Case Of Pilocytic Astrocytoma Research Articles

The importance of escalating molecular diagnostics in patients with low-grade pediatric brain cancer.

Pilocytic astrocytomas are the most common pediatric brain tumors, typically presenting as low-grade neoplasms. We report two cases of pilocytic astrocytoma with atypical tumor progression. Case 1 involves a 12-yr-old boy with an unresectable suprasellar tumor, negative for BRAF rearrangement but harboring a BRAF p.V600E mutation. He experienced tumor size reduction and stable disease following dabrafenib treatment. Case 2 describes a 6-yr-old boy with a thalamic tumor that underwent multiple resections, with no actionable driver detected using targeted next-generation sequencing. Whole-genome and RNA-seq analysis identified an internal tandem duplication in FGFR1 and RAS pathway activation. Future management options include FGFR1 inhibitors. These cases demonstrate the importance of escalating molecular diagnostics for pediatric brain cancer, advocating for early reflexing to integrative whole-genome sequencing and transcriptomic profiling when targeted panels are uninformative. Identifying molecular drivers can significantly impact treatment decisions and improve patient outcomes.

Diagnostic algorithm for pathological evaluation of gliomas in a resource-constrained setting.

Gliomas are the most common primary intracranial tumors. The current World Health Organization (WHO) classification of central nervous system tumors recommends integrated histo-molecular diagnosis of gliomas. However, molecular testing is not available in even most of the advanced centers of our country, and histopathology aided with immunohistochemistry (IHC) is still widely used for diagnosis. Immunohistochemical markers such as iso-citrate dehydrogenase1 (IDH1) and Alpha Thalassemia/Mental Retardation Syndrome X-linked (ATRX) can be reliably used for the correct diagnosis, prognosis, and treatment of gliomas. We aimed to develop a diagnostic algorithm by integrating morphology, IDH1, and ATRX status of gliomas seen in our institute for 1 year. Analytical cross-sectional study. This study included 60 histopathologically confirmed cases of astrocytic (n = 51) and oligodendroglial tumors (n = 9). Clinical, radiological, and histopathological features were noted and tumor grades assigned according to the WHO recommendations. IDH1 and ATRX mutation status was evaluated using IHC. The tumors were divided into three molecular groups on the basis of their IDH1 and ATRX mutation status: (1) Group 1: IDH1 negative and ATRX positive, (2) Group 2: IDH1 positive and ATRX positive, (3) Group 3: IDH1 positive and ATRX negative. The mean age of presentation was 45.0 ± 15.8 years with a male-to-female ratio of 2:1. Seizures, headache, and hemiparesis were the most common modes of presentation. The tumor subtypes studied were glioblastoma (n = 32), anaplastic astrocytoma (n = 7), diffuse astrocytoma (n = 6), oligodendroglioma (n = 6), pilocytic astrocytoma (n = 6), and anaplastic oligodendroglioma (n = 3). IDH1 mutation was present in 26 cases including anaplastic astrocytoma (n = 7), diffuse astrocytoma (n = 6), oligodendroglioma (n = 5), secondary glioblastoma (n = 5), and anaplastic oligodendroglioma (n = 3). ATRX mutation, i. e., loss of ATRX was observed in 17 cases including diffuse astrocytoma (n = 5), anaplastic astocytoma (n = 5), anaplastic oligodendroglioma (n = 3), oligodendroglioma (n = 3), and secondary glioblastoma (n = 1). All six cases of pilocytic astrocytoma were negative for IDH1 and ATRX mutation. There were 34 patients in Group 1 (IDH1- and ATRX +), nine cases in Group 2 (IDH1 + and ATRX +), and 17 patients in Group 3 (IDH1 + and ATRX-). Diagnosis of gliomas should be based on a detailed clinicoradiological and histopathological assessment, followed by genotypic characterization. Evaluation for IDH1and ATRX status has both diagnostic and prognostic value as it helps in differentiating gliomas from reactive gliosis, primary glioblastoma from secondary glioblastoma, and pilocytic astrocytoma (WHO grade I) from diffuse astrocytoma (WHO grade II). Tumors with IDH1 mutations have a better outcome than those with wild-type IDH. IHC can serve as a useful surrogate to conventional molecular tests in resource-constrained settings. By devising an algorithm based on morphological and IHC features, we were able to stratify gliomas into three prognostic subgroups.

