Tumors & Cysts Flashcards
astrocytoma
slow-growing astrocytic tumor composed of bipolar “hair-like” (pilocytic) cells
most common glioma in children
astrocytoma associations
tuberous sclerosis, neurofibromatosis type 1 (NF1), and Li-Fraumeni syndrome
- optic nerve and chiasm glioma associated with NF1
astrocytoma presentation
symptoms of increased ICP (headache, nausea/vomiting), vision loss, ataxia, or cranial nerve deficits depending on location
astrocytoma on imaging
cystic mass with a contrast rim-enhancing nidus or mural nodule with minimal vasogenic edema, dorsally exophytic
most commonly found in the cerebellum
also prefers midline structures such as the brainstem, optic chiasm, hypothalamus, and deep gray matter (basal ganglia)
astrocytoma genes
KIAA1549-BRAF gene fusion is characteristic of this tumor type
astrocytoma pathology
hair-like cytoplasmic fibers (Rosenthal fibers) and eosinophilic granular bodies in stacked bipolar cells
astrocytoma prognosis
90% 10-year overall survival
can be treated with surgical resection alone, and rarely progresses to malignant glioma
classic patient presentation of astrocytoma
child presenting with increased ICP/ataxia found to have a cerebellar cystic mass lesion with enhancing mural nodule
subependymal giant cell astrocytoma (SEGA)
WHO grade 1 tumor almost exclusively seen in pediatric patients with tuberous sclerosis (TS) and before the age of 20
- seen in 5-15% of patients with TS
SEGA symptoms
often asymptomatic
but when symptomatic presents with obstructive hydrocephalus due to location in the foramen of Monro
SEGA imaging
well-circumscribed, partially-calcified intraventricular contrast-enhancing mass near the foramen of Monro
SEGA pathology
large polygonal cells with eosinophilic cytoplasm and a smaller number of giant pyramidal ganglioid astrocytes
SEGA treatment
generally treated initially with mTOR inhibition with everolimus
if acutely symptomatic or growing, can be treated with surgical resection
Tuberous sclerosis review
classically presents with seizures, mental retardation, and adenoma sebaceum. Associated with TSC2/tuberin (most cases) or TSC1/hamartin with cortical or subependymal tubers, hamartomas, renal angiomyolipomas, and cardiac rhabdomyomas
pleomorphic xanthoastrocytoma (PXA)
found in young patients who present with temporal lobe epilepsy
pleomorphic xanthoastrocytoma (PXA) imaging
supratentorial peripheral cystic and contrast-enhancing mass abutting the leptomeninges with enhancing dural tail sign and scalloping of overlying bone
pleomorphic xanthoastrocytoma (PXA) pathology
variable histological features (thus, pleomorphic) with spindle cells, polygonal cells, multinucleated cells, highly variable nuclear size, and astrocytes with eosinophilic granular bodies
pleomorphic xanthoastrocytoma (PXA) genetics
associated with BRAFV600E mutations and homozygous CDKN2A/B deletions
pleomorphic xanthoastrocytoma (PXA) treatment
surgical resection
local recurrence and malignant transformation are common so post-operative radiation is indicated for grade 3 tumors
adult-type diffuse gliomas
astrocytoma, IDH-mutant (grades 2-4)
glioblastoma, IDH-wildtype (grade 4)
astrocytoma, IDH-mutant
patients present with progressive neurologic symptoms dependent on tumor location and/or with seizures
astrocytoma, IDH-mutant imaging
T2-FLAIR mismatch sign often present, with T2 hyperintensity and relative hypointensity on FLAIR sequences
- MR spectroscopy will have an elevated choline peak, low NAA peak, and elevated choline:creatinine ratio
astrocytoma, IDH-mutant pathology grade 2
mitotic activity absent or low without microvascular proliferation, necrosis, or genetic markers that would upgrade the tumor (homozygous deletion of CDKN2A/B)
astrocytoma, IDH-mutant pathology grade 3
mitotic activity present without microvascular proliferation, necrosis, or genetic markers that would upgrade the tumor
- formally known as anaplastic astrocytoma
astrocytoma, IDH-mutant pathology grade 4
microvascular proliferation, necrosis, or genetic markers that would upgrade the tumor present
glioblastoma, IDH-wildtype (grade 4)
formally known as glioblastoma multiforme (GBM)
