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Background: Patients with neurofibromatosis type 1 (NF1) can develop plexiform neurofibromas (PN). Large tumor burden is a predictor for the development of malignant peripheral nerve sheath tumors. Whole-body magnetic resonance imaging (WB-MRI) is the recommended imaging method for the evaluation of PN. WB-MRI is recommended for NF1 patients at transition from adolescence to adulthood. In the absence of internal PN further follow-up WB-MRI is not considered necessary. PN are often detected in early childhood, leading to the assumption that they may be congenital lesions. It remains unclear whether this invariably applies to all patients or whether patients who initially displayed no tumors can still develop PN over time. Therefore, we retrospectively reviewed WB-MRI scans of pediatric patients with NF1 without initial tumor burden and compared these with long-term follow-up scans for presence of newly developed PN., Methods: We retrospectively reviewed WB-MRI scans of 17 NF1-children (twelve male; median age at initial scan: 9 [IQR 6.1-11.9] years) who initially displayed no PN. MRI scans with a follow-up interval of at least 6 years (median follow-up interval: 9 [IQR 5.6-12.4] years) were reviewed in consensus by two radiologists regarding the development of new PN over time., Results: New PN were identified in two out of 17 children without initial tumor burden in follow-up examinations. One of these two patients developed two larger distinct PN of 4.5 cm on the right upper arm and of 2.5 cm on the left thoracic wall between the age of ten and twelve. The second child developed multiple smaller PN along the major peripheral nerves between the age of eleven and 16. In addition, 15 of the children without initial tumor burden did not develop any distinct tumors for a period of at least 6 years., Conclusion: Our results indicate that PN can be newly detected in pediatric patients over time, even if no PN were detected on initial MRI scans. Therefore, it seems reasonable to perform at least a second MRI in pediatric NF1 patients at transition to adulthood, even if they did not display any tumor burden on initial MRI, and when the MRI was performed significantly under the age of 18. With this approach, tumors that may have developed between scans can be detected and patients at risk for complications can be identified., (© 2024. The Author(s).)

Objective: The aim of this study is to evaluate neurofibromatosis type 1 (NF1) patients with whole-body MRI (WBMRI) to investigate the frequency of plexiform neurofibromas (pNFs), diffuse neurofibromas (dNFs), and malignant peripheral nerve sheath tumors (MPNSTs)., Materials and Methods: In this retrospective cross-sectional study, between the years 2015 and 2023, 83 consecutive patients with known NF1 underwent a total of 110 WBMRI screenings for MPNST using a standardized institutional protocol. The lesions are categorized as discrete lesions, pNFs, dNFs, and MPNSTs. Histopathology served as the reference standard for all MPNSTs., Results: Among the 83 patients analyzed, 53 (64%) were women and 30 were men (36%) of ages 36.94±14.43 years (range, 15-66 years). Of the 83 patients, 33 have a positive family history of NF1 and positive genetic studies. Seven of 83 (8%) have only dNF, 20/83 (24%) have pNF, 28/83 (34%) have both dNF and pNF, and 28/83 (34%) have neither. Of the 83 patients, eight (9.6%) were diagnosed with nine total MPNSTs. Age range for patients with MPNSTs at time of diagnosis was 22-51, with an average age of 33.4 years. Only one MPNST (11%) developed from underlying pNF 4 years after WBMRI along the right bronchial tree. Three of eight (37.5%) patients with MPNST died within 5 years of pathologic diagnosis., Conclusion: This study suggests the absence of a predisposition for development of MPNST from pNFs and dNFs in the setting of NF1. As such, these lesions may not need special surveillance compared to discrete peripheral nerve sheath tumors., (© 2023. The Author(s), under exclusive licence to International Skeletal Society (ISS).)

Background: Neurofibromatosis type 1 is a neurocutaneous genetic disorder caused by mutations in the NF1 gene, resulting in the formation of benign tumors called neurofibromas. The most common type of tumor seen in patients with neurofibromatosis type 1 is the slow-growing and benign neurofibroma, with a subtype called plexiform neurofibroma being particularly common and causing pain, functional impairment, and cosmetic disfigurement., Case Presentation: We report the case of a 20-year-old North African female patient with a history of neurofibromatosis type 1 who presented with a growing mass in her right gluteal region, which was later diagnosed as a giant cutaneous neurofibroma. Imaging studies revealed infiltration in several regions, including the urinary bladder wall, resulting in significant bilateral hydronephrosis. The patient is currently being monitored, and no excisional procedures are planned., Conclusions: Neurofibromatosis type 1 can cause a variety of clinical symptoms, including the development of large plexiform neurofibromas. It is important to closely monitor patients with neurofibromatosis type 1 for the early detection of neurofibromas. Early detection and prompt surgical intervention are essential for preventing complications., (© 2024. The Author(s).)

Plexiform neurofibromas (PNs) occur in approximately 50% of patients with neurofibromatosis type 1 (NF1). PNs are rare in the abdominal cavity and especially rare in hepatobiliary lesions. A 31-year-old man with NF1 had a tumor extending along the celiac artery, superior mesenteric artery, and intrahepatic portal vein. We diagnosed him with diffuse PN based on liver tumor biopsy findings and the tumor form. Because the tumor had invaded along the intrahepatic portal vein, surgical resection was deemed difficult, and the patient was followed up with imaging studies. The patient remained asymptomatic without tumor growth.

Neurofibromatosis type 1 (NF1) affects cell growth in neural tissues, resulting in neurofibromas of the internal organs, peripheral nerves and/or autonomic nerves. We describe a highly unusual case of plexiform neurofibroma presenting with lacrimal gland enlargement in an 18 year old male, which led to a diagnosis of NF1.

