Revisiting Management of Pediatric Brain Tumors with New Molecular Insights.

Pediatric central nervous system primitive neuro-ectodermal brain tumors (CNS-PNETs) are rare tumors with ill-defined biological features. In this issue of Cell, Sturm et al. used state-of-the-art methods to interrogate these tumors' biology. Their integrated molecular analyses led them to propose a new molecular classification, with four new entities identified, that should get oncologists' attention.

New Brain Tumor Entities Emerge from Molecular Classification of CNS-PNETs.

Primitive neuroectodermal tumors of the central nervous system (CNS-PNETs) are highly aggressive, poorly differentiated embryonal tumors occurring predominantly in young children but also affecting adolescents and adults. Herein, we demonstrate that a significant proportion of institutionally diagnosed CNS-PNETs display molecular profiles indistinguishable from those of various other well-defined CNS tumor entities, facilitating diagnosis and appropriate therapy for patients with these tumors. From the remaining fraction of CNS-PNETs, we identify four new CNS tumor entities, each associated with a recurrent genetic alteration and distinct histopathological and clinical features. These new molecular entities, designated "CNS neuroblastoma with FOXR2 activation (CNS NB-FOXR2)," "CNS Ewing sarcoma family tumor with CIC alteration (CNS EFT-CIC)," "CNS high-grade neuroepithelial tumor with MN1 alteration (CNS HGNET-MN1)," and "CNS high-grade neuroepithelial tumor with BCOR alteration (CNS HGNET-BCOR)," will enable meaningful clinical trials and the development of therapeutic strategies for patients affected by poorly differentiated CNS tumors.

Extraenteric Malignant Gastrointestinal Neuroectodermal Tumor-A Clinicopathologic and Molecular Genetic Study of 11 Cases.

Malignant gastrointestinal neuroectodermal tumors (MGNETs), also known as "gastrointestinal clear cell sarcoma-like tumors", are very rare, aggressive sarcomas characterized by enteric location, distinctive pathologic features, and EWSR1/FUS::ATF1/CREB1 fusions. Despite identical genetics, the clinicopathologic features of MGNET are otherwise quite different from those of clear cell sarcoma of soft parts. Only exceptional extraenteric MGNET (E-MGNET) has been reported. We report a series of 11 E-MGNETs, the largest to date. Cases diagnosed with MGNET and occurring in nonintestinal locations were retrieved. A clinical follow-up was obtained. The tumors occurred in 3 men and 8 women (range, 14-70 years of age; median, 33 years) and involved the soft tissues of the neck (3), shoulder (1), buttock (2), orbit (1), tongue/parapharyngeal space (1), urinary bladder (1), and falciform ligament/liver (1). Tumors showed morphologic features of enteric MGNET (small, relatively uniform, round to ovoid cells with round, regular nuclei containing small nucleoli growing in multinodular and vaguely lobular patterns, with solid, pseudoalveolar, and pseudopapillary architecture). Immunohistochemical results were S100 protein (11/11), SOX10 (11/11), synaptophysin (3/10), CD56 (7/9), CD117 (3/9), DOG1 (0/4), ALK (4/8), chromogranin A (0/10), HMB-45 (0/11), Melan-A (0/11), tyrosinase (0/4), and MiTF (0/11). Next-generation sequencing results were EWSR1::ATF1 (7 cases), EWSR1::CREB1 (3 cases), and EWSR1::PBX1 (1 case). The EWSR1::PBX1-positive tumor was similar to other cases, including osteoclast-like giant cells, and negative for myoepithelial markers. A clinical follow-up (range, 10-70 months; median, 34 months) showed 4 patients dead of disease (10.5, 12, 25, and 64 months after diagnosis), 1 patient alive with extensive metastases (43 months after diagnosis), 1 patient alive with persistent local disease (11 months after diagnosis), and 4 alive without disease (10, 47, 53, and 70 months after diagnosis). One case is too recent for the follow-up. The clinicopathologic and molecular genetic features of rare E-MGNET are essentially identical to those occurring in intestinal locations. Otherwise, typical E-MGNET may harbor EWSR1::PBX1, a finding previously unreported in this tumor type. As in enteric locations, the behavior of E-MGNET is aggressive, with metastases and/or death from disease in at least 50% of patients. E-MGNET should be distinguished from clear cell sarcoma of soft parts and other tumors with similar fusions. ALK expression appears to be a common feature of tumors harboring EWSR1/FUS::ATF1/CREB1 fusion but is unlikely to predict the therapeutic response to ALK inhibition. Future advances in our understanding of these unusual tumors will hopefully lead to improved nomenclature.

