CNS Tumors Flashcards
Which patients are more likely to have supratentorial tumors?
Which patients are more likely to have infratentorial tumors?
Supratentorial - adults
Infratentorial - kids
What is meant by the following tumor grades:
Grade I
Grade II
Grade III
Grade IV
Grade I: low proliferative potential, possibly of cure by resection.
Grade II: infiltrative, despite low potential, are likely to recur. Possess cytological atypia.
Grade III: require radiation and chemo. Include anaplasia and mitoses (anaplastic astrocytoma).
Grade IV: rapid pre- and post-op evolution with fatal outcome. Microvascular proliferation and/or necrosis.
What are the 4 histological parameters of Gliomas?
How many parameters exist in the following:
Grade II
Grade III
Grade IV
Nuclear atypia
Mitoses
Microvascular proliferation
Necrosis
Grade II - 1 parameter
Grade III - 2 parameters
Grade IV - 3 or 4 parameters
What ages correlate to the following Astrocytomas?
Grade II
Grade III
Grade IV
Grade II - 3rd-4th decade
Grade III - 5th decade
Grade IV - 6th decade or more
Astrocytomas are usually made of what?
What does signs does a brainstem astrocytoma have?
White matter
Long tract and brainstem signs (CN VI dysfunction)
What grades does a Pilocytic Astrocytoma have?
Which ages are most common?
Where is the tumor found?
What is the genetic predisposition?
What is the gross appearance of the tumor?
Grade I and IV
First 2 decades of life
Cerebellum or cerebral hemispheres
NF1, especially optic n. tumors (functional loss of neurofibromin in tumor)
Well-circumscribed, often cystic with a mural nodule
What can be found within a Pilocytic Astrocytoma? (5)
What stain is positive?
Biphasic pattern: loos glial cells with cystic changes and dense piloid tissue.
Hair-like cells with bipolar processes.
Rosenthal fibers
Eosinophilic granular bodies (EGBs)
Optic n. lesions
GFAP+
What is the most common primary brain neoplasm?
What grades can it have?
Where in the brain are they most commonly found?
Glioblastoma
Grade IV/IV
Throughout the brain
What is the difference between primary and secondary glioblastomas? What molecular changes are seen in each?
Primary: older patients and no precursor lesion.
-EGFR and PTEN
Secondary: preceded by lower grade lesion (TP53).
- IDH1
- R132H mutation has a better prognosis!
What is the appearance of Glioblastoma?
Contrast ring enhancing with hypodense central necrosis.
What are the 3 histological hallmarks of Glioblastoma?
- Necrosis: “Serpentine” pattern of necrosis in hypercellular areas.
- Pseudo-palisading of cells around necrosis.
- Vascular/endothelial proliferation.
- may produce a “glomeruloid body”
- VEGF is produced by alignant astrocytes in response to hypoxia.
Who is affected most by Oligodendrogliomas?
Where are these tumors located usually?
What features are seen on histology?
What grades are they?
Which genetic changes might be seen? What is the prognosis?
Adults
Cerebral hemispheres
Calcification
Perinuclear halos - “fried eggs” (artifact)
Delicate anastomosing capillaries - “chicken wire”
Grade II/IV
IDH1 and IDH2 (90%) - favorable
1P19Q loss - favorable
What grade is Anaplastic Oligo?
What is the prognosis?
Grade III/IV
Poor prognosis, similar to glioblastoma
Ependyloma is found in which patients?
What sites does it affect in the brain most?
What grade is it?
What is diagnostic?
First 2 decades of life
4th ventricle: discrete, exophytic, enhancing
Supratentorial: cystic and paraventricular
Grade III - usually supratentorial, mitoses, microvascular proliferation, necrosis; clear cell variant
Ependymal rosettes (true rosettes) are more diagnostic than perivascular rosettes
Which patients are more likely to develop a Choroid Plexus Papilloma?
Where does it occur?
What does it cause?
What would be on the DDx?
Children
Lateral ventricles
Hydrocephalus: obstruction
-increased CSF production
DDx: choroid plexus papilloma in adult vs. metastatic carcinoma
Who is most likely to develop a Colloid Cyst of 3rd Ventricle?
