3. INTRACRANIAL TUMORS (ICTS)
Primary or Metastatic
Occur with equal frequency in adults, but in children
primary tumors are far more common.
Primary ICTs account for
~2% of cancers in adults
20% of all cancers in children.
In children 70% of ICTs arise in Posterior fossa
(infra-tentorial). as
In adults 70% of ICTs arise in Supra-tentorial.
Cranial exposure to ionizing radiation is a risk factor.
4. Because of its location, a benign ICT may have
fatal “malignant” effects.
Malignant ICTs spread by:
Direct infiltration of adjacent tissues
May disseminate within the CNS via CSF.
Gliomas account for 60% of primary ICTs
Meningiomas for 20% & all others 20%.
All CNS tumors behave as malignant clinically
(Limited space)
8. The unique features of CNS tumors – “ICP”
1. They grow in a unique environment: the
intracranial space.
2. The intracranial contents - incompressible Brain and
blood contained within a rigid unyielding bony
structure.
3. Intracranial pathologies (tumors, abscess,
hematoma, infarction, edema, etc.) eventually produce
life threatening increase of the intracranial-pressure:
ICP.
9. Increased Intracranial Pressure (ICP)
Headaches, progressively worsening
Vomiting (morning)
Irritability
Papilledema
rare < 2 y/o - head can expand
“Double vision” with 6th nerve palsy
Head tilt
Bulging fontanelle (infant)
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10. Supratentorial Tumors
Signs depend on age and location:
Younger child:
Developmental delay or loss of milestones
Older child:
Deteriorating school performance
Personality changes
11. Depending on location
Supratentorial tumours:
- Motor weakness
- Sensory changes
- Speech disorders
- Seizures
- Reflex abnormalities
- Hand preference
12. In midline/infratentorial tumours:
- Classical triad of headache, nausea & vomiting
and Papilloedema
- Blurred vision, nystagmus & diplopia
- Disorder of equilibrium, gait & coordination.
- Torticolis: in cerebellar tonsil herniation
Diencephlic syndrome:
- Failure to thrive
- Emaciation & decreased appetite
- Euphoric affect
13. Brain stem tumours:
- Gaze palsy
- Multiple cranial N palsies
- UMN deficits
Optic N pathway tumours:
- Visual disturbances like decreased visual
acuity, marcus gunn pupil, nystagmus &
visual field defects
14. Suprasellar & 3rd Ventricle region tumours
Leads to neuroendocrine disturbances like
DI
Galactorrhoea
Precocious puberty
Delayed puberty
Hypothyroidism
Perinaud syndrome:
- Tumour of pineal region
- C/F : paresis of upward gaze, pupillary dilation, reactive
to accommodation,not to light,eyelid retraction
15. Spinal cord tumours:
- long N tract motor &/or sensory deficits
- Bowel & bladder deficit
- Radicular or back pain
17. ASTROCYTOMAS
Account for ~ 80% of primary ICTS in adults
MC in the cerebral hemispheres
MC Symptoms: headaches, seizures, focal
neurologic deficits ( usually in the anterior or
middle)
Low-grade Astrocytomas:
Gross:
Poorly defined gray-white infiltrative tumors.
Histology:
Hypercellularity; astrocytic nuclei of mild degree of atypia &
astrocytic processes Þ fibrillary background = fingers of
astrocytes
18. Low-grade Astrocytomas
Pilocytic Astrocytomas:
MC in the cerebellum of children & young adults; and
less commonly in the optic nerve, hypothalamic region
or cerebral hemispheres
Morphology:
Cystic, with a tumor nodule in the wall of the cyst.
Composed of bipolar astrocytes, with long hair-like
processes, Rosenthal fibers & Micro-cysts+
calcification = good prognosis
Grow very slowly (some patients have survived for >40
yrs after incomplete resection) & have an Excellent
prognosis
DD: not to confuse with low grade Fibrillary
Astrocytoma
23. Adverse prognostic factors in pt with
high grade Astrocytoma
Older age
Histologic f/o glioblastoma
Poor karnofsky performance status
Unresectable tumour
Pt with unmethylated MGMT
24. Glioblastoma Cerebri
Highly infiltrating, non enhancing tumour
involving more than 2 lobes
Histologically different from Glioblastoma
but behave aggressively & has poor
outcome
T/t: RT + Temozolamide
25. OLIGODENDROGLIOMA
Comprise ~ 5 -15% of Gliomas
Arise in the cerebral white matter
MC in the 4th & 5th decades
Gross:
Well circumscribed, gelatinous, gray masses, with foci
of hemorrhage & calcification.
