Neuro Test 1: Leonard_Tumors Of The Cns And Pns

Front 1

What aspect of a CNS tumor is the primary predictor of biologic behavior (prognosis)?

Back 1

Tumor Histology Appearance

Front 2

In general, adult CNS tumors are located ______

Back 2

supratentorial

Front 3

In general, child CNS tumors are located ______

Back 3

infratentorial

Front 4

Most common CNS tumor in a child (<20 yo)?

Back 4

Astrocytoma

Front 5

How common are metastatic CNS tumors in children

Back 5

Rare!

(50% are metastatic in adults)

Front 6

-altered cognition, personality changes, expressive aphasia (esp. the posterior left anterior frontal gyrus); motor disturbances (esp precentral gyrus --> contrlateral deficits)

-These signs and symptoms would result from a tumor in the ___ lobe

Back 6

frontal lobe

Front 7

-seizures; emotional changes; receptive aphasia

-These signs and symptoms would result from a tumor in the ___ lobe

Back 7

temporal lobe

Front 8

- sensation abnormalities (contralateral)

--These signs and symptoms would result from a tumor in the ___ lobe

Back 8

parietal lobe

Front 9

If a tumor were to cause impaired appreciation of shape, size, weight, texture (astereognosia) you would know it was a ______ -type tumor

Back 9

cortical-type tumor

Front 10

Thalamic Syndrome is caused by a CNS tumor on or near the thalamus and causes ______

Back 10

spontaneous pain

Front 11

A tumor is causing visual field deficits. You know it is affecting the _____ lobe

Back 11

occipital lobe

Front 12

What is the most common primary CNS tumor in adults?

Back 12

GBM

Front 13

Most adult CNS tumors are supratentorial and located in the _______

Back 13

cerebrum

Front 14

Most child CNS tumors are infratentorial and located in the _____ or _________

Back 14

cerebellum

4th ventricle

Front 15

GBM and oligodendroglioma are more commonly seen in what age group?

Back 15

Adults

Front 16

Medulloblastoma and pilocytic astrocytoma are more commonly seen in what age group?

Back 16

Children (20 or younger)

Front 17

You are looking at a CT/MRI with contrast and notice ring-enhancing lesions. What are those?

Back 17

**Ring enhancing lesions**

—discovered on CT/MRI with contrast and present as a **white line around a darker region** --> due to enhancement from increased blood flow at the periphery

Front 18

Name the ring-enhancing lesions of the CNS.

"MAGIC DR"

Back 18

M-etastatic
A-bscess
G-lioma
I-nfarction
C-ontusion

D-emyelinating Diseases
R-adiation necrosis

Front 19

You are giving a contrast MRI to a patient that was determined to have a brain lesion. There is no post-contrast enhancement. What does this mean?

Back 19

No post contrast enhancement = the BBB is intact

-no leakage of contrast into the lesion

Front 20

Vasogenic vs. Cytotoxic vs. Interstitial Cerebral Edema:

-increased BB permeability -->extracellular

• Damaged vessels-inflammation, neovascularization

• White matter > gray matter; steroids helpful

• Tends to have associated edema**

Back 20

Vasogenic Edema

Front 21

Vasogenic vs. Cytotoxic vs. Interstitial Cerebral Edema:

-impaired Na/K ATPase -->intracellular

• Hypoxia/ischemia; intact BBB

• Gray matter = white matter; steroids not helpful

Back 21

Cytotoxic Edema

Front 22

Vasogenic vs. Cytotoxic vs. Interstitial Cerebral Edema:

-transependymal fluid shift --> extracellular

• Due to ­ CSF pressure (hydrocephalus)

Back 22

Interstitial Cerebral Edema

Front 23

Identify the primary cell types that give rise to CNS neoplasms

Back 23

• Glial cells
1. Astrocytes**
2. Oligodendrocytes**
3. Ependymal cells**

• Neurons (*Robbins)

