TUMORS OF THE CENTRAL NERVOUS SYSTEM

NEURO 2 | Dr. Ruben Flores

09/12/2021, 8-10 AM

Extramedullary (Extraaxial)
Contents
- Meningioma
I. Brain Tumors
- Pituitary Adenoma
II. Gliomas
- Vestibular Schwannoma
a. Astrocytoma
Intraventricular
b. Oligodendrogliomas
c. Ependymoma
III. Meningioma AGE INCIDENCE
a. Hemangiopericytoma  adults
IV. Tumors of the Pituitary Gland  supratentorial: 80-85%
V. Vestibular Schwannoma  infratentorial: 15-20%
VI. Lymphomas  children
a. Primary CNS Lymphoma  supratentorial: 40%
VII. Vascular Tumors  infratentorial: 60%
a. Hemangioblastomas
VIII. Metastasis CLINICAL PRESENTATION
a. Brain Parenchymal Metastasis  depends on location of the tumor and rate of growth of tumor
b. Leptomeningeal Metastasis  insidious onset
c. Dural Metastasis  slowly progressive course
IX. Germ Cell Tumors  headache
a. Germinomas  seizure
b. Nondysgerminoma Germ Cell Tumor  mental, behavioral and personality changes
c. Pineal Gland Tumors  lateralizing or focal neurologic deficits
d. Epidermoids  increased intracranial pressure
e. Dermoid Tumors
f. Teratomas TEMPORAL PROFILE
X. Chordomas
XI. Choroid Plexus Papilloma
XII. Colloid Cysts of the Thirrd Ventricle
XIII. Indirect Neurologic Complications of Cancer
a. Paraneoplastic Neurologic Syndromes

WHO HISTOLOGIC CLASSIFICATION: TUMORS OF THE CNS

1. Tumors of Cranial and Spinal Nerves
2. Tumors of the Meninges
3. Tumors of Uncertain Histogenesis- hemangioblastoma
4. Lymphomas and Hematopoietic Neoplasm
5. Germ Cell Tumors
CEREBRAL DYSFUNCTION
6. Cyst and Tumor-like Lesions
 seizure
7. Tumors of the Sellar Regions
 language disorder- aphasia
8. Tumors of Neuroepithelial Tissue
 organic mental, behavioral and personality changes
9. Local Extension from Regional Tumors
 contralateral
10. Metastatic Tumors
 hemiparesis with Babinski & cranial nerve deficits
 hemisensory deficits
BRAIN TUMORS  homonymous hemianopsia/ quadrantanopsia
BRAIN TUMORS
Primary CEREBELLAR DYSFUNCTION
Secondary (Metastatic)  hemisphere lesion
- Brain parenchyma  ipsilateral limb ataxia
- Leptomeninges - intention tremor
- Dural - dysmetria
Benign - dysdiadochokinesia
Malignant  vermis lesion
Intramedullary (Intraaxial)  truncal ataxia
- Glioma  no limb ataxia
- Primary CNS Lymphoma
- Metastatic BRAINSTEM DYSFUNCTION

Page | 1
TUMORS OF THE CENTRAL NERVOUS SYSTEM
NEURO 2 | Dr. Ruben Flores
09/12/2021, 8-10 AM

 “crossed motor/sensory syndrome” neoplastic

 ipsilateral cranial nerve deficits astrocytes

 contralateral hemiparesis with Babinski III Anaplastic Nuclear atypia and

Astrocytoma mitosis
 ipsilateral limb ataxia
II Oligo- Rounded tumor cells, Nuclear atypia,
 internuclear ophthalmoplegia- medial longitudinal fasciculus
dendrogliom “fried egg” occasional mitosis
syndrome a appearance,
network of
INCREASED ICP branching
 headache/ vomiting with: capillaries
 papilledema III Anaplastic Nuclear atypia,
oligo- mitosis,
 diplopia with internal squint (lateral rectus palsy secondary
dendrogliom microvascular
to abducens nerve lesion)
a proliferation,
 deterioration in the level of consciousness necrosis
 bulging fontanel, separation of sutures, rapidly enlarging II Ependymoma Perivascular Well delineated,
head size pseudorosettes moderately cellular
and ependymal
rosettes
ANCILLARY PROCEDURES
III Anaplastic Mitoses,
 skull x-rays ependymoma microvascular
 EEG proliferation,
 perimetry, audiometry pseudopalisading
 cerebral angiography necrosis

 CSF examination  role?