Phosphoprotein-based biomarkers as predictors for cancer therapy.

Disparities in cancer patient responses have prompted widespread searches to identify differences in sensitive vs. nonsensitive populations and form the basis of personalized medicine. This customized approach is dependent upon the development of pathway-specific therapeutics in conjunction with biomarkers that predict patient responses. Here, we show that Cdk5 drives growth in subgroups of patients with multiple types of neuroendocrine neoplasms. Phosphoproteomics and high throughput screening identified phosphorylation sites downstream of Cdk5. These phosphorylation events serve as biomarkers and effectively pinpoint Cdk5-driven tumors. Toward achieving targeted therapy, we demonstrate that mouse models of neuroendocrine cancer are responsive to selective Cdk5 inhibitors and biomimetic nanoparticles are effective vehicles for enhanced tumor targeting and reduction of drug toxicity. Finally, we show that biomarkers of Cdk5-dependent tumors effectively predict response to anti-Cdk5 therapy in patient-derived xenografts. Thus, a phosphoprotein-based diagnostic assay combined with Cdk5-targeted therapy is a rational treatment approach for neuroendocrine malignancies.

Malignant Gastrointestinal Neuroectodermal Tumor: A New Kid on the Block?

ABSTRACT: Also referred to as "osteoclast-rich, clear cell sarcoma-like tumor of the gastrointestinal tract (CCSLGT)," malignant gastrointestinal neuroectodermal tumor is a newly described, rare, aggressive sarcoma that commonly arises in the small bowel, stomach, and colon. Histogenesis is likely from an autonomous nervous system-related primitive cell of neural crest origin. The hallmark genetic finding of EWS-CREB1 or EWS-ATF1 fusion transcripts clinches the diagnosis. Annular constrictive lesions tend to be smaller, show homogenous contrast enhancement on computed tomography, and may present with bowel obstruction. Larger, expansile masses tend to be exophytic and show heterogeneous contrast enhancement. Surgical resection is the mainstay of treatment. Frequent recurrences, metastases, and death from disease in 75% of patients portend a poor prognosis. Targeted chemotherapy based on specific tumor pathways is being developed.

Analysis of Genes Associated with Both Neural Tube Defects and Neuroectodermal Tumors.

BACKGROUND Previous studies have demonstrated that embryo development and the occurrence of tumors are closely related, as key genes, pathways, miRNAs, and other biological mechanisms are involved in both processes. Extensive research has found that abnormal development of nerve ectodermal cells not only leads to neural tube defects (NTDs), but also neuroectodermal tumors. MATERIAL AND METHODS Genes associated with both NTDs and neuroectodermal tumors were obtained from the DisGeNET database. The STRING database was used to construct the protein-protein interaction (PPI) network and the hub genes were visualized using Cytoscape. Additionally, we predicted the miRNAs targeting the identified genes. Sequencing data obtained from an NTDs mouse model and human samples were used to confirm the bioinformatics results. Moreover, a dual-luciferase report assay was used to validate the targeting relationship between the miRNA-gene pairs identified. RESULTS A total of 104 intersection genes of NTDs-related and neuroectodermal tumors-related genes were obtained; 20 of these genes were differentially expressed in NTDs samples and had very close interactions. Among 10 hub genes, we identified 3 important susceptibility genes differentially expressed both in RA-induced NTDs mice and human glioblastoma samples: Ncam1, Shh, and Ascl1. Among these, we found that the Ncam1 expression level was regulated by mmu-miR-30a-5p, and the Ascl1 expression level was regulated by mmu-miR-375-3p. CONCLUSIONS In conclusion, we identified differentially expressed genes and a potential miRNA-mediated regulation mechanism shared between NTDs and neuroectodermal tumors that may guide future studies aiming to find novel therapeutic targets for NTDs or neuroectodermal tumors.

