Tumors Flashcards
Where do a majority of CNS tumors arise in children?
- Posterior fossa –> Cerebellum or brainstem
Do CNS tumors travel outside the CNS?
- Not usually
What can be seen in some pediatric tumors?
- Spread through the CSF in the subarachnoid space
What is the most common CNS tumor overall?
- Glioblastoma
What is the most common CNS tumor in children?
- Embryonal –> Pilocytic astrocytoma and medulloblastoma
Where is the most common location for tumors in adults?
- Supratentorial
What are the different grades of tumors?
- Grade I: low proliferative potential, cure by resection
- Grade II: Infiltrative, despite low proliferative potential –> some atypia
- Grade III: Radiation or chemo –> Atypia and mitoses present
- Grade IV: rapid pre and post op evolution, FATAL outcome –> microvascular proliferation and necrosis
What automatically makes a tumor a grade IV?
- Necrosis
What are the four histologic parameters of grading gliomas?
- Nuclear atypia
- Mitoses
- Microvascular proliferation
- Necrosis
How is grading made for gliomas?
- II = one parameter
- III = two parameters
- IV = 3 or 4 parameters
What are some grade I astrocytomas?
- SEGA
- Pilocytic astrocytoma
What are some grade II astrocytomas?
- Diffuse astrocytoma
- PXA
- Pilomyxoid astrocytoma
What is a grade III astrocytoma?
- Anaplastic astrocytoma
What are some grade IV astrocytomas?
- Glioblastoma
- Giant cell GBM
- Gliosarcoma
What grade is an oligodendroglioma?
- Grade II or anaplastic grade III
- No grade IV so there is longer survival
What happens with risk for astrocytomas as people age?
- Risk of higher grade as people age
- Grade I usually seen in first decade
- Grade II seen in 3rd-4th decade
- Grade III seen in 5th decade
- Grade IV seen in 6th decade and beyond
Where do astrocytomas usually affect?
- White matter
What are some symptoms of a infiltrating astrocytoma (grade II to IV)?
- Seizures
- Headaches
- Focal neuro deficits
What mutation makes for a better prognosis in infiltrating astrocytomas?
- IDH-mutant is better than IDH wild type
- IDH R132H mutant protein IHC
What does an infiltrating astrocytoma look like grossly?
- Poorly defined
- Gray
- Infiltrative tumors
What does an infiltrating astrocytoma look like microscopically?
- Hypercellular
- Elongated, irregular hyperchromatic nuclei
Who is most likely affected by a pilocytic astrocytoma?
- Children in the first decades of life
Where are pilocytic astrocytomas typically found?
- Cerebellum
- Third ventricle
- Optic nerves
What mutation is seen in pilocytic astrocytomas?
- IAA1549-BRAF gene
What predisposes children for pilocytic astrocytomas?
- NF1 predisposes –> especially for optic nerves tumors
What do pilocytic astrocytomas look like?
- Well circumscribed, often cystic with a mural nodule
What is the treatment for pilocytic astrocytomas?
- Resection only
What does radiology show in pilocytic astrocytomas?
- Discrete, contrast enhancing mural nodule
- Lack of surrounding edema
- Cyst
What is seen histologically for pilocytic astrocytomas?
- Biphasic pattern –> loose glial with cystic changes and dense piloid tissue
- Hair-like cells with long bipolar processes
- Rosenthal fibers
- EGBs
What genetic aberrations are seen in glioblastomas?
- CDKN2A deletions
- EGFR or PDGFR gene amplification
- TP53 mutation –> resistance to apoptosis
Who is affected with primary glioblastoma? What mutations are seen?
- Usually in older patients with no precursor lesion
- IDH-wild type, Grade IV
- TERT and EGFR
Who is affected with secondary glioblastoma? What mutations are seen?
- Usually in younger patients with a low grade lesion (TP53)
- IDH1 (R132H better prognosis than wild type) and IDH2
What is seen in glioblastoma?
- Contrast enhancing ring –> hypodense central necrosis imaging
What are the histologic hallmarks of glioblastomas?
- Necrosis –> serpentine pattern
- Pseudo-palisading of cells around necrosis
- Vascular/endothelial proliferation –> VEGF produced by malignant astrocytes in response to hypoxia
What age is affected by oligodendrogliomas?
- People in 4th or 5th decades
What area do oligodendrogliomas affect?
- Cerebral hemispheres
- Predilection for white matter
What are the symptoms of oligodendrogliomas?
- Neurologic complaints for several years
- Calcifications usually restricted to the cortex, curvilinear or gyriform distribution
What do oligodendrogliomas look like histologically?
- Perineuronal satellitosis
- Perivascular aggregation and subpial accumulation of tumor cells
- Perinuclear halos –> look like fried eggs
- Delicate anastomosing capillaries –> looks like chicken wire
What are the most common mutation in oligodendrogliomas?
- IDH1 and IDH2 –> Favorable prognosis
- 1P19Q loss –> favorable prognosis
What is seen in anaplastic oligodendroglioma? Prognosis?
- Vascular hypertrophy and necrosis
- Often retains geometric vascularity
- Poor prognosis
Who is most affected by ependymomas?
