Neurology Clinical Presentation

Brain Tumors - Depends on location of the tumor and rate of growth of the
December 17-19, 2007 tumor
- Insidious onset
WHO Histologic Classification of Tumors of the CNS - Slowly progressive tumors
1. Tumors of Neuroepithelial Tissue - Headache
2. Tumors of Cranial and Spinal Nerves - Usually becoming severe & slowly progressive,
3. Tumors of the Meninges tumor should be a suspect
4. Tumors of Uncertain Histogenesis - Seizure
- Ex: Hemangioblastoma from primitive vascular - Adult onset seizures – tumors should be
structures suspected
5. Lymphomas and Hematopoietic Neoplasm - Childhood onset seizures – tumors are rare but
6. Germ Cell Tumor signs of focal neurologic deficits should make
- Ex: Germinoma – common in pineal gland area one suspicious of a tumor
7. Cysts and Tumor-like lesions - Mental, behavioral and personality changes
- Usually in the third ventricle - Also when becoming severe & slowly
8. Tumors of the Sellar Regions progressive, suspect a brain tumor
9. Local Extension from Regional Tumors - Lateralizing or focal neurologic deficits
10. Metastatic Tumors - Increased ICP

Note: Brain tumors are mostly derived from glial cells rather than
the neural cells.
Tumors of the CNS can be:

Primary

Secondary (metastatic) may lodge into the ff structures:
- Brain parenchyma – most common area of metastases
- Leptomeninges – pia mater & arachnoid
- Dural space
Benign
Malignant
- A tumor can be benign histologically. However, due to
location, for example in an eloquent area, it can
become malignant if it causes signs & symptoms
Extramedullary (Extraaxial)
- Meningioma
- Pituitary adenoma
- Vestibular schwanomma
Intramedullary (Intraaxial) – mostly manifesting as seizures
- Glioma – glial cell tumor in the brain parenchyma
- Primary CNS Lymphoma
- Metastatic
Intraventricular
Look at it now! ☺
** When you see a lymphoma in the brain parenchyma, it is
primary CNS tumor. When you see a lymphoma in the
leptomeninges, it is usually a metastatic lesion.
** Of the most common primary brain tumors, only glioma is
intramedullary in location. Meningioma, pituitary adenoma &
vestibular schwannoma (2nd, 3rd & 4th most common, respectively)
are all extramedullary)
** To reiterate, the onset of brain tumors is insidious & the course
is slowly progressive. (As oppose to stroke, which has an acute
onset & a rapid clinical course)
Cerebral Dysfunction
- Seizure
- Language disorder—aphasia (motor area lesion: Broca’s
aphasia; sensory lesion: Wernicke’s aphasia)
- Organic mental, behavioral personality changes
- Contralateral lesion of the cerebrum manifests the following:
- Hemiparesis with Babinski reflex & cranial nerve
deficits
- Hemisensory deficits
- Homonymous hemianopsia/quadrantanopsia
**The nature of the contralateral manifestations of a cerebral
lesion is due to the decussation of the corticobulbar &
corticospinal tracts coming from the cerebrum.
Cerebellar Dysfunction
- Hemisphere lesion
- Ipsilateral limb ataxia
- intention tremor
- dysmetria
- dysdiadochokinesia
- Vermis lesion
- truncal ataxia
- no limb ataxia
** An example of a vermis tumor is medulloblastoma in children
which manifests with truncal ataxia.
** With the cerebellum in close relation to the 4th ventricle, a
lesion appearing in the cerebellum may compress this ventricle &
cause obstructive hydrocephalus.

Age Incidence Brainstem Dysfunction

- Adults - “Crossed motor or sensory syndrome”
- Supratentorial: 80-85% - Ipsilateral cranial nerve deficits
- Intratentorial: 15-20% - Contralateral hemiparesis with Babinski
- Children - Ipsilateral limb ataxia
- Intratentorial: 60% - Internuclear ophthalmoplegia—median longitudinal
- Supratentorial: 40% fasciculus syndrome

** Therefore, cerebral tumors are more common in adults while

cerebellar & brainstem tumors are more common in children.

**Boundary between supratentorial & infratentorial is the

tentorium cerebelli.
 Increased ICP I. GLIOMAS
Headache/vomiting with: - Most common primary brain tumor
a. Papilledema - 50% of all symptomatic brain tumors
- The abducens n. has the longest intracranial route - Incidence increases with advancing age
making it vulnerable to alterations even if ICP is in the - Peak in 8th and 9th decades
upper portion above the pons - No known environmental factors
b. Diplopia with internal squint (lateral rectus palsy secondary - No behavioral lifestyle choices
to abducens nerve lesion) - Ionizing radiation: the only clear risk factor
- As a focal lesion, lateral rectus palsy will localize the - Originate from glial cells or their stem cell precursors
lesion in the pons or pontine glioma - Include:
- But when associated with ↑ ICP, lesion may be a. Astrocytoma
cerebral, cerebellar or in the brainstem due to the long b. Oligodendroglioma
route of the abducens nerve c. Ependymoma
c. Deterioration in the level of consciousness - WHO Classification Basis
d. Bulging fontanel, separation of sutures, rapid enlarging head a. Increased cellularity
size b. Nuclear atypia
c. Endothelial proliferation
Temporal Profile of Brain Abnormalities d. Necrosis
- Onset of Illness - Can be located anywhere – from the cerebrum, cerebellum
- Course of Illness or brainstem. If it appears in the brainstem, the most
Toxin &
common location is the pons.
Vascular Metabolic
A. Astrocytoma
- Most common glioma
Infection
Neurologic Impairment