 neuroimaging studies ASTROCYTOMA
 cranial/ spine CT scan/MRI with or without contrast  Grade I (Pilocytic Astrocytomas)
 primary in children and young adults
TREATMENT  focal astrocytoma may be associated with
 surgery neurofibromatosis type I (NF-1)
 radiotherapy  unusually excellent prognosis
 chemotherapy  Grade II (Diffuse or Fibrillary Astrocytoma)
 most common in cerebral hemisphere in young adults
 low grade or benign histologically
GLIOMAS
 most common primary brain tumor  infiltrative
 50% of all symptomatic brain tumors  complete resection not possible
 incidence increases with advancing age  latent potential for malignant transformation
 th th
peak in 8 and 9 decades  Grade III (Anaplastic Astrocytoma)
 no known environmental factors  Grade IV (Glioblastoma Multiforme)
 no behavioral or lifestyle choices  CSF seeding
 ionizing radiation- the only clear risk factor - malignant cells in the CSF may form
 originate from glial cells or their stem cell precursors  distant foci in spiral roots
 include:  widespread meningeal gliomatosis
 astrocytoma  extraneural metastasis
 oligodendrioma - to bone and lymph nodes (very rare) after a
 ependymoma craniotomy
 WHO classification basis  high grade gliomas
 increased cellularity  20% of all intracranial tumors
 nuclear atypia  55% of gliomas
 endothelial proliferation  80% of gliomas of the cerebral hemispheres in adults
 necrosis  peak incidence middle to late adult
 males/females: 1.61
Grade WHO Criteria for Tumor Criteria for Grade  no familial predilection
Designation Type  prognosis
I Pilocytic Bipolar and Piloid cells, Rosenthal  median survival
astrocytoma multipolar fibers, eosinophilic - glioblastoma multiforme: 1 year
astrocytes, long granular bodies, low - anaplastic astrocytoma: 3 years
processes, cellularity
- low grade astrocytoma: 5 years
microcytes
- others survive a decade or more, most die from
II Astrocytoma Well-differentiated Nuclear atypia,
fibrillary or increased cellularity transformation of tumor to higher grade

Page | 2
TUMORS OF THE CENTRAL NERVOUS SYSTEM
NEURO 2 | Dr. Ruben Flores
09/12/2021, 8-10 AM

Grade 1: Pilocytic Astrocytoma Grade II: Fibrillary Astrocytoma

Pseudopalisading around the necrosis

in GBM.

Gliomas (High/Low Grade)

Grade III: Anaplastic Astrocytoma Grade IV: Glioblastoma

High-grade or malignant gliomas Low-grade gliomas typically are non-

appear as contrast-enhancing mass enhancing lesions that diffusely
lesions, which arise in white matter and infiltrate the brain and may involve a
are surrounded by enema. large region of brain. Low-grade
gliomas are usually best appreciated
on T2-weighted MRI lesions.

Glioblastoma Multiforme

Giant Cell Astrocytoma

GBM has crossed midline in “butterfly”

pattern.

OLIGODENDROGLIOMAS
 derived from oligodendrocytes or
their precursors
 5-7% of all intracranial gliomas
Anaplastic Astrocytoma
 most often in the 3rd and 4th
decades
 males/females: 2:1
 found primarily in cerebral
hemispheres
 highly infiltrative
 may metastasize distantly in
ventricular and subarachnoid spaces
 calcification is common
 “fried egg” cells
Anaplastic astrocytomas have increased pleomorphism, enlarged nuclei, and
most importantly, increased proliferative activity that is reflected as increased  usually (glial fibrillary acidic protein) GFAP negative
mitotic activity. A mitotic figure (arrow) is presented in this field. There should  majority are low grade lesions which have the potential to
be no necrosis or endothelial proliferation in anaplastic astrocytoma. The
transform over time to anaplastic oligodendroglioma
presence of either or both are suggestive of worse biological behavior.
 may acquire astrocytic features which may develop into
glioblastoma multiforme
Glioblastoma Multiforme  radiosensitive

Page | 3
TUMORS OF THE CENTRAL NERVOUS SYSTEM
NEURO 2 | Dr. Ruben Flores
09/12/2021, 8-10 AM