SURG-08. 5-Aminolevulinic acid (5-ALA)-guided resection of pediatric brain tumors

BACKGROUND: 5-Aminolevulinic acid (5-ALA)-guided resection of gliomas in adults enables better differentiation between tumor and normal brain, allowing a higher degree of resection, and improved patient outcomes. In recent years, several reports have emerged regarding the use of 5-ALA in other brain tumor entities, including pediatric brains tumors. Since gross total resection (GTR) of many brain tumors in children is crucial, the role of 5-ALA-guided resection requires elucidation. METHODS: A systematic literature review of EMBASE and MEDLINE/PubMed databases revealed 20 eligible publications encompassing 186 5-ALA-guided operations on pediatric brain tumors. To reduce bias, publications were revised independently by two authors. RESULTS: 5-ALA-guided resection enabled the surgeons to identify the tumor more easily and was considered helpful mainly in cases of glioblastoma (GBM, 21/27, 78%), anaplastic ependymoma WHO grade III (10/14, 71%), and anaplastic astrocytoma (4/6, 67%). In contrast, cases of pilocytic astrocytomas (PAs) and medulloblastomas 5-ALA-guided surgery did not show consistent fluorescent signals and 5-ALA was considered helpful only in 12% and 22% of cases, respectively. Accumulation of fluorescent porphyrins seems to depend on WHO tumor grading. In case fluorescence signal was considered helpful, it was associated to a greater degree of resection. One study showed an association between visible fluoresce signal and concentration of protopophyrin IX (PPIX) concentration. A threshold of 4μg/ml was required in order to visualize the fluorescence signal. The rate of adverse events related to 5-ALA was negligible, especially new postoperative sequelae. CONCLUSION: 5-ALA could play a role in resection of malignant, contrast enhancing, supratentorial pediatric brain tumors. At present, we are conducting a prospective phase I-II multicenter clinical trial to evaluate side effects and feasibility of 5-ALA guided surgery

A clinical and morphological analysis of a retinal and optic nerve astrocytic hamartoma case

A clinical and morphological description of a case of pilocytic astrocytoma (astrocytic hamartoma) of the retina and optic nerve in an 11-year old girl is presented. The clinical and instrumental characteristics of the tumor are determined by ultrasound and MRI tests. Detailed cytological and pathomorphological description of the tumor, which is rarely observed, is given. The tumor poses a threat to the eye and requires that the eyeball be removed.

HGG-19. 5-AMINOLEVULINIC ACID (5-ALA)-GUIDED RESECTION OF PEDIATRIC BRAIN TUMORS

Between tumor and normal brain, allowing a higher degree of resection, and improved patient outcomes. In recent years, several reports have emerged regarding the use of 5-ALA in other brain tumor entities, including pediatric brains tumors. Since gross total resection (GTR) of many brain tumors in children is crucial, the role of 5-ALA-guided resection requires elucidation.MethodsA systematic literature review of EMBASE and MEDLINE/PubMed databases revealed 20 eligible publications encompassing 186 5-ALA-guided operations on pediatric brain tumors. To reduce bias, publications were revised independently by two authors.Results5-ALA-guided resection enabled the surgeons to identify the tumor more easily and was considered helpful mainly in cases of glioblastoma (GBM, 21/27, 78%), anaplastic ependymoma WHO grade III (10/14, 71%), and anaplastic astrocytoma (4/6, 67%). In contrast, cases of pilocytic astrocytomas (PAs) and medulloblastomas 5-ALA-guided surgery did not show consistent fluorescent signals and 5-ALA was considered helpful only in 12% and 22% of cases, respectively. Accumulation of fluorescent porphyrins seems to depend on WHO tumor grading. In case fluorescence signal was considered helpful, it was associated with a greater degree of resection. One study showed an association between visible fluoresce signal and concentration of protopophyrin IX (PPIX) concentration. A threshold of 4μg/ml was required in order to visualize the fluorescence signal. The rate of adverse events related to 5-ALA was negligible, especially new postoperative sequelae.Conclusion5-ALA could play a role in resection of malignant, contrast enhancing, supratentorial pediatric brain tumors. At present, we are conducting a prospective phase I-II multicenter clinical trial to evaluate side effects and feasibility of 5-ALA guided surgery.

