Pathology of CNS II

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• Pathology of CNS - II
• Dr.RAJI AL-HADITHI MD,FCAP

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• TUMORS OF CNS
• Brain tumors10-17/100,000 , 20 of childhood
  tumors
• Spinal cord tumors 1-2/100,000
• BrainSpinal cord tumors 101

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Specific Features

• Location within the brain may be more
• important than nature of tumor
• Most glial tumors have infiltrative growth
  pattern, metastasis is exceptional.
• Identical histological categories of tumors
• may differ in prognosis according to
• location the age of the patient.
• Histological distinction between benign and
  malignant tumor may be subtle.

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• Present localizing signs with or ? ICP
• Classified according to cell of origin
• degree of differentiation
• In children, 70 are primary infra- tentorial
  (posterior fossa)
• In adults 70 supratentorial are primary or
  secondary
• Tumors may dedifferentiate by time
• Heterogenous morphology

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• Classification of Tumors
• 1- Glial cells ? Glioma
• I- Astrocytoma
  variants
• ii- Oligodendroglioma
• iii-Ependymoma
• iv- Microglioma
• 2- Primitive Neuroectodermal cells ?
• Medulloblastoma,
  Neuroblastoma
• 3- Arachnoid cells ? Meningioma
• 4- Nerve Sheath? Schwannoma (Neurilemmoma),
  Neurofibroma
• 5- Lymphoreticular cells ? Lymphoma
• 6- Others

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• 1- ASTROCYTOMA
• Commonest glial tumour
• Different types
• Different age groups
• Solid or cystic, calcification , necrosis
• GRADE is extremely important.
• Mutated P53 is important in some.

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,
CT / Glioblastoma Multiforme
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ASTROCYTOMA/ GRADE

• -Four grades Pilocytic Astrocytoma(grade 1, WHO)
  Diffuse fibrillary astrocytoma
• (grade 11,WHO)
• Anaplastic
  Astrocytoma(grade111)
• Glioblastoma
  multiforme
• (grade 1V)
• Grading 1-Nuclear pleomorphism
• 2- Mitotic activity
• 3- Vascular
  proliferation
• 4- NECROSIS

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Astrocytoma / Types

• I- Pilocytic Astrocytoma
• - Most in children,Cerebellum, 3rd v,optic
  n
• - Low grade,often cystic
• - Contains microcysts Rosenthal Fibers
  ,Hyaline granular bodies.No necrosis or mitoses
• -Excellent prognosis
• II-Diffuse Fibrillary Astrocytoma
• - Any age, any site ,more in cerebrum
• - Low grade / high grade
• - May dedifferentiate

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• III-?Anaplastic Astrocytoma
• - More cellular
• - More vascular
• - Numerous Gemistocytes
• -Mitotic activity
• IV- Glioblastoma Multiforme
• - More in adults
• - Cellular pleomorphic tumor
• - Very vascular
• - NECROSIS is present, palisading
• -Very bad prognosis(mean survival 8-10m)
• This grading system is important in outlining
• type of therapy

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• 2- OLIGODENDROGLIOMA5-15 of glioma
• - More in adults , cerebrum
• - Small uniform cells with clear cytoplasm
  - Calcification is common, psammoma body,
  perinuclear halo(fried egg appearance)
• - Often mixed with astrocytoma
• -Chromosomal abnormality ch19 and ch1
• 3- EPENDYMOMA
• - Any age may be affected
• - Arise in ventricles , more in 4th.
• - May arise in spinal canal, more in
  adults
• - Features Perivascular
  pseudorosette
• Ependymal true
  rosettes
• - Disseminates in CSF

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Ependymoma in 4th.ventricle
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Ependymal Rosettes
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• 4- MEDULLOBLASTOMA
• - Midline cerebellar tumor in
• children
• - May be lateral, more in young adults
• - Primitive neuroepithelial tumor,
  malignant small cell ( blue cell tumor)
• - Microscopy Homer Wright Rosettes
• - Hydrocephalus ?ICP occur early
• - Radiation chemotherapy better
• -CSF dissemination

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CT- Medulloblastoma
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Medulloblastoma
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Medulloblastoma/ Rosettes
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• 5- LYMPHOMA
• - Primary or secondary to systemic
• lymphoma.
• - High grade B cell Lymphoma
• - Most frequent in AIDS patients
• 6- HEMANGIOBLASTOMA
• - Benign cerebellar cystic tumours
• - Vascular architecture with lipid
• laden macrophages
• -Erythropoietin like sub Polycythemia.
• 7- Atypical teratoid/rhabdoid tumor highly
  aggressive , infants and young children.
  

