CNS tumors with PLAGL1-fusion: beyond ZFTA and YAP1 in the genetic spectrum of supratentorial ependymomas.

A novel methylation class, "neuroepithelial tumor, with PLAGL1 fusion" (NET-PLAGL1), has recently been described, based on epigenetic features, as a supratentorial pediatric brain tumor with recurrent histopathological features suggesting an ependymal differentiation. Because of the recent identification of this neoplastic entity, few histopathological, radiological and clinical data are available. Herein, we present a detailed series of nine cases of PLAGL1-fused supratentorial tumors, reclassified from a series of supratentorial ependymomas, non-ZFTA/non-YAP1 fusion-positive and subependymomas of the young. This study included extensive clinical, radiological, histopathological, ultrastructural, immunohistochemical, genetic and epigenetic (DNA methylation profiling) data for characterization. An important aim of this work was to evaluate the sensitivity and specificity of a novel fluorescent in situ hybridization (FISH) targeting the PLAGL1 gene. Using histopathology, immunohistochemistry and electron microscopy, we confirmed the ependymal differentiation of this new neoplastic entity. Indeed, the cases histopathologically presented as "mixed subependymomas-ependymomas" with well-circumscribed tumors exhibiting a diffuse immunoreactivity for GFAP, without expression of Olig2 or SOX10. Ultrastructurally, they also harbored features reminiscent of ependymal differentiation, such as cilia. Different gene partners were fused with PLAGL1: FOXO1, EWSR1 and for the first time MAML2. The PLAGL1 FISH presented a 100% sensitivity and specificity according to RNA sequencing and DNA methylation profiling results. This cohort of supratentorial PLAGL1-fused tumors highlights: 1/ the ependymal cell origin of this new neoplastic entity; 2/ benefit of looking for a PLAGL1 fusion in supratentorial cases of non-ZFTA/non-YAP1 ependymomas; and 3/ the usefulness of PLAGL1 FISH.

Incidence and outcome of pseudoprogression after radiation therapy in glioblastoma patients: A cohort study.

Background: Differentiating post-radiation MRI changes from progressive disease (PD) in glioblastoma (GBM) patients represents a major challenge. The clinical problem is two-sided; avoid termination of effective therapy in case of pseudoprogression (PsP) and continuation of ineffective therapy in case of PD. We retrospectively assessed the incidence, management, and prognostic impact of PsP and analyzed factors associated with PsP in a GBM patient cohort. Methods: Consecutive GBM patients diagnosed in the South-Eastern Norway Health Region from 2015 to 2018 who had received RT and follow-up MRI were included. Tumor, patient, and treatment characteristics were analyzed in relationship to re-evaluated MRI examinations at 3 and 6 months post-radiation using Response Assessment in Neuro-Oncology criteria. Results: A total of 284 patients were included in the study. PsP incidence 3 and 6 months post-radiation was 19.4% and 7.0%, respectively. In adjusted analyses, methylated O6-methylguanine-DNA methyltransferase (MGMT) promoter and the absence of neurological deterioration were associated with PsP at both 3 (p < .001 and p = .029, respectively) and 6 months (p = .045 and p = .034, respectively) post-radiation. For patients retrospectively assessed as PD 3 months post-radiation, there was no survival benefit of treatment change (p = .838). Conclusions: PsP incidence was similar to previous reports. In addition to the previously described correlation of methylated MGMT promoter with PsP, we also found that absence of neurological deterioration significantly correlated with PsP. Continuation of temozolomide courses did not seem to compromise survival for patients with PD at 3 months post-radiation; therefore, we recommend continuing adjuvant temozolomide courses in case of inconclusive MRI findings.

The benefit of complete resection of contrast enhancing tumor in glioblastoma patients: A population-based study.

