Brain Tumor Imaging in Adolescents and Young Adults: 2021 WHO Updates for Molecular-based Tumor Types.

Published in 2021, the fifth edition of the World Health Organization (WHO) classification of tumors of the central nervous system (CNS) introduced new molecular criteria for tumor types that commonly occur in either pediatric or adult age groups. Adolescents and young adults (AYAs) are at the intersection of adult and pediatric care, and both pediatric-type and adult-type CNS tumors occur at that age. Mortality rates for AYAs with CNS tumors have increased by 0.6% per year for males and 1% per year for females from 2007 to 2016. To best serve patients, it is crucial that both pediatric and adult radiologists who interpret neuroimages are familiar with the various pediatric- and adult-type brain tumors and their typical imaging morphologic characteristics. Gliomas account for approximately 80% of all malignant CNS tumors in the AYA age group, with the most common types observed being diffuse astrocytic and glioneuronal tumors. Ependymomas and medulloblastomas also occur in the AYA population but are seen less frequently. Importantly, biologic behavior and progression of distinct molecular subgroups of brain tumors differ across ages. This review discusses newly added or revised gliomas in the fifth edition of the CNS WHO classification, as well as other CNS tumor types common in the AYA population.

Network connectivity underlying episodic memory in children: Application of a pediatric brain tumor survivor injury model.

Episodic memory involves personal experiences paired with their context. The Medial Temporal, Posterior Medial, Anterior Temporal, and Medial Prefrontal networks have been found to support the hippocampus in episodic memory in adults. However, there lacks a model that captures how the structural and functional connections of these networks interact to support episodic memory processing in children. Using diffusion-weighted imaging, magnetoencephalography, and memory tests, we quantified differences in white matter microstructure, neural communication, and episodic memory performance, respectively, of healthy children (n = 23) and children with reduced memory performance. Pediatric brain tumor survivors (PBTS; n = 24) were used as a model, as they exhibit reduced episodic memory and perturbations in white matter and neural communication. We observed that PBTS, compared to healthy controls, showed significantly (p < 0.05) (1) disrupted white matter microstructure between these episodic memory networks through lower fractional anisotropy and higher mean and axial diffusivity, (2) perturbed theta band (4-7 Hz) oscillatory synchronization in these same networks through higher weighted phase lag indices (wPLI), and (3) lower episodic memory performance in the Transverse Patterning and Children's Memory Scale (CMS) tasks. Using partial-least squares path modeling, we found that brain tumor treatment predicted network white matter damage, which predicted inter-network theta hypersynchrony and lower verbal learning (directly) and lower verbal recall (indirectly via theta hypersynchrony). Novel to the literature, our findings suggest that white matter modulates episodic memory through effect on oscillatory synchronization within relevant brain networks. RESEARCH HIGHLIGHTS: Investigates the relationship between structural and functional connectivity of episodic memory networks in healthy children and pediatric brain tumor survivors Pediatric brain tumor survivors demonstrate disrupted episodic memory, white matter microstructure and theta oscillatory synchronization compared to healthy children Findings suggest white matter microstructure modulates episodic memory through effects on oscillatory synchronization within relevant episodic memory networks.

Imaging of pediatric brain tumors: A COG Diagnostic Imaging Committee/SPR Oncology Committee/ASPNR White Paper.

Tumors of the central nervous system are the most common solid malignancies in children and the most common cause of pediatric cancer-related mortality. Imaging plays a central role in diagnosis, staging, treatment planning, and response assessment of pediatric brain tumors. However, the substantial variability in brain tumor imaging protocols across institutions leads to variability in patient risk stratification and treatment decisions, and complicates comparisons of clinical trial results. This White Paper provides consensus-based imaging recommendations for evaluating pediatric patients with primary brain tumors. The proposed brain magnetic resonance imaging protocol recommendations balance advancements in imaging techniques with the practicality of deployment across most imaging centers.

Radiomic Features Based on MRI Predict Progression-Free Survival in Pediatric Diffuse Midline Glioma/Diffuse Intrinsic Pontine Glioma.