26. Histology:
Sheets of cells with rounded nuclei surrounded
by a halo of clear cytoplasm (fried egg
appearance).
There is often a delicate network of capillaries
& scattered foci of calcification (psammoma
bodies)
Grows slowly, presents commonly with seizures,
prognosis is better than Astrocytoma, average
survival is 5-10 yrs (with modern therapeutic
approaches)
28. EPENDYMOMA
Arise from the Ependymal lining of the ventricles or
the central canal of the spinal cord
Arise in the
Fourth ventricle in children & young adults
Spinal cord in the middle aged.
Morphology:
Highly cellular, tumor cells have regular nuclei
May exhibit epithelial features with formation of
“rosettes” (Flexner Landsteiner) also perivascular pseudo-rosettes
(homer Wright)
Most tumors are well differentiated
29. 4th ventricle tumors:
May cause hydrocephalus, usually can’t
be completely removed
CSF dissemination may occur
Average survival is ~ 4 yrs
30. Myxo-papillary Ependymomas
Arise in the filum terminale of the spinal cord
Prognosis depends on completeness of surgical
excision
32. MEDULLOBLASTOMAS
Second MC ICT of childhood (after Astrocytomas).
Occurs exclusively in the cerebellum.
Derived from fetal external granular layer of
cerebellum.
Grows rapidly & occludes CSF flow ®
hydrocephalus.
33. Seeds through CSF ® implants around the
spinal cord & cauda equina (need irradiation
of the whole Neuraxis).
Histology:
Extremely cellular, anaplastic, small round or
carrot-shaped cells with hyperchromatic nuclei,
N/C, may form Homer-Wright pseudo-rosettes
Highly malignant, yet radiosensitive & 5-yr
survival 75%.
36. MENINGIOMA
Usually Benign slow-growing tumors of adults, F/M
3:2
Originate from meningothelial cells of the arachnoid.
Usually solitary ( multiple meningiomas Þ NF2 )
Morphology:
Firm rounded masses, adherent to the dura and
compressing the underlying brain (no infiltration).
Histologic variants include:
Syncytial, fibroblastic, transitional, Psammomatous &
papillary ( propensity to recur).
37. Malignant Meningioma is very rare
Infiltrates the underlying brain, shows
marked nuclear atypia, mitoses, & foci
of necrosis.
Other rare sarcomas of meninges
include:
Hemangiopericytoma, malignant fibrous
histiocytoma & Fibrosarcoma.
40. NERVE SHEATH TUMORS
1. Schwannomas:
Benign tumors of Schwann cells
MC in the vestibular branch of the VIII CN at the cerebello-pontine
angle (acoustic neuroma) ® tinnitus & hearing loss
Also involve branches of the trigeminal nerve & dorsal nerve
roots
Tumors are encapsulated, attached to one side of the nerve;
axons do not pass through the tumor
Consist of
Antoni -A areas of high cellularity
Antoni -B myxoid areas
42. 2. Neurofibromas:
Benign tumors composed predominately of Schwann cells, but also
containing fibroblasts & perineural cells
May involve single or multiple dorsal spinal nerve roots (multiple in
patients with von Ricklinghausen's disease – NF1)
CN involvement is extremely rare
May present as
Localized fusiform enlargement of a nerve or
Extensively infiltrate along the nerve ® “ropy enlargement” of the
nerve & it’s branches (plexiform Neurofibroma)
Plexiform neurofibromas are usually part of NF1, excision is
very difficult
Histology:
Wavy spindle shaped cells, myxoid collagenous stroma with
interspersed nerve fibers
44. METASTATIC ICTS
Very rare in children.
Common Primaries:
Broncho-genic small cell undifferentiated (oat cell) ca.,
Breast ca., Malignant melanoma, RCC. & Colon ca.
Sites of metastases:
Cerebral cortex 80%;
Rest are in the cerebellum & brain stem.
50% are multiple; at the junction between the gray &
white matter.
Vertebral column is a common site for metastases of
Breast & Prostatic carcinomas
Thoracic spine 60%, Cervical 20% & Lumbar 20%
Treatment : Radiotherapy
45. CHOROID PLEXUS PAPILLOMA
MC in children Arising from the lateral
ventricles
In adults they are found MC in the 4th ventricle
Present with Hydrocephalus
Due to either over-production of CSF or to
obstruction of the ventricular system.
