Paediatric cns tumours
Reading File
Finding Sources
Finding Sources
Searching PubMed
"pediatric brain tumors" AND "central nervous system"
Finding Sources
Finding Sources
Reading File
Reading File
Finding Sources
Reading File
Finding Sources
Finding Sources
Reading File
Finding Sources
Finding Sources
Reading File
Reading File
Reading File
I now have comprehensive information. Let me compile a thorough, well-structured answer.
Paediatric CNS Tumours
Brain tumours are the most common solid tumours of childhood and the leading cause of cancer-related death in the paediatric age group. They account for ~20-25% of all childhood cancers. Unlike adults (where metastases dominate), primary CNS tumours predominate in children.
Epidemiology and Distribution
Frequency by histology (from the SEER registry, Bradley & Daroff):
| Histology | % of All Paediatric CNS Tumours | Median Age |
|---|---|---|
| Gliomas (total) | 52.9% | 6 yrs |
| - Pilocytic astrocytoma | 17.6% | 7 yrs |
| - Other low-grade glioma | 14.3% | 6 yrs |
| - High-grade glioma | 11.1% | 7 yrs |
| Embryonal tumours | 15.0% | 4 yrs |
| - Medulloblastoma | 9.3% | 6 yrs |
| - AT/RT | 2.3% | 1 yr |
| - PNET | 2.2% | 3.5 yrs |
| Ependymal tumours | 5.5% | 4 yrs |
| Pineal region tumours | 4.4% | 6.5 yrs |
| Choroid plexus tumours | 2.3% | 1 yr |
| Cranial nerve tumours | 4.7% | - |
Key anatomical fact: In children, posterior fossa (infratentorial) tumours predominate (~60%), in contrast to adults where supratentorial lesions are more common. Common posterior fossa tumours: medulloblastoma, pilocytic astrocytoma of cerebellum, ependymoma of 4th ventricle, brainstem glioma.
Clinical Presentation
General features of raised intracranial pressure (ICP):
- Morning headaches (worse on waking, may wake child from sleep)
- Projectile vomiting (often without nausea)
- Papilloedema
- Diplopia (VI nerve palsy - false localising sign)
- Sunset sign (Parinaud's) in infants
- Bulging fontanelle / increasing head circumference in infants
Cerebellar signs (posterior fossa tumours):
- Truncal ataxia, broad-based gait, frequent falls
- Dysmetria, dysdiadochokinesia
- Nystagmus, head tilt
Focal signs vary by location - hemiparesis, visual field defects, seizures (more common in supratentorial tumours), endocrine dysfunction (craniopharyngioma).
Major Tumour Types
1. Medulloblastoma (WHO Grade IV)
The prototype embryonal CNS tumour and the most common malignant brain tumour of childhood. - Adams & Victor's Principles of Neurology
Key facts:
- Accounts for ~20% of childhood brain tumours; 9.3% of all paediatric CNS tumours
- Arises in the posterior cerebellar vermis and roof of 4th ventricle
- Males outnumber females ~3:1 (varies by molecular subgroup)
- Peak age: 4-8 years; >50% occur before age 10
- Strong tendency to disseminate via CSF pathways ("drop metastases")
WHO 5 Molecular Classification (4 subgroups - Bradley & Daroff):
| Subgroup | % | Age | Sex | Genetics | Prognosis |
|---|---|---|---|---|---|
| WNT-activated | 10-15% | Children/adults | M=F | CTNNB1 mutation, monosomy 6 | Excellent (>90% survival) |
| SHH-activated, TP53 wild-type | ~25% | Infants & adults | M=F | PTCH, SMO, SUFU mutations | Intermediate |
| SHH-activated, TP53 mutant | ~5% | Children | M>F | TP53 mutation | Poor |
| Non-WNT/non-SHH (Groups 3 & 4) | ~60% | Children | M>>F | MYCN amp, CDK6 amp (Gr3), chr17 gain | Poor (Gr3) to Intermediate (Gr4) |
Germline syndromes:
- Gorlin syndrome (nevoid basal cell carcinoma): PTCH mutation - SHH medulloblastoma
- Turcot syndrome: APC/mismatch repair mutations - WNT or SHH medulloblastoma
- Li-Fraumeni syndrome: TP53 - SHH-TP53 mutant subgroup
Histology:
- Small round blue cells, hyperchromatic nuclei, minimal cytoplasm, numerous mitoses
- Homer Wright (neuroblastic) rosettes in ~50%
- Variants: classic, desmoplastic/nodular, anaplastic/large cell, medulloblastoma with extensive nodularity (MBEN)
Treatment:
- Maximal safe surgical resection
- Craniospinal irradiation (CSI) + posterior fossa boost
- Adjuvant chemotherapy (cisplatin-based)
- 5-year survival >80% with combined modality treatment
- WNT tumours: trials exploring radiation de-escalation given excellent prognosis
- Age <3 years: radiation deferred, chemotherapy-first strategies used