Purpose: Biopsy-based assessment of H3 K27 M status helps in predicting survival, but biopsy is usually limited to unusual presentations and clinical trials. We aimed to evaluate whether radiomics can serve as prognostic marker to stratify diffuse intrinsic pontine glioma (DIPG) subsets. Methods: In this retrospective study, diagnostic brain MRIs of children with DIPG were analyzed. Radiomic features were extracted from tumor segmentations and data were split into training/testing sets (80:20). A conditional survival forest model was applied to predict progression-free survival (PFS) using training data. The trained model was validated on the test data, and concordances were calculated for PFS. Experiments were repeated 100 times using randomized versions of the respective percentage of the training/test data. Results: A total of 89 patients were identified (48 females, 53.9%). Median age at time of diagnosis was 6.64 years (range: 1-16.9 years) and median PFS was 8 months (range: 1-84 months). Molecular data were available for 26 patients (29.2%) (1 wild type, 3 K27M-H3.1, 22 K27M-H3.3). Radiomic features of FLAIR and nonenhanced T1-weighted sequences were predictive of PFS. The best FLAIR radiomics model yielded a concordance of .87 [95% CI: .86-.88] at 4 months PFS. The best T1-weighted radiomics model yielded a concordance of .82 [95% CI: .8-.84] at 4 months PFS. The best combined FLAIR + T1-weighted radiomics model yielded a concordance of .74 [95% CI: .71-.77] at 3 months PFS. The predominant predictive radiomic feature matrix was gray-level size-zone. Conclusion: MRI-based radiomics may predict progression-free survival in pediatric diffuse midline glioma/diffuse intrinsic pontine glioma.

MRI Radiogenomics of Pediatric Medulloblastoma: A Multicenter Study.

Background Radiogenomics of pediatric medulloblastoma (MB) offers an opportunity for MB risk stratification, which may aid therapeutic decision making, family counseling, and selection of patient groups suitable for targeted genetic analysis. Purpose To develop machine learning strategies that identify the four clinically significant MB molecular subgroups. Materials and Methods In this retrospective study, consecutive pediatric patients with newly diagnosed MB at MRI at 12 international pediatric sites between July 1997 and May 2020 were identified. There were 1800 features extracted from T2- and contrast-enhanced T1-weighted preoperative MRI scans. A two-stage sequential classifier was designed-one that first identifies non-wingless (WNT) and non-sonic hedgehog (SHH) MB and then differentiates therapeutically relevant WNT from SHH. Further, a classifier that distinguishes high-risk group 3 from group 4 MB was developed. An independent, binary subgroup analysis was conducted to uncover radiomics features unique to infantile versus childhood SHH subgroups. The best-performing models from six candidate classifiers were selected, and performance was measured on holdout test sets. CIs were obtained by bootstrapping the test sets for 2000 random samples. Model accuracy score was compared with the no-information rate using the Wald test. Results The study cohort comprised 263 patients (mean age ± SD at diagnosis, 87 months ± 60; 166 boys). A two-stage classifier outperformed a single-stage multiclass classifier. The combined, sequential classifier achieved a microaveraged F1 score of 88% and a binary F1 score of 95% specifically for WNT. A group 3 versus group 4 classifier achieved an area under the receiver operating characteristic curve of 98%. Of the Image Biomarker Standardization Initiative features, texture and first-order intensity features were most contributory across the molecular subgroups. Conclusion An MRI-based machine learning decision path allowed identification of the four clinically relevant molecular pediatric medulloblastoma subgroups. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Chaudhary and Bapuraj in this issue.

Response assessment in diffuse intrinsic pontine glioma: recommendations from the Response Assessment in Pediatric Neuro-Oncology (RAPNO) working group.

