Management and prognosis of malignant peripheral nerve sheath tumors: The experience of the French Sarcoma Group (GSF-GETO)

BackgroundMalignant peripheral nerve sheath tumors (MPNST) are a rare subtype of soft tissue sarcoma. They can arise in irradiated fields, in patients with type 1 neurofibromatosis (NF1), or sporadically. MPNST exhibit an aggressive behaviour, and their optimal management remains controversial. An unsolved issue is whether NF1-related and sporadic forms of MPNST have a different prognosis, and should be managed differently.Material and methodsAdult and paediatric patients with histologically confirmed MPNST treated between 1990 and 2013 in French cancer centres of the GSF/GETO network, were included in this retrospective study.ResultsA total of 353 patients (37% with NF1 and 59% with sporadic tumours) were analysed. Median age at diagnosis was 42 years (range 1–94). The majority of tumours developed in the limbs, were deep-seated and of high grade. Two hundreds and ninety four patients underwent a curative intent surgery. Among them, 60 patients (21%) had neoadjuvant treatment (mainly chemotherapy), and 173 (59%) had adjuvant treatment (mainly radiotherapy). For operated patients, median progression free and overall survival (OS) were 26.3 months and 95.8 months, respectively. In multivariate analysis, poor-prognosis factors for OS were high grade, deep location, locally advanced stage at diagnosis, and macroscopically incomplete resection (R2). NF1 status was not negatively prognostic, except in the recurrence or metastatic setting, where NF1-related MPNST patients treated with palliative chemotherapy showed worse survival than patients with sporadic forms.ConclusionTo our knowledge, our series is the largest study of patients with MPNST reported to date. For operated patients, we showed a worse prognosis for NF1-related MPNST, due to different clinical features at diagnosis, more than NF1 status itself. The French sarcoma group is now conducting correlative analyses on these patients, using the latest molecular tools.     

神经纤维瘤病1型并慢性髓性白血病一例及文献复习

神经纤维瘤病是一组三种异质性疾病，包括神经纤维瘤病1型（NF1）、神经纤维瘤病2型（NF2）和神经鞘瘤病。NF1是这三种疾病中最常见的一种，临床表现多样，其主要特征是良性皮肤病变，包括神经纤维瘤和咖啡斑等。慢性髓性白血病是骨髓造血干细胞克隆性增殖形成的恶性血液肿瘤。检索PUBMED只发现3例关于慢性髓性白血病与神经纤维瘤病1型共存的报道。而通过复习相关文献，我们注意到在合并患有神经纤维瘤病1型的慢性髓性白血病患者，在发病机制及治疗上均有部分重叠。现我们报道1例面部巨大神经纤维瘤病1型患者并发慢性髓性白血病的病例。     

Neuropsychological evaluation and parental assessment of behavioral and motor difficulties in children with neurofibromatosis type 1

Neurofibromatosis type 1 (NF1) is an autosomal dominant multisystem disorder, with large inter and intrafamilial clinical variability and uncertain prognosis. In children with NF1 cognitive disorders, learning difficulties and behavioral problems are common.The present study aims to establish the neuropsychological and behavioral profiles of 78 patients with NF1, aged between 5 and 18 years, and to examine the relationship between these profiles and the transmission of NF1 (sporadic vs. familial), clinical manifestations, and environmental factors.We used several questionnaires completed by parents and neuropsychological tests.The results confirmed specific neuropsychological disabilities in children with NF1, especially involving visuospatial and fine motor skills, learning difficulties and behavioral problems. Cognitive difficulties were significantly more frequent in patients with familial than in those with sporadic NF1. All parental questionnaires were correlated with each other, but parental reports were not associated with FSIQ, SES, school status, and clinical manifestations of the disease.Neuropsychological tests were poorly related to parental reports of cognitive and behavioral difficulties.     

Circle of Willis abnormalities in children with neurofibromatosis type 1

Background and purposeThe aim of the study was to assess anatomical variants and abnormalities in cerebral arteries on magnetic resonance angiography in 67 children with neurofibromatosis type 1 (NF1).Materials and methodsThe study included 67 children aged 9 months to 18 years (mean 6.6 years). Control group comprised 90 children aged 2–18 years (mean: 11.8 years). All patients were examined at 1.5 T scanner.ResultsWe found cerebral arteriopathy (moyamoya disease) in one child (1.5%) in the study group. No aneurysms were found. Twenty-nine NF1 children (43.3%) had arterial anatomical variants. In 13 of them, more than one variant was diagnosed (44.8% of group with variants, 19.4% of study group). In control group, 19 children (21.1%) had variants, including four children with more than one variant (21% of group with variants, 4.4% of control group). Arterial variants were more common in NF1 patients compared with control group (p = 0.026, binomial test for two proportions). Percentage of multiple variants was higher in study group than in control group, but this difference was not significant. Variants were more frequent on left side than on the right one (significant difference in control group; p = 0.022, McNemara test). In study group, the number of left-sided anomalies (25) was similar to that of right-sided ones (22). There was no correlation between gender and variants, unidentified bright objects and variants or between optic gliomas and variants.ConclusionsOccurrence of arterial variants in NF1 patients was twofold higher than in control group. Multiple variants were more frequent in the study group although the difference did not reach statistical significance. Features of cerebral arteriopathy were found in one child with NF1.     

