Desmoplastic Infantile Astrocytoma Research Articles

Congenital Tumors-Magnetic Resonance Imaging Findings with Focus on Rare Tumors.

Congenital tumors are rare and, owing to this rarity, there is limited information on many of them. A total of 839 fetal and postnatal MRI studies performed in the first 3 months of life were retrospectively reviewed. They were performed with the use of 1.5 T scanners. Seventy-six tumors were diagnosed based on fetal MRI between 20 and 37 gestational weeks, and 27 were found after birth, from 1 day of age to 3 months of life. Teratomas were the most common tumors in our dataset, mainly in the sacrococcygeal region (SCT), followed by cardiac rhabdomyomas and subependymal giant cell astrocytomas (SEGA) associated with TSC, and neuroblastomas. The group of less common tumors consisted of infantile fibrosarcomas, malignant rhabdoid tumors, mesoblastic nephromas and Wilms tumor, craniopharyngiomas, brain stem gliomas, desmoplastic infantile astrocytoma, choroid plexus carcinoma, glioblastoma, hemangiopericytoma, rhabdomyosarcoma, melanoma, mesenchymal hamartomas of the chest wall and the liver, and juvenile xanthogranuloma, with special consideration of blue rubber bleb nevus syndrome. MRI plays a significant role in further and better characterization of congenital tumors, leading to a correct diagnosis in many cases, which is crucial for pregnancy and neonatal management and psychological preparation of the parents. No diagnosis is impossible and can be absolutely excluded.

Recurrent TRAK1::RAF1 Fusions in pediatric low-grade gliomas.

Fusions involving CRAF (RAF1) are infrequent oncogenic drivers in pediatric low-grade gliomas, rarely identified in tumors bearing features of pilocytic astrocytoma, and involving a limited number of known fusion partners. We describe recurrent TRAK1::RAF1 fusions, previously unreported in brain tumors, in three pediatric patients with low-grade glial-glioneuronal tumors. We present the associated clinical, histopathologic and molecular features. Patients were all female, aged 8 years, 15 months, and 10 months at diagnosis. All tumors were located in the cerebral hemispheres and predominantly cortical, with leptomeningeal involvement in 2/3 patients. Similar to previously described activating RAF1 fusions, the breakpoints in RAF1 all occurred 5' of the kinase domain, while the breakpoints in the 3' partner preserved the N-terminal kinesin-interacting domain and coiled-coil motifs of TRAK1. Two of the three cases demonstrated methylation profiles (v12.5) compatible with desmoplastic infantile ganglioglioma (DIG)/desmoplastic infantile astrocytoma (DIA) and have remained clinically stable and without disease progression/recurrence after resection. The remaining tumor was non-classifiable; with focal recurrence 14 months after initial resection; the patient remains symptom free and without further recurrence/progression (5 months post re-resection and 19 months from initial diagnosis). Our report expands the landscape of oncogenic RAF1 fusions in pediatric gliomas, which will help to further refine tumor classification and guide management of patients with these alterations.

High-grade desmoplastic infantile astrocytoma in a 1-year-old child with Down’s syndrome: a case report

