Probable clonal origin of neurofibrosarcoma in a patient with hereditary neurofibromatosis

A neurofibroma, a fibroma, a primary neurofibrosarcoma, and four neurofibrosarcoma metastases from a woman with hereditary neurofibromatosis who was heterozygous (GdB/GdA-) for the X-linked enzyme glucose-6-phosphate dehydrogenase were studied to determine the number of cells from which the tumors developed. Both enzyme types were observed in the benign tumors in proportions similar to those present in seven different normal tissues studied. These findings indicated that the benign tumors arose from many cells. In marked contrast, only type A activity was detected in the primary neurofibrosarcoma and in all of the metastases. Two or more steps probably were involved in the development of neurofibrosarcoma in this patient: the inherited genetic mutation producing neurofibromatosis and a rare event or combination of events that permitted a single cell to undergo malignant proliferation.