Intraoperative contrast-enhanced ultrasound for intramedullary spinal neoplasms: patient series

BACKGROUNDPrimary intramedullary spinal tumors cause significant morbidity and death. Intraoperative ultrasound as an adjunct for localization and monitoring the extent of resection has not been systematically evaluated in these patients; the effectiveness of intraoperative contrast-enhanced ultrasound (CEUS) remains almost completely unexplored.OBSERVATIONSA retrospective case series of patients at a single institution who had consented to the off-label use of intraoperative CEUS was identified. Seven patients with a mean age of 52.8 ± 15.8 years underwent resection of intramedullary tumors assisted by CEUS performed by a single attending neurosurgeon. Histopathological evaluation revealed 3 cases of hemangioblastoma, 1 case of pilocytic astrocytoma, 2 cases of ependymoma, and 1 case of subependymoma. Contrast enhancement correlated with gadolinium enhancement on preoperative magnetic resonance imaging. Intraoperative CEUS facilitated precise lesion localization and myelotomy planning. Dynamic CEUS studies were useful in demonstrating the blood supply to lesions with a dominant vascular pedicle. Regardless of contrast uptake, the differential enhancement between spinal cord tissue and neoplasm assisted in determining interface boundaries.LESSONSIntraoperative CEUS constitutes a useful adjunct for the intraoperative delineation of contrast-enhancing intramedullary tumors and in vivo confirmation of gross-total resection. Systematic investigation is needed to establish the role of CEUS for resection of intramedullary spinal tumors of various pathologies.

Is it a new culprit? “TERT promoter mutation” in an aggressive pediatric pilocytic astrocytoma

Recent advances in the genomic study have revolutionized the discovery of molecular biomarkers in glioma not only to aid in targeted therapy but also to prognosticate character of tumor and outcome of a patient.The usually benign nature of pilocytic astrocytoma (PA) can now be challenged with the discovery of genomic alterations that could promote more aggressive clinical behavior. CDKN2A deletion and ATRX gene inactivation or mutation have been the most common molecular alterations in worse prognosis.We will discuss a case of pilocytic astrocytoma showing the progressive recurrence with pilomyxoid features and the presence of TERT promoter mutation.

Surgical management of primary and secondary pilocytic astrocytoma of the cerebellopontine angle (in adults and children) and review of the literature

Glial tumors in the cerebellopontine angle (CPA) are uncommon and comprise less than 1% of CPA tumors. We present four cases of pilocytic astrocytoma of the CPA (PA-CPA) that were treated in our department. Patients who received surgical treatment for PA-CPA from January 2004 to December 2019 were identified by a computer search of their files from the Department of Neurosurgery, Tübingen. Patients were evaluated for initial symptoms, pre- and postoperative facial nerve function and cochlear function, complications, and recurrence rate by reviewing surgical reports, patient documents, neuroradiological data, and follow-up data. We identified four patients with PA-CPA out of about 1500 CPA lesions (~ 0.2%), which were surgically treated in our department in the last 16 years. Of the four patients, three were male, and one was a female patient. Two were adults, and two were children (mean age 35 years). A gross total resection was achieved in three cases, and a subtotal resection was attained in one case. Two patients experienced a moderate facial palsy immediately after surgery (House–Brackmann grade III). In all cases, the facial function was intact or good (House–Brackmann grades I–II) at the long-term follow-up (mean follow-up 4.5 years). No mortality occurred during follow-up. Three of the patients had no recurrence at the latest follow-up (mean latest follow-up 4.5 years), while one patient had a slight recurrence. PA-CPA can be safely removed, and most complications immediately after surgery resolve in the long-term follow-up.