Poor prognostic factors: Brainstem invasion, leptomeningeal spread at diagnosis, age <3 years, MYCN amplification, anaplastic/large cell histology, Group 3 molecular subtype
2. Pilocytic Astrocytoma (WHO Grade I)
- Most common low-grade glioma of childhood; most common overall brain tumour in children
- Typically cerebellar (but also optic pathway, hypothalamus, brainstem)
- Optic pathway glioma: strongly associated with Neurofibromatosis type 1 (NF1) - BRAF-KIAA1549 fusion
- Characteristic biphasic histology: loose microcystic areas + compact bipolar Rosenthal fibres
- Cystic with mural nodule on MRI (classic cerebellar pilocytic)
- Excellent prognosis after complete resection; can be observed if NF1-associated and asymptomatic
3. Ependymoma
- Arises from ependymal lining cells of ventricles
- ~70% originate in the 4th ventricle (posterior fossa); predominantly in childhood
- The other 30% are supratentorial or spinal
- Males affected ~2x more than females
- Molecular groups (WHO 5): ZFTA-fusion positive, YAP1-fusion positive, Posterior Fossa Group A (PFA - infants, worse prognosis, loss of H3K27me3), Posterior Fossa Group B (PFB - older children, better prognosis)
- Clinical: similar to medulloblastoma - raised ICP, vomiting, cerebellar signs; more protracted course
- May extend through foramina of Luschka/Magendie, invade medulla
- Treatment: surgical resection (complete resection is key prognostic factor) + conformal radiotherapy
4. Craniopharyngioma
- 2-5% of all CNS tumours; most symptomatic in first two decades - Bradley & Daroff
- Arises from Rathke pouch remnants in the sellar/suprasellar region
- Two types:
- Adamantinomatous (childhood predominant): CTNNB1 (beta-catenin) mutation, cystic, calcified, "motor oil" fluid, wet keratin - diagnostic on biopsy
- Papillary (adult predominant): BRAF V600E mutation, solid, 3rd ventricle
- Calcification in ~75% of cases - visible on plain skull X-ray and CT
- Clinical: visual field defects (bitemporal hemianopia), hypopituitarism (growth failure, diabetes insipidus, delayed puberty), hydrocephalus, cognitive impairment
- Treatment: surgery ± radiotherapy; challenging due to hypothalamic involvement; targeted BRAF inhibition explored for papillary subtype
5. Diffuse Intrinsic Pontine Glioma (DIPG) / Diffuse Midline Glioma H3K27-altered
- Highly aggressive brainstem tumour occurring predominantly in children (median age 5-7 years)
- H3 K27M mutation (histone 3) in ~80% - now classified as Diffuse Midline Glioma H3K27-altered, WHO Grade 4
- Clinical: rapid onset of cranial nerve palsies + long tract signs + ataxia (the classic triad)
- Biopsy now recommended for molecular profiling
- Radiotherapy provides temporary benefit (6-8 weeks)
- Median survival: ~9-11 months; remains one of the deadliest paediatric cancers
- ONC201 (dopamine receptor antagonist) showing promise for H3K27M-mutant tumours
6. Atypical Teratoid/Rhabdoid Tumour (AT/RT)
- Highly malignant embryonal tumour; median age 1 year (mainly infants and toddlers <3 years)
- Defined by SMARCB1 (INI1) or SMARCA4 loss (SWI/SNF chromatin remodelling complex)
- Histology: rhabdoid cells + primitive neuroectodermal, mesenchymal, epithelial elements
- Infants with AT/RT should have germline SMARCB1 testing (rhabdoid tumour predisposition syndrome)
- Very aggressive; dismal prognosis (median survival <12 months historically)
- Intensive multimodal treatment improving outcomes in select cases
7. Choroid Plexus Tumours
- Predominantly first year of life; 75% in first decade
- Choroid plexus papilloma (CPP, WHO Grade I) vs. carcinoma (CPC, WHO Grade III)
- Present with hydrocephalus (overproduction of CSF ± obstruction)
- Strong association with Li-Fraumeni syndrome (TP53 germline) in CPC
- Surgical resection curative for CPP
8. Pineal Region Tumours
- Include germinoma (most common), teratoma, pineoblastoma, pineocytoma
- Germinoma: peak adolescent age, highly radiosensitive, excellent prognosis
- Pineoblastoma: embryonal tumour, can be associated with bilateral retinoblastoma ("trilateral retinoblastoma")
- Parinaud's syndrome (upgaze palsy, convergence-retraction nystagmus, lid retraction) from dorsal midbrain compression
Imaging
MRI is the gold standard for evaluation. CT useful acutely (calcification detection, hydrocephalus).
