Lecture 40 - Neuropathology and CNS Tumors

Question 1

________, optic disc swelling, is a STRONG indicator of increased ICP (intracranial pressure). Also, Cushing’s triad, which includes Increased ______, Decreased ______, and Irregular ______, is a strong sign.

Answer 1

Papiledema

Increase BP

Decreased HR

Irregular Breathing

Question 2

Increased ICP can also lead to Herniation. Look for patients presenting with decreased level of _______, _____ nerve palsy (“blown pupil”), and Posturing (abnormal flexion or extension of Arms and Legs).

Why does 3rd nerve palsy result in “blown pupil?”

Answer 2

Consciousness

3rd nerve palsy

It’s because the Autonomic fibers are around the periphery of the 3rd nerve, so they are the first to become compressed with brain herniation.

Question 3

Know these different types of Herniations

Answer 3

Question 4

Of brain tumors, which three types are most responsive to chemotherapy?

Answer 4

Meduloblastoma

Oligodendroglioma

Glioblastoma (low grade)

Question 5

Most Brain tumors are NOT primary; they are mets. They usually present as _______ (multiple or single?) lesions that are _______ (sharply or not well?) circumscribed and are commonly found at the _____-_____ boarder. _____ and _____ are the most common sites from which metastatic brain tumors arise.

In which structure of the brain is it RAREST to find primary tumors?

Answer 5

Multiple

Sharply circumscribed

Grey-white boarder

Breast and Lung

Cerebellum (VAST majority are mets)

Question 6

Meningeal _______ refers to invasion of the meninges with carcinoma, which clouds their appearance. Look for glandular invasion into the _______ space.

Answer 6

Meningeal Cacinomatosis

Subarachnoid

Question 7

There tends to be a difference in the location of priary brain tumors between children and adults. Where do they tend to form in each population?

Answer 7

Children –> Infratentorial region

Adults –> Supratentorial region

Thus, if you see an Adult presenting with an Infratentorial (e.g.cerebellar) tumor, think mets.

Question 8

Meningiomas arise from _________ cells with mutations in or around the _____ gene on chromosome _____ (or complete loss of the _____ arm). They are _______ (location), and so Extra-axial –> the issue is that they compress the brain, not ivade it.

Answer 8

Meningothelial cells

NF2 gene

22

22q arm

Intradural

Question 9

“Meningothelial ______” and “_______ bodies” are characteristic histological findings of Meningiomas.

Answer 9

Meningothelial Whorls

Psammoma bodies

Question 10

________ are the msot common Primary (and infiltrating) brain tumors.

________ Astrocytomas are a Primary brain tumor more common in Children, so they often form in the _______.

Answer 10

Glioblastomas

Pilocytic Astrocytomas

Cerebellum

Question 11

Pilocytic Astrocytomas are among brain tumors that arise from the ______ independent pathway. They often form in the _______, but can be in other locations.

If they are not part of NF1 syndrome, they are considered sporadic, which have a high frequency of Tandem duplications leading to an oncogenic _______ fusion gene with activation of the _______ pathway.

Pilocytic Astrocytomas are considered WHO grade ____.

Answer 11

IDH Independent pathway

Cerebellum

BRAF fusion gene

MAPK pathway

WHO grade 1

Question 12

Astrocytomas and Infiltrating brain tumors are graded 2-4. What are the defining features of Grade 4?

Answer 12

Microvascular proliferation and Necrosis

Question 13

Infiltrating Gliomas tend to disseminate through _____ _____ tracts. Dissemination through _____ is rare with Gliomas (it’s more common with Embryonal tumors and Glioblastomas). These only rarely metastasize outside the brain.

Answer 13

White Matter tracts

CSF

Question 14

The following are Astrocytoma classifications:

Diffuse Fibrillary Astrocytoma is WHO Grade ____

Anaplastic Astrocytoma is WHO Grade ____

Glioblastomas are WHO Grade ____.

Keep in mind Diffuse Fibrillary and Anaplastic Astrocytomas almost invariably progress to Glioblastomas, BUT de novo Glioblastomas (IDH INDEPENDENT pathway) are the most common.

Answer 14

2

3

4

Question 15

Glioblastomas (WHO Grade 4) have characteristic two pathognomonic features on histology:

1. ________ necrosis
2. _______ proliferation

Answer 15

1, Palisading necrosis

2. Microvascular proliferation

Notice the pink necrosis with Palisading cells around it

Question 16

Oligodendrogliomas are defined by loss of chromosomes ____ and ____ AND IDH 1/2 mutations.

Answer 16

1q and 19q

Question 17

_________ are primary brain tumors that arise in the Ventricles. In children, they arise in the _____ ventricle. Histologically, they exhibit characteristic Vascular _______ (areas of acellularity around a blood vessel with cellularity on the outside of the acellular area).

Answer 17

Empyndymomas

4th ventricle

Vascular Pseudorosettes

Question 18

________ are embryonal tumors that arise in the Cerebellum. Remember that embryonal tumors of the brain, especially these, are the most likely to disseminate via ______.

Answer 18

Medulloblastoma

CSF

Question 19

Primary brain ________ are rare, unless the patient is Immunocompromised/immunosuppressed. These tumors are often multifocal with areas of necrosis. Look out for patients who have received transplants.

Do these arise most often from B or T cells? Also know that _____ can be found in these tumor cells.

Answer 19

Lymphoma

B-cell most often.

EBV can be found in tumor cells (should make sense since it invades B cells)

Question 20

__________ are WHO Grade 1 and have a Variegated appearance on histology (dry and wet keratin with mixed cellularity.) They appear in young children and older adults (bimodal age distribution).

Answer 20

Craniopharyngiomas

Question 21

What’s the difference between a Neurofibroma and Schwannoma?

The Vestibular branch of CN _____ is a common point of origin for Schwannomas.

Answer 21

Neurofibromas are tumors of the Nerves, themselves. Schwannomas arise from Schwann cells AROUND the nerve, so they can be reoved while sparing the nerve, unlike with neurofibromas.

CN VIII

Question 22

Schwannomas have a very characteristic _______ appearance histologically.

Answer 22

Biphasic

Question 23

Neurofibromatosis Type 1 arises from autosomal ______ mutations in chromosome _____11.2. Look for patients with Cafe-au-lait spots.

_________ Neurofibromas indicate the patient likely has NF1 until proven otherwise. It has a characteristic “bag of worms” appearance on histology.

Answer 23

Dominant

17q 11.2

Plexiform Neurofibromas

Question 24

Neurofibromatosis Type 2 is very rare, and it paradoxically doesn’t present with Neurofibromas. It arises from a mutation in ______ gene on chromosome ____ 12. Look for Bilateral vestibular _______ in these patients.

Answer 24

Merlin

22q 12

Schwannomas