Optimising the conduct of clinical trials for diffuse intrinsic pontine glioma involves use of consistent, objective disease assessments and standardised response criteria. The Response Assessment in Pediatric Neuro-Oncology working group, consisting of an international panel of paediatric and adult neuro-oncologists, clinicians, radiologists, radiation oncologists, and neurosurgeons, was established to address issues and unique challenges in assessing response in children with CNS tumours. A working group was formed specifically to address response assessment in children and young adults with diffuse intrinsic pontine glioma and to develop a consensus on recommendations for response assessment. Response should be assessed using MRI of brain and spine, neurological examination, and anti-inflammatory or antiangiogenic drugs. Clinical imaging standards are defined. As with previous consensus recommendations, these recommendations will need to be validated in prospective clinical trials.

Recommendations for Long-Term Follow-up of Adults with Heritable Retinoblastoma.

PURPOSE: To generate recommendations for long-term follow-up of adult survivors of heritable retinoblastoma. DESIGN: We convened a meeting of providers from retinoblastoma centers around the world to review the state of the science and to evaluate the published evidence. PARTICIPANTS: Retinoblastoma is a rare childhood cancer of the retina. Approximately 40% of retinoblastoma cases are heritable, resulting from a germline mutation in RB1. Dramatic improvements in treatment and supportive care have resulted in a growing adult survivor population. However, survivors of heritable retinoblastoma have a significantly increased risk of subsequent malignant neoplasms, particularly bone and soft tissue sarcomas, uterine leiomyosarcoma, melanomas, and radiotherapy-related central nervous system tumors, which are associated with excess morbidity and mortality. Despite these risks, no surveillance recommendations for this population currently are in place, and surveillance practices vary widely by center. METHODS: Following the Institute of Medicine procedure for clinical practice guideline development, a PubMed, EMBASE, and Web of Science search was performed, resulting in 139 articles; after abstract and full-text review, 37 articles underwent detailed data abstraction to quantify risk and evidence regarding surveillance, if available. During an in-person meeting, evidence was presented and discussed, resulting in consensus recommendations. MAIN OUTCOME MEASURES: Diagnosis and mortality from subsequent neoplasm. RESULTS: Although evidence for risk of subsequent neoplasm, especially sarcoma and melanoma, was significant, evidence supporting routine testing of asymptomatic survivors was not identified. Skin examination for melanoma and prompt evaluation of signs and symptoms of head and neck disease were determined to be prudent. CONCLUSIONS: This review of the literature confirmed some of the common second cancers in retinoblastoma survivors but found little evidence for a benefit from currently available surveillance for these malignancies. Future research should incorporate international partners, patients, and family members.

Eye Movements and White Matter are Associated with Emotional Control in Children Treated for Brain Tumors.

OBJECTIVE: Children treated for brain tumors often experience social and emotional difficulties, including challenges with emotion regulation; our goal was to investigate the attention-related component processes of emotion regulation, using a novel eye-tracking measure, and to evaluate its relations with emotional functioning and white matter (WM) organization. METHOD: Fifty-four children participated in this study; 36 children treated for posterior fossa tumors, and 18 typically developing children. Participants completed two versions of an emotion regulation eye-tracking task, designed to differentiate between implicit (i.e., automatic) and explicit (i.e., voluntary) subprocesses. The Emotional Control scale from the Behavior Rating Inventory of Executive Function was used to evaluate emotional control in daily life, and WM organization was assessed with diffusion tensor imaging. RESULTS: We found that emotional faces captured attention across all groups (F(1,51) = 32.18, p < .001, η2p = .39). However, unlike typically developing children, patients were unable to override the attentional capture of emotional faces when instructed to (emotional face-by-group interaction: F(2,51) = 5.58, p = .006, η2p = .18). Across all children, our eye-tracking measure of emotion regulation was modestly associated with the parent-report emotional control score (r = .29, p = .045), and in patients it was associated with WM microstructure in the body and splenium of the corpus callosum (all t > 3.03, all p < .05). CONCLUSIONS: Our findings suggest that an attention-related component process of emotion regulation is disrupted in children treated for brain tumors, and that it may relate to their emotional difficulties and WM organization. This work provides a foundation for future theoretical and mechanistic investigations of emotional difficulties in brain tumor survivors.

