TUMORS NEW Flashcards
OLD CLASSIFICATION OF CNS TUMORS
OLD CLASSIFICATION OF CNS TUMORS
OLD CLASSIFICATION OF CNS TUMORS
OLD CLASSIFICATION OF CNS TUMORS
The glioblastomas are largely defined by the features of
________ and _______of nonneural elements such as
vascular proliferation and are set apart from anaplastic
astrocytomas on the basis not only of their histology but
also by a later age of onset than astrocytoma and a more
rapid course.
necrosis and anaplasia
For many years, thinking about the pathogenesis ofprimary CNS tumors was dominated by the _________________of Bailey and Cushing, which was based on the
assumed embryology of nerve and glia cells.
histogenetic theory
One prominent theory was that most tumors arise from neoplastic transformation of mature adult cells ________
dedifef rentiation
In fact, the cells of origin of the major types of brain
tumors have not been unequivocally identified or, in many
cases, they appear to arise from_____________
that reside in the brain
pluripotential stem cells
Medulloblastomas, polar spongioblastomas,
optic nerve gliomas, and pinealomas occur mainly
before the age of ________years, and meningiomas and glioblastomas are most frequent in the _______decade of life.
20
sixth
The _________associated with neurofibromatosis and
tuberous sclerosis and the cerebellar hemangioblastomas
of _________are the best examples of a genetic
determinant
gliomas
von Hippel-Lindau
The rare familial disorders of multiple endocrine
neoplasia and multiple hamartomas are associatedwith an increased incidence of ________ and ________respectively
anterior pituitary tumors
and meningiomas,
Because of this capacity to transform the cellular genome, the virus product is called an________
oncogene;
Because of this capacity to transform the cellular genome, the virus product is called an_________
oncogene;
More recently, single nucleotide polymorphisms
have been identified that in combination predispose to
certain childhood tumors such as _________, or to
the more aggressive forms of various tumors
neuroblastoma
over 50 percent of astrocytomas have deletions within this gene
tumor suppressor gene p53 on chromosome 17p;
mutations in the genes that code for __________are common in gliomas and oligodendrogliomas
and their presence relates to less tumor progression.
isocitrate dehydrogenase(IDH1
and 2)
oligodendrogliomas that have combined deletions in
___________respond well to chemotherapy
and this property increases survival
chromosomes 1p and 19q
various changes such as the amplification of the
__________oncogene has been associated with an aggressive clinical course and poor outcome in neuroblastoma and
medulloblastoma.
MYCN
approximately 50 percent of gliomas there is an overexpression or a mutant form of________ and ____________ suggesting a role for these in the progression of certain tumor types.
epidermal growth factor receptor (EGFR) and of plateletderived transforming growth factor receptor (PDGFR),
These high-grade gliomas account for approximately 20
percent of all intracranial tumors and for more than 80
percent of gliomas of the cerebral hemispheres in adults
GBM and Anaplastic Astrocytoma
The peak incidence is in middle adult life (mean age for
the occurrence of glioblastoma is approximately ______years, and ________years for anaplastic astrocytoma
60
46
In GBM,
Extraneural metastases, involving ___________, are very
rare; usually they occur only after a craniotomy
bone and lymph nodes
Approximately _______percent of glioblastomas
occupy more than one lobe of a hemisphere; between
_______percent show multicentric foci of growth and
thereby simulate metastatic cancer.
50
3 and 6
Gross appearance of GBM
The tumor has a variegated appearance, being a
mottled gray, red, orange, or brown, depending on the
degree of necrosis and presence of hemorrhage, recent or
old.
