Intracranial Neoplasms and Paraneoplastic Disorders Flashcards
Germ Cell Tumors (6)
Germinoma Embryonal Carcinoma Yolk Sac Tumor (Endodermal Sinus Tumor) Choriocarcinoma Teratoma Mixed Germ Cell Tumors
Most common forms of glioma
astrocytic tumors
Grading represent a spectrum in terms of growth potential
degree of nuclear atypia
cellularity mitoses
vascular proliferation
features of glioblastomas (2)
necrosis and anaplasia of nonneural elements
subdivision of ependymomas (4)
2C
2M
cellular
myxopapillary
clear cell
mixed types
classifications of meningiomas (4)
based on cytoarchitecture and genetic origin
MFAM
meningothelial or syncitial
fibroblastic
angioblastic
malignant
histology: hypercellularity with pleomorphism of cells and nuclear atypia
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
GBM
variegated appearance distinguish GBM from anaplastic astrocytoma
Genetic Changes in GBM for
- old pts
- young
- amplification of the EGFR gene
2. mutations of the p53 gene
True of False
progression of astrocytomas and oligodendrogliomas to more malignant forms has been related to the enzyme isocitrate degydrogenase , encoded by genes IDH1 and IDH2
True
p645
presence of mutations in the genes that code for IDH 1 and 2 relates to less tumor progression and better outcomes
natural history in GBM
<20% survive one year after onset of symptoms
10% live beyond 2 years
survival with anaplastic astrocytoma in years
3-5 years
cranial irradiationto a total dose of 6000cGy increases survival by ___ months
% months
Stupp trial temozolomide
median survival of 14.6 months with radiation and tmz
12.1 months with radiation
2 year survival 10 to 27%
drug is administered daily 75mg/m2 concurrently with RT and after a hiatus of 4 weeks given 5 d every 28 d for 6 cycles
complications of TMZ
thrombocytopenia and leukopenia in 5 to 10% of patients
rare cases of pneumocystis carinii
response to TMZ if with high levels of methyltransferase protein (MGMT)
resistant to chemo
True or False
Almost all GBM recur within 2cm of their original site and 10 percent develop additional lesions at distant locations
True
Antiangiogenic agents, VEGF inhibitor, sometimes given in combination to chemo may delay progression and greaty reduce cerebral edema
bevacizumab
Median survival for anaplastic astrocytoma
2-5 years or longer
histologic classifications of astrocytoma (4)
- protoplasmic/ fibrillary
- gemistocytic (enlarged cells distended with hyaline and eosinophilic material)
- pilocytic (elongated bipolar cells)
- mixed astrocytoma-oligodendroglioma
T/F
cerebral astrocytoma is a slowly growing tumor of infitrative character with a tendency in some cases to form large cavities or pseudocysts
True
T/F
fine granules of calcium may be deposited in parts of the tumor, but calcium in a slow-growing intracerebral tumor is more characteristic of an oligodendroglioma
True
survival rate after excision of cystic astrocytoma of cerebellum
5 yera survival of greater than 90%
outcome is less assured when the tumor involves the brainstem
prognosis of low grade supratentorial tumors
10 year survival after operation was from 11-40% if with 5,300cGy given postopt
high grade glioma, 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
Gliomatosis cerebri
True or False
Imaging gliomatosis cerebri
contrast enhancement is scant
true
constitute 5 to 7 % of intracranial gliomas
derived from oligodendrocytes or their precursor cells
may occur at any age, most often 30-40
earlier peak at 6-12 yrs
Oligodendroglioma
pink gray color, multilobar relatively avascular and firm (tougher than surrounding brain)
tendency to encapsulate and form calcium and small cysts
Oligodendroglioma
most common site for oligodendroglioma, often deep in white matter with one or more streaks of calcium but little or no surrounding edema
frontal and temporal lobes 40-70 %
intratumoral calcification can be seen in more than half of theses cases
oligodendroglioma
differentials for oligodendroglioma with calcification seen on scan but with the context of seizures
AVM or low grade astrocytoma
oligodendroglioma
loss of certain alleles on chromosome ____ has been predictive of a high degree of responsiveness to _____ chemo regimen
similar loss of chromosome ____ has been associated with longer survival
chrom 1p - responsive to chemo
PCV procarbazine, cyclophosphamide, vincristine)
chrom 19q - with longer survival
type of ependymoma localized exclusively in the filum terminale
myxopapillomatous
Most common glioma of spinal cord
ependymoma
most common cerebral site for ependymoma
4th ventricle
grayish, pink, firm, cauliflower-like growths
in the cerebrum (lateral ventricle) reddish gray, softer and more clearlyd emarcated
originates from the dura mater or arachnoid
meningioma
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 psammoma bodies
*notable electron microscope characteristic - formation of very complex interdigitations between cells and the presence of desmosomes
most common type of meningioma
meningothelial or syncytial
Most common locations of meningiomas
dural folds
frontoparietal parasagittal convexities, falx, tentorium cerebelli, sphenoid wings, olfactory groove, tuberculum sellae
90% are supratentorial
Grading of astrocytoma tumors
Grade I: pilocytic astrocytoma, pleomorphic xanthoastrocytomas, subependymal giant cell astrocytomas
Well-differentiated astrocytoma Grade II
Anaplastic Astrocytoma Grade III
GBM Grade IV
astrocytoma associated with Tuberous sclrerosis
subependymal giant cell astrocytomas
choroid plexus tumors divided into two classes
papillomas and carcinomas
50% of astrocytomas have deletions within this gene
tumor suppressor gene p53
After development of astrocytoma, progression to a more malignant grade may be triggered by defects in the: (3)
p16-retinoblastoma gene signaling pathway
Loss of chromosome 10 (90% of high-grade glioma)
over expression of Epidermal Growth Factor gene
T/F
Oligodendrogliomas that have combined deletions in
chromosomes 1p and 19q respond well to chemotherapy
and this property increases survival.