Indolent course of brainstem tumors with K27M-H3.3 mutation.

Diffuse intrinsic pontine glioma (DIPG) is characterized by a short history of brainstem symptoms and well-known magnetic resonance imaging features with a fatal outcome. However, we report three unusual cases of brainstem tumors with an initial indolent and protracted course, which subsequently developed the classical imaging and clinical features of DIPG. Our findings support this notion that K27M is an early event in development and suggest that the emergence of additional events resulted in rapid progression after a long period of latency. Identification of such markers of aggressive behavior in the context of an indolent course is needed for better characterization and treatment management.

Predictors of neuropsychological late effects and white matter correlates in children treated for a brain tumor without radiation therapy.

BACKGROUND: Little is known about cognition and predictors of neuropsychological outcomes in pediatric low-grade glioma (PLGG) survivors treated without radiation therapy. This research expands upon our previous work by further identifying the cognitive profile of PLGG patients treated without radiation therapy, investigating the specific medical and demographic variables that predict functioning, and examining white matter structure and its relationship to neuropsychological performance. PROCEDURE: Nineteen PLGG patients (11-19 years) were administered the Wechsler Intelligence Scale for Children/Wechsler Adult Intelligence Scale, and subtests from the Woodcock-Johnson Tests of Cognition (visual matching, rapid picture naming, and pair cancellation) and Cambridge Neuropsychological Test Automated Battery (pattern recognition memory, delayed matching to sample, intra-extra dimensional set shift, motor screening task, rapid visual information processing, and spatial span). RESULTS: The sample had normative weaknesses in verbal working memory, brief attention/vigilance, psychomotor speeded output, visual perception and matching, overall cognition, working memory, and processing speed. Increased surgeries or subtotal resections, hydrocephalus, shunting procedures, chemotherapy, NF1, and supratentorial location were predictive of cognitive deficits. Broad white matter involvement of the frontal, temporal, parietal, and occipital lobes as well as the cerebellum, as inferred from diffusion tensor imaging indices of decreased fiber orientation and increased water diffusion, was related to many cognitive difficulties. CONCLUSIONS: This study comprehensively examines cognitive functioning in PLGG patients treated without radiation therapy, predictors of cognition, and its relation to white matter structure. Our findings indicate that medical and demographic variables other than radiation therapy can lead to cognitive late effects with diffuse white matter involvement.

Changes in White Matter Microstructure Impact Cognition by Disrupting the Ability of Neural Assemblies to Synchronize.

Cognition is compromised by white matter (WM) injury but the neurophysiological alterations linking them remain unclear. We hypothesized that reduced neural synchronization caused by disruption of neural signal propagation is involved. To test this, we evaluated group differences in: diffusion tensor WM microstructure measures within the optic radiations, primary visual area (V1), and cuneus; neural phase synchrony to a visual attention cue during visual-motor task; and reaction time to a response cue during the same task between 26 pediatric patients (17/9: male/female) treated with cranial radiation treatment for a brain tumor (12.67 ± 2.76 years), and 26 healthy children (16/10: male/female; 12.01 ± 3.9 years). We corroborated our findings using a corticocortical computational model representing perturbed signal conduction from myelin. Patients show delayed reaction time, WM compromise, and reduced phase synchrony during visual attention compared with healthy children. Notably, using partial least-squares-path modeling we found that WM insult within the optic radiations, V1, and cuneus is a strong predictor of the slower reaction times via disruption of neural synchrony in visual cortex. Observed changes in synchronization were reproduced in a computational model of WM injury. These findings provide new evidence linking cognition with WM via the reliance of neural synchronization on propagation of neural signals.SIGNIFICANCE STATEMENT By comparing brain tumor patients to healthy children, we establish that changes in the microstructure of the optic radiations and neural synchrony during visual attention predict reaction time. Furthermore, by testing the directionality of these links through statistical modeling and verifying our findings with computational modeling, we infer a causal relationship, namely that changes in white matter microstructure impact cognition in part by disturbing the ability of neural assemblies to synchronize. Together, our human imaging data and computer simulations show a fundamental connection between WM microstructure and neural synchronization that is critical for cognitive processing.

