Childhood Primary Brain Tumors Notes

NOTES NOTES CHILDHOOD PRIMARY BRAIN TUMORS GENERALLY, WHAT ARE THEY? PATHOLOGY & CAUSES ▪ Most common solid tumor in children < 15 years old ▪ 20% of all childhood cancer ▪ Most pediatric brain, spinal cord tumors are primary tumors; originate from central nervous system (CNS) cells ▪ Most common types ▫ Astrocytomas, medulloblastomas, ependymomas, brainstem gliomas ▪ Better prognosis (generally) than adult brain tumors RISK FACTORS ▪ Biologically-male > biologically-female individuals ▪ Varies with tumor type COMPLICATIONS ▪ Dependent on tumor type, location, grade, child’s age ▪ Dependent on size, location, malignant potential of tumor; lesion’s mass effect → complications ▫ Increased intracranial pressure (ICP) → headache, nausea, vomiting ▫ Vision, balance, gait disturbance (common) ▫ May be mental changes, normal growth/ development disturbance 526 OSMOSIS.ORG SIGNS & SYMPTOMS ▪ May be subtle (slow-onset)/progress quickly ▪ Headache, nausea/vomiting ▫ Morning often worse (waking up) ▫ Cough, exercise, body-position change may exacerbate headache ▪ Mental change ▫ Personality/behaviour change, concentration difficulty ▪ Other associated symptoms ▫ Balance/gait disturbance; visual disturbance/loss; hearing/speech difficulty; weakness; numbness DIAGNOSIS DIAGNOSTIC IMAGING CT scan/MRI ▪ Head ▫ Identify lesion’s size, location LAB RESULTS Biopsy ▪ Open surgery/stereotactic biopsy (definitive diagnostic tool) ▪ Determine type, stage, grade ▫ Grade: degree of differentiation (tumor cells) ▫ Stage: extent of spread (tumors cells)

Chapter 67 Childhood Primary Brain Tumors Lumbar puncture ▪ Cerebrospinal fluid (CSF) analysis → malignant cell detection OTHER DIAGNOSTICS ▪ Visual field examination ▫ ↑ ICP → mass effect/swelling → detect central/peripheral vision defects ▪ Childhood primary brain tumor grades ▫ Based on World Health Organization (WHO) grading system (see table) TREATMENT ▪ Depends on tumor size/location, child’s age ▪ Goals ▫ Eliminate tumor, relieve symptoms, restore brain function MEDICATIONS ▪ Chemotherapy ▫ Residual tumor/metastasis ▪ Corticosteroids, diuretics ▫ Reduce swelling, alleviate associated ↑ ICP symptoms ▪ Pain management SURGERY ▪ Resection OTHER INTERVENTIONS ▪ Radiation ▫ Residual tumor/metastasis OSMOSIS.ORG 527

CRANIOPHARYNGIOMA osms.it/craniopharyngioma PATHOLOGY & CAUSES ▪ Rare benign non-glial epithelial CNS tumor ▫ Often within sellar/suprasellar space ▪ Hypothesis ▫ Derived from Rathke’s cleft/squamous cell crests along craniopharyngeal duct ▪ Gross pathology ▫ Cholesterol crystals in “motor oil”-like fluid within tumor, homogeneous TYPES DIAGNOSIS DIAGNOSTIC IMAGING CT scan/MRI ▪ Mass visualization ▪ Other common findings ▫ Suprasellar region calcification, one/ more supra/parasellar region cysts Histopathology ▪ Cysts with stratified squamous epithelium, cholesterol crystals, keratin pearls ▪ Adamantinomatous ▫ Primarily children, often single/multiple cysts ▪ Papillary ▫ Adults (almost exclusively), solid lesions RISK FACTORS ▪ Bimodal age distribution ▫ 5–14 years old (children), 50–70 years old (adults) COMPLICATIONS ▪ Hypopituitarism, hydrocephalus, ↑ ICP SIGNS & SYMPTOMS ▪ Headache, nausea, vomiting ▪ Visual disturbance/loss (i.e. bitemporal hemianopia) ▪ Endocrine abnormality ▫ Affects growth, thyroid/adrenal function, diabetes insipidus ▪ Behavioral change (ie. hypersomnia) 528 OSMOSIS.ORG Figure 67.1 An MRI scan of the head in the sagittal plane demonstrating a craniopharyngioma, adamantinomatous subtype. The tumor has clear solid and cystic components with abundant calcification.

