3. CNS Tumors
Learning objectives
To discuss
Benign and malignant tumours of the CNS and Familial tumour
syndromes in terms of genetics, clinical features, associated
lesions, and complications, clinical course
Learning outcomes
At the end of the lecture the student will be able to
Classify the tumours of the brain
Discuss types, age and sex predominance, incidence, clinical
presentation, morphology and clinical course-prognosis of common brain
tumours
Discuss the common familial tumour syndromes associated with brain
tumours
4. CNS Tumors
Tumors of the CNS are a larger proportion of
cancers of childhood
CNS tumors in childhood differ from those in
adults both in histologic subtype and location
In childhood tumors are likely to arise in the
posterior fossa
In adults - supratentorial
8. CNS Tumors
Tumors of the nervous system may arise
from
Cells of the coverings
Cells intrinsic to the brain
Other cell populations within the skull
Metastases (spread from elsewhere in the
body )
9. CLASSIFICATION OF CNS TUMOURS
1. TUMOURS OF THE GLIAL TISSUE – (GLIOMAS)
2. TUMOURS OF NEURONS
3. MIXED TUMOURS WITH GLIAL & NEURONAL
COMPONENTS
4. POORLY DIFFERENTIATED AND EMBRYONAL
TUMOURS
5. TUMOURS OF THE MENINGES
6. PERIPHERAL NERVE SHEATH TUMOURS
7. METASTATIC TUMOURS
8. PRIMARY CNS LYMPHOMA
9. Miscellaneous TUMOURS
10. CLASSIFICATION
TUMOURS OF THE GLIAL
TISSUE – (GLIOMAS)
Astrocytoma
Oligodendroglioma
Ependymoma
TUMOURS OF NEURONS
Gangliocytoma
Neuroblastoma
Ganglioneurocytoma
Gliomatosis cerebri
Cerebral neuroblastoma
Central neurocytoma
MIXED TUMOURS WITH TUMOURS OF
GLIAL & NEURONAL THE
COMPONENTS
MENINGES
Ganglioglioma
Meningioma
Dysembryoplastic
Neuroepithelial tumour PERIPHERAL
NERVE
(DNT)
SHEATH
POORLY
DIFFERENTIATED AND TUMOURS
EMBRYONAL
Schwannoma
TUMOURS
Neurofibroma
Medulloblastoma
Malignant
Atypical
nerve sheath
teratoid/rhabdoid
tumourtumour
MPNST
Medulloepithelioma
(Malignant
Dysplastic
Schwannoma
Gangliocytoma of the )
cerebellum (Lhermitte –
Duclos disease)
Polar spongioblastoma
Miscellaneous
TUMOURS
Hemangioblastoma
Craniopharyngiom
a
Pituitary tumours
Mesenchymal
tumours
METASTATIC
TUMOURS
PRIMARY
CNS
LYMPHOMA
11. Tumors of the nervous system have unique
characteristics
Histologic distinction between benign and
malignant lesions
The pattern of growth
The anatomic site of the neoplasm
The pattern of spread
12. CNS-Tumours
• Incidence of CNS tumors ranges from 10 to 17 per
100,000
• Half to three-quarters are primary tumors, rest are
metastatic
• 70% of childhood CNS tumors arise in the
posterior fossa
• In adults tumours arise within the cerebral
hemispheres above the tentorium.
• Distinction between benign & malignant lesions is
less evident
13. CNS-Tumours
• Ability to surgically resect infiltrating glial
neoplasms without compromising neurologic
function is limited
• Anatomic site of the neoplasm can have lethal
consequences irrespective of histologic
classification
14. CNS-Tumours
• Pattern of spread of primary CNS neoplasms
differs -Even the most highly malignant Gliomas
rarely metastasize outside the CNS
• The subarachnoid space provides a pathway for
spread - occur in highly anaplastic as well as in
well-differentiated neoplasms that extend into the
CSF pathways.
