CNS Tumors
CNS Tumors
What Do You Need to Know?
- Most common brain tumor overall = metastasis; most common primary malignant brain tumor = glioblastoma (IDH-wildtype, grade 4); most common primary brain tumor (benign + malignant) = meningioma
- Most common pediatric brain tumor = pilocytic astrocytoma (grade 1, cerebellar, BRAF fusion, excellent prognosis); most common malignant pediatric brain tumor = medulloblastoma
- 2021 WHO CNS5 classification integrates molecular markers into tumor diagnosis — IDH mutation status, 1p/19q codeletion, H3K27M alteration, and MGMT methylation are now essential
- IDH mutation = better prognosis in diffuse gliomas; IDH-wildtype diffuse astrocytic tumor in adults is classified as glioblastoma regardless of histologic grade if molecular criteria are met
- 1p/19q codeletion defines oligodendroglioma and predicts chemosensitivity (PCV regimen); MGMT promoter methylation predicts temozolomide response in glioblastoma
- Hemorrhagic metastases mnemonic “MR CT”: Melanoma, Renal cell carcinoma, Choriocarcinoma, Thyroid — gray-white junction predilection
- Genetic syndromes: NF1 → optic glioma; NF2 → bilateral vestibular schwannomas + meningiomas; VHL → hemangioblastoma; TSC → SEGA
- Pseudopalisading necrosis + microvascular proliferation = glioblastoma; psammoma bodies = meningioma; Rosenthal fibers = pilocytic astrocytoma; Homer Wright rosettes = medulloblastoma
WHO Grading Overview
WHO CNS5 Classification (2021)
- The 5th edition of the WHO Classification of CNS Tumors fundamentally shifted from a purely histologic system to an integrated molecular-histologic approach
- Molecular markers are now required for accurate classification of many tumor types
- Key principle: tumors with identical histology but different molecular profiles are now classified as distinct entities with different prognoses and treatment responses
Grading System
| WHO Grade | Biologic Behavior | Examples |
|---|---|---|
| Grade 1 | Low proliferative potential; possible cure with surgery alone | Pilocytic astrocytoma, schwannoma, most meningiomas |
| Grade 2 | Infiltrative, low mitotic activity; tendency to recur and progress | Astrocytoma IDH-mutant (grade 2), oligodendroglioma (grade 2) |
| Grade 3 | Histologic evidence of malignancy (anaplasia, high mitotic activity) | Anaplastic astrocytoma IDH-mutant, anaplastic oligodendroglioma |
| Grade 4 | Highly malignant; rapid growth, necrosis, microvascular proliferation | Glioblastoma IDH-wildtype, diffuse midline glioma H3K27-altered, medulloblastoma |
IDH Mutation — The Central Dividing Line
- IDH-mutant gliomas: Younger patients (20s–40s), frontal lobe predilection, better prognosis, longer survival
- IDH-wildtype gliomas: Older patients (>55), aggressive behavior; diffuse astrocytic gliomas with IDH-wildtype status are classified as glioblastoma if they carry TERT promoter mutation, EGFR amplification, or +7/−10
- IDH1 R132H is the most common mutation (~90% of IDH-mutant gliomas) — detectable by immunohistochemistry
- IDH mutations produce 2-hydroxyglutarate (2-HG) — an oncometabolite detectable by MR spectroscopy
Board Pearl
IDH status is the single most important molecular marker in diffuse gliomas. IDH-mutant = better prognosis across all grades. Under WHO CNS5, a histologically low-grade diffuse astrocytic tumor that is IDH-wildtype is reclassified as glioblastoma (grade 4) if it has TERT promoter mutation, EGFR amplification, or +7/−10 chromosomal changes — regardless of the absence of necrosis or microvascular proliferation.
