Tumors Flashcards
Are CNS tumors metastatic or primary?
50-50 both
What type of tumors present as multiple, well-circumscribed lesions at the gray-white junction?
Metastatic tumors
What are common sources of metastatic tumors in the brain?
lung, breast, kidney
How are primary tumors classified?
cell type origin
–> astrocytes, meningothelial, ependymal, oligodendrocytes, etc
Are adult CNS tumors supratentorial or infratentorial>
supratentorial (meninges and cerebrum)
What are the most common CNS tumors in adults?
glioblastoma
schwannoma
meningioma
Are children CNS tumors supratentorial or infratentorial?
infratentorial (cerebellum and brainstem)
What are the most common CNS tumors in children?
pilocystic astrocytoma
medulloblastoma
ependymoma
Do primary CNS tumors metastasize?
No, locally destructive
What tumor is a common primary malignant, high-grade tumor of astrocytes in adults?
GBM/ glioblastoma
What tumor arises in the cerebral hemispheres and characteristically crosses the corpus callosum (butterfly lesion)?
glioblastoma
Does glioblastoma have a good prognosis?
no–> grade 4/4 astrocytoma
What tumors are GFAP +?
ASTROCYTOMAS:
glioblastoma
pilocytic astrocytoma
Briefly describe the histology of glioblastoma
regions of necrosis surrounded by pseudo-palisading tumor cells and endothelial cell proliferation
What should you immediately think of if you have an adult patient with new onset of seizures?
brain tumor!
What is a benign tumor of astrocytes and is the most common CNS tumor in children?
pilocytic astrocytoma (1/4)
Where are pilocytic astrocytomas usually found?
cerebellum (kids)
rare adult–>cerebrum
What tumor is characteristically described as a well-circumscribed, cystic lesion with a mural nodule?
pilocytic astrocytoma
What does biopsy of a pilocytic astrocytoma show?
Rosenthal fibers, eosinophilic granular bodies
biphasic pattern (loose and dense) with hair-like cells that have bipolar processes (AKA pilocyte)
What tumor grade has low proliferative potential and can be cured by resection (AKA benign)?
grade 1/4
What tumor grade is infiltrative with low proliferative potential and likely to recur?
grade 2/4
–>cytological atypia
What tumor grade is anaplastic with mitosis and requires radiation and chemo for treatment?
grade 3/4
What tumor grade is rapid evolution with fatal outcome and microvascular proliferation and/or necrosis?
grade 4/4
What are the 4 histological parameters of gliomas?
nuclear atypia
mitosis (mitotic figures)
microvascular proliferation
necrosis
What tumor grade has 1 glioma parameter?
2
What tumor grade has 2 glioma parameters?
3
What tumor grade has 3-4 glioma parameters?
4
What tumor grade is a diffuse astrocytoma?
2
What tumor grade is a anaplastic astrocytoma?
3
What is the general rule of age versus astrocytoma tumor grade?
lower grade–>young
high grade–>old
2–>30-40s
3–>50s
4–>60+
Are astroctyomas grey or white matter lesions?
white matter–>surround neurons (center of brain, outside of spinal cord)
If there was a brainstem astrocytoma, what CN dysfunction would you see?
CN VI, also long tract and brainstem signs
What does a diffuse astrocytoma look like?
raw scallop (vs cooked scallop being nml white matter)
grade 2
How can you differentiate diffuse vs anaplastic astrocytomas?
2 vs 3
pearly look vs atypia and numerous cells
What age does pilocytic astrocytoma affect?
under 20
What gene predisposes you to pilocytic astrocytoma, especially on optic nerve fibers?
NF1
–> functional loss of neuofibromin
What genes are involved in primary glioblastomas?
later in life without precursor lesion
EGFR and PTEN
What mutations confer a better prognosis in glioblastoma?
IDH1 and IDH2
–> R132H mutation of IDH1
Secondary glioblastomas occur…
in younger patients that are preceded by a lower grade lesion
—> TP53
typically treated as kid, years later glioblastoma forms
Where can you find glioblastomas?
throughout the brain, crosses corpus callosum to spread
What does glioblastoma look like?
contrast ring enhancing
central necrosis
What are the 3 histology hallmarks of glioblastoma?
1) serpentine necrosis
2) pattern
pseudo-palisading cells around necrosis (perpendicular walls around necrosis)
3) vascular or endothelial proliferation
What tumor makes up 10-15% of gliomas and occurs primarily in adults in the cerebrum?
oligodendroglioma
What is the hallmark term for oligodendrogliomas?
calcification
–>restricted to cortex with curvilinear or gyriform distribution
Describe histology of oligodendroglioma
Fried egg (perinuclear halos)
Chicken wire (anastomosing capillaries)
surround neurons, vasculature and pia mater
What grade are most oligodendrogliomas?
2/4, well differentiated
What mutated genes are the most common in oligodendrogliomas?
IDH1 and IDH2
Do IDH1 and 2 confer a favorable prognosis in oligodendroglioma?
yes
What gene loss is favorable in oligodendrogliomas?
