Tumors of the CNS

1. BRAIN AND PITUITARY
TUMORS
PRESENTER: AMPAIRE EGIDIUS.
SUPERVISOR: DR MUSINGUZI

2. OUTLINE
• Anatomical aspect of brain and pituitary gland.
• Embryological aspect of brain and pituitary
• Definition
• Epidemiology
• Pathophysiology and pathogenesis
• Clinical presentation
• Diagnosis
• Management.
• Prognosis.

3. ANATOMY OF THE BRAIN
• The brain; part of the central nervous system inside the cranial cavity
and is continuous with the spinal cord through the foramen magnum.
• Its composed of three main structural divisions;
Cerebrum
Brain stem
Cerebellum.

4. ANATOMY OF THE BRAIN CONT…
CEREBRAL HEMISPHERES;
• Structurally, each cerebral hemisphere is divided into four major
anatomical lobes:
 frontal,
 parietal,
 occipital, and
 temporal.
• The frontal lobes are located anteriorly and are separated from
the more posterior parietal lobe by the central sulcus (sulcus of
Rolando).

5. Laterally, the frontal lobe is separated from the temporal lobe
by the lateral sulcus (fissure of Sylvius).
 Along the midline, the cerebral hemispheres are separated
from one another by the longitudinal fissure (interhemispheric
fissure, sagittal fissure).
The path to and from the cerebral cortex is achieved through
various white matter pathways coursing through the spinal cord,
brainstem, and cerebral hemispheres.

6. Cerebrum hemisphere lobes

7. Ventricular system.

9. MENINGES
Within the bony encasement of the skull and vertebral column,
the CNS is surrounded by three concentric, connective tissue
coverings called meninges, which act to support and stabilize
the brain and spinal cord.
The outermost covering is the dura mater, a tough, fibrous
sheet composed of two layers.
 The outer periosteal layer is adherent to the skull, and the
inner meningeal layer lies against the underlying arachnoid
mater.

10. Deep to the dura mater is the arachnoid mater.
 The pia mater forms a thin, veil-like layer that closely follows
the gyri and sulci on the surface of the brain.
 The pia and arachnoid matter are separated by a
subarachnoid space that contains CSF and the major blood
vessels supplying the brain.

11. Coronal section of the cranial meninges: dura mater,
arachnoid mater, and pia mater.

12. BRAIN STEM
The brainstem is a stalk like structure within the posterior
cranial fossa of the skull connecting the forebrain and spinal
cord.
 From rostral to caudal, the brainstem consists of the midbrain,
pons, and medulla oblongata.
Broadly speaking, the brainstem has three main functions:
 It is a conduit for tracts ascending and descending through
the CNS;

13.  It houses cranial nerve nuclei III to XII (note that the CNXI is in
the cervical spinal cord); and
 It is the location for reflex centers related to respiration,
cardiovascular function, and regulation of consciousness.
 Externally, each portion of the brainstem has a distinct
appearance and structural features that define its many
functional roles.

14. Posterior aspect of the brainstem.

15. Arterial branches on the inferior surface of
the brain, which form the circle of Willis.

17. CEREBELLUM
The cerebellum is the largest structure of the hindbrain.
 It resides within the posterior cranial fossa and is composed of two large
hemispheres, which are connected by the vermis in the midline.
 Functionally, the cerebellum plays a role in maintaining balance and
influencing posture and is responsible for coordinating movements
by synchronizing contraction and relaxation of voluntary muscles.
Within the posterior cranial fossa, the cerebellum is covered by the
tentorium cerebelli of the dura mater and connects to the posterior surface
of the brainstem via the superior, middle, and inferior cerebellar
peduncles.
 Anteriorly, the cerebellum forms the roof of the fourth ventricle

18. Cerebellum; Anterior and inferior view.

19. Embryology of the brain.
During the third week of development the outermost layer of
the embryo—the ectoderm—thickens to form a neural plate .
This plate develops a longitudinally running neural groove,
which deepens so that it is flanked on either side by neural
folds.
 These folds further develop and eventually fuse during a
process called neurulation to form a long tubelike structure
called the neural tube with an inner lumen called the neural
canal.

20. Continued proliferation of the cells at the cephalic end cause
the neural tube to dilate and form the three primary brain
vesicles.
 Caudally, the neural tube lengthens and narrows to form the
spinal cord.
The neural canal forms the cavities of the ventricular system in
the brain and central canal of the spinal cord.

21. The brain develops from enlarged cranial part of the neural tube.
 At about end of fourth week, enlarged cephalic part shows three distinct
dilatations called primary brain vesicles.
 Craniocaudally these are;
 prosencephalon (forebrain),
 mesencephalon(midbrain), and
 rhombencephalon (hindbrain).
Their cavities form ventricular system of adult brain.
During fifth week both prosencephalon and rhombencephalon subdivide
into two vesicles, thus producing five secondary brain vesicles.

