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Purpose: About 10% of patients with neurofibromatosis type 1 (NF-1) develop malignant peripheral nerve sheath tumours (MPNST) mostly arising in plexiform neurofibroma (PN); 15% of MPNST arise in children and adolescents. 2-[ 18 F]fluoro-2-deoxy-d-glucose ([ 18 F]FDG)-PET (where PET is positron emission tomography) is a sensitive method in differentiating PN and MPNST in symptomatic patients with NF-1. This study assesses the value of [ 18 F]FDG-PET imaging in detecting malignant transformation in symptomatic and asymptomatic children with PN., Methods: Forty-one patients with NF-1 and extensive PN underwent prospective [ 18 F]FDG imaging from 2003 to 2014. Thirty-two of the patients were asymptomatic. PET data, together with histological results and clinical course were re-evaluated retrospectively. Maximum standardised uptake values (SUVmax) and lesion-to-liver ratio were assessed., Results: A total of 104 examinations were performed. Mean age at first PET was 13.5 years (2.6-22.6). Eight patients had at least one malignant lesion; four of these patients were asymptomatic. Two of four symptomatic patients died, while all patients with asymptomatic malignant lesions are alive. All malignant tumours could be identified by PET imaging in both symptomatic and asymptomatic patients. All lesions judged as benign by [ 18 F]FDG imaging and clinical judgment were either histologically benign if removed or remained clinically silent during follow-up. SUVmax of malignant and benign lesions overlapped, but no malignant lesion showed FDG uptake ≤3.15. Asymptomatic malignant lesions were detected with a sensitivity of 100%, a negative predictive value of 100% and a specificity of 45.1%., Conclusion: Malignant transformation of PN also occurs in asymptomatic children and adolescents. Detection of MPNST at early stages could increase the possibility of oncologically curative resections., (© 2017 Wiley Periodicals, Inc.)

Background . Malignant peripheral nerve sheath tumours (MPNSTs) are difficult to diagnose and treat and contribute to significant morbidity and mortality for patients with Neurofibromatosis-1 (NF-1). FDG-PET/CT is being increasingly used as an imaging modality to discriminate between benign and malignant plexiform neurofibromas. Objectives . To assess the value of FDG-PET/CT in differentiating between benign and malignant peripheral nerve lesions for patients with Neurofibromatosis-1. Methods . A systematic review of the literature was performed prior to application of stringent selection criteria. Ultimately 13 articles with 796 tumours were deemed eligible for inclusion into the review. Results . There was a significant difference between mean SUV max of benign and malignant lesions (1.93 versus 7.48, resp.). Sensitivity ranged from 89 to 100% and specificity from 72 to 94%. ROC analysis was performed to maximise sensitivity and specificity of SUV max cut-off; however no clear value was identified (range 3.1-6.1). Significant overlap was found between the SUV max of benign and malignant lesions making differentiation of lesions difficult. Many of the studies suffered from having a small cohort and from not providing histological data on all lesions which underwent FDG-PET/CT. Conclusion . This systematic review is able to demonstrate that FDG-PET/CT is a useful noninvasive test for discriminating between benign and malignant lesions but has limitations and requires further prospective trials., Competing Interests: The authors declare that they have no competing interests.

Background: Individuals with Neurofibromatosis type 1 (NF1) are at risk for developing malignant peripheral nerve sheath tumors (MPNST), which frequently arise in preexisting plexiform neurofibromas (PN). Magnetic resonance imaging (MRI) with volumetric analysis and 18-fluorodeoxyglucose-positron emission tomography (FDG-PET) were utilized to monitor symptomatic nodular lesions., Procedure: Patients with NF1 and PN on a NCI natural history trial were monitored for total body tumor volume (TTV) using volumetric MRI. FDG-PET was performed in individuals with a nodular well-demarcated lesion ≥3 cm if they were growing, painful, or there was a prior history of MPNST (target lesions). Asymptomatic nodular lesions were evaluated as non-target lesions., Results: Fifteen patients (8m, 7f) median age of 18.3 years (range, 10-45 years) had a single target and non-target (n = 46) nodular lesions identified on MRI. Target lesions arose within (n = 8) or outside (n = 3) a PN, and all but 1 had increased FDG uptake. FDG uptake was increased in non-target lesions but to a lesser degree. FDG uptake in the surrounding PN was low, similar to background activity. Pathologic evaluation performed in 11 patients demonstrated neurofibroma (n = 6), atypical neurofibroma (n = 2) and malignancy (n = 3)., Conclusions: Nodular target lesions identified on MRI in individuals with NF1 and PN demonstrate increased FDG uptake similar to MPNST, but may be benign on biopsy. Nodular target lesions may be at greater risk for malignant transformation, but their biologic and clinical behavior has not been well studied. Careful longitudinal evaluation will be required to better understand the malignant potential of these lesions., (Copyright © 2012 Wiley Periodicals, Inc.)