 radiotherapy  standard treatment for anaplastic

oligodendroglioma
 correlated with loss of heterozygosity of chromosome 1p19q
(1p/19q LOH or deletion)
 many respond to chemotherapeutic agents
 PCV regimen: Procarbazine, Lomustine, and Vincristine
 prognosis
 medial survival
- low-grade oligodendrogliomas: 8-16 years
- anaplastic oligodendrogliomas: 5 years
 tumors that have 1p/19q LOH have the best prognosis
 many patients die from malignant transformation of their MENINGIOMA
tumors  originate from arachnoid cells (meningothelial cap cells
normally seen in arachnoid villi)
Oligodendroglioma  2nd most common primary brain tumor (about 15%)
 20% of all posterior fossa tumors (w/ asymptomatic cases-
40% or more)
 7% of all posterior fossa tumors
 3-12% of cerebellopontine angle tumors
 most diagnosed in 6th and 7th decades
 F:M  3:2 to 2:1
 multiple in 5-15% (NF-2)
“Fried egg cells”
 90% intracranial, 10% intraspinal (spinal meningioma- 10x in
women)
EPENDYMOMA
 all familial meningiomas occur with NF-2
 arise from ependymal cells (intraventricular tumor)  rare in children (more in boys)
 more common in children  rare with dural attachments
 10% of pediatric intracranial tumors  usually intraventricular or posterior fossa
 5% of adult intracranial tumors  commonly with sarcomatous changes
 most common in the 4th ventricle  frequently with NF-2
 ataxia, vertigo, increased ICP  growth rate
 may grow in brain parenchyma without obvious attachment to  less than 1cm per year
the ventricular system  tumor doubling time: 1.27-14.35 years
 spinal lesions more common in adults
 intracranial ependymomas predominate in children
ETIOLOGY
 histologically
 radiotherapy: only established risk factor for meningioma
 perivascular pseudorosettes: tumor cells arrange
 radiation induced tumors tend to occur over convexities
themselves radially around blood vessels
- multiple
 ependymal or Homer-Wright rosettes: tumor cells
- histologically malignant
arrange themselves around a central lumen
- more likely to recur
 GFAP positive
 head trauma: not confirmed risk factor
 loss of chromosome 22, particularly 22q
 viral infection (SV-40): data are unconvincing
 CSF seeding (“drop metastasis”)
 estrogen receptors marginally present
 cranial MRI
 less affinity for estrogen as the receptor in breast cancer
 heterogenous, well delineated lesion with prominent
 progesterone receptors
contrast enhancement
 expressed in 80% of women with meningiomas
 occasional hemorrhage and calcification
 expressed in 40% of men with meningiomas
 prognosis
 molecular genetic studies of men with gliomas:
 5-year survival  40-50%
 loss of 22q in 80% of sporadic meningiomas (deletion of
 10-year survival  47-68%
NF-2 tumor suppressor gene at 22q11 and lack of protein
 better prognosis
product merlin)
- young age
 all familial meningiomas occur with NF-2
- infratentorial
- NF-2 patients are at increased risk of meningiomas,
- gross total excision
vestibular schwannomas, both frequently multiple
- low grade histology

Ependymal Rosettes PATHOLOGY

Page | 4
TUMORS OF THE CENTRAL NERVOUS SYSTEM
NEURO 2 | Dr. Ruben Flores
09/12/2021, 8-10 AM

 nodular tumors occasionally

meningioma en plaque (sheet
like formation)
 highly vascular
 encapsulated and attached to
the dura (blood supply from
external carotid artery)
 hyperostosis of adjacent
bone CRANIAL CT SCAN
 isointense or slightly hyperintense
HISTOLOGICALLY  smooth, sometimes lobulated distinct
 benign margins with dural tail attachments
 typical features:  strong and homogenous enhancement
 whorls of  edema is variable
arachnoid cells  hyperostosis: 20%
surrounding a
central hyaline MR ANGIOGRAPHY AND VENOGRAPHY
material that  has replaced standard angiography
eventually
calcifies to form psammoma bodies
 no characteristic cytologic marker

WHO
 cellular, cytologic atypia, mitosis, necrosis TREATMENT
A. Typical or benign
B. Atypical or malignant- rare SURGERY
▪ other histologic features of anaplasia often present:  complete excision may cure many
mitosis, pleomorphism, necrosis meningiomas
▪ aggressive (+ brain invasion)  the extent of resection is the most
▪ systemic metastasis in 50% important in determining recurrence
- bone  for recurrence: reresection
- liver
- lung RADIATION THEARPY
 residual tumor after surgery
CLINICAL MANIFESTATIONS  recurrent tumor
 atypical or malignant histology
 asymptomatic- found incidentally by MRI
 symptoms
 tumor location
- by compression of underlying neural structures
 site of predilection
- cerebral convexity (Sylvian and parasagittal areas)
- falx cerebri
- skull base
 olfactory groove
 tuberculum sella
 sphenoid ridge
 cerebellopontine angle

DIAGNOSIS

CRANIAL MRI
 isointense (65%) or hypointense (35%) in T1 and T2
 intense and homogenous enhancement with gadolinium

Page | 5
TUMORS OF THE CENTRAL NERVOUS SYSTEM
NEURO 2 | Dr. Ruben Flores
09/12/2021, 8-10 AM

