Medulloblastoma is an embryonal, malignant brain tumor that arises in the cerebellum and is the most common malignant pediatric posterior-fossa tumor. WHO 2021 stratifies medulloblastoma into four molecular subgroups — WNT-activated, SHH-activated, Group 3, and Group 4 — which differ in developmental cell of origin, driver alterations, age distribution, metastatic propensity, and prognosis. All subgroups share a posterior-fossa location, derivation from cerebellar progenitor populations, and a clinical syndrome dominated by raised intracranial pressure (headache, vomiting) and cerebellar dysfunction (ataxia). Standard care for children >3 years is maximal-safe resection followed by craniospinal irradiation and multi-agent chemotherapy; subgroup-specific de-escalation and targeted-therapy strategies (e.g., SHH-pathway inhibitors, WNT-subgroup radiation reduction) are active areas of investigation. Subgroup-specific molecular detail is curated in separate dismech entries (e.g., `Medulloblastoma_WNT_Activated`, `Medulloblastoma_SHH_Activated`); Group 3 and Group 4 are not yet curated.
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name: Medulloblastoma
creation_date: '2026-05-12T00:00:00Z'
updated_date: '2026-05-12T19:00:00Z'
description: >-
Medulloblastoma is an embryonal, malignant brain tumor that arises in the
cerebellum and is the most common malignant pediatric posterior-fossa
tumor. WHO 2021 stratifies medulloblastoma into four molecular subgroups —
WNT-activated, SHH-activated, Group 3, and Group 4 — which differ in
developmental cell of origin, driver alterations, age distribution,
metastatic propensity, and prognosis. All subgroups share a posterior-fossa
location, derivation from cerebellar progenitor populations, and a clinical
syndrome dominated by raised intracranial pressure (headache, vomiting) and
cerebellar dysfunction (ataxia). Standard care for children >3 years is
maximal-safe resection followed by craniospinal irradiation and multi-agent
chemotherapy; subgroup-specific de-escalation and targeted-therapy strategies
(e.g., SHH-pathway inhibitors, WNT-subgroup radiation reduction) are active
areas of investigation. Subgroup-specific molecular detail is curated in
separate dismech entries (e.g., `Medulloblastoma_WNT_Activated`,
`Medulloblastoma_SHH_Activated`); Group 3 and Group 4 are not yet curated.
categories:
- Central Nervous System Neoplasm
- Pediatric Brain Tumor
- Embryonal Tumor
- Molecularly Defined Tumor
has_subtypes:
- name: WNT
display_name: WNT-Activated Medulloblastoma
description: >-
Approximately 10% of medulloblastomas. Driven by CTNNB1 exon 3 mutations
or germline APC mutations. Best prognosis (>95% long-term survival);
candidate for treatment de-escalation. Curated as
`Medulloblastoma_WNT_Activated`.
- name: SHH
display_name: SHH-Activated Medulloblastoma
description: >-
Approximately 30% of medulloblastomas. Driven by PTCH1/SMO/SUFU loss or
GLI2/MYCN amplification, with TP53 mutation status further stratifying
prognosis under WHO 2021. Bimodal age distribution (infants and adults).
Curated as `Medulloblastoma_SHH_Activated`.
- name: Group 3
description: >-
Approximately 25% of medulloblastomas. MYC amplification is common; high
metastatic rate and worst prognosis among the four subgroups. Not yet
curated as a separate dismech entry.
