Posterior fossa tumors in children: current insights.

While in adults most intracranial tumors develop around the cerebral hemispheres, 45 to 60% of pediatric lesions are found in the posterior fossa, although this anatomical region represents only 10% of the intracranial volume. The latest edition of the WHO classification for CNS tumors presented some fundamental paradigm shifts that particularly affected the classification of pediatric tumors, also influencing those that affect posterior fossa. Molecular biomarkers play an important role in the diagnosis, prognosis, and treatment of childhood posterior fossa tumors and can be used to predict patient outcomes and response to treatment and monitor its effectiveness. Although genetic studies have identified several posterior fossa tumor types, differing in terms of their location, cell of origin, genetic mechanisms, and clinical behavior, recent management strategies still depend on uniform approaches, mainly based on the extent of resection. However, significant progress has been made in guiding therapy decisions with biological or molecular stratification criteria and utilizing molecularly targeted treatments that address specific tumor biological characteristics. The primary focus of this review is on the latest advances in the diagnosis and treatment of common subtypes of posterior fossa tumors in children, as well as potential therapeutic approaches in the future.   Conclusion: Molecular biomarkers play a central role, not only in the diagnosis and prognosis of posterior fossa tumors in children but also in customizing treatment plans. They anticipate patient outcomes, measure treatment responses, and assess therapeutic effectiveness. Advances in neuroimaging and treatment have significantly enhanced outcomes for children with these tumors. What is Known: • Central nervous system tumors are the most common solid neoplasms in children and adolescents, with approximately 45 to 60% of them located in the posterior fossa. • Multimodal approaches that include neurosurgery, radiation therapy, and chemotherapy are typically used to manage childhood posterior fossa tumors What is New: • Notable progress has been achieved in the diagnosis, categorization and management of posterior fossa tumors in children, leading to improvement in survival and quality of life.

[Pediatric Posterior Fossa Tumors].

Posterior fossa tumors tend to entail obstructive hydrocephalus, and urges initiating prompt treatment. Prevalent pathologies include medulloblastoma, ependymoma, pilocytic astrocytoma, and atypical teratoid/rhabdoid tumor(AT/RT). In most cases, maximal safe resection is related to better prognosis. In some cases of ependymoma and AT/RT with high vascularity, second-look surgery with neoadjuvant chemotherapy is effective. The treatment strategy should be tailored according to each tumor.

Acute Myeloid Leukemia Presenting as a Posterior Fossa Tumor.

Extramedullary leukemia in pediatric acute myeloid leukemia can manifest as a myeloid sarcoma (MS), also known as granulocytic sarcoma or chloroma, in a variety of sites, or as leukemic blasts in the cerebrospinal fluid. Isolated MS of the central nervous system is rare. We report a case of acute myeloid leukemia with central nervous system-MS presenting as a posterior fossa mass mimicking a primary intracranial tumor.

Epithelioid Sarcoma Arising in a Long-Term Survivor of an Atypical Teratoid/Rhabdoid Tumor in a Patient With Rhabdoid Tumor Predisposition Syndrome.

Rhabdoid tumor predisposition syndrome (RTPS) is defined as the presence of a SMARCB1 or SMARCA4 genetic aberration in a patient with malignant rhabdoid tumor. Patients with RTPS are more likely to present with synchronous or metachronous rhabdoid tumors. Based on the current state of rhabdoid tumor taxonomy, these diagnoses are based largely on patient demographics, anatomic location of disease, and immunohistochemistry, despite their nearly identical histologic and immunohistochemical profiles. Thus, the true distinction between such tumors remains a diagnostic challenge. Central nervous system atypical teratoid/rhabdoid tumor (AT/RT) is a rare, aggressive, primarily pediatric malignancy with variable histologic features and a well documented association with loss of SMARCB1 expression. Epithelioid sarcoma (ES) is a rare soft tissue tumor arising in patients of all ages and characteristically staining for both mesenchymal and epithelial immunohistochemical markers while usually demonstrating loss of SMARCB1 expression. To our knowledge we herein present the first documented case of a patient with RTPS who presented with metachronous AT/RT and ES.