most common and most destructive of the diffuse gliomas
glioblastoma, IDH-wildtype (grade 4) imaging
contrast ring-enhancing lesions with significant vasogenic edema. lesions can also have internal necrosis and can extend through the corpus callosum (butterfly lesion)
glioblastoma, IDH-wildtype (grade 4) genetics
IDH-1/2 mutations are associated with secondary GBM arising from a lower-grade glioma
tumors without microvascular proliferation or necrosis can still be classified a “molecular” glioblastoma if genetic testing shows TERT promotor mutation, EGFR gene amplification, or gain of 7/loss of 10 chromosome copy number alterations
glioblastoma, IDH-wildtype (grade 4) pathology
cells with increased mitotic activity with pseudopalisading necrosis and microvascular endothelial proliferation
glioblastoma, IDH-wildtype (grade 4) treatment
maximal safe resection followed by intensity-modulated radiation therapy (IMRT) plus concomitant temozolomide (alkylating chemotherapy) followed by adjuvant temozolomide
- methylation of MGMT gene associated with better treatment response to temozolomide
- bevacizumab, a monoclonal antibody that inhibits vascular endothelial growth factor (VEGF) can be used in recurrent or progressive GBM
- another alkylating agent, lomustine, is often used as a second-line treatment or in recurrent gliomas
high yield gliomas
pilocytic astrocytoma (Grade 1)
diffuse astrocytoma (grade 2)
anaplastic astrocytoma (grade 3)
glioblastoma (grade 4)
pilocytic astrocytoma: grade
1
pilocytic astrocytoma: cell of origin
astrocyte
pilocytic astrocytoma: typical age
children, young adults
pilocytic astrocytoma: location
cerebellum, optic pathway
pilocytic astrocytoma: imaging
cystic mass with enhancing nodule
pilocytic astrocytoma: key molecular markers
BRAF-KIAA1549 fusion
pilocytic astrocytoma: MGMT status
not typically assessed
pilocytic astrocytoma: histology
biphasic (compact and loose areas), Rosenthal fibers
pilocytic astrocytoma: prognosis
excellent, often curable
pilocytic astrocytoma: treatment
surgery alone often curable
diffuse astrocytoma: grade
2
diffuse astrocytoma: cell of origin
astrocytes
diffuse astrocytoma: typical age
30-40 years
diffuse astrocytoma: location
cerebral hemispheres
diffuse astrocytoma: imaging
T2/FLAIR hyperintense, non-enhancing
diffuse astrocytoma: key molecular markers
IDH mutation, ATRX loss
diffuse astrocytoma: MGMT status
often methylated
diffuse astrocytoma: histology
low cellularity, no mitoses
diffuse astrocytoma: prognosis
5-year survival: 65-70%
diffuse astrocytoma: treatment
surgery, RT if progression
anaplastic astrocytoma: grade
3
anaplastic astrocytoma: cell of origin
astrocytes
anaplastic astrocytoma: typical age
40-50 years
anaplastic astrocytoma: location
cerebral hemispheres
anaplastic astrocytoma: imaging
T2/FLAIR hyperintense, may enhance
anaplastic astrocytoma: key molecular markers
IDH mutation, ATRX loss
anaplastic astrocytoma: MGMT status
often methylated
anaplastic astrocytoma: histology
increased cellularity, mitoses
anaplastic astrocytoma: prognosis
5-year survival: 25-30%
anaplastic astrocytoma: treatment
surgery, RT, +/- chemotherapy
glioblastoma: grade
4
glioblastoma: cell of origin
astrocytes
glioblastoma: typical age
50-60 years
glioblastoma: location
cerebral hemispheres
glioblastoma: imaging
enhancing mass with necrosis and edema
glioblastoma: key molecular markers
IDH wildtype (primary), EGFR amplification
glioblastoma: MGMT status
variable
glioblastoma: histology
high cellularity, mitoses, necrosis, microvascular proliferation
glioblastoma: prognosis
median survival: 12-15 months
glioblastoma: treatment
surgery, RT, chemotherapy (TMZ)
IDH
isocitrate dehydrogenase
ATRX
alpha-thalassemia/mental retardation syndrome X-linked
EGFR
epidermal growth factor receptor
MGMT
O6-methylguanine-DNA methyltransferase
TMZ
temozolomide
location of pediatric brain tumors by age: <3
supratentorial > infratentorial
location of pediatric brain tumors by age: 3-10 years old
infratentorial > supratentorial
location of pediatric brain tumors by age: 10+ years old
supratentorial = infratentorial