BackgroundDown’s syndrome is the most common chromosomal abnormality in humans. It has been associated with central nervous system tumors such as primary acute lymphoblastic leukemia and germinomas, but desmoplastic infantile astrocytoma has not yet been reported with Down’s syndrome. Desmoplastic infantile astrocytoma is a rare intracranial tumor that mostly occurs in the first 2 years of life. It usually presents as a large, aggressive tumor with both solid and cystic components. Genetically, it has been linked to the BRAF V600E mutation. Despite the rapid growth pattern, it usually has a favorable prognosis after neurosurgical excision. The presence of this extremely rare, genetically linked tumor, and its combination with Down’s syndrome, the most common human genetic defect, makes this a very novel clinical presentation. It also raises a very research-worthy question of an undiscovered link between these two genetic disorders.Case presentationIn this case, we report a 1-year-old Pakistani origin male child with Down’s syndrome, who presented with progressive macrocephaly and developmental regression over the last 2 months. He was unable to sit by himself, and had lost his handgrip bilaterally. Down’s Syndrome was diagnosed soon after birth, based on typical facial features and presence of palmar crease, and later confirmed karyotypically for Trisomy 21. Upon presentation, initial blood tests did not show any abnormality. Magnetic resonance imaging of the brain was done, and showed a mixed intensity cystic mass with solid dural component posteriorly in the right parieto temporo occipital region. Craniotomy was performed, and about 85% of the tumor mass was excised. Histological examination and immunochemistry confirmed the suspected radiological diagnosis of desmoplastic infantile astrocytoma. After surgical excision, our patient gradually reacquired his previously regressed developmental milestones. Unfortunately, the remaining mass, which could not be excised due to its attachment to the highly vascular dura mater, showed regrowth on repeat brain magnetic resonance imaging. As his parents did not consent to further surgery, chemotherapy was offered as the next treatment option to prevent tumor regrowth.ConclusionsThis case report highlights the need for more case data and research to understand desmoplastic infantile astrocytoma, and their genetic correlation with Down’s syndrome. From a clinical standpoint, since desmoplastic infantile astrocytoma has a good postresection prognosis in a majority of early-diagnosed clinical cases, pediatricians, radiologists, and pathologists should consider desmoplastic infantile astrocytoma in their initial differential diagnosis in Down’s syndrome patients with macrocephaly and developmental regression during the first 2 years of life.

Desmoplastic Infantile Astrocytoma in a 47-day Old Male Infant with Four-year Follow-up: A Rare Case Report and Literature Review

Desmoplastic infantile astrocytoma/ganglioglioma (DIA/DIG) is a rare mixed neuronalglial solid cystic brain tumor found in infantile cerebral hemispheres. The main presentation of the tumor is the rapidly enlarging of the head circumference with hydrocephalus and seizure. DIA is classified as a WHO Grade 1 brain tumor but, due to the rarity of the tumor, few studies are available on tumor survival and prognosis. Herein, we report a 47-day-old male infant diagnosed with DIA and the four-year follow-up.

Desmoplastic infantile astrocytoma with atypical phenotype, PTEN homozygous deletion and BRAF V600E mutation

Desmoplastic infantile astrocytoma (DIA) is rare, cystic and solid tumor of infants usually found in superficial cerebral hemispheres. Although DIA is usually benign, uncommon cases bearing malignant histological and aggressive clinical features have been described in the literature. We report a newborn patient who was diagnosed with a DIA and died postresection. Pathologic examination revealed that the main part of the tumor had benign features, but the internal region showed areas with a more aggressive appearance, with higher-proliferative cells, anaplastic GFAP positive cells with cellular polymorphism, necrosis foci, vascular hyperplasia with endothelial proliferation and microtrombosis. Genetic study, performed in both regions of the tumor, showed a BRAF V600E mutation and a homozygous deletion in PTEN, without changes in other relevant genes like EGFR, CDKN2A, TP53, NFKBIA, CDK4, MDM2 and PDGFRA. Although PTEN homozygous deletions are described in gliomas, the present case constitutes the first report of a PTEN mutation in a DIA, and this genetic feature may be related to the malignant behavior of a usually benign tumor. These genetic findings may point at the need of further and deeper genetic characterization of DIAs, in order to better understand the biology of this tumor and to obtain new prognostic approaches, a better clinical management and targeted therapies, especially in malignant cases of DIA.