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• 7- MENINGIOMA
• Arise from meninges in brain or spinal cord.
• More in adult females
• Progeteron receptors identified
• Many types
• Psammamatous, Angioblastic, Transitional,
  Meningotheliomatous and fibroblastic, Papillary,
  Secretory, Clear cell and others.
• Usually benign but may recur(WHO G1)
• May be atypical(WHO G2) or Anaplastic(WHO G3)
• Brain invasion is most important criterion for
  malignancy

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Meningioma
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Meningioma
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8- METASTATIC TUMORS

• Account for about 25-50 of solid intracranial
  tumors
• Solid tumors
• Lung
• Breast
• Melanoma.
• Kidney.
• GIT
• Meningeal carcinomatosis
• Marked edema is often seen around metastasis
• Well delineated margin
• Paraneoplastic syndromes may occur e.g neuropathy

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Metastatic Melanoma
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9- OTHER TUMORS

• I- Colloid cyst of third ventricle
• 2- Germ cell tumors, germinoma
• 3- Tumors of pineal gland,Pineoblastoma
• 4- Tumors of pituitary, adenoma
• 5- Craniopharyngioma, suprasellar, cystic,

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10-Tumours of Peripheral Nervous System

• Mainly Schwannomas Neurofibromas
• More in adults, more in Neurofibromatosis I
• May be multiple
• Usually benign, rarely malignant (MPNST)
• Schwannoma encapsulated in peripheral,
• spinal, cranial sites ( Acoustic Neuroma)
• Neurofibromas are diffuse or nodular lesions in
  skin or subcutaneous tissue

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• Demyelinating Diseases

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• A group of diseases in which there is
  preferential
• loss of myelin with preservation of axon
• Peripheral nervous system is spared
• Include
• Inherited diseases involving myelin synthesis
  turnover e.g. Leukodystrophies(dysmyelination)
• Acquired diseases
• Viral infection by JC virus ? PML
• Acute disseminated
  encephalomyelitis
• Central Pontine Myelinolysis
• Idiopathic or acquired Multiple
  Sclerosis

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Multiple Sclerosis(MS)

• Relapsing and remitting disease
• Young adults (20-40), more in females
• Genetic predisposition HLA-DR2, 25 in twins
• Acquired environmental factors ? Immune insult
• - CD4 CD8 T lymphocytes in lesions
• - AB against myelin components complement
• are identified in lesions
• - CSF ?Oligoclonal band
• Ig G against myelin basic
  protein
• ?protein , ?lymphocytes.
• Characteristic patches in white matter ( CT, MRI)

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MS pathology

• Patchy demyelination in white matter of brain ,
  periventricular areas , optic nerves in spinal
  cord
• - Acute stage(Active plaque) Soft pink
  plaque
• Myelin breakdown , phagocytosis peri-
• vascular lymphocytic infiltration ,
  edema
• Chronic stage(Inactive plaque) Hard grey plaques
• Total myelin loss, no inflammation, loss of
  oligodendrocytes , reactive gliosis
• - Shadow plaques ? remyelination

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Multiple Sclerosis / A B stains for
myelin(Lugol fast blue) C Preservation of axons
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• Clinical features
• limb weakness 40
• parasthesia 20
• optic neuritis 20
• diplopia 10
• bladder dysfunction 5
• vertigo 5
• Death due to chest or urinary infection ,
  pressure
• sores .etc.

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• Acquired Metabolic Toxic Disorders

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Metabolic Toxic Disorders

• Liver disease Hepatic Encephalopathy
• Wilson Disease? Alzheimer type II astrocyte
• Toxic Disorders
• - metals
• - Industrial chemicals
• - Alcohol
• - Methotrexate ? white matter
  demyelinization
• - Ionizing radiation ? white matter
  ischemia

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Nutritional Diseases

• Thiamine deficiency? Wernicke encephalopathy
• nerve
  damage
• - Pathology hemorrhage in mamillary bodies
  ?
• hemosiderin deposition ?
  gliosis
• - End result Memory loss peripheral
  neuropathy
• Vitamin B12 deficiency ? Pernicious anemia
• Subacute Combined Degeneration of spinal
  cord
• - Myelin loss in dorsal lateral columns
• - Result in motor sensory loss

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• Degenerative Disease

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• Gradual loss of neurologic function affecting
  selective populations of neurons
• Unknown causes, some familial
• No effective treatment
• Classified according to neurological
  manifestation
• Dementia
• Postural / Movement disorders
• Combined

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Degenerative disorders
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Dementia

• Mainly disorder of the elderly
• Global impairment of intellect, reason and
  personality without loss of consciousness
• Classified into
• - Primary degenerative diseases
• e.g. Alzheimers Disease, Picks d. ,
  Parkinsons d.
• - Secondary e.g. Multi-infarct dementia
• Infections
• Chronic
  subdural hematoma