Treatment outcome of optic pathway glioma in children with diencephalon syndrome

Objective To explore the clinical treatment outcomes of the optic pathway glioma in children with diencephalic syndrome. Methods The clinical data of 8 cases of optic pathway glioma with diencephalic syndrome were analyzed retrospectively who were admitted to Department of Neurosurgery, Beijing Children′s Hospital, Capital Medical University from July 2015 to December 2018. The range of the children′s ages was from 8.0 to 42.2 months. No weight gain was reported in all those patients before the age of 1 year, and they showed a cachexia state of extreme emaciation at admission. The range of children′s preoperative weights was from 5.5 to 11.5 kg. The weight-for-age Z score was lower than -2 in all 8 patients who underwent microsurgical resection of tumor followed by chemotherapy post operation. Results Among the 8 cases of optic pathway glioma combined with diencephalic syndrome, subtotal resection was achieved in 7 cases, near-total resection in 1, and there was no death related to operation. Postoperative pathological examination confirmed 2 cases of pilocytic astrocytoma and 6 cases of pilomyxoid astrocytoma. The range of follow-up period of 8 children was from 1 to 18 months, the range of postoperative weight was from 8.0 to 20.0 kg, the weight of all patients increased to various degrees, and some of the patients′ clinical symptoms were alleviated. One patient died after discharge, and chemotherapy was applied to the rest of 7 patients. Residual tumor shrank in 4 patients, progressed in 2 and disseminated in 1. Conclusions Subtotal tumor resection in children with optic pathway gliomas and diencephalic syndrome could significantly improve the symptom of emaciation and alleviate some other symptoms. There seems to be great variability in the tumor sensitivity to postoperative chemotherapy. Key words: Glioma; Child; Optic pathway glioma; Diencephalic syndrome; Treatment outcome

Surgical treatment of low-grade brain tumors associated with epilepsy.

To explore the strategy of surgical treatment of low-grade brain tumors associated with epilepsy. Clinical data of 158 patients with low-grade brain tumors were collected from January 2011 to December 2017 in Guangdong Sanjiu brain hospital. All patients received Preoperative evaluation. Lesion site: 18 cases were located in multiple cerebral lobes, 10 cases were in the functional zones, 130 cases were in the non-functional zones (including 74 cases were in the medial of temporal lobe). The surgical strategy included subtotal resection, gross-total resection and enlarged resection. Postoperative effects were evaluated by Engel classification. A total of 158 patients underwent surgical treatment, among these patients, only 1 patient underwent intracranial electrode implantation. Surgical methods: 34 cases of subtotal resection, 3 cases of gross-total resection, 119 cases of enlarged resection (including Anterior temporal lobectomy in 74 cases) and 2 case of Selective hippocampal amygdalectomy. The final pathology suggested that there are 74 cases of ganglionglioma, 25 cases of dysembryoplastic neuroepithelial tumors, 9 cases of pilocytic astrocytoma, 16 cases of oligodendroglioma, 10 cases of pleomorphic xanthoastrocytoma, 4 case of diffuse astrocytoma, 9 cases of unclassified astrocytoma, 11 case of oligoastrocytoma. The follow-up time was between 1 and 7 years, with an average of 3.44±1.77 years. Postoperative recovery: 147 patients had an Engel Class I outcome, 10 patients were in Engel Class II, 1 patient was in Class IV. The strategy of surgical treatment of low-grade brain tumors associated with epilepsy should pay more attention to the preoperative assessment of the epileptogenic zone. The tumor is not exactly the same as the epileptogenic zone, and the strategy of surgical treatment depends on the tumor feature as well as whether it was located in temporal lobe or involved in functional areas.

