Lecture 8 and 12 -- CNS Tumors + Path

Question 1

what is the most common malignancy to the brain?

Answer 1

Metastatic disease – 50% from the Lung

Question 2

where do most ped tumors occur? where do most adult tumors occur?

Answer 2

Peds – 75% in Posterior Fossa

Adults – 75% in cerebral hemispheres

Question 3

WHO grading system (using astrocytoma as an example; describe the progression and associated micropath at each grade)

Answer 3

Grade 1 – ?

Grade 2 – Diffuse Astrocytoma – some atypical cells but no mitotic activity

Grade 3 - Anaplastic Astrocytoma – Increased cellularity and mitotic activity

Grade 4 - Glioblastoma – vascular proliferation/endothelial patches, necrosis, pseudopalisading

Question 4

What is meant by the term “diffuse”?

Answer 4

infiltrate the brain as individual cells; wonder out into the brain parenchyma

therefore technically non curable and start as grade 2 tumors

Question 5

Glioblastoma –

pathognomonic micropathology finding?

Answer 5

Psuedopalisading

Question 6

Primary vs secondary glioblastomas?

Answer 6

Primary – Preseents as glioblastoma, not an evolving precursor lesion.

Secondary – Evolves from Precursors

Question 7

Glioblastoma –
Median survival and pathogenesis?

Treatment ?

marker to test for?

Answer 7

the most common Primary CNS Malignancy
<12 month median survival. Characteristic rapid progression, significant mass effect, edema

Treatment: Cannot resect
Tx = Radx + Temozolomide

MGMT methylation

Question 8

What is the significance of an MGMT mutation for Glioblastoma treatment?

Answer 8

MGMT negates the effect of Temozolomide
therefore if there is an MGMT methylation, the gene is silenced and patient responds better to Temozolomide therapy

Unmethylated MGMT = negative prognostic factor (irrespective of treatment)

Question 9

Anaplastic oligodendroglioma –

Pathognomonic pathology?

genetic mutation/marker ?

prognostic significance?

Answer 9

Friend Egg with Chicken wire

1p/19q Co Deletion – positive prognostic factor

Question 10

name 3 low grade gliomas ?

what is the standard therapy?

what is the median survival time?

Answer 10

§ Diffuse astrocytoms – 5 years
Oligoastrocytoma – 7.5 years
Oligodendroglioma – 10 years

13.3 year Median Survival – with RT + PCV

Question 11

Ependymoma –
who ?

Gross path ?

buzzword for histo path?

Answer 11

more common peds tumors

Gross Path - well demarcated lesions

Histopath –
Pseudorossettes – lack true lumen

Rossettes – True Lumen

Question 12

• Myxopapillary Ependymoma –

where does it occur?
presenting symptom?
benign vs malignant?

Answer 12

benign lesion of the filum terminale

Sx – back pain

Question 13

pituitary Adenomas –
How common?
where do they occur?
presenting symptoms related to this location?

what percentage are secretory?

Answer 13

10-15% of all CNS neoplasms

Arise in Sela Tursica
Can lead to diplopia/bitemporal hemianopia

70% are secretory

Question 14

Treatment for prolactinoma?

Treatment for GH secreting tumor?

Answer 14

Prolactima – Dopamine Agonists (Bromocriptin, Cabergoline)

GH secreting tumors – Octreotide (somatostatin analog)

+ radiotherapy

Question 15

Meningioma

• how common is it?
• from what cells do they originate? where do they arppear?

Answer 15

The most common benign CNS Primary (90% are benign)

• Arise from arachnoid cap cells
• commonly at the dural base and well circumscribed

Question 16

Meningioma –
molecular pathology?
Histopathology?

Answer 16

– Loss of 22q12.2 tumor suppressor (including Merlin/Schwannoma)

– Histo: “Whorls” and Psammoma bodies

Question 17

Meningioma Treatment?

what is the best predictor of failure/recurrence?

Answer 17

GTR

STR + External Beam Radiation

	• Extent of the resection is predictor of failure

Question 18

name 4 childhood primary tumors

Answer 18

Pilocytic Astrocytoma (benign, good prognosis)

medulloblastoma (Malignant)

Ependyoma (poor prognosis)

Craniopharyngioma (Benign)

Question 19

Pilocytic Astrocytoma –
where does it commonly occur?