• Other neuroepithelial cells – choroid plexus**

• Embryonal (primitive neuroepithelial cells) – Medulloblastoma**

• Cells of the meninges (“arachnoid cap cells”) – Meningioma**

• Hematolymphoid (lymphocytes) – Lymphoma**

• Germ cells** – can arise outside gonads; tend to arise midline

Front 24

Identify the neuroepithelial cells that can give rise to CNS tumors

Back 24

• Glial cells
1. Astrocytes**
2. Oligodendrocytes**
3. Ependymal cells**

• Neurons (*Robbins)

• Other neuroepithelial cells – choroid plexus**

• Embryonal (primitive neuroepithelial cells) – Medulloblastoma**

• Cells of the meninges (“arachnoid cap cells”) – Meningioma**

Front 25

WHO Grade I-IV:

- may be curative with surgery

• Low proliferative activity

• Typically well-circumscribed; good potential for surgical cure

Back 25

WHO Grade I

Front 26

WHO Grade I-IV:

-typically survive > 5 yrs

• Low proliferative activity

• Infiltrative; often recur; may progress to higher grade

Back 26

WHO Grade II

Front 27

WHO Grade I-IV:

-typically survive ~ 2-3 yrs

• Greater proliferative potential; more aggressive behavior

• Generally treated with adjuvant chemo/XRT

Back 27

WHO Grade III

Front 28

WHO Grade I-IV:

-typically < 1 yr survival

• **High proliferative** activity; tumor necrosis; “glomeruloid” endothelial proliferation/neovascularization

• Typically “not curable

Back 28

WHO Grade IV

Front 29

A 10-yo boy has had persistent headaches for the past three months. On P.E., he is afebrile. He has an ataxic gait. CT scan of his head shows a 4-cm cystic mass in the right cerebellar
hemisphere. Cerebral ventricles are enlarged. A lumbar puncture is performed: CSF protein is elevated, but glucose is normal. Neurosurgery is performed and the mass is removed and evaluated.

The mass has a thin cyst wall and contains gelatinous material and a mural nodule. Microscopic analysis shows GFAP-positive cells with long, hair-like processes.

The most likely diagnosis is …

Back 29

Pilocystic Astrocytoma

**MOST COMMON CNS TUMOR OF CHILDREN**

Front 30

BUZZWORDS:

Cystic with mural nodule

One of most common pediatric brain tumors **CHILDREN **

Cerebellum

Rosenthal fibers—“carrots”

Back 30

Pilocystic Astrocytoma

Front 31

 WHO Grade

**Fibrillary** histologic features most common

~ 15% of astrocytomas

Peak ~30-40 y (adults)** YOUNG ADULTS**

**Frontal white matter; disrupts gray-white junction

5 yr survival with total resection + XRT = 70%

**50% will progress to higher grade over time

**Micro**
• No mitoses; hemorrhage is relatively rare

- May see microcalcifications

•↑ p53 staining (mutated form of p53)**

Back 31

Diffuse Infiltrating Astrocytoma - Adult

(No post-contrast enhancement = BBB intact)

Front 32

WHO Grade III**

- Increased cellularity, cytologic atypia (pleomorphism)**

-Mitotic figures are present; +/- endothelial proliferation; no necrosis; rare calcification

- Immunoperoxidase stains for proteins present in actively cycling cells can indicate growth fraction of tumor (e.g., MIB-1 stain)

~30% of astrocytomas

Peak age 40-60 yo **OLDER ADULTS**—>likely d/t progression of lower grade lesions)

Back 32

Anaplastic Astrocytoma

Front 33

WHO Grade IV**

~ 50% of astrocytomas

**Most frequent primary brain tumor in adults**

Peak age: 45-60 yo **OLDER ADULTS**

-Most common location: deep frontotemporal

-Molecular: ­ EGFR (Chromosome 7)—epidermal GF expression receptor

Back 33

Glioblastoma Multiforme (GBM)

• Primary GBM – arise de novo (from nothing, brand new tumor, arose as GBM)

**Older patients

-EGFR mutations/amplifications early


• Secondary GBM – arise via progression from lower-grade glioma

**Younger patients

-p53 mutations early & ­PDGF-A receptor signaling late

Front 34

**Imaging**

• Postcontrast injection CT MR studies, many are characterized by a bright (“enhancing”) ring

• Ring surrounds a region of hypodensity (central necrosis)

