Cancer, Childhood Brain Tumors

Article Author:
Surabhi Subramanian
Article Editor:
Tahani Ahmad
Updated:
1/8/2019 11:40:30 PM
PubMed Link:
Cancer, Childhood Brain Tumors

Introduction

Pediatric brain tumors are the most common type of solid childhood cancer and only second to leukemia as a cause of pediatric malignancies. They are classified into: congenital brain tumors (CBT) (diagnosed antenatally in the first 60 days of life),  tumors of the infancy (younger than 1 year of age), and older children. Prognosis of pediatric brain tumors depends on age at presentation, histological type, and extent of resectability. CBT behaves in different ways than pathologically similar tumors in older children. For example, low-grade gliomas show increased aggressiveness while high-grade gliomas exhibit sightly better prognosis in very young children compared to their older counterparts.[1][2]. With the advances in imaging techniques, molecular biology and genetics, pediatric brain tumors are increasingly being diagnosed early in the disease course, sub-grouped, and targeted with more specified treatment strategies.[3]

This article reviews the congenital group with emphasis on the most common types in this category, specifically; teratoma, choroid plexus papilloma, desmoplastic infantile tumors (DIA/DIG), glioblastoma multiforme (GBM), and medulloblastoma.

Etiology

Despite advances in medical knowledge there is no definite cause for brain tumors identified. Combination of genetic and environmental factors are suspected to come into play in the pathogenesis of brain tumors. Multiple known cancer predisposition syndromes show associations with brain tumors, for example, DICER1, Li-Fraumeni, and other neurocutaneous syndromes such as neurofibromatosis, tuberous sclerosis, and Von-Hippel Lindau. Further elaboration of the pathogenesis of brain tumor is beyond this review.

Epidemiology

Pediatric brain tumor incidence varies among different countries. It ranges from 1.15 to 5.14 cases per 100,000 persons, with the highest rates reported in the United States.[4] The incidence of CBT ranges from approximately 0.3 to 2.9 cases per 100,000 live births in different parts of the world.[5][6] Their prognosis and survival rates depend on the histological subtype and site of tumors.

Major types of CBTs are teratoma (26.6% to 48%), astrocytoma (7.4% to 28.8%), choroid plexus papilloma (3.7% to 13.2%), embryonal tumor (3% to 13%), craniopharyngioma (5.6% to 6.8%), and ependymoma (4.4%).[7]

Pathophysiology

Brain tumors in children are classified as supratentorial and infratentorial. Supratentorial tumors are the commonest in those younger than the age of 3 years while posterior fossa tumors are more common between ages 4 to 10. After puberty, both groups occur with equal frequency.[8]

Congenital brain tumors (CBTs) are tumors that are diagnosed antenatally or within first 2 months of life.[9][10] Teratoma, a germ cell tumor is the most common type of congenital brain tumor. The incidence of teratoma is equally distributed among both genders.[11] 

Choroid plexus papillomas are the third most common mass in the pediatric population after teratomas and gliomas. They can arise from anywhere where choroid plexus is present. Typically, in infants, they arise within the lateral ventricles.[12]

Medulloblastoma is one of the common perinatal tumors and is the most common posterior fossa tumor in the pediatric age group.[13] Medulloblastomas arise from the vermis of the cerebellum. It can cause obstructive hydrocephalus and leptomeningeal seeding along the spinal cord.[14]

Histopathology

The histopathology and molecular basis of brain tumors vary tremendously among the subtypes.

Teratomas

Teratomas are derived from all 3 germ layers.[11] They can be mature, immature, or malignant. Malignant form is the least common among congenital brain tumors.[15]

Gliomas

Gliomas arise from glial precursor cells of the brain and spinal cord. Astrocytic tumors make up a large group of neoplasms that have different clinicopathologic and histological subtypes and grades from (WHO grade I to IV).[16] Gliomas are classified as low grade (WHO grade I/II) and high grade (WHO grade III/IV). For example, pilocytic astrocytoma (WHO grade I) and glioblastoma multiforme (WHO grade IV). Desmoplastic infantile astrocytoma and ganglioglioma (DIA/DIG) are WHO grade I tumors.[16] Congenital (GBM) is a very rare brain tumor (WHO grade IV). This lesion shows clinical and molecular characteristics that are different from their pediatric or adult counterparts and has a better prognosis than the pediatric and adult GBM.[17]

Medulloblastoma

Medulloblastoma is cone of the embryonal brain tumors. According to current WHO classification, besides histopathological features, genetic and molecular subtypes are considered and determine the prognosis.[16]

History and Physical

CBTs are mainly discovered during a third-trimester ultrasound. Antenatal ultrasound may show intracranial mass, hydrocephalus, polyhydramnios, among other signs. In recent years, fetal MRI is increasingly used to confirm findings visualized on ultrasound. Postnatally, common presentations are hydrocephalus, large heads, neurological signs, and sometimes, intraparenchymal hemorrhages.[8] Recent advances in imaging techniques have promoted early detection of all forms of congenital and other pediatric brain tumors.