IDH-1 polymorphisms in pilocytic astrocytomas

As of 2016, isocitrate dehydrogenase (IDH)-1 and IDH-2 mutations are part of the definition of an oligodendroglioma and may be seen in a significant subset of grade II-IV fibrillary astrocytomas. Reports of IDH-1 and IDH-2 alterations in pilocytic astrocytomas have been rare. This study reports two cases of pilocytic astrocytomas which harbored IDH-1 polymorphisms (G105G) (c.315C > T) discovered on polymerase chain reaction (PCR) testing and sequencing. The first was encountered in a 21-year-old male with a right orbital frontal pole mass. The second occurred in a 19-year-old female with a right frontal tumor. Neither tumor stained with antibody to IDH-1 (R132H). No BRAF V600E immunostaining, minimal p53 staining (<5%) and no loss of ATRX staining was noted in both cases. The significance of the IDH-1 findings at this juncture is uncertain. Misdiagnosis of the tumor as a fibrillary astrocytoma or oligodendroglioma due to the presence of an IDH alteration should be avoided.

5-ALA fluorescence-guided surgery in pediatric brain tumors-a systematic review.

5-Aminolevulinic acid (5-ALA)-guided resection of gliomas in adults enables better differentiation between tumor and normal brain tissue, allowing a higher degree of resection, and improves patient outcomes. In recent years, several reports have emerged regarding the use of 5-ALA in other brain tumor entities, including pediatric brains tumors. Since gross total resection (GTR) of many brain tumors in children is crucial and the role of 5-ALA-guided resection of these tumors is not clear, we sought to perform a comprehensive literature review on this topic. A systematic literature review of EMBASE and MEDLINE/PubMed databases revealed 19 eligible publications encompassing 175 5-ALA-guided operations on pediatric brain tumors. To prevent bias, publications were revised independently by two authors. We found that 5-ALA-guided resection enabled the surgeons to identify the tumor more easily and was considered helpful mainly in cases of glioblastoma (GBM, 21/27, 78%), anaplastic ependymoma WHO grade III (10/14, 71%), and anaplastic astrocytoma (4/6, 67%). In contrast, cases of pilocytic astrocytomas (PAs) and medulloblastomas 5-ALA-guided surgery did not show consistent fluorescent signals and 5-ALA was considered helpful only in 12% and 22% of cases, respectively. Accumulation of fluorescent porphyrins seems to depend on WHO tumor grading. One important finding is that when 5-ALA-guided resections were considered helpful, the degree of resection was higher than is cases where it was not helpful. The rate of adverse events related to 5-ALA was negligible, especially new postoperative sequelae. 5-ALA could play a role in resection of pediatric brain tumors. However, further prospective clinical trials are needed.

Magnetic Resonance Imaging and Proton Magnetic Resonance Spectroscopy for Differentiating Between Enhanced Gliomas and Malignant Lymphomas

Although the treatment strategies for malignant lymphomas and gliomas differ, it is usually difficult to preoperatively distinguish between them. Magnetic resonance spectroscopy (MRS) was recently reported to be useful for preoperative diagnoses; however, MRS data analysis using LCModel, which is a quantitative and objective method, was performed in only a few of the existing reports. The clinical characteristics, conventional magnetic resonance imaging findings, and MRS parameters using LCModel were evaluated to identify the factors that can help distinguish between malignant lymphomas and enhanced gliomas. In total, 59 cases were evaluated, including 13 cases of malignant lymphoma, 1 case of pilocytic astrocytoma, 5 cases of grade Ⅱ glioma, 5 cases of grade Ⅲ glioma, and 35 cases of glioblastoma. There was no correlation between clinical characteristics (sex and age) and diagnosis. Neither T1- nor T2-weighted image was useful for differentiation between the 2 forms of tumors, but the apparent diffusion coefficient minimum value was useful for distinguishing malignant lymphomas from gliomas, with an area under the curve (AUC) value of 0.852. MRS analysis using LCModel revealed differences in glutamate (Glu), N-acetylaspartate (NAA)+ N-acetylaspartylglutamate (NAAG), Glu+ glutamine, and Lipid (Lip) 13a+ Lip13b between malignant lymphomas and gliomas. The largest AUC was 0.904, which was obtained for the Glu level, followed by 0.883 and 0.866 for NAA+ NAAG and Lip13a+ Lip13b, respectively. Quantitative analysis of proton-MRS using LCModel is considered to be a valuable method for distinguishing between gliomas and malignant lymphomas.