15. The criteria used to determine malignancy
1. Even highly malignant intracranial neoplasms
generally do not metastasize
2. Destructive infiltration of the brain is the major
criterion of malignancy for intracranial neoplasms.
Neurologic deficits resulting from destructive
invasion by malignant neoplasms are irreversible.
Benign neoplasms, on the other hand, cause
neurologic deficits due to compression; these
often reverse when the neoplasm is removed
16. The criteria used to determine malignancy
3. The rate of growth of neoplasms also correlates
well with malignant behavior .
4. Recurrence after treatment is almost invariable with
malignant intracranial neoplasms.
5. The term benign for any intracranial neoplasm is
probably implies rather that they are slow growing
and do not infiltrate the brain substance.
17. neurological deficit
hydrocephalous
Obstruction to
CSF flow
seizures
compression
irritation
Intracranial
neoplasm
space occupying
Raised ICP
Patho- physiological
affects of intracranial
neoplasms
destruction
oedema
neurological deficit
Raised ICP
18. TUMOURS OF THE GLIAL TISSUE – (GLIOMAS)
Astrocytoma
Oligodendroglioma
Ependymoma
Astrocytoma
Fibrillary astrocytoma
Glioblastoma
Pilocytic astrocytoma, and
Pleomorphic xanthoastrocytoma
19. WHO Grading system for astrocytomas
Variables such as nuclear atypia/mitosis/
endothelial proliferation & necrosis are
scored as
Grade 1 if none = pilocystic astrocytoma
Grade 2 if any one = diffuse astrocytoma
Grade 3 if any two= anaplastic astrocytoma
Grade 4 if three or all = glioblastoma multiforme
20. Fibrillary (Diffuse) Astrocytomas (grade II/IV)
• Most common adult CNS tumour
• 80% of adult primary brain tumors
• Location: cerebral hemispheres, also occur in the
cerebellum, brainstem, or spinal cord
• Fourth through sixth decades
• most common presenting signs and symptoms
are seizures, headaches, and focal neurologic
deficits related to the anatomic site of involvement
21. Fibrillary (Diffuse) Astrocytomas (grade II/IV)
Gross
Poorly defined gray infiltrative
tumor that expands and
distorts the brain
C/S of the tumor - firm or soft
and gelatinous; cystic
degeneration
few centimeters - enormous
lesions
22. Low-grade astrocytoma is seen as
expanded white matter of the left
cerebral hemisphere
thickened corpus callosum and
fornices
23. Fibrillary (Diffuse) Astrocytomas (grade II/IV)
MICRO
Mild to moderate increase in the number of glial cell nuclei
Tumor cells - stellate, spindle-shaped with fiber like
processes
Intervening feltwork of fine, GFAP-positive astrocytic cell
processes that give the background a fibrillary appearance
24. Other types
• Anaplastic astrocytomas (Grade III/IV)
• Gemistocytic astrocytoma :predominant
neoplastic astrocyte shows a brightly eosinophilic
cell body from which emanate abundant, stout
processes
25. Glioblastoma (grade IV/IV)
• Older age group
Morphology
• show variation in the gross appearance : Some
areas are firm and white, others are soft and yellow (the
result of tissue necrosis), and yet others show regions of
cystic degeneration and hemorrhage
• well demarcated from the surrounding brain
tissue, but infiltration beyond the outer margins is
always present
• Gliomatosis cerebri- multiple regions of the brain
are infiltrated by neoplastic astrocytes
26. Glioblastoma multiforme
GROSS
appearing as a necrotic,
hemorrhagic, infiltrating
mass
variation in the gross
appearance of the tumor
from region to region is
Characteristic
Some areas are firm and
white,others are soft and
yellow (the result of tissue
necrosis), and still others
show regions of cystic
degeneration and
hemorrhage
27. Glioblastoma- morphology
MICRO:
•Densely cellular with
nuclear pleomorphism
•Necrosis in a serpentine
pattern
•Tumour cells crowded
along the edges of
necrosis referred to as
pseudopalisading
• When vascular cell
proliferation is extreme,
the tuft forms a ball-like
structure, the glomeruloid
body
30. Pilocytic Astrocytoma (Grade 1)
• Have relatively benign behavior
• They typically occur in children and young adults
• Located in the cerebellum but may also appear in
the floor and walls of the third ventricle, the optic
nerves, and occasionally the cerebral
hemispheres
31. Pilocytic Astrocytoma (Grade 1)
Grossly
well circumscribed
cystic, with a mural
nodule in the wall of
the cyst
cystic astrocytoma of the cerebellum in a child
32. Pilocytic Astrocytoma (Grade 1)
The tumor is composed of bipolar cells with long, thin
“hairlike”processes that are GFAP-positive
Rosenthal fibers,eosinophilic granular bodies, and microcysts
are often present; necrosis and mitoses are rare
33. Oligodendrogliomas (Grade II/IV)
• Constitute 5% to 15% of gliomas ,Fourth and fifth decades.
