CNS: Cancer & Raised ICP

Space-Occupying Lesions (tumor) & Raised Intracranial Pressure

Objectives:

Describe different types of space-occupying lesions in the cranium
Understand the effects of raised intracranial pressure (ICP)

CNS tumours

(general)

Adult brain tumours: supratentorial (top)

Childhood brain t.: infratentorial (below)

Even benign brain tumours (no function) may lead to serious clinical consequences

Depends on the location!

Rare for malignant tumours to metastasise outside CNS (blood flow filtered)

Primary CNS Tumours

Glial (all the support cells)	Astrocytoma (glioblastoma) (infiltrating vs. non-infiltrating)	Astrocytes (benign)
	Ependymoma	Ependymal Cells (lining)
	Oligodendroglioma	Oligodendrocytes (myelin)
Non-glial	Neuronal
	Meningioma	Meningo-endothelial
	Pituitary Adenoma	Pituitary gland
	Schwannoma (acoustic neuroma)	Myelin sheath
Others	Medulloblastoma	Ectodermal layer (children)
Others	Haemangioblastoma	Blood vessels

Glial Tumours

Infiltrating Astrocytomas

80% of adult primary brain tumours

Location	Cerebral Hemisphere (common) Causes the shifting of midline
Clinical Presentation	Seizures, headaches, focal neurological deficits (weakness)
Spectrum of differentiation: (grading)	Well defined tumour (cell-types) have better prognosis Grade II: Diffuse astrocytoma Grade III: ANaplastic astrocytoma Grade IV: Glioblastoma multiforme
Because of “infiltration” of cells, the boundaries between tumour cells and brain tissue is poor. Resection (surgical removal) usually compromises neurological function
Case: Glioblastoma Multiforme (grade IV) Poor prognosis
Histology	Necrosis ( pale pink – loss of nuclear detail) Vascular proliferation, Palisading (lining-up) of nuclei

Non-infiltrating Astrocytomas (pilocytic astrocytoma)

Grade I Astrocytoma
Well differentiated; Benign behaviour
Treatment: Resection
Patients: Children and Young adults

Oligodendrogliomas

Cells that act like the myelin sheath (insulation)

Location	Cerebral hemispheres; often anterior fossa
Histology	Cells: perinuclear “fried egg” appearance Capillary network “chicken wire” (mesh)
Oligodendrogliomas showing chromosome 1p/19q co-deletion have been found to be especially chemosensitive

Ependymomas (glial)

Columnar, Ciliated cells that line the CSF filled ventricles
Location: next to ventricular system (lateral, 3rd, 4th, aqueduct)

Non-Glial Tumours

Ganglioglioma

is low-grade tumor of mixed cell type. It is a type of brain tumor that contains properties of both glial cells and neuronal cells
most frequently occurs in the temporal lobes of children and young adults

Meningiomas

(Adults)

Benign
Meningo-endothelial cells of arachnoid → attaches to Dura
Only type that is not within brain tissue
Associated with mutations in the PTEN tumour suppressor gene

Histology

Whorled patterns of cells (circular nests of swirls)
Psammomatous calcification common

(calcification in concentric rings)

Pituitary Adenoma (benign tissue)

Classified based on hormone they produce

Functional tumours present earlier then non-functional
Non- secreting adenoma = Hypopituitarism
Secreting adenoma = Hyperpituitarism

Clinical Presentation:

Seen as effects in change in hormones balance
No seizures or headaches

Anterior (6): Growth, FSH, LH, ACTH, TSH, Prolactin hormones

Posterior (2): ADH, Oxytocin

Generally affects the anterior pituitary (>)

Associated Syndromes

Genetic correlation : Familial isolated pituitary adenoma (FIPA) autosomal dominant
MEN : Multiple endocrine neoplasia
Pancreatic… (?)

Complication

Acromegaly : > growth hormone
Cushing disease: > ACTH cortisol (weight gain/ fatty deposits)

Treatment:

Medication of hormonal balance rather then resection

Visual field defects:

Tunnel vision: loss of peripheral vision
Due to pituitary tumour compression of optic chiasm (crossing of nasal-half optic nerve)

Acoustic Neuroma : Schwannoma

Benign → Schwann cells of cranial nerve VIII (8)

Association: Neurofibromatosis is a genetic disorder that causes tumors to form on nerve tissue. These tumors can develop anywhere in your nervous system.