Purpose:  High-frequency ultrasound allows the accurate identification of neurofibromas in neurofibromatosis type 1 (NF1). This study aimed to analyze the ultrasound features of neurofibromas in children with NF1, to establish a classification based on the clinical and sonographic patterns of the different types of neurofibromas, and to evaluate the interobserver correlation coefficient (κ) of this classification., Materials and Methods:  In this prospective, single referral center observational study, clinical and ultrasound findings of neurofibromas in children diagnosed with NF 1 were analyzed. To identify the ultrasound patterns, a cluster analysis allowing the inclusion of both clinical and ultrasound data was designed. The κ coefficient was calculated using 9 external evaluators., Results:  265 ultrasound scans were performed on a total of 242 neurofibromas from 108 children diagnosed with NF1. Cluster analysis allowed the identification of 9 patterns (Snedecor's F, P < 0.001) classified as "classic" cutaneous neurofibroma, blue-red neurofibroma, pseudoatrophic neurofibroma, nodular subcutaneous neurofibroma, diffuse subcutaneous neurofibroma, congenital cutaneous neurofibroma, congenital plexiform neurofibroma, congenital diffuse and plexiform neurofibroma, and subfascial neurofibroma. The κ coefficient of the interobserver ratings was 0.82., Conclusion:  Patterns identified in the cluster analysis allow neurofibromas to be classified with a very high interobserver correlation., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Background and Objectives: Internal neurofibromas, including plexiform neurofibromas (PNF), can cause significant morbidity in patients with neurofibromatosis type 1 (NF1). PNF growth is most pronounced in children and young adults, with more rapid growth thought to occur in a subset of PNF termed distinct nodular lesions (DNL). Growth behavior of internal neurofibromas and DNL in older adults is not well documented; yet knowledge thereof is important for patient risk stratification and clinical trial design. The primary objective of this study was to evaluate the long-term growth behavior of internal neurofibromas in adults with NF1. Secondary objectives were to correlate tumor growth behavior with patient-specific, tumor-specific, and patient-reported variables., Methods: In this prospective cohort study, internal neurofibromas were identified on coronal short TI inversion recovery sequences on baseline and follow-up whole-body MRIs (WBMRIs). Tumor growth and shrinkage were defined as a volume change ≥20%. The association between tumor growth and patient-specific (baseline age, sex, and genotype), tumor-specific (morphology, location, DNL presence on baseline WBMRI, and maximum standardized uptake value on baseline PET imaging), and patient-reported variables (endogenous and exogenous hormone exposure, pain intensity, and quality of life) was assessed using the Spearman correlation coefficient and Kruskal-Wallis test., Results: Of 106 patients with a baseline WBMRI obtained as part of a previous research study, 44 had a follow-up WBMRI. Three additional patients with WBMRIs acquired for clinical care were included, generating 47 adults for this study. The median age during baseline WBMRI was 42 years (range 18-70). The median time between WBMRIs was 10.4 years. Among 324 internal neurofibromas, 62.8% (56% of PNF and 62.1% of DNL) shrank spontaneously without treatment and 17.1% (17.9% of PNF and 13.8% of DNL) grew. Growth patterns were heterogeneous within participants. Patient-specific, tumor-specific, and patient-reported variables (including endogenous and exogenous hormone exposure) were not strong predictors of tumor growth., Discussion: Internal neurofibroma growth behavior in older adults differs fundamentally from that in children and young adults, with most tumors, including DNL, demonstrating spontaneous shrinkage. Better growth models are needed to understand factors that influence tumor growth. These results will inform clinical trial design for internal neurofibromas., (© 2022 American Academy of Neurology.)

Background: As a subtype of neurofibromatosis, the plexiform neurofibroma is a benign, autosomally inherited disorder and predisposed to tumour formation. However, life-threatening haemorrhage into facial plexiform neurofibroma is extremely rare., Case Information: In the current study, we showed a facial plexiform neurofibroma case with massive haemorrhage in the cranio-maxillofacial region. An emergent selective angiography of the external carotid artery was performed to identify the offending artery, which was then selectively occluded by the combination of detachable coils and Onyx-34. Thus, the minimally invasive drainage surgery was successfully performed to evacuate the haematoma., Conclusion: We believe the endovascular embolization achieved its purpose by providing an initial salvage strategy for stopping active haemorrhage in plexiform neurofibroma, allowing surgeons to perform open surgery with lower complications rate.

Background/aim: Neurofibromatosis type 1 (NF1) is an autosomal dominant tumor predisposition syndrome that is also characterized by skeletal abnormalities. In the cranial region, skeletal dysplasia is observed that is associated with a characteristic peripheral nerve sheath tumor, the plexiform neurofibroma (PNF). The aim of the study was to determine PNF-associated skeletal asymmetries of the mid-skull and skull base as an indicator of local tumor development., Patients and Methods: The distances of the zygomatic arch, mastoid, and juga measurement points from the interorbital horizontal plane and median sagittal plane were examined on anterior-posterior cephalograms of 168 NF1 patients (females: 82, males: 86) and compared with the findings of a control group. A distinction was made as to whether the patients had developed a facial PNF., Results: The distances of the measurement points from the reference planes differed between the patient and control group (p<0.05). Within the NF1 patients, differences between certain distances were noted when comparing patients with PNF and without PNF (p<0.05). In PNF patients, discrete changes in the skull contour were also detectable on the non-affected side (p<0.05). The caudal measurement point of the skull base showed no changes in the group comparison., Conclusion: The individually very variable facial PNF in NF1 is associated with deformations and misalignments of midfacial bones that follow a pattern quantifiable with cephalometric analysis., (Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