Where does it occur? What does it cause?
What is the outcome?
Young adults
Attached to roof of 3rd ventricle -> obstruct foramen of Monro = non-communicating hydrocephalus
Can be rapidly fatal! Can also be positional.
Who is most likely to develop Medulloblastoma?
What grade is it?
Where do they occur in the brain?
What is seen on histology?
What is the treatment?
Children (20% of tumors in kids)
Grade IV/IV
Cerebellum, midline
Sheets of anaplastic cells, abundant mitoses, Homer-Wright rosettes
Total excision and XRT = 75% survival at 5 years; very radiosensitive sensitive
What are the 4 molecular groups and prognoses of Medulloblastoma?
WNT: older kids, monosomy chr. 6, B-catenin = 5-year survival
SHH: infants and young adults, MYCN = prognosis is intermediate between WNT and groups 3 and 4
Group 3: MYC and 17(I17Q) = worst prognosis
Group 4: I17Q, no MYC, +/-MYCN = poor prognosis
What grade is Atypical Teratoid/Rhabdoid tumor?
Where does it occur?
What molecular stains are used?
What cells are seen on histology?
What molecular changes are seen?
What is the outcome?
Grade IV/IV
Posterior fossa or supratentorial
+ EMA, Vimentin
Rhabdoid cells: eosinophilic cytoplasm with sharp borders and eccentric nucleus; resembles Rhabdomyosarcoma
> 90% have chr. 22 HSNF5/INI1
If < 5 y/o - highly aggressive; usually < 1 year survival
Who is most likely to develop Primary CNS Lymphoma?
Where do they occur most?
What is the cell origin? What marker is positive?
It is often latently infected with what virus?
What is the morphology?
What suggests a CNS primary lesion?
Immunosuppressive individuals - AIDS
Usually multifocal and periventricular
B-cells and CD20+
EBV
Accumulate around vessels
“Hooping” = cells separated by reticulin and silver stain is chaacteristic of CNS primary
Where do Germ Cell tumors occur?
What ethnicity is most common?
What should be ruled-out?
What is the prognosis?
What markers are used to track response to treatment?
Along the midline
-pineal gland (males mostly) and suprasellar
Japanese
Mets of gonadal germ cell to CNS is common, so must be R/O
Good - excellent response to XRT and chemo
AFP and bHCG
What is a Pinecytoma?
Who is at a greater risk?
What is the differentiation?
What is a Pineblastoma?
Who is at a greater risk?
What is the differentiation?
What gene is implicated often?
Pinecytoma: well-differentiated; low-grade usually adults
Pineblastoma: poorly-differentiated; high-grade with mitoses and necrosis; usually kids
-RB gene mutation
What age is most common to develop a Meningioma?
Where does it spread?
What induces the tumor?
What is the gene association?
Which one is associated with a lower grade histology?
What is it composed of?
What stain is positive?
> 3rd decade
Penetrates bone - hesitant to invade brain, so will compress it instead
Radiation
NF2
TRAF7 - lower grade and more stable
Dura based - meningothelial cell origin of arachnoid
EMA+
What are histological findings of a Meningioma?
What is meant by En Plaque?
The “secretory subtype” is determined by what positive stain? What mutations does it have?
What are the differences between Atypical II/IV and Anaplastic II/IV?
Whorled clusters of monotonous cells and Psammoma bodies
Sheet-like spread of tumor along surface of dura
PAS+; TRAF7 and KLF4 mutations
Atypical II/IV: > 4 mitoses /10hpf
-Clear and Choroid II/IV more aggressive
Anaplastic II/IV: > 20 mitoses/10hpf; resembles sarcoma
-Papillary and Rhabdoid subtypes
What is the association with Meningioma and pregnancy?
They are slightly more common in women (3:2)
Approx. 70% express PR (some express ER)
About half of women found relief of symptoms within 1 week post-partum
What are 3 major sites that metastasize to the brain?
What are 2 more uncommon tumors, but often go to brain?
Hemorrhage is associated with which primary tumors? (4)
Meningeal metastasis are common. What is the site of intraparenchymal metastases?
