast-like cells predominated in storiform areas of the fibrous subtype; histiocyte-like cells and undifferentiated cells predominated in the giant cell subtype; intermediate cells predominated in the myxoid subtype. Acid phosphatase activity was found in lysosomes and myelin figures of the histiocyte-like cells in fibrous type MFH. The giant cell subtype of bone MFH has been transplanted serially into syngeneic rats and is now at the 17th generation. Transplantability exceeded 80%; doubling time was 3.8 to 6.1 days. Until the 3rd generation, the histology of the original tumor was retained; from the 4th generation, however, giant cells and xanthoma cells were no longer observed, and the tumor was composed mainly of undifferentiated cells. These results indicate that (a) MFH induced in the rat by 4-HAQO have an ultrastructure similar to human MFH and (b) the giant cell subtype transplanted serially is gradually transformed with a probable selection of stem cells and undifferentiated cells.