Gross path?

Histopath?

Answer 19

Posterior Fossae (Cerebellum)

Gross Path; Cystic appearance with “mural nodule”

Histo Path? Biphasic Architecture + rosenthal Fibers

Question 20

medulloblastoma 
classified as a ...? 
where does it occur?
Gross Path? 
Histopath? 

Tendency for what other manifestation?

pathogenesis/progression?

Treatment?

Answer 20

Primitive Neuroendocrine Tumors (PNET), but occurs in the cerebellum and therefore Medulloblastoma

Gross Path – Poorly circumscribed with necrotic hemorrhage

Histopath – Homer Write Pseudorossettes

Tendency for CSF obsturction leading to hydrocephalus

Progression: disease is very aggressive and spreads through the CSF

Treatment: Surgical treatment followed by Craniospinal Radiation and Chemotherapy

Question 21

Craniopharyngioma

• who gets these tumors?
• benign vs malignant?
• Arises from what embryological structure?
  Treatment ?

Answer 21

Benign tumor of children, but there is bimodal distribution and adults can get them too

Arise from remnants of Rathke’s Pouch

Treatment: GTR > STR + RT

Question 22

Hemangioblastoma –
associated with what familial disease?

imaging findings?
where does it commonly present?

produces what hormone?

Histology?

Answer 22

A/w Von Hippel Lindau

imaging: Cystic Mural nodule in the cerebellum

Can produce EPO and lead to secondary polycythemia

Histo: Thin walled capillaries with minimal intervening parenchyma

Question 23

what is the classic peripheral nerve sheath tumor?

Answer 23

8th cranial nerve schwannaoma

Question 24

8th cranial nerve schwannoma

aka

• where is the lesion seen on imaging?

Histopath findings?

commonly seen in what tumor syndrome?

Answer 24

aka Vestibular schwannoma

Imaging: Cerebellopontine angle;

Histo:
Antoni A – pink with “Verocay bodies” — (the nuclear free zones)

Antoni B – pale

Commonly seen with NF2

Question 25

Treatment for Vestibular schwanomma ?

risk of the treatment

Answer 25

If unilateral – Surgery
Risk - Deafness

Radiation

If Bilateral – Bevacizumab;

Question 26

Name 4 tumor syndromes ?

Answer 26

NF1 –

NF2 –

Tuberous Sclerosis

Von Hipple Lindau

Question 27

NF1 –
genetic mutation?
Associated lesions ?
Pathognomonic histo?

Answer 27

Loss of Neurofibromin Gene (tumor suppressor gene)

lesions – Cafe Au Lait, Lisch Nodules of the Iris, skin tumors, pheocromocytoma

Plexiform neurofibroma –

Question 28

NeuroFibromatosis Type 2

• genetic mutation?
• Classic Tumor ?

Answer 28

merlin/schannomin (tumor suppressor loss)

Specific for Bilateral 8th nerve schwannomas

Question 29

Tuberous Sclerosis –

genetic mutation?

CNS Lesions ?

Common manifestation?

Answer 29

Two genes which comprise a tumor suppressor complex; either can be mutated (chromosome 9 or chromosome 16)

CNS lesions — cortical tubers; subependymal nodules, subependymal giant cell astrocytomas (obstructing outflow)

Present with Seizures

Question 30

Von Hipple Lindae Disease

common tumor?
what other locations may tumors be outside the CNS

genetic mutation?

Answer 30

hemangioblastomas of the CNS

Renal cell carcinomas, Pheochromocytoma

	○ Loss of tumor suppressor gene on chromosome 3p25.3 --- involved with HIF1 metabolism

Question 31

chromosome(s) involved in Tuberous sclerosis ?

types of tumors found

common presentation

Answer 31

9 and 16

Facial tubers

cortical tubers

Subependylmal nodules

Subependymal giant cell astrocytoma (if it obstructs CSF flow) == pathognomoninc for this disease

sz

Question 32

tumors which can present with NF2

Answer 32

bilateral 8th nerve schwannomas

Ependyomas, meningiomas