Chapter 67 Childhood Primary Brain Tumors TREATMENT MEDICATIONS ▪ Endocrine replacement therapy: specific endocrine deficiency-dependent SURGERY ▪ Resection OTHER INTERVENTIONS ▪ Radiotherapy Figure 67.2 A histological section of a craniopharyngioma, adamantinomatous type. The tumor is composed of cystic spaces, calcifications and keratin. EPENDYMOMA osms.it/ependymoma PATHOLOGY & CAUSES ▪ Uncommon glial tumor ▫ Arises from ependymal cells lining ventricular system, spinal cord’s center ▪ Located intracranially (children), within spinal canal (adults) ▪ Often form ependymal pseudorosettes ▫ Tumor cells arranged around vessels, fibrils pointing towards vessel TYPES ▪ Five subtypes: WHO grade classification ▫ Subependymoma: grade I ▫ Myxopapillary ependymoma: grade I ▫ Ependymoma: grade II ▫ RELA fusion–positive ependymoma: grade II/grade III (with RELA gene change) ▫ Anaplastic ependymoma: grade III RISK FACTORS ▪ Neurofibromatosis type II (NF2)-diagnosed individuals (more common) COMPLICATIONS ▪ Fourth ventricle blockage → hydrocephalus → headache, nausea, vomiting ▪ Tumor mass effect SIGNS & SYMPTOMS ▪ Headache, visual disturbance/loss, nausea, vomiting, ataxia (gait, balance disturbance), vertigo, papilledema, cranial-nerve palsy, seizure/focal neurologic deficit, back pain, limb numbness/weakness OSMOSIS.ORG 529

DIAGNOSIS TREATMENT DIAGNOSTIC IMAGING MEDICATIONS CT scan ▪ Hyperdense with enhancement, commonly see cysts, calcifications SURGERY MRI ▪ Hypointense lesion, extension into Luschka foramen may be seen ▪ Chemotherapy ▪ Resection OTHER INTERVENTIONS ▪ Adjuvant radiotherapy LAB RESULTS Histological examination ▪ Cells with round/oval nuclei, dense fibrils forming canal structure ▪ Perivascular pseudorosettes ▫ Cells arranged around vessels with thin ependymal processes directed inwards ▪ Immunohistochemical markers include glial fibrillary acid protein, epithelial membrane antigen CSF cytology ▪ Guides tumor staging Figure 67.4 An MRI scan of the head of a child demonstrating an ependymoma in the posterior fossa, compressing the cerebellum. 530 OSMOSIS.ORG Figure 67.3 The histological appearance of an ependymoma. The tumor is composes of monomorphic cells which form ependymal rosettes, with a central clearing.

Chapter 67 Childhood Primary Brain Tumors MEDULLOBLASTOMA osms.it/medulloblastoma PATHOLOGY & CAUSES ▪ Most common pediatric malignant primary brain tumor ▫ Arises from cerebellum’s primitive neuroepithelial cells ▪ Usually forms midline mass along roof of fourth ventricle (between brainstem/ cerebellum) ▪ WHO grade IV classification TYPES ▪ Categorized as desmoplastic, classic, largecell, anaplastic, variants ▪ Gene expression profiling recognizes four molecular subgroups Wingless (WNT) ▪ Excellent prognosis ▪ 1:1 biologically male/biologically female ratio ▪ 10–12 years old (peak incidence) ▪ Classic histology (majority) ▪ Often CTNNB1 gene (encodes betacatenin) mutation Sonic Hedgehog (SHH) ▪ Intermediate prognosis ▪ 1:1 biologically male/biologically female ratio ▪ Infants < four years old, adults > 16 years old ▪ Classic, large-cell, anaplastic, desmoplastic, with extensive nodularity Group 3 ▪ Poor prognosis ▪ 2:1 biologically male/biologically female ratio ▪ 4–16 years old ▪ Classic/large-cell anaplastic histology, associated with Myc amplification, poorly-defined lesions (better contrast enhancement than group 4 lesions) Group 4 ▪ Poor prognosis ▪ 2:1 biologically male/biologically female ratio ▪ 4–16 years old ▪ Classic histology, well-defined lesions (limited contrast enhancement) RISK FACTORS ▪ 2:1 biologically male/biologically female ratio ▪ 3–8 years old ▪ Certain inherited familial syndromes ▫ Ataxia-telangiectasia, Rubinstein–Taybi syndrome, Gorlin syndrome, Turcot’s syndrome, Li–Fraumeni syndrome COMPLICATIONS ▪ Frequent metastasis → other brain, spinal cord parts ▪ Fourth ventricle blockage → hydrocephalus → headache, nausea, vomiting ▪ Tumor’s mass effect SIGNS & SYMPTOMS ▪ Headache; nausea; vomiting; ataxia (gait/ balance disturbance), falls; diplopia; papilledema; positional dizziness, nystagmus; bulging anterior fontanelle; visual disturbance/loss DIAGNOSIS DIAGNOSTIC IMAGING CT scan ▪ Often appear as vermis mass → fourth ventricle effacement → obstructive hydrocephalus ▪ Hyperdense, +/- cysts, +/- calcifications OSMOSIS.ORG 531

MRI ▪ Heterogeneous mass; calcification, necrosis, cyst formation ▪ May see surrounding edema LAB RESULTS Histological examination ▪ Variable cellular atypia ▪ Homer Wright rosette; dark tumor cells spherically arranged around pale eosinophilic neurofibrils ▪ INI1-positive (tumor suppressor gene marker) Lumbar puncture ▪ CSF analysis ▫ Malignant cell detection TREATMENT Figure 67.5 An MRI scan of a child in the sagittal plane demonstrating a medulloblastoma. In childhood, they commonly arise in the posterior fossa at the roof of the fourth ventricle. MEDICATIONS ▪ Chemotherapy SURGERY ▪ Tumor resection OTHER INTERVENTIONS ▪ Radiotherapy Figure 67.6 A medulloblastoma forming Homer–Wright rosettes, with no central clearing. 532 OSMOSIS.ORG

