This document discusses various types of embryonal brain tumors that occur in children. It begins by providing background on the incidence of childhood cancers and CNS tumors specifically. It then lists and describes the main embryonal brain tumor types seen in children, including medulloblastoma, atypical teratoid/rhabdoid tumor, embryonal tumor with multilayered rosettes, pineoblastoma, and pituitary blastoma. For each tumor type, it discusses characteristics such as age of onset, location, histopathological features, molecular markers, treatment approaches, and prognosis. It emphasizes the importance of molecular classification in determining treatment strategies and clinical outcomes for these tumors.

1. EMBRYONAL BRAIN TUMORS IN
CHILDREN
DR. AARTI TYAGI,
Moderator – DR. URMI MUKHERJEE
Department of Pathology.
(Max Superspeciality hospital
New Delhi)

2. • Cancer in childhood is rare with only 1:600 children developing
malignancy by the age of 15 years.
• 20 -25% of childhood tumors are of CNS origin
Of primary CNS tumour in children , low grade
Asrtocytomas are the most common
• CNS tumours are now the most common cause of
death for children with malignancy

3. EMBYONAL BRAIN TUMOURS IN
CHILDREN
•
•
•
•
•
•
Medulloblastoma
Atypical Teratoid/ Rhabdoid Tumours
Embryonal Tumors with Multilayered Rosettes
Primitive Neuroectodermal Tumor
Pineoblastoma
Pituitary blastoma

4. MEDULLOBLASTOMA

5.  EMBRYONAL TUMOURS OF THE CEREBELLUM” AND ARE
 THE COMMONEST EMBRYONAL TUMOUR OF THE BRAIN.
 Arise in cerebellum and projects into 4thventricle
 Present with Ataxia,often manifested as decreased school
performance/clumsiness and ocular signs eg. Nystagmus or squint
 Peak incidence at the age of 4 –5 yrs In children and 25 yrs in adults
 Approximately 20% of Medulloblastoma present in infants younger
than 2 years old

6. Pathological
SUBTYPES
Classic medulloblastomas- 70-80%
Features
1.
2. Desmoplastic/nodular- 7%
3. Medulloblastoma with extensive nodularity
(MBEN) - 3%
4. Anaplastic Grouped together
and accounts for
10% to 2%.5. Large Cell

7. •
•
•
•
Classical Medulloblastoma.
M/E-
Highly cellular
Diffuse sheets of
primitive cells with out
Significant nodule
formation and anaplasia or
large cell change,
Mitoses- may be
abundant and
occasional ,
Homer-Wright rosettes
and perivascular
pseudorosettes present

8. •
Homer-Wright rosettes (groups of tumor cells
arranged in a
circle around a fibrillary center).

9. • Positive stains
• NSE, synaptophysin, Vimentin, Desmin, Nestin
• Focal GFAP.
•
•
Molecular / cytogenetics description
Isochromosome (17q) or 17p-
• 5-30% overexpress c-myc or N-myc;
• C-myc overexpression is associated with poor prognosis

10. • Differential diagnosis
• Lymphoma: diffusely infiltrates CNS until it mixes with normal and reactive
fibrillar cells
• PNET
• Ependymoma

11. Desmoplasmic/nodular
E Medulloblastoma
• D E F I N E D B Y – presence of nodules ( Round pale
islands) of better differentiated tumor cells separated by zones of darker
tumor cells
 Within the nodules,there is no signifant reticulin deposition but the
internodular regions shows extensive reticulin deposition.
 The surrounding darker tumor cells are more primitive appearing with
brisk mitotic activity.
• Desmoplastic medulloblastoma has a better prognosis than the classic form

12. Desmoplasmic/nodular medulloblastoma
• nodular (b/c of its architecture)
• desmoplastic ( because it is permeated by (reticulin) fibers that give it a firm
consistency)
• M/E-

13. Medulloblastoma with extensive nodularity
• Low power view, numerous pale
islands,with shapes of the nodules are
much more pleomorphic
• The nodules are composed of a uniform population of tumor cells. The
background is reticulin-free & rich in neuropil-like tissue. Mitosis is not
significantly increased. The cells often show streaming in parallel rows

14. •
•
•
•
Anaplastic Medulloblastoma
M/E-
Highly anaplastic nuclei
with high rate of mitosis &
apoptosis.
• Primitive looking cells
with nuclear molding.
• Some are
composed of large cells
with rounded vesicular nuclei
• Poor prognosis (than
classical
medulloblastoma).