The impact of tracheostomy timing on clinical outcomes and adverse events in intubated patients with infratentorial lesions: early versus late tracheostomy.

We evaluated the association between the timing of tracheostomy and clinical outcomes in patients with infratentorial lesions. We performed a retrospective observational cohort study in a neurosurgical intensive care unit (ICU) at a tertiary academic medical center from January 2014 to December 2018. Consecutive adult patients admitted to the ICU who underwent resection of infratentorial lesions as well as tracheostomy were included for analysis. Early tracheostomy was defined as performed on postoperative days 1-10 and late tracheostomy on days 10-20 after operation. Univariate and multivariate analyses were used to compare the characteristics and outcomes between both cohorts. A total of 143 patients were identified, and 96 patients received early tracheostomy. Multivariable analysis identified early tracheostomy as an independent variable associated with lower occurrence of pneumonia (odds ratio, 0.25; 95% CI, 0.09-0.73; p = 0.011), shorter stays in ICUs (hazard ratio, 0.4; 95% CI, 0.3-0.6; p = 0.03), and earlier decannulation (hazard ratio, 0.5; 95% CI, 0.4-0.8; p = 0.003). However, no significant differences were observed between the early and late tracheostomy groups regarding hospital mortality (p > 0.999) and the modified Rankin scale after 6 months (p = 0.543). We also identified postoperative brainstem deficits, including cough, swallowing attempts, and extended tongue as well as GCS < 8 at ICU admission as the risk factors independently associated with patients underwent tracheostomy. There is a significant association between early tracheostomy and beneficial clinical outcomes or reduced adverse event occurrence in patients with infratentorial lesions.

The role of external ventricular drainage for the management of posterior cranial fossa tumours: a systematic review.

Posterior cranial fossa tumours frequently develop hydrocephalus as first presentation in up to 80% of paediatric patients and 21.4% of adults, although it resolves after tumour removal in 70-90% and 96%, respectively. New onset hydrocephalus is reported in about 2.1% of adult and 10-40% of paediatric patients after posterior fossa surgery. There is no consensus concerning prophylactic external ventricular drainage (EVD) placement that is frequently used before posterior fossa lesion removal, as well in those cases without clear evidence of hydrocephalus. The aim of the study was to define the most correct management for patients who undergo posterior fossa tumour surgery, thus identifying cohorts of patients who are at risk of persistent hydrocephalus prior to surgery. A systematic review of literature has been performed, following PRISMA guidelines. Most of the studies reported CSF shunt only in the presence of hydrocephalus, whereas only a few authors suggested its prophylactic use in the absence of signs of ventricular dilatation. Predictive factors for postoperative hydrocephalus has been identified, including young age (< 3 years), severe symptomatic hydrocephalus at presentation, EVD placement before surgery, FOHR index > 0.46 and Evans index > 0.4, pseudomeningocele, CSF leak and infection. The use of pre-resection CSF shunt in case of signs and symptoms of hydrocephalus is mandatory, although it resolves in the majority of cases. As reported by several studies included in the present review, we suggest CSF shunt also in case of asymptomatic hydrocephalus, whereas it is not indicated without evidence of ventricular dilatation.

Neuropsychological Profile in Children with Posterior Fossa Tumors with or Without Postoperative Cerebellar Mutism Syndrome (CMS).

Cerebellar mutism syndrome (CMS) is a common surgical sequela in children following posterior fossa tumor (PFT) resection. Here, we analyze the neuropsychological features associated with PFT in children, focusing particularly on the differential profiles associated with the presence or absence of CMS after surgery. We further examine the effect of post-resection treatments, tumor type, and presence/absence of hydrocephalus on surgical outcome. Thirty-six patients diagnosed with PFT (19 with and 17 without CMS) and 34 age- and gender-matched healthy controls (HCs) were recruited. A comprehensive neuropsychological evaluation was conducted in all patients postoperatively and in HCs, including an assessment of general cognitive ability, motor skills, perception, language, memory, attention, executive functions, and academic competence. CMS was found to be a clinical marker of lower neuropsychological profile scores across all cognitive domains except auditory-verbal processing and visual memory tasks. PFT patients not presenting CMS exhibited milder impairment in intellectual functioning, motor tasks, reasoning, language, verbal learning and recall, attention, cognitive executive functions, and academic competence. High-grade tumors were associated with slower processing speed and verbal delayed recall as well as alterations in selective and sustained attention. Hydrocephalus was detrimental to motor functioning and nonverbal reasoning. Patients who had undergone surgery, chemotherapy, and radiotherapy presented impaired processing speed, verbal learning, and reading. In addition to the deleterious effects of PFT, post-resection PFT treatments have a negative cognitive impact. These undesired consequences and the associated tumor-related damage can be assessed using standardized, long-term neuropsychological evaluation when planning rehabilitation.

