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Skeletal Radiology Apr 2024The 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),...
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.
Topics: Male; Humans; Female; Adult; Neurofibrosarcoma; Cross-Sectional Studies; Retrospective Studies; Neurofibroma; Neurofibromatosis 1; Neurofibroma, Plexiform; Nerve Sheath Neoplasms; Magnetic Resonance Imaging
PubMed: 37903998
DOI: 10.1007/s00256-023-04497-z -
The Journal of Hand Surgery... Oct 2023Plexiform schwannoma is an uncommon benign tumour that grows in a plexiform pattern. We report a 47-year-old man with a mass on the palmar aspect of the...
Plexiform schwannoma is an uncommon benign tumour that grows in a plexiform pattern. We report a 47-year-old man with a mass on the palmar aspect of the metacarpophalangeal joint of the right index finger that had been growing gradually for more than 10 years. The mass was palpated from the distal carpal tunnel to the ulnar aspect of the proximal interphalangeal joint of the index finger, with tingling and numbness sensation. The tumour was a multinodular tumour involving the first common palmar digital nerve to the ulnar proper palmar digital nerve. It was resected and reconstructed with a sural nerve graft. Plexiform schwannoma is rare in the digital nerve, with only six cases reported. Generally, classic schwannomas can be enucleated without causing neurologic deficits; however, plexiform schwannoma may require nerve resection. There have been reports of recurrence of plexiform schwannoma; definitive resection and long-term follow-up are necessary. Level V (Therapeutic).
Topics: Male; Humans; Middle Aged; Neurilemmoma; Paresthesia; Fingers; Neurosurgical Procedures; Wrist
PubMed: 37881820
DOI: 10.1142/S2424835523720190 -
Clinical Trials (London, England) Apr 2024We developed an observer disfigurement severity scale for neurofibroma-related plexiform neurofibromas to assess change in plexiform neurofibroma-related disfigurement...
BACKGROUND/AIMS
We developed an observer disfigurement severity scale for neurofibroma-related plexiform neurofibromas to assess change in plexiform neurofibroma-related disfigurement and evaluated its feasibility, reliability, and validity.
METHODS
Twenty-eight raters, divided into four cohorts based on neurofibromatosis type 1 familiarity and clinical experience, were shown photographs of children in a clinical trial (NCT01362803) at baseline and 1 year on selumetinib treatment for plexiform neurofibromas ( = 20) and of untreated participants with plexiform neurofibromas ( = 4). Raters, blinded to treatment and timepoint, completed the 0-10 disfigurement severity score for plexiform neurofibroma on each image (0 = not at all disfigured, 10 = very disfigured). Raters evaluated the ease of completing the scale, and a subset repeated the procedure to assess intra-rater reliability.
RESULTS
Mean baseline disfigurement severity score for plexiform neurofibroma ratings were similar for the selumetinib group (6.23) and controls (6.38). Mean paired differences between pre- and on-treatment ratings was -1.01 (less disfigurement) in the selumetinib group and 0.09 in the control ( = 0.005). For the disfigurement severity score for plexiform neurofibroma ratings, there was moderate-to-substantial agreement within rater cohorts (weighted kappa range = 0.46-0.66) and agreement between scores of the same raters at repeat sessions ( > 0.05). In the selumetinib group, change in disfigurement severity score for plexiform neurofibroma ratings was moderately correlated with change in plexiform neurofibroma volume with treatment ( = 0.60).
CONCLUSION
This study demonstrates that our observer-rated disfigurement severity score for plexiform neurofibroma was feasible, reliable, and documented improvement in disfigurement in participants with plexiform neurofibroma shrinkage. Prospective studies in larger samples are needed to validate this scale further.
Topics: Child; Humans; Neurofibroma, Plexiform; Neurofibromatosis 1; Prospective Studies; Reproducibility of Results
PubMed: 37877369
DOI: 10.1177/17407745231206402 -
BMC Research Notes Oct 2023In epidemiological and experimental research, high folic acid intake has been demonstrated to accelerate tumor development among populations with genetic and/or...
OBJECTIVE
In epidemiological and experimental research, high folic acid intake has been demonstrated to accelerate tumor development among populations with genetic and/or molecular susceptibility to cancer. Neurofibromatosis type 1 (NF1) is a common autosomal dominant disorder predisposing affected individuals to tumorigenesis, including benign plexiform neurofibromas; however, understanding of factors associated with tumor risk in NF1 patients is limited. Therefore, we investigated whether pregestational folic acid intake modified plexiform-like peripheral nerve sheath tumor risk in a transgenic NF1 murine model.