True
p645
Which of the ffg means good survival/less tumor progression
a. mutations in the genes that code for IDH 1 and 2 in gliomas and oligodendrogliomas
b. combined deletions in chrom 1p and 19q in oligodendrogliomas
c. amplifications of MYCN gene
d. A and B
e. B and C
D. A and B
amplification of MYCN oncogene - aggressive course, poor outcome in neuroblastoma and medulloblastoma
p645
VEGF is found in extremely high concentrations in
Meningiomas
Imaging findings of vasogenic vs cytotoxic edema
both cytotoxic and vasogenic
decreased attenuation on CT
hyperintensity on T2 MRI
cytotoxic : reduced diffusivity on DWI (increased anisotropy)
vasogenic: elevated diffusivity (reduced anisotropy)
dosing of Mannitol 25% solution
- 5 to 1.0g/kg over a period of 2 to 10 mins
* hyeprtonic saline are equally effective, 3,7, 23 %
characteristics of headache in brain tumor
slight, dull, episodic
dull or sharp, intermittent
nocturnal occurrence, presence on first awakening, deep, nonpulsatile quality
BUT these are not specific
Convulsions have of been observed in ___ to ____% of all patients with cerebral tumors
20-50%
T/F
A first seizure during adulthood is always suggestive of brain tumor and, in the authors’ experience, has been the most common initial manifestation of primary and metastatic neoplasm.
True
p649
T/F
In high grade gliomas
Malignant cells carried in the CSF may rarely form distant foci on spinal roots or cause a widespread meningeal gliomatosis.
True
p.650
T/F
In high grade gliomas
Extraneural metastases involving the bone and lymph nodes are common.
False
very rare
p650
How many percent of GBM
occupy more than one lobe of a hemisphere?
show multicentric foci of growth, simulating metastases
occupy more than one lobe of a hemisphere - 50%
show multicentric foci of growth, simulating metastases - 3-6%
Management in GBM
feasible resection, combined with chemo and RT
chemo - carmustine or lomustine increase survival slightly
cisplatin, carboplatin
-GMT group: clear but small benefit of chemo
tyrosine kinase inhibitors for GBM
erlotinib, gefitinib
Survival in GBM with
aggressive surgical removal and radiotherapy
no treatment
aggressive surgical removal and radiotherapy - 12 months
no treatment - 7-9 months
how many percent of patients with astrocytoma present with seizures
70%
2/3
imaging pilocytic vs fibrillary astrocytoma
pilocytic
T1 - iso, hypointense,
T2 - hyperintense
sharply demarcated with smooth borders,marked enhancement of nodular solid
Fibrillary
T1 - hypointense
T2 - hyperintense
less well-defined borders and little or no contrast enhancement
T/F
The natural history of the low-grade gliomas is to
grow slowly and eventually undergo malignant transformation.
True
p653
Low and Intermediate Grade Astrocytome
A number of studies have come to the conclusion
that delaying radiation in younger patients may
avoid the consequences of
dementia
hypopituitarism
T/F
Prognosis in Gliomatosis cerebri is good.
The prognosis is variable but generally poor, measured in months to a few years from the time of diagnosis.
T/F
Some of the oligodendrocytes have intense immunoreactivity to GFAP.
