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Tumors of Nervous System

DODY NOVRIAL
LABORATORIUM OF PATHOLOGY
MF-JSU
Epidemiology

Annual incidence : 10-17 per 100.000 for intraspinal


tumor.
Half to three quarters are primary tumors
The rest are metastatic tumors
Tumors of the CNS account for 20% of all cancers of
childhood.
The 5-year survival rates : 22-32%
Unique Characteristic

The distinction between benign and malignant is less


evident
Surgical therapy without compromising neurologic
function is limited
The anatomic site of tumors can have lethal
consequences irrespective of histological
classification
Pattern of spread of primary CNS tumors differs
from that of other tumors.
Classification

Four major classes of CNS tumors :


Gliomas
Neuronal Tumors
Poorly Differentiated Neoplasms
Meningioma
GLIOMAS

Gliomas derived from glial cells


Include :
 Astrocytomas
 Oligodendrogliomas
 Ependymomas.
Astrocytomas

World Health Organization (WHO) classification


 Grade I:
pilocytic astrocytoma, subependymal giant cell astrocytoma
 Grade II:
well-differentiated diffuse astrocytoma, pleomorphic
xanthoastrocytoma
 Grade III:
anaplastic astrocytoma
 Grade IV:
glioblastoma multiforme (GBM)
Astrocytomas Grade I

 Most common in children


 Associated with neurofibromatosis type I
 Locations- cerebellum, wall third ventricle, optic nerve, temporal lobe,
thalamus, basal ganglia
 Clinical course
– Grow slowly, low rates of cell proliferation
– Better survival with surgical excision
– 5-year survival 85%; 10-year survival 79%
– Malignant transformation rare
– Infiltration of the meninges does not adversely affect prognosis
Astrocytomas Grade I

 Discrete cystic mass; radiographically a cystic tumor with


enhancing mural nodule(s)
 Microscopic pathology
– Nuclear pleomorphism—a degenerative change
– Mitoses rare
– Vascular proliferation and sclerosis common
– Biphasic appearance
Astrocytomas Grade II

 20% of all gliomas, 10–15% of all astrocytic tumors


 Incidence 1.4 new cases/1 million population/year, fourth
decade peak
 >90% derived from fibrillary astrocytes, arise in white
matter
 Frontal lobe > parietal > temporal > occipital
 Noncontrast enhancing, ill-defined region of low density on
CT scan
 Seizures, sensorimotor deficits, increased intracranial
pressure, altered mentation
Astrocytomas Grade II

 Grossly a solid tumor, infiltrative growth pattern, obliterate


gray–white junction, subtle color change (yellow/tan or
gray)
 Microscopic
– Unevenly distributed hypercellularity
– Rare or absent mitoses
– Irregular nuclear contours, hyperchromatic nuclei
– Mild nuclear pleomorphism
Low Grade Astrocytomas
Astrocytomas Grade III

 Similar to grade II astrocytoma


 Age of onset : decade later
 Survival : 3 years
 Contrast enhancement , more mass effect
 TP53 mutation, deletion of CDKN2A/p16 gene
 Microscopic pathology
– Hypercellularity with more prominent nuclear pleomorphism
– Mitotic figures more readily identifiable
– No necrosis
 Cell proliferation rate greater than low-grade astrocytoma
Astrocytomas Grade III
Astrocytoma Grade IV (GBM)

 Most common in adult , 50% of all gliomas


 Age of onset : 50-60 y/o
 Survival : 1 year after treatment
 Supratentorial structure : deep white matter, basal ganglia,
thalamus
 Multiforme : heterogeneous
 Gross : well-circumscribed, microscopically infiltrative
 “Butterfly lesion” : spread via corpus callosum to opposite
site
Astrocytoma Grade IV (GBM)

 Microscopic pathology
– Geographic necrosis
– Perinecrotic pseudopalisading by tumor cells
– Usually areas of prominent cellularity and nuclear
pleomorphism
– Readily identifiable mitotic figures
– Vascular “endothelial” proliferation
 Variants : giant cell glioblastoma, small cell glioblastoma, gliosarcoma
(temporal)
 Genetically best characterized brain tumor
Astrocytoma Grade IV (GBM)
Oligodendroglioma (Low Grade)

