CNS Tumors

Question 1

General CNS information

Answer 1

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

Question 2

Where are CNS tumors more likely to be found in children vs adults?

Answer 2

Children = posterior fossa

Adults = supratentorial

Question 3

Glioma

Answer 3

Tumors of the brain parenchyma that can be generated from the following cells:

• oligodendrocytes = oligodendrogliomas
• astrocytes = astrocytomas
• ependymal cells = ependymomas

Question 4

Astrocytomas

Answer 4

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

Question 5

3 groups of astrocytomas

Answer 5

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

Question 6

Microscopic characteristics of diffuse astrocytomas

Answer 6

Increase in number of glial cells

GFAP- positive astrocytomas cells are present

Not a district boundary of normal vs cancer cells

Question 7

How do you differentiate anaplastic astrocytomas from glioblastomas

Answer 7

Both look similar histologically however, necrosis and/or microvascular proliferation are present in glioblastoma

Question 8

Brainstem gliomas

Answer 8

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)

Question 9

Oligodendrogliomas

Answer 9

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

Question 10

What CNS tumors show Isocitrate dehydrogenase (IDH) genes

Answer 10

Grade 2 astrocytomas (diffuse)

Oligodendrogliomas

Question 11

What CNS tumors often show mutations of promoters in the telomerase gene?

Answer 11

Glioblastomas

Question 12

What CNS tumors often show co-deletion of 1p and 19q chromosomal segments?

Answer 12

Oligodendrogliomas

Question 13

What mutations are common in CNS tumors but are not specific for a particular tumor?

Answer 13

EGF receptor mutations

Tyrosine kinase mutations

P53/RB mutations

Question 14

Polycystic astrocytoma

Answer 14

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

Question 15

What is the most common mutation in pilocytic astrocytoma?

Answer 15

Gain-of-function mutations in the serine-threonine kinase (BRAF)
- increases MAPK activation

Question 16

Ependymoma

Answer 16

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)

Question 17

Neuronal tumors vs gliomas

Answer 17

Far less frequent and are usually lower grade in lesions

More commonly shows seizures

Neuronal tumors show synaptophysin and neuofilaments as markers.

Question 18

Embryonal (primitive) neoplasms

Answer 18

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)

Question 19

Medulloblastoma

Answer 19

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

Question 20

What are the three distinct groups of medulloblastoma?

Answer 20

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

Question 21

Primary CNS lymphomas

Answer 21

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)

Question 22

Germ cell tumors in the CNS

Answer 22

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

Question 23

Meningiomas

Answer 23

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

Question 24

Metastasis tumors in the CNS

Answer 24

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

Question 25

Tuberous sclerosis

Answer 25

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

Question 26

Pathogenesis of tuberous sclerosis

Answer 26

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

Question 27

Von hipped-Lindua disease

Answer 27

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

Question 28

Pathogenesis of Von hipped-lindau disease

Answer 28

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