1P19Q loss
What other CNS tumor is similar to the prognosis of glioblastoma (bad)?
anaplastic oligodendroglioma (3/4)
What tumor has vascular hypertrophy and necrosis, retains geometric vascularity, increases with increased N:C ratio and cellularity, and is found as nodules in 2/4 tumors?
anaplastic oligodendroglioma (3/4)
What tumor is sown as a calcified tumor in the white matter, usually along the frontal lobe, that may present with seizures?
oligodendroglioma
When does an ependymoma occur?
under 20 years
Where is the most common site of a ependymoma?
supratentorial in the 4th ventricle–> discrete, exophytic (stick out), enhancing
What grade is ependymoma typically?
3/4
Histology of ependymoma
ependymal rosettes more diagnostic than perivascular rosettes (pathoma says vice versa)
What tumor is most common in children in lateral ventricles and causes obstructive hydrocephalus d/t increased CSF production?
choroid plexus papilloma
What tumor is:
-in young adults and attached to the roof of the 3rd ventricle
- causes obstructive (non-comm) hydrocephalus
- rapidly fatal
- positional
colloid cyst of 3rd ventricle
What is the main malignant embryonal tumor in children?
medulloblastoma (4/4)
What are the 4 molecular group associated with medulloblastoma?
WNT–> older kids, monosomy Chr 6 with 90% 5 year survival
SHH–> MYCN amp with intermediate prognosis
Group 3: MYC amp and 17(I17Q) in infants and kids, WORST PROGNOSIS
Group 4: I17Q, no MYC, poor prognosis
Where can you find medulloblastoma?
cerebellum in midline, occludes CSF
Histology of medulloblastoma
anaplastic cell sheets (small, round, blue cells)
abundant mitoses
Homer-Wright rosettes
How does medulloblastoma spread?
CSF to cauda equina
What is medulloblastoma derived from?
neuroectoderm of cerebellum
What are differential dx for medulloblastoma?
ependymoma (perivascular pseudorosettes but less cellular and more fibrillar)
pilocytic astrocytoma (cystic, biphasic, low cellularity)
high grade infiltrating astrocytoma (more pleomorphic)
atypical teratoid/rhabdoid tumor (AT/RT less than 2yo, large cells)
metastatic carcinoma (adult patients)
Where is AT/RT found?
atypical teratoid/rhabdoid tumor
posterior fossa or supratentorial
What components are found in AT/RT?
EMA
Vimentin
What cells are found in AT/RT?
Rhabdoid cells–>eosinophilic cytoplasm with sharp borders and eccentric nucleus
—>resemble rhabdomyosarcoma
What gene/chromosome do 90% of people with AT/RT have?
Chr 22, hSNF5/INI1
What is the prognosis of AT/RT?
less than 1 year survival, highly aggressive
4/4
Who would get a primary CNS lymphoma?
immunocompromised (AIDS) or transplant patient
frequency increases over 60
How do primary CNS lymphomas spread?
multifocal periventricular spread
involvement outside CNS is late and rare
What is the origin of primary CNS lymphoma?
B cell (CD20+)
aggressive with latent EBV or organ transplant
Histology of primary CNS lymphoma
HOOPING accumulate around vessels
–>cells separated by reticulin and silver stain
Where do primary germ cell tumors in the brain occur?
midline
What are some CNS germ cell tumors?
pineal and suprasellar
M or F predominance of pineal germ cell tumor?
Male
When do germ cell tumors occur?
90% under 20
10% Japanese
Can gonadal germ cells metastasize to CNS?
yes and common
Does germinoma respond to radiation and chemo?
yes, good response
What is the most common pineal tumor?
germinoma
What pineal tumor is well differentiated (neuronal), low grade and in adults?
pinecytoma
What pineal tumor is high grade with necrosis and mitosis, in kids, spreads throughout CNS and has RB gene?
pineblastoma
What is the most common benign CNS tumor in adults?
meningioma
When does meningioma occur?
after 30 years
–>slow growing but compresses brain d/t attached to dura (can penetrate bone)
What tumor is radiation induced?
meningioma (1/4)
What mutation should you consider if multiple meningiomas?
NF2 (22q12)
higher grade tumor
Do sporadic meningiomas have the NF2 gene?
yes, 50-60%
What is the most common gene in meningioma besides NF2?
TRAF7
lower histo grade and mora stable than NF2
What is the origin of meningioma?
benign tumor of arachnoid cells in dura
EMA+
Gross appearance of meningioma
calcified psammoma bodies
en plaque (sheet like spread of tumor along surface of dura)
Histology of meningioma
whorled cluster of monotonous cells
psammoma bodies
What meningioma subtype has PAS+ droplets, TRAF7 and KFL4 mutations?
secretory
Describe atypical 2/4 meningioma
more aggressive with increased recurrence
XRT mutation, increased cellularity and mitoses
more prominent nucleoli and necrosis
clear and chordoid 2/4 more aggressive
Describe anaplastic/malignant 2/4 meningioma
resembles high grade sarcoma
high mitosis
papillary and rhabdoid subtypes
M or F predominance of meningiomas
Women, specifically pregnancy (increases frequency of presentation, not incidence)
What do 70% of meningiomas express?
