1. Brain Tumors
5th year neuroscience
M.Jamous M.D.

2. INCIDENCE: Second common cancer in children
Accounts for 3.5% of all deaths in pediatric age group.
25% of all tumors in adults are in the brain.

3. Aetiology: Most primary tumors are sporadic and of unknown aetiology.
Fewer than 5% are associated with hereditary syndromes that predispose to neoplasia.

4. Aetiology: 1. Sex – gliomas commoner in males
meningiomas commoner in females
Exposure to ionizing radiation implicated
in the genesis of
meningiomas
gliomas
nerve sheath tumors
Primary CNS lymphoma – is associated with immunodeficiency

5. Occupational exposures
multifactorial
Being male
Race
Age
Family
history
Occupational exposures

6. Heritable syndromes with increased risk of CNS tumours
Gene locus
Gene
Type of CNS tumour
NF type 1
17q11
NF1
Neurofibro
Mameningioma
optic nerve glioma
NF2
22q12
Meningioma, schwannoma
Tuberous sclerosis
9q34,16p13
TSc1/TSC2
SEGA
Vonhippel
3p35
VHL
Haemangioblastoma
Li-Fraumani
17q13
p53
glioma
Gorlin’s syndrome
9q31
PNET

7. Presentation - Neurological deficit 68% - HA 54% - Seizures 26%
(Depends on location, size, and type of tumor)
- Neurological deficit 68%
45% motor weakness
Mental status changes
- HA 54%
- Seizures 26%

8. Presentation - Increased intracranial pressure
- Cerebral edema
- Increased intracranial pressure
- Focal neurologic deficits
- Obstruction of flow of CSF
- Pituitary dysfunction
- Papilledema (if swelling around optic disc)

9. Clinical Presentation
Insidious onset
Headache
Seizure
Mental, behavioral and personality changes
Lateralizing or focal neurologic deficits
Increased ICP
Slowly Progressive Tumors

10. Course of Illness

11. Ipsilateral limb ataxia
Cerebellar tumor
Hemisphere lesion
Ipsilateral limb ataxia
Intention tremor
Dysmetria
Vermis lesion
Dysdiadochokinesia
Truncal ataxia
No limb ataxia

12. Site of brain tumors Adults Supratentorial: 80-85%
Infratentorial: 15-20%
- Children
- Infratentorial: 60%
- Supratentorial: 40%

13. Primary Secondary originates in the brain.
made up of cells that have spread (metastasized) to the brain .
Secondary
Primary vs. secondary:

14. Localized Invasive spread to surrounding areas confined to one area
easier to remove
Invasive
spread to surrounding areas
more difficult to remove completely

15. Intraaxial Extraaxial Intraventricular mostly manifesting as seizures
Meningioma
Pituitary adenoma
Vestibular schwanomma
Intraaxial
mostly manifesting as seizures
Glioma
Primary CNS Lymphoma
Metastatic
Intraventricular

16. Benign Malignant Cancerous slow-growing Fast-growing and aggressive
Noncancerous
do not spread to surrounding tissue.
Malignant
Cancerous
Fast-growing and aggressive
can invade nearby tissue and also are more likely to recur after treatment.

17. WHO Histologic Classification of Tumors of the CNS
Tumors of Neuroepithelial Tissue
Tumors of Cranial and Spinal Nerves
Tumors of the Meninges
Tumors of Uncertain Histogenesis
Hemangioblastoma from primitive vascular structures
Lymphomas and Hematopoietic Neoplasm
Germ Cell Tumor
Ex: Germinoma – common in pineal gland area
Cysts and Tumor-like lesions
Usually in the third ventricle
Tumors of the Sellar Regions
Local Extension from Regional Tumors
Metastatic Tumors

18. Neurons

19. Glial Cells
Schwann Cell
Astrocyte
Microglia
Oligodendrocyte

20. - Neuroepitelial tumors :
1. Astrocytoma
I, II benign
III (anaplastic astrocytoma) - malignant
IV (gliobastoma multiforme)
2. Oligodendroglial tumors
Oligodendroglioma
3. Ependymal tumors
Ependymoma

21. 4. Mixed gliomas
5. Neuroepitelial tumors – unknown etiology
6. Chorioidal plexus tumors
Papiloma
papilocarcinoma
7. Neuronal and mixed neuronalglial tumors
8. Pineal parenchymal tumors
9. Tumors with neuroblastic or glioblastic elements (embryonal tumors)
Meduloblastoma

22. - Tumors of sellar region
1. Pituitar adenoma
2. Pituitar carcinoma
3. craniopharyngioma
- Hemopoetic tumors
CNS lymphoma

