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CENTRAL NERVOUS

SYSTEM
PART 2: CNS
TUMORS
VOLTAIRE C. YABUT,M.D. DPSP
CNS TUMORS
intracranial 10-17 : 100,000 population
Intraspinal 1-2: 100,000 population

Primary ½-¾
Metastatic – remainder

20% of childhood tumors


 Posterior fossa (70%)
 Adults – cerebral hemispheres
CNS TUMORS
Distinction between benign and malignant
less distinct
Limited ability to resect without compromise of neuro
function
Anatomic site can have lethal consequences
Rarely metastasize outside CNS
 subarachnoid space – brain and spinal cord seeding
CNS TUMORS
4 Major Classes
 Gliomas
 Neuronal tumors
 Poorly differentiated neoplasms
 Meningiomas
GLIOMAS
Astrocytomas
Oligodendrogliomas
Ependymomas
GLIOMAS
Astrocytomas
Categories:
Fibrillary
Glioblastoma
Pilocytic
Pleomorphic Xanthoastrocytoma
GLIOMAS
Astrocytomas
Categories:
Fibrillary (Diffuse) Astrocytoma
80% of adult primary brain tumors
Cerebral hemisphere
Cerebellum, brainstem, spinal cord
Age: 40 – 60
Symptoms: seizures, headaches, focal neuro deficits
GLIOMAS
Astrocytomas
Categories:
Fibrillary (Diffuse) Astrocytoma
Morphology:
well differentiated
less differentiated
GLIOMAS
Astrocytomas
Categories:
Fibrillary (Diffuse) Astrocytoma
Morphology:
poorly defined
gray infiltrative tumor expand and distort the brain
few cm’s to displace entire hemispheres
firm or gelatinous
cystic degeneration

Gliomatosis cerebri - multiple regions of the brain infiltrated by


neoplastic astrocytes
GLIOMAS
Astrocytomas
Categories:
Fibrillary (Diffuse) Astrocytoma
Microscopic:
mild to mod inc in number of glial cell nuclei
variable nuclear pleomorphism
GFAP (+) astrocytic cell processes
Anaplastic
densely cellular
Mitotically active

Gemistocytic
Neoplastic astrocytes
Brightly eosinophilic cell body, stout processes
ASTROCYTOMA
GEMISTOCYTIC ASTROCYTOMA
GLIOMAS
Astrocytomas
Categories:
Glioblastoma (Glioblastoma Multiforme)
variable gross appearance
Firm white to soft and yellow
Well demarcated with infiltration beyond outer margin

Microscopic:
Similar to Anaplastic
Necrosis – “pseudopalisading”
Vascular or endothelial proliferation – “glomeruloid body”
GLIOBLASTOMA
GLIOMAS
Astrocytomas

WHO Grading
Grade I/IV Pilocytic
Grade II/IV Well differentiated astrocytomas
Grade III/IV Anaplastic
Grade IV/IV Glioblastoma
GLIOMAS
Astrocytomas

Molecular Genetics
Inactivation of p53
Overexpression of PDGF-A and its receptors
Transition to higher grade associated with additional
disruption of tumor suppressor genes, the RB genes,
p16/CDKNZA gene, putative tumor suppressor on
chromosome 19q
GLIOMAS
Astrocytomas
Clinical Features:
Presenting symptoms depend in part on location of
tumor and growth rate
Well-differentiated remain static, progress slowly
 Mean survival 5 years
Anaplastic present with rapid deterioration, very poor
prognosis
Current treatment (resection, radiotx, chemotx)
8 – 10 mos surivival
< 10% alive after 2 yrs
GLIOMAS
Astrocytomas
Categories:
Pilocytic
 Children and young adults
 Cerebellum, floor and wall of 3rd ventricles, optic nerves,
cerebral hemispheres
GLIOMAS
Astrocytomas
Categories:
Pilocytic
Morphology
often cystic, with mural nodule in the cyst wall
If solid, well circumscribed, less frequently infiltrative
GLIOMAS
Astrocytomas
Categories:
Pilocytic
Microscopic:
 Bipolar cells with long thin “hairlike” processes that are GFAP (+)
 Rosenthal fibers
 Eosinophilic granular bodies
 Microcysts
 Increase no. of blood vessels
 Necrosis and mitosis uncommon
 Narrow infiltrative border
PILOCYTIC ASTROCYTOMA
GLIOMAS
Astrocytomas
Categories:
Pilocytic
Clinical
Grow very slowly
Cerebellar tumors treated with resection
Rarely have p53 mutations or other changes found in
diffuse fibrillary
GLIOMAS
Astrocytomas
Categories:
Pleomorphic Xanthoastrocytoma
Relatively superficial
Temporal lobe
Children and young adults
Long history of seizures
GLIOMAS
Astrocytomas
Categories:
 Pleomorphic Xanthoastrocytoma