The characteristic histologic findings of glioblastomaare ___________, ____________ and ______________; identifiable astrocytes with fibrils in
combination with primitive forms in many cases; tumor
giant cells and cells in mitosis; hyperplasia of endothelial
cells of small vessels; and necrosis, hemorrhage, and
thrombosis of vessels.
hypercellularity with pleomorphism of cells
and nuclear atypia
This __________distinguishes
glioblastoma from the anaplastic astrocytomas,
which show frequent mitoses and atypical cytogenic
features but no grossly necrotic or hemorrhagic areas
variegated appearance
In GBM,
The vasculature and fibroblasts
can undergo a sarcomatous transformation giving the
tumor a mixed appearance that is termed______
gliosarcoma
The natural history of untreated glioblastoma is well
characterized. Fewer than _______percent of patients survive for 1 year after the onset of symptoms and only about ________percent live beyond 2 years
20
10
In GBM , Age is an important prognostic factor; fewer than_________ percent of patients older than age 60 years survive for 18 months, in comparison to two-thirds of patients younger than age ________years
10
40
Survival with anaplastic astrocytoma is somewhat better,
typically________
3 to 5 years
In pts with GBM who have Sz,
Serious skin reactions (erythema multiforme
and Stevens-Johnson syndrome) may occur in patients
receiving _______at the same time as cranial radiation
phenytoin
In GBM,
Cranial irradiation to a total dose of
__________increases survival by 5 months on average
6,000 cGy
In pts with GBM,
It had been considered for several decades that the
addition of chemotherapeutic nitrosourea agents such
as ______ and _________increase
survival slightly
carmustine (BCNU) or lomustine (CCNU)
The methylating agent ________given in the
form of an orally administered prodrug, has lower toxicity
and has been shown in several trials to produce slightly
superior vs other chemo agents in treating GBM
temozolomide,
In a large trial conducted by Stupp and colleagues, the median survival was 14.6 months with radiation and temozolomide, compared to 12.1 months with radiation alone, but 2-year survival was more than doubled from____________
10 to 27 percent
How to administer TMZ
The
drug is administered daily (75 mg/m2) concurrently with
radiotherapy and, after a hiatus of 4 weeks, given for 5 d
every 28 d for 6 cycles.
Main complications of TMZ
Its main complications are thrombocytopenia
or leukopenia in 5 to 10 percent of patients, and
rare cases of Pneumocystis carinii pneumonia
In GBM, Hegi and colleagues found a relationship between the epigenetic silencing of the promoter of this gene _________ and the response to temozolomide.
(“methylation status”)
In GBM
there may be an interaction
between MGMT methylation and mutations in other
genes such as_________
IDH1
In the Tx of GBM,
Tyrosine kinase inhibitors (_______ and ______) have
been developed in response to the upregulation of EGFR
erlotinib, gefitinib
Almost all glioblastomas recur within ________of their original site and _______ percent develop additional lesions at distant locations.
2 cm
10
In pts with recurrent GBM,
Reoperation is sometimes undertaken for local recurrences. The most aggressive approach-a second surgery and chemotherapy-can prove effective and has been generally used in patients younger than age __________years
whose original operation was many months earlier.
40
A promising approach for recurrent malignant
gliomas is the use of drugs that target the tumor’s
vasculature. Antiangiogenic agents such as_____
a VEGF inhibitor, sometimes given in combination with
chemotherapy, may delay progression and greatly reduce
cerebral edema, therefore diminishing the requirement
for corticosteroids, but also do not________
bevacizumab,
prolong survival
A recent but preliminary provocative observation from retrospective series has been that patients with glioblastoma receiving _______, ostensibly for concurrent CMV infections, had better survival than those who did not
receive the drug
valganciclovir
The lower-grade astrocytomas (grade II in the WHO classification),which constitute between ________percent
of cerebral gliomas, may occur anywhere in the brain or
spinal cord
25 and 30
Favored sites for anaplastic astrocytoma
cerebrum, cerebellum, hypothalamus, optic nerve
and chiasm, and pons
Astrocytomas of the _______arise mainly in adults in their third and fourth decades or earlier;
astrocytomas in other parts of the nervous system, particularly the______ and _____, are more frequent in children and adolescents.