RARE-19. Molecular characterization and treatment response of metastatic DIA/DIG

INTRODUCTION: Desmoplastic infantile astrocytoma (DIA) and desmoplastic infantile ganglioglioma (DIG) are glioneuronal tumors of early childhood. Surgical resection is usually sufficient to cure these benign tumors. The presence of metastatic seeding is rare and has been reported as an adverse prognostic factor. We present 2 cases of young children with recurrent metastatic DIA/DIG to describe their presentation, therapeutic management and outcome and to highlight the importance of molecular characterization of these rare tumors to guide adjuvant therapy. CASES DESCRIPTION: The first patient developed metastatic recurrence after initial gross total resection (GTR) of a localized DIG. The disseminated relapse was treated with monthly carboplatin and vincristine (CB/VCR). Complete response was achieved after 15 cycles and the patient has remained in continuous complete remission for 5 years. Post hoc molecular analysis of the tumor revealed a BRAF-RDX fusion. The second patient presented with a disseminated intraventricular relapse following an incomplete resection of a DIA associated with a SPECC1L-NTRK2 fusion. The patient received 2 cycles of CB/VCR with minimal response and was then switched to Larotrectinib leading to a very good partial response (VGPR) 3 months into therapy and has remained on treatment since then with significant clinical improvement. DISCUSSION/ CONCLUSION: In our 2 cases, metastatic recurrence was responsive to adjuvant therapy leading to complete response with conventional chemotherapy in the first one and to VGPR with NTRK inhibitor in the second patient. Early molecular characterization of these benign tumors is critical in case of incomplete resection or metastatic seeding to widen therapeutic options and maximize chance of cure. Response with NTRK inhibitor appears rapid and significant but the total duration of treatment and sustainability of response after discontinuation remain unknown.

The molecular characteristics of low-grade and high-grade areas in desmoplastic infantile astrocytoma/ganglioglioma.

Desmoplastic infantile astrocytomas and gangliogliomas (DIA/DIGs) are rare brain tumours of infancy. A distinctive feature of their histopathology is a combination of low-grade and high-grade features. Most DIA/DIGs can be surgically resected and have a good prognosis. However, high-grade features often dominate recurrent tumours, some of which have a poor outcome. In this study, we test the hypothesis that low-grade and high-grade areas in DIA/DIGs have distinct molecular characteristics. Tissue samples from microdissected low-grade and high-grade areas in 12 DIA/DIGs were analysed by DNA methylation profiling, whole exome sequencing, RNA sequencing and immunohistochemistry to search for potential differences at multiple molecular levels. Copy number variants among tumours and between the two morphologically distinct areas were infrequent. No recurrent genetic alterations were identified across the tumour series, and high-grade areas did not have additional genetic alterations to explain their distinct morphology or biological behaviour. However, high-grade areas showed relative hypomethylation in genes downstream of the transcription factors SOX9 and LEF1 and evidence of a core SOX9 transcription network alongside activation of the BMP, WNT and MAPK signalling pathways. This study contributes to our knowledge of molecular genetic alterations in DIA/DIGs, uncovers molecular differences between the two distinct cell populations in these tumours and suggests potential therapeutic targets among the more proliferative cell population in DIA/DIGs.

Prevalence of BRAFV600 in glioma and use of BRAF Inhibitors in patients with BRAFV600 mutation-positive glioma: systematic review.