23. - Tumors from germinative cells - Meningioma.
- Tumors of cranial and spinal cord nerves
Neurinoma (Schwannoma)
Neurofibroma
- Local tumors
Chondrosarcoma
Chondrocarcinoma
- Metastatic tumors

25. Common types of brain tumors

26. GLIOMAS Most common primary brain tumor
50% of all symptomatic brain tumors
Incidence increases with advancing age
Ionizing radiation: the only clear risk factor
Originate from glial cells or their stem cell precursors

27. GLIOMAS
Include:
Astrocytoma
Oligodendroglioma
Ependymoma

28. Astrocytoma Most common glioma Cerebral astrocytoma (more in adults)
Cerebellar astrocytoma (more in children)
Brain stem (children)

29. WHO GRADING SYSTEM for gliomas
Benign
Grade I-Pilocytic astrocytoma
Moderate cellularity-no anaplasia or mitotic activity
Grade II-Low-grade astrocytoma
Cellularity, anaplasia, mitoses
Grade III- Anaplastic astrocytoma
Same as Grade III plus microvascular proliferation and necrosis
Grade IV-Glioblastoma

30. WHO Classification: a. Increased cellularity b. Nuclear atypia
c. Endothelial proliferation
d. Necrosis

31. Grade I: Pilocytic Astrocytomas Primary in children & young adults
Focal astrocytoma may be associated with:
Neurofibromatosis type I (NF-I)
excellent prognosis

33. Grade II: Diffuse or Fibrillary Astrocytoma
Most common in the cerebral hemisphere in young adults
Low grade or benign histologically
Infiltrative – usually a problem because the tumor cannot be resected completely if this is a characteristic of the tumor
Latent potential for malignant transformation

35. Grade III: Anaplastic Astrocytoma Grade IV: Glioblastoma multiforme
Grades III and IV are high-grade gliomas
55% of gliomas
Peak incidence middle to late adulthood

38. MANAGEMENT FOR GLIOMAS

39. Prognosis of Astrocytomas
Median survival
GBM: 1 year
Anaplastic astrocytoma: 3 years
Low-grade astrocytoma: 5 years
Most die from transformation of tumor to higher grade

40. Oligodendroglioma Derived from oligodendrocytes or their precursors
Oligodendrocytes produce the white matter in the brain
5-7% of all intracranial gliomas.
Frequently with calcifications.
Frontal lobe
Most often in the 3rd and 4th decades
Highly infiltrative
Round regular “fried-egg” cells

43. “fried egg cells of oligodendroglioma”

44. Prognosis of Oligodendroglioma
Median Survival
Low-grade oligodendrogliomas: 8-16 years
Anaplastic oligodendrogliomas: 5 years
Tumors that have 1p/19q LOH—best prognosis
Many patients die from malignant transformation of the tumor

45. Ependymoma Arise from ependymal cells (an intraventricular tumor)
More common in children
Most common in the 4th ventricle
Spinal lesions more common in adults
Intracranial ependymomas predominate in children

48. Prognosis 10-year survival: 47-68% Better prognosis: Young age
Infratentorial
Gross total excision
Low-grade histology

49. MENINGIOMA Second most common primary brain tumor.
Originate from arachnoid cap cells (meningoepithelial cap cells normally seen in arachnoid villi).
20% of all intracranial tumors (with asymptomatic cases—40% or more).
Less than 1 cm per year (very slow growth but can recur)
Tumor doubling time: 1.27 to years

50. MENINGIOMA

51. MENINGIOMA Most diagnosed in 6th % 7th decades Female: Male—3:2 to 2:1
Multiple in 5-15% (NF-2)
90% intracranial
10% intraspinal
Spinal meningioma: 10x in women
All familial meningiomas occur with NF-2.
Rare in children (more in boys)
- Rare with dural attachments
- Usually Intraventricular or posterior fossa
- Frequently with NF-2

52. ESTROGEN receptors in meningioma
- Expressed in 80% of women with meningiomas
- Expressed in 40% of men with meningiomas
Hormonal therapy

55. Management: Surgery
Complete excision may cure many meningiomas
The extent of resection is the most important in determining recurrence
For recurrence: reresection

56. Radiation Therapy for meningioma
Residual tumor after surgery
Recurrent tumor
Atypical or malignant histology

57. TUMORS OF THE PITUITARY GLAND
Third most common primary
brain tumor
Often asymptomatic
Incidence at autopsy:
1.7 – 24%
Most common in adults in
the 3rd and 4th decade

