Topic: Brain and Spine Tumors

Lecturer: Dr. Gayao

Lecture: Brain and Spine Tumors
Lecturer: Dr Gayao
Outline
Introduction
Incidence
Pathophysiology
Classification system
Brain Tumors
Type
Clinical manifestations
Diagnostic tools
Management/Treatment Guidelines
Spine Tumors
Type
Clinical manifestations
Diagnostic tools
Management/Treatment Guidelines

Brain tumors could be broadly categorized into 2

groups
Primary Brain Tumors tumors that arise
from cells of the brain parenchyma
Secondary Brain Tumors tumors that
spread to the brain

Primary brain tumors

BRAIN TUMORS
Could be characterized/described in several ways:
1. Clinically the neoplasmic mass because of
its size or location could cause symptoms of mass
effect and neurologic deficits
2. Tissue according to the group of cells and
associated extracellular matrix whose growth are
uncoordinated and exceeds that of normal tissue.
Grade I: circumscribed, biphasic, bipolar and
multipolar cells, fibers, microcysts, granular
bodies; no/rare mitotic figures, no/rare vascular
proliferation, no/focal necrosis
Grade II: moderately hypercellular, monotonous
cells, mild nuclear atypia, no/minimal mitotic
activity
Grade III: increased cellularity and diffuse
infiltration, increased nuclear atypia, increased
mitotic activity
Grade IV: vascular proliferation, necrosis,
crowded anaplastic cells, marked nuclear atypia,
brisk mitotic activity
3. Cellular individual cells differ from normal
cells in size, shape, pigmentation, nuclear size.
As tumors become more malignant, features of
cellular anaplasia becomes more pronounced

** intra-axial: within the brain parenchyma

extra-axial: outside the brain parenchyma

Secondary Brain Tumors

4. Biochemical Rapidly growing tumor cells may

rely more heavily on the glycolytic than on
oxidative metabolism
5. Immunologic Cell surface markers, many of
which contribute to the altered growth
characteristics of tumor cells
e.g. receptors for growth factor receptors and
extracellular matrix protein
6. Chromosomal Loss or gain of entire
chromosomes,
deletions,
rearrangement
or
duplication of parts of the chromosomes

Trans by: Jocine Toledano Neuro Transcom YL3 2015

7. Genetic alteration in DNA base sequence that

changes either the expression of genes or the
structure of the proteins the genes encode
Pathophysiology
Origin of brain tumors is essentially a genetic
question consisting of 3 parts:
1. What fundamental genetic alterations
underlie the development of the tumor?
2. What causes these genetic alterations?
3. What host factors allow these genetic
alterations to be manifested as tumors?

What host factors allow these genetic alterations to

be manifested as tumors?
Tumor heterogeneity
Heterogenous tumor cells constitute a
substrate for selection of progressively more
malgnant tumor, rapidly proliferating with
greater genetic lability
Invasiveness
Angiogenesis
Immune suppression
Brain Tumors Incidence
CBTRUS: (Central Brain Tumor Registry of the
United States)

Genetic alterations underlie the development

of the tumor

Primary Brain and CNS

Tumors

20.6 / 100,000

Malignant

7.3 / 100,000

Non-malignant

13.3 / 100,000

Females

22.3 / 100,000

Males

18.8 / 100,000

US Population

SEER (Surveillance, Epidemiology, and End

Results) program
Primary MALIGNANT
Brain and CNS Tumors

6.5 / 100,000

Males

7.7 / 100,000

Females

5.4 / 100,000

Primary NON
MALIGNANT Brain
and CNS Tumors

6.5 / 100,000

Males

10.6 / 100,000

Females

16.1 / 100,000

US Population
Age distribution of CNS Tumors

What causes these genetic alterations?