Adult Tumors — Diffuse Gliomas
Classification of Adult-Type Diffuse Gliomas
| Tumor | WHO Grade | Key Molecular Features | Histology | Prognosis |
|---|---|---|---|---|
| Astrocytoma, IDH-mutant | 2, 3, or 4 | IDH1/2 mutation, ATRX loss, TP53 mutation; NO 1p/19q codeletion | Diffusely infiltrating fibrillary astrocytes; anaplasia and necrosis in higher grades | Better than IDH-wildtype GBM; grade-dependent (median ~5–10 yrs grade 2; ~3–5 yrs grade 3; ~2–3 yrs grade 4) |
| Oligodendroglioma, IDH-mutant & 1p/19q-codeleted | 2 or 3 | IDH1/2 mutation + 1p/19q codeletion (both required); TERT promoter mutation common | “Fried egg” cells (perinuclear halo, artifact), chicken-wire vasculature, frequent calcifications | Best prognosis among diffuse gliomas; highly chemosensitive (PCV regimen); median survival >10–15 yrs |
| Glioblastoma, IDH-wildtype | 4 | IDH-wildtype; EGFR amplification, TERT promoter mutation, +7/−10 chromosome changes; MGMT methylation in ~40% | Pseudopalisading necrosis, microvascular proliferation (glomeruloid vessels); highly pleomorphic | Worst prognosis; median survival ~14–16 months with standard treatment (Stupp protocol: surgery + RT + temozolomide) |
| Diffuse midline glioma, H3K27-altered | 4 | H3K27M mutation (histone H3); IDH-wildtype | Diffusely infiltrating; variable histology | Very poor prognosis; median survival <1 year; includes DIPG (pediatric pontine), thalamic, and spinal cord gliomas |
Board Pearl
Oligodendroglioma requires BOTH IDH mutation AND 1p/19q codeletion for diagnosis under WHO CNS5. The 1p/19q codeletion results from an unbalanced translocation t(1;19)(q10;p10). If a tumor has IDH mutation but retains 1p/19q → it is an astrocytoma, IDH-mutant (check for ATRX loss and TP53 mutation). The presence of 1p/19q codeletion predicts excellent response to PCV chemotherapy (procarbazine, CCNU/lomustine, vincristine).
Glioblastoma — Key Details
- Most common malignant primary brain tumor in adults (~50% of all gliomas)
- Demographics: Peak age 55–70 years; male predominance (M:F ~1.6:1)
- Location: Hemispheric white matter; frontal and temporal lobes most common; can cross corpus callosum → “butterfly glioma”
- Imaging: Ring-enhancing mass with central necrosis, irregular borders, surrounding edema, mass effect
- MGMT promoter methylation: Present in ~40% of GBM; silences DNA repair enzyme → tumor cannot repair temozolomide-induced DNA damage → better response to temozolomide and improved survival
- Stupp protocol (standard of care): Maximal safe resection → concurrent radiation (60 Gy/30 fractions) + daily temozolomide → adjuvant temozolomide (6 cycles)
- Tumor treating fields (TTFields / Optune): Alternating electric fields disrupt mitosis; shown to improve survival when added to maintenance temozolomide
- Pseudoprogression: Transient increase in enhancement on MRI 2–6 months after chemoradiation (especially with MGMT methylation) — mimics tumor recurrence but is a treatment effect; do NOT change therapy prematurely
Clinical Pearl
Pseudoprogression vs. true progression in GBM: Pseudoprogression occurs in up to 30% of GBM patients (more common with MGMT methylation) at 2–6 months post-chemoradiation. MR perfusion (low rCBV) and MR spectroscopy (no elevated choline) can help distinguish from true recurrence. Updated RANO criteria require confirmation of progression on follow-up imaging or clinical deterioration. Premature treatment changes based on a single MRI can deprive patients of effective therapy.
Adult Tumors — Other Types
Non-Glial and Extra-Axial Tumors
| Tumor | Key Features | Histology / Markers | Associations |
|---|---|---|---|
| Meningioma | Most common extra-axial tumor; dura-based, well-circumscribed; most are WHO grade 1 (benign); “dural tail” sign on MRI; calcifications common; parasagittal, convexity, and sphenoid wing most common sites | Psammoma bodies (concentric calcified whorls); EMA+, vimentin+; whorled pattern of meningothelial cells | NF2 (merlin/schwannomin loss); chromosome 22q deletion; prior radiation; female predominance (hormonal receptors); progesterone-receptor positive |
| Schwannoma | Vestibular schwannoma (CN VIII) is most common; arises from Schwann cells; well-encapsulated; cerebellopontine angle mass | Antoni A (compact, palisading nuclei) + Antoni B (loose, myxoid); Verocay bodies (nuclear palisades); S100+ | NF2 → bilateral vestibular schwannomas (pathognomonic); sporadic cases are unilateral |
| Primary CNS Lymphoma (PCNSL) | Diffuse large B-cell lymphoma (DLBCL); periventricular location; homogeneous enhancement; “ghost tumor” (melts away with steroids, then recurs); multifocal in 50% | B-cell markers (CD20+, CD79a+); perivascular cuffing (angiocentric growth); high Ki-67 | EBV-associated in immunocompromised (HIV/AIDS, transplant); avoid steroids before biopsy (can cause false-negative); treat with high-dose methotrexate-based regimen, NOT whole-brain RT alone |
| Hemangioblastoma | Highly vascular; cerebellar (most common posterior fossa tumor in adults); cystic with vividly enhancing mural nodule | Stromal cells with lipid-laden vacuoles; rich capillary network; not a metastatic tumor | VHL syndrome (chromosome 3p deletion); can produce EPO → secondary polycythemia; also retinal angiomas, pheochromocytoma, renal cell carcinoma |