most common pediatric brain tumors: suprasellar
craniopharyngioma
optic hypothalamic glioma
most common pediatric brain tumors: overall
pilocytic astrocytoma
medulloblastoma
ependymoma
most common pediatric brain tumors: supratentorial/cerebral hemispheres
pilocytic astrocytoma
ganglioglioma
PXA pleomorphic xanthoastrocytoma
most common pediatric brain tumors: infratentorial/cerebellar
medulloblastoma
pilocytic astrocytoma
ependymoma
oligodendrogliomas: WHO grade
2 or 3
oligodendrogliomas: molecular markers
associated with 1p/19q co-deletion and IDH mutations
- 1p/19q co-deletion patients have a better overall prognosis compared to astrocytic tumors which are 1p/19q normal
oligodendrogliomas: imaging
partially calcified T2 heterogeneous, hyperintense subcortical/cortical mass with patchy or minimal contrast enhancement
oligodendrogliomas: location
most often found cortically in the frontal or temporal lobesq
oligodendrogliomas: typical age
4th or 5th decade of life
oligodendrogliomas: pathology
cells with a “Fried egg” appearance with monotonous round nuclei, surrounded by prominent perinuclear halos
oligodendrogliomas: treatment
surgical resection followed by radiation and chemotherapy
ependyma tumors classification
based on anatomic site, histopathology, and molecular features
supratentorial ependymomas: location
more frequently in frontal and parietal lobes
supratentorial ependymomas: imaging
irregular contrast enhancement, often with cysts or calcifications
supratentorial ependymomas: molecular findings
fusion gene involving ZFTA or YAP1
supratentorial ependymomas: treatment
surgical resection followed by radiation
posterior fossa ependymomas: location
most frequently in the fourth ventricle, can arise in the cerebellopontine angle
posterior fossa ependymomas: presentation
related to mass effect/hydrocephalus from fourth ventricular obstruction
- headache, vomiting, lethargy, rapid head circumference increase in infants
posterior fossa ependymomas: imaging
homogenous mass within the fourth ventricle
spinal ependymoma: location
intradural, intramedullary lesion of the spinal cord
spinal ependymoma: imaging
contrast-enhancing, well-circumscribed lesion often associated with syrinx
myxopapillary ependymoma: location
intradural, extramedullary lesion of the spinal cord, most often in the lumbar spine
myxopapillary ependymoma: imaging
contrast-enhancing, well-circumscribed lesion; often described as “sausage-like” in appearance
MYCN-amplified ependymoma: location
intradural, extramedullary lesion of the spinal cord, most often in the cervical spine
MYCN-amplified ependymoma: prognosis
aggressive compared to other ependymomas
spinal ependymomas
spinal ependymoma
myxopapillary ependymoma
MYCN-amplified ependymoma
subependymoma: grade
WHO grade 1
subependymoma: location
most often found incidentally in the ventricles
subependymoma: pathology
monomorphic cells with round/oval nuclei and salt and pepper chromatin and perivascular pseudorosettes
choroid plexus papilloma/carcinoma: cells of origin
choroid plexus cells
choroid plexus papilloma/carcinoma: typical age
often presents in infants, most occurring before age 1 but can occur at any age
choroid plexus papilloma/carcinoma: presentation
symptoms of increased ICP due to overproduction of CSF
choroid plexus papilloma/carcinoma: imaging
an intraventricular highly contrast-enhancing lesion usually located in the lateral or 4th ventricle
choroid plexus papilloma/carcinoma: treatment
surgical resection
neuronal and mixed neuronal-glial tumors
ganglioglioma
desmoplastic infantile astrocytoma and ganglioma
dysembrionic neuroepithelial tumor (DNET)
central neurocytoma
ganglioglioma: grade
low-grade tumor, but can be more aggressive
ganglioglioma: imaging
cystic mass with a mural nodule
ganglioglioma: location
often arising in the temporal lobe
ganglioglioma: presentation
can often lead to refractory epilepsy
ganglioglioma: typical age
most common in children and young adults
ganglioglioma: key molecular markers
BRAF mutations, IDH negative
ganglioglioma: pathology
biphasic tumors with neuronal and glial elements
which tumors are associated with BRAF mutations?