1.
Radiation
2.
Chemicals
3.
Viral

Trans by: Jocine Toledano Neuro Transcom YL3 2015

Survival based on WHO grading

Brain tumor by histologic type (take note)

Gliomas by histologic type

WHO grading of tumors

Grade I

Tumors of low proliferative potential

Possibility of cure following surgical
resection alone

Grade II

Generally infiltrative in nature

Despite low proliferative nature, may tend to
recur
Some tend to progress to higher grade

Grade III

Generally reserved for lesions with

histological evidence of malignancy (atypia
and mitotic activity)
Patients receive adjuvant radiation and/or
chemotherapy

Grade IV

Cytologically malignant
Mitotically active, necrosis prone neoplasm
Rapid post operative disease evolution
Fatal outcome

Grade I

Curative when gross total excision is done

Grade II

Survival of > 5 years

Grade III

Survival of 2-3 years

Grade IV

Survival ~ 1 year

WHO Classification of CNS Tumors

Tumors of Neuroepithelial Tissue
Tumors of cranial and paraspinal nerves
Tumors of the Meninges
Lymphomas and Hemopoietic Neoplasms
Germ Cell Tumors
Tumors of the Sellar Region
Metastatic Tumors
TUMORS OF NEUROEPITHELIAL TISSUE
Astrocytic tumors

Pilocytic astrocytoma

Subependyml giant cell tumors

Pleomorphic xanthoastrocytoma

Diffuse astrocytoma

Fibrillary

Gemistocytic

Protoplasmic
Anaplastic astrocytoma
Glioblastoma
Oligodendroglial tumors
Oligodendroglioma
Anaplastic Oligodendroglioma
Oligoastrocytic tumors
Oligoastrocytoma
Anaplastic Oligoastrocytoma
Tumors of Neuroepithelial Tissue
Ependymal tumors
Subependymoma
Myxopapillary ependymoma
Ependymoma

Cellular

Papillary

Clear Cell

Tancytic
Anaplastic ependymoma
Choroid plexus tumors
Choroid plexus papilloma
Choroid plexus carcinoma
Neuronal and Mixed neuronal-glial tumors
DNET

Trans by: Jocine Toledano Neuro Transcom YL3 2015

 Gangliocytoma
Central neurocytoma
Paraganglioma
Tumors of Neuroepithelial Tissue
Tumors of the Pineal region
Pineocytoma
Pineal parenchymal tumor
Pineoblastoma
Embryonal tumors
Medulloblastoma
PNET
Atypical teratoid / rhabdoid tumor
Pilocytic Astrocytoma
WHO grade I
subgroup of astrocytomas with better
prognosis (10 year survival: 94%) than
infiltrating astrocytoma
Age < 20yo in 75%
Common locations:
Cerebellar hemisphere
Optic nerve/chiasm
hypothalamus
Radiologic: discrete appearing, contrast
enhancing lesion, often with cystic with mural
nodule
AKA:
Cystic cerebellar astrocytoma
Juvenile pilocytic astrocytoma
Optic gliomas if it occurs on optic nerve
Hypothalamic gliomas
Treatment
Cerebellar PCA
Maximal surgical excision of the tumor
without producing deficit
Excision of the nodule is sufficient, cyst wall
is non neoplastic
Optic Glioma
Optic nerve sparing chiasms excision
If chiasm is involve biopsy, chemotherapy
or radiotherapy

Lesion at the optic chiasm

Diffuse Astrocytoma
AKA Low Grade Diffuse Astrocytoma
WHO grade II
3 cell types
Fibrillary (most common)
Gemistocytic (prone to progress to high
grade)
Protoplasmic
Predilection for temporal, posterior frontal and
anterior parietal lobe

Clinical presentation
Most commonly seizures
Headache
Imaging: Tumor does not significantly enhance
with contrast
Genetic markers
Loss of heterozygosity on chromosome 10
& 17
Alteration of tumor suppressor gene at 9p,
13q, 19q and 22q
Transformation of the p53 gene
Dedifferentiation: Major cause of morbidity
with low grade astrocytoma is dedifferentiation
to a more malignant grade
Once dedifferentiation occurs, median survival
is 2-3yrs
Treatment

Surgery although tumor is low grade,

many opt to do surgery because of risk of
progression to higher grade

Radiation increases progression free

survival but no effect on overall survival

Chemotherapy

Observation

Glioblastoma
AKA: Glioblastoma multiforme (GBM)
WHO grade IV
Most common primary brain tumor, it is also
the most malignant