| Tumour | Characteristic MRI finding |
|---|---|
| Medulloblastoma | Midline posterior fossa, hyperdense on CT, enhancing, restricted diffusion |
| Pilocytic astrocytoma | Cystic + enhancing mural nodule (cerebellum) |
| Ependymoma | 4th ventricle, "toothpaste" extension through foramina, calcification |
| Craniopharyngioma | Sellar/suprasellar, cystic + solid + calcification ("90% calcify") |
| DIPG | Expansile T2-hyperintense pontine mass, minimal enhancement |
| AT/RT | Heterogeneous, haemorrhage, restricted diffusion |
The ependymoma MRI from Adams & Victor's (Figure 30-12 in the textbook) shows an ependymoma filling the 4th ventricle on both coronal T2 and axial FLAIR sequences.
Genetic Syndromes Associated with Paediatric CNS Tumours
| Syndrome | Gene | CNS Tumour |
|---|---|---|
| Neurofibromatosis 1 | NF1 | Optic pathway glioma, pilocytic astrocytoma |
| Neurofibromatosis 2 | NF2 | Ependymoma, schwannoma, meningioma |
| Gorlin syndrome | PTCH1 | SHH medulloblastoma |
| Turcot syndrome | APC / MMR | Medulloblastoma, glioblastoma |
| Li-Fraumeni syndrome | TP53 | Choroid plexus carcinoma, glioma, medulloblastoma |
| Tuberous sclerosis | TSC1/TSC2 | Subependymal giant cell astrocytoma (SEGA) |
| VHL | VHL | Cerebellar haemangioblastoma |
| Rhabdoid tumour predisposition | SMARCB1 | AT/RT |
Principles of Treatment
- Surgery: Maximal safe resection is the cornerstone. Complete resection strongly predicts outcome in ependymoma and pilocytic astrocytoma.
- Radiotherapy: Craniospinal irradiation (CSI) for medulloblastoma; local conformal RT for ependymoma. Avoided in children <3 years due to neurocognitive toxicity.
- Chemotherapy: Cisplatin/vincristine/CCNU-based regimens for medulloblastoma; used to delay RT in infants.
- Targeted therapies:
- Vismodegib/sonidegib (Hedgehog inhibitors) for SHH medulloblastoma
- BRAF inhibitors (dabrafenib + trametinib) for BRAF V600E-mutant gliomas and papillary craniopharyngioma
- ONC201 for H3K27M-mutant DIPG
- VEGFR inhibitors for recurrent ependymoma
- Molecular profiling (DNA methylation array, next-gen sequencing) is now standard at diagnosis for treatment stratification.
Long-Term Sequelae
Survivors of paediatric CNS tumours face significant late effects:
- Neurocognitive decline (especially after craniospinal irradiation in young children)
- Endocrine dysfunction: growth hormone deficiency, hypothyroidism, precocious/delayed puberty (especially craniopharyngioma, suprasellar tumours)
- Second malignancies (radiation-induced)
- Hearing loss (cisplatin ototoxicity)
- Leukoencephalopathy (methotrexate + radiation)
- Psychosocial and quality-of-life issues
Sources:
- Adams & Victor's Principles of Neurology, 12th Ed., Ch. 30 - Medulloblastoma, ependymoma, craniopharyngioma sections
- Bradley & Daroff's Neurology in Clinical Practice, Ch. 72 & 75 - Embryonal neoplasms and paediatric brain tumours table
- Robbins & Kumar Pathologic Basis of Disease - Embryonal tumours chapter
This is a shared conversation. Sign in to Orris to start your own chat.