CNS & pituitary tumors

Embryonal tumors

Medulloblastoma

Medulloblastoma


Editorial Board Member: P.J. Cimino, M.D., Ph.D.
Deputy Editor-in-Chief: Chunyu Cai, M.D., Ph.D.
Arnault Tauziede-Espariat, M.D., Ph.D.

Last author update: 21 June 2023
Last staff update: 6 February 2024

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PubMed Search: Medulloblastoma

See Also: Desmoplastic medulloblastoma

Arnault Tauziede-Espariat, M.D., Ph.D.
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Cite this page: Tauziede-Espariat A. Medulloblastoma. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/cnstumormedulloblastoma.html. Accessed May 19th, 2024.
Definition / general
  • 4 genetically defined groups and 4 histologically defined groups (Nature 2017;547:311)
    • Genetically defined: (a) WNT (for wingless integration site) activated, (b) SHH (sonic hedgehog) activated (either TP53 mutant or TP53 wild type), non-WNT / non-SHH, either (c) medulloblastoma group 3 or (d) medulloblastoma group 4 (Nature 2017;547:311)
    • Histologically defined: classic, desmoplastic / nodular, medulloblastoma with extensive nodularity and large cell / anaplastic medulloblastoma (Neuropathol Appl Neurobiol 2002;28:257)
Essential features
ICD coding
  • ICD-10:
    • C71 - malignant neoplasm of brain
    • C71.6 - malignant neoplasm of cerebellum
Epidemiology
  • Medulloblastoma is the most common CNS embryonal tumor of childhood and is second only to pilocytic astrocytoma for all intracranial neoplasms (Acta Neuropathol 2012;123:473)
  • Classic medulloblastoma (Acta Neuropathol 2012;123:473)
    • Non-WNT / non-SHH tumors or WNT activated
    • Midline location
  • Desmoplastic / nodular medulloblastoma (Acta Neuropathol 2012;123:473)
    • Cerebellar hemispheres and midline
    • Bimodal age distribution
    • Gorlin syndrome: nevoid basal cell carcinoma syndrome
    • SHH activated
    • Favorable outcome in young children compared to nondesmoplastic
  • Medulloblastoma with extensive nodularity (Acta Neuropathol 2012;123:473)
    • Closely related to desmoplastic medulloblastoma
    • SHH activated
    • Predominantly occurs in infants
    • Excellent outcome
  • Large cell / anaplastic medulloblastoma (Acta Neuropathol 2012;123:473)
    • Undifferentiated cells with marked nuclear pleomorphism, prominent nucleoli, cell wrapping and high mitotic count and apoptotic counts
    • Associated with all genetic variants but more common in SHH activated and in group 3
Sites
  • Fourth ventricle or cerebellar parenchyma
Clinical features
  • Signs and symptoms of increased intracranial pressure (headache, nausea, vomiting)
Diagnosis
  • Diagnosis of medulloblastoma requires histologic examination of tumor tissue and molecular genetic analyses
  • Integrated pathology diagnosis that includes both morphologic subtype and molecular subgroup along with any additional molecular data is recommended (Pediatr Dev Pathol 2022;25:23)
Radiology description
Prognostic factors
  • 3 prognostic subgroups (high risk, low risk and standard risk) depending on (Neuro Oncol 2021;23:1163)
    • Clinical findings: age at diagnosis, presence or absence of metastases at diagnosis, extent of resection of the tumor (Neuro Oncol 2021;23:1163)
    • Histopathological findings: histological group (large cell / anaplastic = poor prognosis; desmoplastic / nodular = good prognosis), presence of tumor cells in the cerebrospinal fluid (Neuro Oncol 2021;23:1163)
    • Biological / molecular findings: immunohistochemical / genetic subgroup (non-WNT / non-SHH = groups 3 and 4 having a poor prognosis; WNT activated = good prognosis), SHH activated TP53 mutation (associated with a poorer prognosis), MYC / MYCN amplification (associated with a poorer prognosis) (Neuro Oncol 2021;23:1163)
Case reports
Treatment
Gross images

Images hosted on other servers:
Cerebellar tumor extending into fourth ventricle

Cerebellar tumor extending into fourth ventricle

Microscopic (histologic) description
  • Classic medulloblastoma (Neuropathol Appl Neurobiol 2002;28:257)
    • Small, blue, round cell tumor
    • Syncytial arrangement of densely packed undifferentiated cells (embryonal cells)
    • Mitosis with apoptotic bodies
    • Homer Wright rosettes
  • Desmoplastic / nodular medulloblastoma (Neuropathol Appl Neurobiol 2002;28:257)
    • Densely packed, undifferentiated cells with hyperchromatic and pleomorphic nuclei that produce dense intercellular reticulin fiber network with nodular reticulin free zones
  • Medulloblastoma with extensive nodularity (Neuropathol Appl Neurobiol 2002;28:257)
    • Expanded lobular architecture due to reticulin free nodular zones becoming enlarged and rich in neuropil-like tissue
  • Large cell / anaplastic medulloblastoma (Neuropathol Appl Neurobiol 2002;28:257)
    • Anaplasia with marked nuclear pleomorphism, high mitotic count and high apoptotic count
    • Nuclear molding and cell wrapping
  • Medulloblastomas with melanotic or myogenic differentiations (Neuropathol Appl Neurobiol 2002;28:257)
Microscopic (histologic) images

Contributed by Arnault Tauziede-Espariat, M.D., John DeWitt, M.D., Ph.D., Meaghan Morris, M.D., Ph.D.,
Nirupama Singh, M.D., Ph.D. and Eman Abdelzaher, M.D., Ph.D.


