Pediatric Neurosurgical Neuropathology Brain tumors are second only to leukemias in children Brain tumors are the most common solid organ tumor in children 70% of pediatric brain tumors are in the posterior fossa Pilocytic astrocytoma Medulloblastoma Ependymoma

CNS tumors: pediatric vs. adult Adults: 70% of tumors are supratentorial meningioma pituitary adenoma High grade astrocytoma Anaplastic astrocytoma (grade III) Glioblastoma multiforme (grade IV astrocytoma) Pediatric: 70% in posterior fossa pilocytic astrocytoma (cerebellar astrocytoma) medulloblastoma

Brain tumors: intro Intracranial neoplasms Tumors of the spinal cord Primary Secondary Metastatic Local invasion Tumors of the spinal cord

Primary brain tumors: intro Primary brain tumors are rare 2.5% of all cancer deaths Second most common type of tumor in children There are over 100 different brain tumors Most common types Astrocytomas Grades I-IV Medulloblastomas primitive neuroectodermal tumor-PNET Meningiomas Pituitary adenomas

Clinical presentation Clinical symptoms depend upon: Age, location, and type of tumor and grade Symptoms may include: Increased intracranial pressure secondary to obstruction of CSF at aqueduct hydrocephalus (infants), headache, papilledema, vomiting seizures focal neurological deficits hormonal changes (pituitary adenoma) visual changes (diplopia, field defects) Pituitary adenoma - pressure on optic chiasm

CNS tumors: diagnosis Symptoms prompt neuroimaging CT and MRI intra-axial vs. extra-axial Location of tumor contrast enhancement typical of high grade also in some low grade, i.e., pilocytic astrocytomas

CNS tumors: location Extra-axial Cerebral hemispheres meningiomas Cerebral hemispheres grade II-III astrocytomas, GBM Crossing corpus callosum - GBM optic nerve - pilocytic astrocytoma (NF-1) Sella - Pituitary adenoma Peri-III ventricle - Pilocytic astrocytoma, GBM

CNS tumors: location posterior fossa (in children) brainstem (pons) pilocytic astrocytoma medulloblastoma brainstem (pons) pontine glioma (astrocytoma) spinal cord low-grade astrocytomas (grade I and II)

Pilocytic astrocytomas Most common in children Grade I astrocytoma Cerebellum (posterior fossa), optic nerve Thalamic, spinal cord, cerebral Discrete, well circumscribed mass Often with associated cystic area Contrast enhancing Histologic appearance: Biphasic: piloid cells and microcystic areas Rosenthal fibers no mitoses

Pilocytic astrocytomas Tumor of cerebellum, often with cyst, biphasic, Rosenthal fibers, piloid cells

Astrocytoma - high grade Astrocytoma grade II and III are very, very rare in the pediatric population Grade IV - glioblastoma multiforme Diffusely infiltrating glial tumor of cerebral hemispheres Contrast enhancing tumor Histological appearance: Densely cellular, with marked nuclear pleomorphism Numerous mitoses Endothelial proliferation Necrosis with pseudopallisading

Glioblastoma (grade IV) Less common in children than adults, typical pathology (necrosis with psuedopallisading)

Pontine glioma Diffuse expansion of pons, usually high grade astrocytoma (III-IV)

Medulloblastomas PNET of posterior fossa in children Histologic appearance: Densely cellular “small blue cell tumor” Numerous mitoses Apoptotic (karyorrhectic) cells Endothelial proliferation Necrosis neuronal or glial differentiation Homer Wright rosettes GFAP positive cells

Medulloblastoma Mass arising in roof of fourth ventricle Homer Wright rosettes

Ependymoma Mass arising in floor of fourth ventricle Perivascular pseudorosettes

Meningiomas Discrete non-invasive tumor Histologic appearance: Extra-axial, pushes into brain Attached to dura Hyperostosis or invasion of skull common Histologic appearance: Fibroblastic or menigothelial cells Meningothelial whorls Psammoma bodies Rare in children, may be intraventricular (lateral ventricles)

Meningiomas Extra-axial tumor, meningothelial cells, whorls and psammoma bodies

Ganglioglioma Cerebrum, cervicomedullary, often with cystic component Increased numbers of neurons (some binucleate) and increased glial cells (usually astrocytic)

Craniopharyngioma Heterogeneous, cystic mass in suprasellar region Basiloid layer, stellate reticulum, “wet” keratin, often calcified

Choroid plexus papilloma Lateral ventricle in children (fourth ventricle in adults)

Germ cell tumors Germinoma Teratoma Pineal - 99% males, most are germinomas Suprasellar - often mixed germ cell tumor, 50% female Tertomas are rare

Metastatic tumors The most common “brain” tumor in adults is metastatic Metastatic tumors are rare in children The most common metastatic tumor in children is osteosarcoma Local extension of malignant tumors of vertebral bodies (Ewing’s sarcoma) or paravertebral soft tissues (neuroblastoma) are not uncommon

Other tumors Subependymal giant cell astrocytoma (SEGA) Intraventricular tumor in Tuberous sclerosis Desmoplastic infantile ganglioglioma (DIG) Superficial cerebral tumor in infants Dysembryoplastic neuroepithelial tumor (DNET) Hamartomatous lesion associated with seizures Atypical teratoid rhabdoid tumor (ATR, AT/RT) Infants, posterior fossa, very malignant Eosinophilic granuloma A type of Langerhans cell histiocytosis Single discrete osteolytic lesion in skull Meningioangiomatosis Hamartomatous superficial cerebral lesion associated with seizures

Hereditary syndromes Neurofibromatosis type I Café-au-lait spots Dermatofibromas, multiple optic nerve gliomas, bilateral plexiform neurofibroma Malignant peripheral nerve sheath tumor Neurofibromatosis type II bilateral acoustic neuroma multiple meningiomas ependymomas