- Cerebral astrocytoma (more in adults)

- Behavioral changes
- Seizures
- Hemiparesis
Neoplasm - Language difficulty
- Cerebellar astrocytoma (more in children)
- Hemisphere
- Ataxia
Degenerative - Brain stem (children)
- Pons
- CN deficits
1 2 3 4 5 6 7 2 3 4 2 3 4 5 6 2 3
Days Weeks Months Years Grade WHO Designation Criteria for Tumor Criteria for Grade
Type
I Pilocytic astrocytoma Bipolar & multi-polar Piloid cells,
astrocytes, long Rosenthal fibers,
processes, microcytes eosinophilic granular
bodies, low cellularity
II Astrocytoma Well-diff Nuclear atypia,
fibrillary or neoplastic increased cellularity
astrocytes
Ancillary Procedures III Anaplastic - Nuclear atypia &
- Skull X-ray astrocytoma mitosis
- EEG IV Glioblastoma - Nuclear atypia,
- Perimetry, audiometry multiforme mitosis + endothelial
- Cerebral angiographs proliferation &
- CSF examination necrosis
- Its role is questionable in brain tumors. Usually there II Oligodendroglioma Bounded tumor cells, Nuclear atypia
is normal sugar content but protein is elevated “fried egg” occasional mitosis
because the tumors release proteases that destroy the appearance, network
BBB allowing proteins to come in. of branching capillaries
- Neuroimaging studies III Anaplastic - Nuclear atypia
- Cranial/Spinal CT Scan with or without contrast Oligodendroglioma Mitosis,
Microvascular
Treatment of Brain Tumors proliferation
- Surgery Necrosis
- Radiotherapy II Ependymoma Perivascular Well delineated,
- Gamma knife: indicated for tumors <3.2cm pseudorosettes moderately cellular &
- Very expensive ependymal rosettes
- Chemotherapy III Anaplastic Microvascular
ependymoma proliferation,
pseudopalisading
necrosis
Grade I: Pilocytic Astrocytomas
- Primary in children & young adults
- Focal astrocytoma may be associated with
neurofibromatosis type I (NF-I)
- Unusually excellent prognosis
Grade II: Diffuse or Fibrillary Astrocytoma
- Most common in the cerebral hemisphere in young adults
- Low grade or benign histologically
- Infiltrative – usually a problem because the tumor cannot
be resected completely if this is a characteristic of the tumor
- Complete resection not possible
- Latent potential for malignant transformation
Grade III: Anaplastic Astrocytoma
Grade IV: Glioblastoma multiforme
- Grades III and IV are high-grade gliomas
- 20% of all intracranial tumors
- 55% of gliomas
- 80% of gliomas of the cerebral hemispheres in adults
- Peak incidence middle to late adulthood
- Males/females = 1.61
- No familial predilection
Glioblastoma Multiforme
- CSF seeding:
- Malignant cells in the CSF may form:
a. Distant foci in spinal roots
b. White spread meningeal gliomatosis
- CSF seeding implies that GBM can go to the CSF
spaces such as the subarachnoid space &
communicate with the ventricular system
- Extraneural metastasis
- To bone & lymph nodes (very rare) after a craniotomy
- Pseudopalisading around the necrosis is common in GBM
- Can cross the midline in a “butterfly” pattern: this shows the
aggressive nature of this tumor because the midline is
composed of a tough dura
Anaplastic Astrocytoma
- Have increased pleomorphism, enlarged nuclei and most
importantly, increased proliferative activity that is reflected
as increased mitotic activity.
- There should be NO necrosis or endothelial proliferation.
Presence of either/both is suggestive of worse biological
behavior.
Imaging: High- and Low-Grade Gliomas
- High-grade or malignant gliomas: appear as contrast-
enhancing mass lesions which arise in white matter & are
surrounded by edema
- Low-grade gliomas: typically non-enhancing lesions that
diffusely infiltrate brain tissue & may involve a large region
of brain
- Low-grade gliomas are usually best appreciated on T2-
weighted MRI scans.
Prognosis of Astrocytomas
- Median survival
- GBM: 1 year
- Anaplastic astrocytoma: 3 years
- Low-grade astrocytoma: 5 years
- Others survive a decade or more
- Most die from transformation of tumor to higher grade
B. Oligodendroglioma
- Derived from oligodendrocytes or their precursors
- Oligodendrocytes produce the white matter in the
brain
- 5-7% of all intracranial gliomas
- Most often in the 3rd and 4th decades
- Males:females = 2:1
- Found primarily in cerebral hemispheres, within the brain
parenchyma
- Highly infiltrative
- May metastasize distantly in ventricular & subarachnoid
spaces like the GBM (CSF seeding)
- Round regular “fried-egg” cells
- Calcification: common
- Usually GFAP negative (glial fibrillary acidic protein
staining)
- Highly infiltrative
- Majority are low-grade lesions which have the potential to
transform over time to anaplastic oligodendroglioma
- May acquire astrocytic features which may develop into
GBM
- Radiosensitive & Chemosensitive
- 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
“fried egg cells of oligodendroglioma”
Prognosis of Oligodendroglioma
Median Survival
- Low-grade oligodendrogliomas: 8-16 years
- Anaplastic oligodendrogliomas: 5 years
- Tumors that have 1p/19q LOH—best prognosis
- Many pxs die from malignant transformation of the tumor
C. Ependymoma
- Arise from ependymal cells (an intraventricular tumor)
- More common in children
- 10% pediatric intracranial tumors
- 5% of adult intracranial tumors
- Most common in the 4th ventricle
- Ataxia, vertigo, increased ICP
- May grow in brain parenchyma without obvious
attachment to the ventricular system
- Spinal lesions more common in adults
- Intracranial ependymomas predominate in children
Histological Characteristics of Ependymoma
- Perivascular pseudorosettes
- Tumor cells arranges themselves radially around
blood vessels
- Ependymal or Homer-Wright Rosettes
- Tumor cells arrange themselves around a central
lumen
- GFAP positive
- Loss of chromosome 22 particularly 22q
- CSF seeding (“drop metastasis”)
- From the 4th ventricle to the subarachnoid space
down to the spinal cord causing spinal cord
manifestations
Cranial MRI
- Heterogenous well-delineated lesion with prominent
contrast enhancement
- Occasional hemorrhage and calcification
Prognosis
- 5-year survival: 40-50%
- 10-year survival: 47-68%
- Better prognosis:
- Young age
- Infratentorial
- Gross total excision
- Low-grade histology
II. MENINGIOMA Clinical Manifestations
- Second most common primary brain tumor - Some are asymptomatic—found incidentally by MRI
- Originate from arachnoid cells (meningoepithelial cap - But may have symptoms:
cells normally seen in arachnoid villi) - Tumor location: by compression of underlying neural
- 20% of all intracranial tumors (with asymptomatic structures
cases—40% or more) - Sites of predilection
- 7% of all posterior fossa tumors - Cerebral convexity (Sylvian & parasagittal areas)
- 3-12% of cerebellopontine angle tumors - Falx cerebri
- Most diagnosed in 6th % 7th decades - Skull base
- Female: Male—3:2 to 2:1 - Olfactory groove
- Multiple in 5-15% (NF-2) - Sphenoid ridge
- 90% intracranial - CP angle
- 10% intraspinal - Tuberculum sella
- Spinal meningioma: 10x in women
- All familial meningiomas occur with NF-2
- Rare in children (more in boys)
- Rare with dural attachments This is the parasagittal area
- Usually Intraventricular or posterior fossa of the brain: lower
- Commonly with sarcomatous changes extremities are affected
- Frequently with NF-2 when a lesion occurs here