| Pituitary adenoma | Most common sellar mass; functional (hormone-secreting) vs. nonfunctional; macroadenoma (>1 cm) can compress optic chiasm → bitemporal hemianopia | Uniform cells; immunohistochemistry for hormones (prolactin, GH, ACTH, etc.) | Prolactinoma = most common functional type (treat with dopamine agonists: cabergoline, bromocriptine); pituitary apoplexy = acute hemorrhage into adenoma → sudden headache, visual loss, hypopituitarism |
Board Pearl
PCNSL “ghost tumor”: Steroids cause rapid lympholysis → dramatic shrinkage of enhancement on MRI. This is why steroids must be withheld before biopsy whenever possible — administering steroids can render the biopsy non-diagnostic. If steroids were already given, wait for the tumor to regrow before biopsy. PCNSL is treated with high-dose IV methotrexate-based chemotherapy, NOT standard CHOP (cannot cross BBB effectively).
Pediatric Tumors
Overview
- Brain tumors are the most common solid tumors in children and the leading cause of cancer-related death in pediatrics
- Posterior fossa tumors predominate in children (unlike adults where supratentorial tumors are more common)
- Key posterior fossa tumors: pilocytic astrocytoma (cerebellum), medulloblastoma (4th ventricle), ependymoma (4th ventricle)
Major Pediatric Brain Tumors
| Tumor | Grade | Location / Features | Histology / Molecular | Prognosis |
|---|---|---|---|---|
| Pilocytic astrocytoma | 1 | Most common pediatric brain tumor; cerebellum (most common), optic pathway; cystic with enhancing mural nodule | Rosenthal fibers (corkscrew eosinophilic fibers), eosinophilic granular bodies; biphasic (compact + loose); BRAF-KIAA1549 fusion | Excellent (>95% 10-year survival); surgical cure often possible |
| Medulloblastoma | 4 | Most common malignant pediatric brain tumor; posterior fossa / 4th ventricle (midline); drop metastases via CSF (requires craniospinal MRI and CSF cytology for staging) | Homer Wright rosettes (tumor cells around central neuropil); small round blue cells; synaptophysin+ | Molecular subgroup-dependent (see below) |
| Ependymoma | 2–3 | 4th ventricle (posterior fossa most common in children); can cause obstructive hydrocephalus; tends to extend through foramina of Luschka/Magendie | Perivascular pseudorosettes (GFAP+ processes radiating around vessels — most characteristic); true ependymal rosettes (less common); ZFTA-RELA fusion in supratentorial type | Depends on extent of resection and molecular subtype; gross total resection improves outcomes |
| Craniopharyngioma | 1 | Suprasellar; arises from Rathke pouch remnants; can compress chiasm → bitemporal hemianopia; can cause hypothalamic dysfunction and panhypopituitarism | Adamantinomatous (children): calcifications, “motor oil” cyst fluid, wet keratin, CTNNB1 (β-catenin) mutation Papillary (adults): rarely calcifies, solid, BRAF V600E mutation |
Benign but locally aggressive; recurrence common after incomplete resection; significant endocrine morbidity |
| ATRT (Atypical Teratoid/Rhabdoid Tumor) | 4 | Age <3 years; posterior fossa most common; highly aggressive; can mimic medulloblastoma on imaging | INI1 (SMARCB1) loss on immunohistochemistry (diagnostic); rhabdoid cells with eccentric nuclei | Very poor (median survival <1 year without aggressive multimodal therapy) |
| Diffuse midline glioma (DIPG) | 4 | Pontine (classic DIPG); also thalamic, spinal cord; diffusely expands the pons; diagnosed clinically + MRI (biopsy historically not required) | H3K27M mutation; now classified as diffuse midline glioma, H3K27-altered | Dismal; median survival ~9–11 months; radiation provides temporary improvement; no effective chemotherapy to date |
Medulloblastoma Molecular Subgroups
| Subgroup | Key Features | Prognosis |
|---|---|---|
| WNT-activated | ~10% of cases; monosomy 6; nuclear β-catenin; often older children; rarely metastatic | Best prognosis (>90% 5-year survival); clinical trials exploring treatment de-escalation |
| SHH-activated | Sonic hedgehog pathway; bimodal age (infants and adults); lateral cerebellar (hemispheric); PTCH1, SMO, SUFU mutations | Intermediate; targeted therapies (vismodegib/sonidegib) for SHH-driven tumors; TP53 mutation within SHH subgroup confers very poor prognosis |
| Group 3 | MYC amplification common; predominantly male infants/children; frequently metastatic at diagnosis | Worst prognosis (~50% 5-year survival); high rate of leptomeningeal dissemination |
| Group 4 | Most common subgroup (~35%); isochromosome 17q; male predominance | Intermediate prognosis |
Board Pearl
Medulloblastoma molecular subgroups for boards: WNT = best prognosis (monosomy 6, nuclear β-catenin). Group 3 = worst prognosis (MYC amplification, disseminated disease). SHH = targetable with hedgehog pathway inhibitors (vismodegib). Always stage medulloblastoma with craniospinal MRI + CSF cytology because of high risk of drop metastases through the CSF (leptomeningeal spread).