 10–25% of glial neoplasms


 Long history of signs and symptoms (mean 1–5 years)
prior to diagnosis
 Seizures, headaches most common symptoms; about 20%
hemorrhage
 Adults >children; mean age 35–45 years; slight male
predominance
 White matter origin
 Frontal lobe is the most common site
Oligodendroglioma (Low Grade)

Microscopic pathology
 Sheets of cells, scant cytoplasm, rounded central nucleus, vesicular
chromatin
 Vacuolated “fried egg” appearance—formalin fixation artifact
 Minimal nuclear pleomorphism
 Arcuate or “chicken wire” vascular pattern
 Calcification—prominent at periphery, seen in 80–90% of cases
 Cortical invasion
 May see meningeal invasion with desmoplasia
 Subpial and perineuronal arrangement of tumor cells
 May see microcystic change
 Rare mitoses at most
Oligodendroglioma (Low Grade)
Oligodendroglioma (High Grade)

 Pleomorphic nuclei
 Mitoses, often >5 mitotic figures per high-power fields
 Vascular proliferation
 Necrosis
 Increased cellularity
 Worse prognosis than low-grade tumor, median survival
3–4 years
 1p and 19q chromosome deletions associated with
increased likelihood of chemoresponsiveness
Oligodendroglioma (High Grade)
Ependymoma (Low Grade)

 6–12% of tumors, children


 1–2% of brain tumors, adult
 Any ventricle (especially 4th) and spinal cord
(intramedullary); most common tumor of the spinal cord
 71% infratentorial
 Obstruction of CSF related signs and symptoms at
presentation
 Grossly: soft lobular, discrete mass, well demarcated
Ependymoma (Low Grade)

Microscopic pathology
 Extreme fibrillarity
 Nuclei round to oval, “carrot-shaped”
 Dense nuclear chromatin
 Slight nuclear pleomorphism
 Infrequent mitoses
 Perivascular pseudorosettes
 True ependymal rosettes
 Blepharoplasts—intracytoplasmic, basal bodies of cilia, best seen
ultrastructurally
 Variants: cellular, papillary, clear cell, tanycytic, melanotic,
lipomatous, giant cell, signet ring cell; no difference in prognosis
associated with these variants
 May see focal calcification/ossification/ cartilage
Ependymoma (Low Grade)
Ependymoma (High Grade)

Rare
Precise histological criteria to distinguish from
ordinary ependymoma are not well defined
Increased mitoses
Nuclear and cellular pleomorphism
Hypercellularity
Vascular proliferation
Focal necrosis frequent
Ependymoma (High Grade)
Neuronal Tumors

Dysembryoplastic neuroepithelial tumor


Embryonal tumors/Primitive Neuroectodermal
tumors
Medulloblastoma (Poorly Differentiated)
Dysembryoplastic Neuroepithelial Tumor (WHO grade I)

 DNT
 Benign quasi hamartomatous tumor
 Childhood and early adult
 Excellent prognosis
 Supratentorial, intracortical : Temporal lobe
 long history of Intractable seizure
 Multinodular, adjacent cortical dysplasia
 Biopsy : resemble oligodendroglioma
 Floating neuron, mucin rich cortical nodule
 No cortical/subcortical invasion
Embryonal tumors/
Primitive Neuroectodermal tumors

 PNET : umbellar term


 Small blue cell tumors
- Medulloblastoma (prototype)
- peripheral nervous system PNET
- CNS variants : supratentorial PNET (sPNET)
: pineoblastoma, central neuroblastoma,
ependymoblastoma, medulloepithiloma
- PNETs of special sensory organ
: retinoblastoma, olfactory neuroblastoma
- AT/RT
Embryonal tumors/
Primitive Neuroectodermal tumors
Medulloblastoma
(Poorly Differentiated Neoplasm)

