Background:
Literature indicates that 15–20% of patients with Neurofibromatosis type 1 (NF1) develop optic pathway gliomas (OPGs). Thus, routine surveillance of children with NF1 is essential. We describe a uniform cohort undergoing standardised ophthalmologic and magnetic resonance imaging (MRI) screening.
Methods:
MRI reports were retrospectively reviewed for children and adolescents with NF1 followed at the Medical University of Vienna between 1999 and 2023. Ophthalmological data included visual acuity, optical coherence tomography, optic nerve atrophy, disc edema, proptosis, squint and nystagmus. OPGs were classified according to modified DODGE classification. Variables were recorded at first and last MRI, first evidence of OPG, and before and after treatment.
Results:
Overall, 349 consecutive patients with NF1 were included; 315 underwent at least one brain MRI (age at first MRI, 0.2–23.6 years). OPGs were identified in 90 patients (25.8%; median age, 3.8 years; range, 1.2–22.5). At first MRI, only 18 patients were symptomatic. The most recent MRI was performed at a median age of 9.5 years (range, 1.2–30.2). At this time OPGs remained detectable in 74 patients (Dodge A=33, B=4, C=3, AB=12, AC=1, BC=1, ABC=20). Squint occurred in 50 patients, abnormal visual behaviour in 55, nystagmus in 8, proptosis in 10, optic atrophy in 73 eyes and disc edema in 7.
Conclusion:
We describe one of the largest NF1-OPG cohorts to date. MRI screening identified OPGs at higher frequencies than previously reported. Future analysis of imaging and ophthalmologic data will correlate imaging findings with visual outcomes.

Background: The molecular similarity between gliomas in patients with neurofibromatosis type 1 (NF1) and their sporadic counterparts remains poorly understood. We therefore performed an in-depth molecular characterization of a cohort of 42 NF1-associated gliomas.

Methods: DNA isolated from macrodissected areas with high tumor content was subjected to whole-exome sequencing and genome-wide DNA methylation profiling (HumanMethylationEPIC v2 beadchips). Methylation classes were assigned according to EpiGnostix v12.8 and Methylscape profiler.

Results: The cohort consisted of 41 patients of whom 55% were male with a median age at histological diagnosis of 56 years. Twelve patients were younger than 18 years. Median follow-up was 39 months (IQR 14–139) and at last follow-up, 41% had died. Molecular profiling was successfully performed in 33 NF1-associated gliomas. Methylation profiling predominantly classified tumors as pilocytic astrocytoma (PA) or high-grade astrocytoma with piloid features (HGAP), although 19 gliomas remained unclassified. Ten gliomas clustered with the recently described subclass “PA, arising in NF1”, supporting this as a distinct molecular entity characterised by few genomic alterations. These patients had a median follow-up of 139 months (IQR 121–159) with one death after 20 months. The genomic landscape was consistent with known patterns: PA-like gliomas harboured few additional somatic variants and copy number aberrations, whereas HGAPs frequently exhibited CDKN2A/B deletions and ATRX mutations.

Conclusion: PAs arising in NF1 likely constitute a distinct molecular subgroup characterised by few genomic alterations and a relatively favorable clinical course. These findings support the recognition of NF1-associated PA as a biologically distinct entity within the spectrum of gliomas.

Background: Advances in care for adults with neurofibromatosis type 1 (NF1)-associated low-grade glioma (LGG) are hindered by limited knowledge of the impact of clinical features, molecular alterations, and treatment approach on survival.

Methods: Individuals ≥18 years of age with NF1 and histologically confirmed LGG diagnosed between 2005-2023 were included. Retrospective clinical, molecular, and imaging data were centrally analyzed.

Results: Seventy-five patients met eligibility criteria, of which 44% were male. The median age at diagnosis was 29.3 years (range 18.0-65.8). The prevalent tumor locations were cerebral hemisphere (31%) and cerebellum (29%). Gross total resection (GTR) was achieved in 28%. Predominant histology was pilocytic astrocytoma (56%) and diffuse astrocytoma (13%). Molecular analysis was performed in 48% of tumors at diagnosis, identifying recurrent alterations in NF1 (90%), CDKN2A/B (12%), FGFR1 (9%), ATRX (9%), and PIK3CA (5%). Median overall survival (OS) was 6.6 years (95% CI 4.6-NR). Inferior OS was associated with WHO grade 2 classification (P=0.020), incomplete resection (P=0.004), and ATRX (P<0.001) or CDKN2A/B (P<0.001) alterations; elevated Ki67 (>5%) showed modest association (HR 1.9, P=0.091). OS did not differ by age, sex, FGFR1, or PIK3CA status. Initial management was surgery alone in 68%; 33% received radiation and 19% received a MEK inhibitor at any time. Repeat pathologic sampling of the target glioma occurred in 13 patients: 6 revealed high-grade glioma at that time.

Conclusion: Histology alone is insufficient to predict outcomes for adults with pathologically sampled NF1-LGG. Molecular testing is necessary for more accurate clinical risk stratification.

