Neoplasms Of The Nervous System

Introduction

Primary (3/4) or metastatic•

of deaths from malignancy 2% •
Second most common neoplasm in children (20%) after leukemia •
((more likely arise in posterior fossa
:CNS neoplasms are different from neoplasms of otherorgans •
Criteria of malignancy are different & less evident○
Patten of growth of low-grade tumors may still include ○
infiltration of large regions of brain  serious clinical effects &
poor prognosis
Even benign ones may cause death due to compression of vital ○
”structures “Location of the tumor is important
Malignant neoplasms rarely metastasize outside of CNS ○
The subarachinoid space provides a pathway for spread ○
Ability to surgically resect infiltrating glial tumors without ○
compromising neurologic functions is limited

Classification of Primary CNS Tumors

:”A. Gliomas “derived from glial cells

:Astrocytoma .1
:Can be classified as
( Pilocytic astrocytoma (WHO- I.1
:Fibrillary “infiltrating or diffuse” astrocytomas .2
( Low grade astrocytoma (WHO- II○
( Anaplastic astrocytoma (WHO- III ○
( High grade “glioblastoma multiforme” (WHO- IV ○
Pilocytic Astrocytoma.1
Typically occur in children & young adults
Common sites: cerebellum, 3rd ventricle & optic nerve
Relatively benign & have excellent prognosis if resectable
:Gross
Well-defined͵
Often cystic with small mural nodule in wall͵
:Microscopic
”Bipolar cells with hairlike processes “pilocytic͵
GFAP +ve͵
Rosenthal fibers͵
Eosinophilic granular bodies͵
Microcystic areas͵
No mitosis or necrosis͵
Fibrillary Astrocytomas.1
Account for 80% of adult 1ry brain tumors
Most frequent in 4th-6th decades
Mainly in cerebral hemispheres
Most common presenting symptoms: seizures, headaches & focal
neurologic deficits
They have tendency to become less well differentiated over time

1
Prognosis depends on age, location & histological grade “GBM has a
”very poor prognosis
Rx: Resection if possible + radio & chemo mean survival of 8-10
months. <10% are alive after 2 yrs
Low-Grade Astrocytoma
Poorly defined & infiltrative͵
Expand , distort parenchyma & obliterate grey/white matter͵
boundaries
Infiltration beyond grossly evident margins is always present͵
Transition between neoplastic & normal tx is indistinct͵
Increased numbers of irregularly distributed, mildly atypical &͵
pleomorphic astrocytes with intervening background of fine GFAP
+ve
(astrocytic cell processes (fibrillary appearance͵
Anaplastic astrocytoma
demonstrates marked cellularity with marked pleomorphism &͵
increased mitotic activity
Glioblastoma Multiforme
Gross: Infiltrative with irregular areas of Hg, necrosis & cystic changes•
Micro: Serpentine necrosis with pseudo-palisading nuclei & vascular or•
endothelial cell proliferation

:Oligodendroglioma .2
of gliomas 5-15%
(Occur in adults (4th & 5th decade
Occur in cerebral hemispheres mainly in white matter
:Can be subdivided into
Low-grade
(High-grade (anaplastic
Prognosis is better than astrocytomas, anaplastic is worse
Rx: Surgery + chemo + radio  average survival of 5-10 yrs
Most common genetic abnormality is loss of heterozygosity of
chromosome 1p &19 q  consistent & long-lasting Rx response
Gross
Gelatinous, grey, infiltrative mass͵
May show cysts, focal hemorrhage & calcification͵
Calcification may be seen in up to 90% of tumors &range from͵
microscopic foci to massive depositions
They are helpful clues for radiologic Dx͵
microscopic
Sheets of regular cells with rounded, uniform nuclei which are͵
surrounded by a clear perinuclear cytoplasmic halo
Typically contains delicate network of anastomosing capillaries͵
Anaplastic tumors: increased cellularity, pleomorphism, mitosis &͵
necrosis Calcification

:Ependymoma .3
:In children
In first 2 decades of life
Account for 5-10% of 1ry brain tumors in this age group
Typically occurs near 4th ventricle

2
 :In adults
Occurs most commonly in spinal cord Mainly in setting of
neurofibromatosis type2
CSF dissemination is common
The clinical outcome of completely resected supratentorial & spinal
ones is better than for those in posterior fossa
:Gross
In 4th ventricle they are typically solid or papillary masses ͵
extending from the ventricluar floor
:Microscopic
Perivascular pseudorosettes: Processes of cells are radiating around͵
blood vessels
Ependymal rosettes: Processes of cells are radiating around lumina͵

: ” B. Primitive Neuroepithelial Neoplasms “PNET

Are composed of embryonal “primitive” cells
Occur predominantly, but not exclusively in children
:They include
*  Medulloblastomas
 Pineoblastoma
 Ependymoblastoma
 Medulloepithelioma
*  Neuroblastoma