pilocytic astrocytoma
PXA
ganglioglioma
desmoplastic infantile astrocytoma and ganglioglioma: grade
WHO grade 1
desmoplastic infantile astrocytoma and ganglioglioma: typical age
often before age 2, more often in males
desmoplastic infantile astrocytoma and ganglioglioma: presentation
rapid increase in head size
desmoplastic infantile astrocytoma and ganglioglioma: imaging
large cystic tumor with a peripheral solid component attached to the meninges of frontal or parietal lobes
desmoplastic infantile astrocytoma and ganglioglioma: treatment
surgical resection
desmoplastic infantile astrocytoma and ganglioglioma: location
meninges of frontal or parietal lobes
dysembrionic neuroepithelial tumor (DNET): grade
grade 1 tumor
dysembrionic neuroepithelial tumor (DNET): location
cortical gray matter associated with cortical dysplasia most often in temporal lobes
dysembrionic neuroepithelial tumor (DNET): complications
temporal lobe epilepsy
dysembrionic neuroepithelial tumor (DNET): pathology
myxoid clear areas with floating neurons
dysembrionic neuroepithelial tumor (DNET): imaging
wedge-shaped cystic cortical mass lesion with a “soap-bubble” appearance, typically non-enhancing
central neurocytoma: grade
grade 2
central neurocytoma: presentation
signs/symptoms of increased ICP
central neurocytoma: imaging
a cystic/bubbly lesion within the lateral ventricle near the foramen of Monro, often attached to the septum pellucidum
central neurocytoma: pathology
neurocytic rosettes and uniform round blue cells. they are “neurocytic” in morphology and may closely resemble oligodendrogliomas, but with no IDH mutation or 1p/19q co-deletion
central neurocytoma: treatment
surgical resection
pineal region tumors
pineoblastoma
pineocytoma
pineoblastoma: imaging
calcified heterogenous soft tissue mass in the pineal region with enhancement
pineoblastoma: typical age
seen primarily in children
pineoblastoma: presentation
can lead to hydrocephalus secondary to mass effect
pineoblastoma: pathology
densely cellular primitive neuroectodermal tumors that often form Homer Wright (medulloblastoma-type) rosettes
pineoblastoma: treatment
gross total resection followed by radiation and chemotherapy
pineocytoma: imaging
contrast-enhancing midline lesion with irregular borders
pineocytoma: presentation
often present with symptoms of hydrocephalus or mass effect
pineocytoma: pathology
small mature pinealocytes with round/ovoid nuclei forming pineocytomatous rosettes
pineocytoma: treatment
often curative with surgical resection alone
embryonal tumors
medulloblastoma
medulloblastoma: frequency
most common malignant brain tumor in childhood (20-25% of pediatric CNS neoplasms)
medulloblastoma: associations
Li-Fraumeni syndrome and familial adenomatous polyposis (FAP)
medulloblastoma: imaging
a midline round lesion along the fourth ventricle between the brainstem and cerebellum
medulloblastoma: pathology
Homer-Wright rosettes with no lumen, with necrosis, and pseudopalisades
medulloblastoma: prognosis
can seed and develop disseminated metastatic disease all along the neuraxis
medulloblastoma: treatment
gross total resection followed by craniospinal irradiation and chemotherapy
tumors of the meninges
meningioma
meningioma: imaging
well-circumscribed dural-based extra-axial diffuse and homogenous enhancing lesion with a “dural tail”
meningioma: pathology
calcified concentric psammoma bodies with a “whorled architector”
meningioma: associations
NF2 patients can present with multiple meningiomas
meningioma: treatment
observation for asymptomatic low grade tumors
if symptomatic, resection is performed
radiotherapy is considered if the meningioma is WHO grade 3
Foster Kennedy Syndrome
if located in the olfactory groove tumors (especially meningiomas) can cause Foster Kennedy Syndrome: unilateral visual loss with compressive optic atrophy in one eye and contralateral papilledema in the other, also with anosmia
tumors of the cranial (and spinal) nerves
schwannoma
neurofibroma
optic nerve glioma
carcinomatosis meningitis
lymphomatous meningitis
schwannoma: location
most commonly arise on CN VII/VIII complex but can arise on any cranial nerve except I and II, which do not have SChwann cells
schwannoma: imaging
contrast enhancing mass usually within the internal auditory canal or cerebellar pontine angle
schwannoma: pathology
areas of compact elongated cells with nuclear palisades called Verocay bodies
schwannoma: association
bilateral acoustic schwannomas are pathognomonic for patients with NF2
neurofibroma: grade and location
benign tumors, typically on peripheral nerves
neurofigroma: associations
associated with neurofibromatosis type 1 (NF1)
optic nerve glioma: location
typically occurs in CN II and along the visual pathway
optic nerve glioma: types
astrocytomas, either fibrillary (60%) or pilocytic (40%)
