E. R. Flotte MD, 2009
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Genetics, Basic Science, and
Experimental Treatments
Spinal Tumors
Incidence
·
Neonates: Teratoma > PNET > GBM > Choroid Plexus Tumor
·
Children:
o
Infratentorial: cerebellar
astrocytoma > brain stem glioma > medulloblastoma > ependymoma.
o
Supratentorial:
astrocytoma >craniopharyngioma > optic glioma
Radiology
·
MR-Spectroscopy:
o
May
be used to differentiate tumor from radiation necrosis, abscess, etc.
o
Tumor:
↑ Choline (& choline:creatinine ratio), ↓ NAA
o
Not
specific for different tumor types. Varies within areas of same tumor.
o
May
be used to guide biopsies
o
May
be predictive of treatment response (animal studies)
·
Diffusion Tensor
Imaging:
Localizes subcortical motor pathways – useful for preoperative planning to
determine if tumor infiltrates or displaces motor tracts
·
Differentiating tumor
from radiation necrosis: PET scan (best, 85% accuracy), MR-Spect, SPECT scan.
·
ADC higher in neoplasms than in abscesses (JN1/07)
·
Remember
differential for round, enhancing masses (especially in basal cisterns):
(giant) cerebral aneurysms – check CTA/MRA – do not biopsy.
Pathology
·
MIB-1: Antibody that
stains cells in mitosis – used to determine the mitotic index of tumors.
Generally a higher index indicates a worse prognosis. Recognizes the same
epitope as the Ki67 antibody, but unlike Ki67 it can be used in frozen, paraffin-embedded,
or decalcified tissue.
Antiepileptics
·
Metaanalysis of 12 studies
showed AEDs are not effective in preventing first seizures. AAN recommends AEDs
not be used routinely preop, and should be weaned after 1 week postop (Glantz MJ Neurology5/00)
Surgery
Extent of Resection:
·
Berger
classification: Total: 100% resection
(no enhancement); Subtotal: <10cm3 residual or
>90% resection; Partial >10cm3
residual or <90% resection
·
Intracavitary
catheter with subcutaneous (Ommaya) reservoir used to aspirate recurrent cysts
·
Audio: The Future of Surgical NeuroOncology – Wilson CB
Radiation
·
Hypoxic, nonproliferating cells are
radioresistant
·
Maintain
patient on steroids during XRT (Decadron 1mg BID)
·
Types:
o
Whole Brain (WBRT)
o
Conformal
·
Dose: Glioma: 60Gy conformal; Met: 30-45Gy WBRT
·
Re-irradiation possible at 8yrs
·
Spinal cord
tolerance: 50Gy in 2Gy/d fractions – 5% risk of myelopathy. 2mm margin between
tumor and cord.
·
Radiation effects:
o
Early (days) = edema, reversible, treat
with steroids.
o
Early-delayed (weeks –
months) = demyelination
o
Late-delayed (6-24mo) =
necrosis, irreversible. May require surgical resection
o
Risk
of dementia with WBRT: Reported to be 15% at 1year and 50% at 2 years (see also
Nieder C 1998). However this is controversial, no prospective studies have been
done.
o
Other
SE: alopecia, dermatitis, cataracts, blindness, somnolence syndrome
·
Radiosensitizers: Gadolinium, RSR-13. Show no survival benefit.
Brachytherapy
·
Seeds: inserted through implanted catheters. 125I or 192Ir
used. 30-60% of patients develop necrosis requiring resection.
·
Gliasite catheter:
Balloon
catheter implanted, filled with 125I solution (Iotrex) saline. No
longer in production.
Chemotherapy
Alkylating Agents
·
Most cause cumulative
myelosuppression, pulmonary fibrosis (limits use to 12-18mos). Resistance
mediated by O6-MGMT (see below).
·
BCNU (Carmustine): IV. Used for gliomas.
Treatment repeated every 8-10 weeks after myelosuppression resolved (begins
week 4-5). Repeat enhanced scan before each dose & if progression seen
switch drugs.
·
CCNU (Lomusine):Oral.