cerebral hemispheres
posterior fossa and optic nerves
Histologic classification of astrocytoma
_______or fibrillary;
_______(enlarged cells distended with hyaline and eosinophilic material);
_______ (elongated, bipolar cells);
and mixed astrocytomaoligodendroglioma
types.
protoplasmic
gemistocytic
pilocytic
In astrocytoma, The most common type is
composed of well-differentiated fibrillary astrocytes. The
tumor cells contain ______________,
which is a useful diagnostic marker in biopsy specimens
glial fibrillary acidic protein (GFAP)
Cerebral astrocytoma is a slowly growing tumor of
infiltrative character with a tendency in some cases to
form_______ or _________
large cavities or pseudocysts
It may not be possible on clinical or imaging grounds
to distinguish low-grade gliomas from a number of raretumors in childhood such as the______
dysembryoplastic neuroepithelioma (DNET)
In about two-thirds of patients with astrocytoma, the first symptom is a _________, and between 60 and 75 percent of patients have recurrent seizures in the course of their illness
focal or generalized seizure
___________types are sharply demarcated, with smooth borders and little edema. On Tl-weighted MRl, they are isointense or hypointense; on T2 sequences, hyperintense, and there tends to be marked enhancement of the nodular solid portion of the tumor after gadolinium infusion
Pilocytic
Treatment of ow grade astrocytoma
removing accessible tumors when they are discovered,
and another, of observing the patient by sequential
imaging to determine if the tumor has transformed into
a more aggressive mode
Most important aspect in treating cerebral astocytoma to prevent recurrency
resection
of the tumor nodule is of singular importance in
delaying or preventing a recurrence
Natural Hx of LGG
The natural history of the low-grade gliomas is to
grow slowly and eventually undergo malignant transformation
In LGG, An extensive randomized trial of early radiotherapy in adults demonstrated that median progression-free survival was extended to __________ years by early treatment in comparison to 3.4 years for
observation only and radiation treatment that was initiated
when signs of progression occurred, but that overall
survival was unaffected, averaging just over________ years in
both groups
5.3
7
In this variant of high-grade glioma there is a diffuse
infiltration of neoplastic glial cells, involving much of one
or both cerebral hemispheres with sparing of neuronal
elements but without a discrete tumor mass
G l i o m atos i s C e re b ri
If there is a syndrome that can be associated early on with
gliomatosis, in our experience it has been a nondescript
_____________sometimes mistaken
for depression or a subacute dementia, or pseudobulbar
palsy may be the first manifestation.
frontal lobe behavioral syndrome
What differentiates PCNSL from Gliomatosis on MRI?
Contrast enhancement is scant, differentiating the tumor from cerebral lymphoma, which otherwise may have a similar appearance
Peak age of ODG
most often in the third
and fourth decades, with an earlier peak at 6 to 12 years.
It is relatively infrequent,
Gross appearance of ODG
pink-gray color and multilobular form, its relative avascularity and firmness (slightly tougher than surrounding brain), and its tendency to encapsulate and form calcium and small cysts.
Most oligodendrogliomas, however, are grossly indistinguishable from other gliomas, and a proportion-up to half in some series-are mixed oligoastroet;tomas, suggesting that the precursor cell is________
pluripotential
In ODG
By extending to the pial surface
or ependymal wall, the tumor may metastasize distantly
in ventricular and subarachnoid spaces, accounting for
________percent of the series of gliomas with meningeal dissemination
11
Imaging of ODG
The appearance on imaging studies is variable, but
the most typical is a hypodense (on CT) or T2 hyperintense
(on MRI) heterogenous mass near the cortical surface with
relatively well-defined borders
In ODG
loss of certain
alleles on chromosome ______has been predictive of a high degree of responsiveness to the below-described PCV chemotherapy regimen, and a similar loss on chromosome _____________ has been associated with longer survival
1p
19q
__________has been the conventional treatment for oligodendroglioma
Surgical excision followed by radiation
therapy
T or F
Well-differentiated oligodendrogliomas should
probably not receive radiation if seizures are well controlled
and there are no neurologic deficits
T
In ODG
loss of regions on ________, median survival was over 10 years.