Neurofibromatosis is usually diagnosed in childhood or early adulthood

Other Tumours

Medulloblastoma

A type of PNET (primitive neuroectodermal tumour)

Risk: Children

Location: Cerebellum

starts in the region of the brain at the base of the skull, called the posterior fossa
tumors tend to spread to other parts of the brain and to the spinal cord (metastatic)

May be associated with MYC amplification-transcription factor (more aggressive tumours)

Histology: “small round blue cell tumour”

Haemangioblastoma

Risk: Children
Originate from the vascular system of the CNS

Location: Cerebellum

Association:

Von Hippel-Lindau disease, an inherited autosomal dominant condition
Retinal angiomas, pancreatic cysts, pheochromocytoma and renal cell carcinoma.

Primary CNS Lymphoma (microglioma)

Most common CNS tumour in immunocompromised individuals (AIDs)

Aggressive; poor response to chemotherapy compared with peripheral lymphomas

Prognosis

Mean: 12-18 months
(3-4%) max: 5 years

Metastatic Tumour

Most common brain tumours seen in community hospitals

Mostly metastatic carcinoma (skin/tissue lining organs)
Lung, breast, kidney, GIT, Choriocarcinoma (uterus)

Location: grey-white matter junction

Raised Intracranial Pressure

Causes

Cerebral Oedema	Vasogenic Cytotoxic Hydrocephalus (CSF block -prevents drainage) Compressive (ISF block)
Hypertension/ Stroke/ Aneurysm	…

CSF flow : Choroid plexus → ventricles → Subarachnoid space → villi → Sinuses

Cerebral Oedema

Vasogenic: caused by blood-brain barrier disruption and increased vascular permeability, allowing fluid to shift from the intravascular compartment to the intercellular spaces of the brain
Cytotoxic: An increase in intracellular fluid secondary to neuronal, glial or endothelial cell membrane injury, e.g. in someone with a generalised hypoxic/ischaemic insult or with metabolic damage
Hydrocephalus: which results from obstruction of CSF bulk flow pathways.Distension of the collecting channels proximal to the block leads to retrograde flooding of the EC compartment with the formation of periventricular edema.

(e.g. block aqueduct → enlargement of ventricles)

If develops in infancy before closure of the cranial sutures, there is enlargement of the head (skull separates)

Progression

Cerebral oedema extremely common after a substantial head injury, esp. in children
May be related to DAI(diffuse axonal injury) and to concussion
Brain weight may increase by 100g, mainly in the white matter (original 1300~1400)
Cerebral oedema may be the only intracranial abnormality found at autopsy after a substantial head injury has occurred

Vasogenic

Brain Hemorrhage

Cytotoxic

Diffuse Axonal Injury (white matter)

Hypoxic Injury (lack of oxygen)

Cardiac arrest, stroke, asphyxial death, CO poisoning

Hydrocephalus

Brain Tumour

Herniation

Causes: (Increased ICP)

Cerebral oedema
Focal Lesion (haemorrhage / tumours / abscess)

If brain expansion is severe enough, will get herniation

Types:

Subfalcine (cingulate): the cingulate gyrus gets displaced under the falx cerebri
Transtentorial: the medial aspect of the temporal lobe is compressed against the free margin of the tentorium – uncus of temporal lobe is “squeezed” out
Tonsillar: displacement of the cerebellar tonsils through the foramen magnum (“coning”)

Subfalcine : Astrocytoma with white matter oedema and compression of lateral ventricle

Causes midline shift

Secondary Brainstem Haemorrhage

“Duret Haemorrhage”

small linear areas of bleeding in the midbrain and upper pons of the brainstem. They are caused by a traumatic downward displacement of the brainstem
Often accompany progressive transtentorial herniation
Believed to be due to distortion or tearing of penetrating veins and arteries supplying the upper brainstem

Summary

Primary CNS tumours: glial, non-glial, other
Don’t forget metastatic tumours, lymphomas
Raised ICP and herniation common final mechanism of death for space-occupying lesions in CNS

Children/ Young Adults	Non-infiltrating Astrocytoma Gangliomas Acoustic Neuroma; Schwannoma Medulloblastoma (ectodermal) Hemangioblastoma (vessels)
Adult	Infiltrating Astrocytoma Meningiomas Metastatic
Mix	Oligodendrogliomas Ependymomas Pituitary Adenoma Lymphoma