Can 18FDG-PET detect malignant transformation of neurofibromas in patients with neurofibromatosis type I?

Aims: Neurofibromatosis type 1 (NF1) is a frequent hereditary disease and is caused by mutations of the NF1 gene (17q22.1). Benign tumors of the peripheral nerve sheath, termed neurofibromas, are the hallmark feature. Transformation into malignant peripheral nerve sheath tumors (MPNSTs) occurs in about 10% and results in very poor survival rates. Increased glucose metabolism in tumor cells visualized by 18fluorodeoxyglucose (18FDG) positron emission tomography (18FDG-PET) has frequently been used as a marker of malignant transformation. Here, we present a NF1 patient in whom positive 18FDG-PET of a neurofibroma suggested malignant transformation, while post-operative histopathology did not demonstrate malignancy. Methods: In a 17-year old girl with NF1 and multiple neurofibromas abdominal MRI revealed a new presacral tumor of 25mm diameter. 6 months later, MRI revealed an increased tumor size of 35mm diameter. Radiologically the hypodense tumor had sharp margins and did not suggest malignant transformation, but MRI characteristics clearly differed from all other neurofibromas. In 18FDG-PET we found an increased glucose uptake 60 minutes after injection. This was highly suggestive of malignant transformation so that the tumor was surgically excised. Histopathology demonstrated a neurofibroma with many S100-pos. cells and areas of increased cellularity but without any sign of malignancy. The proliferation index, measured by Ki-67 antigen, was below 5%. Conclusion: 18FDG-PET has been shown to be a valuable tool in determining malignant change in neurofibromas. However, false-positive results need to be considered before an operation is recommended. Measurement at 200min after injection is recommended while earlier measurements seem to produce more false-positive results. Some authors suggest premalignant changes on a cellular level in neurofibromas with positive 18FDG-PET but benign histology. Perhaps 18FDG-PET might be able to detect malignant transformation at a very early stage when histopathology alone does not allow diagnosis of malignancy.