Trans by: Jocine Toledano Neuro Transcom YL3 2015

 Primary GBM arise without evidence of less

malignant precursors
Secondary GBM develop by malignant
degeneration
Imaging:
The enhancing ring is cellular tumor.
The non enhancing center may represent
necrosis or cyst.
Tumor cells are present >15mm beyond
the ring
Spread via
Tracking through white matter
Corpus callosum butterfly glioma
CSF pathways
Treatment
Surgery
Radiation
Chemotherapy
* Even with maximal treatment median survival is
1 yr

Irregular lesion

Oligodendroglioma
WHO grade II or III
Frequently present with seizures
Predilection for the frontal lobes
Histology: classic fried egg cytoplasm and
chicken wire vascularity
Imaging: Calcifications are common
Treatment
Surgery
Chemotherapy for all
Radiotherapy for anaplastic trasformation
Prognosis
10 yr survival 10-30%

Choroid Plexus Papilloma

WHO grade I
Location:
Children: Supratentorial
Adults: Infratentorial
Presentation:
Symptoms of increased ICP
Headache
Nausea/Vomiting
Craniomegally
Treatment
Surgery
Chemotherapy and Radiation has no role

Medulloblastoma
WHO grade IV
A small cell embryonal tumor of the cerebellum
found predominantly in children
Arises in the cerebellar vermis in the region of
the apex of the roof 4th ventricle
Compromises 30-55% of posterior fossa tumors.
Most common malignant pediatric brain tumor
Presentation:
Headache
Nausea/vomiting

Trans by: Jocine Toledano Neuro Transcom YL3 2015

Ataxia
Irritability, lethargy and macrocrania in
infants
Imaging:
Cranial CT or MRI
Spinal MRI to check for drop metastasis
Treatment

Surgery debulk as much as possible

without causing neurologic injury

Radiotherapy Craniospinal. MB are

highly radiosensitive
Chemotherapy MB are moderately
chemosensitive
Prognosis
Poor prognosticators
Age < 3yo
Drop metastasis
Tumor residual > 1.5cm2
Ependymoma
WHO grade II
Arise from ependymal cells lining the cerebral
ventricles and central canal of the spinal cord
Most often occur in the floor of the 4th ventricle
Ependymoma
Presentation:
Increase ICP Headache, N/V, ataxia
CN VI and VII palsies
Imaging
Cranio-spinal MRI
Treatment
Gross total removal
Radiotherapy on tumor bed, cranio-spinal if
with drop mets
Chemotherapy limited role

TUMORS OF CRANIAL AND PARASPINAL

NERVES
Schwannoma

Cellular

Plexiform

Melanotic
Neurofibroma

Plexiform
Perineurioma
Malignant peripheral nerve sheath tumor

Schwannoma
WHO grade I

Most frequently in middle aged and elderly

adults with a predilection for females (F:M 1.5 2 : 1)
Clinical presentation depends on the size of the
tumor, the nerve of origin and the exact location
Intracranial Schwannoma
Trigeminal schwannoma
Facial Nerve
Vestibular schwannoma (most common)
Vestibular schwannoma
Arises from the superior vestiular nerve at
the Obersteiner-Redlich zone
Arise as a result of loss of a tumor
suppressor gene at the long arm of
chromosome 22
If present bilaterally it is associated with
Neurofibromatosis type 2
Presenting symptoms
Hearing loss
Tinnitus
Dysequilibrium
Evaluation
Cranial MRI
Pure tone audiogram
Speech discrimination score
Treatment
Expectant management
Radiation therapy
Surgery
Chemotherapy

TUMORS OF THE MENINGES

Lymphomas and Hemopoietic Neoplasms
Germ Cell Tumors
Tumors of the Sellar Region
Metastatic Tumors
Tumors of the Meninges
Tumors of meningothelial cells
Meningioma
Mesencymal tumors

