Khan - Brain Tumors Flashcards
(47 cards)
1
Q
How common are brain mets?
A
- Estimated 35% of cancer pts will devo brain mets
- REMEMBER: these are the most common brain tumor
- NOTE: brain tumors are relatively less common compared to other cancers
2
Q
How can the rate of change in ICP reflect the grade of the tumor causing it?
A
- P-V curve: progression to right side of the curve may take years in low-grade tumor
- INC ICP will happen more rapidly in malignant, high grade tumor
3
Q
When should anticonvulsants be used in pts with brain tumors? Which ones should be avoided?
A
- Seizures are treated ONLY if they occur
- Use anticonvulsants that do NOT induce hepatic enzymes
1. Do NOT use valproic acid bc it affects PLTs (can cause thrombocytopenia)
4
Q
What is the mainstay of tx for most brain cancers? Exception?
A
- RADIATION is still the mainstay of tx for most cancers
- Only brain tumor for which radiation is not the mainstay of tx is CNS lymphoma bc chemo is very effective
5
Q
What are the 2 big chemo drugs to remember for brain cancer?
A
- Temozolomide
- Bevacizumab
6
Q
What does malingering mean?
A
Pt is faking it
7
Q
What is paranode syndrome?
A
- PRESSURE ON TECTUM, usually due to a tumor of the pineal gland (glioma or germinoma)
- This is a dorsal midbrain syndrome where pts can’t look up due to pressure on Oculomotor nuclei sup rectus fibers from the medial nucleus -> dysfunctional
1. Nucleus of Cajal in midbrain works like PPRF for vertical gaze - Also puts pressure on aqueduct, which can lead to hydrocephalus and headache
- Non-specific effect of abducens paralysis: this can happen anytime you get ICP; speculation that this happens over petrous bone
8
Q
What does bilateral abducens paralysis suggest?
A
Raised ICP (non-specific sign)
9
Q
What are pressure waves? How can they be tx’d?
A
- PRESSURE WAVES: INC intra-thoracic pressure leads to momentary reduction in drainage of venous fluid from the brain -> small INC in non-compliant brain causes exponential rise in CSF pressure, which can offset perfusion pressure of the brain
1. May lead to transient visual obscurations (BLURRING)
2. Post pressure (basilar - PCA) < anterior, and more susceptible to these changes - TX: reduce pressure -> spinal tap to detect pressure of tumor cells and cell markers of different cell types
1. If you do this at wrong time, you CAN KILL THE PT, i.e., tonsillar or other herniation -> will lead to respiratory arrest (Arnold Chiari)
2. CURATIVE in terms of symptoms if all CSF pathways normal
10
Q
What is the survival rate of GBM?
A
- One of the worst tumors to have (survival <1%)
- NOTE: study where CMV infection tx’d, and survival rates were incredible
11
Q
Briefly describe neuropoiesis (image).
A
12
Q
How are tumor stem cells implicated in brain cancers? How does this affect their makeup?
A
- Growing evidence supports presence of tumor stem cells in different cancers, incl. GLIAL TUMORS
- Glial tumors are differentiated into different types and may have different clinical behavior
- Mixed glial/neuronal tumors also possible containing neoplastic neuronal and glial components:
1. GANGLIOGLIOMA - Mixed glial tumors also possible, e.g., OLIGO-ASTROCYTOMA
13
Q
Provide some examples of CNS tumors, and their cells of origin.
A
- Hemangioblastoma: from blood vessels
- Neurofibroma/SCHWANNOMA: from NN
- LYMPHOMA: from tracfficking WBC’s
- Germinoma: from nests of germ cells
- MENINGIOMA: from arachnoid capillary cells
- Chordoma/chondrosarcoma: from bone
- Extracranial cancer may enter via blood stream (mets)
- NOTE: these can arise from any structure present intracranially; devo cysts can also mimic brain tumor
14
Q
What are the most common primary brain tumors?
A
- # 1 = infiltrative astrocytoma
- # 2 = GBM
15
Q
What are the 5 brain tumors we are responsible for? Categories?
A
- PRIMARY CRANIAL:
1. Intra-axial:
a. Glioma
b. Pituitary
c. Lymphoma
2. Extra-axial: external to brain parenchyma
a. Meningioma
b. Acoustic neuroma - NOTE: don’t forget about mets and spinal cord tumors
16
Q
What are the definitive and possible risk factors for CNS tumors?