Normal Pituitary & Pituitary Chromophobe Adenoma

HEMANGIOPERICYTOMA
 pituitary carcinoma
 meningeal tumor derived from pericytes (smooth muscle cells
 highly invasive
associated with small blood vessels
 rapidly growing and
anaplastic
TUMORS OF THE PITUITARY GLAND  unequivocal diagnosis
 often asymptomatic
relies on presence or
 3rd most common primary brain tumor
distant metastasis
 incidence at autopsy: 1.7-24%
 most common in adults in the 3rd-4th decades
CLINICAL MANIFESTATIONS
 10% in children and adolescents
 not hereditary except MEN-1 (multiple endocrine neoplasia)  mass effect
 compression of neural and vascular structures
- headache
PATHOLOGY
- hypopituitarism
 microadenoma
- visual symptoms
 less than 1cm
 visual loss
 symptoms by excess
 visual field abnormality  bitemporal hemianopsia
hormone secretion
is the most common
 macroadenoma
- papilledema rare
 more than 1cm
- may enlarge during pregnancy
 symptoms by
- 5% of pituitary adenoma present with pituitary
compressing normal pituitary gland and neural structure
apoplexy
 endocrine active (secretory)
 prolactinoma: most common endocrine active tumor
 growth hormone
 ACTH: Cushing’s disease
 FSH and LH
 endocrine inactive (non-secretory or null cell adenoma)
 10%- mixed secretory tumor
 histology
 almost all are histologically
benign
 pituitary carcinoma, rare
 macroadenomas
- may invade dura, bone
- may infiltrate surrounding
structure
- locally invasive pituitary adenomas are always
histologically benign
- pleomorphism and mitotic figure insufficient for
diagnosis of cancer (may be seen in benign adenomas)
- invasive character independent of growth rate

Page | 6
TUMORS OF THE CENTRAL NERVOUS SYSTEM
NEURO 2 | Dr. Ruben Flores
09/12/2021, 8-10 AM

DIAGNOSIS
 cranial MRI: best way to evaluate pituitary pathology

Microadenoma
Lateral view of a chromophobe
adenoma. This radiograph offers a side
view of the expanded sella (between
the orbit on the left and the radio-
dense mastoid on the right,

Coronal T2-weighted magnetic Sagittal T1-weighted magnetic

resonance image shows a resonance image without contrast
hyperintense, extraaxial mass in the shows a dumbbell-shaped sellar mass
region of the sella with superior invading the clivus with significant
PITUITARY APOPLEXY (intracranial) and inferior (sphenoidal) mass effect on the corpus callosum,
 hemorrhage or infarction of pituitary adenoma extensions. frontal lobes, and ventricular system.
 sudden onset of headache, nausea, vomiting, visual loss, an inferior extension reaches the soft
palate.
diplopia, altered mental status
 diagnosis by CT or MRI
TREATMENT
 treatment  emergency surgery
 surgery
 transsphenoidal approach: procedure of choice
 hormone replacement
 radiation therapy: complementary to surgery in preventing
progression or recurrence
 radiosurgery: not used for (1) large tumors and (2) tumors
<3mm distance from optic apparatus

This is a cross-section of an old infarct of the pituitary showing infarct (yellow) VESTIBULAR SCHWANNOMA
surrounded by normal pituitary (brown). The infarct zone shows yellow fibrillar  acoustic neuroma; acoustic neurofibroma
appearance.
 arises from Schwann cells of the vestibular branch of the 8 th
cranial nerves
 4th most common primary brain tumor
 5-10% of intracranial tumors
 most common tumor of the cerebellopontine angle
 peak age: 40-60 years old
 F:M= 2:1
 bilateral tumors in less than 5%
 defining characteristic of NF-2
 grow slowly: less than 2mm per year
 many tumors are large and even cystic before they become
(on the right) with the infarcted neurotic area (on the left). Notice the ghost symptomatic
architecture and the acellular area of infarction in this case of Sheehan’s
syndrome.

Page | 7
TUMORS OF THE CENTRAL NERVOUS SYSTEM
NEURO 2 | Dr. Ruben Flores
09/12/2021, 8-10 AM

Malignant Schwannoma

Malignant schwannomas can be difficult to diagnose and are usually more

than 5cm in diameter by the time they are brought to the attention of a
medical professional and identified. Similar to most other types of cancers, the
PATHOLOGY
tumors are treated with one or more of the following: surgery, chemotherapy,
 gross: yellowish with areas of or radiotherapy. The five-year survival rate associated with malignant
schwannomas is low, primarily due to poor response of the tumors to available
cystic degeneration
treatments and metastasis to the lungs and other areas of the body. Patients
 histologic: that usually have the best outlook are those that are young and have relatively
 Antoni A: areas with small tumors able to be removed via surgical means.
densely packed tumor cells
 Antoni B: areas with looser CLINICAL FEATURES
pattern of stellate cells with  progressive unilateral hearing loss
long irregular processes  tinnitus: 70%
 unsteady gait (disequilibrium): 20%
 facial numbness: 30%
 facial weakness: 9%
 decreased corneal reflex

DIAGNOSIS
 gadolinium enhanced MRI
 best technique for diagnosis
 hyperintense on T2 MRI

This is an example of a schwannoma. It typically has dense areas called Antoni

A (black arrow) and looser areas called Antoni B (blue arrows). The cells are
elongated (spindle shaped) and the nuclei have a tendency to line up as you
see here in the Antoni A area. Like normal Schwann cells, schwannoma cells are
each surrounded by a basement membrane.