Microscopic:
neoplastic occ bizarre astrocytes
nuclear atypia can be extreme and may suggest high grade
astrocytoma
abundant reticulin deposits
relative circumscription
chronic inflammatory cell infiltrates
absence of necrosis and mitotic activity
GLIOMAS
Astrocytomas
Categories:
 Pleomorphic Xanthoastrocytoma

WHO grade II/IV


80% survival rate at 5 years
GLIOMAS
Oligodendrogliomas
 5 - 15%
 Age: 40 – 50

 Seizures for several years

 Predilection for white matter, cerebral hemispheres


GLIOMAS
Oligodendrogliomas
Morphology:
well-circumscribed, gelatinous, gray masses
often with cysts, focal hemorrhage and calcification
Microscopic:
Sheets of regular cells with spherical nuclei containing finely
granular chromatin surrounded by clear halo of cytoplasm
Delicate network of anastomosing capillaries
Calcifications in 90%
Low mitotic activity
WHO grade II/IV
Anaplastic oligodendrogliomas – increased cell density, nuclear
anaplasia, inc mitotic activity, necrosis
OLIGODENDROGLIOMA
GLIOMAS
Oligodendrogliomas
Molecular genetics:
loss of heterozygosity for chromosomes 1p and 19q
If without other alterations consistent and long lasting
response to chemotherapy and radiation

Clinical Features:
Better prognosis than astrocytomas
Ave 5 – 10 years survival
GLIOMAS
Ependymomas
 Arise next to ependyma-lined ventricular system
 First 2 decades – 4th ventricle
 5 – 10% of primary brain tumors
Adults – most common in spinal cord
GLIOMAS
Ependymomas

Morphology:
 In 4th ventricle, solid or papillary masses
 Intraspinal, sharply demarcated
Microscopic:
 Cells with regular, round to oval nuclei with abundant granular
chromatin
 Dense fibrillary background
 Rosettes, canals
 Perivascular pseudorosettes
 GFAP (+)
EPENDYMOMA
GLIOMAS
Ependymomas

Morphology:
Well-differentiated – WHO Grade II/IV
Anaplastic ependymomas – WHO Grade III/IV

Myxopapillary ependymomas – occur in filum terminale of


spinal cord
Papillary elements in myxoid background
GLIOMAS
Ependymomas
Molecular genetics:
 Spinal ependymomas associated with Neurofibromatosis 2
and NF2 gene on chromosome 22
Clinical features:
 Posterior fossa ependymomas manifest with hydrocephalus
sec to obstruction of 4th ventricle
 Prognosis is poor
 CSF dissemination is common
GLIOMAS
Ependymomas
Other tumors associated with other cell type
that forms the venticular system:
 Subependymomas
 Choroid plexus papillomas

 Colloid cyst of the third ventricle


NEURONAL TUMORS

Ganglion cell tumors


Contain ganglion cells
Gangliocytoma – entire population of lesion
Ganglioglioma – admixture with glial neoplasm

Slow growing
Glial components occ become anaplastic and progress rapidly
Present with seizure disorder
WHO grade I-II/IV
NEURONAL TUMORS

OTHER TUMORS WITH GLIAL AND


NEURONAL COMPONENTS
Dysembryoplastic neuroepithelial tumor (DNT)
 Low grade tumor of childhood
 Seizure disorder

 Slow growth

 Good prognosis
NEURONAL TUMORS

TUMORS WITH ONLY NEURONAL ELEMENTS


Cerebral neuroblastoma
 Rare, occur in children, highly aggressive
 Resemble peripheral neuroblastomas
 Homer Wright rosettes
Central neurocytoma
 Low grade neuronal tumors
 Lateral and third ventricles
 Resemble oligodendroglioma
POORLY DIFFERENTIATED
NEOPLASMS