carcinomatosis meningitis: presentation
multiple cranial neuropathies
lymphomatous meningitis: presentation
multiple cranial neuropathies
lymphomas and hematopoietic tumors
hemangioblastoma
CNS lymphoma
intravascular lymphoma
hemangioma
multiple myeloma
langerhans cell histiocytosis
hemangioblastoma: imaging
contrast-enhancing nodule surrounding a non-enhancing cyst in the posterior fossa with little vasogenic edema
hemangioblastoma: pathology
large vacuolated stromal cells and variably sized small vascular structures
hemangioblastoma: associations
commonly seen in patients with Von-Hippel Lindau (VHL) syndrome
CNS lymphoma: imaging
can have a highly variable appearance ranging from diffusely infiltrative, to a solid margin, to lobulated margins
lesions can have variable enhancement and possible diffusion restriction
CNS lymphoma: location
tend to be located within the basal ganglia or periventricular white matter and can involve the corpus callosum
CNS lymphoma: immunocompetent patients
lesions more likely unifocal and are uniformly contrast enhancing
CNS lymphoma: immunocompromised patients
lesions may be multifocal and are ring enhancing
CNS lymphoma: pathology
positive staining for B cell marker, CD20
CNS lymphoma: associations
the elderly and immunocompromised patients are at risk of CNS lymphoma, especially if EBV positive
CNS lymphoma: treatment
standard initial treatment is combination therapy that includes high-dose methotrexate
in select patients, consolidative therapy with autologous stem cell transplant is performed after initial treatment
intravascular lymphoma: presentation
presents as a B-cell driven disease that has multi-organ involvement that may involve the central nervous system
if CNS involvement, patients present with multiple small brain infarcts
intravascular lymphoma: pathology
lymphoma cells within the blood vessels
hemangiomas: imaging
lesion with a “popcorn” appearance with a perimeter of increased signal due to hemosiderin
hemangiomas: complications
lesions at an increased risk of bleeding
multiple myeloma: associations
will involve the bony structures and can lead to compression fractures
multiple myeloma: imaging
salt and pepper pattern with diffuse heterogeneous lesions of vertebrae
langerhans cell histiocytosis: cells of origin
due to uncontrolled monoclonal proliferation of Langerhans cells
langerhans cell histiocytosis: pathology
Langerhans cells have large, convoluted, and folded nuclei and are CD1a positive
langerhans cell histiocytosis: typical age
most common in children and female predominant
langerhans cell histiocytosis: imaging
lytic lesions in the skull and severe vertebral compression fractures with vertebra plana configuration
germ cell tumors
germinoma
germinoma: epidemiology
most common pineal region neoplastic lesion
germinoma: imaging
solid, contrast-enhancing midline pineal mass near the 3rd ventricle
germinoma: pathology
small reactive lymphocytes and large neoplastic germ cells with clear cytoplasm
histologically similar to cells in the ovaries and testes
germinoma: male/female
males much higher risk than females
germinoma: associations
should be considered in patients who are young and develop diabetes insipidus
sella region tumors
craniopharyngioma
pituitary macroadenoma
pituitary microadenoma
hypothalamic hamartoma
craniopharyngioma: imaging
partially calcified cystic/solid multi-compartmental suprasellar mass
craniopharyngioma: cells of origin
derived from Rathke pouch epithelium
craniopharyngioma: differential diagnosis
Rathke cleft cyst (RCC)
suprasellar arachnoid cyst
hypothalamic/chiasmatic astrocytoma
pituitary adenoma
(epi-)dermoid tumors
thrombosed aneurysm
germinoma or mixed germ cell tumor with cystic compionent(s)
Rathke cleft cyst (RCC) compared to craniopharyngioma
noncalcified, less heterogeneous, look for intracystic nodule, does not enhance, “claw” sign (enhancing pituitary draped around cyst)
suprasellar arachnoid cyst compared to craniopharyngioma
noncalcified, no enhancement
hypothalamic/chiasmatic astrocytoma compared to craniopharyngioma
solid or with small cystic/necrotic components, calcification is rare; robust enhancement is common
pituitary adenoma compared to craniopharyngioma
rare in prepubescent children, isointense with the brain, enhances strongly, can mimic CP when cystic and hemorrhagic
(epi-)dermoid tumors compared to craniopharyngioma
minimal or no enhancement
thrombosed aneurysm compared to craniopharyngioma
contains blood products, look for residual patent lumen, phase artifact
germinoma or mixed germ cell tumor with cystic component(s) compared to craniopharyngioma
CSF spread common, calcification rare
pituitary macroadenoma: epidemiology
most common suprasellar mass in adults
pituitary macroadenoma: presentation
can lead to compression of the optic chiasm
pituitary macroadenoma: imaging