Etiology of Meningioma
- Radiotherapy
- Only established risk factor for meningioma
- Radiation-induced tumors tend to occur over
convexities
- multiple
- histologically malignant
- more likely to recur
- Head trauma: not a confirmed risk factor
- Viral infection (SV-40): data are unconvincing
- Estrogen receptors marginally present: less affinity for ** A convulsion affecting the lower extremities, suspect a
estrogen as the receptor in breast cancer meningioma in the parasagittal area.
- That is why meningioma can grow during pregnancy
- Progesterone receptors ** Base of the skull = CN can be found here
- Expressed in 80% of women with meningiomas
- Expressed in 40% of men with meningiomas Cranial CT Scan
- Isointense or slightly hyperintense
Pathology - Smooth, sometimes lobulated distinct margins with dural tail
- Nodular tumors occasionally meningiomas en plaque attachments
(sheer-like formation) - Strong and homogenous enhancement
- Highly vascular - Edema is variable
- Encapsulated and attached in the dura (blood supply from - Hyperostosis—20%
external carotid artery) - Isointense (65%) or hypointense (35%) in T1 and T2
- Hyperostosis of adjacent bone (bone proliferation) - Intense and homogenous enhancement with gadolinium

Histological Characteristics Angiography

- Benign - Hypervascular mass
- Typical features: - If preoperative, perform embolization to reduce the risk
- Whorls of arachnoid cells surrounding a central hyaline of intraoperative bleeding
material that eventually calcifies to form PSAMMOMA
BODIES MR Angiography & Venography
- No characteristic cytologic marker - Has replaced standard angiography

WHO Classification of Meningioma Growth Rate of Meningioma

- Cellularity, cytologic atypia, mitosis, necrosis
A. Typical or benign
B. Atypical or malignant (rare)
- other histologic features of anaplasia often
present: mitosis, pleomorphism, necrosis
- aggressive (+brain invasion)
- systemic metastases in 50%
* Bone
* Liver
* Lung
- Less than 1 cm per year (very slow growth but can recur)
- Tumor doubling time: 1.27 to 14.35 years
Surgery
- Complete excision may cure many meningiomas
- The extent of resection is the most important in determining
recurrence
- For recurrence: reresection
Radiation Therapy
- Residual tumor after surgery
- Recurrent tumor
- Atypical or malignant histology