A 16-year-old male presented with solitary occipital plexiform neurofibroma, which had grown slowly over several years to reach giant size, thereby mimicking a "double head." There were no features of neurofibromatosis type 1. Total excision of the neurofibroma was done by infiltrating adrenaline circumferentially around the tumor before scalp incision. The feeding arteries were identified in the dense connective tissue above the aponeurosis and ligated or cauterized. Dissection was then carried out in the loose areolar tissue preserving the periosteal layer. There was no evidence of malignant transformation on histopathology, and 5-year follow-up showed no tumor recurrence., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Neurofibromatosis type-1 (NF1)-associated plexiform neurofibromas (PN) are peripheral nerve sheath tumors that can significantly affect the quality of life. Until recently, surgery was the only treatment for these tumors. However, in most cases, surgery cannot achieve complete tumor removal and carries a high risk of postoperative deficits. Therefore, the recent approval of the MEK inhibitor selumetinib for the treatment of NF1-associated PN provides a long-awaited novel therapeutic option. Here, we report our experience with MEK inhibitor treatment in 12 pediatric NF1 patients with inoperable symptomatic PN. Eight patients received trametinib (median therapy duration 12.13 months and range 4-29 months), and four patients received selumetinib (median therapy duration 6.25 months and range 4-11 months). Volumetric magnetic resonance imaging (MRI) after 6 months of treatment was available for seven trametinib patients (median tumor volume reduction of 26.5% and range 11.3-55.7%) and two selumetinib patients (21.3% tumor volume reduction in one patient and +3% tumor volume change in the other one). All patients reported clinical benefits such as improved range of motion or reduced disfigurement. Therapy-related adverse events occurred in 58.3% of patients and mainly consisted of skin toxicity, paronychia, and gastrointestinal symptoms. Two patients discontinued trametinib treatment after 14 and 29 months when severe skin toxicity occurred and no further reduction of tumor size was observed. In one patient, discontinuation of therapy resulted in a 27.2% tumor volume increase as demonstrated on volumetric MRI 6 months later. Our data show that MEK inhibition is a novel therapeutic approach for inoperable PN with promising results and a manageable safety profile., Competing Interests: P.V. and N.R.D. declared no conflict of interest. T.R. received consulting fees from AstraZeneca., (Thieme. All rights reserved.)

Clinical Problem: Neurofibromatosis type 1 (NF1) and tuberous sclerosis (TS) are among the most common genetic diseases. Bone and soft tissue manifestations are common disease manifestations., Standard Radiological Procedure and Evaluation: The standard radiological procedure is magnetic resonance imaging (MRI). All macroscopic disease manifestations can be diagnosed radiologically and observed during the course. Specific complications such as plexiform neurofibromas and malignant peripheral nerve sheath tumors (MPNST) in NF1 are readily visible on MRI. Differentiation of plexiform neurofibromas and MPNST is uncertain and requires follow-up., Recommendation for Practice: MRI is the most important procedure for the investigation of soft tissue and bone manifestations of NF1 and TS., (© 2021. Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Competing Interests: Competing interests: None declared.

Introduction: Plexiform neurofibromas (PNF) in neurofibromatosis type 1 (NF1) are usually diagnosed in childhood and can grow rapidly during this period. In 10% of patients, PNF involve the orbital-periorbital area and may cause visual problems including glaucoma, visual loss from amblyopia (deprivational, strabismic, or refractive), optic nerve compression, or keratopathy. Ptosis, proptosis, and facial disfigurement lead to social problems and decreased self-esteem. Complete surgical removal involves significant risks and mutilation, and regrowth after debulking is not uncommon. Inhibitors of the RAS/MAPK pathway have recently been investigated for their activity in PNF. We administered the oral MEK inhibitor trametinib to five young children with NF1 and PNF of the orbital area, with visual compromise and progressive tumor growth; and followed them clinically and by volumetric MRI., Methods: Treatment was initiated at a mean age of 26.8 months (SD ± 12.8) and continued for a median 28 months (range 16-51). Doses were 0.025 mg/kg/day for children aged > 6 years and 0.032 mg/kg/day for those aged < 6 years., Results: Volumetric MRI measurements showed a reduction of 2.9-33% at 1 year after treatment initiation, with maximal reductions of 44% and 49% in two patients, at 44 and 36 months, respectively. No change in visual function was recorded during treatment. One child reported decreased orbital pain after 2 weeks; and another, with involvement of the masseters, had increased ability to chew food. Toxicities were mostly to skin and nails, grades 1-2., Conclusions: Trametinib can decrease tumor size in some young children with orbital PNF and may prevent progressive disfigurement.