Medulloblastoma
Atypical Teratoid/Rhabdoid Tumor (AT/RT)
POORLY DIFFERENTIATED
NEOPLASMS

Medulloblastoma
Predominantly in children
Exclusively in the cerebellum
Largely undifferentiated
Morphology
 Midline of cerebellum
 Lateral in adults

 Well circumscribed, gray and friable


POORLY DIFFERENTIATED
NEOPLASMS

Medulloblastoma
Microscopic:
 Extremely cellular, sheets of anaplastic cells
 Little cytoplasm
 Hyperchromatic nuclei, elongated or crescent
shaped
 Mitosis abundant
 (+) Ki-67 markers
 Express neuronal (neurosecretory granules, Homer
Wright rosettes) and glial (GFAP) phenotypes
MEDULLOBLASTOMA
POORLY DIFFERENTIATED
NEOPLASMS

Medulloblastoma
Molecular Genetics:
Loss of short arm of chromosome 17

Clinical features:
 Highly malignant
 Prognosis dismal in untreated patients
 radiosensitive
 Better survival following complete resection
 75% 5-year survival rate for total excision and radiation
POORLY DIFFERENTIATED
NEOPLASMS

Atypical Teratoid/Rhabdoid Tumor (AT/RT)


Highly malignant tumor of young children
Posterior fossa and supratentorial compartments
“rhabdoid cells” resembling those of a rhabdomyosarcoma
90% - Loss of genetic material from chromosome 22
Very young patients – before age 5
Live less than a year after diagnosis
OTHER PARENCHYMAL
TUMORS

 Primary CNS Lymphoma


 Germ cell tumors
 Pineal Parenchymal Tumors
OTHER PARENCHYMAL
TUMORS

Primary CNS Lymphoma


 2% of extranodal lymphomas
 1% of intracranial tumors
 Most common CNS neoplasm in immunosuppressed (AIDS)
 Occur in multiple sites WITHIN the brain parenchyma
 Majority B-cell origin
 Poor response to chemotherapy
OTHER PARENCHYMAL
TUMORS

Germ cell tumors


 Midline
 Most common in pineal and suprasellar regions

 0.2% to 1% of brain tumors among Europeans

 10% of brain tumors in Japanese

 90% occur during first two decades

 More common are teratomas


OTHER PARENCHYMAL
TUMORS

Pineal Parenchymal Tumors


Arise from pineocytes
Pineocytomas – well-differentiated
Pineoblastomas – high grade tumors
MENINGIOMAS
Benign tumors of adults
Attached to dura
Arise from meningothelial cell of arachnoid
External surface of brain as within the ventricular
system
MENINGIOMAS
Morphology:
Rounded, bosselated, polypoid masses
Well-defined dural base that compress underlying brain
but easily separated from it
May extend to overlying bone
Encapsulated with thin fibrous tissue
“en plaque” variant – spreads in sheetlike fashion along
the surface of dura
Most are WHO grade I/IV
MENINGIOMAS
TYPES
Syncytial
Fibroblastic
Transitional
Psammomatous
Secretory
Microcystic
Atypical meningiomas – mitotic index of 4 or more mitosis/10 hpf, 3 or
more atypical features (inc cellularity, small cells with high N:C ratio,
prominent nucleoli, patternless growth, necrosis)
Anaplastic (malignant)Meningioma
 WHO grade III/IV
 Mitosis >20/10 hpf
MENINGIOMA
MENINGIOMAS
Clinical Features:
Slow growing
Vague nonlocalizing symptoms or focal findings referable
to compression of underlying brain
Common sites: parasagittal aspect of brain convexity,
dura over latera convexity, wing of sphenoid, olfactory
groove, sella turcica, foramen magnum
Usually solitary
Multiple tumors assoc with acoustic neuroma or glial
tumors suggest neurofibromatosis type 2
METASTATIC TUMORS
Mostly carcinomas
Common primary sites (80%): lung, breast, skin
(melanoma), kidney, GIT
Meninges are frequently involved
Present clinically as mass lesions, may
occasionally be the first manifestation of cancer
Grossly form sharply demarcated masses, at gray
matter-white matter junction, surrounded by zone
of edema
BRAIN METASTASES
PARANEOPLASTIC SYNDROMES