In neonates and older children, the clinical presentation depends on the site of tumor involvement. Supratentorial tumors commonly present with limb weakness followed by convulsions and altered consciousness.[18] Infratentorial tumors commonly present with signs of raised intracranial pressure (ICP).[18]

Evaluation

Teratoma is typically present as mixed echogenic and cystic intracranial mass on antenatal ultrasound during the second and third trimester.[19] MRI shows heterogeneous signal intensity on T1/T2. It appears as a mixed density lesion in CT with coarse calcification. The presence of fat is a good clue to the diagnosis. Supratentorial location is more common than infratentorial.

Glioblastoma multiforme is a high-grade astrocytoma, typically presents as a large, ill-defined, intracranial mass occupying most of one hemisphere or spread through the corpus callosum into the other hemisphere. It appears as an echogenic heterogeneous mass on ultrasonography.[20] It usually presents with features of raised ICP.[20]

Choroid plexus papilloma typically presents as enhancing intraventricular mass on CT and iso-hypo intense on T1 and iso-hyperintense on T2 MRI.[21] It commonly causes hydrocephalus.

Medulloblastoma typically presents as a midline posterior fossa tumor growing into the fourth ventricle. It appears hyperdense on CT-scan, has variable intensity on T1/T2 MRI with diffusion restriction and varying contrast enhancement [22]

Treatment / Management

The principal treatment for CBT is surgery aiming for gross total resection.[23] The extent of the CBT and the general condition of the patient are important determinants of surgical outcome.[8] Adjuvant therapies are not widely used in neonates. Craniospinal radiotherapy results in significant developmental retardation and is avoided during the first 3 years of life.[24]

Differential Diagnosis

Abscess

Neonatal brain abscess occurs as a relatively rare complication of bacterial meningitis in 1.3% to 4.0% neonates.[25] Several congenital CNS infections like TORCH (toxoplasmosis, rubella, cytomegalovirus, and herpes simplex) infections may mimic metastatic disease from extracranial neoplasms in children.

Intracranial Hemorrhage

Aging of hematoma may mimic tumors on imaging especially in subacute and chronic stage which shows central clot retraction and peripheral enhancement with/without surrounding edema on CT and MRI. MRI sequences like SWI for blood products, DWI and MRS, are especially helpful. An underlying vascular malformation is better studied with MRI angiography or CT angiogram than routine sequences.[26]

Ischemic Stroke

Ischemic arterial or venous stroke may mimic tumor on imaging. A diagnostic dilemma arises typically when imaging shows mass effects and/or irregular contrast enhancements, advanced MRI sequences like DWI and perfusion MRI can throw further light. As a general rule, if the edema shows restricted diffusion, then tumoral edema is the culprit. However, clinical history and knowledge of arterial and venous territory involved are the basis for an accurate diagnosis.

Neurocutaneous Syndromes

Neurofibromatosis (NF), tuberous sclerosis(TS), Sturge-Weber syndrome, Von-Hippel Lindau (VHL) and hereditary telangiectasia are well-known syndromes with central nervous system (CNS) manifestations that are non-neoplastic. These syndromes are known to predispose to specific types of brain tumors. For example, NF-1 could be associated with low-grade gliomas. TS may be associated with SEGA (subependymal giant cell astrocytomas) and hemangioblastomas  are seen in VHL. Physicians may find it challenging to differentiate between the non-neoplastic NF-related myelin vacuolation spots and low-grade glioma in settings of NF-1. Cortical and subcortical T2 hyperintense tubers in tuberous sclerosis may mimic gliomas.

Prognosis

Congenital brain tumors have a poor prognosis with an overall survival of less than 30%.[8] Several factors such as malignant histological type, size, and location of the tumor, stage of fetal development, and treatment-related complications play a significant role in survival outcome.[27]

Complications

Complications vary with type, site of tumor and treatment protocol with acute and long-term complications.

Deterrence and Patient Education

Team work is key in successful management of brain tumors.  Full and detailed education of families and involvement in the decision-making process as appropriate is of paramount value. The treatment protocols are usually discussed at multidisciplinary meetings to explore the best treatment options available and the expected prognosis of the patient. Support and counseling to the family during treatment makes a big difference. Genetic testing and profiling are offered sometimes for the families to help in prognosis and family counseling.

Enhancing Healthcare Team Outcomes

Early detection of brain tumors is of paramount importance on the outcome. Knowledge of the signs and symptoms and keeping this possibility in the differential diagnosis and work-up is vital. This usually starts with the pediatrician, nurse practitioner, and family physician or emergency department physician. Neurosurgeons are the major pillars of care in most cases, and there is usually a collaborative role with interprofessional teams including oncology, diagnostic imaging, pathology, radiotherapy, nursing, rehabilitation, and social workers.