Chapter 67 Childhood Primary Brain Tumors PILOCYTIC ASTROCYTOMA osms.it/pilocytic-astrocytoma PATHOLOGY & CAUSES ▪ Primary tumor ▫ Arises from astrocytes ▫ AKA juvenile pilocytic astrocytoma/ cystic cerebellar astrocytoma ▪ Mainly occurs in children (majority 0–30 years old) ▪ Often arises in cerebellum, hypothalamic region, along optic pathway ▪ Tumors slow growing, benign (WHO grade I) ▪ Associated with cyst formation, often wellcircumscribed ▪ Strong neurofibromatosis type I (NF-1) association ▪ Microscopic appearance ▫ Elongated hair-like projections, Rosenthal fibers (characteristic feature) ▪ Spectroscopy/perfusion MRI head ▫ Determines tumor grade LAB RESULTS Biopsy ▪ Mass ▫ Heterogeneous/homogeneous/mixed; cystic; solid; with/without hemorrhage, necrosis OTHER DIAGNOSTICS ▪ Ophthalmological evaluation/visual field testing ▫ May detect visual field deficit SIGNS & SYMPTOMS ▪ Altered mental status; headache, nausea, vomiting; gait disturbance, ataxia; weakness; seizure; visual disturbance, nystagmus, papilloedema; aphasia/ dysphasia DIAGNOSIS DIAGNOSTIC IMAGING CT scan ▪ Lesion (hypodense), calcification/ hemorrhage area (hyperdense) MRI (head) ▪ Range of appearances ▫ Cystic component(s) with mural nodule (enhancing, nonenhancing cyst wall); heterogeneous, mixed solid; homogeneous solid Figure 67.7 A brain biopsy smear from a pilocytic astrocytoma demonstrating malignant astrocytes with pleomorphic, hyperchromatic nuclei. In addition there is an eosinophilic granular body, commonly seen in such tumors. TREATMENT MEDICATIONS ▪ Chemotherapy OSMOSIS.ORG 533

SURGERY ▪ Resection (location often prohibits total resection) OTHER INTERVENTIONS ▪ Radiotherapy ▪ Observation (when asymptomatic) Figure 67.8 The histological appearance of a pilocytic astrocytoma. There are bipolar neoplastic cells arranged in fascicles with elongated hair-like processes. PINEALOMA osms.it/pinealoma PATHOLOGY & CAUSES ▪ Rare tumor that arises from cells in the pineal region ▪ May result in endocrine disruption, obstructive hydrocephalus, and compression of adjacent structures (cerebellum, brainstem) ▪ Occurs any age; malignancy more common in children (< eight years old) TYPES ▪ Four pinealoma types ▫ Germ cell tumors ▫ Papillary tumors ▫ Pineal parenchymal cell tumors ▫ Glial cell tumors ▪ Other miscellaneous tumors and cysts in the pineal region RISK FACTORS ▪ RB1 gene inheritance ▪ Previous radiation exposure 534 OSMOSIS.ORG COMPLICATIONS ▪ Precocious puberty ▫ Homeostatic hypothalamic-pituitary axis disruption → puberty onset in biologically-male individuals (< nine years old), biologically-female individuals (< eight years old) ▫ ↓ melatonin production (may result) → impaired circadian rhythm regulation ▪ Physical ventricular system obstruction → ↑ ICP → hydrocephalus SIGNS & SYMPTOMS ▪ Parinaud’s syndrome (upward gaze paralysis, pupillary areflexia), pseudo-Argyll Robertson pupils, convergence-retraction nystagmus, eyelid reaction (Collier’s sign) ▪ Headache; nausea; vomiting; visual, balance, gait disturbance; fatigue/ irritability; insomnia

Chapter 67 Childhood Primary Brain Tumors DIAGNOSIS DIAGNOSTIC IMAGING Head CT scan/MRI ▪ May appear cystic/partially cystic ▪ Often lobulated, seen as heterogeneous mass ▪ Usually 2.5–4 cm/1–1.6in wide, well circumscribed in pineal region; contrastenhanced rim in cystic forms TREATMENT SURGERY ▪ Resection +/- shunt (drain excess CSF) OTHER INTERVENTIONS ▪ Adjuvant radiotherapy (malignant tumors) LAB RESULTS ▪ Hormonal evaluation ▫ Melatonin (indicates pineal gland pathology) ▪ Lumbar puncture ▫ CSF analysis for detection of malignant cells ▫ α-fetoprotein/β-HCG tumor markers indicate germinal origin ▪ Biopsy ▫ Determines type, stage; open surgery/ stereotactic biopsy OTHER DIAGNOSTICS ▪ Visual field examination ▫ Defect detection: central, peripheral vision; swelling around optic nerve (↑ ICP sign) OSMOSIS.ORG 535