Schwannoma

Notice the whirly swirly pattern and how the cell nuclei are closely bunched TREATMENT
together almost as if they’re forming a fence (Verocay bodies). Schwannomas  surgery
are benign spindle cell tumors that occur along the edges of peripheral nerves.
They can usually be removed without damaging the nerve itself.
 radiosurgery: excellent alternative for tumors less than 3 cm in
diameter

Page | 8
TUMORS OF THE CENTRAL NERVOUS SYSTEM
NEURO 2 | Dr. Ruben Flores
09/12/2021, 8-10 AM

Intradural Extramedullary Schwannoma  MRI: hypointense on T1 relative to gray matter; borders

not well demarcated
- on contrast: dense and homogenous in
immunocompetent
- edema mild to moderate
- MRI may show diffuse ependymal spread not
appreciated on CT

Cerebellopontine Angle (CPA) Tumors

1. Vestibular Schwannoma
2. Meningioma
3. Cholesteatoma (Epidermoid)
4. Trigeminal Neuroma

SCHWANNOMA NEUROFIBROMA
Eccentric placement in nerve Hallmark tumor of NF-1
fascicle IMMUNOCOMPROMISED
Gross total resection normally Plexiform neurofibroma: cord-like
 associated with:
possible enlargement of nerve twigs
 AIDS
Spindle cells, axons, myxoid
background  renal transplantation
Patent nerve intermingle with  ataxia telangiectasia
tumor  rheumatoid arthritis
 Wiskott-Aldrich syndrome
LYMPHOMAS  IgA deficiency
 metastatic (CNS)  occurs in the 3rd and 4th decades
 almost exclusively with non-Hodgkin’s lymphoma (NHL)  almost always multiple; DO NOT have the typical
 leptomeninges: 10% periventricular location
 epidural space: 3-5%  increased preponderance of the immunoblastic subtype
 rarely brain parenchyma (<1%)  hemorrhage, necrosis, and calcification common
 Hodgkin’s lymphoma  neuroimaging
 epidural spinal cord compression  with contrast: ring enhancement (corresponding to
 rarely leptomeningeal and brain parenchyma necrosis)
 primary CNS lymphoma  diagnosis
 brain parenchyma (>90%)  histologic confirmation from:
- brain
PRIMARY CNS LYMPHOMAS - CSF
- vitreous humor
 gross and microscopic pathology, clinical manifestations
IMMUNOCOMPETENT
are identical in immunocompetent and
 3% of all intracranial neoplasms
immunocompromised
 7% of all malignant lymphomas
 clinical manifestations
 peak incidence: 5th-7th decade
 symptoms of space-occupying lesions
 M:F= 3:2
- headache
 pathology
- personality change
 single or multiple parenchymal brain lesions (>90%)
- lateralizing or focal neurologic deficits
 primary leptomeningeal lymphoma
 primary intramedullary lymphoma of spinal cord (rarest)
TREATMENT
 primary ocular lymphoma (uvea or vitreous lesions)
 corticosteroids
 98%: B cell tumors
 surgery is not helpful therapeutically
 2%: T cell tumors
 radiation: PCNSL is highly responsive to radiotherapy
 grossly: fleshy with ill-defined borders
 chemotherapy: PCNSL is chemosensitive
 histologically: cells are closely packed with characteristic
perivacular concentration
 neuroimaging
 single or multiple lesions, often periventricular
 most common in supratentorial, particularly frontal lobe
 CT scan: isodense of hyperdense pre-contrast

Page | 9
TUMORS OF THE CENTRAL NERVOUS SYSTEM
NEURO 2 | Dr. Ruben Flores
09/12/2021, 8-10 AM

VASCULAR TUMORS
 histologically indistinguishable
 hemangioblastoma
- confined to posterior fossa
- no dural attachment
 angioblastic meningioma
- located above and below tentorium
- has significant dural attachment
- identical to other meningiomas
 hemangiopericytomas
- derived from pericytes (smooth muscle cells of small
blood vessels) Hemangioblastoma (H&E): Lipid laden (arrow) stromal cells with thin vascular
- recognized elsewhere in the body channels (double arrow) with prominent endothelial cells and pericytes.

HEMANGIOBLASTOMAS
 composed of primitive vascular elements
 1-2% of intracranial neoplasms
 all ages but more frequently in young and middle-aged adults
 predominantly males
 20% familial
 10-20%: part of von Heppel-Lindau disease
 hemangioblastoma
 angiomatoses of retina
 cysts of kidney and pancreas Hemangioblastoma (frontal section of the cerebellum before fixation). Reddish
 occasionally: renal cell carcinoma and capillary nevi of skin neoplastic growth in the vermis bulging into the fourth ventricle. This tumour
generally arises in the cerebellum, but one or more leptomeningeal,
 predominantly in the cerebellum (most common in the
intracranial or intraspinal, localizations are possible.
paramedian cerebellar hemisphere)
 large cysts with yellow proteinaceous fluid von Hippel-Lindau Syndrome Cystic Hemangioblastoma
 resemble the cyst and mural nodule of cystic cerebellar
astrocytoma but with distinctive vascular appearance