Metastatic Brain Tumors
Overview
- Most common brain tumor overall — outnumber primary brain tumors ~10:1
- Occur in 20–40% of systemic cancer patients
- Predilection for the gray-white matter junction (watershed zone where blood vessels narrow, trapping embolic tumor cells)
- Usually well-circumscribed, round, multiple; surrounded by vasogenic edema disproportionate to tumor size
Primary Sources (by Frequency)
- Lung — #1 source overall (~40–50%); both small cell and non-small cell
- Breast — #2 overall; HER2+ and triple-negative subtypes have highest CNS tropism
- Melanoma — highest per-capita propensity to metastasize to the brain; frequently hemorrhagic
- Renal cell carcinoma — hypervascular, hemorrhagic; can present as solitary metastasis years after nephrectomy
- Colorectal — less common but increasing with improved systemic disease control
Hemorrhagic Metastases
- Mnemonic: “MR CT”
- Melanoma
- Renal cell carcinoma
- Choriocarcinoma
- Thyroid carcinoma
- Hemorrhagic brain metastasis can be the presenting manifestation of occult systemic malignancy
- Any lobar hemorrhage in a cancer patient → consider hemorrhagic metastasis
Leptomeningeal Carcinomatosis (Leptomeningeal Metastasis)
- Tumor cells disseminate through the CSF and coat the leptomeninges
- Most common primaries: breast, lung, melanoma, hematologic malignancies
- Presentation: Multifocal cranial neuropathies, radiculopathies, headache, communicating hydrocephalus, cognitive decline
- Diagnosis: CSF cytology (may need repeated LPs; sensitivity ~50% on first tap, ~80% with three taps); MRI with gadolinium shows leptomeningeal enhancement
- Prognosis: Very poor (median survival 6–8 weeks untreated; 3–6 months with treatment)
Clinical Pearl
Solitary brain metastasis vs. solitary cerebral metastasis: “Solitary” means the brain lesion is the only known site of metastatic disease (including no other extracranial metastases). “Single” means one brain lesion but may have other systemic metastases. This distinction matters because a truly solitary brain metastasis may benefit from surgical resection followed by radiation, with potentially longer survival.
Board Pearl
Gray-white junction predilection of brain metastases: Tumor emboli travel through progressively smaller arteries and become trapped at the gray-white junction where vessel caliber narrows. Multiple ring-enhancing lesions at the gray-white junction with surrounding edema in a cancer patient = metastatic disease until proven otherwise. Melanoma has the highest per-capita brain metastasis rate but lung cancer causes the most brain metastases overall due to higher incidence.