• Cerebral hemispheres, with a predilection for white matter.
Morphology
• Grossly they are well-circumscribed, gelatinous, gray
masses, often with cysts, focal hemorrhage, and
calcification
• Microscopically the tumors are composed of sheets of
regular cells with spherical nuclei containing finely
granular chromatin surrounded by a clear halo of
cytoplasm (fried egg appearance)
• The tumor typically contains a delicate network of
anatomizing capillaries(chickenwire)
• Calcification seen in 90% of cases
36. Ependymomas- (Grade II/IV)
•Arise next to the ependyma - lined ventricular system
•First two decades of life - - they typically occur near the
fourth ventricle
•In adults, the spinal cord is their most common location;
tumors in this site are frequent in the setting of
neurofibromatosis type 2
Gross:
• Solid/papillary masses extending from the floor of
the ventricle
• Variant :Myxopapillary ependymomas occurs in
the filum terminale of the spinal cord
37. ependymoma arising from the
ependymal lining of the fourth
ventricle above the brainstem
and bulging toward the
cerebellum
CT scan
horizontal section of the
brain reveals a large
ependymoma of the fourth
ventricle
38. Ependymomas- (Grade II/IV)
Cells with regular, round to oval nuclei with abundant granular
chromatin in a dense fibrillary background
Tumor cells may form gland-like round or elongated structures
(rosettes, canals) that resemble the embryologic ependymal canal
39. • Subependymomas are solid, sometimes calcified,
slow-growing nodules attached to the ventricular
lining and protruding into the ventricle
• Choroid plexus papillomas can occur anywhere
along the choroid plexus and are most common in
children (lateral ventricles). In adults, they are
found in the fourth ventricle.
• There are rare cases of choroid plexus carcinoma
41. NEURONAL TUMORS
• Central neurocytoma: low-grade neoplasm found
within and adjacent to the ventricular system characterized
by evenly spaced, round, uniform nuclei and often islands
of neuropil
• Gangliogliomas are tumors with a mixture of glial
elements, usually a low-grade astrocytoma, and matureappearing neurons
• Dysembryoplastic neuroepithelial tumor is a distinctive,
low-grade childhood tumor
42. Embryonal (Primitive) Neoplasms
Medulloblastoma
•neuroectodermal origin, retain cellular features of
primitive, undifferentiated cells.
•accounts for 20% of the brain tumors in children
•Location :exclusively in the cerebellum.
Morphology
•Grossly : well circumscribed, gray, and friable
•Microscopically : highly cellular and are composed of
diffuse masses of small, undifferentiated oval or round
cells, like a lymphoma
Rosette formation- are groups of tumor cells
arranged in a circle around a fibrillary center
45. MENINGIOMAS (mostly Grade I/IV)
• predominantly benign tumors of adults, usually
attached to the dura
• That arise from the meningothelial cell of the
arachnoid.
