CNS Tumors Flashcards
General CNS information
10-17/100,000 per year
- much lower frequency then other tumors
- however, they are most common in children, with 20% of childhood tumors being CNS tumors.
Roughly 50-75% are primary tumors (start within the CNS itself), the other 25% is metastatic
Tumors do not have premalignant or institutions stages
Brain tumors are generally poor prognosis
Brain tumors rarely metastasis outside of the CNS
Where are CNS tumors more likely to be found in children vs adults?
Children = posterior fossa
Adults = supratentorial
Glioma
Tumors of the brain parenchyma that can be generated from the following cells:
- oligodendrocytes = oligodendrogliomas
- astrocytes = astrocytomas
- ependymal cells = ependymomas
Astrocytomas
The majority of adult glioma (80%)
Most frequently produced in the 40-60s and usually found in the cerebral hemispheres
Symptoms:
- seizures
- headaches
- focal neurologic defects based on area of tumor in the cerebrum
3 groups of astrocytomas
Diffuse astrocytoma (grade 2)
- mean survival of greater than 5 years
- often remain static for several years, and then develop a rapid clinical deterioration
Anaplastic astrocytoma (grade 3)
Glioblastoma (grade 4)
- very poor prognosis with median survival = 15 months
Microscopic characteristics of diffuse astrocytomas
Increase in number of glial cells
GFAP- positive astrocytomas cells are present
Not a district boundary of normal vs cancer cells
How do you differentiate anaplastic astrocytomas from glioblastomas
Both look similar histologically however, necrosis and/or microvascular proliferation are present in glioblastoma
Brainstem gliomas
Occur usually in the 10-20s and make up of 20% of all brain tumors in these ages
Have three subgroups:
- intrinsic pontine gliomas = (most common and deadly)
- cervicomedullary junction glioma = (exophytic and less deadly)
- dorsally exophytic gliomas = (very benign)
Oligodendrogliomas
Account for 15% of gliomas
Most common in the 40-50s
Slow growing tumors that often show calcifications and anastomosis capillaries
Patients often complain of several years of seizure activity
- lesions are mostly in the frontal/temporal lobes
Survival depends on grade (2 = 10-20 years; 3= 5-10)
- dont metastasis
What CNS tumors show Isocitrate dehydrogenase (IDH) genes
Grade 2 astrocytomas (diffuse)
Oligodendrogliomas
What CNS tumors often show mutations of promoters in the telomerase gene?
Glioblastomas
What CNS tumors often show co-deletion of 1p and 19q chromosomal segments?
Oligodendrogliomas
What mutations are common in CNS tumors but are not specific for a particular tumor?
EGF receptor mutations
Tyrosine kinase mutations
P53/RB mutations
Polycystic astrocytoma
Benign tumors that affect 10-20 years of age
Most common in the cerebellum, 3rd ventricle, optic pathways and spinal cord
almost always are associated with a cyst connected to it
Show rose that fibers and Microcysts as well as GFAP-positive cells
What is the most common mutation in pilocytic astrocytoma?
Gain-of-function mutations in the serine-threonine kinase (BRAF)
- increases MAPK activation
Ependymoma
Most often arise near the ventricle system (4th ventricle especially) and occur in ages 10-20
*if an adult gets it, it occurs most commonly near the spinal cord and in the co-presence of neurofibromatosis type 2 condition
Show rosettes and canals as well as perivascular pseudorosettes (tumors around a vessel)
Neuronal tumors vs gliomas
Far less frequent and are usually lower grade in lesions
More commonly shows seizures
Neuronal tumors show synaptophysin and neuofilaments as markers.
Embryonal (primitive) neoplasms
Tumors that arise from the neuroectoderm and have a “small round cell” appearance
The subtype medulloblastoma is the most common form (20% of all pediatric tumors)
Medulloblastoma
Predominantly in children and always near the cerebellum
Always shows neuronal markers
- one of the few CNS tumors that are highly malignant w/ very poor survival rate
- however, is very susceptible to chemotherapy and radiation (radiosensitive)
- can be 75% 5 year survival rates with chemo
What are the three distinct groups of medulloblastoma?
Based on core pathogenic pathways and driver mutations that are present
1) WNT pathway activation in B-catenin
- most favorable prognosis
2) hedgehog pathway and PTCH1 loss-o-function
- intermediate prognosis
3) MYC overexpression
- poor prognosis
Primary CNS lymphomas
Are almsot always large B-cell lymphomas
Most common CNS tumor in immunocompromised patients
- all patients are positive for EBV
Is aggressive and deadly (poor prognosis)
Germ cell tumors in the CNS
Most common in the pineal and suprasellar regions
More common in younger patients <20 yrs and in the Japanese populations
- also male dominant
Most common form is the germinoma which is similar to testicular semi MOA
Meningiomas
Predominately benign tumors that are in the arachnoid meningothelila cells
Usually adults only and are attached to the dura directly
Usually only seen due to vague non-localizing symptoms or symptoms suggesting compression of the brain
Prognosis is variable based on size, location, grade
** very associated with neurofibromatosis type 2 and loss-of-function mutations in NF2 tumor gene
Metastasis tumors in the CNS
Most are carcinomas with roughly 50% accounting for all intracranial tumors
Most common metastasis site to the brain come from the following:
- lung
- breast
- skin
- kidney
- GI tract
Form sharp demarcated masses and elicit local edema swelling
Tuberous sclerosis
Is an autosomal dominant syndrome that is characterized by the development of hamartomas and benign neoplasms throughout the body (include INO brain)
Show cysts and extra cerebral lesions as well.
- can also show cutaneous lesions
- associated seizures often respond poorly to anti-epileptic drugs
Pathogenesis of tuberous sclerosis
Results from disruption of either TSC1 (Hamartin gene) or TSC2 (Tuberin gene)
Both negatively regulate mTOR kinase
- used to sense cells nutrient status and regulate metabolism, this loss results in increased cell growth
Von hipped-Lindua disease
autosomal dominant disroder where the individuals develop hemangioblastomas
Is associated with pancreatic, liver and kidney cysts
- also predisposes one to renal cell carcinoma and pheochromocytoma
Disease frequency = 1/40,000
Pathogenesis of Von hipped-lindau disease
Loss-o-function mutation in the VHL gene and protien production With concomitant increase in HIF levels.
- causes mass produce of red blood cells and polycythemia