Molecular Markers Summary
Key Molecular Markers in CNS Tumors
| Marker | Associated Tumor(s) | Clinical Significance |
|---|---|---|
| IDH1/2 mutation | Astrocytoma, oligodendroglioma | Better prognosis in diffuse gliomas; IDH-wildtype in adults = glioblastoma (with additional molecular criteria) |
| 1p/19q codeletion | Oligodendroglioma (defining feature) | Required for oligodendroglioma diagnosis; predicts chemosensitivity (PCV); better prognosis |
| MGMT promoter methylation | Glioblastoma | Predicts temozolomide response; silences DNA repair → tumor cannot repair alkylating agent damage; improved survival |
| EGFR amplification | Glioblastoma IDH-wildtype | Common (~40%); EGFRvIII variant is a therapeutic target; diagnostic criterion for GBM if IDH-wildtype |
| BRAF V600E mutation | Pleomorphic xanthoastrocytoma, ganglioglioma, papillary craniopharyngioma | Targetable with BRAF inhibitors (vemurafenib, dabrafenib); also seen in some pilocytic astrocytomas |
| BRAF-KIAA1549 fusion | Pilocytic astrocytoma | Most common alteration in pilocytic astrocytoma; activates MAPK pathway; diagnostic marker |
| H3K27M mutation | Diffuse midline glioma | Defines the entity; grade 4 regardless of histology; very poor prognosis |
| INI1 (SMARCB1) loss | ATRT | Loss of INI1 expression on IHC is diagnostic; distinguishes ATRT from medulloblastoma in young children |
| TERT promoter mutation | Glioblastoma, oligodendroglioma | Telomerase activation → immortalization; diagnostic criterion for GBM (if IDH-wildtype); seen in both GBM and oligodendroglioma |
| Ki-67 / MIB-1 | All CNS tumors | Proliferation index; higher = more aggressive; supports grading but not diagnostic alone |
Genetic Syndromes & Associated Tumors
Tumor Predisposition Syndromes
| Syndrome | Gene / Chromosome | Inheritance | Associated CNS Tumors | Other Features |
|---|---|---|---|---|
| Neurofibromatosis Type 1 (NF1) | NF1 (17q11.2) — neurofibromin (RAS-GAP) | AD | Optic pathway glioma (pilocytic astrocytoma), brainstem glioma, other astrocytomas | Café-au-lait spots (≥6), neurofibromas, Lisch nodules, axillary/inguinal freckling, UBOs on MRI |
| Neurofibromatosis Type 2 (NF2) | NF2 (22q12) — merlin/schwannomin | AD | Bilateral vestibular schwannomas (hallmark), meningiomas (multiple), ependymomas | Posterior subcapsular cataracts; fewer skin lesions than NF1 |
| Von Hippel-Lindau (VHL) | VHL (3p25) — VHL protein (ubiquitin ligase) | AD | Hemangioblastoma (cerebellar, spinal, retinal) | Renal cell carcinoma (clear cell), pheochromocytoma, pancreatic cysts/NETs, EPO-producing hemangioblastoma → polycythemia |
| Tuberous Sclerosis Complex (TSC) | TSC1 (9q34, hamartin) or TSC2 (16p13, tuberin) — mTOR pathway | AD | Subependymal giant cell astrocytoma (SEGA) — near foramen of Monro → can cause hydrocephalus; treat with mTOR inhibitor (everolimus) | Cortical tubers, subependymal nodules, cardiac rhabdomyomas, renal angiomyolipomas, facial angiofibromas, ash-leaf spots, seizures (infantile spasms), intellectual disability |
| Li-Fraumeni | TP53 (17p13) | AD | Gliomas (especially astrocytomas), choroid plexus carcinoma | Breast cancer, sarcomas, adrenocortical carcinoma, leukemia — multiple cancers at young age |
| Turcot syndrome (APC type) | APC (5q21) | AD | Medulloblastoma | Familial adenomatous polyposis (FAP); colon polyps/cancer |
| Turcot syndrome (MMR type) | MLH1, MSH2, MSH6, PMS2 (mismatch repair) | AD | Glioblastoma | Hereditary nonpolyposis colorectal cancer (Lynch syndrome) |
| Gorlin syndrome (Nevoid basal cell carcinoma) | PTCH1 (9q22) — Hedgehog pathway | AD | Medulloblastoma (desmoplastic/SHH subtype) | Multiple basal cell carcinomas at young age, odontogenic keratocysts, skeletal anomalies, calcified falx cerebri |
Board Pearl
NF1 vs. NF2 tumor associations: NF1 (chromosome 17) = optic glioma + neurofibromas + café-au-lait spots. NF2 (chromosome 22) = bilateral vestibular schwannomas + meningiomas + ependymomas. Remember: NF2 = 2 schwannomas (bilateral). A unilateral vestibular schwannoma is sporadic; bilateral = NF2 until proven otherwise. Turcot syndrome has two types: APC → medulloblastoma, MMR → glioblastoma (mnemonic: APC-MB, MMR-GBM).