Neurofibromatosis Type 1 and Primary Hyperparathyroidism with Spinal Deformity and Osteoporosis

The association of Neurofibromatosis type 1(NF1) and primary hyperparathyroidism (PHPT) is a well described but very rare entity. This association supports the hypothesis of a variant of multi-endocrine neoplasia syndrome. We report a 52-year-old woman with NF1, PHPT and spinal deformity. She had cutaneous lesions of neurofibromatosis. X-ray imaging has shown severe kyphoscoliosis and bone mineral density measurement has revealed severe osteoporosis. Significant increases in blood calcium and parathormon level were measured. Parathyroid adenoma was determined by ultrasound and MIBI scan. Hyperparathyroidism and hypercalcaemia resolved after surgical removal of adenoma. The general condition of the patient was improved significantly after two months of medical and physical therapy. All NF1 patients who have severe skeletal deformities, osteoporosis, and motor activity loss should be investigated for the concurrence of PHPT.     

Posterior-only spinal fusion without rib head resection for treating type I neurofibromatosis with intra-canal rib head dislocation

OBJECTIVES:

Patients with Type I neurofibromatosis scoliosis with intra-canal rib head protrusion are extremely rare. Current knowledge regarding the diagnosis and treatment for this situation are insufficient. The purpose of this study is to share our experience in the diagnosis and surgical treatments for such unique deformities.

METHODS:

Six patients with Type I neurofibromatosis scoliosis with rib head dislocation into the spinal canal were diagnosed at our institution. Posterior instrumentation and spinal fusion without intra-canal rib head resection via a posterior-only approach was performed for deformity correction and rib head extraction. The efficacy and outcomes of the surgery were evaluated by measurements before, immediately and 24 months after the surgery using the following parameters: coronal spinal Cobb angle, apex rotation and kyphosis of the spine and the intra-canal rib head position. Post-operative complications, surgery time and blood loss were also evaluated.

RESULTS:

Patients were followed up for at least 24 months post-operatively. The three dimensional spinal deformity was significantly improved and the intra-canal rib head was significantly extracted from the canal immediately after the surgery. At follow-up 24 months after surgery, solid fusions were achieved along the fusion segments, and the deformity corrections and rib head positions were well maintained. There were no surgery-related complications any time after the surgery.

CONCLUSIONS:

Systematic examinations are needed to identify patients with Type I neurofibromatosis scoliosis with rib head dislocation into the canal who can be treated by posterior-only spinal fusion without rib head resection.     

Is there a relationship between executive functions and academic success in children with neurofibromatosis type 1?

The present study aimed to compare the executive function (EF) of children with neurofibromatosis type 1 (NF1) to those of typically developing children and to investigate whether those abilities could predict the child's academic success in terms of academic skills and enablers. Twenty-nine children with NF1 and 27 age-and-gender-matched controls (aged 8–16 years) were examined with two tests to measure EF in an ecologically valid manner: the Behavioural Assessment of the Dysexecutive Syndrome in Children (BADS-C) and the parent questionnaire for the Behavior Rating Inventory of Executive Function (BRIEF). In order to evaluate academic success we used the Academic Competence Evaluation Scales (ACES). The performance of the NF1 group was significantly lower on the Water and Key search subtest of the BADS-C and on four scales of the BRIEF: initiate; working memory; plan/organise and organisation of materials. Significant correlations and predictive models via regression analysis were generated for: BADS-C, BRIEF and ACES scores. Based on these findings, children with NF1 have executive dysfunction that partially accounts for their difficulties in academic achievements.     

Characterization of early onset neurofibromatosis type 2

Neurofibromatosis type 2 (NF2) is an autosomal dominant multiple neoplasia syndrome of the central nervous system. The aim of the present study was to characterize the clinical course of early onset NF2. The specific Japanese disease registry for NF2 in 2010 was analyzed retrospectively. The male:female ratio for the 312 patients identified in the database was 1:1.29. The median age at onset was 25 years (range 2–76 years), with 31.3% of patients exhibiting symptoms at <20 years of age. Patients with an age at onset of <20 years were found to have more frequent spinal cord and extravestibular cranial nerve involvement, cutaneous signs, and convulsions than patients with a later age at onset. Of patients younger than 18 years of age, half did not exhibit hearing problems; in contrast, they frequently had other cranial nerve schwannomas, cranial meningioma, spinal cord tumors, and subcutaneous schwannoma. There were weak but significant positive correlations between symptomatic periods and disability scores in patients with an age of onset of ?20 years (R = 0.225; P < 0.01) and those with an earlier age of onset (R = 0.306; P < 0.01). Although there were no significant differences in disability scores between genders or patients with an age at onset of <20 versus ?20 years, patients with an earlier age at onset had significantly higher disability scores for spinal symptoms than patients with an age at onset of ?20 years. Atypical extravestibular presentation is common in early onset NF2, with more prominent spinal symptoms.