True
p654
accounts for 11% of the series of gliomas, that may metastasize distantly in ventricular and subarachnoid spaces when the tumor extends to the pial surface of ependymal wall
Oligodendroglioma
characteristics of anaplastic ependymoma
high mitotic activity
endothelial proliferation
nuclear atypia
necrosis
imaging characteristic of ependymoma
heterogenous hyperdense mass with fairly uniform contrast enhancement
calcification and some degree of cystic changes are common in supratentorial tumors
T/F
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 sixth and seventh decades of life. Some
are familial.
True
p656
most frequent acquired genetic defects of meningiomas are truncating (inactivating) mutations in the
neurofibromatosis 2 gene (merlin) on chrom 22q
imaging findings meningioma
ready visualization with contrast-enhanced CT and MRl
which reveal their tendency to calcify as well as their prominent vascularity
preponderance in Men peak- 5th thru 7th decade 3rd of 4th decade in patients with AIDS origin: lymphocytes (diffuse large cell type) tumor cells: B lymphocytes
CNS lymphoma
T/F CNS lymphoma
- may arise in any part of cerebrum, cerebellum, brainstem
- may be solitary or multifocal
- commonly periventricular in location
- 2/3 of patients with ocular lymphoma will have cerebral involvement in a year
T 1. may arise in any part of cerebrum, cerebellum, brainstem - 60% cerebral
T 2. may be solitary or multifocal
T 3. commonly periventricular in location
T 4. 2/3 of patients with ocular lymphoma will have cerebral involvement in a year
T/F
CNS lymphoma has a high tendency to developing necrosis.
False
p659
imaging findings for CNS lymphoma
one or several dense (hypercellular), homogeneous, enhancing, infiltrating, nonnecrotic, nonhemorrhagic, periventricular masses is characteristic
T/F
Diagnosis of CNS lymphoma is possible with CSF examination.
false
p659
Preferred method for diagnosis in CNS lymphoma
Stereotactic needle biopsy is the preferred method of
establishing the histologic diagnosis in sporadic cases.
treatment for CNS lymphoma
intravenous methotrexate 3.5g/m2 and citrovorum administered at 2-3 week intervals and at times continued indefinitely if the treatment is tolerated
trial: Batchelor T and Grossman S. (NABTT 96-07) High Dose Methotrexate Alone
MTX IV 8g/m2
T/F
Ocular lymphomas is eradicated by radiation therapy.
True
p659
survival in CNS lymphoma on IV methotrexate approach of treatment
non-AIDS survival 3.5 years, 4 years or more if radiation is given subsequently
some patients are alive for 10 years
Metastases to the skull and dura are particularly common in
breast and prostate
The metastatic tumors most likely to be single come from
kidney
breast
thyroid
adenocarcinoma of the lung
hemorrhagic metastases
melanoma chroioepithelioma lung thyroid kidney
CT with and without contrast will detect metastases with as size of
1 cm
subcentimeter - MRI should be done
Paraneoplastic disorders in CA
sensory neuronopthies and Lambert-Eaton myasthenic syndrome - usually with Carcinoma of the Lung
cerebellar degeneration - ovarian and other carcinomas, Hodgkin disease
necrotizing myelopathy
limbic encephalitis
opsoclonus - myoclonus syndrome
Treatment options for Brain Mets
WBRT
10 doses of 300cGy each
steroids
High-dose focused RT
Results of one RT comparing SRS vs WBRT in pts with 1-4 mets
No difference in survival
BUT there was a reduction in the frequency of recurrence at other sites in the brain with WBRT
T/F
Intrathecal and intraventricular chemotherapy are not
thought to be of value in the treatment of parenchymal
metastases.
True
p662
The average period of survival in cases of brain metastases, even with therapy
6 months
CSF findings in carcinomatous meningitis
increased CSF pressure
elevated protein
low glucose
lymphocytic pleocytosis up to 100 or fewer
in a few patients CSF findings are Normal
Treatment in Carcinomatous Meningitis
radiation therapy to symptomatic areas
followed by in selected cases, Intraventricular methotrexate
median duration survival after diagnosis of carcinomatous meningitis
6 months
Involvement of NS in Leukemia
incidence
acute vs chronic leukemia
lymphocytic vs myelocytic
more common in acute and lymphocytic
ALL
T/F
Extradural compression o f the spinal cord o r cauda
equina is the most common neurologic complication
of all types of lymphoma.
True
p663
T/F
Systemic lymphoma rarely metastasizes to the brain.
True
p663
Chromosomal studies of medulloblastomas
reveal a deletion on the distal part of chromosome ____
distal to the p53 region.