RESULTS
We observed no significant differences in overall survival according to folate group. Relative to controls (180 days), median survival did not statistically differ in deficient (174 days, P = 0.56) or supplemented (177 days, P = 0.13) folate groups. Dietary folate intake was positively associated with RBC folate levels at weaning, (P = 0.023, 0.0096, and 0.0006 for deficient vs. control, control vs. supplemented, and deficient vs. supplemented groups, respectively). Dorsal root ganglia (DRG), brachial plexi, and sciatic nerves were assessed according to folate group. Mice in the folate deficient group had significantly more enlarged DRG relative to controls (P = 0.044), but no other groups statistically differed. No significant differences for brachial plexi or sciatic nerve enlargement were observed according to folate status.
Topics: Humans; Pregnancy; Female; Animals; Mice; Neurofibromatosis 1; Folic Acid; Neurofibroma; Neurofibroma, Plexiform; Nerve Sheath Neoplasms
PubMed: 37848948
DOI: 10.1186/s13104-023-06515-8 -
Skeletal Radiology Apr 2024To compare MRI features of sporadic and neurofibromatosis syndrome-related localized schwannomas and neurofibromas.
OBJECTIVES
To compare MRI features of sporadic and neurofibromatosis syndrome-related localized schwannomas and neurofibromas.
METHODS
In this retrospective study, our pathology database was searched for "neurofibroma" or "schwannoma" from 2014 to 2019. Exclusion criteria were lack of available MRI and intradural or plexiform tumors. Qualitative and quantitative anatomic (location, size, relationship to nerve, signal, muscle denervation) and functional (arterial enhancement, apparent diffusion-weighted coefficient) MRI features of sporadic and syndrome-related tumors were compared. Statistical significance was assumed for p < 0.05.
RESULTS
A total of 80 patients with 64 schwannomas (sporadic: 42 (65.6%) v. syndrome-related: 22 (34.4%)) and 19 neurofibromas (sporadic: 7 (36.8%) v. syndrome-related: 12 (41.7%)) were included. Only signal heterogeneity (T2W p=0.001, post-contrast p=0.03) and a diffused-weighted imaging target sign (p=0.04) were more frequent with schwannomas than neurofibromas. Sporadic schwannomas were similar in size to syndrome-related schwannomas (2.9±1.2cm vs. 3.7±3.2 cm, p = 0.6), but with greater heterogeneity (T2W p = 0.02, post-contrast p = 0.01). Sporadic neurofibromas were larger (4.6±1.5cm vs. 3.4±2.4 cm, p = 0.03) than syndrome-related neurofibromas, also with greater heterogeneity (T2W p=0.03, post-contrast p=0.04). Additional tumors along an affected nerve were only observed with syndrome-related tumors). There was no difference in apparent diffusion coefficient values or presence of early perfusion between sporadic and syndrome-related tumors (p > 0.05).
CONCLUSIONS
Although syndrome-related and sporadic schwannomas and neurofibromas overlap in their anatomic, diffusion and perfusion features, signal heterogeneity and presence of multiple lesions along a nerve are differentiating characteristics of syndrome-related tumors.
Topics: Humans; Retrospective Studies; Nerve Sheath Neoplasms; Peripheral Nervous System Neoplasms; Neurofibroma; Neurilemmoma; Neurofibromatoses; Magnetic Resonance Imaging
PubMed: 37845504
DOI: 10.1007/s00256-023-04479-1 -
Neuro-oncology Advances 2023
PubMed: 37841697
DOI: 10.1093/noajnl/vdad125 -
The British Journal of Dermatology Jan 2024Neurofibromatosis type 1 (NF1) is characterized by the highly variable and unpredictable development of benign peripheral nerve sheath tumours: cutaneous (cNFs),...
BACKGROUND
Neurofibromatosis type 1 (NF1) is characterized by the highly variable and unpredictable development of benign peripheral nerve sheath tumours: cutaneous (cNFs), subcutaneous (scNFs) and plexiform (pNFs) neurofibromas.
OBJECTIVES
To identify neurofibroma modifier genes, in order to develop a database of patients with NF1.
METHODS
All patients were phenotypically evaluated by a medical practitioner using a standardized questionnaire and the causal NF1 variant identified. We enrolled 1333 patients with NF1 who were genotyped for > 7 million common variants.
RESULTS
A genome-wide association case-only study identified a significant association with 9q21.33 in the pNF phenotype in the discovery cohort. Twelve, three and four regions suggestive of association at the P ≤ 1 × 10-6 threshold were identified for pNFs, cNFs and scNFs, respectively. Evidence of replication was observed for 4, 2 and 6 loci, including 168 candidate modifier protein-coding genes. Among the candidate modifier genes, some were implicated in the RAS-mitogen-activated protein kinase pathway, cell-cycle control and myelination. Using an original CRISPR/Cas9-based functional assay, we confirmed GAS1 and SPRED2 as pNF and scNF candidate modifiers, as their inactivation specifically affected NF1-mutant Schwann cell growth.
CONCLUSIONS
Our study may shed new light on the pathogenesis of NF1-associated neurofibromas and will, hopefully, contribute to the development of personalized care for patients with this deleterious and life-threatening condition.