Common sites of involvement
• Parasagittal aspect of the brain convexity
• Dura over the lateral convexity
• Wing of the sphenoid
• Olfactory groove, sella turcica
• Foramen magnum
• Ectopic meningiomas
46. MENINGIOMAS (mostly Grade I/IV)
Macro:
• usually rounded masses, bosselated or polypoid
appearance
• Extension into the overlying bone may be present
• The surface of the mass is usually encapsulated
• Usually, they displace brain tissue without invading it
• Some meningiomas grow flat on the surface of the brain
– en plaque variant
47. Morphology-Micro - types
• Syncytial appropriately named for the whorled clusters of
cells that sit in tight groups without visible cell membranes
• Fibroblastic with elongated cells and abundant collagen
deposition between them
• Psammomatous with numerous psammoma bodies,
apparently forming from calcification of the syncytial nests
of meningothelial cells
• Secretory with PAS-positive intracytoplasmic droplets and
intracellular lumens by electron microscopy
• Transitional which share features of the syncytial and
fibroblastic types
• Microcystic with a loose, spongy appearance
• Atypical, Anaplastic ,Papillary and Rhabdoid
50. METASTATIC TUMORS
• Metastatic lesions, mostly carcinomas, account
for approximately a quarter to half of intracranial
tumors
• The five most common primary sites are lung,
breast, skin (melanoma), kidney, and
gastrointestinal tract, accounting for about 80%
of all metastases.
• The Meninges are also a frequent site of
involvement by metastatic disease.
• Intraparenchymal metastases form sharply
demarcated masses, often at the gray matterwhite matter junction
• The boundary between tumor and brain
parenchyma is well defined microscopically as
well; melanoma is one tumor that does not
always follow this rule
51. METASTATIC TUMORS
Metastatic melanoma
multicentricity and well-demarcated
margins
The dark pigment in the tumor
nodules in this case is characteristic
of most malignant melanomas
Carcinomas that metastasize to
the brain parenchyma reach the
brain via arterial channels most
commonly encountered in the
territory of the middle cerebral
artery, often implant at graywhite junctions, typically well
circumscribed
52.
53. PERIPHERAL NERVE SHEATH TUMORS
arise from cells of the peripheral nerve, including
Schwann cells
perineurial cells
fibroblasts
Many express Schwann cell characteristics,
including the presence of S-100 antigen
MPNST -Malignant Peripheral Nerve Sheath Tumor
(MPNST, Malignant Schwannoma) :Are highly
malignant sarcomas that are locally invasive
54. Schwannoma
• These benign tumors arise from the neural crestderived Schwann cell and are associated with
neurofibromatosis type 2.
• common location - cerebellopontine angle usually
attached to vestibular branch of the eighth nerve
• Elsewhere within the dura, sensory nerves are
preferentially involved, including branches of the
trigeminal nerve and dorsal roots
• When extradural, most commonly found in
association with large nerve trunks, where motor
and sensory modalities are intermixed
55. Site: in the acoustic
(eighth cranial)
nerve at the
cerebellopontine
angle
Patients may
present with hearing
loss
Schwannomas
extra-axial, circumscribed and encapsulated and range from
small and solid to large, irregular, cystic, and hemorrhagic
tumors
56. Micro : Two growth patterns
Antoni A pattern
elongated cells with
cytoplasmic processes
arranged in fascicles
Regions of
nuclear palisading
The "nuclear-free zones" are
termed
Verocay bodies
Antoni B Pattern
The tumor is less densely
cellular
With a loose meshwork of
cells- looser, myxoid
regions
57. Neurofibromas
Two forms
cutaneous neurofibroma
• The most common form occurs in the skin
(cutaneous neurofibroma) or in peripheral nerve
(solitary neurofibroma).