·
Temozolomide
(Temodar):
Better tolerated. Oral equivalent of dacarbazine (DTIC), prodrug, penetrates
BBB. Used for gliomas, mets (FDA approved only for recurrent anaplastic
astrocytoma). 150mg/m2 for 5d every 28d. Can deplete O6-MGMT in
tumor cells. Less myelosuppression (non-cumulative).
·
Glidel: BCNU wafers.
Dissolve over 2-3 weeks. Prior IV BCNU not predictive/exclusionary. Up to 8
wafers. Cost $10K. Repeat implantation possible. Wafer may be present up to 232
days postop. May cause enhancement. Can place safely w/small openings into
ventricle.
·
Procarbazine: Oral
Platinum
Compounds
·
Cisplatin,
Carboplatin:
non-classical alkylating agents, used as salvage therapy
Protein-Tyrosine
Kinase Inhibitors
·
Imatinib mesylate
(Gleevec):
blocks BCR-ABL, c-kit, PDGFR. Oral, low SE.
Topoisomerase
inhibitors
·
Topotecan,
Irinotecan, Etoposide
·
Irinotecan
(CPT-11) is being studied for use in GBM
Vinca
alkaloids
·
Vincristine
Taxanes
·
Paclitaxel
Anti-angiogenesis:
·
Thalidomide,
endostatin, interferon, SU5416, PTK787
·
Bevacizumab (Avastin) is monoclonal antibody VEGF-inhibitor
Differentiation
agents
·
Accutane
(cis-retinoic acid), fenretinide
Matrix
metalloproteinase inhibitors
·
Marimistat,
prinomastat
Combination
·
PCV: CCNU 110mg/m2,
Procarbazine 60mg/m2 on d8-21, Vincristine 1.4mg/m2 on d8 & d29 every 8
weeks.
·
Agents
may be given IV or IA (3-5x higher drug concentration, but higher toxicity),
with or without BBB disruption (mannitol).
·
Chemotherapy Resistance:
o
O6-MGMT: (O6-methylguanine-methyltransferase) or
AGAT. Enzyme in tumor cells that causes resistance to alkylating agents. Gene
deactivated by promoter hypermethylation. Controversial whether level predicts
response to nitrosoureas.
Diagnosis
·
Findings
on brain biopsy for rapid neurologic worsening: Josephson
SA JN1/07 (PSCNL = primary CNS lymphoma)
·
Consensus is that no noninvasive approach has emerged as being
able to reliably discern whether a ring-enhancing lesion is tumor or abscess,
and therefore early biopsy is generally considered essential for definitive
diagnosis.
·
AAN guidelines for the management of patients with AIDS state only an isolated ring-enhancing
lesion in the setting of negative toxoplasmosis serology requires
early biopsy. Otherwise, a trial of pyrimethamine and sulfadiazine is
considered appropriate for treatment of presumptive toxoplasmosis.
|
|
Astrocytomas
Grading
·
Kernohan (4 tier)
·
Daumas-Duport: AKA St Anne/Mayo. Criteria: nuclear atypia, mitoses, endothelial
proliferation, necrosis. Grade 1 = 0 criteria; Gr2 = 1 criteria (4yr survival);
Gr3 = 2 (1.6yr); Gr4 = 3 or 4 (8mo)
·
WHO:
o
(Grade I: pilocytic)
o
Grade II: nuclear atypia,
cellularity
o
Grade III: mitotic
activity
o
Grade IV: atypia, mitoses,
endothelial proliferation, and/or necrosis
·
“Malignant Glioma” =
Grades 3 & 4.
