• Imaging findings of various pediatric brain tumors with pathological correlation

• Pediatric brain tumors associated with various genetic syndromes

• Overview of molecular biology, genetics and future targeted treatment of pediatric brain tumors

Imaging, pathology and molecular biology of pediatric brain tumors Neuroradiologists, Neuroscientists Pediatric brain tumors are a leading cause of cancer-related death in children. In recent years, new technologies of molecular and genetic analysis of pediatric brain tumors have provided abundance of biological information. This has resulted in refining tumor classification into clinically relevant subgroups with potential clinical implications and future treatment. This lecture demonstrates imaging findings, pathologies and associated genetic syndromes of various pediatric brain tumors with an overview of molecular biology, genetics and future targeted treatment of pediatric brain tumors.The purpose of this lecture is to demonstrate imaging findings and pathology of pediatric brain tumors and associated genetic syndrome, and an overview of the recent developments in molecular biology and genetics. This knowledge is important not only for the diagnosis of pediatric brain tumors but also for management and future treatment. Therefore, it is useful for guiding future research of pediatric brain tumors.

• Review recent publications

• Demonstrate imaging findings and pathology of various pediatric brain tumors

• Give an overview of genetic and molecular biology

CT and MRI findings of various pediatric brain tumors are demonstrated with an emphasis on diffusion-weighted imaging and the ADC map. The imaging findings are discussed in correlation with the pathology and associated genetic syndromes. The pediatric brain tumors and genetic syndromes in this lecture include pilocytic/pilomyxoid astrocytoma with neurofibromatosis type 1 (NF1), subependymal giant cell astrocytoma with tuberous sclerosis, pleomorphic xanthoastrocytoma, diffuse astrocytoma, anaplastic astrocytoma, glioblastoma, ganglioglioma, oligodendroglioma, ependymoma, choroid plexus papilloma, atypical choroid plexus papilloma, choroid plexus carcinoma, dysplastic gangliocytoma of cerebellum (Lhermitte-Duclos) with Cowden disease, desmoplastic infantile ganglioglioma (DIG), pineocytoma, pineoblastoma, papillary tumor of the pineal region (PTPR), medulloblastoma with Gorlin syndrome, or Turcot syndrome, CNS primitive neuroectodermal tumor (PNET), atypical teratoid/rhabdoid tumor (ATRT), embryonal tumors with abundant neuropil and true rosettes (ETANTR), meningioma with Gorlin syndrome or ataxia telangiectasia, craniopharyngioma and teratoma.

This lecture provides an overview of recent molecular biology, genetics and future targeted therapy of pediatric brain tumors in correlation with imaging and pathologic findings. Low grade gliomas account for half of all pediatric brain tumors. Pilocytic astrocytoma is often seen in the cerebellum and ganglioglioma in the temporal lobe. NF1-associated low grade gliomas affect the optic pathway or brainstem. Pediatric low grade gliomas rarely display IDH or TP53 mutations or 1p/19q loss but are defined by mitogen-activated protein kinase (MAPK) pathway activation. BRAFV600E activating point mutation is prevalent in ganglioglioma and pleomorphic xanthoastrocytoma. BRAF inhibitors, such as vemurafenib and dabrafinib have been tested in BRAF-mutant pediatric tumors. Medulloblastomas are the second common type of pediatric brain tumors and reveal the marked genetic heterogeneity including four unique molecular subgroups (Wnt, SHH, group C, group D). Desmoplastic medulloblastoma is predominantly seen in SHH tumors, whereas large cell or anaplastic medulloblastoma is found in group C and D tumors. Wnt tumors show the most favorable prognosis and primarily consisted of classic medulloblastoma, whereas group C tumors have the worse prognosis composed mostly of classic, large cell and anaplastic medulloblastomas. The large cell or anaplastic subtype is associated with increased ADC with ring enhancement and tumor necrosis. Increased understanding of the molecular biology of meduloblastoma has not yet manifested in more effective therapies. High-grade gliomas (anaplastic astrocytoma and glioblastoma) account for 15–20 % of pediatric brain tumors. EZH2 inhibitors harboring mutations of chromatin remodeling genes show promise for the treatment of high-grade glioma. Ependymoma accounts for 8 to 10 % of pediatric brain tumors. 90 % of ependymoma in children arise intracranially and two thirds in the posterior fossa. Ependymoma is classified into two subgroups (Group A and B). Recent data indicate that EZH2 inhibitors hold promise in treatment of Group A ependymoma. ATRT is a highly aggressive embryonal tumor that accounts for 1–2 % of pediatric brain tumors. ATRT commonly presents infratentorially in infants and young children and supratentorially in those aged 6–18 years. Germline mutation of SMARCB1 is associated with worse outcome. The most promising targeted agents are Aurora A kinase inhibitors and EZH2 inhibitors.

Diagnostic imaging findings of pediatric brain tumors correlated with pathology, molecular biology and genetics are important not only for the diagnosis but also for patient’s management and treatment as well as for guiding future research.