Involve the peripheral and central nervous systems


Most common in small cell carcinoma of the lung
Examples
Paraneoplastic cerebellar degeneration
Limbic encephalitis
Subacute sensory neuropathy
Eye movement disorders, opsoclonus
Retinal degeneration
Stiff-man syndrome
Lambert-Eaton myasthenic syndrome
PERIPHERAL NERVE SHEATH
TUMORS
Arise from Schwann cells, perineurial cells,
fibroblasts
Express S-100 antigen, melanocytic
differentiation
PERIPHERAL NERVE SHEATH
TUMORS

 Schwannoma
 Neurofibroma
 Malignant
Peripheral Nerve Sheath Tumor
(MPNST, Malignant Schwannoma)
PERIPHERAL NERVE SHEATH
TUMORS

Schwannoma
 Neural crest-derived Schwann cell
 Assoc with Neurofibromatosis type 2

 Well circumscribed, encapsulated masses

attached to nerve but can be separated from it


 Firm, gray masses

 Cystic and xanthomatous change


PERIPHERAL NERVE SHEATH
TUMORS

Schwannoma
Microscopic:
Mixture of two growth patterns
Antoni A – pattern of growth of elongated cells with
cytoplasmic processes arranged in fascicles in areas
of moderate to high cellularity with little stromal
matrix
Antoni B – pattern of growth,less densely cellular
with loose meshwork of cells along with microcysts
and myxoid changes
SCHWANNOMA
PERIPHERAL NERVE SHEATH
TUMORS

Schwannoma
Clinical Features:
 Most common in cerebellopontine angle, attached to
vestibular branch of 8th cranial nerve
 Tinnitus and hearing loss

 “Acoustic neuroma” (vestibular schwannoma)


PERIPHERAL NERVE SHEATH
TUMORS
Neurofibroma
Two types:
Cutaneous neurofibroma (skin) or Solitary neurofibroma (peripheral
nerve)
 Dermis and subcutaneous fat
 Well-delineated, unencapsulated
 Spindle cells
 Stroma highly collagenized
Plexiform neurofibroma – occur only in NF1
 Involve major nerve trunks, potential for malignant transformation
 Frequently multiple
 Loose myxoid background, low cellularity
 Schwann cells, multipolar fibroblastic cells, inflammatory cells
PERIPHERAL NERVE SHEATH
TUMORS

Malignant Peripheral Nerve Sheath Tumor (MPNST,


Malignant Schwannoma)
 Highly malignant sarcoma
 Locally invasive, frequently leading to multiple recurrences
and metastasis
 Arise de novo or from transformation of plexiform
neurofibroma
 Assoc with NF type 1
 “Triton tumor” – with rhabdomyoblastic differentiation
FAMILIAL TUMOR SYNDROMES

 Neurofibromatosis Type 1 (NF1)


 Neurofibromatosis Type 2 (NF2)
 Tuberous sclerosis
 Von Hippel Lindau Disease
FAMILIAL TUMOR SYNDROMES

Neurofibromatosis Type 1 (NF1)


 Autosomal-dominant disorder
 Neurofibromas (plexiform and solitary)

 Gliomas of optic nerve

 Lisch nodules

 Café au lait spots

 Propensity to undergo malignant degeneration


FAMILIAL TUMOR SYNDROMES

Neurofibromatosis Type 2 (NF2)


Autosomal-dominant disorder
Bilateral VIII nerve schwannomas
Multiple meningiomas
Ependymomas of spinal cord
Schwannosis
Meningioangiomatosis
Glial hamartia
FAMILIAL TUMOR SYNDROMES

Tuberous sclerosis
Autosomal-dominant
Hamartomas
 Cortical tubers
 Subependymal hamartomas
Benign neoplasms involving the brain and other tissues
Renal angiomyolipomas
Retinal glial hamartomas
Pulmonary lesions
Cardiac rhabdomyomas
Cysts in liver, kidneys, pancreas
Cutaneous lesions e.g. Angiofibromas,Shagreen patches, ash-leaf
patches, subungal fibromas
FAMILIAL TUMOR SYNDROMES

Von Hippel Lindau Disease


 Autosomal-dominant
 Capillary hemangioblastomas within the cerebellar
hemispheres, retina, less commonly in brain stem and spinal
cord
 Cysts in pancreas, liver, kidneys
 Renal cell carcinoma
 Associated with polycythemia in 10% of hemangioblastomas
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