·
Audio: Gliomas Quo Vadis – Rutka JT
Diffuse
(Low Grade) Astrocytoma
Incidence
·
Radiation only known risk – studies from survivors at Hiroshima & Nagasaki ,
and XRT for tinea capitis in children in Israel
Genetics
·
P53
(65%), PDGFR (60%)
Histology
Subtypes:
1. Fibrillary: occurs in white matter; firm; GFAP
(+)
2. Protoplasmic: soft, translucent
expansion of cortex; microcysts, mucoid; GFAP (-)
3. Gemistocytic:
o
Defined
as >20% gemistocytes
o
Worse
prognosis
o
p53
mutation more common (80%);strongly GFAP(+)
Diagnosis
·
>50%
present with seizures only, no deficits
·
LGA
presenting with chronic epilepsy has a longer survivial and is likely to
dedifferentiate
·
Usually
has decreased glucose utilization by PET, but dedifferentiated areas may
be hot - can guide biopsy/resection
·
Imaging
diagnosis is wrong in 33-50% (45% were AA, 5-7% nonglial)
o
Biopsy
may be guided by PET, perfusion-weighted MRI
·
Average
30% enhance – has worse prognosis, 7x higher recurrence (although some studies
show no effect on survival)
Treatment
Observation
·
Serial
MRIs
·
Role
is controversial.
o Supported by Recht 92: no difference
in survival if surgery is deferred until growth, transformation, or intractable
seizures
o Piepmeier 87: <40yo, seizures
only: serial scans; >40yo, deficits, enhancement or mass effect:
aggressive treatment
Surgery
·
Lobar
= GTR; deep = Biopsy + XRT
·
Early
surgery, extent of resection have not been proven to
prolong survival. No RPT has been performed, only retrospective trials:
o Studies showing benefit of aggressive
resection: Berger 94 (all w/GTR disease free @ 4yrs; < 10cm3
residual better survival); Laws JN84 (STR 32% 5ys; GTR 61% 5ys); 4 others.
o Studies showing no benefit to surgery:
Piepmeier 87, Shibamato 93, Lunsford 95 (Biopsy + XRT)
o EORTC 22845: 5yr survival 75% for GTR,
60% for STR, 50% for biopsy (Karim AB IJROBP 2002)
o Reviews: Keles GE JN11/01
– comment Laws
ER.
·
Stereotactic
Biopsy: Sampling error - 33-66% (foci of AA)
Radiation Therapy
·
Extent:
T2 area on MRI + 2-3cm margin
·
Dose:
No difference b/t 45 and 60Gy (EORTC 96, RTOG 98)
·
Controversial:
adjuvant or at recurrence. Favored in patients >50yo with residual tumor
o RPT: EORTC 22845 showed no benefit to
postop 45-60Gy XRT (Karim AB IJROBP 2002)
o Several retrospective studies show
benefit; 7 show no benefit. May induce regression, symptom palliation, improve
TTP; no survival benefit.
o Timing: no survival difference if XRT
is delayed until progression (EORTC 98)
·
One
recommendation: Fibrillary or protoplasmic = 45-55Gy if residual tumor
present. Gemistocytic = adjuvant XRT regardless of extent of resection
Radiosurgery
·
Used
for small inaccessible tumors - unproven. Fractionated SRT used (25Gy in 5
fractions) (Simonova G JN1/05S)
Chemotherapy
·
Not
used as adjuvant, considered for recurrence. PCV, temodar used. Peds:
multiagent (instead of XRT)
Recurrence
·
>50%
5yr recurrence after GTR only for adults <40yo (RTOG 9802 – Shaw EG JN11/08)
·
Effectiveness of treatment is not well studied; Laws 84:
treatment makes no difference. Usually needs biopsy or re-resection to rule out
progression.
Prognosis
·
Median
survival range 8-12yrs (increase may represent lead-time bias)
·
Prognostic
factors: Age most important; also enhancement, size, histology, KPS.