A
- DEFINITIVE: ionizing radiation
1. Immunosuppression: iatrogenic, chemo, AIDS
2. Genetic syndromes - POSSIBLE: electromagnetic fields, incl cell phone use
1. Diet, occupation
2. Infections: HIV, EBV (linked to CNS lymphoma in immunosuppressed pts, esp. after bone marrow transplant and in AIDS), HTLV
17
Q
What hereditary syndromes are associated with brain tumors (table)?
A
18
Q
What is the relevance of a pressure-volume curve for brain tumors?
A
- Cerebral perfusion pressure is difference bt MAP and ICP (CSF and interstitial pressure)
- As intracranial volume slowly INC (see graph), such as with tumor growth, ICP remains fairly constant until compliance threshold reached
- At this stage, small volume INC causes large INC in ICP -> PLATEAU WAVE (other card)
19
Q
What is the plateau wave phenomenon?
A
- Once ICP reaches compliance threshold (due to growing tumor), small volume INC causes large INC in ICP
- At this stage, intermittent INC in ICP (see graph) may exceed cerebral perfusion pressure (plateau waves) and cause multiple symptoms:
1. From focal weakness, numbness, mental status changes, and seizure-like activity (global or focal hypovolemia in the brain) - Aka, plateau wave phenomenon
20
Q
What are the GENERAL signs and symptoms of CNS tumors?
A
- HEADACHE: due to raised ICP or local irritation and often non-specific (may have migraine features and show laterality)
1. Suspect tumor if: a) worse on awakening with improvement w/in 1 hour, b) new onset at any age, 3) change in character or severity of headaches in chronic headache pt - VOMITING: may or may not be assoc w/nausea and occurs more often on awakening (more comm in kids)
1. Suggests tumor if vomiting immediately follows an acute onset headache, suggesting ICP - MENTAL STATUS CHANGES: depression, irritability, apathy
- NOTE: these are all results of INC ICP, which may stretch basal blood vessels or dura, causing pain
1. INC ICP may also reduce cerebral perfusion (MAP - ICP = perfusion pressure), and result in ischemic symptoms
21
Q
What are the FOCAL signs and symptoms of CNS tumors?
A
- PAPILLEDEMA: often asymptomatic (may have visual changes) and more comm in kids/yng adults than old
- SEIZURES: partial (focal) or generalized with episodic alterations in smell, taste, personality, memory, motor, or sensory function, depending on origin of neural discharge (pathogenesis unclear, but may be due to entrapped neurons in tumor or pressure from infiltrating tumor edge)
- FOCAL NEURO DEFICITS: will vary by location, and include, but not limited to -> weakness (pre-central gyrus), paresthesias (post-central gyrus), visual impairment (optic pathway/occipital lobe), personality changes (frontal lobe)
1. These may or may not be reversible depending on: cause (tumor invasion vs. edema vs. compression) and time since onset of deficit
22
Q
What is the etiology of CNS tumor signs and symptoms?
A
- Invasion or compression of adjacent neural or vascular structures: can lead to hemorrhage or cerebral vascular accident
- Obstruction of CSF pathways -> hydrocephalus -> INC ICP
1. SUNSET SIGN: upgaze paresis w/eyes appearing driven downward (lower portion of pupil may be covered by lower eyelid, and sclera may be seen bt upper eyelid and iris) - Herniation from mass effect
- Cerebral hypoperfusion bc INC ICP
23
Q
What are the 5 brain herniation mechanisms?
A
- 1) Subfalcine herniation of cingulate gyrus: may compress ACA and CVA
- 2) Diencephalic downward herniation: compression of upper brainstem causes drowsiness, impaired vertical gaze (SUNSET SIGN), and uni- or bilateral sm pupils due to involvement of SYM fibers (Horner’s)
- 3) Classical uncal herniation: ipsilateral CN III palsy and contra or ipsilateral hemiparesis
- 4) Upward herniation through tentorium: may cause ipsilateral CN III, Horner (mid-position unreactive pupil) and contralateral hemiparesis
- 5) Tonsillar herniation: BP changes, weakness, resp disturbance, weakness, Horner
24
Q
What are the diagnostics for CNS tumors?