23. Derivatives of vesicles of the neural tube

24. CEREBRAL VASCULATURE
Vascular supply to the brain is divided into the anterior circulation arising
from the internal carotid arteries and posterior circulation from the
vertebral arteries .
 The internal carotid arteries arise from the branching of the common
carotid arteries at the level of the fourth cervical vertebra.
Upon exiting the cavernous sinus, the internal carotid artery gives rise to
the ophthalmic artery and then continues superiorly to give off the
posterior communicating artery and anterior choroidal arteries before
terminating as the anterior and middle cerebral arteries.
The two anterior cerebral arteries anastomose proximally via the anterior
communicating artery, anterior to the optic chiasm.

25. Inferior/ventral view of the brain exposing the circle of Willis, which is completed
by the anterior and posterior communicating arteries.

26. VENOUS DRAINAGE
Venous drainage of the cerebral hemispheres follows a system
of deep veins, superficial veins, and dural venous sinuses
before reaching the internal jugular vein.
 Before reaching the internal jugular veins, the superficial and
deep veins connect to the dural sinuses located between the
periosteal and meningeal layers of the dura.

27. Venous branches of the brain.

28. BRAIN TUMORS.
The term ‘brain tumor’ applies to a wide array of pathologies of the
brain in accordance to the World Health Organization (WHO)
classification.
Can be primary or secondary(metastatic tumors).
Secondaries are the commonest malignant tumour in the brain.
 Metastasis occurs usually from lung (commonest),nasopharynx or
from any other organ in the body.

29. Epidemiology
• Approximately 19 people per 100 000 are diagnosed with a primary
brain tumour every year.
• Primary brain tumours represent 1.5% of all cancers.
• Eight percent of all primary cancers arises in the CNS.
• In adults, it constitutes the sixth largest group of cancers and in
children the CNS is the commonest site for solid tumours.
• Most adult brain tumours are supratentorial but 60% of tumours in
tumours in children are infratentorial and arise in the posterior
posterior fossa.
• Secondary tumours are more common than primary tumours.

30. Classification
The WHO classifies primary brain tumours on the basis of cell
of origin and histological grade.
Common adult primary brain tumours include
 gliomas and meningiomas (15–20% of total),
 pituitary adenomas (10–15% of total) and
 vestibular schwannomas.
 Grade 1 is applied to ‘benign’ lesions, while grade 4 implies
high-grade malignancy.

31. Primary brain tumuors
The majority of primary brain tumors are sporadic.
Some brain tumors are linked with known genetic abnormalities.
Neurofibromatosis type 1...mutation on chromosome 17, associated
with astrocytomas .
Neurofibromatosis type 2 ....a mutation on chromosome 22,
associated with schwanomas.

32. Chromosomal abnormalities
associated with brain tumours.

33. Primary brain tumors according to their
occurrence.
 GLIOMAS (43%).
 MENINGIOMAS (18%)
 SCHWANNOMA (8%)
 PITUITARY TUMOURS (12%).
 CRANIOPHARYNGIOMAS (5%).
 BLOOD VESSEL TUMOURS (2%).

34. GLIOMAS
• Include;
Astrocytoma
 Oligodendroglioma
 Mixed tumours
a. Astrocytomas;
 are the commonest type.
They are usually malignant.
They can occur anywhere in the cerebral hemispheres, cerebellum or
brainstem.

35.  Peak incidence is in 4th decade.
They can be diffuse, solid or cystic.
They contain starshaped cells resembling adult neuroglial cells.
 Astrocytic gliomas are graded as Grades I, II, III, IV based on the
quantity of adult cells and primitive cells.

36. Astrocytoma: WHO classification
Grade I:Pilocytic
Grade II: Diffuse
Grade III: Anaplastic
Grade IV: Glioblastoma multiforme
Glioblastoma multiforme—It is high grade aggressive type of
astrocytoma.
It is treated by surgical removal/debulking; high dose radiotherapy,
chemotherapy with carmustine inserted into the surgical cavity and
oral temozolomide.
 Median survival is 12 months;

37. s

39. b. Oligodendrogliomas:
 They are slow growing tumour commonly arising from frontal lobes,
 lasts for years;
shows calcification.
c. Spongioblastoma polare:
 They arise from primitive spongioblasts,
 affects optic chiasma, 3rd ventricle and hypothalamus.
They are both operable and radiosensitive.

40. e. Ependymomas:
 Here cells resemble ependymal cells; can occur throughout the
hemispheres.
They arise from cells lining the ventricles of the brain and central
canal of the spinal cord.
They are common in 4th ventricle;
common in younger individual; blocks CSF circulation causing
hydrocephalous.

