Malignant peripheral nerve sheath tumors in neurofibromatosis type 1 arise from distinct nodular lesions: A retrospective imaging analysis.

Background: People with neurofibromatosis type 1 (NF1) have an 8%-13% lifetime risk of developing malignant peripheral nerve sheath tumors (MPNST). Atypical neurofibromas (AN) and atypical neurofibromatous neoplasms of uncertain biologic potential (ANNUBP) have been described as precursors to MPNST. AN/ANNUBP often appear as distinct nodular lesions (DNL) that are ≥3 cm in longest diameter. To assess the hypothesis that most MPNST originate in preexisting DNL, we performed a retrospective review of MRIs obtained prior to the MPNST diagnosis in people with NF1. Methods: Study subjects were identified at two NF centers, University Hospital Hamburg-Eppendorf in Germany and the National Cancer Institute in Bethesda, Maryland, USA. We confirmed the location of MPNST on the MRI performed at the time of histopathological diagnosis and analyzed distinguishing imaging features at the site of MPNST on prior MRIs. Results: Thirty subjects with NF1 and 35 histologically confirmed MPNST were included in the analysis. Twenty-six MPNST (74%) were detected incidentally on surveillance MRI. In 32 of 35 MPNST (91%), a pre-existing DNL could be detected at the site of subsequent malignancy on prior MRIs. Thirteen DNL gradually emerged within a plexiform neurofibroma (PN) during observation, and 19 DNL were already established on the first available scan. The median time from DNL detection to MPNST diagnosis was 5.1 years (range 0.5-15.7). Conclusions: Most NF1-related MPNST develop from preexisting DNL. However, we cannot estimate what percentage of DNL will transform to MPNST. Assessing the risk of malignant transformation of DNL in NF1 requires prospective studies.