Pediatric Brain Tumor Genetics: What Radiologists Need to Know.

Brain tumors are the most common solid tumors in the pediatric population. Pediatric neuro-oncology has changed tremendously during the past decade owing to ongoing genomic advances. The diagnosis, prognosis, and treatment of pediatric brain tumors are now highly reliant on the genetic profile and histopathologic features of the tumor rather than the histopathologic features alone, which previously were the reference standard. The clinical information expected to be gleaned from radiologic interpretations also has evolved. Imaging is now expected to not only lead to a relevant short differential diagnosis but in certain instances also aid in predicting the specific tumor and subtype and possibly the prognosis. These processes fall under the umbrella of radiogenomics. Therefore, to continue to actively participate in patient care and/or radiogenomic research, it is important that radiologists have a basic understanding of the molecular mechanisms of common pediatric central nervous system tumors. The genetic features of pediatric low-grade gliomas, high-grade gliomas, medulloblastomas, and ependymomas are reviewed; differences between pediatric and adult gliomas are highlighted; and the critical oncogenic pathways of each tumor group are described. The role of the mitogen-activated protein kinase pathway in pediatric low-grade gliomas and of histone mutations as epigenetic regulators in pediatric high-grade gliomas is emphasized. In addition, the oncogenic drivers responsible for medulloblastoma, the classification of ependymomas, and the associated imaging correlations and clinical implications are discussed. ©RSNA, 2018.

Volumetric assessment of tumor size changes in pediatric low-grade gliomas: feasibility and comparison with linear measurements.

PURPOSE: We report a retrospective comparison between bi-dimensional RANO criteria and manual volumetric segmentation (MVS) in pediatric low-grade gliomas. METHODS: MRI FLAIR or T1 post contrast images were used for assessment of tumor response. Seventy patients were included in this single center study, for each patient two scans were assessed ("time 0" and "end of therapy") and response to therapy was evaluated for both methods. Inter-reader variability and average time for volumetric assessment were also calculated. RESULTS: Fourteen (20%) of the 70 patients had discordant results in terms of response assessment between the bi-dimensional measurements and MVS. All volumetric response assessments were in keeping with the subjective analysis of tumor (radiology report). Of the 14 patients, 6 had stable disease (SD) on MVS and progressive disease (PD) on 2D assessment, 5 patients had SD on MVS and partial response (PR) on 2D assessment, 2 patients had PD on MVS and SD on 2D assessment, and 1 patient had PR on MVS and SD on 2D analysis. The number of discordant results rises to 21(30%) if minor response is integrated in the response assessment. MVS was relatively fast and showed high inter-reader concordance. CONCLUSION: Our analysis shows that therapeutic response classification may change in a significant number of children by performing a volumetric tumor assessment. Furthermore, MVS is not particularly time consuming and has very good inter-reader concordance.

Smaller hippocampal subfield volumes predict verbal associative memory in pediatric brain tumor survivors.

The developing hippocampus is highly sensitive to chemotherapy and cranial radiation treatments for pediatric cancers, yet little is known about the effects that cancer treatents have on specific hippocampal subfields. Here, we examined hippocampal subfield volumes in 29 pediatric brain tumor survivors treated with cranial radiation and chemotherapy, and 30 healthy developing children and adolescents. We also examined associations between hippocampal subfield volumes and short-term verbal memory. Hippocampal subfields (Cornus Ammonis (CA) 1, CA2-3, dentate gyrus (DG)-CA4, stratum radiatum-lacunosum-moleculare, and subiculum) were segmented using the Multiple Automatically Generated Templates for Different Brains automated segmentation algorithm. Neuropsychological assessment of short-term verbal associative memory was performed in a subset of brain tumor survivors (N = 11) and typically developing children (N = 16), using the Children's Memory Scale or Wechsler's Memory Scale-third edition. Repeated measures analysis of variance showed that pediatric brain tumor survivors had significantly smaller DG-CA4, CA1, CA2-3, and stratum radiatum-lacunosum-moleculare volumes compared with typically developing children. Verbal memory performance was positively related to DG-CA4, CA1, and stratum radiatum-lacunosum-moleculare volumes in pediatric brain tumor survivors. Unlike the brain tumor survivors, there were no associations between subfield volumes and memory in typically developing children and adolescents. These data suggest that specific subfields of the hippocampus may be vulnerable to brain cancer treatments, and may contribute to impaired episodic memory following brain cancer treatment in childhood.