Chrom 17
accounts for the neoplastic transformation of cerebellar stem cells at various stages of their differentiation into tumor cells
in Medulloblastoma
Amplification or overexpression of the transcription factor ______ is associated with poorer prognosis
MYCN
imaging Medulloblastoma
high signal intensity on both Tl- and T2-weighted MRIs heterogeneous enhancement
typical location adjacent to and extending into the fourth ventricle.
fairly well demarcated from the adjacent brain tissue
Treatment for Medulloblastoma
maximal resection + chemo + RT of the entire neuraxis improves the rate and length of disease-free survival
survival in Medulloblastoma
combination of Sx, chemo, RT
5-year survival in more than 80% of patients
T/F
Medulloblastoma
The presence of desmoplastic features is associated with a poor prognosis independent of the type or treatment.
False
Better prognosis
most common solid tumor of childhood
arises from the adrenal medulla and sometimes metastasizes widely
Neuroblastoma
Paraneoplastic complication associated with Neuroblastoma
polymyoclonus with opsoclonus and ataxia
CNS neoplasms of neuroectodermal origin
Primitive Neuroectodermal Tumor
tumor most often associaten with von-Hippel Lindau disease
dizziness, ataxia of gait, or of ICP from the compression of the 4th ventricle
in some instances with associated retinal angioma or hepatic and pancreatic cysts
tendency later to develop malignant adrenal and renal tumors
Hemangioblastoma of the Cerebellum
age of onset 15 - 50 yrs
Blakc whites and asians are equally affected
4 types of pineal tumors
germinoma
non-germinomatous GCT
pinealoma (pineocytoma, atypical pineocytoma, pineoblastoma)
and a glioma
also known as dysplastic cerebellar gangliocytoma, is a rare tumour of the cerebellum
Lhermitte-Duclos Disease
Associated with Cowden Disease ( tumors of breast, thyroid, endometrial)
appearance in imaging of dysplastic cerebellar gangliocytoma
indistinnt mass of tiger stripe appearance
as a result of alternating layers of dysmorphic cerebellar cells
tumor commonly associated with tuberous sclerosis
subependymal giant cell astrocytoma
what is an inhibitor of mTOR complex reduces the sie of tumor and ameliorates seizures in Tuberous Sclerosis
Everolimus
hallmark of NF 2
bilateral schwannoma
occurs before age 21
autosomal dominant
criteria for NF 1
2/7 of the following
- Six or more café-au-lait spots or hyperpigmented macules =5 mm in diameter in prepubertal children and 15 mm postpubertal
- Axillary or inguinal freckles (>2 freckles)
- Two or more typical neurofibromas or one plexiform neurofibroma
- Optic nerve glioma
- Two or more iris hamartomas (Lisch nodules), often identified only through slit-lamp examination by an ophthalmologist
- Sphenoid dysplasia or typical long-bone abnormalities such as pseudarthrosis
- First-degree relative (eg, mother, father, sister, brother) with NF1
benign epithelioid tumor
origin: cell rests (remnants of the Rathke pouch) at the junction of the infundibular system and pituitary gland
tumor is oval round, smooth surface
wall of the cysts and solid parts of tumor consists of cords and whorls of epithelial cells
Craniopharyngioma
imaging Craniopharyngioma
increased signal on T1 because of cholesterol content
decreased T2 signal
adenomas of the pituitary are most often composed of
chromophobe cells
acidophil cells in the pituitary produce which hormones
prolactin
growth hormone
TSH
Basophil cells of pituitary produce which hormones
ACTH
B-lipotropin
LH
FSH
how many percent of tumors are prolactin secreting
60-70%
T/F
pituitary tumors usually arise as discrete nodules in the anterior part of the gland or
adenohypophysis
True
growth hormone antagonist introduced to reduce many of the manifestations of acromegaly
pegvisomant
Cushing syndrome vs Cushing disease
Syndrome - effects of cortisol excess from - excessive administration of steroids, adenoma of adrenal cortex, ACTH-producing bronchial carcinoma, other carcinomas that produce ACTH
Disease - excessive secretion of pituitary ACTH
Cushing disease clinical manifestations
truncal obesity hypertension abdominal striae hyperglycemia osteoporosis some: mental disorder
diagnosis of Cushing Disease
demonstration of increased concentration of plasma and urinary cortisol
–these levels are not suppressed by small doses of dexamethasone 0.5mgQID but they are suppressed by high doses 8mg daily
dopamine agonist given in prolactinoma
bromocriptine 0.5 to 1.25mg daily
analogue of somatostatin, given in cases of acromegaly
octreotide
200mg/d
increased in divided doses to 1,600mg by increments of 200mg weekly
this syndrome occurs as a result of infarction of an adenoma that has outgrown its blood supply
characterized by acute onset of headache that may be retro-orbital, frontal, bitemporal, or generalized ophthalmoplegia, bilateral visual loss, coma
Pituitary apoplexy
arises from the remnants of the primitive notochord
located often within the clivus (from dorsum sella to foramen magnum) and in the sacrococcygeal region
affects males more than female
locally invasive but do not metastasize
Chordoma
treatment for chordoma
excision and radiation
Lambert-Eaton syndrome, antibody binds to
voltage-gated calcium channels at NMJ
encephalitic process associated with carcinoma of the bronchus, usually of the small cell type
affects the medial temporal lobes, adjacent nuclei, brainstem, cerebellum or gray matter of SC
subacute, progressive
distinct features: confusiona-agitated state, memory defect, seizures - sometimes focal, hallucinations and dementia
Encephalomyelitis associated with Carcinoma and Limbic Encephalitis
Most patients with small cell lung cancer and any of
the types of paraneoplastic encephalomyelitis have been
found to harbor circulating polyclonal IgG antibodies
______ that bind to the nuclei of neurons in many regions of the brain and spinal cord, dorsal root ganglion cells, and peripheral autonomic neurons.