Background: New treatment modalities have not been widely adopted for patients with glioblastoma (GBM) after the addition of temozolomide to radiotherapy. We hypothesize that increased extent of resection (EOR) has resulted in improved survival for surgically treated patients with glioblastoma at the population level. Methods: Retrospective analysis of adult patients operated for glioblastoma in the population of South-Eastern Norway. Patients were stratified into Pre-temozolomide- (2003-2005), temozolomide- (2006-2012), and resection-focused period (2013-2019) and evaluated according to age and EOR. Results: The study included 1657 adult patients operated on for supratentorial glioblastoma. The incidence of histologically confirmed glioblastoma increased from 3.7 in 2003 to 5.3 per 100 000 in 2019. The median survival was 11.4 months. Complete resection of contrast-enhancing tumor (CRCET) was achieved in 386 patients, and this fraction increased from 13% to 32% across the periods. Significant improvement in median survival was found between the first 2 periods and the last (10.5 and 10.6 vs. 12.3 months; P < .01), with a significant increase in 3- and 5-year survival probability to 12% and 6% (P < .01). Patients with CRCET survived longer than patients with non-CRCET (16.1 vs. 10.8 months; P < .001). The median survival doubled in patients ≥70 years and (12.1 months). Survival was similar between the time periods in patients where CRCET was achieved. Conclusions: We demonstrate an improved survival of GBM patients at the population level associated with an increased fraction of patients with CRCET. The data support the importance of CRCET to improve glioblastoma patient outcomes.

Investigating survival, quality of life and cognition in PROton versus photon therapy for IDH-mutated diffuse grade 2 and 3 GLIOmas (PRO-GLIO): a randomised controlled trial in Norway and Sweden.

INTRODUCTION: The use of proton therapy increases globally despite a lack of randomised controlled trials demonstrating its efficacy and safety. Proton therapy enables sparing of non-neoplastic tissue from radiation. This is principally beneficial and holds promise of reduced long-term side effects. However, the sparing of seemingly non-cancerous tissue is not necessarily positive for isocitrate dehydrogenase (IDH)-mutated diffuse gliomas grade 2-3, which have a diffuse growth pattern. With their relatively good prognosis, yet incurable nature, therapy needs to be delicately balanced to achieve a maximal survival benefit combined with an optimised quality of life. METHODS AND ANALYSIS: PRO-GLIO (PROton versus photon therapy in IDH-mutated diffuse grade 2 and 3 GLIOmas) is an open-label, multicentre, randomised phase III non-inferiority study. 224 patients aged 18-65 years with IDH-mutated diffuse gliomas grade 2-3 from Norway and Sweden will be randomised 1:1 to radiotherapy delivered with protons (experimental arm) or photons (standard arm). First intervention-free survival at 2 years is the primary endpoint. Key secondary endpoints are fatigue and cognitive impairment, both at 2 years. Additional secondary outcomes include several survival measures, health-related quality of life parameters and health economy endpoints. ETHICS AND DISSEMINATION: To implement proton therapy as part of standard of care for patients with IDH-mutated diffuse gliomas grade 2-3, it should be deemed safe. With its randomised controlled design testing proton versus photon therapy, PRO-GLIO will provide important information for this patient population concerning safety, cognition, fatigue and other quality of life parameters. As proton therapy is considerably more costly than its photon counterpart, cost-effectiveness will also be evaluated. PRO-GLIO is approved by ethical committees in Norway (Regional Committee for Medical & Health Research Ethics) and Sweden (The Swedish Ethical Review Authority) and patient inclusion has commenced. Trial results will be published in international peer-reviewed journals, relevant conferences, national and international meetings and expert forums. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registry (NCT05190172).

Survival in a consecutive series of 467 glioblastoma patients: Association with prognostic factors and treatment at recurrence at two independent institutions.