Surgical treatment of low grade brain tumors associated with epilepsy in children

Objective To explore the strategy of surgical treatment for children with low-grade tumors associated with epilepsy. Methods Clinical data of 30 patients with low grade tumors (ages: 1-14 years) were retrospectively reviewed who underwent surgery from January 2011 to June 2016 at Department of Neurosurgery, Guangdong Sanjiu Brain Hospital. Lesions were located in multiple cerebral lobes in 8 cases, in functional zones in 8 and in non-functional zones in 14 cases (including 10 cases with lesions in the medial temporal lobe). The surgical strategy included subtotal resection, gross-total resection and enlarged resection. Postoperative effects were evaluated by Engel classification. Results A total of 30 patients underwent surgical treatment. Subtotal resection was achieved in 8 cases, gross-total resection in 5 and enlarged resection in 17 (including 9 cases undergoing anterior temporal lobectomy and 1 case of selective amygdalohippocampectomy). The final pathology suggested that there were 11 cases of ganglioglioma, 8 cases of dysembryoplastic neuroepithelial tumor, 2 cases of pilocytic astrocytoma, 3 cases of oligodendroglioma, 3 cases of pleomorphic xanthoastrocytoma, 1 case of diffuse astrocytoma , 1 case of oligoastrocytoma and 1 case of meningioma. The follow-up duration was 1-6 years, with an average of 3.0±1.6 years. For postoperative recover: 28 cases had an outcome of Engel Class I, 1 patient was in Engel Class Ⅱ and 1 patient was in Class Ⅳ. Conclusions For surgical treatment for children with low-grade tumors associated with epilepsy, more attention should be paid to preoperative assessment of the epileptogenic zone. The tumor is not exactly the same as the epileptogenic zone and the strategy of surgical treatment depends on the tumor characteristics as well as whether it is located at temporal lobe or involved in functional areas. Key words: Epilepsy; Child; Brain neoplasms; Low grade; Neurosurgical procedures

Abstract 640: Histopathologic and molecular features in a subset of pilocytic astrocytomas in a tertiary African hospital