Consist of papillae with fibrovascular stalks
covered with a cuboidal or columnar ciliated
epithelium, recapitulating the structure of the
normal choroid plexus.
46. COLLOID CYST OF THE THIRD VENTRICLE
A non-neoplastic cystic lesion
Morphology:
Having a thin fibrous capsule, a lining of Cuboidal to
columnar epithelium & containing gelatinous
Proteinaceous material.
Attached to the roof of the third ventricle at the
foramina of Munroe & may cause sudden
obstruction of the CSF flow ® acute non-communicating
hydrocephalus ® brain herniation
& death
Symptoms: headaches (often positional), “drop
attacks”, incontinence
Goblet cells are confirmatory
47. MISCELLANEOUS (MIDLINE) TUMORS
Pinealomas:
True pineocytomas are extremely rare, may also have
pineoblastomas
Germinomas:
MC in the pineal & suprasellar regions in adolescents &
young adults
Closely resemble testicular Seminomas & ovarian
Dysgerminomas
Other GCTs (Teratomas & Choriocarcinomas) also
occur
48. Craniopharyngioma
Benign cystic tumors of children &
adolescents
Develop in the suprasellar region ®
Hypopituitarism
Originate from remnants of Rathke’s
pouch & contain squamous & columnar
epithelium
calcifications are common.
49. CNS LYMPHOMA
Primary CNS lymphomas
Account for ~1% of ICTs
MC CNS neoplasm in AIDS & other
immunosuppressed patients often arise deep
within the cerebral hemispheres & are commonly
bilateral
Lymphoma cells exhibit an angiocentric
distribution
Usually are B-cell lymphomas & many appear to be
EBV-related.
50. PCNSL: Pathophysiology
Focal Lesion most common presentation:
others include diffuse, uveal,
leptomeningeal, and intramedullary.
Infiltrates normal brain diffusely.
Spreads along CSF pathways.
Rarely spreads outside the CNS.
51. Secondary CNS lymphomas
Lymphomas arising outside of the CNS rarely
involve the brain parenchyma
May involve the meninges, intradural spinal nerve
roots & epidural space
52. Leptomeningeal Carcinomatosis
Occurs in 5-8% of patients with solid
tumors
Most common tumors to metastasize to the
leptomeninges are small cell carcinoma (9-
18%), and NHL (5-29%)
Other tumors include non-small cell lung,
breast, melanoma, and G.U.
53. Leptomeningeal Carcinomatosis:
Clinical Presentation
SYMPTOMS SIGNS
Headaches 33% Reflex assymetry(71%)
Lower Motor Weakness 38%
Weakness 60%
Parasthesias 34%
Back/Neck Pain 26% Sensory Loss 27%
Radicular Pain 33% CN III Paresis 20%
Diplopia 20% CN VII Paresis 17%
Mental Status change 17%
59. 4. von Hippel-Lindau disease
Hemangioblastomas of the cerebellum,
retina, brain stem & spinal cord
Cysts of liver, kidney & pancreas
incidence of RCC, may be bilateral
~ 10% of Hemangioblastomas Þ
polycythemia
Total surgical removal is curative
62. Evaluation on emergency basis
Complete history, physical examination &
neurologic assessment with neuroimaging
For primary tumours: MRI with gadolinium
contrast is the gold standard.
Low grade glioma: FLAIR MRI
MRI better than CT: Tumor of suprasellar,
optic path, infratentorial & pituitary region
63. Specific investigations
Neuroendocrine dysfunction evaluation : in tumor
of suprasellar,midline, pituitary & optic chiasmal
region
Serum & CSF bHCG and AFP: germ cell T
Lumbar Puncture:
- Indication: Medulloblastoma, ependymoma & germ
cell tumours
- C/I : newly dx hydrocephalous sec. to CSF flow
obstruction, tumour causing supratentorial midline
shift & infratentorial tumours.
64. MMAANNAAGGEEMMEENNTT
Multimodal i.e. surgery +/- chemoradiation
Symptomatic & definitive
Definitive:- depends on specific tumour
type
65. Symptomatic
Glucocoticoids: decrease perilesional edema &
improve neurologic function
- DDeexxaammeetthhaassoonnee is the DOC bcoz of low
mineralcorticoid activity
Seizure: anticonvulsants
- leviteracetam, topiramate, lamotrigine, valproic acid &
Lacosamide
- Phenytoin & carbamazepine should be avoided as
they may hamper the action of chemo bcoz they are
enzyme inducers.