41. 2. MENINGIOMAS (18%):
They are usually globular, arising from the arachnoids.
Tumour gets attached to the dura.
 It gets blood supply from dural arteries and veins, from emissary veins and
veins of diploe and scalp.
 Along these veins tumour cells invade the bone, causing bone destruction
and reactive hyperostosis.
Meningiomas are classified as:
 fibroblastic,
 endothelial and,
 angioblastic.
 Microscopically: It contains whorls of spindle cells, with central hyaline
material, with psammoma bodies.

43. CT scan head showing large meningioma
frontal region.

45. 3. SCHWANNOMA (8%)
Common in auditory nerve, also called as acoustic neuroma.
Occurs in the internal auditory meatus which projects into the
cerebellopontine angle (C- P angle), compressing 5, 6, 7, 8th nerves.
 It presents with compressive features like;
unilateral deafness,
 trigeminal neuralgia,
 squint and,
 cerebellar compression syndrome.
Note: First sign in acoustic neuroma is loss of corneal reflex.

46. SECONDARY BRAIN TUMOURS
• Secondaries are the commonest malignant tumour in the brain.
• Metastasis occurs usually from lung (commonest), nasopharynx or
from any other organ in the body.
• Common site.. Gray –white mater junction.
• Other sites include;Cerebellum and meninges.
• Usually by Hematogeneous spread

47. Tissue of origin for brain metastases
(approximate).

48. MRI is the best for diagnosis;
Lesions are typically well circumscribed, round, and multiple.
Management include:
Craniotomy plus whole brain radiotherapy
Palliation.

49. T1-weighted magnetic resonance imaging with contrast. Two right
occipital lung metastases are demonstrated. They are well demarcated
and enhance with gadolinium contrast.

51. Clinical Features of brain tumors
Initial period of silent growth.
 Focal syndromes with epilepsy.
 Raised intracranial pressure with headache, vomiting, deterioration of
level of consciousness, altered vision, slow pulse, high BP,
papilloedema.
 Brain displacement and stage of coning.

52. Patterns of deficit generally
associated with certain tumours.

53. Investigations
 X-ray skull:
May show;
Calcifications like in meningiomas, craniopharyngiomas.
Separation of sutures.
A beaten silver appearance.
Lateral displacement of pineal body.
Hyperostosis, expansion, destruction in skull bones.

54.  Isotope scan.
 CT scan.
 MRI.
 Positron Emission Tomography (PET).
 Carotid angiogram (Introduced by Egas Moniz).
 Ventriculography.
 EEG.

55. Treatment
 Relief of raised intracranial pressure:
 Ventricular tap and drainage through a posterior parietal burr hole.
 Tapping of cystic tumours and abscesses.
 Administration of mannitol.
 Emergency decompression by partial removal of tumour.
 Steroid therapy—dexamethasone.

56. Establishment of pathological diagnosis:
 Burr-hole and biopsy.
 Craniotomy and biopsy using brain cannula.
 Frozen section biopsy.
 CT guided stereotactic biopsy.

57.  Removal of benign tumours—by different craniotomy approaches.
 Decompressive surgeries for malignant tumours.
 Shunt surgeries to drain CSF—ventriculoperitoneal shunt or
ventriculoatrial shunt.
 Radiotherapy—external radiotherapy is used as primary treatment
or as an adjuvant therapy after surgery.
Chemotherapy is occasionally used—Temozolamide.

58. Prognosis
Tumour which is benign and surgically accessible has better
prognosis.
Without treatment, median survival is 1.5months.
Poor prognostic factors: >60yrs, tumor location(periventricular, basal
ganglia, brain stem, cerebellum)

59. Brain tumours in children
Brain tumours are the most common solid tumours in children.
Neonates develop predominantly neuroectodermal tumours in
supratentorial locations:
 teratoma;
 primitive neuroectodermal tumour (PNET);
 high-grade astrocytoma;
 choroid plexus papilloma/carcinoma.

60. Older children tend to suffer infratentorial tumours, especially:
medulloblastoma (an infratentorial PNET);
 ependymoma;
 pilocytic astrocytoma.

61. Embryology of pituitary gland.
The hypophysis rests upon the hypophysial fossa of the sphenoid
bone in the center of the middle cranial fossa and is surrounded by a
small bony cavity (sella turcica).
The pituitary gland develops from two distinct elements:
The anterior pituitary (adenohypophysis) arises from Rathke’s pouch,
an upward growth from the ectodermal roof of the stomodeum.
The posterior pituitary (neurohypophysis) arises from a downward
growth from the floor of the diencephalon.

62. The fully developed pituitary gland is pea-sized and weighs
approximately 0.5g
Adenohypophysis constitutes roughly 80%
Receives majority of blood supply from the paired superior
hypophyseal arteries which arise from medial aspect of the internal
carotid artery.