Hemangiopericytoma
- Meningeal tumor derived from pericytes (smooth muscle
cells associated with small blood vessels)
III. TUMORS OF THE PITUITARY GLAND - As tumor grows forward to the sella → compress the
- Third most common primary brain tumor basal dura → headache → affected pain-sensitive
- Often asymptomatic intracranial structures
- Incidence at autopsy: 1.7 – 24% - Basal dura is a pain-sensitive intracranial structure
- Most common in adults in the 3rd and 4th decade
- 10% incidence in children & adolescents  Hypothalamus + thalamus
- Not hereditary except MEN-1 (multiple endocrine neoplasia) - Form the lateral wall of the 3rd ventricle
- Any pathology in the ventricular system will cause
Pathology accumulation of CSF proximal to the block →
- Microadenoma hydrocephalus
- Less than 1cm
- Symptoms due to excess hormone secretion (or  Suprasellar region – region of the hypothalamus
hyperfunctioning) - An example of a suprasellar tumor is a
a. Growth hormone craniopharyngoma in children & adults
b. Gonadotropin - A craniopharyngoma can compress the third ventricle &
c. Thyroid hormone cause the ff: (hydrocephalus with signs of increased ICP)
d. Adrenal hormone - Headache
e. Prolactin hormone - Vomiting
- Macroadenoma - Papilledema
- More than 1cm - Nowadays, pituitary adenoma usually does not grow until
- Symptoms due to compressing normal pituitary gland the region of the hypothalamus because visual problems
and neural structure causing hypofunctioning prompt consult & diagnosis.
- Endocrine Active (Secretory) - Papilledema is also rare because it manifests late in the
- Prolactinoma course of the tumor. Before that happens, patient must
- Most common secretory intrasellar endocrine have been diagnosed already
active tumor - Obstructive hydrocephalus: rare because of diagnosis at
- Secreted either by microadenoma or visual problem level
macroadenoma
- Growth hormone  Pituitary Apoplexy
- Before closure of epiphysis → gigantism - Hemorrhage or infarction of pituitary adenoma
- After closure of epiphysis → acromegaly - Sudden onset of headache, nausea, vomiting, visual loss,
- ACTH: Cushing’s Syndrome diplopia, altered mental status
- FSH and LH - Diagnosis by CT or MRI
- Endocrine Inactive (Non-secretory or null cell adenoma) - Treatment  emergency surgery
- 10% mixed secretory tumor
- Histological characteristics: Note:
- Almost all are histologically benign **If px has amenorrhea check the ff structures:
- Pituitary CA: rare - Ovary: estrogen & progesterone problem
- Macroadenomas - Pituitary gland: may be the problem due to FSH and LH
- May invade dural bone hyposecretion
- May infiltrate surrounding structure - Hypothalamus: may be the problem due to GnRH
- Locally invasive pituitary adenomas are nearly hyposecretion
always histologically benign - If px is not pregnant, by visual examination, she may have
- Pleomorphism and mitotic figure insufficient for bilateral hemianopsia or monocular blindness. Therefore
diagnosis of carcinoma (may be seen in benign ruling out pregnancy.
adenomas)
- Invasive character independent of growth rate **A pituitary tumor need not to be a microadenoma to secrete
- Pituitary Carcinoma endocrine hormone. Macroadenoma can also secrete hormones.
- Highly invasive
- Rapidly growing & anaplastic Diagnosis
- Unequivocal diagnosis relies on presence of - X-ray – will show you ballooning of the sella turcica
distant metastasis - Cranial MRI
- Best way to evaluate pituitary pathology
Clinical Manifestations of Tumors of the Pituitary Gland
 Mass effect (of the growing tumor) Treatment
- Compression of neural and vascular structures - Surgery
- Headache Transsphenoidal approach: procedure of choice
- Hypopituitarism - Hormone replacement
- Visual symptoms - Radiation Treatment
- visual loss Complementary to surgery in preventing progression
- visual field abnormality: bitemporal hemianopsia or recurrence
is the most common - Radiosurgery
- Papilledema is rare NOT used for:
- May enlarge with pregnancy - large tumors
- 5% of pituitary adenoma present with pituitary - tumors less than 3 mm distance from optic
apoplexy apparatus
Optic chiasm
- Between hypothalamus & sella turcica
- When this is compressed → bitemporal hemianopsia
Optic nerve
- When this is compressed → ipsilateral blindness
Optic tract
- When this is compressed → contralateral homonymous
hemianopsia
Diaphragma sella
- The dura that covers sella turcica
IV. VESTIBULAR SCHWANNOMA Schwannoma Neurofibroma
- A.k.a acoustic neuroma or acoustic neurofibroma Eccentric placement in nerve Hallmark tumor of NF-1
- Used to be called acoustic schwannoma, but the lesion is in fascicle
the vestibular apparatus, not in the acoustic portion or the Gross total resection normally Plexiform neurofibroma
cochlea possible cordlike enlargement of nerve
- 4th most common tumor twigs
- Arises from schwann cells of the vestibular branch of the 8th Spindle cells, axons, myxoid
cranial nerve background
- 5-10% of intracranial tumors Patent nerve intermingles with
- Most common tumor of the cerebellopontine angle (next is tumor
meningioma) Harder to remove because the
- Peak age: 40-60y/o tumor is together with the
- F:M—2:1 nerve
- Bilateral tumors in less than 5%
Defining characteristic of NF-2 Histologic Characteristics
- Grows slowly - Antoni A: areas with densely packed tumor cells
Less than 2mm per year - Antoni B: areas with loose pattern of stellate cells with long
- Many tumors are large and even cystic before they become irregular processes
asymptomatic - Notice the whirly swirly pattern and how the cell nuclei are
closely bunched together almost as if they’re forming a
** 2 components of the CN VIII is the acoustic & vestibular fence
portion. - Schwannomas are benign spindle cell tumors that occur
** When thinking of a cranial nerve deficit due to a tumor, the along the ropes of peripheral nerves. They can usually be
tumor must be in the base of the brain or base of the skull removed without damaging the nerve itself.
Clinical Manifestations of Vestibular Schwannoma Malignant Schwannoma
- Usually based on the affected nerve - Can be difficult to diagnose and are usually >5cm in
- Progressive unilateral hearing loss diameter by the time they are brought to the attention of a
- A more persistent or consistent finding in medical professional and identified.
schwannomas - Similar to most other types of cancers, the tumors are
- If your suspicion is a schwannoma & px presents with treated with one or more of the ff: surgery, chemotherapy or
unilateral hearing loss, the px may be deaf for the rest radiotherapy.
