CM Neuro Brain Tumors

Brian lesion

area of damaged or abnormal brain tissue - tumor, stroke, trauma, infection, cyst

brain tumor

abnormal growth of cells in brain - usually a solid mass

can be malignant (1/3) or benign (2/3)

primary or secondary

intra-axial or extra-axial

intra vs extra axial brain tumors

within or outside brain parenchyma

intraventricular

brain cyst

fluid-filled sac within brain often filled with CSF

can be malignant or benign

brain tumor RFs

radiation exposure

genetics - neurofibromatosis 1&2, li-fraumeni syndrome, turco & goblin syndromes

FHx (2x greater risk)

NOT RFs: alcohol, smoking, cosmetics

ionizing radiation exposure & effects

breaks DNA and generates free radicals -> cellular damage

occupational - medicine, dental, hospital, nuclear power plants, plane travel, mining operations

environmental - soil, air, water

glial vs non-glial brain tumors

glial = support cells for neurons (such as astrocytes, oligodendrocytes, microglial cells)

non-glial = all other cells within nervous system (neurons, endothelial)

where are schwannoma brain tumors?

cerebellar/brainstem region

Sx of brain tumors

HA (1/3) - intermittent, progressive; exacerbated by cough, lying, sleep

N/V, seizures, LOC, focal neurologic deficit, nonspecific cognitive +/or personality changes, asymptomatic

sx based on location in brain

see screenshot

HA red flags

abnormal neurologic findings

hx of malignancy

new onset >50yo

progressive or atypical

ddx for headaches based on onset

acute, subacute or chronic - see screenshot

diagnostics for brain tumor

CT for fast results

gold standard: MRI w & w/o contrast

screening for secondary malignancy if needed - CT (not necessary if its believed brain tumor is primary)

brain tumor or lesion evaluation

neurosurgery, heme/onc consult

clinically unstable or ER/inpatient imaging -> send to hospital

next steps: biopsy +/or surgical resection

stereotactic bx, neuropathology analysis

brain tumor staging or grading

no staging - rare for it to spread outside nervous system

low grade I,II

high grade III,IV

low grade brain tumor

grade I - benign, slow-growing, common in peds

grade II - relatively slow-growing, recurrence and spread possible

high grade brain tumor

III - malignant, spread seen

IV - malignant, fast-growing, vascular proliferation, centralized necrosis in tumor

WHO brain tumor classification

includes molecular parameters that differentiate tumors + histopathology appearance

growth pattern, h=behavior, isocitrate dehydrogenase mutation status

isocitrate dehydrogenase (IDH) mutations

occur in infiltrative astrocytoma pathogenesis

IDH enzyme converts isocitrate to alpha-ketoglutarate; mutations causes conversion to 2-hydroxyglutarate instead which is onchometabolite - accumulation leads to malignant gliomas

glioma brain tumors

astrocytoma - glioblastoma multiforme

ependymoma

oligodendroglioma

astrocytoma

from astrocytes

rarely metastasize but can seed through CSF

astrocytoma grading

I - well-circumscribed, non-infiltrating

II - diffuse

III - anapestic

IV - diffusely infiltrative, glioblastoma multiforme

low-grade astrocytoma

primarily pediatrics and young adults

M>F

variability in stability of tumors

commonly found in bilateral cerebral hemispheres - frontal and temporal lobes

low grade pilocytic astrocytoma

6% of all brain tumors

MC glioma in pediatric population (median age dx ~8yo)

common in bilateral cerebellar hemispheres

usually curable with complete resection - almost 100% 5yr survival

low grade pilomyxoid astrocytoma

grade II

more malignant variant of pilocytic astrocytoma

infants and young children around 10mo old

risk: local recurrent, spreading

highest incidence ages of pediatric brain tumors

15-19yo then 0-4yo

M>F

pediatric brain tumors

1/3 in posterior fossa

MC astrocytic, craniopharyngiomas, medulloblastomas, germ cell, ependymal

possible RF of maternal drugs

infiltrative astrocytomas

MC brain primary neoplasm in adults

Grade II and high grade III, IV

diffuse astrocytoma

Grade II

common in peds

usually in frontotemporal lobe and brainstem

younger age and location impact survival

5yr <50%

anapestic astrocytoma

WHO grade III

mean age 40yo at dx

high risk of recurrence and progression; vascular proliferation possible

20-58% 5yr survival rate - dependent on age and location

glioblastoma multiforme

WHO grade IV

12-15% all brain tumors

MC primary malignant brain tumor in adults - usually seen in adults 4th-7th decade

commonly seen in bilateral cerebral hemispheres

most are de novo (no IDH mutations; <10% evolve from lower grade)

12-18 month survival after diagnostic

5% 5yr survival rate

oligodendroglioma

originate from oligodendrocytes

low grade to anapestic (grade 3)

slow growing but can be rapid

5-6% of glial neoplasms

frontal and temporal lobes of cerebral hemispheres

1p/19q chromosome co-deletions in 80-90%; may have IDH mutations

can have calcifications and cystic components

oligodendroglioma prognostics

median survival 15-20yrs

5yr survival 75%

associated with improved response rates to treatment compared to other gliomas

ependymoma

arise from ependymal cells of ventricle lining

5-6% of glioma tumors

children <14 (infratentorial) and 35-45yo (supratentorial)

ependymoma classification

I - subependymal, myxopapillary ependymoma

II - classic and variants

III - anaplastic

MC brain tumor overall

meningioma

(glioblastoma MC malignant brain tumor)

ependymoma

commonly associated hydrocephalus, also intratumoral calcification, cystic components, hemorrhage