Mutations in _________also appear to confer survival benefit. Mixed oligodendrogliomas and astrocytomas should generally be treated like astrocytomas, but temozolomide probably suffice to treat both components
1p
IDH1
There is also a __________type of ependymoma,
localized exclusively in the filum terminale of the
spinal cord
myxopapillomatous
this is the most common glioma of the spinal cord
ependymoma
MC sites for IC ependyoma
The most common cerebral site is the fourth ventricle;
less often they occur in the lateral or third ventricles
In ependymo,a, The
tumor cells tend to form rosettes with central lumens or,
more often, circular arrangements around blood vessels
pseudorosettes
T or F,
the postoperative survival of ependymoma is
poor
T
Tx of ependymoma
Surgical removal is supplemented by radiation therapy, particularly to address the high rate of seeding of the ventricles and spinal axis
Meningiomas represent approximately 15 percent
of all primary intracranial tumors; they are more common
in women than in men (2: 1) and have their highest
incidence in the _______ and _______decades of life
sixth and seventh
The most frequent acquired genetic defects of meningiomas are truncating (inactivating) mutations in the
_________on chromosome_______
neurofibromatosis 2 gene (merlin)
Chromosome abberations associated with meningioma
1p, 6q, 9p, 10q, 14q, and 18q
Meningiomas
also elaborate a variety of soluble proteins, some of which
__________are angiogenic and probably relate to both the
highly vascularized nature of these tumors and their
prominent surrounding edema
(VEGF)
The cells of meningiomas are relatively uniform,
with round or elongated nuclei, visible cytoplasmic
membrane, and a characteristic tendency to encircle one
another, forming whorls and _________(laminated
calcific concretions).
psammoma bodies
EM characteristics of Meningioma
formation of very complex interdigitations
between cells and the presence of desmosomes
MC form of meningioma
Currently neuropathologists recognize
a meningothelial (syncytial) form as being the most common.
Characteristic of Meningioma on Angiography
These changes
are reflected by homogeneous contrast enhancement and
by “tumor blush” on angiography
Most difficult to remove Meningioma
Tumors that lie beneath the hypothalamus, along the medial part of the sphenmd bone and parasellar region, or anterior to the brtem e the most difficult to remove surgically.
In PCNSL
There is a preponderance of men, with the peak incidence
m the _________decades of life, or in the third
and fourth decades in patients with______
fifth through seventh
AIDS.
Cells of origin of PCNSL
lymphocytes and lymphoblasts
In PCNSL,
The B lymphocyte or
lymphoblast is the tumor cell, whereas the_____
and _________are secondary interstitial reactions
fine reticulum
“microgliacytes”
Location of PCNSL
with _______percent being the cerebral hemispheres;
they may be solitary or multifocal.
A periventricular localization is common.
Vitreous, uveal, and retinal (ocular) involvement occurs in__________ percent of cases;
60
10 to 20
The pia and arachnoid may be infiltrated, and a
purely meningeal form of B-cell lymphoma that involves
peripheral and cranial nerves.
It presents
with painful, predominantly motor polyradiculopathies.
neurolymphomatosis
PCNSL forms a pinkish gray; soft, ill-defined,
infiltrative mass in the brain, difficult at times to distinguish
from an_______
astrocytoma
Several of our cases of meningeal and cranial nerve
lymphoma with similar histologic characteristics to primary
CNS lymphoma were complications of chronic lymphatic
leukemia, a type of so-called_________
Richter transformation
In PCNSL,
The immunohistochemical demonstration
in CSF of monoclonal lymphocytes or an elevated betamicroglobulin points to____
leptomeningeal spread of the
tumor
In PCNSL,
the median survival of patients
treated in this way has been _____months and less in those with AIDS and in individuals who are otherwise immunocompromised.