- name: Group 4
description: >-
The most common subgroup (approximately 35%). Heterogeneous drivers
including MYCN amplification and SNCAIP duplication; intermediate
prognosis. Not yet curated as a separate dismech entry.
pathophysiology:
- name: Cerebellar Progenitor Proliferation
description: >-
All molecular subgroups arise from cerebellar progenitor populations and
converge on dysregulated proliferation in the developing cerebellum. WNT
tumors derive from lower-rhombic-lip progenitors and SHH tumors from
external-granule-layer granule-neuron precursors; the subgroup-specific
oncogenic pathways (WNT/beta-catenin, Sonic Hedgehog, MYC-driven programs)
feed a common proliferative phenotype in cerebellar granule-lineage cells.
evidence:
- reference: PMID:35489737
reference_title: "Molecular Stratification of Medulloblastoma: Clinical Outcomes and Therapeutic Interventions."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "Medulloblastoma (MB) is the most common malignant pediatric posterior fossa"
explanation: Establishes medulloblastoma as the most common malignant pediatric posterior-fossa tumor, anchoring the cerebellar-progenitor framing of the disease.
cell_types:
- preferred_term: cerebellar granule cell
term:
id: CL:0001031
label: cerebellar granule cell
biological_processes:
- preferred_term: cell population proliferation
modifier: INCREASED
term:
id: GO:0008283
label: cell population proliferation
- preferred_term: cerebellum development
modifier: ABNORMAL
term:
id: GO:0021549
label: cerebellum development
locations:
- preferred_term: cerebellum
term:
id: UBERON:0002037
label: cerebellum
phenotypes:
- category: Neurological
name: Headache
description: >-
Headache from increased intracranial pressure due to obstructive
hydrocephalus, typically worse in the morning. Common at presentation
across molecular subgroups.
phenotype_term:
preferred_term: Headache
term:
id: HP:0002315
label: Headache
- category: Neurological
name: Ataxia
description: >-
Cerebellar ataxia reflecting tumor involvement of cerebellar structures;
truncal with midline tumors, appendicular with lateral hemispheric tumors.
phenotype_term:
preferred_term: Ataxia
term:
id: HP:0001251
label: Ataxia
- category: Neurological
name: Vomiting
description: >-
Vomiting from raised intracranial pressure, characteristically in the
morning; a common presenting symptom across subgroups.
phenotype_term:
preferred_term: Vomiting
term:
id: HP:0002013
label: Vomiting
- category: Neurological
name: Macrocephaly
description: >-
Increased head circumference in infants due to hydrocephalus from CSF
obstruction; may be the presenting sign in young infants before other
cerebellar signs emerge.
phenotype_term:
preferred_term: Macrocephaly
term:
id: HP:0000256
label: Macrocephaly
- category: Neurological
name: Papilledema
description: >-
Optic-disc swelling from raised intracranial pressure; may produce
visual symptoms if prolonged.
phenotype_term:
preferred_term: Papilledema
term:
id: HP:0001085
label: Papilledema
treatments:
- name: Surgical Resection
description: >-
Maximal safe resection is the first-line treatment across molecular
subgroups. Extent of resection is prognostic; near-total or gross-total
resection is achievable in most cases.
treatment_term:
preferred_term: surgical procedure
term:
id: MAXO:0000004
label: surgical procedure
- name: Craniospinal Irradiation
description: >-
Craniospinal irradiation (CSI) is standard for medulloblastoma due to the
risk of leptomeningeal dissemination. CSI is generally avoided in children
<3 years to limit neurocognitive late effects, and dose-reduction trials
are exploring lower-intensity CSI for the favorable-prognosis WNT
subgroup.
treatment_term:
preferred_term: radiation therapy
term:
id: MAXO:0000014
label: radiation therapy
- name: Chemotherapy
description: >-
Multi-agent adjuvant chemotherapy is standard. In infants, intensive
chemotherapy regimens are used to delay or avoid radiation; in the WNT
subgroup, de-escalation trials are exploring reduced-intensity regimens.