Quick Reference Table
CNS Tumors at a Glance
| Tumor | Classic Location | Hallmark Histology | Key Molecular Marker | Must-Know Pearl |
|---|---|---|---|---|
| Glioblastoma | Cerebral hemispheres; crosses corpus callosum | Pseudopalisading necrosis, microvascular proliferation | IDH-wildtype, EGFR amp, TERT, +7/−10 | Most common malignant primary; MGMT methylation predicts TMZ response |
| Oligodendroglioma | Frontal lobe (cortex) | Fried egg cells, chicken-wire vessels, calcifications | IDH-mutant + 1p/19q codeletion | Best prognosis among diffuse gliomas; PCV-sensitive |
| Meningioma | Convexity, parasagittal, sphenoid wing | Psammoma bodies, whorled cells, EMA+ | NF2 / chromosome 22q loss | Most common extra-axial tumor; dural tail sign |
| Schwannoma | Cerebellopontine angle (CN VIII) | Antoni A & B, Verocay bodies, S100+ | NF2 mutation | Bilateral = NF2; unilateral = sporadic |
| PCNSL | Periventricular | B-cell lymphoma, perivascular cuffing | CD20+ | Ghost tumor; avoid steroids before biopsy |
| Pilocytic astrocytoma | Cerebellum (children) | Rosenthal fibers, biphasic pattern | BRAF fusion | Most common pediatric brain tumor; excellent prognosis |
| Medulloblastoma | 4th ventricle / posterior fossa | Homer Wright rosettes, small blue cells | WNT, SHH, Group 3, Group 4 | Drop metastases; WNT = best, Group 3 = worst prognosis |
| Ependymoma | 4th ventricle (children); spinal cord (adults) | Perivascular pseudorosettes | ZFTA-RELA fusion (supratentorial) | Can cause obstructive hydrocephalus |
| Craniopharyngioma | Suprasellar | Adamantinomatous (calcifications, motor oil fluid) vs. papillary | CTNNB1 (adam.) / BRAF V600E (papillary) | Rathke pouch remnant; bitemporal hemianopia |
| Hemangioblastoma | Cerebellum | Stromal cells, lipid vacuoles, rich capillary network | VHL (3p25) | VHL-associated; EPO → polycythemia |
| ATRT | Posterior fossa (age <3) | Rhabdoid cells; INI1 loss on IHC | SMARCB1 (INI1) loss | Must distinguish from medulloblastoma; very aggressive |
| Diffuse midline glioma | Pons (DIPG), thalamus, spinal cord | Diffuse infiltration | H3K27M | Grade 4 by definition; dismal prognosis |
| Metastatic tumor | Gray-white junction; multiple | Matches primary tumor | N/A | Most common brain tumor overall; lung = #1 source |
Clinical Pearl
Posterior fossa tumors in children — quick differentiation: Midline cerebellar mass in a child = pilocytic astrocytoma (cystic, mural nodule) vs. medulloblastoma (solid, 4th ventricle, enhancing). A 4th ventricle mass extending through foramina = ependymoma. Age <3 with aggressive posterior fossa mass = think ATRT (check INI1). Diffuse pontine expansion = DIPG / diffuse midline glioma, H3K27-altered.
References
- Louis DN, Perry A, Wesseling P, et al. The 2021 WHO Classification of Tumors of the Central Nervous System: a summary. Neuro Oncol. 2021;23(8):1231-1251.
- Weller M, van den Bent M, Preusser M, et al. EANO guidelines on the diagnosis and treatment of diffuse gliomas of adulthood. Nat Rev Clin Oncol. 2021;18(3):170-186.
- Stupp R, Mason WP, van den Bent MJ, et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005;352(10):987-996.
- Hegi ME, Diserens AC, Gorlia T, et al. MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med. 2005;352(10):997-1003.
- Taylor MD, Northcott PA, Korshunov A, et al. Molecular subgroups of medulloblastoma: the current consensus. Acta Neuropathol. 2012;123(4):465-472.
- Ostrom QT, Price M, Neff C, et al. CBTRUS Statistical Report: Primary Brain and Other Central Nervous System Tumors Diagnosed in the United States in 2015–2019. Neuro Oncol. 2022;24(Suppl 5):v1-v95.
- Ropper AH, Samuels MA, Klein JP, Prasad S. Adams and Victor's Principles of Neurology. 12th ed. McGraw-Hill; 2023.
- Brat DJ, Aldape K, Colman H, et al. cIMPACT-NOW update 5: recommended grading criteria and terminologies for IDH-mutant astrocytomas. Acta Neuropathol. 2020;139(3):603-608.