Lipoma

Angiolipoma

Leiomyoma

Osteoma

Osteosarcoma

Hemangioma

Hemangiopericytoma
Primary Melanotic lesions

Diffuse melanocytosis

Melanocytoma

Malignant melanoma

Trans by: Jocine Toledano Neuro Transcom YL3 2015

Meningioma
WHO grade I, II, or III depending on subtype
Slow growing extra axial tumor arising from the
arachnoid cap cells
2nd most common primary intracranial tumor
Location:

Grade

Degree of Removal

Gross total excision of tumor and dural

attachment

II

Gross total excision of tumor

coagulation of the dural attachment

III

Gross total excision, without coagulation of

attachment

IV

Partial excision of tumor

Biopsy

and

LYMPHOMAS AND HEMOPOIETIC

NEOPLASMS
Malignant lymphomas
Plasmacytoma
Granulocytic sarcoma
Parasagittal
Convexity
Tubercullum sella
Sphenoid ridge
Olfactory groove
Falx
Lateral ventricle
Tentorial
Spinal
Presenting symptom would depend on the
location of the tumor
Imaging:
Cranial CT scan with contrast
Cranial MRI with contrast
Cerebral angiogram
Spinal MRI for spinal meningioma
Treatment:
Surgery
Radiotherapy for atypical and anaplastic
subtypes
Recurrence in 10 years
Simpson I excision 8%
Simpson II excision 18%
Simpson III excision 28%
Simpson Grading of Meningioma Excision

CNS Lymphoma
May be primary or secondary
Ssuspected with homogenously enhancing
lesions in the central grey matter, corpus
callosum, periventricular
Presenting symptoms
Mental status changes
Symptoms of inc ICP
Generalized seizures
Diagnostics
MRI no pathognomonic feature. Difficult to
determine if tumor is subependymal
Ghost tumor disappears when steroids
are given
CSF studies elevated protein and cell
count, positive cytology in 10%
Treatment
Surgery for biopsy purposes only
Radiotherapy Whole brain but lower dose
compared to other primary CNS tumors
Chemotherapy
Methotrexate
Prognosis
No treatment 1.8-3.3 months
RT median survival 10 mos
Chemo median survival of 41 mos

GERM CELL TUMORS

Germinoma
Embryonal carcinoma
Yolk sac tumor
Choriocarcinoma

Trans by: Jocine Toledano Neuro Transcom YL3 2015

Teratoma
Mixed germ cell tumor
Pineal Region Neoplasm
Tumors in this region are more common in
children
Pineal Tumors
Pineal cell tumors

Pineocytoma

Pineoblastoma
Germ cell tumors

Germinoma

Non Germinomatous germ cell

tumor (NGGCT
Embryonal carcinoma
Choriocarcinoma
Endodermal sinus tumor
teratoma
Diagnostic
Tumor markers
B-HCG choriocarcinoma
Alpha fetoprotein (AFP) endodermal
sinus tumors
Placental alkaline phospahatase (PLAP)
germinoma

Germinoma based on Japanese (43-70%) and

European (21-44%) Studies is the most
common tumor in this region
Presentation:
hydrocephalus
Nausea/vomiting
Parinauds syndrome
Precocious puberty
Management:
- Surgery
- Biopsy
- CSF diversion
- Trial Radiotherapy???

TUMORS OF SELLAR REGION

Craniopharyngioma
- Adamantinomatous
- Papillary
Granular cell tumour
Pituicytoma
Spindle cell oncocytoma of the adenophypophysis

Pituitary Tumors
Most are benign adenomas arising from the
anterior pituitary (adenophypophysis)
Neurohypophyseal tumors are rare
Microadenoma if tumor is < 1cm
Macroadenoma if tumor > 1cm
May be classified by endocrine function

Prolactin secreting

Thyroid hormone secreting

Growth hormone secreting

Cortisol secreting
Presentation

Endocrine disturbance

Mass effect
Optic chiasm bitemporal
hemianopsia
3rd ventricle Obstructive
hydrocepahlus
Caverous sinus Cranial nerve
palsy