61. Pathology Microadenoma Macroadenoma - Less than 1cm
- Symptoms due to excess hormone secretion (or hyperfunctioning)
a. Growth hormone
b. Gonadotropin
c. Thyroid hormone
d. Adrenal hormone
e. Prolactin hormone
Macroadenoma
- More than 1cm
- Symptoms due to compressing normal pituitary gland and neural structure causing hypofunctioning

62. Pathology Endocrine Active (Secretory)
Prolactinoma
Most common secretory intrasellar endocrine active tumor
Secreted either by microadenoma or macroadenoma
Growth hormone
Before closure of epiphysis ® gigantism
After closure of epiphysis ® acromegaly
ACTH: Cushing’s Syndrome
FSH and LH
Endocrine Inactive (Non-secretory or null cell adenoma)

63. Histological characteristics:
Almost all are histologically benign
Pituitary CA: rare

64. Pituitary Carcinoma Highly invasive Rapidly growing & anaplastic
Diagnosis relies on presence of distant metastasis

65. Clinical Manifestations of Tumors of the Pituitary Gland
Compression of neural and vascular structures
Headache
Hypopituitarism
Visual symptoms
visual loss
visual field abnormality: bitemporal hemianopsia is the most common
Papilledema is rare
5% of pituitary adenoma present with pituitary apoplexy

66. VISUAL FIELD PATHWAYS

67. bitemporal hemianopsia

68. Pituitary Apoplexy Hemorrhage or infarction of pituitary adenoma
Sudden onset of headache, nausea, vomiting, visual loss, diplopia, altered mental status
Diagnosis by CT or MRI
Treatment emergency surgery

69. Treatment
Surgery
Hormone replacement
Radiation Treatment
Radiosurgery

70. Medulloblastoma (MB)
Most common malignant primary brain tumor of child age group.
Small cell embryonal tumor of the cerebellum.
Usually arise in the cerebellar vermis in the region of the apex of the 4th ventricle.
Often presents with signs and symptoms of hydrocephalus.
All Medulloblastomas are WHO grade IV.

71. Epidemiology Overall account ~ 7% all brain tumors.
10-20% of brain tumors in pediatric age group.
40% of tumors of the posterior fossa.
Peak incidence at the age of 5 –6 yrs In children and 25 yrs in adults.
male : female (3:2)

72. Raised ICT: Due to obstructive or non communicating hydrocephalus
Clinical Features
Raised ICT: Due to obstructive or non communicating hydrocephalus

73. Clinical features….cont’
Presenting symptoms are related to the age of the patient.
infants (with open cranial sutures): irritability, anorexia, failure to thrive, macrocephaly and setting sun sign.
The younger, nonverbal patient presents with behavioral changes, listlessness, irritability, vomiting, and decreased social interactions.
Older children and adults headache, especially upon awakening in the morning.

75. Combination of: Surgery Radiotherapy chemotherapy
Treatment:
Combination of:
Surgery
Radiotherapy
chemotherapy

76. Hemangioblastoma
-Highly vascular , well circumscribed solid or cystic tumor of the CNS or retina.
-The most common primary intra-axial tumor of the posterior fossa in adult.
-May occur sporadically or as a part of vHL syndrome (in 20% of the cases).
-May be associated with polycythemia

77. epidemiology
1-2.5 % of all intracranial tumors.
Sporadic cases tend to occur in the 4th decade of life , while cases associated with vHL syndrome tend to occur early.

78. presentation
Signs and symptoms of cerebellar Hemangioblastoma are those of post.fossa mass lesion:
Headache
Nausea and vomiting
Cerebellar signs
Obstructive hydrocephalus

81. Cns lymphoma May be primary or secondary.
Suspected with homogenously enhancing lesion.
Diagnosis highly likely if tumor seen in conjunction with uveitis.
Primary B-cell lymphoma.

82. Conditions with increased risk of primary CNS lymphoma:
Collagen vascular diseases.
Immunosuppression
In transplanted patients.
AIDS (PCNSL occur in 10 % of AIDS patients)
Epstein – Barr virus (associated with almost 100 % of PCNSL)

85. METASTATIC BRAIN TUMORS
Cerebral metastases are the most common brain tumor seen clinically, comprising slightly more than half of brain tumors.
15-30% of patients with cancer (Ca) develop cerebral mets.

86. primary tumor was never identified
percentages of patients developing brain metastases for specific primary histologies:
lung cancer18-64%
breast cancer 2-21%
melanoma 4-16% %
colorectal cancer 2-12
Kidney 1-8%
thyroid 1-10%
unknown primary 1-18%
In up to 26% of cases, the
primary tumor was never identified

87. Secondary tumors
CT MRI

88. Spinal tumors