of his life. - The 5yr survival rate associated with malignant
- As compared to a meningioma, which is also a CP schwannomas is low, primarily due to poor response of the
angle tumor, unilateral hearing loss may not be tumors to available tx and metastasis to the lungs & other
present or may disappear. In schwannoma, hearing areas of the body.
loss is persistent - Good prognosis:
- Unsteady gait (dysequilibrium/vertigo): 20% young px
- As the schwannoma grows very slowly, the brain may relatively small tumors which are completely
have the capability of adjusting. So, initially, vertigo removed via surgical means
may manifest. But after some time, vertigo may
disappear. Diagnosis
- Facial numbness (CN V): 30% - Gadolinium-enhanced MRI
- Facial weakness (CN VII): 9% Best technique for diagnosis
- Tinnitus: 70% Hyperintense on T2 MRI
- Decreased corneal reflex
- Closing of the eye lids may be inappropriate due to Treatment
affectation of the CN V - Surgery
- Tumor encroaching on acoustic regionpx becomes deaf - Radiosurgery: excellent alternative for tumors less than 3cm
- Tumor usually grows up to press on 5th cranial nerve in diameter
(causes facial numbness), medially to compress 7th cranial
nerve (causes facial weakness) V. LYMPHOMA
- Usually doesn’t involve the 6th cranial nerve first
- Common cranial nerves involved in vestibular schwannoma Look! But you have to understand! ☺
(in order): CN VIII, VII, V (875) - Lymphoma can be primary in the CNS or they can be
metastatic
Remember this! Listen to this! Very Nice!☺ - When they are primary, it is usually in the brain parenchyma
CN II, III – pupillary reflex, localize at the midbrain >90% of the time
CN V and VII – corneal reflex, localize at the pons - When metastatic, it usually goes to the leptomeninges
CN IX – gag reflex, localize at the medulla
Metastatic Lymphomas (CNS)
Cerebellopontine Angle (CPA) Tumors - Almost exclusively with Non-Hodgkin’s Lymphoma
1. Vestibular Schwannoma - They usually metastasize to the ff:
2. Meningioma (2nd most common; pxs not deaf) 1. Leptomeninges
3. Cholesteatoma (Epidermoid) - Most common location of a metastatic lymphoma
4. Trigeminal Neuroma: does not involve 8th CN. Therefore, no intracranially
cochlear dysfunction; only consider due to proximity - Composed of the pia & the arachnoid which
surrounds the subarachnoid space
- Therefore, a metastatic lymphoma in the
leptomeninges is a tumor in the subarachnoid
space
- Therefore, from the SAS it can travel to the other
ventricle
2. Epidural space – 3-5%
3. Rarely brain parenchyma - <1%
Hodgkin’s Lymphoma Treatment
- Metastasize to the epidural space → epidural spinal cord - Corticosteroids: cytotoxic effect on lymphomas  will
compression decrease in size
- Rarely leptomeningeal & brain parenchyma - Surgery is not helpful therapeutically
- Radiation
Primary CNS Lymphomas (PCNSL) PCNSL is highly responsive to radiotherapy
- Most common site is the brain parenchyma in the cerebrum - Chemotherapy
- In contrast to what has been always known, CNS lymphoma PCNSL is chemosensitive
can also develop in immunocompetent individuals, not only
to those who are immunocompromised VI. VASCULAR TUMORS
A. Immunocompetent
Histologically indistinguishable
- 3% of all intracranial neoplasms a. Hemangioblastoma
- 7% of all malignant lymphomas - confined to posterior fossa in the cerebellum
- Peak incidence: 5th-7th decade - no dural attachment (meningioma is the one with
- M:F—3:2 dural attachment)
- Pathology: b. Angioblastic meningioma
- Single or multiple parenchymal brain lesions (>90%) - located above & below the tentorium
- Primary leptomeningeal lymphoma - has significant dural attachment
- Primary intramedullary lymphoma of spinal cord (rarest) - identical in other meningiomas
- Primary ocular lymphoma (uvea or vitreous lesions) c. Hemangiopericytoma
- 98%: B-cell tumors - derived from pericytes (smooth muscle cells of
- 2%> T-cell tumors small blood vessels)
- Grossly: - recognized elsewhere in the body
- Fleshy with ill-defined borders
- Histologically: Hemangioblastoma
- Cells are closely packed with characteristic - Composed of primitive vascular elements
perivascular concentration - 1-2% of intracranial neoplasms
- Neuroimaging: - All ages are affected but more frequently in young & middle-
- Single or multiple lesions often periventricular aged adults
- Most common in supratentorial, particularly frontal lobe - Predominantly males
- CAT Scan: isodense or hyperdense pre-contrast - 20% familial
- MRI - 10-20% part of von Hippel-Lindau Disease
- Hypointense on T1 relative to gray matter borders; Hemangioblastoma
NOT well-demarcated Angiomatosis of retina
- On contrast: dense & homogenous on Cysts of kidneys and pancreas
Immunocompetent Occasional renal cell carcinoma & capillary nevi of skin
- Edema: mild to moderate - Adult with cerebellar tumor same as pilocytic astrocytoma
- MRI may show diffuse ependymal spear not (cystic tumor)  hemangioblastoma
appreciated on CT - Any tumor encroaching on vestibular system will cause
obstructive effects. Therefore, increase ICP.
B. Immunocompromised - Predominantly in the cerebellum (most common in the
- Pxs with or who underwent: paramedian cerebellar hemisphere)
AIDS - Large cysts with yellow proteinaceous fluid
Renal transplantation - Resemble the cyst & mural nodule of cystic cerebellar
Ataxia telangiectasia astrocytoma but with distinctive vascular appearance &
Rheumatoid arthritis angiogram
Wiskott-Aldrich Syndrome - May be multiple
IgA deficiency Vertebral angiogram showing hemangioblastoma
- Occurs in the 3rd and 4th decades
- Almost always multiple. Do not have the typical Clinical Features of Cerebellar Masses
periventricular location - Headache
- Increased preponderance of the immunoblastic - Papilledema
- Hemorrhage, necrosis & calcifications are common - Ataxia: focal neurologic deficit of hemangioblastoma
- Neuroimaging with contrast-ring enhancement - Polycythemia
(corresponding to necrosis) Erythropoietic substance from cystic fluid
Diagnosis: CT angiogram
Diagnosis Treatment: surgery
- Histologic confirmation from: - evacuation of cyst
Brain - removal of mural nodule
CSF
Vitreous humor Look at this! Very nice! ☺
- Gross & microscopic pathology and clinical manifestations - If I ask you what is the cerebellar tumor in adults that is
are identical in immunocompetent & immunocompromised assoc with polycythemia, the answer is Hemangioblastoma.
pxs - What will be the focal deficit of Hemangioblastoma? Limb
- Use tissue biopsy for differentiation ataxia