BackgroundDetailed prevalence estimates of BRAFV600 mutations and BRAF inhibitor (BRAFi) treatment responses in V600-mutant glioma will inform trial development.MethodsOur systematic review analyzed overall prevalence of BRAFV600 mutations in glioma and BRAFi treatment response.ResultsBased on 13 682 patients in 182 publications, the prevalence of BRAFV600 in epithelioid glioblastoma (eGBM) was 69% [95% CI: 45–89%]; pleomorphic xanthoastrocytoma (PXA): 56% [48–64%] anaplastic pleomorphic xanthoastrocytoma (aPXA): 38% [23–54%], ganglioglioma (GG): 40% [33–46%], and anaplastic ganglioglioma (aGG): 46% [18–76%]. Prevalence in astroblastoma was 24% [8–43%], desmoplastic infantile astrocytoma (DIA): 16% [0–57%], subependymal giant cell astrocytoma (SEGA): 8% [0–37%], dysembryoplastic neuroepithelial tumor (DNET): 3% [0–11%], diffuse astrocytoma (DA): 3% [0–9%], and pilocytic astrocytoma (PA): 3% [2–5%]. We reviewed 394 V600-mutant gliomas treated with BRAFi from 130 publications. One hundred and twenty-nine pediatric low-grade gliomas showed 4 (3.1%) complete response (CR); 53 (41.1%) partial response (PR); 64 (49.6%) stable disease (SD) and 8 (6.2%) progressive disease (PD). 25 pediatric high-grade gliomas showed CR; PR; SD; PD in 4 (16.0%); 10 (40.0%), 4 (16.0%); and 7 (28.0%) respectively. Thirty-nine adult low-grade gliomas showed CR; PR; SD; PD of 4 (10.3%); 17 (43.6%); 16 (41.0%) and 2 (5.1%) respectively. Ninety-seven adult high-grade gliomas showed CR; PR; SD; PD of 6 (6.2%); 31 (32.0%); 27 (27.8%); and 33 (34.0%) respectively.Conclusions BRAFV600 prevalence is highest in eGBM, PXA, aPXA, GG, aGG, and lower in astroblastoma, DIA, SEGA, DNET, DA, and PA. Our data provide the rationale for adjuvant clinical trials of BRAFi in V600-mutant glioma.

Prevalence of BRAF V600 in primary gliomas: a systematic review

Abstract Aims Glioma is a fatal disease that causes significant years of life lost to an individual. Mutations in the driver gene BRAF, such as the V600 alteration, may contribute to gliomagenesis in adults and children through abnormal signaling causing uncontrolled cell proliferation. The use of BRAF-inhibitor drugs including Vemurafenib and Dabrafenib have shown a favorable response in 48% and 50% of melanoma patients with BRAF V600 mutations respectively. BRAF inhibitors and MEK inhibitors have shown efficacy in certain paediatric gliomas in the recurrent setting. Despite the potential benefit of BRAF inhibitors, the prevalence of BRAF V600 within primary gliomas is not fully discovered. Some studies identify the prevalence to be over 50%, while others find the prevalence to be around 1%. We performed a comprehensive systematic review to determine the prevalence of BRAF V600 within the adult and paediatric glioma population in different diagnostic groups. Method A systematic literature search was performed using Ovid MEDLINE and Embase from genesis to the 22nd October 2020. Studies were not restricted by language. Studies were eligible if patients were histologically diagnosed according to WHO guidelines as a primary glioma evaluating the prevalence of BRAF V600 and included ≥ 10 primary glioma patients. The review protocol was registered in PROSPERO (CRD42019127704). Search results were managed using Endnote. Two independent reviewers assessed the eligibility of the publications using Rayyan, conflicts were evaluated by a third reviewer. Included articles were extracted by one reviewer and confirmed by a second reviewer. Risk of bias assessments were conducted using Hoy et al’s risk of bias tool. Results were synthesized using “metaprop” in R. The meta-analysis was carried out in R which produced forest plots. Results Our cohort included 182 studies with a total of 13669 adult and paediatric glioma patients classified diagnostically according to WHO guidelines. Among 48 glioma entities, BRAF V600 was identified most commonly in epithelioid glioblastoma with a prevalence of 69% (95% confidence interval (CI): 45-89%), followed by pleomorphic xanthoastrocytoma with a prevalence of 56% (95% CI: 48-64%), anaplastic pleomorphic xanthoastrocytoma with a prevalence of 38% (95% CI: 23-54%), ganglioglioma with a prevalence of 40% (95% CI: 33-46%), and anaplastic ganglioglioma with a prevalence of 46% (95% CI: 18-76%). Other glioma entities were found to have a prevalence of BRAF V600, these include astroblastoma (24%), desmoplastic infantile astrocytoma (16%), subependymal giant cell astrocytoma (8%), dysembryoplastic neuroepithelial tumour (3%), diffuse astrocytoma (3%), and pilocytic astrocytoma (3%). Conclusion To our knowledge, this is the largest systematic review examining the prevalence of BRAF V600 in adult and paediatric glioma classified according to diagnostic WHO criteria. However, there were some limitations in this review. The sample sizes of some studies were very small, and the method of mutational analysis for BRAF V600 varied between papers. We found BRAF V600 in a significant prevalence of epithelioid glioblastoma, pleomorphic xanthoastrocytoma, anaplastic pleomorphic xanthoastrocytoma, ganglioglioma, and anaplastic ganglioglioma. Of interest, BRAF V600 mutation was found in a lower prevalence of astroblastoma, desmoplastic infantile astrocytoma, subependymal giant cell astrocytoma, dysembryoplastic neuroepithelial tumour, diffuse astrocytoma, and pilocytic astrocytoma. Consideration of assessment of BRAF V600 mutation may enable further treatment options with BRAF and/or MEK inhibitors in these particular diagnostic entities.