Newly Diagnosed Metastatic Intracranial Ependymoma in Children: Frequency, Molecular Characteristics, Treatment, and Outcome in the Prospective HIT Series.

BACKGROUND: Data on frequency, clinical presentation, and outcome of primary metastatic intracranial ependymoma in children are scarce. PATIENTS AND METHODS: Prospective data on patients younger than 21 years with metastatic intracranial ependymoma at first diagnosis, registered from 2001 to 2014 in the HIT-2000 trial and the HIT-2000 Interim Registry, were analyzed. RESULTS: Of 453 registered patients with intracranial ependymoma and central neuropathology review, initial staging included spinal magnetic resonance imaging in all patients and lumbar cerebrospinal fluid (CSF) analysis in 402 patients. Ten patients (2.2%) had metastatic disease, including three with microscopic CSF positivity only (M1 metastasis stage, 0.7% of patients with CSF staging). Location of the primary tumor was supratentorial in four patients (all supratentorial RELA-fused ependymoma [ST-EPN-RELA]) and within the posterior fossa in five patients (posterior fossa ependymoma type A [PF-EPN-A], n = 4; posterior fossa ependymoma not further classifiable, n = 1), and multifocal in one patient.All four patients with ST-EPN-RELA were alive in first or second complete remission (CR) 7.5-12.3 years after diagnosis. All four patients with macroscopic metastases of posterior fossa or multifocal ependymoma died. Three patients with initial M1 stage (ST-EPN-RELA, n = 1; PF-EPN-A, n = 2) received chemotherapy and local irradiation and were alive in second or third CR 3.0-9.7 years after diagnosis. Progression-free and overall survival of the entire cohort at 5 years was 13% (±6%), and 58% (±16%), respectively. CONCLUSION: Primary metastatic disease is rare in children with intracranial ependymoma. Prognosis may depend on molecular subgroup and extent of dissemination, and relevance of CSF analysis for initial staging remains to be clarified. IMPLICATIONS FOR PRACTICE: Childhood ependymoma presenting with metastasis at first diagnosis is very rare with a frequency of 2.4% in this population-based, well-characterized cohort. Detection of microscopic metastases in the cerebrospinal fluid was extremely rare, and impact on prognosis and respective treatment decision on irradiation field remains unclear. Initial metastatic presentation occurs in both supratentorial RELA-fused ependymoma and posterior fossa ependymoma. Prognosis may differ according to extent of metastasis and biological subgroup, with poor prognosis in diffusely spread metastatic posterior fossa ependymoma even after combination therapy with both intensive chemotherapy and craniospinal irradiation, which may help to guide individual therapeutic decisions for future patients.

Magnetic resonance spectroscopy in posterior fossa tumours: the tumour spectroscopic signature may improve discrimination in adults among haemangioblastoma, ependymal tumours, medulloblastoma, and metastasis.