Purpose: To describe a series of children with extensive PNF or treatment refractory PLGG treated on a compassionate basis with trametinib., Methods: We report on six patients with NF-1 treated with trametinib on a compassionate basis at British Columbia Children's Hospital since 2017. Data were collected retrospectively from the patient record. RAPNO and volumetric criteria were used to evaluate the response of intracranial and extracranial lesions, respectively., Results: Subjects were 21 months to 14 years old at the time of initiation of trametinib therapy and 3/6 subjects are male. Duration of therapy was 4-28 months at the time of this report. All patients had partial response or were stable on analysis. Two patients with life-threatening PNF had a partial radiographic response in tandem with significant clinical improvement and developmental catch up. One subject discontinued therapy after 6 months due to paronychia and inadequate response. The most common adverse effect (AE) was grade 1-2 paronychia or dermatitis in 5/6 patients. There were no grade 3 or 4 AEs. At the time of this report, five patients remain on therapy., Conclusion: Trametinib is an effective therapy for advanced PNF and refractory PLGG in patients with NF-1 and is well tolerated in children. Further data and clinical trials are required to assess tolerance, efficacy and durability of response, and length of treatment required in such patients., (© 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Purpose: Patients with neurofibromatosis type 1 (NF1) frequently develop plexiform neurofibromas (PNs), which can cause significant morbidity. We performed a phase II trial of the MAPK/ERK kinase inhibitor, mirdametinib (PD-0325901), in patients with NF1 and inoperable PNs. The primary objective was response rate based on volumetric magnetic resonance imaging analysis., Methods: Inclusion criteria included age ≥ 16 years and a PN that was either progressive or causing significant morbidity. First-dose pharmacokinetics were performed. Patients completed patient-reported outcome measures. Patients received mirdametinib by mouth twice a day at 2 mg/m 2 /dose (maximum dose = 4 mg twice a day) in a 3-week on/1-week off sequence. Each course was 4 weeks in duration. Evaluations were performed after four courses for the first year and then after every six courses. Patients could receive a maximum of 24 total courses., Results: Nineteen patients were enrolled, and all 19 received mirdametinib. The median age was 24 years (range, 16-39 years); the median baseline tumor volume was 363.8 mL (range, 3.9-5,161 mL). Eight of the 19 patients (42%) achieved a partial response of the target PN by course 12, and 10 (53%) had stable disease. One patient (5%) developed progressive disease at course 8. Significant and durable decreases were observed in pain ratings., Conclusion: To our knowledge, this analysis represents the first characterization of the activity and pharmacokinetics of mirdametinib in patients with NF1 and PNs and is the first published response study for MAPK/ERK kinase inhibitors in adults with NF1 and PNs. Mirdametinib given at 2 mg/m 2 /dose (maximum dose, 4 mg) twice daily in a 3-week on/1-week off sequence resulted in a 42% partial response rate with preliminary evidence of reduction in pain.

Plexiform neurofibroma is mainly associated with neurofibromatosis type 1 and is seldom observed in the liver. Its occurrence in the liver without neurofibromatosis type 1 is even rarer. We report an extremely rare case of plexiform neurofibroma of the liver diagnosed by laparoscopic biopsy in a patient without neurofibromatosis type 1. The patient was a 35-year-old man who had neither clinical signs nor any family history of neurofibromatosis type 1. Abdominal ultrasonography, as part of a health screening, had detected a hepatic tumor. Subsequent contrast ultrasonography, computed tomography, and magnetic resonance imaging showed the tumor extending from the retroperitoneal space around the aorta to the hepatic hilum and distal portal branches in the right hepatic lobe, gallbladder, and left hepatic lobe. 18 F-fluorodeoxyglucose positron emission tomography showed no abnormal accumulation. Histopathological examination of the tumor obtained laparoscopically led to a diagnosis of plexiform neurofibroma. Because the patient was asymptomatic with no features of malignancy, he was only monitored and managed. At follow-up 10 years later, computed tomography showed a decrease in tumor size. It is important to recognize that, while rare, plexiform neurofibroma can occur without neurofibromatosis type 1. We recommend follow-up instead of unreasonable surgery in such cases.

Background: Understanding the natural history of non-malignant peripheral nerve sheath tumors (PNSTs) in neurofibromatosis type 1 (NF1) is critical to optimal clinical care and the development of meaningful clinical trials., Methods: We longitudinally analyzed growth of plexiform neurofibromas (PNs) and of PNSTs with distinct nodular appearance (distinct nodular lesions [DNLs]) using volumetric MRI analysis in patients enrolled on a natural history study (NCT00924196)., Results: DNLs were observed in 58/122 (45.6%) patients (median 2 DNLs/patient). In DNLs that developed during follow-up, median age of development was 17 years. A moderate negative correlation was observed between the estimated PN growth rate and patients' age at initial MRI (Spearman's r [95% CI]: -0.60 [-0.73, -0.43], n = 70), whereas only a weak correlation was observed for DNLs (Spearman's r [95% CI]: -0.25 [-0.47, 0.004]; n = 61). We observed a moderate negative correlation between tumor growth rate and baseline tumor volume for PNs and DNLs (Spearman's r [95% CI]: -0.52 [-0.67, -0.32] and -0.61 [-0.75, -0.42], respectively). Spontaneous tumor volume reduction was observed in 10 PNs and 7 DNLs (median decrease per year, 3.6% and 7.3%, respectively)., Conclusion: We corroborate previously described findings that most rapidly growing PNs are observed in young children. DNLs tend to develop later in life and their growth is minimally age related. Distinct growth characteristics of PNs and DNLs suggest that these lesions have a different biology and may require different clinical management and clinical trial design. In a subset of PNs and DNLs, slow spontaneous regression in tumor volume was seen., (Published by Oxford University Press on behalf of the Society for Neuro-Oncology 2020.)

Background: Respiratory distress is a frequent occurrence in neonates, typically caused by a variety of pulmonary conditions. Accurate diagnosis of the cause is vital to appropriately treat neonates and prevent long-term complications. Neck masses rarely cause respiratory distress in this setting but should be considered when clinical signs indicate., Methods: The authors present the patient with a neonate born at term who developed stertor, respiratory distress requiring intubation, and repeated failure to extubate., Results: Physical examination showed right-sided lower and midface enlargement with a firm mass mostly over the parotid and right neck. Both computerized and magnetic resonance tomography demonstrated a right-sided neck mass. Surgical exploration revealed extensive tumor burden emanating from the great auricular, hypoglossal, and other nerves of the neck, including invasion of the carotid sheath encasing the artery. Excisional biopsy showed plexiform neurofibroma, and pathognomonic for neurofibromatosis type 1. The decision was made to pursue medical management, as complete excision would have resulted in increased morbidity due to the involvement of multiple cranial nerves. The patient underwent microlaryngoscopy, bronchoscopy, and tracheostomy and was started on Trametinib chemotherapy., Conclusion: Neonatal airway obstruction can rarely be caused by unanticipated mass lesion, such as plexiform neurofibroma. A high index of suspicion must be maintained for early onset mass lesions causing respiratory obstruction to inhibit early disease progression and avoid potentially fatal sequelae.