Desmoplastic infantile astrocytoma and ganglioglioma: a series of 12 patients treated at a single institution.

Desmoplastic infantile astrocytomas and gangliogliomas (DIA/DIG) usually present with a large size, large cystic component, large dural implant, encasement of big vessels, clinical presentation within 18 months of life, high incidence of seizures and overall good prognosis, even if tumour surgery can be very challenging at first procedure. We retrospectively reviewed clinical and radiological data of patients diagnosed with desmoplastic infantile tumours who were surgically treated between 2008 and 2019. The series included 12 patients. The median age at surgery was 91 days. The average tumour volume was 212 cm3. Cystic components were predominant ranging from 0 to 295 cm3. Active hydrocephalus was pre-operatively evident in 5 cases. Eight patients (66.6%) received total or subtotal removal, three of them (25%) underwent partial removal, and one patient (8.3%) received a biopsy. One patient died within 24 h after surgery due to severe hypotension, as a consequence of significant intraoperative blood loss. Overall, seven (58.3%) patients were reoperated on the tumour after the first procedure: 4 patients were operated twice; 3 patients were operated 3 times. Two patients presented remote localizations and underwent chemotherapy. At last follow-up, 7 patients were tumour-free, 2 are alive with stable disease, and 2 are alive with progressive disease (leptomeningeal seeding). Desmoplastic infantile tumours are rare giant neonatal tumours. Total removal is the goal of treatment, but prognosis remains good even if total removal is not achieved. In case of tumour progression or epilepsy from residual tumour, reoperation is the first option, with chemotherapy reserved to unresectable or disseminated cases with mixed results, while, to date, radiotherapy still plays no role.

LGG-32. CLINICAL OUTCOME OF PEDIATRIC GLIOMAS IN SINGLE INSTITUTION

Gliomas in children are rarer than in adult, then treatment strategies might vary from facility to facility. We report clinical features and outcome of pediatric glioma in our institution. Twenty-nine patients diagnosed with glioma, exclude ependymoma, 14 boys and 15 girls, among 98 pediatric brain tumor patients treated at Kagoshima University Hospital since 2006 were reviewed histopathology, extent of resection, adjuvant therapy and outcome, etc. Mean age at surgery was 10.4 (S.D. 5.6) years. Median follow-up period was 19.1 months. Histopathological diagnosis comprised 8 pilocytic astrocytoma, 3 ganglioglioma, 2 subependymal giant cell astrocytoma, 5 WHO grade Ⅱ astrocytoma, 8 glioblastoma, and desmoplastic infantile astrocytoma, anaplastic astrocytoma and astroblastoma were one case each. Tumor resection was performed in 24 cases, and 5 cases underwent biopsy. Chemotherapy was performed in 15 cases and irradiation was performed in 9 cases. Out of 5 WHO grade Ⅱ astrocytoma cases, 2 cases underwent biopsy following chemotherapy, 1 case underwent biopsy only and other 1 case underwent total resection. The four cases show long survival ranged from 71 to 136 months without irradiation. All of eight glioblastoma cases show poor prognosis ranged from 8.6 to 26.7 months regardless of chemo-radiotherapy. In management for pediatric brain tumor patients, irradiation is often laid over until recurrence. In WHO grade Ⅱ astrocytoma, the treatment strategy might be reasonable using appropriate chemotherapy even though biopsy cases.

