Tumours of the nervous system are the third most common childhood tumours after leukaemia and lymphomas, accounting for up to 20% of all tumours (1,2,3,4). Paediatric CNS tumours constitute approximately 35% of all childhood malignancies and remain the leading cause of cancer-related deaths in children. (5) In the absence of large population based tumour registries, literature reports exclusively profiling paediatric CNS tumours from India is sparse and limited to few hospital based data. (6,7). Our study attempts to add to the available national data on Pediatric CNS tumours by collecting data categorized according to the most recent WHO classification. We have also attempted to compare our data with published national and international data. We believe that this information can assist the field of paediatric brain tumour research by planning treatment protocols and strategies.
The incidence of paediatric CNS tumours in India is not well documented whereas in the United States it is approximately 5.67 per 100,000 person-years. (11) The pathogenesis of most brain tumours in children is unclear but a genetic association and radiation exposure are probable risk factors (25,26) Neurofibromatosis type 1 (NF-1), tuberous sclerosis, Li-Fraumeni syndrome, Gorlin syndrome and Turcot syndromes are few of the genetic conditions associated with paediatric CNS tumours. The mean age in our series was 10.2 years which is similar to the one reported from other centres in India and comparable to the that reported from France (9 years) and China (12.6 years). (5,6,12,18,19) The most commonly affected age group was 11–15 years (34%), which is again similar to the that reported from Vellore, India but much higher than the European (1–4 years), Japanese (5–9 years), and French (5–9 years) series [6, 12, 14, 15]. More than 50% of all tumours occurred after age 11 and more than 80% after age 5. Only five children (3.1%) were between the ages 0 and 1 year which is lower than the data from Taiwan (6.2%) (20).
Similar to what has been reported in other series, boys were affected more frequently than girls in our series (1.54:1). This ratio, however, is higher than that seen in Europe and most Asian countries (China, Korea, Iran) but lower than Brazil. (4,15,16–19,27). As observed in other series, supratentorial tumours (58.8%%) were more common than the infratentorial tumours (34.8%) in our series too. This preferential involvement for supratentorial compartment has been uniformly observed in almost all paediatric CNS tumour series (3,10,11,12,14,16,18,19,22). However, studies from Pakistan and Iran, however have observed preferential involvement of Infratentorial compartment. (8,9,13,14,15,21,28). Another uniform observation confirmed in our series too is that supratentorial tumours are more common in infants and children up to 3 years of age and again after age 10, whereas between ages 4 and 10 Infratentorial tumours are more common (3,12,14,16,17,18,19,22). Another interesting observation with regards to the age linked pathological profile of tumours is that younger children have a higher incidence of tumours of embryonal origin, such as medulloblastoma or atypical teratoid/rhabdoid tumour (ATRT), whereas older patients tend to have tumours of glial origin.(6,7)
Central nervous system tumours include a diverse spectrum of neoplasms and differ significantly from adult brain tumours with regards to their sites of origin, clinical presentation, histological features and their outcome. Metastasis, glial neoplasms and meningeal tumours constitute the predominant CNS tumour types in adults. In children besides gliomas, other major tumour types include embryonal neoplasms and craniopharyngiomas. In our study, the most common brain tumours in descending order are a) Astrocytomas, neuroglial tumours b) embryonal tumours c) craniopharyngiomas. This is similar to what was reported in other Indian centres. Jain et al’s analyses of nearly 4000 paediatric CNS tumours complied from seven major tertiary neurosurgical centres in India and Asirvatham et al’s study of 1000 tumours from one centre in South India revealed a similar profile. (6,7) However, in a large meta-analysis Rickert et al observed that internationally, ependymomas are the third most common tumours followed by craniopharyngioma. (22) This trend can be seen in the data from Canada, Germany, Sweden, and Morocco while figures from Korea and Brazil are similar to Indian data. (3,4,6,7,23, 24,25,27,28) Report from a single institute in China, showed craniopharyngiomas to be the second commonest tumour.(18,26,30). Our study correlates with other Indian studies suggesting that the spectrum of brain tumours in Indian children seems to resemble Western studies. (6,7)
In our series majority of the tumours were glial neoplasms (45.5%). The overall frequency of astrocytomas is around 40% in Europe and varies between 25% and 35% in other Asian countries like Japan, China, Korea and Pakistan (14,15,18,19,21,22,23,29). In our series too, among astrocytomas, Pilocytic astrocytoma was the most common (60%) which is similar to that reported in other studies (15,22). Amongst pilocytic astrocytomas, visual pathway gliomas which involve the optic nerve, chiasm, tract, and optic radiations accounted for 5.6% of all our paediatric CNS tumours. In most reported series visual pathway gliomas account for 4–8% of all brain tumours in children and are frequently associated with NF-1.(25, 30,31) Children with High grade gliomas (HGGs) have an overall poor prognosis despite intensive therapy and approximately 20% of all childhood gliomas are HGGs which include anaplastic astrocytoma (AA),diffuse intrinsic pontine glioma (DIPG), and glioblastoma multiforme (GBM).(30,32,33) The frequency of GBM and high grade gliomas in our study was only 11.1% of all astrocytomas, lesser than that reported by Cho et al. (17.2%) (16). Brain stem gliomas (BSGs), now classified as diffuse midline gliomas, H3 K27Mmutant, account for 10–15% of all paediatric CNS tumours. (10,34). Our series, however, had only three biopsy proven case of brain stem gliomas. This is probably related to the fact that most brain stem gliomas undergo direct radiotherapy without biopsy confirmation. Ependymomas are the third most common brain tumour in children and account for approximately 8–10% of all childhood CNS tumours. (35). Our series, however, had only ten ependymomas all of them except one located in the posterior fossa. The standard of care for most paediatric glial neoplasms except brain stem gliomas and visual pathway gliomas is maximal safe resection followed by adjuvant therapy. The use of irradiation in children younger than 3 years remains controversial, but chemotherapy is typically used to delay or avoid irradiation to avoid the long-term consequences.