What is carcinomatosis? Which 2 tumors are commonly implicated?
Lung (35%), breast (20%), melanoma (10%)
Choriocarcinoma (rare) but mets to brain
Renal cell carcinoma lead to late mets
Melanoma, Choriocarcinoma, RCC and lung
Gray/white matter junction
Tumor nodules spread along the surface or brain and cord; lung and breast most commonly
What antibody is positive in Subacute Cerebellar Degenration paraneoplastic syndrome?
What is the process of the syndrome?
Which cancers is it associated with?
PCA-1
Destruction of Purkinjes, gliosis and mild chronic inflammatory infiltrate
Women with ovarian, uterine or breast cancer
Which of the following antibodies/receptors are associated with which primary process?
ANNA-1
NMDA-receptor
VGKC-somplex antibody
What do they cause generally?
ANNA-1: small cell lung cancer (CNS and PNS)
NMDA-receptor: ovarian teratomas (hippocampus)
VGKC-complex antibody: peripheral neuropathy (VG K+ channels)
Limbic encephalitis - these symptoms often appear before malignancy is suspected
Eye movement disorders, like opsoclonus, is a paraneoplastic syndrome associated with which malignancy?
Neuroblastoma in kids
What paraneoplastic syndrome affects voltage-gated Ca++ channels?
Lambert-Eaon myasthenic syndrome
NF1 is associated with which lesion?
Inheritance and prevalence:
What are 4 other associations?
Pheochromocytoma
AD, 1/3000
Neurofibromas of peripheral nerves
Cafe-au-lait spots
Optic n. glioma
Lisch nodules - pigmented nodules of iris
VHL is associated with which 2 lesions?
What are 3 other associations?
Pheochromocytoma, Paraganglioma (rare)
Renal cell carcinoma
Hemangioblastoma
Pancreatic endocrine neoplasm
What is the normal function of NF1 gene?
What is the normal function of NF2 gene?
NF1: negatively regulates RAS signaling (neurofibromin)
NF2: integrates cytoskeletal signaling (merlin)
What is the mutation association with the following:
Cowden syndrome
Li-Fraumeni syndrome
Turcot syndrome
Gorlin syndrome
Cowden syndrome: PTEN -> IK3/AKT
Li-Fraumeni syndrome: TP53
Turcot syndrome: APC
Gorlin syndrome: PTCH -> upregulation of SHH
What is the inheritance of TSC? What are the symptoms?
What is the protein and location of TSC1 and TSC2?
What are the major associated tumors? (4)
AD (1/6000) - seizures, autism, MR
TSC1: chr. 9Q34 - Hamartin
TSC2: chr. 16P13.3 - Tuberin
Hamartomas
Retinal angiomyolipomas
Cardiac rhabdomyomas
Cutaneous lesions: Shagreen patches (localized cutaneous thickenings) and Ash-leaf patches (hypopigmented areas)
What are the molecular consequences of VHL disease?
What is the inheritance?
What are classic conditions/tumors seen? (5)
VHL mutation downregulates HIF-1, which regulates expression of VEGF
AD
Polycythemia Hemangiomas of CNS (cerebellum and retina) Cysts in pancreas, liver and kidneys Renal cell carcinoma Pheochromocytoma
NF2 is associated with which lesion?
Which 2 other lesions are of increased prevalence?
Inheritance and prevalence:
Bilateral Schwannomas (CN VIII) Meningiomas and Ependymomas
AD, 1/40-50K
Where do Schwannomas occur? What marker is positive?
What is an associated tumor?
What gene is defective?
What is seen in the Antoni A variant?
Cerebellar pontine angle - S100+
Acoustic neuroma = CN VIII dysfunction
NF2 - loss of merlin
Verocay bodies = palisading nuclei around “nuclear free zones”
What appearance is associated with Plexiform Neurofibroma? What is a possible complication?
What is the gene association?
“Bag of worms” - may cause malignant transformation to MPNST
NF1
What is a malignant peripheral nerve sheath tumor (MPNST)?
What is a subtype?
A tumor that arises in 85% ofhigh-grade tmors and about 1/2 of NF1 patients
Triton tumor - Rhabdomyoblastic differentiation