Introduction: Patients with Neurofibromatosis type 1 (NF1) develop plexiform neurofibromas (PNF) and cutaneous neurofibromas. These tumors are a major cause of the patient's morbidity and mortality. An influence of estrogen and progesterone on tumor growth has been suggested but reports on growth or malignant transformation of tumors during pregnancy remain anecdotal. The purpose of this study was to quantify growth of cutaneous and plexiform neurofibromas in NF1 patients during pregnancy, and to assess the onset of NF1 related symptoms., Material and Methods: Retrospectively, 13 mothers with NF1 were included and compared to nullipara, nulligravida, age-matched women with NF1. All women received whole-body magnetic resonance imaging (MRI) before and after pregnancy or after a matched time period. Presence of plexiform and cutaneous neurofibromas was evaluated. PNF were subjected to semi-automated volumetry (MedX). The sum of the longest diameters (SLD) of representative cutaneous neurofibromas was determined for both groups. Clinical symptoms and subjective tumor growth were assessed., Results: PNF were identified in 12/26 women (46.2%). Follow up showed neither new PNF nor a significant difference in growth rate (median tumor-growth/year: pregnant group-0.38% (IQR -1.1-5.4%) vs control group 3.59% (IQR -2.1-5.5%; P = 0.69). Malignant transformation of PNF was not observed. There was a significant growth of cutaneous neurofibromas in both groups (median SLD increase: pregnant group 17mm; P = 0.0026 / control group 12mm; P = 0.0004) The difference in increase of SLD was not significant (P = 0.48). Singular cutaneous neurofibromas in the pregnant group displayed high levels of tumor growth (>20%/year). NF1-associated symptoms and subjective tumor growth were not significantly increased in pregnant patients., Conclusions: Growth of plexiform and cutaneous neurofibromas in pregnant patients is not significantly different compared to non-pregnant patients. Cutaneous neurofibromas show a significant increase in growth over time in both, pregnant and non-pregnant patients and NF1 related clinical symptoms do not significantly aggravate during the course of pregnancy., Competing Interests: The authors have declared that no competing interests exist.

Background: "Kissing" neurofibromas (KNs) are a unique group of spinal tumors found in neurofibromatosis type 1 (NF1) patients. These are bilateral neurofibromas that approximate each other at the same level, with significant impingement compression of the cord or thecal sac. The best management options and surgical strategies for NF1 patients with KN have not been standardized., Methods: We conducted a retrospective study evaluating adult NF1 patients with KN. All patients are followed routinely at the Gilbert Israeli NF Center. Patients' files were reviewed for natural history, imaging features, surgical technique, and surgical outcome., Results: Twelve patients with at least 1 pair of KN were identified (6 females). Median age at spinal presentation was 24 (range 17-48). KNSs were located at the cervical (n = 8) and lumbar (n = 8) region, with no thoracic involvement. Seven of the 12 patients were operated; all underwent surgery due to cervical compression with progressive myelopathy. Four patients remained asymptomatic during the follow-up period. Three patients underwent multiple operations. Operative outcome was favorable in 71% of patients, with marked overall motor improvement or stabilization of neurologic deterioration. Two patients who entered surgery with a low functional reserve deteriorated after surgery., Conclusions: In our series, KN caused progressive cord compression in 7 of the 8 patients with cervical tumors. No intervention was needed for lumbar tumors. Cervical tumors should be followed closely, with a low threshold for intervention. NF1 patients harboring KN should be followed both clinically and radiologically for life., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Neurofibromatosis type 1 (NF1) is a multisystem phakomatosis. The intrathoracic manifestations of NF1 are protean. We describe a rare case of a plexiform neurofibroma infiltrating the mediastinum and lungs with multiple endobronchial neurofibromata. To our knowledge, a mediastinal plexiform neurofibroma extending into the lungs on CT has not been reported., (© 2018 The Royal Australian and New Zealand College of Radiologists.)

Background: Neurofibromatosis (NF) is an autosomal dominant genetic disorder, and NF type 1 (NF1) is one of the most common forms. Plexiform neurofibroma (PNF) is one of the characteristic expressions of NF1. The proper treatment for patients with craniofacial PNF is surgery. The evaluation methods for the surgical outcome of these patients are still controversial. As a consequence, a one-stage surgical technique and an appropriate evaluation method for patients with craniofacial PNF were discussed in this article., Methods: This research is a retrospective study. Nine patients with craniofacial PNF were included in this study. They had undergone a one-stage surgical technique of tumor debulking and nasolabial fold reconstruction. Three methods had been applied to evaluate the surgical outcome., Results: Significant improvement was observed in 8 patients. Eight patients were assessed by the relatively objective evaluation method. Obvious symmetry improvement was calculated using Mimics software in 7 patients., Conclusion: The surgical technique could achieve good surgical outcomes in both functional and cosmetic terms. Additionally, the relatively objective evaluation technique based on Mimics software could be a more convincing method for evaluating the surgical outcomes of craniofacial patients with PNF.