OBJECTIVES: Assessing a posterior fossa tumour in an adult can be challenging. Metastasis, haemangioblastoma, ependymal tumours, and medulloblastoma are the most common diagnostic possibilities. Our aim was to evaluate the contribution of magnetic resonance spectroscopy (MRS) in the diagnosis of these entities. METHODS: We retrospectively evaluated 56 consecutive patients with a posterior fossa tumour and histological diagnosis of ependymal tumour, medulloblastoma, haemangioblastoma, and metastasis in which good-quality spectra at short (TE 30 ms) or/and intermediate (TE, 136 ms) TE were available. Spectra were compared using the Mann-Whitney U non-parametric test in order to select the spectral datapoints and the intensity ratios that showed significant differences between groups of lesions. Performance of these datapoints and their ratios were assessed with ROC curves. RESULTS: The most characteristic signatures on spectroscopy were high choline (Cho) in medulloblastoma (p < 0.001), high myoinositol (mIns) in ependymal tumours (p < 0.05), and high lipids (LIP) in haemangioblastoma (p < 0.01) and metastasis (p < 0.01). Selected ratios between normalised intensity signals of resonances provided accuracy values between 79 and 95% for pairwise comparisons. Intensity ratio NI3.21ppm/3.55ppm provided satisfactory discrimination between medulloblastoma and ependymal tumours (accuracy, 92%), ratio NI2.11ppm/1.10ppm discriminated ependymal tumours from haemangioblastoma (accuracy, 94%), ratio NI3.21ppm/1.13ppm discriminated haemangioblastoma from medulloblastoma (accuracy, 95%), and ratio NI1.28ppm/2.02pmm discriminated haemangioblastoma from metastasis (accuracy, 83%). CONCLUSIONS: MRS may improve the non-invasive diagnosis of posterior fossa tumours in adults. KEY POINTS: • High choline suggests a medulloblastoma in a posterior fossa tumour. • High myoinositol suggests an ependymal lesion in a posterior fossa tumour. • High lipids suggest a metastasis or a haemangioblastoma in a posterior fossa tumour.

PHOX2B is a reliable immunomarker in distinguishing peripheral neuroblastic tumours from CNS embryonal tumours.

AIMS: The PHOX2B gene regulates neuronal maturation in the brain stem nuclei associated with cardiorespiratory function and in the autonomic sympathetic and enteric nervous system. PHOX2B expression is a reliable immunomarker for peripheral neuroblastic tumours; however, no systematic evaluation of central nervous system (CNS) embryonal tumours was included in the studies. We encountered two cases in which the differential diagnosis included neuroblastoma and CNS embryonal tumour, and we hypothesised that PHOX2B immunostain would be helpful in establishing the diagnosis. METHODS AND RESULTS: PHOX2B immunostain was performed on 29 paediatric cases, with adequate controls: one retroperitoneal embryonal tumour in a child with retinoblastoma (index 1), one posterior fossa embryonal tumour in a child with a neuroblastoma (index 2), seven medulloblastomas, four atypical teratoid/rhabdoid tumours (ATRT), four retinoblastomas, six pineoblastomas, four embryonal tumours with multilayered rosettes (ETMR) and two CNS embryonal tumours, not elsewhere classified. Cell lineage immunomarkers (GFAP, OLIG2, synaptophysin, NeuN, CRX, PGP 9.5), immunosurrogates for molecular alterations (beta-catenin, INI1, Lin-28), array CGH and OncoPanel were performed as needed. Medulloblastomas, ATRTs, ETMRs, retinoblastomas and CNS embryonal tumours not elsewhere classified were essentially negative for PHOX2B. Two of six pineoblastomas had significant PHOX2B expression, while the rest were negative. Index 1 was negative for PHOX2B and PGP 9.5 and positive for CRX, consistent with retinoblastoma. Index 2 had diffuse PHOX2B expression, MYCN amplification and no copy number changes of medulloblastoma, in keeping with neuroblastoma. CONCLUSION: PHOX2B antibody is helpful in distinguishing between peripheral neuroblastic and CNS embryonal tumours, which are immunonegative, with the caveat that a subset of pineoblastomas has significant expression.

Posterior fossa recurrence of WHO grade II and III supratentorial gliomas.