Pituitary Apoplexy
Due to sudden expansion of
adenoma due to hemorrhage or
necrosis
Surgical emergency
Give
glucocorticoid
immediately
Diagnostics:

Formal visual fields

Endocrine screening
Cortisol
TSH, T4
Prolactin
FSH, LH
IGF-1

Imaging Cranial MRI

Trans by: Jocine Toledano Neuro Transcom YL3 2015

Prolactin
(ng/ml)

Interpretation

Situation

3-30

Normal

Normal physiologic

25-150

Mod elevated

> 150

Markedly
elevated

Fewer number of Mets

Female gender
Sources of Brain Mets

Prolactinoma
Stalk effect

Primary

Lung

44

Breast

10

Kidney

GI

Melanoma

Undetermined

10

Prolactinoma

Management
Prolactinoma - may opt medical treatment
using bromocriptine
Growth hormone secreting may opt
medical treatment using octreotide
Surgery
Radiotherapy

SPINE TUMORS
Could be classified into 3 groups

Brain Metastasis
Most common brain tumor seen clinically
They compromise more than half of brain
tumors

Route of metastatic spread to the brain is

usually hematogenous, although local extension
do occur

Imaging Solitary Mets

CT: at time of diagnosis 50% are solitary
on CT
MRI: same patient have an MRI, <30%
will be solitary
Treatment
Surgery
Stereotactic radiosurgery
Whole brain RT
Chemotherapy
Brain Metastasis

Factors associated with better prognosis

Karnofsky score >70
Age < 60 yo
Metastasis to brain only ( no systemic
mets)
Controlled primary

Group

Description

Extradural (ED)

55
%

Outside the cord, in

vertebral bodies and
epidural tissues

Intradural
Extramedullary
(IDEM)

40
%

Arise
leptomeninges
roots

Intradural
Intramedullary (IDIM)

5
%

Arise in spinal cord

substance. Invade and
destroys tracts and
grey matter

in
or

EXTRADURAL
A. Metastatic compromises majority of ED
tumors
B. Primary spinal cord tumors very rare
1.
Chordomas
2.
Osteoma
3.
Osteoblastoma
4.
Aneurysmal bone cyst
5.
Vertebral hemangioma

Spinal Epidural Metastases

Suspected in a cancer patient with back pain that
persist in recumbency
80% of primary site: Lung, breast, prostate, GI,
lymphoma
Routes of Metastasis

Arterial

Trans by: Jocine Toledano Neuro Transcom YL3 2015


Venous via Batsons plexus

perinervous
Presentation

Pain

local pain at level of involvement,

increased with recumbency

Radicular shooting pain at

dermatome of involved nerve

Mechanical exacerbated by
movement

Motor dysfunction

Sensory dysfunction

Spinal epidural metastases

Treatment

Surgery to reduce pain, stabilize and preserve

ambulation

Surgery not recommended for prognosis <3-4

months survival, poor medical condition

Radiotherapy

A.
B.
C.
D.

INTRADURAL EXTRAMEDULLARY
Meningomas
Neurofibromas/Schwanomas
Lipomas
Misc.
Spinal Meningioma
Peak age: 40-70yo
Female:male ratio 4:1
90% completely intradural
Location
82% thoracic

10

15% cervical
2% lumbar
Recurrence rate with complete excision 7%

Spinal Schwannoma
Slow growing benign tumors
Most (75%) arise from the dorsal (sensory)
rootlets
Early symptoms are often radicular
Recurrence is rare after total excision

A.
B.
C.

INTRADURAL INTRAMEDULLARY
Astrocytoma 30%
Ependymoma 30%
Misc 30%

Spinal Ependymoma
Slight male predominance
Peak in 3rd to 6th decade
50% occurs in filum, next is cervical
It is the most common glioma of the lower
cord, conus and filum

Usually Myxopapillary subtype (WHO gr I)

Treatment excision (most are encapsulated)

NOTE: memorize the pie graph, simpson grading

and the tumors of the pineal tumor. Know the
grading of the tumors and read on parinaud's
syndrome.

Trans by: Jocine Toledano Neuro Transcom YL3 2015