Malignant gastrointestinal neuroectodermal tumor: Cytologic, histologic, immunohistochemical, and molecular pitfalls.

Malignant gastrointestinal neuroectodermal tumor (GNET) is a rare malignant primary gastrointestinal mesenchymal tumor which can be diagnosed via fine-needle aspiration (FNA) cytology. In the context of FNA, the diagnosis requires a cell block and the use of significant resources including immunohistochemical stains and molecular testing. The differential diagnosis of GNET includes clear cell sarcoma (CCS), gastrointestinal stromal tumor (GIST), gastric schwannoma, metastatic melanoma, malignant perivascular epithelioid cell tumor (PEComa) and granular cell tumor, among others. Here we describe a case which was initially diagnosed as malignant granular cell tumor by FNA which was later revised to GNET following the finding of an EWSR1-ATF1 fusion gene rearrangement.

[Malignant gastrointestinal neuroectodermal tumor: clinicopathological analyses of four cases].

Objective: To investigate the clinicopathological features, diagnosis, differential diagnosis, and molecular alterations of malignant gastrointestinal neuroectodermal tumor (MGNET). Methods: Four cases of MGNET were collected at Fujian Provincial Hospital, from July 2013 to January 2019. H&E and immunohistochemical staining were retrospectively evaluated, together with genetic mutation analysis of EWSR1. The relevant literature was systematically reviewed. Results: There were two male and two female patients, with an age range of 34-81 (median 57) years. Tumor sizes ranged from 5-9 (median 6.8) cm. Microscopy showed diffuse and flaky growth of tumor cells, some of which were small and round. The tumor cells were arranged in solid, flaky, nested or pseudoadenoid patterns. The tumor cells were epithelioid, oval, short spindled, or small, with round or oval nuclei. The cytoplasm was eosinophilic or clear. Osteoclast-like multinucleated giant cells were scattered focally. Mitosis was about (2-10)/10 HPF. Immunohistochemically, the tumor cells were positive for S-100 protein (4/4), SOX10 (4/4), Syn (2/4), INI1 (4/4), H3K27Me3 (4/4) and vimentin (4/4). Ki-67 index was 15%-90%. Gene mutation detection confirmed EWSR1 mutation in all four cases, and C-KIT/PDGFRα genes were not mutated in two cases. Conclusions: MGNET is a rare high grade malignant soft tissue tumor. The diagnosis is based on clinicopathological, immunophenotypic, and molecular pathology features. The primary treatment for MGNET is complete surgical excision and chemotherapy; the prognosis is poor.

[Clear cell sarcoma or gastrointestinal neuroectodermal tumor (GNET) of the tongue? Case report and review of the literature of an extremely rare tumor localization]. / Sarcome à cellules claires ou tumeur neuroectodermique gastro-intestinale de la langue ? Une observation avec revue de la littérature dans une localisation exceptionnelle.