Homozygous mutation in PRUNE1 in an Oji-Cree male with a complex neurological phenotype.

The PRUNE1 gene encodes a member of the phosphoesterases (DHH) protein superfamily that is highly expressed in the human fetal brain and involved in the regulation of cell migration. Homozygous or compound heterozygous PRUNE1 mutations were recently identified in five individuals with brain malformations from four families. We present a case of a 2-year-old male with a complex neurological phenotype and abnormalities on brain MRI. Re-annotation of clinical whole-exome sequencing data revealed a homozygous likely pathogenic variant in PRUNE1 (c.521-2A>G). These results further delineate a new PRUNE1-related syndrome, and highlight the importance of periodic data re-annotation in individuals who remain without a diagnosis after undergoing genome-wide testing. © 2017 Wiley Periodicals, Inc.

Visualization and segmentation of reciprocal cerebrocerebellar pathways in the healthy and injured brain.

Detailed information regarding the neuroanatomy of reciprocal cerebrocerebellar pathways is based on well-documented animal models. This knowledge has not yet been fully translated to humans, in that the structure of reciprocal cerebrocerebellar pathways connecting the cerebellum with frontal lobe has not been shown in its entirety. We investigated the impact of injury and age on cerebrocerebellar pathway microstructure using diffusion tensor imaging (DTI) and probabilistic tractography. We used medulloblastoma (MB) as an injury model due to the known impact of tumor/treatment on the cerebellum, one of the main nodes of cerebrocerebellar pathways. We delineated and segmented reciprocal cerebrocerebellar pathways connecting the cerebellum with frontal lobe in 38 healthy children (HC) and 34 children treated for MB, and compared pathway segment DTI measures between HC and MB and across three age cohorts: childhood, early adolescence, and late adolescence. Pathway compromise was evident for the MB group compared to HC, particularly within posterior segments (Ps<0.01). Though we found no age effect, group differences in microstructure were driven by pathway segment (posterior) and age cohort (adolescence), which may reflect the extent of injury to the posterior fossa following treatment for MB and age cohort differences in radiation treatment protocol in our sample. We have examined the microstructure of reciprocal cerebrocerebellar connections in the pediatric brain and have found that these pathways are injured in MB, a clinical population treated with surgery, radiation, and chemotherapy. Our findings support the late effects literature describing white matter injury emergence in the years following treatment for MB.

Diabetes insipidus in pediatric germinomas of the suprasellar region: characteristic features and significance of the pituitary bright spot.

The pituitary bright spot is acknowledged to indicate functional integrity of the posterior pituitary gland, whilst its absence supports a diagnosis of central diabetes insipidus (DI). This feature was evaluated, together with the incidence and clinical characteristics of DI in children with suprasellar/neurohypophyseal germinomas. We performed a review of all suprasellar (SS) or bifocal (BF) germinoma pediatric patients treated in Toronto since 2000. Demographics, symptomatology, treatment outcome and imaging were evaluated. Nineteen patients fulfilled inclusion criteria (10 SS, 9 BF; median age 12.5 years (6.2-16.8 years)). All remained alive at 6.4 years median follow-up (1.2-13.7 years) after receiving chemotherapy and radiotherapy (13 focal/ventricular, four whole brain, two neuraxis), with only one progression. All had symptoms of DI at presentation with a symptom interval above one year in eight cases (42 %). Desmopressin was commenced and maintained in 16 patients (84 %). The pituitary bright spot was lost in most diagnostic interpretable cases, but was appreciated in three patients (18 %) who had normal serum sodium values compared to 'absent' cases (p = 0.013). For two such cases, spots remained visible until last follow-up (range 0.4-3.3 years), with one still receiving desmopressin. No case of bright spot recovery was observed following therapy. Protracted symptom intervals for germinoma-induced central DI may reflect poor clinical awareness. Explanations for persistence of the pituitary bright spot in symptomatic patients remain elusive. Desmopressin seldom reverses the clinical features of germinoma-induced DI to allow discontinuation, nor does treatment cause bright spot recovery.