Subdural hydroma; A postoperative complication of desmoplastic infantile ganglioglioma and astrocytoma: A report of two cases and literature review

Abstract Introduction Desmoplastic infantile ganglioglioma (DIG) and desmoplastic infantile astrocytoma (DIA) are rare benign childhood intracranial tumors that are classified under neural and mixed glioneuronal tumors. Although many authors have written on surgical treatment of these disease conditions and indicated satisfactory outcomes, no author have written on the postoperative formation of a subdural hydroma after surgery. Case presentation We present two cases of DIG and DIA infants in whom we achieved total or subtotal tumor resection and observed postoperative hydroma as complications. Their main symptoms were vomiting, seizures and head enlargement. In both cases magnetic resonance imaging (MRI) revealed huge solid-cystic mass located in left frontal, temporal and parietal lobes. Histopathological staining confirmed the diagnosis of DIG and DIA in both cases. A second surgery may be required in patients with this kind of postoperative complication if clinical and radiological imaging evaluation reveal deteriorating of the patient's condition otherwise conservative treatment usually gives a total resolution of this complication. Conclusion The pathophysiology of this occurrence after surgery is as the result of a potential space created after excision of tumor and subsequent influx of CSF into the potential space between the subdural.

Desmoplastic Infantile Ganglioglioma/Astrocytoma (DIG/DIA) Are Distinct Entities with Frequent BRAFV600 Mutations.

Desmoplastic infantile ganglioglioma (DIG) and desmoplastic infantile astrocytoma (DIA) are extremely rare tumors that typically arise in infancy; however, these entities have not been well characterized in terms of genetic alterations or clinical outcomes. Here, through a multi-institutional collaboration, the largest cohort of DIG/DIA to date is examined using advanced laboratory and data processing techniques. Targeted DNA exome sequencing and DNA methylation profiling were performed on tumor specimens obtained from different patients (n = 8) diagnosed histologically as DIG/DIGA. Two of these cases clustered with other tumor entities, and were excluded from analysis. The remaining 16 cases were confirmed to be DIG/DIA by histology and by DNA methylation profiling. Somatic BRAF gene mutations were discovered in 7 instances (43.8%); 4 were BRAFV600E mutations, and 3 were BRAFV600D mutations. Three instances of malignant transformation were found, and sequencing of the recurrence demonstrated a new TP53 mutation in one case, new ATRX deletion in one case, and in the third case, the original tumor harbored an EML4-ALK fusion, also present at recurrence. DIG/DIA are distinct pathologic entities that frequently harbor BRAFV600 mutations. Complete surgical resection is the ideal treatment, and overall prognosis is excellent. While, the small sample size and incomplete surgical records limit a definitive conclusion about the risk of tumor recurrence, the risk appears quite low. In rare cases with wild-type BRAF, malignant progression can be observed, frequently with the acquisition of other genetic alterations.Implications: DIG/DIA are a distinct molecular entity, with a subset frequently harboring either BRAF V600E or BRAF V600D mutations. Mol Cancer Res; 16(10); 1491-8. ©2018 AACR.

Novel suprasellar location of desmoplastic infantile astrocytoma and ganglioglioma: a single institution's experience.