A
- Hx/PE: clues for initial dx and suspected location
1. Gradually progressive neuro symptoms and deficits are highly suggestive of underlying tumor (more quickly in CVA migraine and seizures, and more slowly in degenerative disorders) -
MRI w/and w/o contrast enhancement: study of choice for a suspected tumor (GOLD STANDARD)
1. MRI superior to CT in differentiating tumors from vascular malformations and o/lesions, but CT better at ID’ing calcifications, yielding clues as to patho of the tumor (i.e., oligodendroglioma) - Definitive dx can ONLY be achieved via tissue biopsy, with exception og primary CNS lymphoma (PCNSL), where malignant cells may be found in CNS via LP
25
What are the 2 types of MRI?
- T1 WEIGHTED: water (i.e., CSF, _tumor, edema) is *hypointense*_ (dark), so DEC signal or darker than surrounding brain
1. Injected contrast that leaks across disrupted BBB w/in tumors *hyperintense* (bright), so INC signal or brighter than surrounding brain
- T2 WEIGHTED: CSF/edema/tumor hyperintense (bright) -\> can differentiate edema from infiltrating tumor bc _edema spares cortex_ and tumor does not
1. Stationary and moving water both bright/white
26
What type of MRI is this? Difference bt the 2 images? What do you see?
- **T1 weighted MRI**
1. LEFT is T1 and RIGHT is T1 with contrast
- Large ring enhancing tumor in L frontal lobe, incl _mass effect_ with midline shift
- Tumor has grown rapidly, outstripping its blood supply, and leading to _central necrosis_ (dark area)
- All of these are indicative of a highly malignant tumor, most likely a _grade IV astrocytoma_ (GBM)
27
What is a glioma? Subtypes? Grades?
- Umbrella term describing tumors derived from the supporting glial cells of the CNS
- Major _subtypes_: 1) astrocytoma, 2) ependymoma, 3) oligodendroglioma
- _Most common primary CNS tumor_: \>50% of all 1o tumors
- Low-to-high grade based on behavior, imaging, and histopathological features (_low-grade more common in young_ and high-grade more common in \>50):
1. Grade 1 = juvenile pilocystic astrocytoma
2. G2 = low-grade astrocytoma (may degenerate to higher grade after many years)
3. G3 = anaplastic astrocytoma
4. G4 = **GBM** (most common glioma)
28
How does histo grading work for gliomas?
- Lowest grade: well-differentiated, no nuclear atypia, and low mitotic index
- INC de-differentiation, higher mitotic index, vascular proliferation, necrosis determine higher tumor grade
- NOTE: _tumor blood vessels have immature BBB, resulting in leakage of dye on MRI_ imaging
29
What are the imaging and histo features of gliomas (low-grade vs. high)?
- _LOW-GRADE_ are infiltrative, slow-growing, and do NOT produce severe mass effect
1. Hyperintense on T2 or FLAIR images (L upper image) and do NOT enhance with contrast (right image upper row T1 after contrast)
- Note _features of a HIGHLY MALIGNANT glioma_ in the bottom row: an ENHANCING MARGIN, necrotic center, surrounding edema, MASS EFFECT
30
What therapeutics are used to tx brain tumor symptoms?
- STEROIDS (e.g., Dexamethasone): reduces vasogenic edema and improves ICP (restore BBB)
1. Dramatic, but _temporary improvement in neuro symptoms_
- ANTICONVULSANTS: non-hepatic enzyme inducing, i.e., Levetiracetam, Lacosamide, Gabapentin, etc.
1. Given for focal or generalized seizures caused by tumor
2. No evidence supporting use prior to seizure onset (even though 50% risk), except for: _pts undergoing surgery_ (only for 1 week)
31
What is the DEFINITIVE tx for brain cancer?
- OBSERVATION: tumors that are _not life-threatening_, slow-growing, asymptomatic, sxs controlled medically
- SURGERY: first line of tx for accessible tumors, est. pathologic dx, improves ICP and seizure conrol, and _prolongs survival_ (improved by extent of resection)
- RADIOTHERAPY: _adjunct to sx_ for high-grade gliomas and may be delayed in low-grade; needed for _eradication of infiltrative micro-pops_ of cells missed with resection (also improves survival)
1. Can be assoc w/long-term risk of cognitive decline, stroke, and secondary cancers
32
What are the 5 radiation modalities? Briefly characterize them.