An embryonal tumour of the posterior fossa, Medulloblastoma comprises up to 20% of all paediatric brain tumours.1 and have a male predominance.(25) Based on molecular subtyping medulloblastomas are now subdivided into four groups: wingless (WNT), Sonic hedgehog (SHH), group 3, and group 4 .(9,10,36) Medulloblastoma was the second most common tumour in our study similar to other studies from India and those from Brazil, Iran, and Korea (6,7,16,17). Though individual studies from different countries in Europe did find medulloblastomas to be the second most common tumour, analysis of 19,531 paediatric CNS tumours from the European Database Automated Childhood Cancer Information System found medulloblastomas to be a distant fourth (3%) after astrocytoma (40%), PNET (11%), and ependymoma (5%) (12,15,22). Earlier known as CNS-primitive neuroectodermal tumours (PNETs), supratentorital embryonal tumours represent a group of rare paediatric supratentorial tumours comprising fewer than 3% of paediatric brain tumours and carry a poor prognosis.(25). ATRTs are rare malignant intracranial neoplasms most commonly occurring in infants and young children. They account for only 1–2% of all paediatric brain tumours but approximately 10–20% of CNS tumours in patients younger than 3 years.(25) Our series had four cases (2.5%) each of embryonal tumours and ATRTs all of whom had a poor long term outcome. (22). The standard of care for all these tumours is gross total removal followed by radiation therapy, and chemotherapy, regardless of molecular subtype.
Craniopharyngiomas are slow-growing benign epithelial tumours that arise from embryonic remnants of the Rathke pouch in the suprasellar region adjacent to the optic chiasm and account for approximately 5–10% of paediatric brain tumours.(37) In our series craniopharyngioma constituted 15.2% of our total tumours similar to that reported from Brazil and Korea but higher than that reported from other Indian series (4,6,7,16). In China, craniopharyngioma is the second most common tumour after glial lesions (18,19). Although considered histologically benign tumours, paediatric craniopharyngiomas remain a challenge with respect to treatment options due to the close proximity to many vital structures (38). Surgery with adjuvant radiotherapy for residual/ recurrent lesions remains the mainstay of treatment, with a > 85% progression-free survival rate. (25)
Intracranial germ cell tumours (GCTs) represent approximately 3% of paediatric brain tumours and most commonly arise in midline locations, such as the pineal or suprasellar region (25). The frequency of germ cell tumours varies markedly in different countries ranging from as low as 0.9% in Morocco to as high as 14.3% in Japan, China and oriental countries (7.8–11%). (14,18,19,28). The frequency of germ cell tumours in our series was 2.8% comparable to European literature . Asian countries particularly Korea, China, and Japan, show higher frequency for germ cell tumours and craniopharyngiomas probably related to environmental and/or genetic differences.
Choroid plexus tumours are intraventricular papillary neoplasms derived from the choroid plexus epithelium and account for fewer than 1% of all brain tumours and 3–4% of paediatric intracranial tumours. Approximately 50% of choroid plexus tumours are found in the lateral ventricles, 40% in the fourth ventricle and 5% in the third ventricle and multiple ventricles in the remaining 5%. (25,27). Our series had only two choroid plexus tumours accounting for 1.3% of total tumours. Gross total resection is typically curative for choroid plexus papillomas whereas the invasive nature of choroid plexus carcinomas makes it difficult to achieve complete resection, necessitating the use of adjuvant therapy. (25)
Primary spinal cord tumours are rare CNS tumours and accounted 7.5% of all childhood CNS tumours in our series. Spinal cord tumours can be intramedullary, intradural-extramedullary, and extradural, the most common in children being astrocytomas and ependymomas.(25) In our study, the frequency of nerve sheath tumours 2.5% was similar to that reported by Wong et al. (1.4%) and Bauchetet al. (2%) but less compared to other Indian reports (4.1%) [6, 7, 12, 20].
We also had few unique pathologies in our series. Pediatric meningiomas are known to be rare accounting for 2.5% of paediatric CNS tumours. (39) We had six (3.7%) cases of meningiomas most of them in skull base locations. We also had three cases each of histiocytosis and Ewing’s sarcoma and one case of intracranial metastasis from a soft tissue sarcoma in the thigh. We had one case of paediatric pituitary adenoma another rare pathology in childhood. (40)