Abstract Background: Pilocytic astrocytomas are WHO grade I astrocytomas. Worldwide, they have been documented to be the second most common gliomas after WHO grade IV glioblastomas. Definitive diagnosis may be made with traditional hematoxylin and eosin. Increasingly, a number of cases are atypical deceptive in clinical and histopathologic presentation, requiring ancillary immunohistochemical and molecular studies. This study evaluated a subset of pilocytic astrocytomas at the University College Hospital Ibadan. Nigeria. Methods: All cases of Pilocytic Astrocytomas were identified retrospectively within our institutional database over a 12-year period. Inclusion criteria was by availability of the FFPE block. Astrocytic origin was confirmed by GFAP immunohistochemistry; previously stained hematoxylin and eosin slides were reviewed with newly re-sectioned hematoxylin and eosin stained slides along with ancillary Ki-67/MIB immunohistochemistry labelling index. ATRX immunohistochemistry was carried out on all re-sectioned slides. Tissue scrolls were taken for DNA extraction and pyro-sequencing for BRAFV600E BRAF mutation using a Qiagen pyrosequencer. This work was carried out in the molecular neuropathology laboratory at the Texas Children's Hospital, Houston Texas. Results were analyzed using SPSS version 24. Results: 40 cases (30.7%) of all astrocytic neoplasms were documented over this 12-year period. 23(57.5%)of these cases were suitable for analysis in this study. Males accounted for 65.2% of cases. Male: female ratio was 1:0.5. The mean age of all the cases was 14.22+/- 12.90 years, median age of 8 years with an age range of 42 years. 65.2% of all cases were within the 0-15-year age group, 17.4% were within the 16 - 30-year age group while the remaining 17.4% were within the 31 - 45-year age group. Most cases occurred infratentoriallysupratentorially (69.6%). The cerebellum was the commonest location accounting for 47.8%, followed by the supra-sellar region (17.4%). Most cases were centrally sited (47.8%). All cases (100%) showed positive ATRX expression. 3 cases (20%) of BRAF V600E expression were recorded. This included 1 case with malignant/anaplastic features which was previously misdiagnosed as a glioblastoma with suggestive radiologic imaging. Mean age of tumors with BRAF positive expression was 13.95 +/- 12.95years, while the mean age for BRAF negative cases was 17.00 +/-16.97 years. The difference between these ages was not statistically significant. Limitations: The quality of available blocks limited DNA amplification and further analysis in 8 of the cases. Conclusion: This study aims to underscores the importance of BRAF V600E mutations among pilocytic astrocytomas in our environment with regards to its diagnostic and prognostic significance. Citation Format: Michael C. Nweke, Gabriel O. Ogun, Clement A. Okolo, Amos D. Adeleye, Adekunle M. Adesina. Histopathologic and molecular features in a subset of pilocytic astrocytomas in a tertiary African hospital [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 640.

Tectal gliomas: assessment of malignant progression, clinical management, and quality of life in a supposedly benign neoplasm.

OBJECTIVE Tectal gliomas constitute a rare and inhomogeneous group of lesions with an uncertain clinical course. Because these supposedly benign tumors are frequently followed up by observation over many years, the authors undertook this analysis of their own case series in an effort to demonstrate that the clinical course is highly variable and that there is a potential for a progressive biology. METHODS Clinical data analysis of 23 cases of tectal glioma (involving 9 children and 14 adults) was performed retrospectively. Radiographic data were analyzed longitudinally and MR images were evaluated for tumor volume, contrast enhancement, and growth progression. Quality of life was assessed using the EORTC BN20 and C30 questionnaires during follow-up in a subgroup of patients. RESULTS The patients' mean age at diagnosis was 29.2 years. The main presenting symptom at diagnosis was hydrocephalus (80%). Six patients were treated by primary tumor resection (26.1%), 3 patients underwent biopsy followed by resection (13.1%), and 3 patients underwent biopsy only (13.1%). For additional treatment of hydrocephalus, 14 patients (60.9%) received shunts and/or endoscopic third ventriculostomy. Radiographic tumor progression was observed in 47.9% of the 23 cases. The mean time between diagnosis and growth progression was 51.5 months, and the mean time to contrast enhancement was 69.7 months. Histopathological analysis was obtained in 12 cases (52.2%), resulting in 5 cases of high-grade glioma (3 cases of glioblastoma multiforme [GBM], grade IV, and 2 of anaplastic astrocytoma, grade III), 5 cases of pilocytic astrocytoma, 1 diffuse astrocytoma, and 1 ganglioglioma. Malignant progression was observed in 2 cases, with 1 case progressing from a diffuse astrocytoma (grade II) to a GBM (grade IV) within a period of 13 years. Quality-of-life measurements demonstrated distinct functional deficits compared to a healthy sample as well as glioma control cohorts. CONCLUSIONS Analysis of this case series shows that a major subpopulation of tectal gliomas show progression and malignant transformation in children as well as in adolescents. These tumors therefore cannot be considered inert lesions and require histological confirmation and close follow-up. Quality-of-life questionnaires show that tectal glioma patients might benefit from special psychological support in emotional, social, and cognitive functionality.