66. Venous thromboembolism:
- Ass. With 20-30 % patients with high grade
glioma & brain metastasis
- Anticoagulants should be used
prophylactically
67. Astrocytoma: Surgical Treatment
Advantages of Large Resection
Accurate histological grade
Palliation of mass effect
? Improved quality of life
Decreased dexamethasone requirement
? Impact on overall survival
Retrospective studies say yes
No prospective, randomized trials
68. Radiation Therapy & Chemotherapy
Chemotherapy following external beam
radiation is advantageous in adults with
anaplastic gliomas. Much less benefit is seen
in patients with glioblastoma.
The few glioblastoma patients who benefit
tend to be those that live the longest,
suggesting that treatment preferentially
benefits patients with favorable prognostic
factors (i.e. young age, good P.S., minimal
post-op, residual tumor).
69. Glioblastoma
Maximal surgical resection f/b
Partial field external beam radiotherapy with
concomittant Temozolamide f/b
6-12 months of adjuvant Temozolamide
In c/o recurrence: reoperation, BCNU/
bevacizumab
70. Temozolomide
Active metabolite of DTIC
Crosses the blood-brain barrier
Oral dosing: 200mg or 150mg/m2/x5d q4 weeks
Well tolerated: nausea/vomiting,
myelosuppression
Idiosyncratic myelosuppression
71. Temozolomide
Indications:
Relapsed Gr III anaplastic gliomas
Grade IV glioblastoma multiformae
Role in initial therapy uncertain:
Probably equivalent to nitrosourea or PCV for high
grade gliomas
Role as a radiosensitizer highly questionable
(?) effective in oligodendroglioma.
72. Oligodendroglioma: Treatment
Complete surgical resection optimal
Radiation therapy of questionable benefit
Anaplastic oligodendrogliomas are
chemosensitive tumors:
Active regimens include:
Single agent nitrosoureas
PCV
Temozolomide
Other alkylating agents
Chromosomal karyotypes may help predict
therapeutic and clinical outcomes.
73. PCNSL: Treatment
Surgery
For Diagnostic purposes only; extensive
resection contraindicated.
Histologic diagnosis may be difficult from
a stereotactic biopsy.
75. PCNSL: Treatment
• PCNSL recurrent after radiation is often chemotherapy
sensitive, although few (if any) are cured.
• Drugs should possess anti-lymphoma activity and have
at least some ability to traverse a partially disrupted,
if not intact BBB
••Multiple drugs shown to have anti-PCNSL activity
Methotrexate (high-dose)
Procarbazine, CCNU,
Vincristine
BCNU
Ara-C
Cyclophosphamide,
Adriamycin,Vincristine,
Prednisone (“CHOP”).
Decadron
77. Brain Metastases: Treatment
Multiple Metastases
Goals:
1. Palliate neurological symptoms
2 Decrease future neurological morbidity
3. Prolong survival in selected patients
Treatment:
1. Whole brain XRT
2. Chemotherapy for chemosensitive tumors (i.e.
breast cancer, small cell lung carcinoma)
78. Leptomeningeal Carcinomatosis
Goals of Treatment:
Destroy circulating and perineural
neoplastic cells to stabilize or improve
neurologic dysfunction.
Prolong survival in specific tumor types
(lymphoma, leukemia, breast carcinoma).
79. Leptomeningeal Carcinomatosis
Radiation
Treatment:
Involved field for acute cranial or spinal nerve
involvement
No cranial-spinal
Chemotherapy
Intra-CSF: Intrventricular vs. Intrathecal (MTX, ara-C,
Depocyte, Thiotepa)
Ease of administration
Patient Comfort
Optimal CSF drug distribution
Systemic (?)
81. Spinal Cord Compression
Indications for Surgical Interventions:
Chance of restoring/preserving neurological
function (anterior resection)*
Initial presentation from an unknown neoplasm.
Previously irradiated field. *
Vertebral instability. *
Progressive neuroloic deteriation during and
following XRT. *
Intractable pain despite adequate XRT, steroids,
and analgesics.
* The decision to surgically intervene ultimately depends on an
estimate of the morbidity of surgery versus the potential for
significant quality survival.
82. Take home points
Brain tumors are second most common
Brain tumour with best prognosis in
children is JPA & worst prognosis : Brain
stem Gliomas
Over 70% of children diagnosed with
cancer can be cured of their disease.
Management is through multimodal
approach