Therapy of recurrent glioblastoma (GBM) is challenging due to lack of standard treatment. We investigated physicians' treatment choice at recurrence and prognostic and predictive factors for survival in GBM patients from Norway's two largest regional hospitals. Clinicopathological data from n = 467 patients treated at Haukeland and Oslo university hospitals from January 2015 to December 2017 was collected. Data included tumour location, promoter methylation of O6 methylguanine-DNA methyltransferase (MGMT) and mutation of isocitrate dehydrogenase (IDH), patient age, sex, extent of resection at primary diagnosis and treatment at successive tumour recurrences. Cox-proportional hazards regression adjusting for multiple risk factors was used. Median overall survival (OS) was 12.1 months and 21.4% and 6.8% of patients were alive at 2 and 5 years, respectively. Median progression-free survival was 8.1 months. Treatment at recurrence varied but was not associated with difference in overall survival (OS) (p = 0.201). Age, MGMT hypermethylation, tumour location and extent of resection were independent prognostic factors. Patients who received 60 Gray radiotherapy with concomitant and adjuvant temozolomide at primary diagnosis had 16.1 months median OS and 9.3% were alive at 5 years. Patients eligible for gamma knife/stereotactic radiosurgery alone or combined with chemotherapy at first recurrence had superior survival compared to chemotherapy alone (p<0.001). At second recurrence, combination chemotherapy with or without bevacizumab were both superior to no treatment. Treatment at recurrence differed between the institutions but there was no difference in median OS, indicating that it is the disease biology that dictates patient outcome.

Astrocytoma (CNS WHO grade 4), IDH-mutant with co-occurrence of BRAF p.V600E mutation, and homozygous loss of CDKN2A.

Molecular alterations nowadays play a crucial role in the diagnosis of brain tumors. Some of these alterations are associated with outcome and/or response to treatment, including sequence variants of isocitrate dehydrogenase (IDH) at position p.R132 or p.R172. Such IDH variants have so far been described in histone H3-wildtype primary brain tumors only in adult-type diffuse gliomas and are associated with a better outcome compared to their IDH-wildtype counterpart, the glioblastoma. Moreover, homozygous loss of CDKN2A and/or CDKN2B in IDH-mutant astrocytomas shortens the median overall survival regardless of histological features of malignancy. Such tumors are therefore considered to be aggressive and graded as WHO central nervous system (CNS) grade 4 lesions. The coexistence of an IDH-sequence variation and a BRAF p.V600E alteration has only rarely been described in diffuse astrocytomas. Due to the small number of cases, little is known about such neoplasms in terms of clinical behavior and response to treatment. Herein we describe the first case, to our knowledge, of an astrocytoma (CNS WHO grade 4), IDH-mutant, and BRAF p.V600E-mutant with homozygous deletion of CDKN2A. Pathologists should be aware that such an expression profile does exist even in WHO CNS grade 4 astrocytomas, IDH-mutant, and are encouraged to test for the BRAF p.V600E sequence variant as such an alteration may provide additional treatment options.

[Glioblastoma in adults]. / Glioblastom hos voksne.

Glioblastoma is the most common form of primary brain cancer in adults, and the disease has a serious prognosis. Although great progress has been made in molecular characteristics, no major breakthroughs in treatment have been achieved for many years. In this article we present a clinical review of current diagnostics and treatment, as well as the challenges and opportunities inherent in developing improved and more personalised treatment.

Oral and dental late effects in long-term survivors of childhood embryonal brain tumors.

PURPOSE: To investigate oral and dental late effects in survivors of childhood brain tumors medulloblastoma (MB) and central nervous system supratentorial primitive neuroectodermal tumor (CNS-PNET). METHODS: This cross-sectional study assessed oral and dental late effects in MB/CNS-PNET survivors treated before 20 years of age, and with a minimum of 2 years since treatment. Participants went through an oral and radiographic examination. We assessed oral status using the decayed-missing-filled index (DMFT), oral dryness, maximum mouth opening (MMO), fungal infection, and registration of dental developmental disturbances (DDD) in the form of hypodontia, microdontia, and enamel hypoplasia. RESULTS: The 46 participants' mean age at enrolment was 27 ± 12.8 years and at treatment 8.5 ± 5.2 years, and the mean time since treatment was 18.9 ± 12 years. Over a third (35%) of survivors had reduced mouth opening (mean 29.3 ± 5.6 mm (range 16-35)). A significantly lower MMO was found in individuals treated ≤ 5 years compared to survivors treated > 5 years (p = 0.021). One or more DDD were registered in 30.4% of the survivors, with a significantly higher prevalence in individuals treated ≤ 5 years (p < 0.001). Hypodontia was the most prevalent type of DDD. There was no difference in DMFT score in relation to age at treatment. Oral dryness was not frequently reported or observed in these survivors. CONCLUSION: Survivors of childhood MB/CNS-PNET are at risk of oral and dental late effects including reduced mouth opening and DDD. The risk is highest in survivors treated before the age of 5.

