3. 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
4. • Brain and spinal cord tumors are masses of
abnormal cells in the brain or spinal cord that have
grown out of control.
• In most other parts of the body, it is very important
to distinguish between benign (non-cancerous)
tumors and malignant tumors (cancers). Benign
tumors do not grow into nearby tissues or spread to
distant areas, so in other parts of the body they are
almost never life-threatening. One of the main
reasons malignant tumors are so dangerous is
because they can spread throughout the body.
5. Types of Brain and Spinal Cord Tumors in Adults
• Tumors that start in the brain (primary brain tumors) are not the same
as tumors that start in other organs, such as the lung or breast, and
then spread to the brain (metastatic or secondary brain tumors).
• In adults, metastatic tumors to the brain are actually more common
than primary brain tumors. These tumors are not treated the same
way. For example, breast or lung cancers that spread to the brain are
treated differently from tumors that start in the brain.
• Unlike cancers that start in other parts of the body, tumors that start
in the brain or spinal cord rarely spread to distant organs. Even so,
brain or spinal cord tumors are rarely considered benign (non-
cancerous). Unless they are completely removed or destroyed, most
brain or spinal cord tumors will continue to grow and eventually be
life-threatening.
• Primary brain tumors can start in almost any type of tissue or cell in
the brain or spinal cord. Some tumors have mixed cell types. Tumors in
different areas of the central nervous system (CNS) may be treated
differently and have a different prognosis
8. 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 )
CNS Tumors
9. Risk Factors for Brain and Spinal Cord
Tumors
Most brain tumors are not linked with any known risk factors and have no
obvious cause. But there are a few factors that can raise the risk of brain
tumors.
• Radiation exposure
• Today, most radiation-induced brain tumors are caused by radiation to the
head given to treat other cancers. The possible risk from exposure
to imaging tests that use radiation, such as x-rays or CT scans, is not
known for sure.
• Family history
• Most people with brain tumors do not have a family history of the disease,
but in rare cases brain and spinal cord cancers run in families. Some of
these families have well-defined disorders, such as:
• Neurofibromatosis type 1 (NF1)
• Neurofibromatosis type 2 (NF2)
• Tuberous sclerosis
• Von Hippel-Lindau disease
• Li-Fraumeni syndrome
10. Other syndromes
Gorlin syndrome (basal cell nevus syndrome)
Turcot syndrome
Cowden syndrome
Having a weakened immune system
Factors with uncertain, controversial, or unproven effects on brain
tumor risk
Cell phone use
Other factors
Other environmental factors such as exposure to vinyl chloride (a chemical
used to manufacture plastics), petroleum products, and certain other
chemicals have been linked with an increased risk
11. 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
12. CLASSIFICATION
TUMOURS
MIXED TUMOURS WITHTUMOURS OF
GLIAL & NEURONAL
COMPONENTS
Ganglioglioma
Dysembryoplastic
Medulloblastoma
Atypical
teratoid/rhabdoid
tumour
Medulloepithelioma
Dysplastic
Gangliocytoma of the
cerebellum (Lhermitte –
Duclos disease)
Polar spongioblastoma
Neuroepithelial tumour PERIPHERAL
(DNT)
POORLY
DIFFERENTIATED AND TUMOURS
EMBRYONAL
TUMOURS OF THE
GLIAL TISSUE –
(GLIOMAS)
Astrocytoma
Oligodendroglioma
Ependymoma
TUMOURS OF NEURONS
Gangliocytoma
Neuroblastoma
Ganglioneurocytoma
Gliomatosis cerebri
Cerebral neuroblastoma
Central neurocytoma
THE
MENINGES
Meningioma
NERVE
SHEATH
Schwannoma
Neurofibroma
Malignant
nerve sheath
tumour-
MPNST
( Malignant
Schwannoma
)
Miscellaneous
TUMOURS
Hemangioblastoma
Craniopharyngiom a
Pituitary tumours
Mesenchymal
tumours
M E T A S T A T
I C TUMOURS
PRIMARY
CNS
LYMPHOMA
13. 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
14.
15. 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
•
•
•
•
16. 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
17. 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.
18. The majority of CNS tumors (brain and
spinal cord are primary)
Only one fourth to one half are
metastatic
Tumors of the CNS account nearly 20%
of all cancers of childhood.