Clear cells sarcomas (CCS) are exceptionally rare in the tongue, with, to our knowledge, only three previous reports in anglo-saxon literature. Through our case, we will discuss the differential diagnosis of clear cells tumors of the tongue and bring this tumour closer to the newly described entity of the gastrointestinal tract named "clear cells sarcoma-like gastrointestinal (SCCLGI)", recently renamed "gastrointestinal neuroectodermal tumour (GNET)". SCCLGI/GNET share morphological and molecular characteristics with SCC but had until then been observed only in the digestive tract. Our case could be a lingual localization of a SCCLGI/GNET. SCC and SCCLGI/GNET characteristic molecular profil involves EWSR1-ATF1 [t(12; 22) (q13; q12)] and EWSR1-CREB1 [t(2; 22) (q34; q12)] fusion genes, but it is not specific of these tumours.

Review of molecular classification and treatment implications of pediatric brain tumors.

PURPOSE OF REVIEW: Brain tumors are the most common solid tumors and leading cause of cancer-related death in children. The advent of large-scale genomics has resulted in a plethora of profiling studies that have mapped the genetic and epigenetic landscapes of pediatric brain tumors, ringing in a new era of precision diagnostics and targeted therapies. In this review, we highlight the most recent findings, focusing on studies published after 2015, and discuss how new evidence is changing the care of children with brain tumors. RECENT FINDINGS: Genome-wide and epigenome-wide profiling data have revealed distinct tumor entities within, virtually, all pediatric brain tumor groups including medulloblastoma; ependymoma; high-grade and low-grade gliomas; atypical teratoid/rhabdoid tumors; and other embryonal tumors, previously called CNS primitive neuroectodermal tumors. Whenever integrated with clinical information, many molecular alterations emerge as powerful prognostic markers and should thus be used to stratify patients and tailor therapies. SUMMARY: Optimal integration of this newly emerging knowledge in a timely and meaningful way into clinical care is a remarkable task and a matter of active debate. The historical morphology-based classification of tumors is being replaced by a genetic-based classification, and the first generation of molecularly informed clinical trials is underway.

A rare case of paediatric primary central nervous system lymphoma treated with high-dose methotrexate and rituximab-based chemoimmunotherapy and whole brain radiotherapy followed by tumour bed boost with three-dimensional conformal radiation technique.

BACKGROUND: Primary central nervous system lymphomas (PCNSL) are rare in the paediatric population. CLINICAL CASE: A 12-year-old boy presented to our clinic with complaints of multiple episodes of generalised tonic-clonic seizures for 1 year and gradual loss of vision in both eyes for 3 months. Baseline magnetic resonance imaging (MRI) of the brain showed a large (7.2 × 7 cm) enhancing soft tissue lesion in the right frontal lobe causing mass effect and midline shift. With a radiological diagnosis of supratentorial primitive neuroectodermal tumour, he underwent subtotal resection of tumour. The post-operative histopathology revealed diffuse large B cell lymphoma (DLBCL). Systemic lymphoma workup was essentially normal. He received five cycles of chemoimmunotherapy with rituximab, high-dose methotrexate (HDMTX), vincristine and procarbazine and had complete radiological response (CR). This was followed by whole brain radiotherapy (WBRT) to a dose of 36 Gy in 20 fractions and sequential tumour bed boost to a dose of 9 Gy in 5 fractions by three-dimensional conformal technique. Subsequently, he received two cycles of consolidation chemotherapy with high-dose cytarabine. At completion of treatment, 3 and 6 months thereafter, MRI brain showed CR. At last follow-up visit, 13 months from the date of diagnosis, he was disease-free and asymptomatic with the exception of dimness of vision in both eyes due to long-standing bilateral optic atrophy. CONCLUSION: This report highlights the fact that paediatric PCNSL may be effectively treated by a combination of HDMTX and rituximab-based chemoimmunotherapy followed by consolidation with conformal WBRT and tumour bed boost. Lack of awareness of this rare entity may lead to diagnostic delay and potential ramifications as exemplified by chronic atrophic papilloedema and visual loss in the illustrative case.

Malignant gastrointestinal neuroectodermal tumor (clear cell sarcoma-like tumor of the gastrointestinal tract) of the small intestine in a 12-year-old boy.