15. 1. WNT
2. SONIC HEDGEHOG (SHH) pathway
3. GROUP 3( worst outcome)
4. GROUP 4
M O L E C U L A R S U B G R O U P S

16. WNT tumours are seen in children and adults.
 Rarely in infants.
It associated with the most favourable
prognosis
Loss chromosome 6.
• CTNNB1 MUTATION
• ASSOCIATED WITH MAINLY
CLASSICAL, RARELY LCA
WNT pathway (10%)

17.  Abnormalities in SHH pathway are
present in 30% of MB cases, mainly in
infants and young adults
 MB pathology usually
desmoplastic/Nodular.
 PTCH MUTATION LEADS TO THE
ACTIVATION OF SHH PATHWAY
 Prognosis is Intermediate
 SHH up-regulate MYCN gene.
 Tp53 mutations are present in 10-20 %
of SHH tumours(WORST OUTCOME)
SONIC HEDEHOG (SHH) pathway

18. TP 53 M UTATIONS
are present in 10-20% of WNT and SHH MB and very rarely
in the other subtypes.
IN WNT subgroup tumours ,the presence of TP53 mutation
has no significant effect on survival ,in contrast in SHH
medulloblastoma, patients with mutated TP53 have a
significantly poorer outcome , this suggests that testing for
TP53 mutations in SHH group medulloblastoma should
identify the patients with high risk group

19. GROUP 3
 FREQUENCY 20%
 IN INFANTS, RARELY IN ADULTS
 HISTOLOGICAL SUBTYPES : CLASSIC , LCA
 MYC AMPLIFICATION (25%) and ISOCHROMOSOME 17q
 PROGNOSIS IS WORST
GROUP 4
 ISOCHROMOSOME 17q, MYC AMPLIFICATION (6%)
 SEEN IN CHILDREN
 HISTOLOGICAL SUBTYPES : CLASSIC , LCA
 PROGNOSIS IS INTERMEDIATE

20. MOLECULAR SUBGROUPING USING IHC MARKER
IHC :
B CATENIN :
WNT : POSITIVE (NUCLEAR IN > 5% CELLS)
SHH : NEGATIVE
NON WNT/ NON SHH : NEGATIVE
GAB 1 :
SHH : POSITIVE (CYTOPLASMIC)
WNT : NEGATIVE
NON WNT/ NON SHH : NEGATIVE
YAP1 :
WNT : POSITIVE (NUCLEAR & CYTOPLASMIC)
SHH : POSITIVE (NUCLEAR & CYTOPLASMIC)
NON WNT/ NON SHH : NEGATIVE

21. Atypical teratoid / rhabdoid tumor
•
•
•
•
•
•
•
•
•
Comprise 1-2% of all CNS tumours in childhood.
M:F – 1.9:1
Biallelic mutations in the SMARCB1 gene(encodes
Infants and young children (mean age 17 months)
Tumours of cerebellum or CP angle
Usually supratentorial (cerebral or suprasellar)
Poor prognosis- Metastatic d/s and young age
for INI1)
Very aggressive with mean survival 11 months post-surgery
Metastasizes throughout CSF.
DIAGNOSIS REQUIRES IHC for INI1 ,shows loss of Nuclear
immunoexpression in tumour cells ,while endothelial cells
retain immunopositivity, acting as internal control.

22. •Large and pleomorphic
rhabdoid cells with abundant
eosinophilic cytoplasm, often
filamentous cytoplasmic inclusions
and vacuoles
•Eccentric round nuclei
and prominent nucleolus
•May have mucinous background
•May have epithelioid features with
poorly formed glands or Flexner-
Wintersteiner rosettes (tumour rosette
around the cytoplasmic protusions)

23. POSITIVE STAINS
Vimentin, EMA, smooth
muscle actin
Cytokeratin, neurofilament
Focal GFAP, variable
synaptophysin
chromogranin
and
GFAP
EMA VIMENTIN

24. DIFFERENTIAL DIAGNOSIS
•Choroid plexus carcinoma
•Composite rhabdoid tumors
usually INI1+)
(with other component,
•Ependymoma
•Occasional germ cell tumors
•PNET/medulloblastoma

25. SUPRATENTORIAL PRIMITIVE
NEUROECTODERMAL TUMOR
•Rare tumor, usually cerebral hemisphere
•Medulloblastoma like histology
•Disseminate along CSF pathway
•Usually infants and children
•Uniformly small and densely hyperchromatic
of entirely undiff appearance disposed in
patternless sheets
cells
•Desmoplastic mesenchymal components, high
mitotic rates, necrosis and cystic change.