OBJECTIVE/BACKGROUND: Posterior fossa (PF) recurrences of supratentorial (ST) World Health Organization (WHO) grade II and III gliomas are thought to be rare and to have grim prognoses. METHODS: This study entailed searching through our database and reviewing the records of patients with grade II and III ST gliomas who developed PF recurrence with no overt secondary gliomatosis or leptomeningeal spread. RESULTS: Of 2266 grade II and III gliomas, 14 fulfilled the inclusion criteria: 5 oligodendrogliomas (O; 1 OII, 4 OIII); 7 astrocytomas (A; 4 AII, 3 AIII); and 2 oligoastrocytomas (OA; both OAIII). The male/female gender ratio was 10/4, and median age at recurrence was 43 years. Two groups were identified. In one group (n=8; 1 AII, 3 AIII, 2 OAIII, 2 OIII), a rapidly growing contrast-enhancing PF mass (6/8) was associated with ST progression, and median survival time after detection was only 6.5 months despite radiotherapy and/or chemotherapy. In the second group (n=6; 3 AII, 1 OII, and 2 OIII), a non-contrast-enhancing (5/6), asymptomatic (5/6), slow-growing PF mass remained isolated, and treatment with radio- or chemotherapy produced objective responses in three patients and durable stabilization in the remaining three. After a median follow-up of 63months, only one patient died due to delayed recurrence of the ST lesion, while the remaining five patients are still alive. CONCLUSION: Non-contiguous PF relapses of ST grade II and III gliomas are rare. A high-grade ST tumor that is concomitantly progressing appears to be a predictor of poor survival. Conversely, the tumor course may be indolent if the ST lesion is low-grade and non-progressive at the time of PF involvement. The possible mechanism(s) behind this tropism are also discussed.

Infratentorial ganglioglioma mimicking pilocytic astrocytoma.

Majority of tumors arising in posterior fossa in children are pilocytic astrocytoma. However, a small subset of these have a neuronal component that may either be admixed throughout with the glial component or may be segregated to one or two regions within the glial element. Interestingly, the radiological features of this subgroup are also distinctive, showing midline location, frequent cyst formation, hemorrhage, and circumscribed nature. Taken together, both radiological and pathological features can fairly predict the subgroup categorization within infratentorial gangliogliomas (GG), as has been recently elucidated. Moreover, these are characterized by distinct molecular abnormalities that are therapeutically targetable, making their recognition critical. We describe an example of infratentorial tumor with its radiology and morphological features distinct enough to place it under the category of GG, group II or pilocytic astrocytoma with gangliocytic differentiation.
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RETROSPECTIVE COMPARISON OF THREE-DIMENSIONAL CONFORMAL RADIATION THERAPY VS. PREDNISOLONE ALONE IN 30 CASES OF CANINE INFRATENTORIAL BRAIN TUMORS.

Infratentorial tumors are relatively infrequent in dogs and a lack of data makes it difficult to offer prognostic information. Untreated, dogs with these neoplasms have shorter survival times than those with supratentorial tumors. The role of radiation therapy (RT) in the management of infratentorial tumors is poorly defined and tumoral/peritumoral swelling in this site is a potential cause of serious acute side effects. The aim of this retrospective, cohort study was to describe cases of infratentorial tumors treated with fractionated three-dimensional conformal RT (3D CRT) and glucocorticoids (GC), and compare outcomes and survival with dogs affected by tumors in the same location that received GC alone. Thirty patients with a MRI diagnosis of infratentorial tumors were recruited (15 received RT and GC and 15 GC alone). None had mentation changes at presentation. For both groups, MRI and medical records were reviewed; and factors associated with survival were evaluated with Kaplan-Meier product limit survival and Cox regression analysis. Overall median survival time (MST) was 294 days (95% CI 42-545). The MST in the RT group was 756 days (95% CI 209-1302) vs. 89 days (95% CI 34.7-143.3 days) for those dogs treated palliatively with GC alone. This difference was statistically significant (P = 0.001). No other factors (including neurological signs, MRI features, tumor volume and total RT dose) were statistically associated with survival in the RT group. This study suggests that 3D CRT offers a survival advantage for dogs with infratentorial tumors compared to GC alone, and significant complications are uncommon.

Evaluation of chromosome 1q gain in intracranial ependymomas.