·
Bauman
99: RPA: 1)KPS<70, age>40 MS 12mo; 2)KPS>70, age>40, enhances=
46mo; 3)KPS<70, age18-40, no enhancement=87mo; 4)KPS>70, age<40=128mo
(included oligo& mixed glioma)
·
Age:
all pts who transformed were >45yo (Recht 92)
·
Deep
lesions: median survival 2 years - die from local mass effect, not
transformation
·
Enhancement:
7x more likely to recur. 92% enhance @ recurrence
·
Chronic
epilepsy has better prognosis
·
PET: hot areas = worse prognosis
·
Detect recurrence: PET (most sensitive),
SPECT, MRS (>45% increase in choline-Tedeschi 97)
·
MIB-1:
>8% = high risk of transformation, more significant than histology (but 2
studies show MIB-1, p53 not prognostic)
·
50-85%
transform to GBM, average 5 yrs after diagnosis (1.5-10yrs) (13% Piepmeier 87 -
f/u only 5yrs)
·
Transformation heralded by new or worse
seizures or new deficit
·
RTOG 9802: 5 year survival - Favorable LGG =
93%, Unfavorable LGG = 66% (Shaw EG JN11/08)
|
|
Malignant Glioma: Anaplastic Astrocytoma &
Glioblastoma Multiforme (GBM)
·
Reviews: Neurosurgical Focus 4/06
Clinical
·
Mean age 60yo
·
Seizures in 20%
·
GBMs
have not been found to be associated with cell phone use in large studies
(Swedish Interphone Study Group, Neurology 4/0).
·
Only
know risk factor is prior cranial radiation.
Histology
·
GFAP
may be (-) if highly undifferentiated
·
3-6%
multicentric
·
CSF
seeding occurs in 15%: 2mo survival;
consider IT chemo
Genetics
·
Primary GBM: EGFR (60%), MDM2
(50%), p16
·
Secondary GBM (arising from a low
grade glioma): P53 (65%), PDGFR (60%)> AA (LOH19q, Rb)
> GBM (DCC(50%)) .
- Secondary
GBMs account for 28% of GBMs.
·
The expression of MGMT had prognostic value, predicting a
less favorable outcome (12.2-month median survival duration compared with 18.2
months), and furthermore, there was a low likelihood of benefit from
alkylator-based chemotherapy (i.e. BCNU, Temozolomide).
·
EGFR is both
overexpressed (60%) and truncated giving rise to a ligand-independent,
constitutively activated form called EGFRviii
(40%)
·
Loss of PTEN (seen in 50% of cases) results in resistance to EGFR
inhibitors. Without PTEN, the PI3K pathway is constitutively active and
independent of EGFR signaling. Response to EGFR tyrosine kinase inhibitors is
dependent on coexpression of both EGFRviii and PTEN.
Radiology
·
AA
30% nonenhancing; GBM 4% nonenhancing
·
Cerebellar
cases rare but do occur
Treatment
·
Enhanced MRI should be obtained postop & post-XRT.
·
Typical treatment is surgery followed by conformal XRT
(60Gy) and concomitant temozolomide.
·
See Chamberlain MC
NF4/06
Surgery
·
Goals: Diagnosis, relieve symptoms, cytoreduction
·
Effect of extent of resection debated: No RPT.
o
Class II Data: Laws JN9/03,
Sawaya 99, Lacroix
JN8/01 (Resection >98% MS 13mo vs <98% 9mo), McGirt MJ JN1/09
o
Refuted by: Curran 93, Kreth 93, Kreth 99 (surgery only
effective if midline shift is present), Quigley 91.
·
Neurologic morbidity: 40% with PR, 3% with GTR . Major morbidity: 12% surgery, 4% biopsy. (NO7/01)
·
Biopsy gave incorrect diagnosis in 5-40% of cases.
Radiation
·
60Gy Conformal RT standard. Higher doses do
not increase MS. No difference in MS between conformal & WBRT.
o
Conformal RT to 86Gy in progress.
·
Proven to extend MS (4mo to 9mo) by BTSG
(Walker 78), particularly if <65yo, regardless of extent of resection
·
Growth during XRT is very poor prognostic
sign
·
Risk of
death increases by 2%/day waiting for XRT (Do 2000).
Radiosurgery
·
12-16Gy boost after XRT or at recurrence.
·
Newly Diagnosed:
o
Sarkaria 95: 4-20mo improvement over XRT
only.
o
Shrieve 99: MS 20mo, 43% reop for necrosis.
o
Nowkedi N02: SRS + XRT 25mo MS vs XRT 13mo.
o
RTOG 93-05: RPT. GBM <4cm, de novo or
post-op residual. No difference in MS.
