Tumor of The Central Nervous System Flashcards
Brain Tumor Epidemiology
-7.6/100,000 males, 5.4/100,000 females
-100,000 death/year from brain metastases
Prevalence: 122, 000
Lifetime Risk: 0.6%
-35% of patients will get brain metastases
Neuropoiesis
-development of mature neurons & their supportive glial cells from pluripotent stem cells is highly complex process controlled by cell growth promoting & suppressing genes
Primary Brain Tumors
- presence of tumor stem cells (including glial tumors)
- Glioma progenitor cells (astrocytoma, ependymoma, oligodendroglioma)
- Neuronal progenitor cells (neuronal tumors)
- can arise from any structure present intracranially (hemangioblastoma from blood vessels, neurofibroma & schwannoma from nerves, lymphoma from trafficking white blood cells, germinoma from nests of germ cells, meningioma from arachnoid cap cells, chordoma & chondrosarcoma from bone, or an extracranial cancer may enter brain via blood stream (metastases)
- developmental cysts may mimic a brain tumor
Primary Brain Neoplasia Frequency
- meningioma & mixed oligoastrocytoma 2%
- glioblastoma multiforme 40%
- infiltrative astrocytoma 42%
Risk Factors for CNS Tumors
Definitive:
- ionizing radiation
- immunosuppression (latrogenic, chemo, acquired AIDS)
- genetic syndromes
Possible:
- electromagnetic fields (cell phone)
- diet, occupation, infections (HIV, EBV, HTLV)
Pathogenesis of Brain Tumor
-cell growth genes must be over activated or inhibitor genes have to be silenced
Pressure Volume Curve & Intracranial Pressure Waves
- cerebral perfusion pressure is difference b/w mean arterial pressure intracranial pressure (CSF & interstitial pressure)
- as intracranial volume slowly inc. pressure remains constant until brain compliance threshold is reached, then small inc. in volume causes large inc. in pressure
- may exceed cerebral perfusion pressure and cause focal weakness, numbness, mental status change to seizure like activity
- Plateau wave phenomenon*
Signs of CNS Tumors: Headache
- due to raised intracranial pressure or local irritation
- often non-specific but may have migraine features
- suspect tumor if: worsen on awakening with improvement in 1 hr, new onset at any age, change in character or severity of headaches in a chronic headache patient
Signs of CNS Tumors: Vomiting
- may or may not be associated with nausea
- occurs more often on awakening
- more common in children
- suggests tumor if immediately follows an acute onset headache suggesting inc. ICP
Signs of CNS Tumors: Mental Status Changes
-depression, irritability, apathy
Signs of CNS Tumors: Papilledema
-often asymptomatic (may have visual changes)
-more common in children & young adults when compared to elderly
-
Signs of CNS Tumors: Seizures
- partial (focal) or generalized seizures
- episodic alterations in smell, taste, personality, memory, motor or sensory function depending on the origin of neural discharge
Signs of CNS Tumors: Focal Neurologic Deficits
- vary depending on location
- includes: weakness (pre-central gyrus), paresthesias (post-central), visual impairment (optic pathway/occipital lobe), personality changes (frontal lobe)
- may be reversible depending: cause (tumor invasion vs. edema vs. compression
- time since onset of deficit
Etiology of Signs & Symptoms of CNS tumors
- invasion of neuronal or vascular structures
- compression of adjacent neural or vascular structures
- obstruction of CSF pathways - hydorcephalus - inc. ICP
- Herniation from mass effect
- cerebral hypoperfusion b/c of inc. intracranial pressure
Brain Herniation
- Subfalcine herniation of cingulate gyrus, may compress ant. cerebral artery & CVA
- diencephalic downward herniation, compression of upper brainstem causes drowsiness, impaired vertical gaze and uni or bilateral small pupils b/c of sympathetic fiber involvement (horner)
- Classical uncal herniation (ipsilateral oculomotor nerve palsy & contra or ipsilateral hemiparesis)
- Upward herniation through tentorium (ipsilateral oculomotor, Horner, and contralateral hemiparesis)