SMART syndrome: two cases highlighting a complex and rare complication of brain irradiation.

Stroke-like migraine attacks after radiation therapy (SMART) syndrome is a rare complication of radiotherapy with complex neurological impairment. Patients present with neurological symptoms and signs such as migraine, hemianopsia, hemiplegia, aphasia and/or seizures-without recurrence of neoplastic disease. In this report, we describe SMART syndrome in two adult patients 4 and 14 years following brain irradiation, respectively.

Bone mineral density and nutrition in long-term survivors of childhood brain tumors.

BACKGROUND AND AIMS: Childhood cancer survivors are at risk of unwanted late effects. The primary aim of this study was to assess bone mineral density Z-scores (BMDz) in long-term survivors of childhood medulloblastoma (MB) or central nervous system supratentorial primitive neuroectodermal tumor (CNS-PNET). Secondary aims were to describe nutrient intake, vitamin D status, physical activity and explore potential risk factors for decreased BMDz. METHODS: All MB and CNS-PNET survivors treated at Oslo University Hospital from 1974 to 2013 were invited to participate in a cross-sectional study. Dual-energy x-ray absorptiometry (Lunar Prodigy) assessed BMDz lumbar spine, BMDz total body, and lean body mass. Decreased BMDz was defined as a combination of low BMDz -1 to -1.99 and very low BMDz ≤-2. Lean body mass index (LMI) was calculated by dividing lean body mass by the squared height. Nutrient intake was assessed by a 3-day food record. Serum 25(OH)D was analyzed. Physical activity was reported by a questionnaire. Descriptive statistics and multivariable Cox regression analyses were applied. RESULTS: Fifty survivors with a median age of 25.5 years (5.5-51.9) and a median follow-up time of 19.5 years (3.2-40.5) were included. Mean BMDz lumbar spine was -0.8 (SD 1.1, 95% CI: -1.1 to -0.4), and BMDz total body was -0.6 (SD 1.1, 95% CI: -0.9 to -0.3). Decreased BMDz was detected in 48% of the lumbar spine and 34% of the total body measurements. In all, 62% had low calcium, and 69% had low vitamin D intake. 26% of participants had serum 25(OH)D < 50 nmol/L, and 62% reported an inactive lifestyle. Male sex, higher age at diagnosis, and lower LMI were potential risk factors for decreased BMDz. CONCLUSIONS: Long-term survivors of childhood MB and CNS-PNET had decreased BMDz, and risk factors were male sex, higher age at diagnosis, and lower LMI. Inadequate calcium and vitamin D intake, an inactive lifestyle, and a high prevalence of 25(OH)D ≤ 50 nmol/L were detected.

Molecular pathological insights reveal a high number of unfavorable risk patients among children treated for medulloblastoma and CNS-PNET in Oslo 2005-2017.