Background: Childhood NF2-related schwannomatosis (NF2-SWN) is clinically heterogeneous, ranging from asymptomatic familial disease to early, aggressive tumour burden. Predictors of tumour development, tumour onset and survival remain incompletely defined in paediatric cohorts.

Methods: We retrospectively analysed patients diagnosed with NF2-SWN before 16 years of age from a national NF2 database. Clinical, genetic and imaging data were reviewed. Patients were grouped by diagnostic era: pre-2000, 2000–2010 and 2010 onwards. Logistic regression was used to identify predictors of tumour development, and Cox regression was used to assess predictors of tumour onset and survival.

Results: We included 269 patients, of whom 63% were symptomatic at diagnosis. Symptomatic patients were more likely to have de novo variants than asymptomatic patients (72% vs 6%, p<0.0001) and severe genetic disease (NF2 severity grade 3: 42% vs 22%, p=0.0003). Symptomatic presentation predicted development of vestibular schwannomas (OR 7.54), cranial meningiomas (OR 3.61), ependymomas (OR 2.94) and spinal tumours (OR 3.61). De novo variants predicted spinal tumour development (OR 3.24). Symptomatic presentation was associated with earlier onset of vestibular schwannomas (HR 1.71), cranial meningiomas (HR 2.93) and spinal tumours (HR 1.86), while de novo variants predicted earlier spinal tumour onset (HR 2.11). Symptomatic diagnosis predicted poorer overall survival (HR 2.90). Ten-year survival improved across eras: 88%, 97% and 100%, respectively (p=0.014).

Conclusion: Symptomatic presentation and de novo variants identify children with earlier and more aggressive NF2-SWN. Survival has improved substantially since 2000, supporting the impact of specialist multidisciplinary care.

Background:
NF2-Schwannomatosis (NF2-SWN) is associated with multiple meningiomas, often requiring repeat surgical intervention due to their high growth rate and aggressiveness. Predictors of meningioma recurrence in this population remain poorly defined. We aim to evaluate the relationship between genetic markers, histopathology, extent of resection and tumour recurrence.

Methods:
All patients from the Manchester NF2-SWN clinic with a surgically resected meningioma were included. Spinal meningiomas were excluded. Clinical, radiological and genetic data were obtained and statically analysed in SPSS v30.

Results:
Seventy-nine meningiomas were resected in 35 patients. NF2 Genetic Severity Score (GSS) was available for 27 patients; 66.7% (18/27) were tissue mosaic and 29.6% (8/27) had a severe phenotype. Mean age at surgery was 41.7 years (95% CI 13.6–69.8), and median tumour volume was 25.4 cm3 (IQR 6.07–51.1). WHO Grade 2 tumours comprised 10.1% (8/79), while 63.3% (50/79) underwent near-total resection (Simpson Grade 1–2). Post-operative complications occurred in 26.2% of patients (16/61). Local recurrence occurred in 19.0% (15/79) over 400.5 patient-years of follow-up, with a median time to recurrence of 1.95 years (IQR 0.639–2.66). Kaplan–Meier analysis demonstrated differences in recurrence-free survival by GSS (log-rank 9.922, p=0.007), but not by Simpson grade (p=0.606) or WHO grade (p=0.759). Multivariate Cox regression adjusting for Simpson grade showed GSS was not independently associated with recurrence (HR 0.245, 95% CI 0.022–2.787, p=0.257).

Conclusion:
NF2-associated meningiomas are surgically challenging, with high post-operative complication and recurrence rates. Conventional grading systems and genetic severity measures may have limited utility in predicting recurrence in NF2-associated meningiomas.

Background. NF2-related schwannomatosis (SWN-NF2; MIM # 101000) is a rare autosomal dominant tumor predisposition syndrome characterized by bilateral vestibular schwannomas (VS). SWN -NF2 patients can also show schwannomas of the cranial, spinal, peripheral, and cutaneous nerves, meningiomas, and ependymomas. In them endothelial growth factor A inhibitor, bevacizumab, is a systemic treatment option.
Methods.The aim of this study is to retrospectively evaluate SWN-NF2 patient responses to bevacizumab on tumor growth according to REiNS recommendations, hearing outcomesand symptom progression.
Results. Between September 2012 and January 2026 25 patients received Bevacizumab 7.5 mg/kg every 3 weeks, median treatment duration 46.7 months (7-196). Eleven of these patients discontinued bevacizumab (3 for toxicities, 5 for disease progression, 3 for consent withdrawn). The remaining 14 patients are currently receiving bevacizumab treatment.
Brain and spinal MRI showed partial response in 2, stable disease in 18 and progression disease in 5. Median time to progression 46,7 mo. In 3 out 5 patients disease progression was due to meningioma growth. Within 6 months of Bevacizumab discontinuation 3 out of 6 patients who were not progressing, experienced rebound VS growth.
Conclusions.In NF2-SWN patients Bevacizumab can slow tumor growth with a trend toward hearing preservation and delay more aggressive management with irradiation or surgery. New treatment options are needed to better control meningioma growth and to avoid rebound VS growth after Bevacizumab discontinuation.