63. Pituitary tumours
constitutes; I 0-15% of all intracranial tumours
 Majority are benign adenoma
 Prolactinoma-30%
 Nonfunctioning adenoma-20%
 GH secreting adenoma-15%
 ACTH secreting adenoma-10%

64. Most tumours in the sellar region are benign pituitary
adenomas, but pathology in this region can also include
malignant variants, craniopharyngioma, meningioma, aneurysm
and Rathke’s cleft cyst.
Microadenomas are less than 10 mm in size and usually
present incidentally or with endocrine effects.
Macroadenomas are larger than 10 mm, and often present with
visual field deficits.

65. Thirty per cent of adenomas are prolactinomas, 20% are non-
functioning, 15% secrete growth hormone and 10% secrete
ACTH.
It secretes excess growth hormone causing acromegaly in adults and
gigantism in children.
May produce endocrine dysfunction such as galactorrhoea,
primary/ secondary amenorrhoea, Cushing’ syndrome,
acromegaly.

66. Hormonal secretion of the pituitary gland.

67. Acromegaly due to pituitary tumours.

68. Classifications of pituitary tumor
•Classifications I
1. Eosinophil (Acidophil) adenomas: Tumour is usually small.
 Rarely it causes compressive features.
2. Chromophobe adenomas are common in females and in the age group—
20–50 years.
Initially, it is intrasellar and after sometime becomes suprasellar.
Later, it extends intracranially often massively, causing features of
intracranial space occupying lesion.
 It presents with myxoedema, amenorrhoea, infertility, headache, visual
disturbances, bitemporal hemianopia, blindness, intracranial
hypertension, epilepsy.

69. Differential diagnosis of chromophobe adenoma:
 Meningiomas,
 aneurysms.
CT scan, angiogram, X-ray skull are diagnostic.
Treatment is surgical decompression by craniotomy through
subfrontal approach or trans-sphenoidal approach.
 Deep external radiotherapy and steroids are also used.

70. 3. Basophil adenomas
 are usually small.
 They secrete ACTH and
presents as Cushing’s disease with all its features.
4. Prolactin-secreting adenomas causes;
 infertility,
 amenorrhoea and
galactorrhoea.

71. ccc II

72. Other tumours
• They are;
 pineal region tumours,
pituitary adenomas,
craniopharyngiomas,
choroid plexus tumours, etc.

73. Metastases
One-fourth of all cancer patients have intracerebral metastases
at the time of death.
 Common primary sites include;
 the bronchus (50%),
 breast (15%), and
 melanoma (10%).

74. Investigations
 X-ray skull—shows calcifications, destruction of sella turcica,
mass lesion, enlarged pituitary fossa.
 CT scan.
 MRI.
 Hormone assay—like serum prolactin, growth hormone, ACTH,
steroids, sex hormones, etc.

75. Non-functioning pituitary macroadenoma (arrow) compressing the optic chiasm superiorly,
extending into the right cavernous sinus and encasing the right carotid artery.( Rathke’s cleft cyst)

76. Treatment
• They can be divided into medical and surgical line of treatment.
I. Medical
 Acutely raised intracranial pressure (ICP) is treated with IV mannitol 0.5-
1 g/kg body weight.
 Hydrocephalus can be relieved using a CSF diversion system (closed
external ventricular drainage or a ventriculoperitoneal shunt).
 Seizures are treated with lorazepam and phenytoin commonly and
maintained on phenytoin.
 Corticosteroids, especially dexamethasone 4 mg qid is given to reduce
symptoms of raised ICP, which may make surgery easier.

77. II. Surgery
This is the mainstay of treatment.
 The aim of surgery is to obtain a complete tumour excision
without producing a neurological deficit.
This is not always possible due to the site of the tumour, in
which case compromises must be made and a debulking
procedure is done.
 Any residual tissue may be observed or treated with adjuvant
radiotherapy.
 Stereotactic guided surgery is now a well-established
concept in brain surgery allowing more targeted treatment of the
lesion with minimal surrounding damage.

78. III. Radiotherapy
Intracranial tumours are relatively radioresistant, and
radiotherapy is primarily a palliative treatment.
IV. Chemotherapy
 No definite benefit of chemotherapy for the treatment of brain
tumours.
 Temozolomide is a promising new drug for the treatment of
brain tumours.

79. Prognosis.
Surgery offers good prospects for the treatment of benign brain
tumours such as meningioma or pituitary adenoma, but
outcome of treatment of malignant tumours is still poor.

80. References.
• Bailey and love`s short practice of surgery 27th edition.
• SRB`s manual of sugery-5th edition.
• Schwartz`s principles of surgery.