Ependymomas are relatively uncommon gliomas with poor prognosis despite recent advances in neurooncology. Molecular pathogenesis of ependymomas is not extensively studied. Lack of correlation of histological grade with patient outcome has directed attention towards identification of molecular alterations as novel prognostic markers. Recently, 1q gain has emerged as a potential prognostic marker, associated with decreased survival, especially in posterior fossa, high grade tumors. Cases of intracranial ependymomas were retrieved. Tumors were graded using objective criteria to supplement WHO grading. Fluorescence in situ hybridization for 1q gain was performed on formalin-fixed paraffin embedded sections. Eighty-one intracranial ependymomas were analyzed. Pediatric (76%) and infratentorial (70%) ependymomas constituted the majority. 1q gain was seen in 27 cases (33%), was equally frequent in children (34%) and adults (32%), supratentorial (37%) and infratentorial (32%) location, grade II (33%) and III (25%) tumors. Recurrence was noted in 24 cases and death in 7 cases with 5-year progression-free and overall-survival rates of 37% and 80%, respectively. Grade II tumors had a better survival than grade III tumors; histopathological grade was the only prognostically significant marker. 1q gain had no prognostic significance. 1q gain is frequent in ependymomas in Indian patients, seen across all ages, sites and grades, and thus is likely an early event in pathogenesis. The prognostic value of 1q gain, remains uncertain, and multicentric pooling of data is required. A histopathological grading system using objective criteria correlates well with patient outcome and can serve as an economical option for prognostication of ependymomas.

Mature Teratoma Confined to the Posterior Fossa.

Mature teratomas located solely in the posterior fossa are rare. We describe a girl who presented with hydrocephalus caused by a posterior fossa tumor that was ultimately diagnosed as a mature teratoma following complete extirpation. Unusual imaging characteristics which produced confusion preoperatively were, however, very consistent with mature teratomas that are encountered in the gonads. Immature elements were universally absent; therefore, extirpation was curative. Hydrocephalus is unlikely to resolve after tumor removal, and cerebrospinal fluid diversion may be required.

Molecular predictive and prognostic factors in ependymoma.

An ependymoma is an uncommon glial tumor, which arises from different parts of the neuroaxis. Considerable variation in presentation and survival in tumors in different locations after an optimum treatment indicates inherent molecular and genetic differences in tumorigenesis between them. A number of genetic aberrations have been identified to distinctly characterize different subgroups of ependymomas that include a posterior fossa tumor, a supratentorial tumor, and a pediatric tumor. These different groups have substantial genetic alterations, and also distinct demography, clinical characteristics, and prognosis. This article is intended to review the diverse molecular and genetic aberrations that may be helpful in prognostication and prediction of survival in patients suffering from an ependymoma.

[Clinical presentation of supratentorial and infratentorial intracranial tumors in pediatric patients]. / Presentación clínica de tumores intracraneales supratentoriales (ST) e infratentoriales (IT) en pacientes pediátricos.

BACKGROUND: Brain tumors are the second most common malignancy in childhood and they are also the most common solid tumors in children and the most frequent cause of morbidity and mortality associated with cancer in this age. OBJECTIVE: To determine the clinical presentation of supratentorial and infratentorial intracranial tumors in pediatric patients. MATERIAL AND METHODS: An observational, retrospective, cross-sectional comparative study in which records the clinical manifestations of 51 pediatric patients diagnosed with intracranial tumor, according with its location, supra- or infratentorial. RESULTS: 51 patients were analyzed. Tumor location was infratentorial in 32 patients (62.7%) and supratentorial in 19 (37.3%). Cerebellar syndrome occurred in 21 patients (65.6 %) with infratentorial tumor compared with six (31.5 %) with supratentorial tumor (p = 0.04; OR: 3.2; 95% CI: 1.1-12.8). Nystagmus was significantly more common in patients with infratentorial tumors (p = 0.029). Endocrine manifestations were present in four patients (21%) with supratentorial tumor and none of the infratentorial group (p = 0.03). CONCLUSIONS: Cerebellar syndrome was statistically significantly more common in patients with infratentorial when compared with patients with supratentorial. Nystagmus is one of the most common visual impairments in patients with infratentorial tumor. Endocrine disorders are significantly more frequent in patients with supratentorial tumor. The interval between onset of symptoms and diagnosis of intracranial tumor is significantly longer in children with supratentorial tumor because the symptoms are more insidious in onset and are mistaken for other benign conditions.

Association of periventricular nodular heterotopia with posterior fossa cyst: a prenatal case series.

