RAPID GROWTH OF CUTANEOUS METASTASES AFTER SURGICAL RESECTION OF THROMBOSPONDIN-SECRETING SMALL BLUE ROUND-CELL TUMOR OF CHILDHOOD

In animal models, the importance of tumor-derived antiangiogenic facto rs in controlling metastases has been demonstrated by the growth accel eration of distant metastases after surgical excision of a primary tum or mass. We report the case of an infant who developed rapidly growing cutaneous metastases after surgical resection of a neoplasm of an upp er extremity The tumor was undifferentiated, with some morphological f eatures of primitive neuroectodermal tumor. To test the possibility th at the primary tumor was secreting an angiogenic inhibitor, cells from the primary tumor were grown in culture, and the culture medium was t ested with an in vitro endothelial cell migration assay and Western bl ot. The cultured cells secreted sufficiently high levels of an angioge nic inhibitor to overcome the inducing ability of vascular endothelial growth factor and basic fibroblast growth factor. One of the secreted proteins was thrombospondin-l, a potent antiangiogenic glycoprotein. The rapid dissemination of distant metastases after resection of the p rimary tumor in this case suggests that tumor-derived angiogenic inhib itors are important in maintaining the local net balance of angiogenic mediators controlling the growth of micrometastasis. Copyright (C) 19 98 by W.B. Saunders Company.