- Children in first two decades of life
Where are ependymomas usually found?
- Fourth ventricle floor is most common site
- Spinal cord if found in adults
What do grade III ependymomas look like?
- Usually supratentorial with mitoses, microvascular proliferation, necrosis
- Round or oval nuclei
- Fibrillary cytoplasmic processes extends to form meshwork
- Ependymal rosettes –> more diagnostic than perivascular rosettes
What is seen in anaplastic ependymoma?
- Increased cells
- Increased mitosis
- Palisading necrosis
- +/- microvascular proliferation
What is the best predictor of anaplastic ependymoma?
- Extent of surgical resection and molecular subtype
What is a myxopapillary ependymoma?
- Filum terminale
- Cuboidal tumor cells arranged in a papillary pattern around mucin-fibrovascular cores
Where are subependymomas found?
- Lateral or 4th ventricle under ependymal layer
What are some symptoms of subependymomas?
- Slow growing, solid, +/- calcified
- Usually asymptomatic and an incidental finding
- Could cause obstructive hydrocephalus
Where are choroid plexus papillomas found?
- Common in children
- Lateral ventricles
What can choroid plexus papillomas cause?
- Hydrocephalus –> obstruction
What is a colloid cyst of the 3rd ventricle?
- Found in young adults
- Attached to roof of third ventricle
- Can be rapidly fatal
- Can be positional
What can a colloid cyst of 3rd ventricle cause?
- Obstruct foramen of monro causing noncommunicating hydrocephalus
What is a ganglioglioma?
- Mix of mature, neuronal, and glial cells
How do gangliogliomas present?
- Superficial lesions present as seizures; medical refractory epilepsy
- Temporal lobes
What is the activating mutation in gangliogliomas?
- BRAF gene (V600E)
What is dysembryoplastic neuroepithelial tumor (DNET) associated with?
- Associated with epilepsy
What is the treatment for gangliogliomas and DNET?
- Surgical resection
Where are DNETs found? What do they look like?
- Superficial temporal lobes
- Multiple discrete mucin-rich intracortical nodules of small oligodendrocyte like cells
What is the most common embryonal tumor?
- Medulloblastoma
What are some embryonal tumors?
- Medulloblastoma
- Atypical teratoid/rhabdoid tumor (AT/RT)
- Primitive neuroectodermal tumor (PNET)
What are the four groups of medulloblastomas?
- WNT
- SHH
- Group 3
- Group 4
What medulloblastoma group has the best prognosis?
- WNT
What medulloblastoma group has the worst prognosis?
- Group 3/4
What mutation is seen in the WNT medulloblastoma?
- Chr. 6 B-catenin
What mutation is seen in the SHH medulloblastoma?
- MCYN AMP
What mutation is seen in group 3 medulloblastoma?
- MCY and 17(17Q)
What mutation is seen in group 4 medulloblastoma?
- I17Q, no MYC or MYCN
Where are WNT medulloblastomas found?
- Anterior 4th ventricle or middle cerebral peduncle
Where are SHH medulloblastomas found?
- Vermis or lateral cerebellum
What can be seen in medulloblastomas?
- CSF flow can be occluded
- Propensity to spread into the subarachnoid space –> drop metz
What do medulloblastomas look like grossly?
- Well circumscribed
- Gray friable
- May involve leptomeninges
What do medulloblastomas look like histologically?
- Densely cellular, sheets of anaplastic cells
- Abundant mitoses –> KI-67 proliferation marker high)
What is a part of the classic subtype of medulloblastomass?
- Homer-Wright rosettes
- + Synaptophysin
What is a part of the desmoplastic/nodular variant of medulloblastomas?
- Internodular areas of stroma, collagen, and reticulin
- Pale islands of neuropil with neuronal differentiation
What is a part of the large cell/anaplastic variant of medulloblastoma?
- Large irregular vesicular nuclei
- Prominent nucleoli
- Cell wrapping
- High mitotic/apoptotic rate
What is an important feature of medulloblastoma?
- Exquisitely radiosensitive –> WNT has 100% survival rate
What tumors have the PTCH1 gene mutation?
- Desmoplastic medulloblastoma
- Nevoid basal cell carcinoma syndrome
Where are atypical teratoid/rhabdoid tumors found?
- Posterior fossa or supratentorial
What are atypical teratoid/rhabdoid tumors positive for?
- EMA and vimentin
- +/- Smooth muscle actin and keratins
- Neg desmin and myoglobin
What mutation is seen in atypical teratoid/rhabdoid tumors?
- Chr 22; HSNF5/INI1
Who is most likely affected with primary CNS lymphoma?
- Immunosuppressed individuals –> AIDS or transplantation
What are some qualities of primary CNS lymphoma?
- Primary, often multifocal
- Periventricular spread is common
- B-cell origin CD20+
What are people with primary CNS lymphoma typically infected with?
- Latent infection of EBV
What does the morphology of primary CNS lymphoma look like?
- Accumulate around vessels
- “Hooping” = cells separated by reticulin + silver stain
Where are germ cell tumors typically found?