Clinical Manifestations (symptoms of space-occupying lesions) ** Any cerebellar tumor because of the anatomic location of the
- Headache cerebellum in relation to the 4th ventricle, they are assoc with
- Personality change increased ICP because they will compress on the 4th ventricle. →
- Lateralizing on focal neurologic deficits obstructive hydrocephalus
Cerebellar Dysfunction Treatment
- Hemisphere lesion - Whole brain radiotherapy: relief of neurologic symptoms in
Ipsilateral limb ataxia 80%
- intention tremor - At least 48hrs of Dexamethasone (16mg/day) before WBRT
- dysmetria is delivered
- Dysdiadochokinesia - Chemotherapy:
- Vermis lesion Limited role
Truncal ataxia Only at recurrence after surgical & radiotherapeutic
No limb ataxia options exhausted
- Median survival is only 4-6months
Note:
Most common location of medulloblastoma is the vermis which is II. LEPTOMENINGEAL METASTASIS
common in children. - Most common tumor that metastasize in the leptomeninges
is metastatic lymphoma
Prognosis of Hemangioblastoma - 8% of pxs with cancer
- Good alive 5-20 years after surgery - Hematologic malignancies: acute lymphocytic leukemia,
- High incidence of recurrence Non-Hodgkin’s lymphoma
If partial resection - Solid tumor: Breast Ca, Lung Ca, Melanoma, GI Cancer
Multiple tumors
Clinical Findings
METASTASIS - Multi-level signs & symptoms affecting 3 main areas:
Brain parenchymal metastasis Cerebrum
Leptomeningeal metastasis Cranial nerve
Dural metastasis Spinal roots & cord
- CSF examination:
I. BRAIN PARENCHYMAL METASTASIS (+) tumor cells
- Most common part: cerebrum (followed by the cerebellum) (-) tumor marker (CA 15-3 for breast cancer)
- Tumor in cerebellum in adults often Metastatic
- Usually found with disseminating systematic disease Diagnosis
- In some the intracranial disease appears before the - MRI of the spine
systemic cancer - (+) subarachnoid tumor
- Non-small cell lung cancer: most common primary lesion 1. enhancing tumor in cortical sulci
leading to brain metastasis 2. subependymal enhancement
- Melanoma and small cell lung cancer have the greatest 3. enhancing cranial nerves
propensity to metastasize in the brain 4. tumor nodules in cauda equina
- 2 most common metastasis to the brain
1. lungs Treatment
2. breast - Therapy
- Other primary cancers that commonly spread to the brain: 1. Radiotherapy to symptomatic suites
Renal cancer 2. Intrathecal chemotherapy
GI cancer - contraindicated in uncontrolled high ICP
- Tumors that rarely spread to the brain:
Prostate cancer (usually to the bone) Prognosis
Uterine cancer } seldom - Median survival: 4% up to 6 months
Pancreatic cancer } metastasize
- Hemorrhagic metastasis to the brain III. DURAL METASTASIS
- Lung cancer – most common - From direct extension of a calvarial metastasis or from the
- Melanoma overlying bone
- Thyroid - 2 most common tumors that go to the bone is prostate CA
- Choriocarcinoma for males & breast cancer for females
- May present with painless, growing skull lesion with
Clinical Findings headache, seizure & hemiparesis
- Symptoms similar to any space-occupying lesion - MRI may show a tumor similar to meningioma
- Subacute course over 1-2 weeks - Treatment: focal radiotherapy
- Occasionally acute and stroke-like in intratumoral
hemorrhage EMBRYONAL TUMORS
Medulloblastomas
** If I ask you in the quiz, systemic cancer commonly metastasize Supratentorial Primitive Neuroectodermal Tumors
intracranially in the: a. cerebrum b. cerebellum c. brainstem Atypical Teratoid/Rhabdoid Tumors