a large, enhancing sellar/suprasellar mass
pituitary microadenoma: imaging
small focal hypointense sellar mass
pituitary microadenoma: secretory
prolactinoma is most common secretory pituitary adenoma
bromocriptine and cabergoline can be used to suppress prolactin secretion
hypothalamic hamartoma: imaging
a round, non-enhancing, iso-intense mass in the hypothalamus, superior to the infundibulum
hypothalamic hamartoma: presentation
can present with precocious puberty and/or gelastic seizures
cysts and other lesions
colloid cyst
epidermoid cyst
synovial cyst
rathke cleft cyst
arachnoid cyst
mucocele
lipoma
colloid cyst: imaging
hyperdense non-enhancing epithelial-lined cyst of the foramen of Monro
colloid cyst: presentation
at risk of developing obstructive hydrocephalus
- presents with intermittent or persistent headaches due to the increased intracranial pressure from obstruction of CSF outflow
colloid cyst: typical age
peak age of onset is 3rd or 4th decade of life
colloid cyst: treatment
microsurgically, endoscopically, or with biventricular shunts in nonsurgical candidates
epidermoid cyst: imaging
an extra-axial mass with a cystic appearance
- will be low density and similar to CSF on CT scan, like an arachnoid cyst
- on MRI, both arachnoid and epidermoid cysts are hyperintense on T2, but with FLAIR arachnoid cysts become hypointense (like CSF) while epidermoid cysts usually stay hyperintense
- epidermoid cysts also have hyperintensity on DWI which helps to distinguish from an arachnoid cyst as well
epidermoid cyst: compared to arachnoid cyst
- on MRI, both arachnoid and epidermoid cysts are hyperintense on T2, but with FLAIR arachnoid cysts become hypointense (like CSF) while epidermoid cysts usually stay hyperintense
- epidermoid cysts also have hyperintensity on DWI which helps to distinguish from an arachnoid cyst as well
synovial cyst: location
can form adjacent to any joint throughout the body
if they occur in the spine, they can occur in the cervical, thoracic, or lumbar regions
synovial cyst: imaging
well-circumscribed, smooth, extra-dural lesion adjacent to facet joints
calcification within the cyst can also occur
rathke cleft cyst: imaging
cystic lesion of the pituitary stalk
synovial cyst: presentation
radicular pain and symptoms related to compression of the adjacent root
rathke cleft cyst: presentation
commonly present with pituitary dysfunction
arachnoid cyst: location
extra-axial, congenital, space-occupying lesions that displace parenchymal brain tissue and are often asymptomatic
arachnoid cyst: imaging
fluid collection that is isodense/isointense to CSF on all sequences (CT, MRI, FLAIR, DWI)
mucocele: imaging
opacification of the sinus
mucocele: at risk
at risk of abscess formation
lipoma: imaging
an intradural extramedullary sharply circumscribed homogenous mass that suppresses on STIR fat-suppressed sequences
lipoma: location
if found intracranially, they may be near the corpus callosum
milial tumor syndromes of the CNS
neurofibromatosis type 1
neurofibromatosis type 2
tuberous sclerosis
sturge-weber syndomre
von-hippel lindau
li-fraumeni
cowden syndrome
turcot syndrome
NF1: aka
von Recklinghausen disease
NF1: genetics
autosomal dominant disease related to the NF1 gene, which codes for neurofibromin
NF1: non-neurologic findings
cafe-au-lai spots, Lisch nodules, skeletal abnormalities, and axillary freckling
NF1: neurologic lesions
optic nerve gliomas
neurofibromas
NF1: optic nerve gliomas
patients should have yearly eye exams
typically found in the first 6 years of life
small asymptomatic gliomas can be observed, as they may regress
larger, symptomatic lesions are treated with chemotherapy
NF1: neurofibromas
can occur on cutaneous branches of peripheral nerves, including neuronal roots and plexuses
they tend to be slow-growing and can remodel the surrounding bone
lesions encase the nerve and are contrast enhancing
plexiform neurofibromas
seen in NF1 but not seen in NF2
NF2: aka
central neurofibromatosis
NF2: genetics
autosomal dominant disorder related to the NF2 gene, which encodes for merlin on chromosome 22
NF2: presentation
vestibular schwannomas and multiple meningiomas
NF2: presentation
can have bilateral acoustic neuromas, patients usually present in their 20s with tinnitus
NF2: of note
these patients do not form neurofibromas
NF2: mnemonic
NF2 is a story of 2s: 2 nerves affected (typically CN VII or CN VIII), often on 2 sides (bilateral), 2 tumors (schwannomas, meningiomas), chromosome 22
tuberous sclerosis: genetics
autosomal dominant neurocutaneous disorder related to two tumor-suppressor genes: TSC1 (9q34) which encodes hamartin and TSC2 (16q13) which encodes tuberin
TSC1 genetics
9q36 which encodes hamartin
TSC2 genetics
16q13 which encodes tuberin
TS: imaging
cortical tubers which can be foci for seizures, which can be foci for seizures
TS: non-neurologic