BACKGROUND: An unexplained regional difference in survival was observed in previous publications on outcome for children treated for medulloblastoma and supratentorial primitive neuroectodermal tumor (CNS-PNET) in Norway. We aimed now to reevaluate and perform a retrospective molecular-based risk stratification of all embryonal brain tumors (excluding atypical teratoid rhabdoid tumors [ATRT]) in pediatric patients, who underwent surgery and treatment at Oslo University Hospital between 2005 and 2017. PROCEDURE: Specimens from all patients <20 years of age with initial diagnosis of medulloblastoma or CNS-PNET were reviewed. Molecular analyses comprised NanoString gene expression, molecular inversion probe profiling, Sanger sequencing, and 850K-methylation analysis. Whole chromosomal aberration signatures were assessed in standard-risk non-WNT/non-SHH medullobastomas for molecular risk stratification. RESULTS: We identified 53 non-ATRT embryonal tumors among which 33 were medulloblastomas. Molecular genetic parameters including whole chromosomal aberration signatures allowed classification of 17 medulloblastomas as molecular high risk. These patients had a significantly worse 5-year overall survival than the remaining 16 medulloblastoma patients (52.9% vs. 87.1% p = 0.036). Five patients in our cohort had tumors that are considered as new entities in the 2021 classification of tumors of the central nervous system. Five tumors were re-classified as nonembryonal tumors after review. CONCLUSION: Molecular-based risk stratification of standard-risk non-WNT/non-SHH medulloblastoma enabled superior identification of medulloblastomas with dismal prognosis. Our cohort demonstrated a significantly increased fraction of standard-risk non-WNT/non-SHH medulloblastoma with molecular high-risk profile compared to other studies, which might have contributed to previously reported unfavorable outcome data.

Taste and smell function in long-term survivors after childhood medulloblastoma/CNS-PNET.

PURPOSE: To investigate taste and smell function in survivors, with a minimum of 2 years since treatment of childhood medulloblastoma (MB)/central nervous system supratentorial primitive neuroectodermal tumor (CNS-PNET). METHODS: This cross-sectional study included 40 survivors treated ≤ 20 years of age. Taste strips with four concentrations of sweet, sour, salt, and bitter were used to assess taste function in all participants. Score from 0 to 16; ≥ 9 normogeusia, < 9 hypogeusia, and complete ageusia which equals no sensation. No sensation of a specific taste quality equals ageusia of that quality. Thirty-two participants conducted smell testing using three subtests of Sniffin' sticks: threshold, discrimination, and identification. Together they yield a TDI-score from 1 to 48; functional anosmia ≤ 16.00, hyposmia > 16.00- < 30.75, normosmia ≥ 30.75- < 41.50, and ≥ 41.50 hyperosmia. Results were compared with normative data. Survivors rated their taste and smell function using a numerical rating scale (NRS) score 0-10. RESULTS: Forty survivors with a mean time since treatment of 20.5 years, 13 (32.5%) were diagnosed with hypogeusia, nine (22.5%) of these being ageusic to one or more taste qualities. Seventeen (53%) of 32 participants were diagnosed with hyposmia. The mean scores of the olfactory subtests, and TDI score were significantly lower than normative data (P < 0.0001). The mean NRS scores of smell and taste function were 7.9 ± 1.5 and 8 ± 1.3, respectively. CONCLUSION: Our study showed impaired taste and smell function in survivors of childhood MB/CNS-PNET using objective measurements. However, subjective ratings did not reflect objective findings.

Trabectedin for recurrent WHO grade 2 or 3 meningioma: A randomized phase II study of the EORTC Brain Tumor Group (EORTC-1320-BTG).

BACKGROUND: No systemic treatment has been established for meningioma progressing after local therapies. METHODS: This randomized, multicenter, open-label, phase II study included adult patients with recurrent WHO grade 2 or 3 meningioma. Patients were 2:1 randomly assigned to intravenous trabectedin (1.5 mg/m2 every 3 weeks) or local standard of care (LOC). The primary endpoint was progression-free survival (PFS). Secondary endpoints comprised overall survival (OS), objective radiological response, safety, quality of life (QoL) assessment using the QLQ-C30 and QLQ-BN20 questionnaires, and we performed tissue-based exploratory molecular analyses. RESULTS: Ninety patients were randomized (n = 29 in LOC, n = 61 in trabectedin arm). With 71 events, median PFS was 4.17 months in the LOC and 2.43 months in the trabectedin arm (hazard ratio [HR] = 1.42; 80% CI, 1.00-2.03; P = .294) with a PFS-6 rate of 29.1% (95% CI, 11.9%-48.8%) and 21.1% (95% CI, 11.3%-32.9%), respectively. Median OS was 10.61 months in the LOC and 11.37 months in the trabectedin arm (HR = 0.98; 95% CI, 0.54-1.76; P = .94). Grade ≥3 adverse events occurred in 44.4% of patients in the LOC and 59% of patients in the trabectedin arm. Enrolled patients had impeded global QoL and overall functionality and high fatigue before initiation of systemic therapy. DNA methylation class, performance status, presence of a relevant co-morbidity, steroid use, and right hemisphere involvement at baseline were independently associated with OS. CONCLUSIONS: Trabectedin did not improve PFS and OS and was associated with higher toxicity than LOC treatment in patients with non-benign meningioma. Tumor DNA methylation class is an independent prognostic factor for OS.