- _Conventional_: not used anymore bc normal tissue and tumor get same dose
- _Conformal_: different beams of radiation are computer graphically designed to FOCUS ON TUMOR, giving it max dose while normal brain dose reduced
- _Radiosurgery_: high-dose of conformal radiation given in single fraction
- _Brachytherapy_: insertion of radioactive material in tumor cavity
- _Proton therapy_: heavier particles, so depth of radiation can be controlled, sparing normal tissue (COST IS PROHIBITIVE right now)
33
What are some of the ADJUVANT txs for brain tumors?
- CHEMO: conventional regimens incl. single-agent IV BCNU (Carmustine), single-agent PO **Temozolomide** (current _DOC/standard of care_), and combo of Procarb-azine, CCNU (Lomustine), and Vincristine
1. Temozolomide is an alkylating agent that adds 3 months to median survival, and may cause serious _bone marrow suppression_
- BIOLOGICS: anti-angiogenesis agent **Bevacizumab** has shown efficacy in anti-glioma tx (FDA approved)
1. Prevents new blood vessel formation, and stops tumor growth
- Gene therapy, immunotherapy, viral therapy, etc. currently being studied
34
What is MGMT? How does it impact survival?
- Tumor DNA damaged by the alkylating agent Temozolomide is repaired by the enzyme MGMT
- In pts with inactive MGMT, median survival is close to 2 years, while there is no improvement over radiation tx in pts with active MGMT
35
What are the prognostic factors for brain tumors?
- Survival is better if:
1. Younger age
2. Good performance status
3. Tumor grade and histology
4. Degree of tumor resection
5. O6-methyl guanine-DNA methyltrasnferase (MGMT) methylation
6. Isocitrate dehydrogenase 1 (IDH1) mutation
7. 1p and 19q deletion in oligodendroglioma
36
What are the features of meningiomas (imaging, tx, prognosis, etc.)?
- 2-10% of all 1o brain tumors (2nd most comm 1o CNS)
- Peak incidence at _45 years: F_ \> M
- Slow-growing, benign tumors derived from _arachnoid membrane cap cells_ (extra-axial)
1. May spontaneously involute, or cause symptoms via compression
- Subtypes: low-grade (most common), atypical, malignant
- Common LOCATIONS: convexity, parasagittal, optic sheath
- IMAGING: dark on T1 (iso-/hypointense), bright/hyper-intense on T2, diffuse enhancement w/contrast, may see _calcifications_ on CT, _dural tail_
- TX: observation vs. sx vs. radiotherapy (if \<3cm)
- PROGNOSIS: very GOOD relative to most o/types of brain tumors with surgical resection (_NO effective chemo_ at this time)
37
What are the histo and imaging features of meningiomas?
- _Spindle-shaped_ cells arranged in sheets and whorls, and tail of enhancement over dura extending from tumor edge (_dural tail_)
- Diffuse enhancement
- May spontaneously involute and calcify, or cause symptoms by compressing other brain structures
- Majority are low-grade tumors
38
What are the classifications, signs, and symptoms of pituitary tumors?
- 10-15% of all 1o brain tumors (3rd most comm 1o CNS), and most commonly derived from ant pituitary
- CLASSIFICATIONS: microadenomas (\<1cm) most often hormone-secreting/functional
1. Macro (\>1cm) most often non-functional and often grow lg enough to compress and impede function of pituitary gland or stalk
- SIGNS/SYMPTOMS: headache, endocrine dysfunc (galactorrhea (XS PRL), acromegaly (XS GH); can INC or DEC hormones), & visual field defects, incl:
1. Classically, _bitemporal hemianopsia_ starting w/upper quadrant -\> chiasm compression
2. Unilateral blindness: optic N compression
3. Diplopia: invasion of cavernous sinus, compressing CN III, IV, VI
4. Facial numbness: invasion of cavernous sinus, compressing CN V
39
How is bitemporal hemianopsia different in pituitary adenomas than craniopharyngiomas?
- Starts with _upper quadrants in pituitary adenoma_
- Starts with inferior quadrants in craniopharyngioma
40
What are the diagnostics and txs for pituitary adenomas?