treatment_term:
preferred_term: chemotherapy
term:
id: MAXO:0000647
label: chemotherapy
therapeutic_agent:
- preferred_term: cisplatin
term:
id: CHEBI:27899
label: cisplatin
- preferred_term: vincristine
term:
id: CHEBI:28445
label: vincristine
- preferred_term: cyclophosphamide
term:
id: CHEBI:4027
label: cyclophosphamide
- preferred_term: lomustine
term:
id: CHEBI:6520
label: lomustine
notes: >-
This entry is a parent / root-level dismech record for medulloblastoma
organising the four molecular subgroups recognised under WHO 2021. Subgroup-
specific pathophysiology, driver genetics, and subgroup-targeted therapy are
curated in separate dismech files where available
(`Medulloblastoma_WNT_Activated`, `Medulloblastoma_SHH_Activated`). Group 3
and Group 4 entries are scoped as follow-up work.
disease_term:
preferred_term: medulloblastoma
term:
id: MONDO:0007959
label: medulloblastoma
No deep-research provider was invoked for this root-level entry. The
two existing subgroup-specific dismech files
(Medulloblastoma_WNT_Activated, Medulloblastoma_SHH_Activated)
already have full deep-research artifacts in research/ from their
own curation. This root entry was curated directly from the
verified literature already cached in references_cache/ and
shared by both subgroup files; no provider was re-run because the
root scope only synthesises features that are shared across the four
WHO 2021 molecular subgroups (WNT, SHH, Group 3, Group 4).
Medulloblastoma (MONDO:0007959) is an embryonal, malignant brain
tumor that arises in the cerebellum and is the most common malignant
pediatric posterior-fossa tumor. PMID:35489737 ("Molecular
Stratification of Medulloblastoma: Clinical Outcomes and Therapeutic
Interventions") establishes that "Recent WHO (2021) guidelines
stratified MB into four molecular subgroups with four and eight
further subgroups for SHH and non-WNT/non-SHH MB, respectively." The
four subgroups are listed via has_subtypes rather than as a
pathophysiology node — per the reviewer feedback, classification
logic belongs in has_subtypes and description, not in
pathophysiology[].
Cellular origin / shared mechanism. Across subgroups, tumors
derive from cerebellar progenitor populations and converge on
dysregulated proliferation in the developing cerebellum (CL:0001031
cerebellar granule cell, GO:0008283 cell-population proliferation
INCREASED, GO:0021549 cerebellum development ABNORMAL,
UBERON:0002037 cerebellum). WNT tumors derive from lower-rhombic-lip
progenitors; SHH tumors from external-granule-layer granule-neuron
precursors. The subgroup-specific oncogenic pathways
(WNT/beta-catenin, Sonic Hedgehog, MYC-driven programs) feed this
common proliferative endpoint — the single shared pathophysiology
node curated here.
Clinical syndrome. Five HP-bound phenotypes are captured without
frequency: tags (Headache HP:0002315, Ataxia HP:0001251,
Vomiting HP:0002013, Macrocephaly HP:0000256, Papilledema
HP:0001085). Per the PR review the frequency tags were removed
because no quantitative cohort evidence was cited in scope to
support specific frequency bands; reintroduce per the
frequency-evidence SOP once subgroup-pooled clinical-cohort data
are curated.
Management. Three modalities of standard care across subgroups:
- Surgical resection (MAXO:0000004).
- Craniospinal irradiation (MAXO:0000014), generally avoided in
children <3 years to limit neurocognitive late effects.
- Multi-agent chemotherapy (MAXO:0000647) with cisplatin
(CHEBI:27899), vincristine (CHEBI:28445), cyclophosphamide
(CHEBI:4027), and lomustine (CHEBI:6520) as the canonical
agents (added in response to PR review).
NCIT:C3222 (the disease) as the
finding_term and evidenced an epidemiological claim, not a
pathologist-level histological finding. True histology (densely
packed small blue round cells, Homer Wright rosettes,
desmoplastic-nodular vs anaplastic large-cell morphology,
synaptophysin expression) belongs in subgroup-specific entries and
in a future repo-wide reframing of histopathology[] (the WNT and
SHH subtype files carry the same "epidemiology as histopathology"
pattern; flagged for follow-up).