The aim of this study was to describe the clinical presentation, imaging appearance, and differential outcomes based on tumor location in 7 patients with desmoplastic infantile astrocytoma and desmoplastic infantile gangliogliomas (DIA/DIG). Data of 7 patients with histopathology-proven DIA/DIGs and preoperative imaging were retrospectively reviewed, and age, sex, clinical presentation, imaging characteristics, tumor location, surgical procedure, postoperative morbidity, and overall mortality were recorded. Two subgroups of patients with DIA/DIGs were found to exist based on whether their tumor was located in the cerebral hemispheres or suprasellar region. Nearly all patients presented with rapidly enlarging head circumference regardless of tumor location. However, ocular abnormalities, including nystagmus and preference for downward gaze, were specific for patients with suprasellar disease. These patients experienced significant postoperative complications and had poor long-term outcomes. In contrast, patients with hemispheric tumors underwent more extensive resection than patients with suprasellar tumors, had uneventful postoperative courses, and had no documented long-term comorbidities. Postoperative course and long-term outcome for patients with DIA/DIGs were correlated to the anatomical location and radiographic appearance of their tumor at presentation, despite having histologically and molecularly indistinguishable, WHO grade I tumors.

Treatment with vincristine/carboplatin for desmoplastic infantile astrocytoma with multiple cerebrospinal metastasis

Treatment with vincristine/carboplatin for desmoplastic infantile astrocytoma with multiple cerebrospinal metastasis

Supratentorial tumors typical of the infantile age: desmoplastic infantile ganglioglioma (DIG) and astrocytoma (DIA). A review

Desmoplastic infantile gangliogliomas (DIGs) and desmoplastic infantile astrocytomas (DIAs) are tumors typical of the infantile age. A large size, with a mixed solid and cystic component, clinical presentation with progressing signs of increased intracranial pressure, a prominent benign desmoplastic structure at histological examination, and a favorable clinical course in the majority of cases are the prominent features of these tumors. The objective of the present paper was to review the pertinent literature on the topic together with our personal experience, with the aim of an updated review of the subject. Only 28 papers are present in the literature devoted to DIGs and DIAs, most of them reporting on single cases or small series, with a total of 107 patients aged from 5days to 48months with a slight male prevalence. Most of the reported cases refer to supratentorial and hemispheric locations, a few cases involving the hypothalamic region, the posterior fossa, and the spinal cord. The typical MRI appearance is of large mixed solid and cystic tumors with a spontaneous hyperintense T2 appearance of the solid part which also shows a strong contrast enhancement. Mixed ganglionic and astrocytic cells are identifiable in DIGs, whereas DIAs are typically featured by the exclusive presence of glial cells. In both cases, more primitive cells may be observed, which present a higher number of mitoses and these areas can mimic the features of malignant astrocytomas. Surgery represents the treatment of choice; however, radical removal has been reported as possible only in around 30% of the cases: the low age of the patients together with their low weight and the large size of and the hyper-vascularized structure of the tumors represent the main factors limiting surgery. Pure observation is considered as first choice in children undergoing a partial/subtotal tumor resection, chemotherapic regimens being considered in cases of recurrences after a second look surgery. Long-term prognosis is favorable with mortality being related mostly to the rare midline (i.e., hypothalamic) locations, which beyond the functionally relevant site, tend to have an unusually more aggressive histological behavior.

Perinatal (fetal and neonatal) astrocytoma: a review.

IntroductionThe purpose of this review is to document the various types of astrocytoma that occur in the fetus and neonate, their locations, initial findings, pathology, and outcome. Data are presented that show which patients are likely to survive or benefit from treatment compared with those who are unlikely to respond.Materials and methodsOne hundred one fetal and neonatal tumors were collected from the literature for study.ResultsMacrocephaly and an intracranial mass were the most common initial findings. Overall, hydrocephalus and intracranial hemorrhage were next. Glioblastoma (GBM) was the most common neoplasm followed in order by subependymal giant cell astrocytoma (SEGA), low-grade astrocytoma, anaplastic astrocytoma, and desmoplastic infantile astrocytoma (DIA). Tumors were detected most often toward the end of the third trimester of pregnancy.Conclusion A number of patients were considered inoperable since their tumor occupied much of the intracranial cavity involving large areas of the brain. High-grade astrocytomas were more common than low-grade ones in this review. Fetuses and neonates with astrocytoma have a mixed prognosis ranging from as low as 20 % (GBM) to a high of 90 %. The overall survival was 47/101 or 46 %.