Genetically defined

WNT (for wingless integration site) activated
YAP1 immunoreactivity

YAP1 immunoreactivity

Beta catenin immunoreactivity

Beta catenin immunoreactivity



SHH (sonic hedgehog) activated (either TP53 mutant or TP53 wild type)
Sheets of undifferentiated cells

Sheets of undifferentiated cells

Vague nodular formation

Vague nodular formation

Vague nodular formation with reticulin

Vague nodular formation with reticulin

Neuron specific enolase (NSE)

Neuron specific enolase (NSE)

Ki67

Ki67

Synaptophysin

Synaptophysin


Beta catenin

Beta catenin

INI1

INI1

YAP1 immunoreactivity

YAP1 immunoreactivity

GAB1 immunoreactivity

GAB1 immunoreactivity

OTX2 immunoreactivity

OTX2 immunoreactivity



Histologically defined

Classic
Homer Wright rosettes Homer Wright rosettes

Homer Wright rosettes



Desmoplastic / nodular medulloblastoma

Desmoplastic medulloblastoma

Pale nodular islands


Pale islands formed of uniform cells

Tumor in the subarachnoid space

Desmoplastic / nodular medulloblastoma

Desmoplastic / nodular medulloblastoma

Reticulin fibers network

Reticulin fiber network



Medulloblastoma with extensive nodularity
Extensive nodularity Extensive nodularity

Extensive nodularity



Large cell / anaplastic medulloblastoma
Apoptotic bodies, prominent nucleoli

Apoptotic bodies, prominent nucleoli

Cell wrapping

Cell wrapping

Anaplasia in medulloblastoma

Anaplasia in medulloblastoma



Special morphology
Melanocytic differentiation

Melanocytic differentiation

Myogenic differentiation

Myogenic differentiation

Cytology description
  • Clusters of tumor cells with hyperchromatic nuclei
Cytology images

Contributed by Arnault Tauziede-Espariat, M.D.
Cytological findings

MGG staining

Positive stains
Negative stains
Molecular / cytogenetics description

Genetic subgroups Immunohistochemical markers
β catenin
GAB1
YAP1
OTX2 p75 NGFR Filamin A
WNT activated + n - + n and c / - + n - + c
Non-WNT / non-SHH (groups 3 and 4) - - - + n - -
SHH activated - (only c and m) + c + n and c - + c + c
c = cytoplasmic, m = membranous, n = nuclear
Molecular / cytogenetics images

Contributed by Arnault Tauziede-Espariat, M.D.
<i>MYCN</i> amplification

MYCN amplification

Sample pathology report
  • Brain, cerebellar tumor, resection:
    • Classic medulloblastoma (see comment)
    • Comment: Medulloblastoma, WNT activated, CNS WHO Grade 4
    • Molecular pathology findings
      • CTTNB1 p.Ser33Cys mutation
      • Monosomy 6
Board review style question #1

The tumor shown above is found in the cerebellum in a child. What is the diagnosis?

  1. Anaplastic / large cell medulloblastoma
  2. Classic medulloblastoma
  3. Desmoplastic / nodular medulloblastoma
  4. Myomedulloblastoma
Board review style answer #1
C. Desmoplastic / nodular medulloblastoma

Comment Here

Reference: Medulloblastoma
Board review style question #2
Which of the following is true of medulloblastomas?

  1. Medulloblastomas, SHH activated show YAP1 and OTX2 immunoreactivities
  2. Medulloblastomas, WNT activated show YAP1 and GAB1 immunoreactivities
  3. Medulloblastomas, non-WNT / non-SHH show OTX2 expression
  4. Beta catenin cytoplasmic expression is specific of medulloblastomas, WNT activated
  5. p53 overexpression is specific of medulloblastomas, SHH activated
Board review style answer #2
C. Medulloblastomas, non-WNT / non-SHH show OTX2 nuclear expression. Answers A and D are incorrect because medulloblastomas, SHH activated show YAP1 and GAB1 immunoreactivities and beta catenin nuclear expression is specific of medulloblastomas, WNT activated. Answer B is incorrect because medulloblastomas, WNT activated show YAP1 immunoreactivity without GAB1 expression. Answer E is incorrect because p53 overexpression is evidenced in cases of Li-Fraumeni syndrome. Medulloblastomas, SHH activated are frequent in Li-Fraumeni syndrome but other histomolecular subtypes are possible.

Comment Here

Reference: Medulloblastoma
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