Purpose: Neurofibromatosis type 1 (NF1) is a tumour suppressor syndrome and also a bone disease. In the craniofacial region, local skeletal deformities have been recorded in patients with NF1. Obvious syndrome-related alterations of the jaws are particularly conspicuous in the mandible. Here we aimed to analyse the mandibular alterations of NF1-affected individuals from orthopantomograms (OPGs)., Materials and Methods: This study analyses 358 OPGs of 358 patients (mean age, 34.63 years; range, 12.57-69.13 years). The OPGs of 179 patients of Caucasian origin with NF1 were investigated (mean age, 34.84 years; range, 12.83-68.89 years; 44.13% male, 55.86% female). The radiographic findings were compared to those obtained from OPGs of sex- and age-matched controls., Results: Characteristic deformations of the bone regions of interest occur in NF1 patients, especially in patients with plexiform neurofibroma of trigeminal nerve. These findings are always one-sided. The co-occurrence of several skeletal deformations can be expected with very high probability in this patient group., Conclusion: The radiological sign of the unilateral deformed mandible should be included in the diagnostic criteria for NF1. In addition to the diagnostic value in this syndrome, these findings are important for avoiding surgical complications in planned interventions in this region., (Copyright © 2018 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.)

Objectives: Plexiform neurofibromas (PNs) are complex, histologically benign peripheral nerve sheath tumors that are challenging to measure by simple line measurements. Computer-aided volumetric segmentation of PN has become the recommended method to assess response in clinical trials directed at PN. Different methods for volumetric analysis of PN have been developed. The goal of this study is to test the level of agreement in volume measurements and in interval changes using two separate methods of volumetric magnetic resonance imaging analysis., Methods: Three independent volume measurements were performed on 15 PN imaged at three time-points using 3DQI software at Massachusetts General Hospital (MGH) and National Cancer Institute (NCI) and MEDx software at NCI., Results: Median volume differences at each time-point comparing MGH-3DQI and NCI-3DQI were -0.5, -4.2, and -19.9 mL; comparing NCI-3DQI and NCI-MEDx were -21.0, -47.0, and -21.0 mL; comparing MGH-3DQI and NCI-MEDx were -10.0, -70.3, and -29.9 mL. Median differences in percentage change over time comparing MGH-3DQI and NCI-3DQI were -1.7, 1.1, and -1.0%; comparing NCI-3DQI and NCI-MEDx were -2.3, 3.3, and -1.1%; comparing MGH-3DQI and NCI-MEDx were -0.4, 2.0, and -1.5%. Volume differences were <20% of the mean of the two measurements in 117 of 135 comparisons (86.7%). Difference in interval change was <20% in 120 of the 135 comparisons (88.9%), while disease status classification was concordant in 115 of 135 comparisons (85.2%)., Conclusions: The volumes, interval changes, and progression status classifications were in good agreement. The comparison of two volumetric analysis methods suggests no systematic differences in tumor assessment. A prospective comparison of the two methods is planned., (Published by Elsevier Inc.)

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 and Purpose: Neurofibromatosis type 1 is a common tumor predisposition syndrome. The aim of this study was to characterize the radiologic presentation of patients with neurofibromatosis type 1 with widespread spinal disease and to correlate it to clinical presentation and outcome., Materials and Methods: We conducted a historical cohort study of adult patients with neurofibromatosis type 1 with spinal involvement. Longitudinal clinical evaluation included pain and neurologic deficits. Radiologically, spinal involvement was classified according to a novel classification system, and a radiologic risk score was calculated., Results: Two hundred fifty-seven adult patients with neurofibromatosis type 1 are followed in our center. Thirty-four of these patients qualified for inclusion in this study. Three independent factors were found to be associated with increased risk for neurologic deficit: 1) bilateral tumors at the same level in the cervical region that approximated each other, 2) paraspinal tumors at the lumbar region, and 3) intradural lesions. On the basis of these factors, we calculated a combined risk score for neurologic deficits for each patient. We found a clear correlation between patient status and the calculated radiologic risk score. Patients with neurologic deficits were found to have a higher risk score (9 ± 8.3) than patients without neurologic deficits (2.5 ± 2.9, P < .05). Patients who progressed during the follow-up period had significantly higher scores at presentation than patients with stable conditions (9.9 ± 8.73 versus 3.9 ± 5.3, respectively; P < .05)., Conclusions: In this series, neurologic deficit is correlated with tumor burden and subtype. We found no direct correlation with tumor burden and pain. Our novel radiologic classification scoring system may be used to predict increased risk for neurologic morbidity., (© 2017 by American Journal of Neuroradiology.)

Background: Neurofibromatosis type 1 is a relatively common inherited disorder. Patients with neurofibromatosis type 1 are at high risk of developing neurogenic, neuroendocrine and mesenchymal intra-abdominal tumors. Although coexistence of multiple tumors of different types is frequent in neurofibromatosis type 1, simultaneous occurrence of abdominal tumors of three types in very rare., Case Presentation: A 66-year-old lady with neurofibromatosis type 1 presented with painless progressive jaundice for six months. Laboratory investigations revealed iron deficiency anemia and conjugated hyperbilirubinemia. Tumor markers were normal. Abdominal computed tomography showed a 3 × 2 cm heterogenous mass in the periampullary region with mild dilation of the common bile duct and another 2 × 1.7 cm mass in the fourth portion of the duodenum. Endoscopic biopsy confirmed the diagnosis of periampullary carcinoid. At surgery, multiple small nodules were detected at the hepatic hilum. Frozen section suggested them to be neurofibromas. Patient underwent pancreatoduodenectomy and had uneventful recovery with no recurrence at two months. Microscopic examination of the resected specimen confirmed presence of three tumors: periampullary well differentiated neuroendocrine tumor, gastrointestinal stromal tumor of the fourth part of duodenum and plexiform neurofibroma at the hepatic hilum., Conclusion: Patients of neurofibromatosis type 1 with abdominal symptoms should be treated with high index of clinical suspicion and thoroughly evaluated to rule out multiple tumors.