**Micro**

•Palisading necrosis— dense cellularity, striking pleomorphism, and zones of coagulative necrosis lined by “palisading” tumor cells

Endothelial Hyperplasia-complex, “glomeruloid” quality of microvascular proliferation

Back 34

GBM

Front 35

Micro**

• “Chicken-wire”** vasculature—capillary with branching pattern

• **“Fried egg” cytology—yolk – nucleus, w/ surrounding cytoplasm

• Calcifications (~80%)

• Uniform, round nuclei and clear perinuclear halos

Back 35

Oligodendroglioma

Front 36

WHO Grade II – ??? (better 5 yr survival)**

WHO Grade III – anaplastic**

~10% gliomas

Peak age 35-40 yo **YOUNG ADULTS**

- Often mixed with astrocytomas

- Tumors with chromosome 1p/19q deletions**


Micro**

• “Chicken-wire”** vasculature—capillary with branching pattern

• **“Fried egg” cytology—yolk – nucleus, w/ surrounding cytoplasm

• Calcifications (~80%)

• Uniform, round nuclei and clear perinuclear halos

Back 36

Oligodendroglioma

Front 37

- WHO Grades I-III

< 5-9% of 1° CNS tumors

**Bimodal age distribution**
(2) peak ages 1-5yo and <35 yo ** TWO TARGET AGE GROUPS**

**Location** varies with age group*

• Children
~4th ventricle, lateral ventricles

• Adults
~Spinal cord, 4th ventricle

- Account for ~60% of intramedullary spinal cord tumors

**Micro**
• True and pseudorosettes

Back 37

Ependymoma

Front 38

**Ependymoma**

- Cytoplasmic processes of ependymal tumor cells condense about blood vessels to form _____

Back 38

pseudorosettes

Front 39

**Ependymoma**

- True ependymal rosette contains a well-defined

Back 39

central lumen

Front 40

This is a tumor of the choroid plexus and may cause noncommunicating hydrocephalus

Back 40

Choroid Plexus Papilloma

Front 41

Are choroid plexus papillomas more common in adults or children?

Where are they normally located in adults and children?

Back 41

Most common in CHILDREN!!

Children = lateral ventricles

Adults = 4th ventricles

Front 42

Choroid Plexus carcinomas are very rare and occur mostly in ________ (age group)

Back 42

Children

Front 43

- WHO Grade IV (highly aggressive)*

• Small, round(ish) blue cells

- One of most common CNS tumors in children--> cerebellum
** CHILDREN**


**Micro**

• Rosettes and pseudorosettes

•**Homer Wright rosettes**
consist of tumor cell nuclei disposed in circular fashion about tangled cytoplasmic processes --> these structures are indicative of differentiation along neuronal lines

• Cellular enlargement, often prominent nucleoli, and pronounced mitotic and apoptotic activity = features of this aggressive tumor

Back 43

Medulloblastoma

(“medulloblast” – immature cells that can become glia or neurons)

Front 44

- Generalized or localizing presentation

~ 15% of primary intracranial tumors

- Peak age 40-60 yo ** OLDER ADULTS **

**Monosomy chromosome 22**
(22q12 = NF2 gene --> merlin)

- Incidence increased following radiation and in people with NF2

-Arise from arachnoid cap cells (meningothelial cells)

**Well demarcated, firm/rubbery, broad dural base = characteristic**

• MRI may demonstrates thickened and abnormally enhancing dural “tails” extending from the lesional borders —a finding suggestive, though not diagnostic, of this tumor entity

Back 44

**Meningioma**


- 90% cranial; 9% spinal; 1% ectopic

- Multiple in 9%

Front 45

These are uncommon, except when seen in immunocompromised patients**

- Most are of **B-cell origin**

- EBV virus positive

Back 45

Primary CNS Lymphoma

Front 46

- Immunocompromised patients

- B-cell origin

- EBV (+)

• Most often high-grade and relatively poorly responsive to chemotherapy

• May respond initially to corticosteroids

• Typically more responsive to radiation tx

Back 46

Primary CNS Lymphoma

Front 47

A germ cell tumor in the CNS is most likely a ________

***

Back 47

testicular seminoma

Front 48

Where are germ cell tumors in the CNS most likely found?