26. Small blue cell tumor
with round,
hyperchromatic cells,
abundant mitotic
figures and fibrosis

27. With abundant neuropil and true rosettes.

28. POSITIVE STAINS
CD99 (strong membrane
Focal GFAP
staining)
DIFFERENTIAL DIAGNOSIS
Anaplastic glioma
Atypical teratoid/rhabdoid tumor
Central PNET/medulloblastoma
Lymphoma
Melanoma
Rhabdomyosarcoma
Small cell meningioma

29. EMBRYONAL TUMOURS WITH MULTILAYERED
ROSETTES
•Amplification of a miRNA on chromosome
19(C19MC) and over expression of the RNA binding
protein LIN28a.
•Ependymomatous rosettes- Multilayered cells
surrounding a lumen, patches of dense cellularity and
areas of more differentiated tumour with abundant
neurophil.
•Poor prognosis with early progression of disease and
death.

30. ETANR : Embryonal tumours with abundant neurophil and
rosettes (ETANTR)”
BI PHASIC PATTERN , DENSE CLUSTER OF ROUND
OR POLYGONAL SMALL CELLS WITH SCANT CYTOPLASM
NUMEROUS MITOSIS AND APOPTOTIC BODIES
ALONG WITH LARGE HYPOCELLLAR FIBRILARY AREAS
MAY CONTAIN NEUROCYTIC OR
GANGLION CELLS.MULTILAYERED
ROSETTES ARE FREQUENTLY SEEN
EPENDYMOBLASTOMA: Nests and sheets
of Poorly diff embryonal cells which form true
MULTILAYERED ROSETTES
MEDULLOEPITHELIOMA: Tubulo lpapillary
and Trabecular arrangements lined by
pseudostratified epethilium

31. LIN28A immunohistochemistry of
ETANTR
FISH analysis for the amplification
of C19MC (19q13.42) locus is a
very helpful diagnostic tool for
ETMR
probe (green signals)

32. PINEOBLASTOMA
•Second most common
after germ cell tumor
•Germ line mutations in
DICER1
pineal gland tumor
either RB gene or
•Presents with signs related to location of the
tumour in the upper midbrain, with
Parinaud’s syndrome (failure of up-gaze,
pupils that react poorly to light but
respond to accomodation, nystagmus
and lid retraction)

33. •Hydrocephalus- main presenting complaint
•Usually < 20 years
•Frequent CNS metastases or
cause of death
spinal seeding - main
•5 year survival approx. 58%
•Poor prognostic factors:
7+ mitotic figures/10 HPF
Presence of necrosis
No neurofilament staining

34. Dense small nuclei and scant cytoplasm Homer-Wright rosette
Sheets of cells with high grade (anaplastic /
undifferentiated) features including high N/C ratio with
minimal cytoplasm and large hyperchromatic nuclei
•Necrosis, mitotic figures
•Homer-Wright or Flexner-Wintersteiner rosettes

35. Positive stains
NSE, synaptophysin, retinalS-antigen
Differential diagnosis
Glial neoplasms: GFAP+
Medulloblastoma
Pineocytoma: better differentiated cells with more
cytoplasm, smaller cells, no/rare mitotic figures

36. PITUITARY BLASTOMA
• Rare primitive Embryonal tumour of the
pituitary gland
• Typically presents in the first 2 years of life with
Cushing’s syndrome ,with ophthalmoplegia
• Histopathology- Combination of epithelial
structures, small embryonal cells and
secretory cells.
• Express synaptophysin and
chromogranin and some express
pituitary hormones (typically ACTH)
• High frequency of germ line DICER1
mutations

37. KEY POINTS
 Brain tumours are the most common malignancy
related cause of death in children
 Molecular and pathological stratification is critical in
determining the type and intensity of treatment
 Medulloblastoma , the most common embryonal
tumour can be stratified on the basis of histological
and molecular subtypes into high risk( anaplastic/large
cell, MYC amplified) and low risk disease( WNT
subtype)
 Classification of other embryonal tumour types by
molecular approaches is defining new subtypes with
distinct clinical outcomes

38.  Point taken:
Though there exists a wide range of classification ,
The overlapping of morphologies still keeps one in the
diagnostic dilemma, therefore the LOCATION of the
tumour and the MOLECULAR GENETICS are still
considered a major helping tool !!

39. THANK YOU