LG-60OBJECTIVE RESPONSE TO VEMURAFENIB IN A CHILD TREATED FOR METASTATIC DESMOPLASTIC INFANTILE ASTROCYTOMA

LG-60. OBJECTIVE RESPONSE TO VEMURAFENIB IN A CHILD TREATED FOR METASTATIC DESMOPLASTIC INFANTILE ASTROCYTOMA Zdenek Pavelka1, Jitka Berkovcova2, Jarmila Skotakova3, Karel Zitterbart1, and Jaroslav Sterba1; Dept of Pediatric Oncology, University Children’s Hospital, Brno, Czech Republic; Dept of Oncological and Experimental Pathology, Masaryk Memorial Cancer Institute, Brno, Czech Republic; Dept of Pediatric Radiology, Brno, Czech Republic Desmoplastic infantile astrocytoma/ganglioglioma (DIA/DIG) is a rare primary neuroepithelial brain tumour, which typically occurs in infants aged between 1 and 24 months. Knowledge of the genetic background of DIA/ DIG is very limited, recently the presence of BRAFV600E mutation was described in some cases of DIA/DIG. We present a case of 11-month old girl with 5-month history of nystagmus. Magnetic resonance imaging of the brain andspineshowedcontrast enhancingmass inthesuprasellarregionwithspreading into both hemispheres and additional lesions in cerebellum and within the spine. Biopsy of the tumour was performed and histopathology examination revealed desmoplastic infantile astrocytoma. BRAF600E mutation in the tumour cells wasdetected bymoleculargenetic testing.The patient started treatment according to SIOP LGG 1997 protocol with vincristine and carboplatin. After 2 months of therapy, the girl was admitted to our clinic with clinical signs of intracranialhypertension.MRIshowedprogressionof the tumoursize,which lead to development of hydrocephalus. The installation of ventriculo-peritoneal shunt was performed. Due to progression on the first line therapy, we decided to start second line individualized therapy with weekly dose of vinblastine in combination with BRAF inhibitor vemurafenib. After 6 months of therapy with vinblastine + vemurafenib partial remission was documented on MRI together with clinical improvement. Conclusion: BRAF V600E mutation affects a subset of DIAs/DIGs and offers new therapeutic options. Neuro-Oncology 18:iii78–iii96, 2016. doi:10.1093/neuonc/now075.60 #The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Chapter 24 - Rare glial tumors

This chapter describes the epidemiology, pathology, molecular characteristics, clinical and neuroimaging features, treatment, outcome, and prognostic factors of the rare glial tumors. This category includes subependymal giant cell astrocytoma, pleomorphic xanthoastrocytoma, astroblastoma, chordoid glioma of the third ventricle, angiocentric glioma, ganglioglioma, desmoplastic infantile astrocytoma and ganglioma, dysembryoplastic neuroepithelial tumor, papillary glioneuronal tumor, and rosette-forming glioneuronal tumor of the fourth ventricle. Many of these tumors, in particular glioneuronal tumors, prevail in children and young adults, are characterized by pharmacoresistant seizures, and have an indolent course, and long survival following surgical resection. Radiotherapy and chemotherapy are reserved for recurrent and/or aggressive forms. New molecular alterations are increasingly recognized.

Does BRAF V600E Mutation Enable Vemurafenib to be a Universal Candidate for Treating a Plethora of Cancers?

Neurologically, BRAF V600E mutation was detected in cerebellar anaplastic pilocytic astrocytoma, ganglioglioma, desmoplastic infantile astrocytoma, indeterminate cell tumor and interdigitating dendritic cell sarcoma. Hematologically, BRAF V600E mutation was also detected in multiple myeloma and several leukemias (hairy cell, chronic lymphocytic, prolymphocytic and acute lymphoblastic leukaemia).