The objective of this study was to investigate the predictive value of [18F]-fluorodeoxyglucose positron emission tomography (FDG-PET) in detecting malignant transformation of plexiform neurofibromas in children with neurofibromatosis type 1 (NF1). An electronic search of the medical records was performed to determine patients with NF1 who had undergone FDG-PET for plexiform neurofibroma between 2000 and 2011. All clinical, radiologic, pathology information and operative reports were reviewed. Relationship between histologic diagnosis, radiologic features and FDG-PET maximum standardized uptake value (SUV(max)) was evaluated. This study was approved by the Institutional Review Board of our institution. 1,450 individual patients were evaluated in our Multidisciplinary Neurofibromatosis Program, of whom 35 patients underwent FDG-PET for suspected MPNST based on change or progression of clinical symptoms, or MRI findings suggesting increased tumor size. Twenty patients had concurrent pathologic specimens from biopsy/excision of 27 distinct lesions (mean age 14.9 years). Pathologic interpretation of these specimens revealed plexiform and atypical plexiform neurofibromas (n = 8 each), low grade MPNST (n = 2), intermediate grade MPNST (n = 4), high grade MPNST (n = 2), GIST (n = 1) and non-ossifying fibroma (n = 1). SUV(max) of plexiform neurofibromas (including typical and atypical) was significantly different from MPNST (2.49 (SD = 1.50) vs. 7.63 (SD = 2.96), p < 0.001). A cutoff SUV(max) value of 4.0 had high sensitivity and specificity of 1.0 and 0.94 to distinguish between PN and MPNST. FDG-PET can be helpful in predicting malignant transformation in children with plexiform neurofibromas and determining the need for biopsy and/or surgical resection.

Development of malignant peripheral nerve sheath tumors (MPNSTs) is a recognized complication in patients with neurofibromatosis type 1 (NF1). Differentiating benign from malignant lesions can be a difficult clinical problem. Positron emission tomography (PET) is an established method for making this differentiation with a high degree of sensitivity and specificity. There are several reports showing that fluorine-18 fluorodeoxyglucose (FDG) PET is an effective imaging modality for detecting malignant transformation with a sensitivity nearing 100%. There are very few reports of false-negative 18F-FDG PET in a patient with an MPNST. This case report describes a woman with NF1 and a grade 3 MPNST and a negative PET scan. Identification of malignant transformation in NF is a significant clinical challenge. It is important to recognize the potential limitations of 18F-FDG PET in these patients.

Background: The role of FDG-PET for managing patients with plexiform neurofibromas (PN) is unclear. While many PN tumors exhibit periods of rapid growth, others grow slowly or unpredictably and may have periods of relative quiescence. The ability to predict which PN are likely to progress should facilitate a more timely initiation of medical treatments. Since conventional radiographic techniques have limited prognostic value, the use of a functional imaging modality to predict tumor progression is desirable. We hypothesized that PN tumors with high metabolic activity as demonstrated by FDG-PET are more likely to progress in the following year., Methods: All patients were clinically stable, but were considered at high-risk for progression based on anatomical location of PN. FDG-PET scans were performed within two weeks of the baseline MRI study. Standardized uptake values (SUV) were calculated for all focally active index lesions and analyzed for correlation with changes in quantitative MRI over the ensuing year., Results: Fifteen of the 18 enrolled patients showed various degrees of FDG uptake as focal abnormalities, and these abnormalities corresponded to those noted on the MRI scans. Thirteen patients and 19 lesions were evaluable for PN volume change. The SUVmax ranged from 0.9 to 4 (median 1.5). There was a significant difference in the percent increase in PN volume in the following year for lesions that had an SUV > 2 compared to those with lower values (P = 0.016)., Conclusions: These findings support the hypothesis that FDG-PET imaging predicts PN growth rate, and, therefore, may assist clinician decision making with regard to treatment of PN and enrollment in clinical trials.

Background: Malignant peripheral nerve sheath tumours (MPNSTs) are difficult to detect in neurofibromatosis 1 (NF1) individuals. The purpose was to evaluate [(18)F]2-fluoro-2-deoxy-D-glucose positron emission tomography (FDG PET) and PET computed tomography (CT) as a diagnostic tool for MPNST in NF1 patients with symptomatic plexiform neurofibromas and to verify the diagnosis by pathology and clinical follow-up., Patients and Methods: NF1 individuals with symptomatic plexiform neurofibromas underwent clinical evaluation and magnetic resonance imaging. Qualitative FDG PET and PET CT associated with semi-quantitative maximum standard uptake value (SUVmax) assessed possible malignant change. Excision/biopsy verified the diagnosis when possible and clinical follow-up was undertaken in all patients., Results: In all, 116 lesions were detected in 105 patients aged 5-71 years, including 80 plexiform neurofibromas, five atypical neurofibromas, 29 MPNST and two other cancers. Biopsy confirmed the findings in 59 tumours and no MPNST was diagnosed on clinical follow-up of 23 lesions diagnosed as benign on FDG PET and PET CT. FDG PET and PET CT diagnosed NF1-associated tumours with a sensitivity of 0.89 [95% confidence interval (CI) 0.76-0.96] and a specificity of 0.95 (CI 0.88-0.98), but the SUVmax level did not predict tumour grade., Conclusion: FDG PET and PET CT is a sensitive and specific diagnostic tool for NF1-associated MPNST. Other PET tracers will be required to solve the problem of predicting tumour grade.