成人の側頭葉に発生したBRAF V600Eの変異とanaplastic featureを伴ったpilocytic astrocytomaの1例

成人の側頭葉に発生したBRAF V600Eの変異とanaplastic featureを伴ったpilocytic astrocytomaの1例

Coexistent dysembryoplastic neuroepithelial tumour and pilocytic astrocytoma

Dysembryoplastic neuroepithelial tumour (DNET) is an uncommon mixed glioneuronal tumour. DNET is classified as Grade I neoplasm in revised World Health Organization classification of tumors of the nervous system. DNET is commonly seen in the temporal lobe of children and young adults with features of pharmacoresistant complex partial seizures. Tumors arising in association with DNETs are rare. Only two cases of pilocytic astrocytoma (PA) arising in DNETs are reported. Surgical excision is the only successful management with favourable prognosis. The development of recurrence and malignancy after subtotal or even after complete excision challenges the premise of stability and highlights the importance of close clinical follow up. Here, a case of DNET with area of PA is described which helps in understanding the pathogenesis and biological behavior of DNET.

Characterization of the blood brain barrier in pediatric central nervous system neoplasms.

ObjectiveThe normal blood–brain barrier (BBB) is composed of tight junctions between endothelial cells and surrounding astrocyte foot processes. Breakdown of the physiological astrocyte-endothelial cell relationship occurs in adult metastatic and primary brain tumors. However, the astrocyte-endothelial cell relationship has not been studied in pediatric tumors.Materials and MethodsUtilizing specimens from cases of pilocytic astrocytoma (n = 5), medulloblastoma (n = 5), and low-grade diffuse astrocytoma (n = 1), immunofluorescence were performed using primary antibodies against CD31, glial fibrillary acidic protein (GFAP), and aquaporin 4 (AQ4). Clinical, magnetic resonance imaging, operative, and histopathological findings were analyzed.ResultsStrongly-enhancing areas of medulloblastoma exhibited complete BBB breakdown with sparse GFAP and AQ4 staining around CD31-positive vessels. Moderately enhancing regions of pilocytic astrocytomas exhibited regions of intact BBB and vasculature surrounded by dense GFAP staining but reduced and disorganized AQ4 staining, suggesting tumor cells could not fulfill physiological BBB support. Non-enhancing low-grade diffuse astrocytoma demonstrated intact BBB with intense peri-microvasculature GFAP and AQ4 staining. AQ4 stained so strongly that AQ4 visualization alone delineated CD31-positive vessels.ConclusionTaken together, BBB breakdown in pediatric tumors corresponds to a loss of normal endothelial cell-astrocyte foot process relationships. Further development of pharmaceutical agents capitalizing on this disrupted BBB is warranted in medulloblastoma and pilocytic astrocytoma. However, BBB integrity remains a challenge in treating low-grade diffuse astrocytoma before progression toward secondary glioblastoma.

Pilocytic astrocytoma presenting with atypical features on magnetic resonance imaging

Pilocytic astrocytoma, which is classified as a grade I astrocytic tumor by the World Health Organization, is the most common type of glioma in children and young adults. Pilocytic astrocytoma generally appears as a well-circumscribed, contrast-enhancing lesion, frequently with cystic components on magnetic resonance imaging (MRI). However, it has been reported that the MRI appearance of pilocytic astrocytoma may be similar to that of high-grade gliomas in some cases. We here report on 6 cases of pilocytic astrocytoma with atypical MRI findings, including small cyst formation, heterogeneously enhancing tumor nodules, irregularly enhancing tumor nodules, and enhancing tumor nodules with internal hemorrhage. All tumors were successfully resected, and the histological diagnoses were pilocytic astrocytoma. When the tumor is located near a cerebral cistern or ventricle, the risk of leptomeningeal dissemination is increased. Furthermore, partial resection has also been associated with a higher risk of recurrence and leptomeningeal dissemination. To date, all but one patient are alive and recurrence-free. Because the preoperative diagnosis influences the decision on the extent of resection and because of the high risk of leptomeningeal dissemination associated with these tumors, careful and correct diagnosis by MRI is important.