10 to 18
Tx of PCNSL
Glass and colleagues (1994) recommended a treatment
regimen consisting of several cycles of intravenous
methotrexate (3.5 g/m2) and citrovorum, administered at
2- to 3-week intervals and at times continued indefinitely
if the treatment is tolerated
T OR F
IN PCNSL
Cranial irradiation is not
typically part of the initial treatment
T
Ocular lymphoma
is eradicated only by_____
radiation therapy
Cancers of the ______ and ______are exceptional in
that they have a somewhat higher tendency than
this to spread to the posterior fossa
pelvis and colon
Metastases to the skull and dura occur with any tumor that metastasizes to bone, but they are particularly common with carcinoma of the ______,_______ and ______
breast and prostate and in the special case of multiple myeloma
MC brain mets tumors
Lung, Breast, MM, colon/rectum/kidney
The metastatic tumors most likely to be single come from
1.
2.
3.
4.
kidney, breast, thyroid, and adenocarcinoma of the lung
____ and ________more often tend to
be multiple,
Small cell carcinomas and melanomas
Metastases from________ and _________
are often hemorrhagic, but some from the lung, thyroid,
and kidney exhibit this characteristic as well
melanoma and chorioepithelioma
The relative frequency of _____makes it the most
common metastatic tumor to bleed, even though only a
small proportion does so
lung cancer
CT, with and without contrast, will detect practically all sizable (_______) metastases though MRI is more sensitive especially for cerebellar and subcentimeter lesions, and will expose associated leptomeningeal
disease.
1 cm
In the Tx of Brain Mets
One randomized trial comparing stereotactic radiotherapy
alone, or combined with whole-brain radiationfor 1 to 4 metastases, found ______
no difference in survival
but there was a reduction in the frequency of recurrence
at other sites in the brain when whole-brain treatment
was added
In Brain Mets
Prophylactic radiation prolonged survival by
_______and reduced the later emergence of metastasis
to the brain.
1.5 months
In patients with a single parenchymatous metastasis
(shown to be solitary by gadolinium-enhanced MRI),
surgical extirpation may be undertaken provided that:
- growth of the primary tumor and its systemic metastases
is under good control and the
- metastasis is accessible to the surgeon and
- not located in a strategic motor or
language area of the brain
The average period of survival
in cases of brain metastases, even with therapy, is about
_______, but it varies widely and is dominated by the
extent of other systemic metastases.
Between__________ percent of patients live for a year and ________percent for 2 years
6 months
15 and 30
5 to 10
What are the radiosensitive tumors?
lymphoma,
testicular carcinoma, choriocarcinoma, some breast cancers
What is this?
Widespread dissemination o f tumor cells throughout
the meninges and ventricles, a special form of metastatic
cancer, is the pattern in approximately 5 percent of cases
of adenocarcinoma of breast, lung, and gastrointestinal
tract, melanoma, childhood leukemia, and systemic lymphoma.
Ca rci n o m ato u s M e n i n g it i s
Also known is a rare ____________of the meninges that acts in a similar way to carcinomatous
meningitis but has the striking feature of bloody CSF
(1,000 to 10,000 red blood cells per mm3) .
primary malignant melanoma
Tx of Carcinomatous meningitis
This consists of radiation therapy to the symptomatic areas (cranium, posterior fossa, or spine) followed in selected cases by the intraventricular administration of methotrexate
How to give IT MTX in Carcinomatous Meningitis
The
methotrexate is administered into the lateral ventricle via
an Ommaya reservoir (12 mg diluted in preservative-free
saline) or into the lumbar subarachnoid space through a
lumbar puncture needle (12 to 15 mg)