The aim of this paper is a clinical and anatomopathological demonstration of a malignant lesion, a gastrointestinal neuroectodermal tumor (GNET), as an exceedingly rare cause of ileus in the pediatric population. Specifically, we present the case of a 12-year-old boy who showed dramatic weight loss, hypochromic anemia, fever, dehydration, exaggerated granulation of the terminal ileum, and mechanical ileus due to the obstruction by an intramural tumor of the small intestine. A 50cm-long part of the small intestine with pathological stricture was surgically removed, sampled and routinely fixed and stained with hematoxylin and eosin. The additional immunostains that were preformed were: PAS, S-100, HMB-45, NSE, LCA, CK AE1 / AE3, desmin, SMA, vimentin, CD99, NSE, synaptophysin, WT-1, calretinin, and DOG-1. Moreover, fluorescent in situ hybridization (FISH) with the EWSR1 Break Apart FISH Probe was applied. The neoplasm was composed of nests and alveolar patterns of frankly malignant clear cells with immunoreactivity to S-100, vimentin, and CD 99. The FISH technique detected chromosomal breaking at 22q12. The tumor metastasized to both the mesenteric lymph nodes and a number of hepatic segments. With several chemotherapy protocols, repeat laparotomies, and liver thermal ablations, the patient had a 1.5-year-long survival from the moment of diagnosis. The diagnosis of this malignancy requires both histopathological evaluation and molecular analysis, and the follow-up is based on careful clinical imaging of the neoplastic spread in order to apply proper surgical and oncological treatments. In conclusion, the clinical course of GNET was highly aggressive.

Orbital Reconstruction in Neuroectodermal Tumor of the Orbit: Multimodal Treatment Approach.

INTRODUCTION: Primitive neuroectodermal tumors of peripheral origin are very rare, and orbital neuroectodermal tumors are even more uncommon. Only 25 patients with primary orbital involvement in the pediatric age group have been reported. METHODS: In this article, the authors describe their experience in the multimodality treatment approach to treat neuroectodermal tumor of the orbit. The authors also present a male patient 3-year old presenting with a neuroectodermal tumor of the right orbit causing rapidly progressive proptosis. The patient underwent an upper and lateral orbital marginotomy. The entire bone defect was reconstructed with a bone graft, allowing for the reconstruction of the floor and the lateral wall of the middle cranial fossa, the floor of the anterior cranial fossa, the upper and lateral orbital frame, and the right zygomatic bone. Over a period of 16 months, the patient was subjected to chemotherapy. RESULTS: In the postoperative period, a favorable evolution of the disease was observed, with growth in the reconstructed structures, good projection of the orbit and the eyeball, and stable results without tumor recurrence. CONCLUSIONS: The authors present the clinical analysis, surgical management, as well as the chemotherapy treatment established, with follow-ups at 1 and 2 and a half years. This experience shows the effectiveness of multimodality therapy in the treatment of rare tumors of difficult handling.

[Clinicopathologic and molecular characteristics of malignant gastrointestinal neuroectodermal tumors].