Choroid Plexus Tumors in Children: Long-Term Follow-Up of Consecutive Single-Institutional Series of 59 Patients Treated over a Period of 8 Decades (1939-2020).

OBJECTIVE: To present long-term follow-up of a consecutive single-institutional series of patients treated for choroid plexus tumors over 8 decades. METHODS: From 1939 to 2020, 59 children were treated for choroid plexus tumors. Median age at diagnosis was 1.7 years. RESULTS: Gross total resection was achieved in 51 patients (86%). Ten patients (17%) underwent >1 resection. During the first 4 decades of the study (1939-1979), 14 patients with plexus papillomas were treated. Operative mortality was 50%, with 6 of the remaining 7 patients experiencing excellent survival with follow-up periods of 41-81 years. In the last 4 decades (1980-2020), 38 patients had low-grade tumors, and all were alive at the latest follow-up (range, 0.5-39 years). Observed 5-year survival in this subgroup was 100% (n = 30), as was observed 10-year survival (n = 26). One of 7 (14%) patients with atypical choroid plexus papilloma and 3 of 31 patients (10%) with choroid plexus papilloma underwent a second resection owing to recurrent tumor. At last follow-up, 47 patients (80%) were alive; 45 (96%) had a Barthel Index score of 100 and 2 had a Barthel Index score of 50. Today 25 patients are adults (20-59 years old); 17 work full-time, 4 work part-time, and 4 are unable to work. CONCLUSIONS: Low-grade choroid plexus tumors can be cured with gross total resection alone, with excellent long-term survival and functionality. The vast majority of survivors live independently as adults and work full-time. Recurrences are uncommon (8.7%), appear within the first few years after primary surgery, and can be treated with repeat resections.

Neuropsychological functioning in survivors of childhood medulloblastoma/CNS-PNET: The role of secondary medical complications.

Objective To investigate the long-term cognitive consequences of malignant pediatric brain tumor and its treatment, and factors explaining variability in cognitive functioning among survivors. Method: A geographical cohort of survivors of pediatric medulloblastoma (MB) and supratentorial primitive neuroectodermal tumor (CNS-PNET), treated between 1974 and 2013, was invited to participate. Of the 63 surviving patients, 50 (79%) consented to participation. The participants were tested with a battery of neuropsychological tests covering a wide age range. Verbal cognition, nonverbal cognition, processing speed, attention, memory, executive functioning, and manual dexterity were assessed. The participants were between 5:5 and 51:11 years of age at time of assessment. Assessments took place on average 19 years after primary tumor resective surgery. Results: One participant had a severe intellectual disability. For the rest, IQ varied from 52 to 125, with a mean score of 88.0 (SD 19.7). Twenty-eight (56%) of the participants had full-scale IQ scores in the age-average range or above. Gender, age at operation, time since operation, the presence of secondary medical complications, and treatment variables explained 46% of the variability in IQ scores, F(4,44) = 9.5, p<.001. The presence of endocrine insufficiency in combination with either epilepsy and/or hydrocephalus was associated with lowered IQ, lowered processing speed, and memory impairments. Conclusion: Patients treated for childhood MB and CNS-PNET have a lifelong risk of medical sequelae, including impaired cognitive functioning. This study adds to the literature by demonstrating the importance of following neuropsychological functioning closely, especially processing speed, learning, and memory, in survivors who have multiple secondary medical complications.

Neurosarcoidosis resembling multiple meningiomas: A misleading presentation of the disease and diagnostic challenge.