** When does brain metastases become acute? When there is I. PRIMITIVE NEUROECTODERMAL TUMORSS (PNETS)
intratumoral hemorrhage - Arise fro primitive progenitor cells which are pluripotent,
uncommitted neuroectodermal cells with capacity for
Diagnosis differentiation along ependymal, neuronal, glial or even

Cranial MRI with Gadolinium retinal cells
Solitary or multiple - Therefore, a PNET can differentiate into anything!
Lesions are contrast enhancing diffusely when small - Most common malignant pediatric tumor occurring
and ring enhancing when large with well defined predominantly in the posterior fossa (medulloblastoma) but
borders also in the pineal (pinealoblastoma) or other CNS locations
(cortical or spinal PNETS)
** Most of the time, solitary tumor in the brain seen in the MRI can - PNETS arising from distinct locations cannot be
be both primary or metastatic. But multiple brain tumors are distinguished histologically
mostly metastatic lesions. - Histologic appearance is of small round cell tumor with glial
or other types of differentiation in some cases. High
cellularity, mitotic rate and tendency for leptomeningeal
dissemination
 - There mat be positive staining for both neurofilament protein GERM CELL TUMORS (GCT)
& glial fibrillary acidic protein (GFAP) but also for 1. Germinomas
synaptophysin which is more specific for PNET 2. Non-germinomas (very malignant)
- Medulloblastomas (posterior fossa PNETS) have - Embryonal-cell carcinoma
significantly better prognosis than other PNETS. - Endodermal sinus tumor (yolk sac tumor)
- Choriocarcinoma
II. MEDULLOBLASTOMAS (Posterior Fossa PNETS) - Teratocarcinoma
- Specifically PNET of the cerebellum 3. Benign Gram Cell Tumors (intermediate malignancies)
- Derived from fetal external granular cells of the cerebellum - Epidermoids
or rests in the posterior medullary velum - Dermoids
- 30% of Infratentorial tumors in children but uncommon in - Teratomas
adults
- Typically involve the cerebellar vermis; grow to fill the 4th By location:
ventricle and may infiltrate the floor of the ventricle and 1. Pineal GCT: almost exclusively in boys
adjacent structure (brainstem) 2. Suprasellar GCT: boys = girls
- Vermis lesion → truncal ataxia
- Filling the 4th ventricle → ↑ ICP Note:
- May arise laterally especially in older pxs - Suprasellar tumor → craniopharyngoma
- Median age: 5 years - Tumor in the hypothalamus, if you don’t have any
suspicions, might be a glioma
Clinical Features - The pineal gland, when it enlarges, it grows towards the iter
- Increased ICP causing obstructive hydrocephalus
- Unsteadiness (truncal) - The pinealoma can also compress the superior colliculus
- Symptoms duration: less than 3 months which will make an individual unable to look up. This is a
- Recent onset of head tilt from ophthalmoparesis or incipient part of the Parinaud’s syndrome
cerebellar herniation
A. Germinomas
Diagnosis of Medulloblastomas - Half of intracranial GCT
- Cranial CAT scan - Histologically identical to testicular seminoma & ovarian
Isodense or hyperdense dysgerminomas
Enhance homogenously - Arise in the midline, pineal area, suprasellar
With hydrocephalus - Highly malignant
May include small cysts, calcification & hemorrhage - Occasionally seed the CSF
- MRI
Tumor extent B. Nondysgerminoma GCT
PNET can produce leptomeningeal dissemination, - Highly malignant
CSF seeding & drop metastasis - More aggressive than dysgerminoma
- Metastasize to the CSF more frequently than germinoma
Treatment - Endodermal sinus tumors
- Surgery Contain yolk sac element that produces alpha-
- Postoperative radiation therapy fetoprotein (AFP)
- Choriocarcinomas
Prognosis Contain cyst and syncytiotrophoblastic cells that
- 5-year disease-free survival rate: 55% produce β-hCG
High levels of β-hCG and AFP in the CSF indicate the
CRANIOPHARYNGOMAS presence of malignant germ cell element
- From rests of embryogenic tissue located in the Rathke’s C. Pineal Gland Tumors
pouch (anlage of the anterior pituitary gland) - 1% of all intracranial tumors in USA
- Any age; even late adulthood - 4-7% of all intracranial tumors in Asia where GCT are
- 6-10% of intracranial tumors in children common
- More common in children - Here in the Phil., most common is germinoma
- Suprasellar calcification is present seen by plain x-rays
- Small well-circumscribed solid nodules to huge multilocular Clinical Manifestations
cysts with turbid fluid that may contain cholesterol crystals - Increased ICP
- Histologically benign - Direct compression of brain stem and cerebellum
- In region of hypothalamus or 3rd ventricle → ↑ ICP Parinaud’s Syndrome