spread through CSF and metastasize outside of CNS

45% 5yr survival

meningioma

MC primary brain neoplasm

originates in cap cells of arachnoid layer or arachnoid/dural border layer cells

most are benign

common in elderly, F>M

meningioma subtypes

meningiothelial

fibrous

transitional

meningioma classification

I benign, lower recurrence rate, progression variability

II 5-15%, atypical, higher recurrence rate, necrosis can be present

III anaplastic or malignant, rare - poor prognosis

primary central nervous system lymphoma (PCNSL)

form of non-hodgkin lymphoma

MC type is diffuse large b-cell

<3% of brain tumors

RF: immunosuppression - HIV/AIDs

common adjacent to ventricular or arachnoid surface

PCNSL treatment

remission occurs in >50% without treatment

HD methotrexate chemo (not surgery)

pituitary tumors

90% of seller tumors, 10% of brain tumors

HA, endocrinopathies, optic chiasm mass effect related vision deficit

<1cm microadenomas

>1cm macro adenomas

vestibular schwannoma

acoustic neuroma

8% intracranial tumors - 5% secondary to neurofibromatosis I

benign, WHO grade I

MC from vestibular nerve, then trigeminal

hearing loss, tinnitus, facial pain/numbness

vestibular schwannoma / acoustic neuroma tx

radiation & surgery

secondary brain tumors

More common than primary brain tumors

increasing incidence

usually in cerebral hemisphere or cerebellum

surgery if only 1

which cancers are most likely to spread to brain?

Lung MC

breast, melanoma, renal and colorectal

melanoma has highest propensity for metastasizing to brain (40-60% melanoma pt)

medulloblastoma

MC embryonal tumor; 20% of pediatric brain tumors age 5-9 MC

midline/paramedian cerebellum with fourth ventricle compression

1/3 have leptomeningeal dz

1/3 CSF metastasis

medulloblastoma sx

HA, N/V, AMS

leptomeningeal disease

encephalocele

sac-like protrusion of brain and membranes through skull birth defect usually from neural tube closure failure (often in skull base, top/back of skull or between nose and forehead)

often presents in peds but can be adults

epidermoid/dermoid cysts

originate from retained epithelial cells during neural tube development

can have retained hair, sweat and sweat glands

tx: surgical resections

risk for progression to squamous cell carcinoma

colloid cyst

malformation; benign mass in 3rd ventricle

fibrous outer layer, inner ciliated/mucin-producing cells

sx in 3rd-5th decades

HA, CSF obstruction/hydrocephalus

surgery if needed

arachnoid cyst

collections of CSF in arachnoid membranes

1% of adults M>F

sporadic

asymptotic

common in sylvan fissure but can be anywhere in nervous system with arachnoid layer

can enlarge overtime

surgery if symptomatic

cyst ruptures

spontaneous or from trauma

tumor complications

with tumor growth, normal brain tissue displaced, compressed or injured

mass effect

vasogenic edema

ICP

brain herniation

hydrocephalus (obstructing or non)

intracranial hemorrhage

epilepsy

cognitive and psychiatric changes

mass effect

umbrella term for secondary pathological effects caused by brain tumor on local/surrounding normal brain tissue

ventricle compression

displacement of blood vessels

significant -> hydrocephalus and midline shift

tumor-related edema

cerebral edema; leakage of plasma via BBB disruption

intracranial HTN

normal 15mmHg or less

elevated 20+ mmHg

from brain mass growth + edema

intracranial HTN sx

HA, N/V

ataxic gait

papilledema

brain herniation

pressure gradients develop between compartments

supratentorial or infratentorial

tumor-related hemorrhage

Brian tumors can cause overproduction of CSF or block normal flow of CSF leading to hydrocephalus

posterior fossa tumors, choroid plexus tumors, ependymomas

sx: HA, N/V, confusion

tumor-related hemorrhage is common in...

pilocytic ast rocytoma, high grade glioma, metastatic disease

10% of brain metastases manifest as intraparenchymal hemorrhage

tumor-related epilepsy

seizures are common with tumors

10-30% get seizures from brain tumor

caused by type of tumor, tumor burden, location, disruption of BBB, altered NT homeostasis

brain tumors tx for sx

anti seizure medications for patients with seizures and brain tumors or suspected

glucocorticoids (dexamethasone) at HD can reduce cerebral edema, HA, neurologic deficits (NOT in lymphoma)

brain tumor tx

neurosurgical consultation surgery

+ chemo, radiation

brain tumor surgery

resection - can be curative for some

debulking - to help with sx

reasons for surgery - mass effect relief, seizure control, reduce recurrence, improve survival

brain tumor radiation complications

neurocognitive decline

cranial neuropathies

radiation vasculopathy

encephalopathy

radiation encephalopathy

days due to ICP elevation

months - neurological deterioration, somnolence, pseudoprogression

months-years - radiation necrosis, atrophy, ventriculomegaly, leukoencephalopathy

psuedoprogression

responds to steroids whereas actual brain tumor progression will not

brain tumor chemotherapy & biologics

alkylating agents

antimicrotubule agents

antifolate agents

taxanes

topoisomerase inhibitors

inhibition of cell growth pathways - growth factors, growth receptors, cell cycle control proteins, intracellular signal pathway, nuclear transcription factors

immunotherapy

first line glioma treatment

temozolomide - alkylating agent

lab consideration for pt on chemo

chemotherapeutic agents can have changes on their CBC and increased risk fo infection

STUPP protocol

glioblastoma multiform treatment

standard of care - concomitant radiation therapy + temozolomide

meningioma tx

no chemo meds

surgery +/- radiation

intrathecal chemo

for leptomeningeal metastases

(BBB limits chemo agents)