ash-leaf spots, facial angiofibromas, angiomyolipomas, and retinal hamartomas
TS: association
intellectual disability occurs in several cases
TS: subependymal giant cell astrocytomas
5-10% of patients develop SEGAs
TS: mnemonic
TUBERRRS: Tsc2, U(ventricular), Bulk removal, Eosinophilic Rhabdomyosarcoma/Renal angiomyolipoma/Retinal hamartomas, Seizures
sturge weber syndrome: aka
encephalotrigeminal angiomatosis
sturge weber syndrome: gene
neurocutaneous disorder caused by a spontaneous somatic GNAQ gene mutation on chromosome 9 that manifests in a mosaic pattern
because this mutation is somatic (occurs after conception) it is not inherited
sturge weber syndrome: presentation
classic “port-wine stain” (cutaneous angioma) on the face with ipsilateral angiomatosis
sturge weber syndrome: imaging
CT head: parenchymal calcification adjacent to the angiomatosis
MRI: contrast enhancing angiomatosis of the leptomeninges and cortex (seen as “tram track sign” on MRI)
sturge weber syndrome: presentation
variable presentation from asymptomatic to seizures, weakness, etc
Cobb’s syndrome
sturge weber syndrome with spinal dural angioma in the spinal cord with a port-wine stain in the corresponding dermotome
Von Hippel Lindau (VHL): genetics
autosomal dominant disorder that leads to the upregulation of vascular endothelial growth factor (VEGF)
Von Hippel Lindau (VHL): presentation
infratentorial hemangioblastomas and retinal angiomas
Von Hippel Lindau (VHL): non-CNS manifestations
renal cell carcinoma, pheochromocytomas, and pancreatic and renal cysts
Von Hippel Lindau (VHL): mnenoic
VHL: Visceral cysts (kidney, pancreas, genitals), Hemangioblastomas, Light-sensitive (i.e. retinal involvement)
Li-Fraumeni: genetics
autosomal dominant disorder due to mutations of the p53 gene
Li-Fraumeni: presentation
tumors at various sites including breast, bone, blood, and adrenal glands
Li-Fraumeni: CNS
astrocytomas, medulloblastomas, and less commonly primitive neuroextodermal tumors (PNETs)
Cowden syndrome: genetics
autosomal dominant disease secondary to the PTEN tumor suppressor gene
Cowden syndrome: presentation
multiple hamartomas in various tissues, especially the skin and colon
young adults with cerebellar dysfunction or obstructive hydrocephalus
Cowden syndrome: association
associated with Lhermitte-Duclos disease (dysplastic cerebellar gangliocytoma)
Cowden syndrome: pathology
abnormal ganglion cells
Turcot syndrome: aka
mismatch repair cancer syndrome
Turcot syndrome: presentation
multiple colon polyps and an increased risk of colorectal and brain cancers (glioblastoma, medulloblastoma, SGCA)
metastatic cancer
intraparenchymal metastasis
leptomaningeal carcinomatosis
intraparenchymal metastasis: imaging
lesions of intense contrast enhancement surrounded by mild to moderate edema usually at the grey-white junction
intraparenchymal metastasis: common sources
lung (~40-50%)»_space; breast (~15-20%) > melanoma and GI (~10-% each)
intraparenchymal metastasis: causing hemorrhage
melanoma and renal cell carcinoma most likely to cause hemorrhage
intraparenchymal metastasis: meningeal infiltration
breast cancer
tip for which organs metastasize to the brain
when in doubt, paired organs (lungs, breast, and kidneys) and surface organs (skin, GI tract) typically metastasize to the brain
leptomeningeal carcinomatosis: imaging
contrast enhancement along the leptomeninges
leptomeningeal carcinomatosis: work up
when on differential, patients should have the whole neuraxis imaged to look for additional lesions as well as CSF analysis
leptomeningeal carcinomatosis: presentation
obstruction of CSF re-absorption from the malignancy can lead to communicating hydrocephalus
severe headaches, nausea, and vomiting
can improve with large volume lumbar puncture or EVD placement
paraneoplastic disorders: presentation
symptoms often precede cancer diagnosis and thus patients require cancer surveillance for a minimum of 2 years after symptom onset
paraneoplastic disorders
limbic encephalitis
paraneoplastic cerebellar degeneration
lambert-eaton myasthenic syndrome (LEMS)
others (myasthenia gravis, subacute sensory neuronopathy, opsoclonus-myoclonus syndrome, stiff-person syndrome, neuro-myotonia, dysautonomia, myelopathy)
limbic encephalitis: associated
most associated with SCLC, testicular germ cell tumors, or ovarian teratomas
limbic encephalitis: antibodies
several are related including anti-Hu, voltage-gated potassium channels, NMDA receptors, etc
limbic encephalitis: CSF
slightly more than half of patients with autoimmune limbic encephalitis have detectable CNS antibodies
limbic encephalitis: presentation
psychiatric/cognitive abnormalities, seizures, facial and limb dyskinesias, and autonomic instability
limbic encephalitis: imaging
abnormalities in cortical and subcortical regions
limbic encephalitis: EEG