Sarcoidosis is characterized by the presence of noncaseating granulomatous inflammation in the affected organs. Neurosarcoidosis denotes the involvement of the nervous system and can be either isolated or coexisting with extraneural systemic inflammation. The diagnosis of isolated neurosarcoidosis may be challenging due to unspecific symptoms and similar appearances with other disease processes. This report presents an uncommon case of intracranial sarcoidosis mimicking multiple meningiomas. Familiarity with the spectrum of magnetic resonance imaging findings in neurosarcoidosis is crucial to prevent interpretive errors which may in turn lead to an inappropriate diagnosis and treatment.

Outcome after treatment of pediatric supratentorial ependymoma: long-term follow-up of a single consecutive institutional series of 26 patients.

BACKGROUND: Long-term outcome after surgical treatment of supratentorial ependymoma (STE) in children has not been extensively reported. FINDINGS: We identified 26 children who underwent primary tumor resection of STE between 1953 and 2011, with at least 8 years follow-up. Ten patients (38%) had anaplastic and 16 had low grade ependymoma. Four of 15 children (26%) treated in the years 1953-1976 survived more than 5 years, but the observed 10-year survival was only 7%. One patient lived for 37 years, and second surgery for a local recurrent lesion disclosed a glioblastoma, possibly secondary to radiotherapy. In contrast, the observed 5-year survival rate for 11 children treated in the years 1992-2011 was 8/11 (73%) and observed 10- and 25-year survival rates were 70% and 66%, respectively. Eight patients were alive and tumor-free with follow-up periods of 8-27 (median 18) years, all treated after 1992. Five of these long-term survivors were 23-39 years old with full-time (n = 3) or part-time (n = 2) work. The last three patients were still children (9-12 years old): one with good function and two with major neurological deficits. The majority of patients (n = 18) received adjuvant radiotherapy and eight children no adjuvant treatment. Repeated resections for residual or recurrent tumor were necessary in 11 patients (42%), mostly due to local disease with progressive clinical symptoms. Eight patients underwent only one repeat resection, whereas three patients had two or more repeat resections within 18 years after initial surgery. Four patients were tumor-free after repeated resections at the latest follow-up, 2-13 years after last surgery. CONCLUSION: Pediatric STE has a marked risk for local recurrence even after gross total resection and postoperative radiotherapy, but survival has increased following the introduction of modern treatment in recent years. Repeated surgery is an important part of treatment and may lead to persistent tumor control.

Bilateral calcification of the optic nerve sheath: A diagnostic dilemma.

PURPOSE: To present a case of symptomatic optic nerve sheath calcification and highlight clues and pitfalls for the final diagnosis: bilateral optic nerve sheath meningioma. OBSERVATIONS: A 48-year-old man presented with painless vision loss in his left eye and findings consistent with left optic nerve atrophy. Magnetic resonance imaging (MRI) displayed thinning of the left optic nerve without contrast-enhancement or evidence of compressive lesions. A supplementary computed tomography angiography (CTA) exposed scattered dural calcification, which included the optic nerves. This was regarded as an incidental finding. The initial diagnosis was ischemic optic neuropathy. Over the next two years, the vision loss in the left eye progressed. A CT of the orbits revealed extensive calcification surrounding both optic nerves. A second MRI was unchanged in comparison to the first MRI. The diagnosis was changed to idiopathic duro-optic calcification. The vision in the left eye further declined over another two years. Consecutive optical coherence tomography measurements of the peripapillary retinal nerve fiber layer suggested bilateral progressive thinning. A third MRI displayed progression of tubular contrast-enhancement surrounding the optic nerves. On the basis of this finding, the patient was finally diagnosed with a bilateral optic nerve sheath meningioma and received external beam radiotherapy. CONCLUSION AND IMPORTANCE: It is crucial to differentiate an optic nerve sheath meningioma from idiopathic calcification of the optic nerve. In the present case the initial MRI did not detect optic nerve sheath abnormalities. To better demonstrate characteristic calcification, additional CT imaging should be considered when a bilateral optic nerve sheath meningioma is suspected.