- Tonsillar herniation (BP changes, weakness, respiratory disturbance, weakness & Horner syndrome)
CNS Tumor Diagnostics
- H&P
- MRI (contrast enhancement optional), study of choice for suspected tumor
- MRI superior to CT differentiation tumors from vascular malformations & other lesions but CT better identifying calcifications & pathology
- diagnosis by biopsy except primary CNS lymphomas (found in CSF by lumbar puncture)
TI weighted MRI Scan
- water is hypointense (dark), dec. signal or darker than surrounding brain
- injected contrast that leaks across disrupted BBB within tumors appears hyperintense (bright), inc. signal or brighter than surrounding brain
T2 weighted MRI Scan
-CSF/edema/tumor appears hyperintense (bright)
-Differentiating edema from infiltrating tumor on T2
edema spares the cortex
tumor does not spare the cortex
Glioma
- tumors that are derived form supporting glial cells of the CNS
- Subtypes: astrocytoma, oligodendroglioma, ependymoma
- most common primary CNS tumor (>50%)
- low grade (younger), high grade (older than 50)
- Grade 1: juvenile pilocystic astrocytoma
- Grade 2: Low-grade astrocytoma
- Grade 3: Anaplastic astrocytoma
- Grade 4: Glioblastoma multiforme (grade 4, most common)
CNS Tumors: Symptomatic Rx
- Steroids (decadron, dexamethasone)
- reduces vasogenic edema & improves intracranial pressure
- dramatic but temporary improvement in neuro symptoms - Anticonvulsants (non-hepatic enzyme inducing)
- given for focal or generalized seizures caused by the tumor
- no evidence supporting use prior to seizure onset except for patients undergoing surgery (1 week)
CNS Tumors: Definitive Rx
- Observation: reserved for tumor not lifethretening, slow growing, asymptomatic, or symptoms can be controlled by meds
- Surgery: 1st line treatment for accessible tumors, establishes pathologic diagnosis, improves ICP & seizure control, prolongs survival
- Radiotherapy: adjunct to surgery for high-grade, may be delayed in low grade, needed for eradication of infiltrative micro-populations of cells missed with resection
Risk of Radiation Treatment
- cognitive decline
- stroke
- secondary cancers
Radiation Modalities
- conventional
- conformal
- radiosurgery
- brachytherapy
- proton therapy
CNS Tumors: Adjuvant Rx
- Chemo: single-agent IV bis-chloroethyl-nitrosourea (BSNU; carmustine), single-agent oral Temozolomide (current treatment of choice), combo (PCV) of procarbazine, chloroethyl-cyclohexyl nitorsourea, and vincristin
- Biological Agents (anti-angiogenesis Bevacizumab for anti-glioma treatment (FDA approved))
- Others being studied: gene, immuno, viral therapy
CNS Tumors: Prognostic Factors
- better survival: younger age, good performance status, tumor grade & histology, degree of tumor resection, O(6)-methyl guanine-DNA methyltransferase methylation
- isocitrate dehydorgensase mutation
- 1p and 19q deletion in oligodendroglioma
Meningioma
-2-10% of primary brain tumors
~45yr women>men
-derived from arachnoid membrane (arachnoid cap)
-slow growing benign tumors
-subtypes: low grade (most common), atypical, malignant
-Location: convexity, parasagittal, optic sheath
-Imaging: dark on T1, Bright on T2, enhance with contrast, maybe calcifcations on CT, dural tail
-spindle shaped cells arranged in sheets & whorls, & tail of enhancement over dura extending from tumor edge
Meningioma: Treatment & Prognosis
- observation vs. surgery and/or radiotherapy if <3cm
- prognosis: very good relative to most other types of brain tumors
Pituitary Tumors
- 10-15% of all primary brain tumors
- most commonly derived from anterior pituitary
- Microadenomas (1cm): most often no hormones, often grow large enough to cause compression & hypofunction of pituitary gland or compression of the pituitary stalk
Pituitary Tumor: Signs & Symptoms
- Headache
- Endocrine dysfunction (galactorrhea - XS prolactin, acromegaly - XS GH)
- Visual field defects: bitemporal hemianopsia starting with upper quadrant (compression of chiasm), unilateral blindness (optic n. compression)