Tumor volumetric measurements in surgically inaccessible pediatric low-grade glioma.

Tumor measurement is important in unresectable pediatric low-grade gliomas (pLGGs) to determine either the need for treatment or assess response. Standard methods measure the product of the largest 2 lengths from transverse, anterior-posterior, and cranio-caudal dimensions (SM, cm). This single-institution study evaluated tumor volume measurements (VM, cm) in such pLGGs. Of 50 patients treated with chemotherapy for surgically inaccessible pLGG, 8 met the inclusion criteria of having 2 or more sequential MRI studies of T1-weighted Fast-Spoiled Gradient Recalled acquisition. SM and VM were performed by 2 independent neuroradiologists. Associations of measurement methods with defined therapeutic response criteria and patient clinical status were assessed. The mean tumor size at the first MRI scan was 20 cm and 398 cm according to SM and VM, respectively. VM results did not differ significantly from SM-derived spherical volume calculations (Pearson correlation, P<0.0001) with a high interrater reliability. Both methods were concordant in defining the tumor response according to the current criteria, although radiologic progressive disease was not associated with clinical status (SM: P=0.491, VM: P=0.208). In this limited experience, volumetric analysis of unresectable pLGGs did not seem superior to the standard linear measurements for defining tumor response.

Posterior fossa tumors in children: developmental anatomy and diagnostic imaging.

INTRODUCTION: Modern understanding of the relation between the mutated cancer stem cell and its site of origin and of its interaction with the tissue environment is enhancing the importance of developmental anatomy in the diagnostic assessment of posterior fossa tumors in children. The aim of this review is to show how MR imaging can improve on the exact identification of the tumors in the brainstem and in the vicinity of the fourth ventricle in children, using both structural imaging data and a precise topographical assessment guided by the developmental anatomy. RESULTS: The development of the hindbrain results from complex processes of brainstem segmentation, ventro-dorsal patterning, multiple germinative zones, and diverse migration pathways of the neural progenitors. Depending on their origin in the brainstem, gliomas may be infiltrative or not, as well as overwhelmingly malignant (pons), or mostly benign (cervicomedullary, medullo-pontine tegmental, gliomas of the cerebellar peduncles). In the vicinity of the fourth ventricles, the prognosis of the medulloblastomas (MB) correlates the molecular subtyping as well as the site of origin: WNT MB develop from the Wnt-expressing lower rhombic lip and have a good prognosis; SHH MB develop from the Shh-modulated cerebellar cortex with an intermediate prognosis (dependent on age); recurrences are local mostly. The poor prognosis group 3 MB is radiologically heterogeneous: some tumors present classic features but are juxtaventricular (rather than intraventricular); others have highly malignant features with a small principal tumor and an early dissemination. Group 4 MB has classic features, but characteristically usually does not enhance; dissemination is common. Although there is as yet no clear molecular subgrouping of the ependymomas, their sites of origin and their development can be clearly categorized, as most develop in an exophytic way from the ventricular surface of the medulla in clearly specific locations: the obex region with expansion in the cistern magna, or the lateral recess region with expansion in the CPA and prepontine cisterns (cerebellar ependymomas, and still more intra-brainstem ependymomas are rare). Finally, almost all cerebellar gliomas are pilocytic astrocytomas. CONCLUSIONS: A developmental and anatomic approach to the posterior fossa tumors in children (together with diffusion imaging data) provides a reliable pre-surgical identification of the tumor and of its aggressiveness.