Cerebellar Hemangioblastoma

 clinical features of cerebellar masses

 headache
 papilledema

Vertebral Angiogram: Hemangioblastoma  ataxia

 polycythemia: erythropoietic substance from cystic fluid
 diagnosis
 CT
 angiogram
 treatment
 surgery
- evacuation of cyst
- removal of mural nodule

Page | 10
TUMORS OF THE CENTRAL NERVOUS SYSTEM
NEURO 2 | Dr. Ruben Flores
09/12/2021, 8-10 AM

CEREBELLAR DYSFUNCTION
 hemisphere lesion
 ipsilateral limb ataxia
- intention tremor
- dysmetria
- dysdiadochokinesia
 vermis lesion
- truncal ataxia
- no limb ataxia

PROGNOSIS
 good; alive 5-2- years after surgery
 high incidence of recurrence
 if partial resection
 multiple tumors

METASTASIS
- Brain Parenchymal Metastasis
- Leptomeningeal Metastasis
- Dural Metastasis

BRAIN PARENCHYMAL METASTASIS

 usually found with disseminated systemic disease
 in some the intracranial disease appears before the systemic
cancer
 non small cell lung cancer: most common primary lesion
leading to brain metastasis
 melanoma and small-cell lung cancer have the greatest
propensity to metastasize to the brain Brain with metastatic carcinoma, note Metastatic adenocarcinoma
 other primary cancers that commonly spread to the brain flattened gyri and compressed sulci to the brain.
 breast and ventricle.

 renal
TREATMENT
 GI cancers
 whole brain radiotherapy (WBRT): relief of neurologic
 tumor that rarely spread to the brain
symptoms in 80%
 prostate
 at least 48 hours of dexamethasone (16 mg/day) before WBRT
 pancreas
is delivered
 uterine cancers
 chemotherapy
 hemorrhagic metastasis to the brain
 limited role
 lung cancer: most common
 only at recurrence after surgical and radiotherapeutic
 melanoma
options exhausted
 thyroid
 median survival is only 4-6 months
 choriocarcinoma

CLINICAL FINDINGS LEPTOMENINGEAL METASTASIS

 symptoms similar to any space-occupying lesion  8% of patients with cancer
 subacute course over 1-2 weeks  hematologic malignancies (acute lymphocytic leukemia, NHL)
 occasionally acute and stroke-like in intratumoral hemorrhage  solid tumor (breast cancer, lung cancer, melanoma, GI cancer)
 clinical hallmark
DIAGNOSIS  multilevel symptoms and signs that affect 3 main areas:
 cranial MRI with gadolinium: - cerebrum
 solitary or multiple - cranial nerves
 lesions are contrast enhancing - spinal roots and cord
diffusely when small; ring  CSF
enhancing when large with well-  (+) tumor cells
defined borders  (+) tumor markers (cancer antigen 15-3 for breast cancer)
 MRI

Page | 11
TUMORS OF THE CENTRAL NERVOUS SYSTEM
NEURO 2 | Dr. Ruben Flores
09/12/2021, 8-10 AM

 (+) subarachnoid tumor  30% of infratentorial tumors in children but uncommon in

 enhancing tumor in cortical sulci adults
 subependymal enhancement  typically involve the cerebellar vermis, grow to fill the 4 th
 enhancing cranial nerves ventricle, and may infiltrate the floor of the ventricle and
 tumor nodules in cauda equina adjacent structure
 therapy  may arise more laterally, especially in older patients
 radiotherapy to symptomatic sites  median age: 5 years
 intrathecal chemotherapy (contraindicated in uncontrolled  clinical features
high ICP)  increase ICP
 median survival: 4-6 months  unsteadiness
 symptom duration: <3 months
DURAL METASTASIS  recent onset of head tilt from ophthalmoparesis or
incipient cerebellar herniation
 from direct extension of a calvarial metastasis
 diagnosis
 primary with prostate and breast cancer
 cranial CT scan
 may present with painless, growing skull lesion with headache,
- isodense or hyperdense
seizure, and hemiparesis
- enhance homogenously
 MRI may show a tumor similar to meningioma
- with hydrocephalus
 treatment: focal radiotherapy
- may include small cysts,
calcification,
Dural Metastasis: Melanoma
hemorrhage
 MRI
- tumor extent
- possible leptomeningeal dissemination
 treatment
 surgery
 postoperative radiation therapy
 prognosis
 5-year disease-free survival rate: 55%