70% of all childhood tumors arise
infratentorially
About 70% of all CNS tumors in adults arise
supratentorially
19. 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
20. 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.
22. TUMOURS OF THE GLIAL TISSUE – (GLIOMAS)
▪ Astrocytoma
▪ Oligodendroglioma
▪ Ependymoma
Astrocytoma
▪ Fibrillary astrocytoma
▪ Glioblastoma
▪ Pilocytic astrocytoma, and
▪ Pleomorphic xanthoastrocytoma
23. 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
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
• 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. 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
27. 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
•
•
•
28. 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 ependymomasoccurs in
the filum terminale of the spinal cord
•
29. • 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
31. 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 mature-
appearing neurons
• Dysembryoplastic neuroepithelial tumor is a distinctive,
low-grade childhood tumor
32. 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
33. 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
34. 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 matter-
white 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
•
•
•
•
35. 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
36. Schwannoma
• These benign tumors arise from the neural crest-
derived 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
37. 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
•
•
38. 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
39. 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)
40. 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
41. 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
42. 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
43. . 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.
44. 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 (ash-
leaf patches), and subungual fibromas
•
•
•
45. 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
•
46. The clinical course of brain tumors is strongly
influenced by
1. Patterns of growth
- Some glial tumors with low grade histologic features may
infiltrate large portions of brain and lead to serious clinical
deficits and may not be amenable to surgical resection
2. Location of the tumor:
-Any CNS neoplasm regardless of its histologic grade may have
lethal consequences if situated in a critical brain region
-For example a benign meningioma may cause cardiorespiratory
arrest if originate in the medulla oblongata because it may
compress vital centers
-The highly malignant gliomas rarely metastasize outside the CNS
-Tumors such as ependymomas and medulloblastomas are able to
spread through CSF if they encroach upon the subarachnoid space ;
therefore may be associated with implantation along the brain and
spinal cord away from the original tumor site
47. Classification
World Health Organization classification
Primary tumors classified on basis of cell origin
Most primary tumors of neuroepithelial origin
From malignant transformation of astrocytes,
ependymocytes, and oligodendrocytes
Gliomas most common
Arise from astrocytes
Metastases more likely than primary CNS
tumor in patient with known systemic malignant
disease
48. Brain and spinal cord tumor grades
The World Health Organization (WHO) divides brain and spinal cord tumors
into 4 grades (using Roman numerals I to IV), based largely on how the cells
look under the microscope:
• Grade I: These tumors typically grow slowly and do not grow into (invade
or infiltrate) nearby tissues. They can often be cured with surgery.
• Grade II: These tumors also tend to grow slowly but they can grow into
nearby brain tissue. They are more likely to come back after surgery than
grade I tumors. They are also more likely to become faster-growing
tumors over time.
• Grade III: These tumors look more abnormal under the microscope. They
can grow into nearby brain tissue and are more likely to need other
treatments in addition to surgery.
• Grade IV: These are the fastest growing tumors. They generally require
the most aggressive treatment.
49. Clinical Manifestations
Symptoms from intracranial tumors
Compression of brain by tumor and
presence of associated edema
Infiltration and destruction of brain
parenchyma by tumor cells
Rigid cranial cavity so benign and
malignant tumors may cause symptoms
50. Symptoms from primary brain tumors
slowly progressive
Symptoms from metastatic tumors
more acute
Grow more rapidly and associated with
edema
Hemorrhage into tumor
May present with generalized
symptoms from increased intracranial
pressure or focal symptoms from
areas of compromise
51. Generalized symptoms
Headache
Most common generalized symptom and first in
½ of adults
Infrequently from tumor itself but rather from
increased intracranial pressure
Changes in mood or personality
Decrease in appetite
Nausea
Projectile vomiting – in children
Generalized or focal seizures – in 20% of
patients
52. Focal symptoms
Frontal lobe tumors
May be massive before symptoms cause problems
Progressive difficulty with concentration and
memory, personality changes, and lack of
spontaneity
Urinary incontinence and gait disorder
Appearance of primitive reflexes in bifrontal
disease
53. Parietal lobe tumors
Subtle signs or more dramatic like
hemianesthesia
Right: spatial disorientation or left
homonymous hemianopia
Left: receptive aphasia or right
homonymous hemianopia
54. Temporal lobe tumors
Personality changes, auditory
hallucinations, complex partial seizures,
and quadrantanopia
Uncal herniation if large enough
Metastatic spread of primary CNS
tumors to sites outside CNS rare
Spread to meninges and spinal cord
occurs with most malignant CNS
tumors
55. Medical history and physical exam
Imaging tests
Magnetic resonance imaging (MRI) scan
MRI scans The images they provide are usually more
detailed than those from CT scans
Magnetic resonance angiography (MRA) and
magnetic resonance venography (MRV):These
special types of MRI may be used to look at the blood
vessels in the brain. This can be very useful
before surgery to help the surgeon plan an operation.