OBJECTIVE: The association of periventricular nodular heterotopia (PVNH) with posterior fossa cyst (PFC) is documented after birth. We report this association in a series of fetuses. METHODS: Eleven cases (7 females) of PVNH and PFC diagnosed at prenatal imaging were collected in this retrospective multicenter study. The patients were referred to tertiary centers for targeted ultrasonography (US) and Magnetic Resonance Imaging (MRI) following detection of PFC on routine US. Mutations of the filamin A gene (FLNA) were searched for (n = 6). Maternal brain MRI was performed (n = 8). Post-mortem or postnatal data were recorded. RESULTS: Targeted US was performed at a mean gestational age of 29 (range; 23-35) weeks and identified PVNH in 4 cases. At MRI, performed at a mean gestational age of 31 (range; 29-35) weeks, PVNH and PFC were visible in all cases. Those findings were confirmed by postnatal MRI (n = 3), autopsy (n = 7) and/or post-mortem MRI (n = 2) or US (n = 1). Maternal brain MRI showed PVNH in one case. A de novo FLNA mutation was found in four cases. CONCLUSION: We describe a series of PVNH and PFC in fetuses, which underlines the importance of searching for PVNH when PFC is identified at prenatal US. © 2014 John Wiley & Sons, Ltd.

Pediatric infratentorial ganglioglioma.

PURPOSE: Pediatric infratentorial gangliogliomas are exceedingly rare tumors; thus, the factors affecting their outcome are poorly understood and their optimal management has still to be defined. METHODS: We reviewed the literature on pediatric gangliogliomas with a focus on those located in the posterior fossa to study treatment and outcome data. We added to this review some of our clinical cases. RESULTS: We found 100 and 80 cases of brainstem and cerebellar pediatric ganglioglioma, respectively, in our literature review. The surgical management varied from biopsy to gross total resection, and adjuvant treatment was given after incomplete resection or at time of progression. A gross total resection should be attempted to remove the contrast enhancing part of the tumor, which may be possible in most of the cerebellar gangliogliomas and some of the brainstem lesions. The cervicomedullary ganglioglioma seems to be the most infiltrative and least amenable to complete resection. Chemotherapy has a limited role and BRAF mutation was reported in 38 to 54 % of cases. The use of radiotherapy exposes the patient to a risk of malignant transformation and should be reserved for unresectable tumors which progress. CONCLUSION: Pediatric posterior fossa gangliogliomas are rare and challenging tumors due to their frequent infiltrative component involving the brainstem. To date, adjuvant therapy has a limited role that may evolve with time thanks to the use of targeted therapies against BRAF mutation. The surgical resection of well-defined contrast enhancing parts should be attempted even in staged surgeries and balanced with the risks of neurological deterioration.

Posterior fossa tumors in infants and neonates.

INTRODUCTION: Management of posterior fossa tumors in infants and neonates is challenging. The characteristics of the young babies make surgery very difficult, sometimes precluding a safe complete removal. METHODS: A review of the literature was undertaken to examine the incidence, histology, surgical aspects, and prognosis of posterior fossa tumors in the first year of life. Therapeutical strategies of the most frequent tumor types are also discussed in detail. RESULTS: Histology is dominated by tumors with aggressive behavior, such as medulloblastomas, atypical teratoid/rhabdoid tumors, and anaplastic ependymomas. The most important surgical considerations in small children are the small circulating blood volume; the poor thermoregulation; and incomplete maturation of the brain, of the skull, and of the soft tissue. Treatment toxicity is inversely related to the age of the patients. Radiation therapy is usually considered as contraindicated in young children, with few exceptions. Proton therapy is a promising tool, but access to this kind of treatment is still limited. The therapeutic limitations of irradiation render resection of this tumor and adjuvant chemotherapy often the only therapeutic strategy in many cases. CONCLUSIONS: The overall prognosis remains dismal because of the prevalent aggressive histologies, the surgical challenges, and the limitations of adjuvant treatment. Nevertheless, the impressive improvements in anesthesiology and surgical techniques allow, in the vast majority of the cases, complete removal of the lesions with minor sequelae in high-volume referral pediatric centers.