Tumors of the Nervous System

• Primary CNS tumors-3% of all primary tumors, 1.2% of all deaths

• Children-CNS tumors are the 2nd most common malignancy (after lymphoma and leukemia); 60-70%
infrantentorial (cerebellum, brainstem)
o Cerebellum is still growing in children-many pluripotent cells present
• Adults-70% supratentorial (cerebral hemispheres)
• Space-occupying lesion and increased ICP-tumor mass effect, hemorrhage, edema, hydrocephalus
• Altered functions of the tissues-compression and damage of surrounding brain, injury and necrosis of
brain tissue, neurochemical effects and seizures
• Growth of CNS tumors
o Expansion w/defined tumor borders
 Meningiomas
 Ependymomas and choroids plexus papillomas
 Some metastatic tumors
o Infiltrative growth w/individual tumor cell invasion of surrounding brain structures
 Majority of primary tumors including diffuse type of astrocytomas, glioblastomas,
medulloblastomas
• Spread of CNS tumors
o Spread along white matter tracts
 Glioblastomas are known by crossing into the other hemisphere by the corpus
callosum-butterfly lesions
o Spread along pial membrane
 Gliomas may “travel” along the subpial surface of the brain, invade into the
subarachnoid space and diffusely spread through the leptomeninges
o Spread along perivascular space- (Virchow-Robin)
o Spread across the ependyma
 Leading to ventricular and CSF seeding
o Metastases
 Extraneural metastases of CNS tumors are extremeely rare
 Malignant tumors have been reported to metastasize after operative procedures
• Bone, subcutaneous tissues, LNs
• Peritoneal seeding after ventriculo-peritoneal shunts

• Tumors of Neuroepithelial Tissue

o Gliomas (#1 Primary Brain Tumor)
 Astrocytomas
 Oligodendrogliomas
 Ependymomas
 Choroid Plexus Papillomas
o Neuronal and Mixed Neuronal-Glial Tumors
 Central Neurocytomas
 Gangliomas
o Embryonal Tumors
 Medulloblastomas
 Suprantentorial Primitive Neuroectodermal Tumors (PNET)
 Retinoblastomas
• Tumors of the Meninges
o Meningioma
• Tumors of the Peripheral Nerve
o Schwannoma
o Neurofibromas