 Most common form of PNET


 Age of onset :<10 y/o (18-25)
 By definition, originates in cerebellum
 Disseminated along CSF pathway
 5-year survival : 70-80%
 Associated with form of Turcot’s syndrome,
Gorlin’s syndrome
 MYCC and MYCN gene amplification :
aggressiveness of medulloblastoma
Medulloblastoma
(Poorly Differentiated Neoplasm)
Meningeal/Extra Axial Tumors

Most common : meningiomas


Hemangiopericytoma, sarcoma, lymphoma,
schwannoma
Meningioma (WHO grade I)

 Multiple meningioma : NF2


 Meningioma en-plaque : diffuse, carpetlike tumor spread
along dural surface
 WHO classification : 13 morphological types
 Histology : Psammoma body
 Losses of chromosome 22, tumor suppressor gene (NF2),
DAL1 or protein 4.1B on 18p11.3
 MRI : isointense T1W, T2W, homogeneous enhancement,
dural based mass
Meningioma (WHO grade I)
Atypical meningioma (WHO grade II)

Increase risk of recurrence


15-20% of all meningiomas
Mitotic index > 4 mitosis per 10 HPFs
Deletion of 1q, 6p, 10 and 14q
Anaplastic meningioma (WHO grade III) :
mitotic index > 20 per 10 HPFs, highly aggressive
and infiltrative
Nerve sheath tumors

Schwannoma (NF2)
Neurofibroma (NF1)
Schwannoma (neurilemoma)
(WHO grade I)

 Peak 40-50 y/o


 Vestibular portion of 8th cranial nerve
 Bilateral : NF2
 Spinal schwannoma : dorsal root (sensory)
 Dumbell-shaped mass
 Pure schwann cell proliferation (opposed to neurofibroma)
 Typically, capsule and push parent nerve aside
Neurofibroma (WHO grade I)

 Pathognomonic of NF1 : Multiple spinal root involvement


 Fusiform intraneural mass
 Plexiform growth pattern, mixture of cell types (schwann
cell, fibroblast, perineurial-like cell, mast cell)
 Entrap parent nerve
Miscellaneous tumors
CNS lymphoma

Primary lymphoma : multifocal, deep


parenchyma, perivantricular, spare leptomeninges
Systemic (2nd) lymphoma : leptomeninges, spare
parenchyma
Common site : epidural spine
Immunocompromise : associated with EBV
Diffuse large B cell lymphoma
MRI : hypointense T2W, strong homogeneous
enhancement, vasogenic edema
Germ cell tumors

 School-aged children, boy


 Most common : pineal region, suprasellar/hypothalamic
region
 Subarachnoid seeding
 Marker
- germinoma : placenta alkaline phosphatase (PLAP)
- yolk sac tumor : AFP
- choriocarcinoma or syncytiotrophoblast : β-HCG
 Germinoma :100% curable, radiosensitive
 Mixed germ cell tumors , mature teratoma
Hemangioblastoma (WHO grade I)

Peak 40 y/o
VHL disease
Benign, highly vascular tumor
Most common : cerebellum, spinal cord, retina
Cystic tumor with enhancing mural nodule
VHL gene on 3p25-26 (tumor suppressor)
Renal cell carcinoma, pheochromocytoma
Craniopharyngioma (WHO grade I)

Any age (1st two decade)


Remnant of Rathke’s pouch
Location : suprasellar, intrasellar, optic chiasm
Complication : hydrocephalus (3rd ventricle)
Calcified, cystic, solid component
Craniopharyngioma (WHO grade I)
Metastatic Tumors
Epidemiology

Incidence varies among tumor type


Lung 18-63%
Breast 20-30%
Melanoma 18-90%
Ovarian 3%
Prostate 1%
Supratentorial : cerebral blood flow
GI/GU tumors : posterior fossa
Pathophysiology

Hematogenous spread (tumor emboli)

Gray-white junction (narrowing caliber of vessels)

Enlarge in a spherical fashion,


Central necrosis, edema
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