- Many with papilledema due to location in hypothalamus near - paralysis of upgaze (common manifestation)
4th ventricle (?) - light near pupillary dissociation
- nystagmus
Clinical Manifestations - ataxia & dysmetria
- Short stature - Endocrine
- Hypogonadism Secondary effect of hydrocephalus or tumor spread to
- Hypothyroidism the hypothalamic region
- Diabetes insipidus Precocious puberty
- Visual loss Precocious pseudopuberty
- Increased ICP: because of its proximity to the hypothalamus - hypothalamic-gonadal axis not mature
& ventricles
- CT: calcification; bony expansion of the sella, non-adherent Diagnosis
- Plain skull x-ray: may see suprasellar calcification - MRI with gadolinium
Definite histologic diagnosis for optimal patient
Treatment - Radiotherapy
- Drain cyst, resect non-adherent tumor Very radiosensitive
- Postoperation radiotherapy All pxs with pineablastoma NGGCT & disseminated
- Gross total resection germinomas require neuraxis radiotherapy
- Chemotherapy
Most benefit with pinealoblastoma are NGGCT
Prognosis Paraneoplastic Neurologic Syndromes
Germinomas: 80-90% 5-year survival rate following surgery and - Subacute cerebellar degeneration
radiotherapy - Anti-Yo (anti-Purkinje cell) auto-Ab
- Tumors of ovary, fallopian tube, lung
- Opsoclonus/myoclonus
DERMOID TUMORS - Anti-Ri
- Cystic mass with yellow cystic fluid from sebaceous gland - Tumors of breast, fallopian tube, small cell lung
secretion - Limbic encephalitis
- Subacute motor neuropathy
TERATOMAS - Anti-Hu
- Infants & young children - Tumors of small cell lung, Hodgkin, other lymphomas
- Mature teratomas are lobulated and cystic containing - Lambert-Eaton myasthenic syndrome
differentiated tissues such as bone, cartilage, teeth, air or - Anti-voltage (VGCG) Ca channel
intestine - Tumors of small cell lung, Hodgkin, other lymphomas
- Immature & malignant teratomas: less common - Encephalomyelitis
- Tend to occur in the pineal region - Cerebellar degeneration
- Parinaud syndrome, hydrocephalus - Encephalomyelitis
- 4% of childhood intracranial tumors - Anti-Hu, Anti-Ma
- Rx: Surgical resection - Tumors of small cell lung, neuroblastoma, prostate,
breast, Hodgkin, testicular
CHORDOMAS - Stiffman syndrome
- Derived from remnants of the embryonic notochord: gives - Antiamphiphysin
rise to nucleus polposus - Breast
- Sacrococcygeal, clivus elsewhere along the spinal column
- Less than 1% of CNS tumors 4 most common primary brain tumor in adults (In decreasing
- Remain asymptomatic until adult frequency)
- Multiple cranial nerve palsies, erosion of skull base 1. Glioma (astrocytoma)
- Rx: Surgical resection, postoperative radiation therapy 2. Meningioma
3. Pituitary adenoma
EPIDERMOIDS (Cholesteatomas) 4. Vestibular schwannoma
- Most common embryonal CNS tumor
- 2% of all intracranial tumors 4 most common infratentorial brain tumors in children
- Arise within skull tables or adjacent to the dura 1. Cerebellar hemisphere astrocytoma – 30-40%
- Suprasellar region, cerebellopontine angle, skull base, 2. Vermis medulloblastoma – 30-40%
brainstem 3. Brainstem gliomas – 10-20%; pontine astrocytoma
- Encapsulated, pearly appearance may contain cyst fluid with 4. Ependymoma (4th ventricle) – 10-20%
cholesterol crystals
- MRI: Low T1, high T2 signal Supratentorial brain tumors in children
- Treatment: surgical resection 1. Suprasellar region – 20-30%
- Craniopharyngoma
CHOROID PLEXUS TUMORS - Chiasmatic & hypothalamic glioma
- Lateral ventricle - Germinoma
- Most diagnosed before 2 years 2. Pineal/parapineal region – 10%
- Hydrocephalus - Germinoma
- Excess CSF production (which is the cause of
hydrocephalus) 2 most common sites of germinoma
- Pineal gland
COLLOID CYSTS OF THE 3RD VENTRICLE - Suprasellar
- Arise from the anlage of the paraphysis
- Grow in the anterior superior portion of 3rd ventricle
- Small white cysts filled with homogenous gelatinous material
- Become symptomatic during adulthood
- Intermittent hydrocephalus
- Rx: surgical excision

Indirect Neurologic Complications of Cancer (Nonmetastatic or

Paraneoplastic)
- Vascular disorders
- Infections
- Metabolic & nutritional disorders
- Side effects of therapy: This transcription is a combination of Dr. Conde’s & Dr. Poblete’s
- Chemotherapy lecture.
- Radiation Therapy
- Surgery & other diagnostic or therapeutic procedures Transcribed by: Denise Zaballero ☺
- “Remote” or paraneoplastic syndromes Slides from: Fred Monteverde
- May have an autoimmune pathogenesis JB Villegas
Jun Minagawa
Additional notes from: Cecile Ong
Emy Onishi
Mitzel Mata
Patriccia Mendiola
Recorded lecture from: Lala Nieto

We all have a sickness

that cleverly attaches and multiplies
--Dig, Incubus