Anti-Hu
paraneoplastic encephalitis
an acute or subacute psychiatric syndrome
consisting of some combination of hallucinations, panic,
delusions, and incoherence, coupled with seizures, memory disturbance and hypoventilation
malaise, fatigue, headache excessive sleepiness, or
low fever
associated with teratoma - ovary or mediastinum
autonomic overactivity
Anti-NMDA Encephalitis
distinctive syndrome that is associated in most
cases with the anti-Hu antibody
numbness, paresthesias, sometimes painful
lancinating pains at onset
as the illness progresses - all forms of sensation are greatly reduced resulting in disabling ataxia and pseudoathetoid movements
paraneoplastic sensory neuronopathy
subacute onset and steady progression over a period of weeks to months
symmetrical ataxia of gait and limbs - affecting arms and legs more or less equally - dysarthria, nystagmus, vertigo
dancing eyes- dancing feet
pathologically - diffuse degenerative changes of the cerebellar cortex and deep cerebellar nuclei
purkinje cells are affected prominently
Paraneoplastic cerebellar degeneration
antibodies in Paraneoplastic cerebellar degeneration
anti-purkinje cell antibodies
anti-Yo
anti-Hu may also be present
in children, this syndrome is usually a manifestation of neuroblastoma
but more common in adults in relation to breast and small cell lung CA
Opsoclonus-Myoclonus-Ataxia Syndrome
also seen in bronchial CA and gastric CA
andtibody implicated in Opsoclonus-Myoclonus-Ataxia Syndrome
Anti-Ri
in cases of small cell lung CA
not seen in neuroblastoma
Neurologic Disorder:
cerebellar degeneration
Name predominant autoantibody and associated tumors
Anti-Yo (anti-purkinje cell)
ovary, fallopian tube, lung, Hodgkin disease
Neurologic Disorder:
encephalomyelitis including limbic and brainstem encephalitis
Name predominant autoantibody and associated tumors
Anti-Hu
(ANNA 1)
small cell, neuroblastoma, prostate, breast, Hodgkin, testicular
Anti-NMDA, anti-mGluR5 ovarian teratoma and other sites
Neurologic Disorder:
opsoclonus-myoclonus-ataxia
Name predominant autoantibody and associated tumors
Anti-Ri (ANNA2)
Breast, fallopian tube, small cell lung
Neurologic Disorder:
retinal degeneration
Name predominant autoantibody and associated tumors
Antirecoverin (Anti-CAR)
small cell lung, thymoma, renal cell, melanoma
Neurologic Disorder:
Subacute Sensory Neuropathy and Neuronopathy
Name predominant autoantibody and associated tumors
Anti-Hu
(ANNA1)
small cell lung, Hodgkin, other lymphomas
Neurologic Disorder:
Lambert-Eaton myasthenic syndrome
Name predominant autoantibody and associated tumors
Anti-voltage gated calcium channel (VGCG)
small cell lung, Hodgkin, other lymphomas
Neurologic Disorder:
Stiff person syndrome, neuromyotonia
Name predominant autoantibody and associated tumors
Antiamphyphysin, Anti-Caspr2, Anti-GAD
breast, lung
Neurologic Disorder:
Chorea
Name predominant autoantibody and associated tumors
anti-Hu
Anti-CRMP5
Lung, Hodgkin, others
Neurologic Disorder:
Optic neuropathy
Name predominant autoantibody and associated tumors
Anti-CRMP-5
Lung