Objective: To investigate the clinicopathologic and molecular characteristics, diagnostic, differential diagnostic and prognostic features of malignant gastrointestinal neuroectodermal tumor. Methods: Two cases of malignant gastrointestinal neuroectodermal tumor were retrieved; the clinical and radiologic features, histomorphology, immunophenotype, molecular genetics and prognosis were analyzed and the relevant literature reviewed. Results: Case 1 was a 57-year-old male, presented with recurrent abdominal pain and melena. Pelvic imaging showed a circumscribed thickening of the wall of a small intestinal segment, and a malignant lymphoma was favored. Case 2 was a 24-year-old male, presented with recurrent small intestinal malignancy. Imaging demonstrated multiple masses in the peritoneal and pelvic cavities, and a malignant gastrointestinal stromal tumor with multiple metastases was suspected. Grossly both tumors were located mainly in the muscularis propria of small intestine. Case 1 showed a single 5.5 cm tumor; and case 2 consisted of two tumors measuring 4 cm and 6 cm respectively. Microscopic examination of both tumors showed small round blue, but focally spindled or clear tumor cells in solid pattern. The tumor cells had scanty cytoplasm, indistinctive nucleoli and brisk mitoses. Osteoclast-like giant cells were dispersed within the stroma. In case 1 rosette-like and pseudo-papillary growth patterns were noted, and in case 2 there were variable-sized hemorrhagic cysts. By immunohistochemistry, both tumors showed strong and diffuse expression of SOX10 and S-100, and focal to diffuse expression of neuroendocrine markers (CD56 or synaptophysin). Case 2 exhibited focal reactivity to pan-cytokeratin. Both tumors lacked expression of markers associated with gastrointestinal stromal tumor, smooth muscle tumor, melanoma (HMB45 or Melan A), dendritic cell tumor and Ewing sarcoma. Fluorescence in situ hybridization analysis demonstrated EWSR1 rearrangement in both tumors and the next generation sequencing confirmed EWSR1-ATF1 gene fusion in case 2. At follow-up of 16 months, case 1 was recurrence or metastasis free; whereas case 2 showed multiple recurrences and metastases within 19 months although stable disease was transiently achieved when treated with combinations of multidrug and targeted chemotherapy. Conclusions: Malignant gastrointestinal neuroectodermal tumor is a rare and aggressive soft tissue sarcoma with a predilection for small intestine. It has distinctive morphologic, immunohistochemical and molecular characteristics and needs to be distinguished from other small blue round and spindle cell tumors that occur in the gut. Careful attentions to its characteristic histomorphology with the judicious use of immunohistochemistry and molecular genetics can help to distinguish this tumor from its many mimickers.

Activity of c-Met/ALK Inhibitor Crizotinib and Multi-Kinase VEGF Inhibitor Pazopanib in Metastatic Gastrointestinal Neuroectodermal Tumor Harboring EWSR1-CREB1 Fusion.

Malignant gastrointestinal neuroectodermal tumor (GNET) is an aggressive rare tumor, primarily occurring in young adults with frequent local-regional metastases and recurrence after local control. The tumor is characterized by the presence of EWSR1-ATF1 or EWSR1-CREB1 and immunohistochemical positivity for S-100 protein without melanocytic marker positivity. Due to poor responses to standard sarcoma regimens, GNET has a poor prognosis, and development of effective systemic therapy is desperately needed to treat these patients. Herein, we present a patient with a small bowel GNET who experienced recurrent hepatic and skeletal metastases after a primary resection. Comprehensive genomic profiling (CGP) in the course of clinical care with DNA and RNA sequencing demonstrated the presence of an exon 7 to exon 6 EWSR1-CREB1 fusion in the context of a diploid genome with no other genomic alterations. In a clinical trial, the patient received a combination of 250 mg crizotinib with 600 mg pazopanib quaque die and achieved partial response and durable clinical benefit for over 2.8 years, and with minimal toxicity from therapy. Using a CGP database of over 50,000 samples, we identified 11 additional cases that harbor EWSR1-CREB1 and report clinicopathologic characteristics, as these patients may also benefit from such a regimen.

Retrospective analysis of 14 cases of remote epidural hematoma as a postoperative complication after intracranial tumor resection.