- DX: MRI w/and w/o contrast, serum hormone levels (endocrine), visual fields testing (ophthalmology)
- TX: observation
1. SURGERY: _1st-line_ for most tumors, and low morbidity/mortality w/experience neurosurgeon
2. RADIOTX: adjunct for invasive tumors or sub-total resection; for recurrent, unresponsive, or very small tumors not directly adjacent to vital structures like optic N (_late cxs_ incl: damage to optic NN, hypopituitarism, hypothal dysfunction, and secondary malignancy)
3. PHARMACOTX: _Bromocriptine_ and Pergolide (dopamine agonists for PRL; often reduction in tumor size by up to 80%)
a. _Octreotide_: somatostatin for GH-secreting
b. Replacement therapy for pituitary hypofunction
41
What are the features of acoustic neuromas?
- Aka, _vestibular schwannoma_: origin is Schwann cells surrounding vestibular portion of CN VIII; most often arise in internal auditory canal, cerebellopontine angle
- Middle-aged adults (M = F)
- _Benign, slow-growing_ tumors that present w/: hearing loss, tinnitus, headache, dizziness, facial numbness or weakness
- TX: observation, sx excision (excellent outcome), or radiosurgery
- NOTE: **bilateral acoustic neuromas pathognomonic for NF2** (chrom 22)
1. Schwannomas can also arise from other CN's, and even spinal radicles (densely packed and cystic areas on histo)
42
What are the features of CNS lymphoma (dx, tx, prognosis)?
- Commonly affects leptomeninges + deeper _peri-ventricular_ brain parenchyma
1. On the rise, and a malignant transformation of trafficking B-lymphos
- DX: _MRI w/contrast_ may show multiple uniformly enhancing masses w/little or no edema and LP may show _monoclonal pop of B-cells in CSF_ (vitrectomy for tissue dx if ocular involvement)
- TX: if lymphoma suspected, withhold _steroids_ until time of biopsy bc will cause rapid necrosis and poor specimen for patho; _chemo_ (high-dose MTX crosses BBB, Vincristine, Procarbazine), _radiotherapy_
- PROGNOSIS: months for steroids alone; 1 year for tx with radiation; _3-4 yrs after tx w/chemo + radiation_ (_cure possible in younger pts_; highly chemo/radio sensitive)
1. Extent of resection not a prognostic marker
- NOTE: round blue cells, and may be caused by EBV infection in immunocompromised patients
43
What tumors met to the brain? Dxs?
- More common/equally _as devastating as high-grade glioma_
- TYPES: 50% small/non-small cell LUNG cancer (most comm brain mets in M)
1. 15-20% BREAST: most comm brain mets in F
2. 10% melanoma: _highest propensity_ to met here
3. 5% colon cancer
4. Renal cell carcinoma
5. 10% unknown primary
- DXs: primary workup, if indicated (head-to-toe + serum Ca markers), MRI with contrast -\> discrete single or _multiple solid or ring-enhancing nodules_
1. Significant amt of _edema out of proportion_ to size of nodules
44
What is the tx and prognosis for brain mets?
- TX: goal to prolong life w/o further neuro deficit; have to consider #, site, size, histo, age, neuro status, etc.
1. Accessible lesions and stable extracranial disease: sx + whole brain radiotherapy (_WBRT_); prolongs survival and improves QOL
2. Surgically inaccessible: radiosurgery or WBRT
3. _Progressive extracranial disease_ or multiple mets = WBRT only
4. Chemo/hormone therapy for specific histo
- PROGNOSIS: untx'd 4 wks, steroids only 8 wks, other modalities may prolong survival for _up to 12 mos_
45
What is the differential for ring-enhancing lesions in the brain?
- Mets
- High-grade glioma
- Abscess
- Lymphoma
- CVA: cerebral vascular accident
- Demyelination: incomplete or open ring enhancement commonly seen (tumefactive demyelination)
46
What are the signs and symptoms of spinal cord tumors? Classifications?
- Depend on location, but can be:
1. **Pain**: most common presenting symptom
2. Weakness + UMN/LMN motor findings
3. Paresthesias
- CLASSIFIED based on origin (primary or metastatic) and location:
1. _Extra-dural_: majority are spinal METS (70% of spine mets: breast, lung, prostate, RCC, lymphoma, sarcomas)
2. _Intra-dural extramedullary_: schwannomas, neurofibromas, meningiomas
3. _Intradural intramedullary_: astrocytomas (most common in peds), ependymoma (most comm in adults), hemangioblastoma
47
What are the tx options for spinal cord tumors?
- Surgery
- Radiation: conformal, radiosurgery
- Chemo
- Similar principals to tx for intracranial tumors, but sx resection more challenging and chemo less well studied