PR (progesterone receptor)
What accounts for 1/2 intracranial tumors in hospitalized patients?
metastatic carcinoma (metastatic brain tumors)
What are common sources of metastatic brain tumors?
lung>breast>melanoma>kidney>GI
What rare tumor frequently mets to brain?
choriocarcinoma
What is a common malignant tumor but rarely mets to brain?
prostate
What causes hemorrhage in met tumor of brain?
melanoma
choriocarcinoma
renal cell carcinoma
lung
What is a common sit of mets in metastatic brain tumors?
meninges
–>gray/white jxn or intraperenchymal
Metastatic brain tumor in epidural or subdural space can cause…
spinal cord compression
What is carcinomatosis
tumor nodules spread along surface of brain and spinal cord
–> originate from lung and breast
What paraneoplastic syndrome is associated with an ovarian teratoma and the NMDA receptor?
anti-NMDA receptor encephalitis in hippocampal neurons
sx: psych, memory -, seizures, dyskinesia, language dysfxn
What paraneoplastic syndrome is associated with anti-HU antibody in neurons?
encephalomyelitis d/t small cell lung cancer
AKA ANNA-1 Ab
What paraneoplastic syndrome is associated with antibodies against voltage-gated potassium channels?
encephalitis d/t peripheral neuropathy
What paraneoplastic syndrome is associated with opsoclonus-myoclonus ataxia syndrome?
dancing eyes, dancing feet
NEUROBLASTOMA in kids
small cell lung ca in adults
What paraneoplastic syndrome is associated with antibodies to voltage-gated calcium cannels?
Lambert-Eaton myasthenic syndrome
small cell lung cancer
What is the treatment of paraneoplastic manifestations?
immunotherapy to remove circulating Ab
removal of primary tumor
What antibody circulates in subacute cerebellar degeneration (paraneoplastic syndrome)?
PCA-1 in women with ovarian, uterine or breast carcinoma
destroys purkinje cells, gliosis and mild inflammatory infiltrate
What peripheral nerve sheath tumor is S100+?
schwannoma
Where do schwannomas occur?
in cranium: CN VIII @ cerebellar pontine angle
also involves cranial and spinal nerves
What condition shows bilateral schwannomas?
NF2 (neurofibromatosis type 2)
What gene is implicated in schwannoma?
NFR d/t loss of merlin
Histology of schwannomas
mix of Antoni A and B
A: spindle cells with verocay bodies (palisading nuclei around nuclear free zones)
B: hypocellular, myxoid ECM
What do schwannoma patients present with?
acoustic neuroma (misnomer): tinnitus and hearing loss d/t CN VIII
What tumor can transform into malignant peripheral nerve sheath tumors (MPNST)?
plexiform neurofibroma (NF1 or sporadic)
AKA bag of worms
Describe neurofibromas
benign nerve sheath tumors
Are MPNST high or low grade?
85% HIGH grade, half arise in NF1 patients
What is the inheritance pattern of neurofibromatosis type 1?
AD
Describe neurofibromatosis type 1 (NF1)
neurofibromas of peripheral nerves
optic nerve gliomas
lisch nodules (pigmented nodules of iris)
cafe au lait spots (hyperpig cutaneous nodules)
Is NF1 or 2 more common?
NF1
What is the inheritance of NF2?
AD (Same as type 1)
Describe neurofibromatosis type 2
BL schwannomas (CN VIII) @ cerebellopontine angle
increased meningiomas and ependymomas (have NF2 gene mutation)
What inheritance is von hippel-lindaud disease?
AD
Describe von hippel-lindaud disease
hemangioblastomas of CNS (benign tumor of vessels in cerebellum and retina)
cysts of pancreas, liver and kidney
renal cell carcinoma
pheochromocytoma
What gene is implicated in von hippel-lindaud disease?
VHL on chromosome 3
nml downregulates hypoxia induced factor and VEGF, erythropoietin, etc
What do you get in von hippel-lindaud disease due to the deletion of VHL?
polycythemia (too many RBC)
VHL normally regulates erythropoietin–>since deleted, continuously made
What inheritance pattern is tuberous sclerosis?
AD
What are sx of tuberous sclerosis?
seizures, autism, mental retardation
Describe tuberous sclerosis
Harmatomas (beingn tumors)
cortical tubers (seizure-inducing)
renal angiomyolipomas
cardiac rhabdomyomas
subungal fibromas
shagreen patches (localized cutaneous thickening)
ash-lead patches (hypopigmented areas)
What genes are implicated in tuberous sclerosis?
TSC1 (chr 9, hamartin)
TSC2 (chr 16, tuberin)
What familiar tumor has a mutation in PTEN–>IK3/AKT signaling pathway that leads to dysplastic gangliocytoma?
cowden syndrome (AD)
What familiar tumor has mutations in TP53 and medulloblastomas?
li-fraumeni syndrome (AD)
What familial tumor has mutations in APC with medulloblastoma or glioblastoma?
turcot syndrome (AD)
What familial tumor has mutations in PTCH gene–>increase in sonic hedgehog signaling pathway with medullobalstoma?
gorlin syndrome (AD)