- diplopia (invasion of cavernous sinus compressing CN III, IV, VI)
- Facial numbness (invasion of cavernous sinus compressing CN V)
Pituitary Tumors: Diagnostics
-MRI with and without contrast: Serum hormone levels (endocrinology), visual fields test (ophthalmology)
Pituitary Tumors: Treatment
-Observation
-Surgery: 1st line of treatment for most tumors, low mortality with experienced neurosurgeon
-Radiotherapy: adjunct for invasive tumors of subtotal resection, reserved for recurrent or unresponsive tumors or very small tumors that are not directly adjacent to vital structures such as optic nerve late complications: damage to optic nerves, hypopituitarism, hyopthalamic dysfunction, secondary malignancy
-Pharmacotherapy:
Bromocriptin & Pergolide: dopamine agonists for prolactinomas, often show significant reduction in tumor size up to 80%
Octreotide: somatostatin analogue, for GH secreting tumors
Replacement Therapy for pituitary hypofunction
Acoustic Neuroma
-Vestibular Schwannoma
-origin is the Schwann cells surrounding the vestibular portion of CN VIII
-most commonly arise within the internal auditory canal or cerebellopontine angle
-occur in middle aged adults, M = F
-Benign, slow-growing tumors:
hearing loss, tinnitus, headaches, dizziness, facial numbness/weakness
Acoustic Neuroma: Treatment
- observation
- surgical excision, excellent outcome
- radiosurgery
-Bilateral acoustic neuromas are pathognomonic of neurofibromatosis type 2
Primary CNS Lymphoma: Diagnostics
- commonly affects the leptomeninges + deeper periventricular brain parenchyma
- MRI w/contrast may show multiple uniformly enhancing masses with little or no edema
- LP may show monoclonal population of B-cells in the CSF
- Vitrectomy for tissue diagnosis if ocular involvement
Primary CNS Lymphoma: Treatment
- Steroids: if lymphoma is suspected, withhold steroids until time of biopsy (cause rapid necrosis & poor specimen for path)
- Chemo: high dose methotrexate, vincristine, & procarbazine
- Radiotherapy
Primary CNS Lymphoma: Prognosis
- months for steroids alone, 1 year with radiation
- 3-4 yrs following chemo + radiation (cure possible in younger patients)
Brain Metastases
- more common, as bad as high-grade glioma
- 170,000 per year
Tumors that Metastasize to the Brain
- Small/nonsmall cell lung cancer (50%) most common in males
- Breast cancer (15-20%) most common in women
- Melanoma (10%) highest propensity
- Colon cancer (5%)
- Renal Cell Carcinoma
- Unknown (10%)
Brain Metastases: Diagnostics
- primary workup if indicated (head to toe imaging plus serum Ca markers)
- MRI with contrast
- Discrete single/multiple enhancing nodules
- significant amount of edema out of proportion to the size of the nodules
Brain Metastases: Treatment
- goals are to prolong life without incurring further neurological deficit
- Considerations: #, site, size, histologic type, age, neurologic status, status on non-CNS disease, & overall condition of the patient
- Accessible lesion & stable extracranial disease or multiple metastases then WBRT only
- Chemo & hormonal therapy for specific histologies
- Surgically inaccessible: radiosurgery or WBRT
- Progressive extracranial disease or multiple metastases then WBRT only
Brain Metastases: Prognosis
- Untreated - roughly 4 weeks
- Steroids only - roughly 8 weeks
- Other - maybe up to 12 months
Differential Dx of ring enhancing lesions in Brain
- Metastases High Grade Glioma
- Abscess Lymphoma
- CVA Demyelination
Spinal Cord Tumors: Signs & Symptoms
1) pain (most common)
2) Weakness + UMN/LMN motor findings
3) Paresthesias
Spinal Cord Tumors: Classifications
- Based on Origin (primary or metastatic)
- Based on Location
Extra-dural - majority are spinal metastases, 70% of spinal mets (breast, lung, prostate, renal cell, lymphoma, sarcomas)
Intra-dural extramedullary - Schwannomas, neurofibromas, meningiomas
Intra-dural intramedullary - Astrocytomas (peds), Ependymoma (adults), Hemangioblastoma
Spinal Cord Tumors: Treatment
- Surgery
- Radiation (conformal, radiosurgery)
- Chemo