- Along midline
- Pineal and suprasellar
Where are the metz typically found from germ cell tumors?
- Gonadal germ cell tumors typically go to CNS
What is a germinoma?
- Resembles seminoma
- Good response to XRT and chemo
- AFP and BetaHCG can be used to track response
When are meningiomas seen?
- Females in their 3rd decade
- Has a high predominance in women who are pregnant
- Once baby is delivered, then meningioma reduces in size
What happens in meningiomas?
- They enlarge slowly and are reluctant to infiltrate the brain
- Compresses the brain
What is special about meningiomas?
- Will penetrate the brain
What causes meningiomas?
- Radiation induced
What mutation is seen in meningiomas?
- NF2 –> multiple, loss Ch22Q
What should be considered if there are multiple meningiomas are found?
- NF2 diagnosis
What mutations are seen in lower risk meningiomas?
- TRAF7
- KLF4
- AKT1
- SMO
What mutations are seen in higher grade meningiomas?
- TERT
- CDKN2A
What do meningiomas look like?
- Basselated dural mass that is rubbery and round
- Compresses underlying brain
- “En Plaque” sheetlike across the surface of the dura
What do meningiomas look like histologically?
- Calcified psammoma bodies –> sand like consistency
- Whorled clusters of monotonous cells
Where are some places that meningiomas found?
- Left lateral ventricle is favored
- Parasagittal, cerebral convexities, wing of sphenoid bone, sella, olfactory groove, foramen magnum, optic nerve
What is seen in the atypical type of meningiomas?
- Grade II
- More aggressive
- Increased recurrence
What is seen in the anaplastic type of meningiomas?
- Grade III
- Resembles high grade carcinoma or sarcoma
- De novo or malignant progression from lower grade
What is the difference in mitoses between atypical meningioma and anaplastic meningioma?
- Atypical –> ≥4 mitoses
- Anaplastic –> >20 mitoses
What is a rare tumor but has frequent metz to the brain?
- Choriocarcinoma
What is a common malignancy but rarely metz to the brain?
- Prostate
What is a common site of metz in the brain?
- Meninges
- Intraparenchymal = gray/white junction
What is meningeal carcinomatosis?
- Tumor nodules spread through subarachnoid –> cranial and spinal neuropathies from nerve root compression
- Lung and breast most commonly
What is subacute cerebellar degeneration?
- PCA-1 antibody recognizes purkinje cells
- Destruction of purkinje cells, gliosis, and mild chronic inflammatory infiltrate
Who typically has subacute cerebellar degeneration?
- Women with ovarian, uterine, or breast carcinoma
What is limbic encephalitis?
- Subacute dementia
- Affects anterior and medial temporal lobe
What other tumors are seen in cowden syndrome? What is the mutation?
- Dysplastic gangliocytoma
- Mutation in PTN –> IK3/AKT signaling pathway
What other tumors are seen in Li-fraumeni syndrome? What is the mutation?
- Medulloblastomas
- Mutations in TP53
What other tumors are seen in Turcot syndrome? What is the mutation?
- Medulloblastoma or glioblastoma
- Mutations in APC or mismatch repair genes
What other tumors are seen in Gorlin syndrome? What is the mutation?
- Medulloblastoma
- Mutation in PTCH gene resulting in up regulation of SHH pathway
What does the TSC1 gene encode for?
- Hamartin
What does the TSC2 gene encode for?
- Tuberin
What is seen in tuberous sclerosis?
- Hamartomas –> cortical tubers
- Retinal glial hamartomas
- Renal angiomyolipomas
- Cardiac rhabdomyomas
What cutaneous lesions are seen in tuberous sclerosis?
- Angiofibromas, subungual fibromas
- Shagreen patches
- Ash-leaf patches
What is the mutation in von hippel lindau disease?
- VHL on Ch3
What does the VHL gene do?
- Downregulates HIF-1 which regulates expression of VEGF
- Involved in the expression of erythropoietin causing polycythemia
What is seen in von hippel lindau disease?
- Hemangioblastomas of the CNS
- Cysts of pancreas, liver, and kidneys
- Renal cell carcinoma
- Pheochromocytoma
What is seen in neurofibromatosis type 1?
- NF1 gene –> neurofibromin
- Neurofibromas of peripheral nerves
- Optic nerve gliomas
- Lisch nodules
- Cafe au lait spots
What is seen in neurofibromatosis type 2?
- NF2 gene –> merlin
- Bilateral schwannomas (CN VIII)
- Multiple meningiomas, ependymomas of the cervical spinal cord
What is schwannomatosis?
- Same frequency as NF2
- Multiple non vestibular schwannomas throughout the body or single region
What is a schwannoma? What gene is affected?
- S100+
- NF2 –> loss of merlin; even sporadic associated with NF2 gene
What is seen in Antoni A schwannoma?
- Dense
- Eosinophilic spindle cells arranged intersecting fascicles
- Verocay bodies –> palisading nuclei around “nuclear free zones”
SWhat is seen in Antoni B schwannoma?
- Hypocellular
- Myxoid extracellular matrix
- Microcyst formation