PRIMITIVE NEUROECTODERMAL TUMORS (PNETS)

 arise from primitive progenitor cells which are pluripotent,
uncommitted neuroectodermal cells with capacity for
differentiation along ependymal, neuronal, glial or even retinal
cells
 most common malignant pediatric tumor, occurring
predominantly in the posterior fossa (medulloblastoma) but
also in the pineal (pinealoblastoma) or other CNS locations
(cortical or spinal PNETS)
 PNETS arising from distinct locations cannot be distinguished
histologically Craniopharyngiomas
 histologic appearance:  from rests of embryogenic tissue located in the Rathke’s pouch
 small, round cell tumor with glial or other types of (anlage of the anterior pituitary gland)
differentiation in some cases  any age, even late adulthood
 high cellularity  6-10% of intracranial tumors in children
 high mitotic rate  suprasellar
 tendency for leptomeningeal dissemination  small, well-circumscribed solid nodules to huge multilocular
 there may be positive staining for both neurofilament protein cysts with turbid fluid that may contain cholesterin crystals
and GFAP but also for synaptophysin which is more specific  histologically benign
for PNET
 medulloblastomas (posterior fossa PNETS) have significantly
better prognosis than other PNETS

Medulloblastomas (Posterior Fossa PNETS)

 derived from fetal external granular cells of the cerebellum or
rests in the posterior medullary velum

Page | 12
TUMORS OF THE CENTRAL NERVOUS SYSTEM
NEURO 2 | Dr. Ruben Flores
09/12/2021, 8-10 AM

 it is hypo- to isodense on T1 and hyperdense on T2 MRI

images
 intense enhancement with gadolinium is noted
 cystic and calcified components are more homogenous,
whereas teratomas are heterogenous

Germinoma (H&E): Groups of large polygonal or spherical cells with large

This lower power view of a section of craniopharyngioma shows a cystic area central nucleolated nuclei, separated by groups of much smaller lymphocyte
on the left, in the zones to the center, and lower right epithelia producing like cells.
acellular substance, and a loose mesenchyme filling the rest of the field.

NONDYSGERMINOMA GERM CELL TUMOR (NGGCT)

 clinical manifestations
 short stature  highly malignant
 hypothyroidism  more aggressive than dysgerminoma
 diabetes insipidus  metastasize to the CSF more frequently than germinoma
 visual loss  endodermal sinus tumors
 increased ICP  contain yolk sac element that produces alpha-fetoprotein
 CT: calcification; bony extension of the sella nonadherent (AFP)
 treatment  choriocarcinomas
 drain cyst; resect nonadherent tumor, post-operation  contain cyst and syncytiotrophoblastic cells that produce
radiation -hCG
 gross total resection  high levels of -hCG and AFP in the CSF indicate the presence
of malignant germ cell element

GERM CELL TUMORS (GCT)

 Germinomas PINEAL GLAND TUMORS
 Nongerminomas  clinical manifestations
 Embryonal-cell carcinoma  increased ICP
 Endodermal sinus tumor (yolk sac tumor)  direct compression of brainstem and cerebellum
 Choriocarcinoma  Parinaud’s Syndrome
 Teratocarcinoma - paralysis of upgaze
 Benign Germ Cell Tumors - light near pupillary dissociation
 Epidermoids (Cholesteatomas) - nystagmus
 Dermoids - ataxia and dysmetria
 Teratomas  endocrine
 by location: - secondary effect of hydrocephalus or tumor spread to
 pineal GCT: almost exclusively in boys the hypothalamic region
 suprasellar GCT: boys=girls - precocious puberty
- precocious pseudopuberty: hypothalamic-gonadal axis
GERMINOMAS not mature
 half of all intracranial GCT  1% of all intracranial tumors in USA
 histologically identical to testicular  4-7% of all intracranial tumors in Asia where GCT are common
seminoma, ovarian  diagnosis
dysgerminomas  MRI with gadolinium
 arise in the midline, pineal area, - modality for all pineal gland tumors
suprasellar - possible ventricular seeding
 highly malignant  serum & CSF
 occasionally seed the CSF - AFP
 CT: typically reveals a hyperdense - -hCG
enhancing midline mass  CSF: for malignant germ cell elements

Page | 13
TUMORS OF THE CENTRAL NERVOUS SYSTEM
NEURO 2 | Dr. Ruben Flores
09/12/2021, 8-10 AM

 treatment Tumor cells with

 surgery: definite histologic diagnosis for optimal patient abundant clear
cytoplasm, large
management
nuclei and
 radiotherapy: all patients with pinealoblastoma, NGGCT,
prominent (red)
and disseminated germinoma require neuraxis nucleoli.
radiotherapy
 chemotherapy: most benefit with pinealoblastoma and
NGGCT
 prognosis
 germinomas: 80-90% 5-year survival rate following surgery
and radiotherapy

EPIDERMOIDS (CHOLESTEATOMAS)
 most common embryonal CNS tumor
 2% of all intracranial tumors
 arise within skull tables or adjacent to the dura
 suprasellar region, cerebellopontine angle, skull base,
brainstem
 encapsulated, pearly appearance, may contain cyst fluid with
cholesterol crystals
 MRI: low T1, high T2 signal
 treatment: surgical resection

DERMOID TUMORS
 cystic mass with yellow cystic fluid from sebaceous gland
secretion