• These arise sporadically or in association with
neurofibromatosis type 1
• The risk of malignant transformation from these
tumors is extremely small, and cosmetic
concerns are their major morbidity
58. Neurofibromas
Plexiform neurofibroma
•occur only in patients with neurofibromatosis type
1
•frequently multiple and the nerve is irregularly
expanded
•difficulty in surgical removal of these plexiform
tumors when they involve major nerve trunks
•have a significant potential for malignant
transformation
59. Morphology
Gross:
• Present in the dermis and subcutaneous fat or
arise anywhere along a nerve
• not encapsulated
On microscopic examination
- a loose, myxoid background with a low cellularity
A number of cell phenotypes are present
- Schwann cells, Inflammatory cells, Larger
multipolar fibroblastic cells
- areas of collagen bundles, which have a
“shredded carrot" appearance
60.
61. OTHER TUMORS
• Atypical Teratoid / Rhabdoid Tumor - highly
malignant tumor of young child
• Primary CNS lymphoma (PCNSL) It is the most
common CNS neoplasm in immunosuppressed
,are high grade Non-Hodgkin's B-cell ,Poor
prognosis
• Hemangioblastoma :Arises in the cerebellum
Important component of VHL
• Germ Cell Tumors :Occur along the midline, most
commonly in the pineal and the suprasellar
regions. Teratomas are common
Pineal Parenchymal Tumors –
well-differentiated lesions (pineocytomas)
high-grade tumors (pineoblastomas)
62. FAMILIAL TUMOR SYNDROMES
• These are a group of inherited diseases
characterized by the development of
hamartomas and neoplasms throughout
the body with particular involvement of the
nervous system
• Many of the disorders are inherited in an
autosomal-dominant pattern and have
been linked to tumor-suppressor genes
63. FAMILIAL TUMOR SYNDROMES
1)Neurofibromatosis Type 1 (NF1)
Autosomal-dominant characterized by
Neurofibromas
Gliomas of the optic nerve
Pigmented nodules of the iris (Lisch nodules)
Cutaneous hyperpigmented macules (café au lait
spots)
2)Neurofibromatosis Type 2 (NF2)
Autosomal-dominant disorder
Commonly bilateral VIII nerve schwannomas and
multiple meningiomas & Gliomas
64. Neurofibromatosis
an inherited disorder
Affected individual develop
multiple benign neurofibromas
that arise within or are
attached to the nerve trunks
in the skin
On the right side of the neck
and shoulder of this patient,
extensive subcutaneous
neurofibromas have formed
pendulous masses called
plexiform neurofibromas
an increased risk of developing
neurofibrosarcomas
This condition arises from
mutations in the NF1 tumor
suppressor gene
65. .
This patient shows
another typical
feature of
neurofibromatosis:
cafe' au lait spots.
These spots on the
skin (macules) have
light brown
pigmentation.
Neurofibromas are
not seen well in this
picture.
66. FAMILIAL TUMOR SYNDROMES
3)Tuberous Sclerosis
• Autosomal-dominant syndrome
• Characterized by hamartomas and benign
neoplasms involving the brain and other tissues.
• other lesions include renal angiomyolipomas,
retinal glial hamartomas, and cardiac
rhabdomyomas
• Cysts found in the liver, kidneys, and pancreas
•
Cutaneous lesions include angiofibromas, leathery thickenings in
localized patches (shagreen patches), hypopigmented areas (ashleaf patches), and subungual fibromas
67. 4) Von Hippel-Lindau Disease
• Autosomal-dominant disease
• Individuals develop capillary hemangioblastomas
within the cerebellum ,retina, & the brainstem and
spinal cord.
• cysts involving the pancreas, liver, and kidneys
are present
• may develop renal cell carcinoma of the kidney .
5) Others
• Turcot syndrome (APC)– Medulloblastoma
• Gorlin’s syndrome (PTCH)- Medulloblastoma
• MEN syndrome – Schwannomas
• Retinoblastoma (RB1) –
Retinoblastoma,pineoblastoma
• Li FRAUMENI –(P53) Malignant glioma
Editor's Notes
Various glia
Neurons with nucleus, nissl (Franz Nissl) granules, nerve fibers, glia. Glia are many times more common than neurons.