• Tumors of Neuroepithelial Tissue

o Gliomas (#1 Primary Brain Tumor)
 Astrocytomas
• Diffuse (Infiltrating) Astrocytomas-Adults
o Age predilection-adults >>> children
 5th to 7th decade; malignancy increases incidence with age
o Location
 adults-cerebral hemispheres
 children-brainstem
o Presenting symptoms
 Seizures-60-70%
 Headache
 Focal symptoms and signs
o Infiltrative growth w/individual tumor cell invasion of surrounding
brain structures
o Malignancy criteria
 A Atypia-Stages II, III, IV
 M Mitoses-Stages III, IV
 E Endothelial Proliferation-Stage IV
 N Necrosis-Stage IVs
o Astrocytoma-grade II
 Still uses original vessels of the brain
 Atypia and a few mitotic figures
 No endothelial proliferation; No necrosis
 Tend not to be chemosensitive
 Stereotopic biopsy only
 Treat with radiation; surgery is controversial
 Usually return in 5 years-worse grade
o Anaplastic Astrocytoma-grade III
o Glioblastoma Multiforme-grade IV
 Central necrosis
 Border of viable cells-aim here for biopsy
 Rich with vessels that lack tight junctions
 Diffuse infiltration
 Treatment depends on patient age and tumor location
 Atypia, mitoses, endothelial proliferation (vascular hyperplasia,
glomerular appearance, leaky vessels)
 Palisading necrosis (nuclei align around necrotic area) or
Geographic Necrosis
 The most malignant glioma in adults
 Short clinical history (median <3 months)
• Seizures in 1/3 of patients (compare to 60-70% with
diffuse infiltrating astrocytomas)
 • Headache and focal symptoms/signs
 Spread
• White matter tracts, crossing the hemispheres, ventricular
seeding
• Infiltrative growth w/individual tumor cell invasion of
surrounding brain structures
 Prognosis-median survival of 1 year
 Molecular Genetics
• Pathway Leading to Secondary Glioblastoma-patients
tend to be younger
o Low Grade Astrocytoma-P53 mutation (>65%),
PDGF-A, PDGFR-α Overexpression (60%)
o Anaplastic Astrocytoma-LOH 19q (~50%), RB
alteration
o Secondary Glioblastoma (LOH 10, DCC Loss of
Expression, PDGFR-a Amplification)
• Pathway Leading to Primary Glioblastoma-patients tend
to be older
o EGFR amplification (40%), overexpression
(60%)
o MDM2 amplification (<10%), Overexpression
(~50%),
o LOH 10-PTEN mutation (~30%)
o p16 deletion (30-40%)-RB alteration
• Special Categories of Astrocytomas-children
o Pilocytic astrocytoma-grade I
 Age-one of the most common tumors of children; peak incidence
age 10-12 yrs
 Location-midline structures, circumscribed
• Cerebellum
• Optic n and chiasm-optic n glioma is often associated
with NF I-chrmsm 17
• 3rd ventricle region/hypothalamus
• brainstem (often dorsal exophytic)
• Rosenthal Fibers-
o Piloid Pattern
o Biphasic Pattern
 benign behavior-slow growing tumor w/little progression to
malignancy
 surgical treatment
o Pleomorphic Xanthoastrocytoma-Grade II-III
o Supependymal Giant Cell Astrocytoma (Tuberous Sclerosis (TS))-
Grade I, neuro and cutaneous lesion
 Oligodendrogliomas
• Peak incidence in 40s and 50s
• Perhaps 10% of brain tumors
• Frontal and temporal lobes predilection
 •Long clinical histories
•Seizures in up to 90%
•Frequent micro and macrocalcifications
•Malignancy criteria not well established-proliferative index appears to be the
most important
• Molecular genetics have clinical and treatment relevance
• Fried egg appearance
• Branching (chicken wire) vessels
• Oligodendroglioma-Grade II
o LOH 1p
o LOH 19q
• Anaplastic Oligodendroglioma-Grade III
o Increased mitoses +/- endothelial proliferation/necrosis
o 1p/19q deletion associated with better treatment response and longer
disease free time after chemo
o Association w/Longer Survival-1p deletion or LOH (initial biopsy)
 19p or 1p/19q deletion (8.3x)
 5 year survival: 95% vs 38%
 Ependymomas
• Seen in children and young adults
• commonly located in 3rd ventricle
• Ependymal zone-inner epithelial layer of cells bordering the lumen of the
embryonic neural tube and brain, formed during the latter’s stratification and
persisting in a modified form throughout life
• Expansion w/defined tumor borders
 Choroid Plexus Papillomas
• Expansion w/defined tumor borders
o Neuronal and Mixed Neuronal-Glial Tumors
 Central Neurocytomas
 Gangliomas
o Embryonal Tumors
 Medulloblastomas
• Account for >25% of all pediatric brain tumors
o Most frequent primary malignant tumor in children and young adults
• 50% cases arise <10 yo
• Location-cerebellum
• Malignant behavior with great predilection for CSF spread (20-50% prior 1st
operation)
• Infiltrative growth w/individual tumor cell invasion of surrounding brain
structures
• 5-year survival has increased due to good chemo +/- radiation
• A small blue cell tumor like Wilm’s and Lymphomas
• Classic Variant
• Nodular/Follicular Variant
• Isochromosome 17 q
• Loss of chromosome 17p (40%) in a different locus than TP53
 • Amplification of c-myc (large cell variant)
 Suprantentorial Primitive Neuroectodermal Tumors (PNET)
 Retinoblastomas
• Tumors of the Meninges
o Meningioma
 6/100,000/yr=15,000 clinically diagnosed
 1.4% at post mortem
 F>>M-? hormonal action, recall that most gliomas are more common in males
 Age 20-60 years (peak: 45)
 Expansion w/defined tumor borders
 Location: convexity>skull base>spine
 Symptoms: seizures, focal deficits
 Prognosis-usually benign but can re-grow if not totally removed
 Propensity to erode continuous bone
 Superficial location and neural displacement, rather than infiltration, make many
meningiomas good surgical candidates (exception: tumors at base of skull)
 Occur sporadically, iatrogenically, and with NF2
• NF2-Chromosome 22; Central Neurofibromatosis
 Grading
• Meningioma-Grade I, accounts for 90% of meningiomas
• Special Variants of Meningiomas-Grade II
o Chordoid and clear cell
• Atypical Meningioma-Grade II
• Special Variants of Meningiomas-Grade III
o Papillary and Rhabdoid
• Anaplastic (malignant) melanoma-grade III
 Intradural, Extramedullary lesions (extraparenchymal) (like Schwannomas)
 If a slow growing tumor, brain can accommodate with few signs of hydrocephalus
 Meningothelial whorls
 Psammoma bodies
• Tumors of the Peripheral Nerve
o Schwannomas
 Tumors derived of Schwann cells
 Most common locations: CN VIII, other cranial nerves, spinal roots
 Microscopic features: Antoni A & Antoni B areas; Verocay Bodies (parallel, picked,
regimented patterns of cells at the ends of a fibrillar bundle)
 Malignant progression is extremely rare
 Bilateral CN VIII Schwannomas=NF2
 Intradural, extramedullary location
 Dumbbell shaped tumors
o Neurofibromas
 Tumors derived from a mixture of Schwann cells, fibroblasts, perineurial & mast cells
 Common locations: peripheral nerves and roots, skin (nerve twigs)
 May be sporadic or associated with NF1
 May undergo malignant transformation-MPNST (malignant peripheral nerve sheath
tumor) (whereas Schwannomas generally do not transform)
 Usually painless
 Lose nerve function
 Plexiform Neurofibromas (NF1)
  Elephant man picture
 Everyone can have solitary neurofibromas; patients w/neurofibromatosis have multiple
 NF1-bag of potato lesions
• In Children and Young Adults:
o Most frequent primary tumor is Medulloblastoma
o Special categories of Astrocytomas (aka circumscribed)=Pilocytic Astrocytoma
o Ependyoma
o Gangliomas
o Choroid Plexus Papillomas
• In adults:
o Most frequent primary malignant tumor=Glioblastoma (Astrocytoma Grade IV)
o Metastatic Tumors-25-35% of all tumors
 Most common: lung, breast, melanoma, renal cell ca, GI tract
o Meningiomas
 Female:male 2:1
 Many locations
 NF2
o Oligodendrogliomas
o Schwannoma and Neurofibroma (NF1)