·
Recurrence: survival 10-18mo, reop 0-20%, 4
trials
Brachytherapy
·
Seeds:
2mo greater survival, 40% reop for necrosis (BTCG 8701; 1994)
·
Lapierre
1997: RPT. No change in survival but used single catheter.
·
4
phase II trials did show benefit (18-23mo).
·
Gliasite: Intracavitary balloon brachytherapy device
used with liquid I125. No longer in production.
Chemotherapy
·
Temozolomide
(Temodar):
o
Oral
alkylating agent. Current standard of care.
o
Generally
given concurrent with XRT and 5 consecutive days every 28 days, although other
regimens are used.
o
EORTC/NCIC (Stupp NEJM 05):
RPT. Concurrent Temodar and XRT (and continuing 6mos post-XRT) increased MS
from 12 to 14.6mos and 2YS from 10% to 26%.
·
Temodar
was given concurrently with
conventional external-beam radiotherapy for 42 consecutive days (single daily
dose 75 mg/m2), beginning with the first day of radiation. Radiotherapy was
administered for 30 to 34 treatment days as a single 180- to 200-cGy fraction
per day, to yield a total dose of 59.4 to 61.2 Gy. Two to 3 weeks after
conclusion, patients were reevaluated with MRI. If they were clinically and
radiographically stable, patients were then treated with TMZ every 4 weeks
(single daily dose 200mg/m2 for 5 consecutive days) for 6 months.
·
In
patients in the treatment group who had undergone surgical resection survival
was 18.3mo (vs 14.2mo with surgery + XRT only)
·
An analysis of a secondary endpoint
of the EORTC/NCIC trial, that is, health-related quality of life, revealed no
negative effect on this endpoint with the addition of TMZ to radiotherapy
·
In patients with a methylated MGMT promoter median
survival was 21.7mos for patients treated with TMZ (compared with 15.3 months
without TMZ). Notably, in patients with unmethylated MGMT promoter, no
difference was seen between those treated with TMZ and those treated with
radiotherapy only (median survival 12.7 compared with 11.8 months).
·
Prolonged TMZ dosing depletes MGMT
by suicide inactivation, and will probably enter trials this year.
·
Trials using O6-benzylguanine have
found myelosuppression to be dose-limiting, and consequently, tolerable doses
of TMZ (or BCNU) have been considerably less than those achieved without
concurrent O6-benzylguanine administration.
o
16%
grade 3-4 hematologic toxicity.
o
Patients
given PCP prophylaxis (eg Bactrim)
·
Bevacizumab (Avastin) is monoclonal antibody VEGF-inhibitor
which is being studied as a second-line agent for GBM (Narayana A JN1/09).
o
Avastin
is being studied in combination with Irinotecan (CPT-11) (Vredenburgh JJ
JClinOncol 2007 & ClinCancerRes 2007)
·
No
agents other than Temodar has been shown to increase
MS significantly. Metaanalysis for all agents showed 2mo increase in MS,
increased 6mo survival. (Stewart LA Lancet 02)
·
BCNU:
o
Has
generally been replaced by temozolomide. No increase in MS; 1 year survival
increased by 15%; Progression during XRT predictive of BCNU failure.
·
Gliadel: BCNU biodegradable
wafers
o
Placed
in resection cavity. May be covered with
Surgicel (or similar product)
o
Exclusion:
bilateral tumor.
o
Initial
and recurrent: increases MS by 2mos (significant for GBM only when adjusted for
other factors.), KPS decline delayed, 11 of 13 long-term survivors (Brem Lancet 95, Valtonen S
N97, Westphal M NO4/03).
o
Subsequent analysis that excluded a
small population of anaplastic gliomas in which histological features of GBM
were absent resulted in no difference in survival
o
CSF
leak 5% (vs 1% with placebo wafer)
o
May
mimic abscess on postop MRIs.
o
Reimplantation
at subsequent surgery possible.
o
No
contraindications to systemic chemotherapy after Gliadel.
o
Communication
with CSF is not a contraindication.