Magnetic resonance spectroscopy (MRS): This test
can be done as part of an MRI. It measures
56. Patient Evaluation
Careful neuro exam
Contrast-enhanced CT scan or MRI
MRI superior
More useful in imaging posterior fossa
More sensitive in detecting parenchymal invasion
CT scan without contrast not adequate
for primary or metastatic tumors
Cerebral angiography only when tumor
blood supply needed prior to resection
57. Biopsy
Accurate histological diagnosis
Detect other disease like abscess
Open craniotomy or MRI-guided or CT- guided
stereotactic techniques
In 20% of patients with metastatic tumors, CNS
biopsy helpful in identifying primary site
Lumbar puncture
Helpful only if suspect leptomeningeal involvement
Contraindicated when intracranial mass lesion
present
58. - Treatment protocols of CNS tumors are
usually based on WHO classification,
which segregates tumors into four grades
according to their biologic behavior from
grade I to IV
59. Treatment
and respond to chemo and radiation combination
Surgery
Most patients with primary tumors
Many patients with solitary brain metastasis
May relieve symptoms for many months if debulk
tumor when surgical cure unlikely
No extensive resection with brain stem tumors
Radical resection not recommended for tumors in
language or sensorimotor areas, basal ganglia, or
corpus callosum due to neuro dysfunction
Not recommended for CNS lymphoma: multifocal
60. Increased intracranial pressure
don’t need postoperatively
Most patients have brain edema and benefit
from glucocorticoids, usually
dexamethasone
In life-threatening edema with signs of
herniation, can give mannitol with
dexamethasone
Anticonvulsants
Given if develop seizures
Given if at risk of developing seizures before
performing biopsy or surgery: many patients
61.
Converging more than 200 beams of
radiation onto small, well-defined tumors
•
Radiation
• Conventional – external beam
• Uses direct X-rays to whole-brain or focal
area
• Whole-brain radiation associated with long-
term toxicity, like dementia and gait
disturbance
2. Brachytherapy
• Implantation of permanent or temporary
radiation “seeds” within tumor
Allows higher doses to tumor while
preserving normal tissue
•
• “Radiosurgery”
62. Chemotherapy
Not used as sole therapy
Major obstacle is blood-brain barrier
CNS tumors often drug resistant
Biodegradable wafers impregnated with
nitrosurea BCNU placed into tumor after
resection
Oligodendrogliomas unusually sensitive
CNS lymphomas treated with combination
chemo and radiation
63. Spinal Cord Tumors
Much less common than brain
Extradural or intradural
Most extradural are metastasis from other
sites
Intradural described as
Extramedullary: arising outside spinal cord, e.g.
schwannomas and meningiomas
Intramedullary: arising within spinal cord, e.g.
ependymomas and astrocytomas
Most common location is thoracic area
64. Symptoms usually from compression of
normal structures or compromise of
blood supply not invasion of parenchyma
Early symptoms are back pain and distal
paresthesias; then loss of sensation and
weakness below level of tumor and loss of
bowel and bladder control
MRI most useful and mostly replaced
myelography
Urgent evaluation if progressive deficits
65. Treatment with surgical resection
High-grade astrocytoma followed by
radiation
Epidural metastasis treated with high
doses of corticosteroids and surgery or
radiation
Surgical decompression if acute onset of
symptoms or if pathology not known
66. 34
Subdural lipoma demonstrated by MRI in
sagittal section. The lipoma (large arrows) is
severely compressing the spinal cord (small
arrows).