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ALZHEIMERS DISEASE

• Commonest cause of dementia in the west
• age ? 50
• Insidious progressive neurological disorder
• Sporadic or familial (10-15)
• Basic pathogenesis of the disease is linked to
  deposition of amyloid in the brain

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Pathogenesis

• 1- Genetic
• Abnormalities in chromosomes 21, 19, 14, 12, 1
• Chr.21? Amyloid Precursor Protein (APP)
• ?risk in Downs Syndrome
• Presenilin genes (141) ? amyloid
• AD is associated with Apolipo- protein E4
• allele ?in late onset sporadic or familial
  cases
• ? amyloid fiber formation

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• 2- Defects in the processing of APP
• Secretase enzymes ?, ?, ? on APP ? Soluble
  insoluble components
• APP ? Secretase ?
  amyloid
• ? Amyloid deposited in senile plaques wall of
  blood vessels
• This is induced by mutations in presenilin genes
• SORL1 gene mutation-late onset disease.

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• 3- Hyperphosphorylation of the protein Tau
• Tau is a normal protein involved in assembly of
  axonal microtubules their
• stability.
• Hyperphosphorylation leads to tangled
  microtubules are present in the neurofibrillary
  tangles.

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Pathology

• Atrophy of frontal temporoparietal cortex
• Microscopical changes
• 1- Amyloid angiopathy
• 2- Neurofibrillary tangles, mainly in
  pyramidal
• cells of hippocampus
• 3- Senile ( neuritic )plaques, cerebral
  cortex
• 4- Granulovacuolar degeneration in
  pyramidal cells
• Death in 5-15 years

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Atrophy in Alzheimers disease
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Neuritic Plaque
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Amyloid in BV wall neuritic plaque
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Neurofibrillary tangles in neuron
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• PARKINSONISM
• Disturbance of motor function with rigidity, slow
  movements, expressionless facies and tremor
• Adults in the 6th.decade
• Idiopathic Sporadic or familial , ? synuclein
  gene
• Secondary - Trauma, vascular disorders,
  encephalitis, toxic agents, drugs
• - Pathology
• Loss of dopamine-secreting neurons in Substantia
  Nigra ? depigmentation, gliosis
• Concentric laminated inclusions in cytoplasm
• (LEWY BODIES)

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Depigmentasion of S. nigra
Normal
Lewy Body
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• HUNTINGTONS DISEASE
• Hereditary progressive disease
• AD , defect on Ch.4, Huntingtin gene
• - Symptoms in middle age
• Involuntary chorieform movements dementia
• Atrophy of Caudate nucleus Putamen
• frontal cortex due to loss of neurons
• gliosis
• Symmetrical dilatation of lateral ventricles

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AMYOTROPHIC LATERAL SCLEROSIS

• Degenerative disease of motor neurons
• Progressive wasting of muscles with spasticity
• 5 familial, mutant ch. 21, most are idiopathic
• Pathology loss of motor neurons, gliosis,
  axonal degeneration, loss of myelinated fibres in
  lateral corticospinal tracts ? muscle atrophy
• Sites
• 1- Ant. horn cells of spinal cord
• 2- Brain stem nuclei
• 3- Upper motor neurons in cerebral
  cortex

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Loss of myelin in Corticospinal Tracts
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PERIPHERAL NEUROPATHIES

• 1- Nutritional metabolic neuropathies
• 2- Toxic neuropathies
• 3- Inflammatory neuropathies
• 4- Hereditary neuropathies
• 5- Miscellaneous neuropathies
• N.B - Many of the above etiological factors may
  also affect the central nervous system

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AXONAL DEGENERATION

• 1- Wallerian Degeneration Trauma ischemia
• - Axonal degeneration distal to transection
• - Central Chromatolysis
• - Myelin disintegration
• - Axonal regeneration -
  Remyelination
• 2- Distal axonal degeneration Nutritional def.
• toxic causes ? distal symmetrical sensory
  loss
• - Follows disruption of neuron metabolism
• - Dying back of axon with demyelination
• - Regeneration possible

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3- Segmental demyelination

• Axon intact but myelin sheath is broken ?
• bare axon ? myellination ? onion bulb
• If severe ? secondary axonal degeneration
• Leukodystrophies , hereditary, metabolic
  diseases..
• Inflammatory may follow some viral infections,
  mycoplasma, allergic.etc
• e.g. Guillain - Barre Syndrome

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Guillain Barre Syndrome

• Rapidly progressive ascending motor weakness,
  minimal sensory loss
• Respiratory failure
• Findings include infiltration of nerve by
• lymphocytes macrophages , demyelination
• CSF shows ? protein, minimal cells