Medulloblastoma
(Is derived from primitive neuroectodermal cells (undifferentiated
Accounts for 20% of pediatric brain tumors
Occurs predominantly in children (in first 2 decades) and exclusively
(in the cerebellum (midline vermis
In adults “rare” is often found in lateral cerebellar hemispheres
”May lead to hydrocephalus “if obstructing ventricles
Frequently disseminate through CSF
Highly malignant with poor prognosis if untreated, but with
multimodality therapy "radiosensitive” 5ys survival rate may reach
75%
:Gross
Well circumscribed͵
Friable & gray͵
:Micro
Extremely cellular with sheets of anaplastic small blue “primitive”͵
cells with small Homer Wright rosettes “cells are arranged around a
central fibrillary core”. Mitoses are abundant

:C. Neuronal Neoplasms

:They include
 Gangliocytoma
 Ganglioglioma
( Dysembryoplastic neuroepithelial tumor (DNT
 Central Neurocytoma
Occur mainly in children & young adults
Almost all are low-grade

3
 Important causes of seizures
: D. Meningiomas
Are predominantly benign
Are derived form meningothelial cells that invest arachnoid
Are usually attached to dura & are outside brain parenchyma
May occur in cranial vault or spinal cord
Occur mainly in adults, F > M
Multiple meningiomas, especially in association with 8th nerve
schwannomas or glial tumors should raise suspicion of NF-2
of meningiomas not associated with NF2 still have mutations 50% ~
(in NF2 gene on long arm of chromosome 22 (22q
:Gross
Well-defined, firm & lobulated͵
Attached to dura mater͵
Sharp interface with adjacent brain / spinal cord , easily separated͵
Extension into overlying bone maybe present͵
:Microscopic
Syncytial meningiomas = composed of compact cellular whorls.1
Fibroblastic meningiomas = composed of elongated cells with.2
interspersed collagen
Transitional meningiomas = share features of syncytial &.3
fibroblastic types
Secretory meningiomas = has PAS +ve intracytoplasmic droplets &.4
intracellular lumina byEM
Microcystic meningiomas = Has loose & spongy appearance.5
Psammomatous meningioma = numerous psammoma bodies.6

:(E. Germ Cell Tumors (GCTs

Teratomas* & other germinomas
Occur along midline, most commonly in pineal & suprasellar region
occur during 1st two decades 90%
Tumors in pineal region show a strong male predominance
Histologic classification is the similar to testicular tumors. However,
CNS germinoma is the counterpart of testicular seminoma

:(F. Primary Brain Lymphoma (PBL

Account for 2% of extranodal lymphomas & 1% of intracranial
tumors
Majority are diffuse large B-cell lymphomas
It is the most common CNS neoplasm in immunosuppressed (AIDS &
transplant) patients. In these pts lymphomas are nearly all caused
by EBV
In nonimmunosupressed populations the incidence increases after
60 years of age
Often multifocal within CNS
Nodal, extranodal & BM involvement is rare & late complication
Is an aggressive disease with relatively poor response to chemoRx
as compared with peripheral lymphomas

4
 Metastatic Tumors

Accounts for ¼ of intracranial tumors

Brain is a common site for mets
Occur mainly in elderly
The 5 most common 1ry sites: lung, breast & malignant melanoma,
.GIT & kidney
Account for 80% of all cases
Meninges are also a frequent site of involvement by mets
:Morphology
Solitary or multiple
Usually are well demarcated, have sharp interface with adjacent
parenchyma & roughly spherical
Often present at gray matter-white matter junction
Usually surrounded by a zone of edema & reactive gliosis

Tumors - Summary
Tumors of the nervous system may arise from the cells of the coverings
(meningiomas), from cells intrinsic to the brain (gliomas, neuronal tumors,
choroid plexus tumors), or other cell populations within the skull (primary
CNS lymphoma, germ-cell tumors), or they may spread from elsewhere in
the body (metastases). Even low-grade or benign tumors can have a poor
.clinical outcome depending on wherein the brain they occur

Glial tumors are broadly classified into astrocytomas,

oligodendrogliomas, and ependymomas. Increasing tumor malignancy is
,associated with more cytologic anaplasia
increased cell density, necrosis, and mitotic activity. The most aggressive
and poorly differentiated glial tumor is glioblastoma; it contains anaplastic
astrocytes and shows
.striking vascular abnormalities

Metastatic spread of brain tumors to other regions of the body is rare, but
the brain is not comparably protected against spread of tumors from
elsewhere. Carcinomas are more
commonly metastatic to the nervous system than lymphoid malignancies;
sarcomas infrequently metastasize to the brain