Competing Interests: Competing interests: None declared.

Background: Effective medical therapies are lacking for the treatment of neurofibromatosis type 1-related plexiform neurofibromas, which are characterized by elevated RAS-mitogen-activated protein kinase (MAPK) signaling., Methods: We conducted a phase 1 trial of selumetinib (AZD6244 or ARRY-142886), an oral selective inhibitor of MAPK kinase (MEK) 1 and 2, in children who had neurofibromatosis type 1 and inoperable plexiform neurofibromas to determine the maximum tolerated dose and to evaluate plasma pharmacokinetics. Selumetinib was administered twice daily at a dose of 20 to 30 mg per square meter of body-surface area on a continuous dosing schedule (in 28-day cycles). We also tested selumetinib using a mouse model of neurofibromatosis type 1-related neurofibroma. Response to treatment (i.e., an increase or decrease from baseline in the volume of plexiform neurofibromas) was monitored by using volumetric magnetic resonance imaging analysis to measure the change in size of the plexiform neurofibroma., Results: A total of 24 children (median age, 10.9 years; range, 3.0 to 18.5) with a median tumor volume of 1205 ml (range, 29 to 8744) received selumetinib. Patients were able to receive selumetinib on a long-term basis; the median number of cycles was 30 (range, 6 to 56). The maximum tolerated dose was 25 mg per square meter (approximately 60% of the recommended adult dose). The most common toxic effects associated with selumetinib included acneiform rash, gastrointestinal effects, and asymptomatic creatine kinase elevation. The results of pharmacokinetic evaluations of selumetinib among the children in this trial were similar to those published for adults. Treatment with selumetinib resulted in confirmed partial responses (tumor volume decreases from baseline of ≥20%) in 17 of the 24 children (71%) and decreases from baseline in neurofibroma volume in 12 of 18 mice (67%). Disease progression (tumor volume increase from baseline of ≥20%) has not been observed to date. Anecdotal evidence of decreases in tumor-related pain, disfigurement, and functional impairment was observed., Conclusions: Our early-phase data suggested that children with neurofibromatosis type 1 and inoperable plexiform neurofibromas benefited from long-term dose-adjusted treatment with selumetinib without having excess toxic effects. (Funded by the National Institutes of Health and others; ClinicalTrials.gov number, NCT01362803 .).

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.

Neurofibromatosis type 1 (NF1) is the most common of the phakomatoses, which is inherited in an autosomal dominant pattern. Neurofibromas arise from Schwann cells and fibroblasts and plexiform neurofibromas are pathognomonic for NF1, which may arise in any peripheral nerve. The clinical expression of NF1 is extremely variable and gastrointestinal manifestations of NF1 are relatively uncommon. The purpose of this article is to illustrate the abdominal ultrasound, computed tomography, and magnetic resonance imaging findings of abdominopelvic nerve tumours seen in NF1 in both paediatric and adult patients., (Copyright © 2013 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Background/aim: Xenografted benign tumours in immunodeficient mice provide an in vivo model to study tumour biology and the effect of agents on tumour growth. Conventionally, these small grafts can only be monitored upon sacrificing the animals. We evaluated ultrasound biomicroscopy for monitoring such grafts in vivo., Materials and Methods: Small fragments (<10 mm(3)) of a plexiform neurofibroma obtained from patients with established diagnosis of neurofibromatosis type-1 (NF1) were orthotopically-xenografted onto the sciatic nerve of immunodeficient mice and monitored using a high-resolution in vivo micro-imaging system., Results: Grafts were identified in most cases and were distinguished from the surrounding inflammatory host tissues by detailed ultrasonographic signals. Graft sizes could be calculated precisely from serial scan sections and monitored during the whole course of drug treatment., Conclusion: High frequency sonographic measurement is a superior non-invasive method for monitoring small grafts of slowly growing benign tumours in mice in vivo, e.g. plexiform neurofibroma, and is especially suitable for tracing the effects of drugs at multiple time-points, thus allowing a very cost-effective follow-up.

Neurofibromatosis of the urinary tract occurs infrequently: fewer than 70 cases with bladder involvement have been reported to date and of these, only 25 cases occurred in the pediatric population. We describe an unusual case of plexiform neurofibroma and diffuse ganglioneuromatosis of the bladder in a small infant, diagnosed with neurofibromatosis 1 (NF1) at 3 months of age. At the moment, there are no established criteria for the treatment of this rare lesion. Due to the high morbidity, although not very common, bladder involvement should be considered in infants with NF1., (Copyright © 2013 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Unlabelled: Neurofibromatosis type 1 (NF1) is an autosomal dominant inherited disease. Some stigmata of NF1 occur in the orbital region. The aim of this study was to reveal whether alterations of the orbital rim visible on plain radiographs may indicate the presence of a plexiform neurofibroma (PNF), a tumour almost exclusively diagnosed in NF1., Material and Methods: The plain orbital radiographs of 73 patients with NF1 (female: N=37, male: N=36) were investigated for alterations of the orbit. The group was further distinguished according to the presence of orbital PNF (N=53) and/or sphenoid wing dysplasia (N=30). Radiographs from patients with NF1 and with exclusion of PNF in the orbitofacial region were used for comparison (N=20). A special cephalometric analysis (Dental Vision™) was adapted to the demands of this study., Results: Patients with NF1 not affected by an orbitofacial PNF exhibited symmetrical orbits. Unilateral increase in orbital height was associated with ipsilateral PNF. The width of orbits affected by a PNF was often slightly increased compared to the non-affected side. The determination of cephalometrically-defined angles disclosed an erection of the PNF-affected orbit compared to the medio-sagittal plane., Conclusion: Plain radiographs are often the first diagnostic measure used to determine skeletal alterations. This study shows that certain parameters of the orbital rim are useful indicators of a PNF in patients who are unilaterally affected by this lesion in the orbital or orbitotemporal region.