o
Only
approved for up to 8 wafers.
o
May
exclude patient from clinical trials.
o
Has
also been used for aggressive recurrent pituitary adenomas and
craniopharyngiomas (Laws
ER N8/03)
o
MS
21mos for newly diagnosed GTR + Gliadel + XRT + Temodar – McGirt
MJ JN3/09 (retrospective)
·
PCV: Initial report showed benefit in AA (LevinVA 90), not confirmed by
RPT (MRCBTWP JCO
01)
Experimental
Treatment
·
Tyrosine Kinase Inhibitors: Only 10-20% of patients with GBMs respond to
Tarceva (erlotinib) or Iressa (gefitinib), both of which are EGFR inhibitors.
o
There
seems to be no correlation between a patient's response to the drugs and the
function of EGFR. However GBMs that produced both EGFRvIII and PTEN were 51
times more likely to respond and patients had five times longer (243 days
versus 50 days) time-to-progression. (Mischel et al NEJM 11/10/05)
·
IL13-PE38QQR (Neopharma) is IL13 conjugated to
Pseudomonas Exotoxin and is delivered via Convection Enhanced Delivery (CED)
o
IL13
receptors are present in appreciable numbers on malignant glioma cells, but
only to a minimal amount if at all on healthy brain cells.
o
Catheters are implanted in the brain
surrounding the resected tumor cavity
o
45
recurrent GBM patients treated post-tumor resection in the Phase I/II studies
had an overall median survival of 44.0 weeks (95% CI: 36.1-52.4) including 42%
of patients with less than 2 adequately positioned catheters, while patients
with greater than or equal to 2 catheters adequately positioned surviving with
a median of 51.7 weeks (95% CI: 36.1-78.0). Separately, 1-year and 2-year
survival rates for recurrent GBM patients were 40% and 20% respectively.
o
It
is now in Phase III trial, PRECISE
Recurrence
·
Re-resection done if
feasible and (generally) KPS >70; MS 9mos.
·
High quality survival after reop: AA 21mos, GBM 2.5mos.
·
Recurrence
vs. tumor necrosis: Evaluate with PET (or SPECT), biopsy if necessary
Prognosis
·
AA:
MS 2-3yrs
·
Factors:
Age, KPS, Extent of resection.
·
Survival
(GR 3 & 4): XRT only=9.5mo; XRT+BCNU=11mo (avg. BTSG RTOG-ETOG)
·
Glioma
Outcomes Project (Laws ER JN9/03): 41wks.
·
Survival
of primary vs secondary GBM controversial.
·
FDG-PET:
inc glu 5mo, dec glu 19mo survival
·
PET
better indicator than histology?
·
CBF
not significant
·
P53
effect equivocal. MIB-1 less clear than in LGAs.
·
RTOG
93: Age (<>50yo), histology, KPS, mental status, duration of symptoms
(<> 3mo), extent of resection, neurologic function, RT dose
(<>54Gy)
·
10%
have LOH 1p – better prognosis
·
10-25%
incidence CSF seeding
·
10yr
survival 0.5% (
·
Long-term
survivors had higher p53, lower EGFR and MIB-1
Giant
cell Glioblastoma
·
Giant
cells: not dividing, are nonmalignant
·
Slightly
better prognosis. Reports of cure exist with lobectomy & XRT.
Gliosarcoma
·
2%
of GBM. AKA Feigin tumor
·
Superficial,
dural invasion
·
Firm,
circumscribed
·
Fasicles
of spindle cell sarcoma
·
30%
metastasize
·
Sarcoma
comes from vessels, meningeal fibroblasts
|
|
Pilocytic
Astrocytoma
Histology
·
Biphasic
– composed of 2 cell types:
o
1)
compact bipolar cells with Rosenthal fibers (intracytoplasmic composed
of Žßcrystalin, bright blue on Luxol fast blue, may be absent )
o
2)
loose multipolar cells with microcysts and eosinophilic granular bodies
(also seen in PXAs)
·
Hyalinized
Vessels. Occasional oligodendroglial-like cells, plump “protoplasmic” cells.