BACKGROUND: The occurrence of remote epidural hematoma as a postoperative complication after intracranial tumor resection is rare. This study reviewed experiences treating these hematomas and speculated on the causes of this disease. This study reviewed the treatment experience of 14 such cases. METHODS: The 14 patients included 10 males and 4 females, with an age range of 19 to 65 years old. Six cases of tumors occurred in the sellar region, two cases in the lateral ventricle, one case in the fourth ventricle, one case in a cerebellar hemisphere, and four cases in other sites. Among them, five cases were complicated with supratentorial hydrocephalus. The tumors included five cases of meningioma tumors, two cases of pituitary adenomas, three cases of ependymomas, two cases of craniopharyngiomas, one case of astrocytoma, and one case of tuberculosis tumor. For the cases complicated with hydrocephalus, ventricular drainage was provided if needed, and the tumor resection was then performed, with close observation for postoperative changes. If neurological symptoms and disturbance of consciousness occurred, computed tomography (CT) examination was immediately performed. If a remote epidural hematoma was found, the hematoma was evacuated by craniotomy. The patients were followed up after surgery. In the five cases complicated with hydrocephalus, ventricular drainage was first provided for three cases. RESULTS: All of the 14 cases underwent total tumor resection, and postoperative remote epidural hematoma occurred in all cases, including eight cases on the ipsilateral side and adjacent to the supratentorial operative field; two cases occurred on the contralateral side; two cases occurred on bilateral sides; and two cases occurred in distant areas (with infratentorial surgery, the hematoma occurred on the supratentorial area). Postoperative remote epidural hematoma usually occurred 0.5-5 h after the tumor resection, when the tentorial hernia had already occurred. Following tumor resection and epidural hematoma evacuation, 13 patients were discharged with good recovery, and one patient died. CONCLUSIONS: The reduced intracranial pressure due to the intracranial tumor resection may be the cause of this hematoma. This type of epidural hematoma is acute and often occurs before hernia. Thus, the risk of remote epidural hematoma after intracranial tumor resection needs to be made known. Aggressive hematoma evacuation can often result in satisfactory outcomes for patients.

MORPHOLOGICAL PATTERN AND FREQUENCY OF CENTRAL NERVOUS SYSTEM TUMOURS IN CHILDREN.

BACKGROUND: Recent studies, including a comprehensive study by National Cancer Institute, have shown that a significant increase in the incidence of childhood brain tumours makes them the most common paediatric tumour. The objectives of this study were to determine the frequency of central nervous system tumours in paediatric age group (0-12 years), and to segregate various morphologic types according to WHO classification. METHODS: The study included consecutive cases of central nervous system tumours diagnosed in children in the histopathology department at Federal Government Polyclinic, PGMI, Islamabad, during a period of 4.8 years (Jan 2009-Aug 2013). The initial histopathological evaluation of these lesions was performed on H&E stained sections of paraffin embedded tissues. Special stains and immunohistochemistry were performed whenever indicated. RESULTS: Out of 75 cases, 34 (45.3%) were astrocytic tumours, including 16 (47.1%) Pilocytic astrocytomas (WHO Grade-I), 1 (2.9%) diffuse fibrillary astrocytoma (WHO Grade-II), 1 (2.9%) anaplastic astrocytoma (WHO Grade-III) and 16(47.1%) glioblastoma multiforme (WHO Grade-IV); 18 (24%) were embryonal tumours including 17 (94.4%) medulloblastoma (WHO Grade-IV) and 1 (5.6%) neuroblastoma (WHO Grade IV); 10 (13.3%) were craniopharyngiomas (WHO Grade-I) and 5 (6.7%) were ependymal tumours including 1 (20%) myxopapillary ependymoma (WHO Grade-I) and 4 (80%) ependymomas (WHO Grade-II). Miscellaneous entities included 3 (4%) choroid plexus tumours; 1 (2%) anaplastic oligodendroglioma (WHO Grade-III); 1 (2%) atypical meningioma (WHO Grade-II); 1 (2%) schwannoma (WHO Grade-I); 1 (2%) neurofibroma (WHO Grade-I) and 1 (2%) lipoma (WHO Grade-I). CONCLUSION: Astrocytic tumours are the most common central nervous system tumours in paediatric age group and high grade lesions (WHO Grade-IV) constitute the largest category (45.3%).