**

Back 48

Midline --> pineal, suprasellar regions

germinoma = testicular seminoma

Front 49

Most common sources of metastatic CNS tumors?

***

Back 49

- Lung (most commonly)
- Breast
- Melanoma
- Kidney (RCC)
- GI tract
- (Choriocarcinoma ,rare tumor but often w/ mets to brain)

Front 50

What do metastatic CNS tumors look like?

***

Back 50

**Most often multiple**

- Ring-enhancing, sharply demarcated lesions

- Surrounded by zone of edema

**Gray-white junction of cerebrum (where blood is richest, thus where they will most likely travel to)

Front 51

neuromas, Schwannomas, Neurofibromas, Malignant peripheral nerve sheath tumors (MPNST) are all tumors of the _____

Back 51

PNS

Front 52

**non-neoplastic** mass lesion, not malignant—associated w/ trauma)

- Tangled mass of axons, reactive proliferations of
Schwann cells, fibroblasts

**Painful **

Back 52

Neuroma

Front 53

- WHO Grade I

-see MULTIPLE in patients with NF2

- In general, occur as solitary tumors, firm and encapsulated

• Antoni A (dense fibrillary) tissue
**Verocay bodies**: palisades of elongated, bipolar cells around pink fibrillary stroma

• Antoni B (loose reticulated) tissue—looser stroma, fewer cells, and myxoid change

Back 53

Schwannomas

Front 54

Patients with NF2 often have multiple _______

Back 54

***Schwannomas***

• Bilateral vestibular Schwannomas

**Deletion/mutations in NF2 gene, 22q12 (merlin)**

Patients likely present:
-Tinnitis, gait disturbance, vertigo, nausea

Front 55

Can schwannomas be removed surgically?

Back 55

Yes, they are encapsulated!

Front 56

-WHO Grade I

- Composed of Schwann cells, fibroblasts, collagen, reticulin

**Unencapsulated** and infiltrate nerves—not thought to occur intracranially

• Cannot easily surgically remove neoplasm without damage to nerve

Back 56

Neurofibromas

Front 57

Can Neurofibromas be removed surgically?

Back 57

No, they are uncapsulated and often infiltrate nerves!

Front 58

50% of people with a Malignant peripheral nerve sheath tumors (MPNST) have what disease??

Back 58

NF1

Front 59

- WHO Grade III or IV

- Arise de novo or via progression of nerve sheath tumors

• Neurofibromas, possibly Schwannomas

~ 10-15% of neurofibromas in NF1 become malignant

• ~ 75% recur and cause death
↓
Very difficult to tx/cure

Back 59

Malignant peripheral nerve sheath tumors (MPNST)

Front 60

**Chromosome 17**

Inclusion criteria – at least 2 of the following:

• Six café au lait spots

• Two neurofibromas

• One plexiform neurofibroma

• Axillary or inguinal freckling

• Osseous lesion (e.g., sphenoid dysplasia)

• Optic glioma

• Two *Lisch nodules** (iris hamartomas

Back 60

NF1 = von Recklinghausen’s NF-peripheral

90% of NF (MOST COMMON form)

Front 61

 Central type
- Less common, with later onset

- AD

- Chromosome 22

- Associated with bilateral vestibular Schwannomas, meningiomas

Back 61

NF2

Front 62

Paraneoplastic syndromes:

- Antibodies against presynaptic voltage-gated Ca2+ channels of skeletal muscle, and any electrical membrane

**Small cell lung Ca** -Ab association

- Presents as mysthenia gravis presents**

• More commonly associated with thymic hyperplasia/thymoma

Back 62

Lambert Eaton Syndrome

Front 63

Paraneoplastic Syndromes

- Destruction of Purkinje cells -

- Anti-Yo** antibodies

- Breast, ovarian carcinoma

Back 63

Cerebellar degredation

Front 64

Paraneoplastic Syndromes:

**Anti-Hu** antibodies (small cell lung Ca, lymphoma)

- Tend to be related to some underlying immunologic mechanism*

- Associated with some solid tumor of an organ—breast, lung, ovary—and sometimes a lymphoma

Back 64

Sensory Neuropathy