Often calcify.
·
Necrosis,
vascular proliferation, occasional mitoses are not indicative of malignancy
- should be considered “anaplastic
pilocytic astrocytoma”
·
Rarely
undergo malignant transformation (most had undergone previous XRT) but
prognosis better
·
Can
invade subarachnoid space - no prognostic significance, although some
disseminate
·
No
identifying markers
·
64%
infiltrate surrounding brain
·
Unclear
if there is a “diffuse” variant
·
Winston A: microcysts, Rosenthal, oligodendro- glioma
foci (94% 10ys) = “juvenile variant”
·
Winston B: pseudorosettes, inc cellularity, mitosis,
calcification, no cysts (29% 10ys) = “Adult variant”
·
Pilomyxoid Astrocytoma : Hypothalamic/chiasmatic, 2mo to 7yo
(mean 18mo), monomorphous piloid cells in myxoid background, angiocentric
(perivascular clustering) not biphasic, no Rosenthal fibers, more mitoses,
myxoid, more likely to recur or CSF seed
·
Genetics: do not have same genetic changes as diffuse
LGA (i.e. p53 mutations are rare)
Clinical
·
Age:
cerebellar 10yrs, cerebral 22yrs
·
Can
occur in any age (70 yos)
·
Seizures
uncommon (compared to LGA)
Radiology
·
Cyst
wall: nonenhancing 10% had tumor by Bx, enhancing 70% had tumor
·
46%
cystic non-enhanced, 21% cystic enhanced, 17% solid, 16% false cyst (vs Lee 89
- all enhance; KL - 90% enhance)
Locations
·
Cerebellar: 70% vermis, 30%
hemispheric
·
Cerebral hemispheres: May dedifferentiate,
more malignant, adults more common, uncircumscribed, worse prognosis
·
Hypothalamic/optic: Propensity for CSF seeding; posterior
= more malignant. 20% will have NF-1, must rule out
·
Brainstem
Treatment
·
Primary
treatment is surgical
·
GTR:
No XRT; serial MRIs for 10 yrs
·
STR:
XRT controversial (most studies show no benefit). Various chemo regimens used
(most studies mixed with LGA)
·
SRS:
Used in small series, all pts stabilized
Prognosis
·
100%
survival after GTR. STR 80% 20ys.
·
Stability
may be maintained for decades - natural history unclear
·
>8
reported cases of regression, can alternate between
progression and regression. Tumors may regress after partial resection.
Recurrence
·
Cerebellar:
5% GTR, 30% STR
·
All
locations: 25% GTR, 80% STR
·
Recurrence
can occur 4mo to 45yrs after GTR (mean 4yr)
Optic
Glioma
·
Most
are pilocytic, but range up to GBM
·
More
common in children
·
May
involve one or both optic nerves and/or chiasm
·
Sporadic
or with NF1
·
Proptosis,
visual deficits (occur later than optic meningiomas)
·
Treatment
o
One
optic nerve with visual loss: transcranial resection of nerve from orbit to
chiasm
o
Chiasm:
biopsy, partial resection if exophytic; XRT. SRS has been used (JN1/05S)
o
Some
follow with NF1 until visual deterioration develops, and obtain tissue for
non-NF1 cases
|
|
Pleomorphic
Xanthoastrocytoma
Clinical
·
Peak
7-25yrs (range 3-62yrs)
Histology
·
WHO
Grade II
·
Pleomorphic
lipidized GFAP (+) cells with reticulin basement membrane, lymphocytic
infiltrates, multinucleated cells & eosinophilic granular bodies
·
“PXA with anaplastic features” (Grade
III): Rare. Mitoses (>5/10HPF) and/or necrosis (Note PXA with necrosis is
not considered GBM )
·
Postulated
that they arise from subpial astrocytes
·
Some
synaptophysin (+) and some are GFAP (-); 15 reported cases of composite
PXA/Ganglioglioma
·
Epithelial
and angiomatous variants
·
MIB-1
usually <1%
·
p53
mutations in only 25% (vs LGA) no consistent mutations
Imaging