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.

Purpose: Neurofibromatosis 1 (NF1) is a neurocutaneous-skeletal disorder with variable phenotypic expression and an incidence of 1:3,000 worldwide. The objective was to characterize the NF1-related radiologic alterations found in the jaws of these patients., Patients and Methods: In total, 102 patients with NF1 were included in the present study. Six patients had a plexiform neurofibroma in the craniofacial region., Results: Radiologic abnormalities in the jaws were found in 29 of 102 patients with NF1, including 6 patients with plexiform neurofibroma in the head and neck region. The most common radiologic finding was enlargement of the mandibular canal. The most prominent skeletal deformities and alterations of varying severity were detected in the jaws of 6 patients with plexiform neurofibroma. In these patients, the skeletal deformities were seen on the side affected by the tumor and possibly caused by the tumor. In 1 patient, however, the skeletal changes were on the opposite side., Conclusions: Radiologic abnormalities were found in 29 of 102 patients. The most significant findings were profound deformities of the mandible and maxilla in all 6 patients with plexiform neurofibroma, but not in the other patients. The facial bone deformities found in young patients did not progress markedly at older ages with cessation of the patients' growth., (Copyright © 2012 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.)

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.

A 19-year-old female with established neurofibromatosis type 1 (NF1) diagnosis and history of malignant peripheral nerve sheath tumour (MPNST) of the lower extremities showed a tumour of her right upper extremity with a maximum standardised uptake value (SUV) of 5.7 on positron emission/computerised tomography (PET/CT) scan. The extirpated tumour proved to be an atypical plexiform neurofibroma. Immunohistochemical investigations revealed a strong positive reaction of tumour cells for S-100 protein. Epithelial membrane antigen (EMA)-positive perineural cells were demonstrated at the border of the tumour. Scattered nerve fibres were labelled with neurofilament antibodies within the tumour. The maximum Ki-67 labelling index reached 9%. Slight to moderate podoplanin expression of the tumour cells was noted in areas of fibrillary growth. Podoplanin expression has been proposed as a differentiation marker for schwannomas and neurofibromas. This atypical neurofibroma showed a high SUV on PET that is indicative for MPNST. It appears likely that subtypes of Schwann cells express podoplanin. This marker may be useful in distinguishing different Schwann cell populations in neurofibromas.

Purpose: There is little consensus regarding optimal surveillance of optic pathway glioma (OPG) and plexiform neurofibroma (PNF) in childhood neurofibromatosis type 1 (NF1). (18)F-2-Fluoro-2-deoxy-D: -glucose (FDG) positron emission tomography and computed tomography (PET/CT) is employed in the surveillance of adult PNFs; but its utility has neither been specifically studied in children with PNFs nor in children with OPG., Methods: Review of PET/CT studies was performed in NF1 children with OPG or PNF. FDG-avidity of tumours was semi-quantitatively analysed and graded by calculating the maximum standardised uptake value (SUV(max)) [grade 1: <3 (low), grade 2: >3-<4 (intermediate), grade 3: >4 (intense)]., Results: Eighteen children (ten girls; median age: 8.5-years) had PET/CT. Nineteen OPGs were imaged. The SUV(max) could be measured in 16. Ten were grade 1 and three each were grade 2 and grade 3. FDG-avidity reduced from grade 3 to grade 1 in two symptomatic OPGs following chemotherapy and this was associated with clinical improvement. PET/CT diagnosed symptomatic OPGs with a sensitivity of 0.625 [95% confidence interval (CI): 0.259-0.897] and specificity of 0.875 (95% CI: 0.466-0.993). Sixteen PNFs were imaged. Twelve were grade 1 and two each were grade 2 and grade 3. The two grade 3 PNFs were confirmed malignant peripheral nerve sheath tumours. PET/CT diagnosed malignant transformation with a sensitivity of 1.0 (95% CI: 0.197-1.0) and specificity of 0.857 (95% CI: 0.561-0.974)., Conclusion: PET/CT may contribute useful information to the surveillance of OPG in childhood NF1-particularly to identify progressive, symptomatic tumours. As in adults, PET/CT is useful for the detection of malignant transformation in PNFs in children with NF1.

Plexiform neurofibroma at the thoracic inlet has rarely been reported and to our knowledge, the use of a temporary middle claviculectomy approach for thoracic inlet tumors has never been reported. We report a case of plexiform neurofibroma of the first intercostal nerve resected using a temporary claviculectomy approach. An abnormal shadow detected radiographically in a 16-year-old boy led to a diagnosis of neurofibromatosis 1 (NF-1) with a chest wall tumor at the thoracic inlet. The patient underwent resection of the tumor with the right first rib. The resected clavicle was reapproximated with a plate and postoperative shoulder function was satisfactory. The tumor was diagnosed pathologically as a plexiform neurofibroma and the patient's postoperative course was uneventful. The temporary middle claviculectomy approach provides excellent exposure of the subclavian vessels and brachial plexus before resection of the tumor. We recommend this approach for tumors of the anterior thoracic inlet.

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.