Topics: Humans; Neurofibromatosis 1; Neurofibroma, Plexiform; Genome-Wide Association Study; Neurofibroma; Genotype; Repressor Proteins
PubMed: 37831592
DOI: 10.1093/bjd/ljad390 -
Frontiers in Oncology 2023Neurofibromatosis Type 1 (NF1) is one of the most common genetically inherited disorders that affects 1 in 3000 children annually. Clinical manifestations vary widely...
Single-cell RNA sequencing of neurofibromas reveals a tumor microenvironment favorable for neural regeneration and immune suppression in a neurofibromatosis type 1 porcine model.
Neurofibromatosis Type 1 (NF1) is one of the most common genetically inherited disorders that affects 1 in 3000 children annually. Clinical manifestations vary widely but nearly always include the development of cutaneous, plexiform and diffuse neurofibromas that are managed over many years. Recent single-cell transcriptomics profiling efforts of neurofibromas have begun to reveal cell signaling processes. However, the cell signaling networks in mature, non-cutaneous neurofibromas remain unexplored. Here, we present insights into the cellular composition and signaling within mature neurofibromas, contrasting with normal adjacent tissue, in a porcine model of NF1 using single-cell RNA sequencing (scRNA-seq) analysis and histopathological characterization. These neurofibromas exhibited classic diffuse-type histologic morphology and expected patterns of S100, SOX10, GFAP, and CD34 immunohistochemistry. The porcine mature neurofibromas closely resemble human neurofibromas histologically and contain all known cellular components of their human counterparts. The scRNA-seq confirmed the presence of all expected cell types within these neurofibromas and identified novel populations of fibroblasts and immune cells, which may contribute to the tumor microenvironment by suppressing inflammation, promoting M2 macrophage polarization, increasing fibrosis, and driving the proliferation of Schwann cells. Notably, we identified tumor-associated /CD274 ( dendritic cells, which represent the first such observation in any NF1 animal model and suggest the role of the upregulation of immune checkpoints in mature neurofibromas. Finally, we observed that cell types in the tumor microenvironment are poised to promote immune evasion, extracellular matrix reconstruction, and nerve regeneration.
PubMed: 37817770
DOI: 10.3389/fonc.2023.1253659 -
Cureus Sep 2023The most common causes of vision loss in neurofibromatosis 1 (NF1) patients are sequelae from tumors such as optic pathway glioma, plexiform neurofibroma, or secondary...
The most common causes of vision loss in neurofibromatosis 1 (NF1) patients are sequelae from tumors such as optic pathway glioma, plexiform neurofibroma, or secondary glaucoma. Here we report the case of a six-year-old female with anisometropic amblyopia resulting from an isolated unilateral macro-ophthalmia with a known history of NF1. Our patient progressed to light perception vision in the left eye due to a non-neoplastic cause associated with NF1 with at least two years of documented unilateral macro-ophthalmia without any ophthalmology referral or evaluation. This case aims to highlight the importance of early and deliberate ophthalmologic examination in all patients with neurofibromatosis 1 to assess for appropriate visual development and early intervention.
PubMed: 37809258
DOI: 10.7759/cureus.44679 -
Pediatric Neurology Dec 2023Neurofibromatosis type 1 (NF1) is the most common neurocutaneous disease and is caused by mutations in the NF1 gene. The most common clinical features of NF1 are...
BACKGROUND
Neurofibromatosis type 1 (NF1) is the most common neurocutaneous disease and is caused by mutations in the NF1 gene. The most common clinical features of NF1 are pigmentary abnormalities such as café-au-lait spots and inguinal or axillary freckling, cutaneous and plexiform neurofibromas, hamartomas of the iris, optic gliomas, and bone lesions. The aim of this retrospective study was to define the clinical and molecular characteristics of a pediatric sample of NF1, as well as the mutational spectrum and genotype-phenotype correlation.
METHODS
The study included 40 children with clinically suspected NF1. The patients were screened for NF1 mutations by DNA-based sequencing. In addition, all the patients were studied by multiplex ligation-dependent probe amplification (MLPA) to identify any duplications or deletions in NF1. The demographic, clinical, and genetic features of the children were characterized.
RESULTS
A total of 40 children with NF1 were included. Of those, 28 were female and 12 were male. The mean age was 8.91 years. An NF1 variant was discovered in 28 of 40 patients (70%). Among these mutations, intronic mutations were the most frequently detected mutations; 15 of these variants had not been previously reported. Only one patient had a whole NF1 gene deletion.
CONCLUSIONS
This study expands the spectrum of mutations in the NF1 gene. This study also showed that genetic screening using both next-generation sequencing and MLPA had a positive effect on diagnosis and genetic counseling in patients with suspected NF1.
Topics: Child; Female; Humans; Male; Hamartoma; Neurofibroma, Plexiform; Neurofibromatosis 1; Optic Nerve Glioma; Retrospective Studies
PubMed: 37806041
DOI: 10.1016/j.pediatrneurol.2023.08.036