NMDA-related encephalitis can have delta brush pattern
limbic encephalitis: young women
should be evaluated for ovarian teratoma
paraneoplastic cerebellar degeneration: presentation
subacute progression of ataxia, nystagmus, and dysarthria
paraneoplastic cerebellar degeneration: common causes
gynecological (ovarian, uterine, breast) and small cell lung cancers
paraneoplastic cerebellar degeneration: pathology
profound loss of Purkinje cells
paraneoplastic cerebellar degeneration: antibody
anti-Yo is the anti-Purkinje cell antibody
paraneoplastic cerebellar degeneration: MRI
often normal, may have some enhancement near the cerebellum, and may have cerebellar atrophy
paraneoplastic cerebellar degeneration: recovery
slow or partial (postmortem studies show permanent loss of Purkinje cells)
LEMS: presentation
proximal weakness and fatigability, impotence, and ptosis
LEMS: association
paraneoplastic encephalomyelitis and cerebellar degeneration
LEMS: cancer
most often SCLC, 70% have cancer
myasthenia gravis
thymoma
opsoclonus-myoclonus syndrome: presentation
rapid, high-amplitude conjugate eye movements (opsoclonus), myoclonus, ataxia
opsoclonus-myoclonus syndrome: related to
neuroblastoma in children and breast, ovarian, or small cell lung cancer in adults
opsoclonus-myoclonus syndrome: antibody
anti-Ri/ANNA-2 or anti-Hu
stiff person syndrome: antibody
anti-amphiphysin (paraneoplastic) or anti-GAD (more often autoimmune than paraneoplastic)
acetylcholine receptor, MUSK: tumor
thymoma
acetylcholine receptor, MUSK: neurologic symptoms
myasthenia gravis
voltage-gated calcium channel (VGCC) antibody: tumor
small cell lung cancer
voltage-gated calcium channel (VGCC) antibody: neurologic symptoms
LEMS
neuronal ganglionic acetylcholine receptor antibody: tumor
adenocarcinoma
thymoma
neuronal ganglionic acetylcholine receptor antibody: neurologic symptoms
autonomic neuropathy
voltage-gated potassium channel (VGKC) complex (LGI1 and CASPR2): tumor
variable
voltage-gated potassium channel (VGKC) complex (LGI1 and CASPR2): neurologic symptoms
limbic encephalitis
faciobrachial dystonic seizures (LGI1)
LGI1
faciobrachial dystonic seizures
NMDA receptor antibody: tumor
ovarian teratoma
NMDA receptor antibody: neurologic symptoims
limbic encephalitis
ANNA-1 (anti-Hu): tumor
small cell lung cancer
ANNA-1 (anti-Hu): neurologic symptoms
limbic encephalitis, opsoclonus-myoclonus
ANNA-2 (anti-Ri): tumor
small cell lung cancer, breast cancer
ANNA-2 (anti-Ri): neurologic symptoms
opsoclonus-myoclonus, encephlomyelitis, limbic encephalitis
ANNA-3 antibody: tumor
small cell lung cancer
ANNA-3 antibody: neurologic symptoms
limbic encephalitis, myelopathy, peripheral neuropathy
PNMA-1 (anti-Ma1): tumor
testicular cancer, breast cancer, colon cancer
PNMA-1 (anti-Ma1): neurologic symptoms
limbic encephalitis, brainstem encephalitis
PNMA-2 (anti-Ma2): tumors
testicular
PNMA-2 (anti-Ma2): neurologic symptoms
limbic encephalitis, brainstem encephalitis
PCA-1 (anti-Yo): tumor
gynecologic cancers, breast cancer
PCA-1 (anti-Yo): neurologic symptoms
cerebellar degeneration
CRMP-5 (anti CV2): tumor
small cell lung cancer, thymoma
CRMP-5 (anti CV2): neurologic symptoms
chorea, myelopathy, peripheral neuropathy
anti-GAD: tumor
small cell lung cancer, thymoma
anti-GAD: neurologic symptoms
Stiff-person syndrome, cerebellar ataxia, limbic encephalitis
anti-amphiphysin: tumor
breast cancer
anti-amphiphysin: neurologic symptoms
stiff-person syndrome
intraventricular tumors: lateral ventricle
subependymoma, choroid plexus tumors
intraventricular tumors: third ventricle
colloid cyst, SGCA/SEGA, central neurocytoma
intraventricular tumors: fourth ventricle
ependymoma, medulloblastoma
dural based tumors
meningioma, metastases
sellar tumors
pituitary adenoma, craniopharyngioma, rathke cleft cyst
pineal tumors
germinoma, pineal tumors
intramedullary/intraparenchymal tumors
astrocytoma, ependymoma
intradural extramedullary/extraparenchymal tumors
meningioma, neurofibroma, lipoma
extradural extramedullary/extraparenchymal tumors
metastasis, bone-related tumors (lagnerhans cell histiocytosis, multiple myeloma, chordoma)
chordoma
notochord-derived tumor
imaging: a heterogeneous enhancing lesion usually located with the clivus or sacrum
cyst and mural nodule
hemangioblastoma, pilocytic astrocytoma
calcified
meningioma, oligodendroglioma, low-grade astrocytoma, ependymoma, craniopharyngioma
contrast
metastasis, meningioma, astrocytoma, schwannoma
hemorrhagic
metastasis, high-grade astrocytoma, lymphoma, hemangioblastoma
transthyretin
choroid plexus papilloma
TSC1
hamartoma
TSC2
tuber
p53
astrocytoma
CDKN2A
astrocytoma
PTEN
astrocytoma
gain ch7, loss of 9p
astrocytoma
glial fibrillary acidic protein (GFAP) which is expressed in astrocytes and ependymal cells
astrocytoma, oligodendroglioma, ependymoma, gangliocytoma, hemangioblastoma