Pathology: Excisional biopsy:

sections through the suprasellar
lesion show a fragmented, thin-
walled cyst lined by true epidermis
with numerous cutaneous adnexal
appendages. Minimal focal capsular
ossification is present (a lamina of
ossification is noted on low power
Relatively well- microscopy). The lumen of the cyst
defined tumor contains abundant keratinous debris
destructed pineal in the form of squames and
gland and occasional hair shafts.
extending into
recussus pinealis.
TERATOMAS
 infants and young children
 mature teratomas are lobulated and cystic containing
differentiated tissues such as bone, cartilage, teeth, hair, or
intestine
 immature and malignant teratomas less common
 tend to occur in the pineal region
 Parinaud syndrome, hydrocephalus
 4% of childhood intracranial tumors
 treatment: surgical resection

Page | 14
TUMORS OF THE CENTRAL NERVOUS SYSTEM
NEURO 2 | Dr. Ruben Flores
09/12/2021, 8-10 AM

Choroid plexus
papilloma
(transverse
section of the
brainstem and
the cerebellum).
Pinkish, granular
growth in the
lateral recess of
the fourth
ventricle, at the
Mature teratoma (MT x16). Partially cystic pineal gland tumor composed of a cerebellopontine
mixture of tissues derived rom the three embryonal layers: epidermis,
angle.
sebaceous glands, cartilage, connective tissue, and secretory endodermal
epithelium. Mature teratomas can also occur in the suprasellar region or, more
rarely, in the brain parenchyma.

CHORDOMAS
 derived from remnants of the
embryonic notochord
 sacrococcygeal, clivus, elsewhere along
the spinal column
 <1% of CNS tumors
 remain asymptomatic until adult
 multiple cranial nerve palsies, erosion of COLLOID CYSTS OF THE THIRD VENTRICLE
skull base  arise from the anlage of the paraphysis
 treatment  grow in the anterior superior portion of 3 rd ventricle
 surgical resection  small white cysts filled with homogenous gelatinous material
 postoperative radiation therapy  become symptomatic during adulthood
 intermittent hydrocephalus
Pathology of  treatment: surgical excision
chordoma.
Lobulated tumor
INDIRECT NEUROLOGIC COMPLICATIONS OF
with epithelial
cords separated
CANCER (NONMETASTATIC OR PARANEOPLASTIC)
by mucinous
 vascular disorders
material  infections
(hematoxylin  metabolic and nutritional disorders
phloxine-saffron,  side effects of therapy:
magnification  chemotherapy
x25).
 radiation tehrapy
 surgery and other diagnostic or therapeutic procedures
Pathology of
chordoma. At  “remote” or paraneoplastic syndromes
higher  may have an autoimmune pathogenesis
magnification,
vacuolated PARANEOPLASTIC NEUROLOGIC SYNDROMES
neoplastic cells
and occasional
 Subacute cerebellar degeneration
physaliphorous  Opsoclonus/ Myoclonus
cells are observed  Limbic encephalitis
(hematoxylin-  Subacute motor neuropathy
phloxine saffron,  Sensory neuropathy
magnification
 Lambert-Eaton myasthenic syndrome
x225).
 encephalomyelitis

CHOROID PLEXUS PARANEOPLASTIC NEUROLOGIC SYNDROMES

PAPILLOMA Cerebellar degeneration anti Yo (anti Purkinje cell) autoantibody
 lateral ventricle tumors of ovary, fallopian tube, lung
Encephalomyelitis anti-Hu, anti-Ma
 most diagnosed before 2 yrs.
tumors of small cell lung, neuroblastoma,
 hydrocephalus
prostate, breast, Hodgkin, testicular (Ma)
 excess CSF production Lambert Eaton anti-VGCC (voltage gated calcium channel)
tumors of small cell lung, Hodgkin, other

Page | 15
TUMORS OF THE CENTRAL NERVOUS SYSTEM
NEURO 2 | Dr. Ruben Flores
09/12/2021, 8-10 AM

lymphomas
Subacute sensory anti-Hu
neuropathy and tumors of small cell lung, Hodgkin, other
neuronopathy lymphomas
Opsoclonus/ Myoclonus anti-Ri
ataxia tumors of breast, fallopian tube, small cell lung
Stiffman syndrome anti-amphiphysin
breast

4 Most Common Primary Brain Tumors in Adults

 Glioma (astrocytoma)
 Meningioma
 Pituitary adenoma
 Vestibular schwannoma

4 Most Common Infratentorial Brain Tumors in Children

 Cerebellar hemisphere astrocytoma: 30-40%
 Vermis medulloblastoma: 30-40%
 Brainstem gliomas: 10-20%
 pontine astrocytoma
 Ependymoma (4th ventricle): 10-20%

Supratentorial Brain Tumors in Children

 suprasellar region (20-30%)
 craniopharyngioma
 chiasmatic and hypothalamic glioma
 germinoma
 pineal/ parapineal region (10%)
 germinoma

2 Most Common Sites of Germinoma

 pineal gland
 suprasellar

Page | 16