Chapter 23: Tumors

Question 1

Tumors of the nervous system have unique characteristics that set them apart from neoplastic processes elsewhere in the body. What are they?

Answer 1

• These tumors do not have morphologically evident
premalignant or in situ stages comparable to those of
carcinomas.
• Even low-grade lesions may infiltrate large regions of
the brain, leading to serious clinical deficits, inability to
be resected, and poor prognosis.
• The anatomic site of the neoplasm can influence
outcome independent of histologic classification due to local effects (e.g., a benign meningioma may cause cardiorespiratory arrest from compression of the medulla).
• Even the most highly malignant gliomas rarely spread outside of the CNS.

Question 2

What are gliomas?

Answer 2

Gliomas are tumors of the brain parenchyma are classified as astrocytomas, oligodendrogliomas, and ependymomas

Question 3

Which type of glioma is the most common?

Answer 3

(diffuse) astrocytoma (80%)

Question 4

What symptoms do patients with astrocytoma present with?

Answer 4

Seizures, headaches, and focal neurologic deficits related to the anatomic site of involvement

Question 5

How can astrocytomas be stratisfied/classified based on histologic features?

Answer 5

Diffuse astrocytoma (grade II), anaplastic astrocytoma (grade III), and glioblastoma (grade IV), with increasingly grim prognosis as the grade increases

Question 6

What is the prognosis of astrocytomas

just read this once

Answer 6

Diffuse astrocytomas can be static for several years, but at some point they progress; the mean survival is more than 5 years. Eventually, patients suffer rapid clinical deterioration that is correlated with the appearance of anaplastic features and more rapid tumor growth. Other patients present with glioblastoma from the outset. Once the histologic features of glioblastoma appear, the prognosis is very poor; with treatment (resection, radiotherapy, and chemotherapy), the median survival is only 15 months.

Question 7

What type of glioma is second most common (for 5-15%)?

Answer 7

Oligodendrogliomas

Question 8

Where in the brain are astrocytomas and oligodendrogliomas often found?

Answer 8

Astrocytomas: cerebral hemispheres
Oligodendroglioma: cerebral hemispheres (mainly frontotemporal lobes)

Question 9

Several classes of tumor-causing genetic alterations have been described in gliomas. What are these?

(I don’t think you ought to know this)

Answer 9

• Mutations in isocitrate dehydrogenase (IDH) genes are commonly observed in grade II astrocytomas and oligodendrogliomas
• Mutations in the promoter for telomerase, which contribute to the immortalization of tumor cells, are seen in glioblastomas and other astrocytic tumors
• Co-deletion of 1p and 19q chromosomal segments are present in oligodendrogliomas
• Other genetic alterations, which are also common in tumors outside the CNS, include mutations that lead to overexpression of the EGF receptor and other receptor tyrosine kinases or disable p53 or RB

Question 10

Where do midline gliomas arise most commonly?

Answer 10

In the brain stem (specifically in the pons) and also occur in the spinal cord and thalamus

Question 11

True/false: Midline gliomas are infiltrative and result in significant neurologic impairment because of the disruption of critical nearby structures

Answer 11

True

Question 12

True/false: Although midline gliomas not show typical high-grade features such as necrosis or vascular proliferation, they often behave aggressively

Answer 12

True

Question 13

True/false: Pilocytic astrocytomas are relatively benign tumors that typically affect elderly

Answer 13

False, they affect children and young adults

Question 14

Where are pilocytic astrocytomas often located?

Answer 14

Cerebellum, they may also involve the third ventricle, optic pathways, spinal cord and occasionally cerebral hemispheres

Question 15

Where are ependymomas often located?

Answer 15

Next to the ependymalined ventricular system, including the central canal fo the spinal cord

Question 16

Which is more common, gliomas or neuronal tumors?

Answer 16

Gliomas, neuronal tumors rarely occur

Question 17

True/false: Neuronal tumors are typically lower-grade lesions that often present with seizures

Answer 17

True

Question 18

What are the different types of neuronal tumors?

I don’t think you ought to know this

Answer 18

• Central neurocytoma is a low-grade neoplasm found within and adjacent to the ventricular system (most commonly the lateral or third ventricle); it is characterized by evenly spaced, round, uniform nuclei and often islands of neuropil.
• Dysembryoplastic neuroepithelial tumor is a distinctive, low-grade tumor of children and young adults that grows slowly, often manifests as a seizure disorder, and carries a favorable prognosis after resection. It typically is located in the superficial temporal lobe and consists of small, round neuronal cells arranged in columns and around central cores of processes.
• Gangliogliomas are tumors with a mixture of glial elements, usually a low-grade astrocytoma and mature-appearing neurons. Most of these tumors are slow growing, and often manifest with seizures. About 20% to 50% of gangliogliomas harbor point mutations in the BRAF gene.

Question 19

How do embryonal (primitive) neoplasms appear?

Answer 19

Some tumors of neuroectodermal origin have a primitive “small round cell” appearance that is reminiscent of normal progenitor cells encountered in the developing CNS. Differentiation is often limited, but may progress along multiple lineages.

Question 20

What is the most common type of embryonal primitive neoplasm?

Answer 20

Medulloblasta (only in children)

Question 21

True/false: medulloblastoma is benign of origin

Answer 21

False, it is highly malignant. Luckily, it is very radiosensitive

Question 22

Genetic analysis of medulloblastoma has revealed several subtypes associated with different clinical outcomes. Current approaches separate medulloblastoma into distinct groups with different core pathogenic pathways or driver mutations. What are the examples of oncogenic pathways in these tumors?

Answer 22

• Wnt pathway activation, most commonly associated with gain of function mutations in the gene for β-catenin; these have the most favorable prognosis of all of the genetic subtypes and are commonly classic-type tumors.
• Hedgehog pathway activation, most commonly associated with loss of function mutations in PTCH1, a negative regulator of the Hedgehog; these tumors have an intermediate prognosis, but the concomitant presence of TP53 mutation confers a very poor prognosis.
• MYC overexpression, due to MYC amplification as well as other changes that result in increased expression; these tumors have the poorest prognosis.

Question 23

True/false: other parenchymal tumors is the primary central nervous system lymphoma and germ cell tumors

Answer 23

True (lymphoma is often associated with EBV)

Question 24

True/false: Meningiomas are predominantly malignant tumors that arise from arachnoid meningothelial cells and are often attached to the dura

Answer 24

False, benign

Question 25

Which tumors account for approximately one-fourth to one-half of intracranial tumors?

Answer 25

Metastatic tumors, mostly carcinomas

Question 26

What is most often the origin of metastatic tumors?

Answer 26

Lung, breast, skin (melanoma), kidney and GI-tract

Question 27

What is a distinct characteristic of metastases?

Answer 27

Metastases form sharply demarcated masses, often at the grey-white matter junction, and elicit local edema. The boundary between tumor and brain parenchyma is sharp at the microscopic level as well, with surrounding reactive gliosis.

Question 28

In addition to the direct and localized effects produced by metastases, paraneoplastic syndromes may involve the peripheral and central nervous systems, sometimes even preceding the clinical recognition of the malignant neoplasm. Many patients with paraneoplastic syndromes have antibodies against tumor antigens. What are some of the most common patterns?

(i dunno but don’t think you need to know this)

Answer 28

• Subacute cerebellar degeneration
• Limbic encephalitis
• Subacute sensory neuropathy
• Syndrome of rapid-onset psychosis, catatonia, epilepsy, and coma

(what symptoms + effect these have see p885-886)

Question 29

What familial tumor syndrome do you have to know for the exam?

Answer 29

Tuberous Sclerosis

(this is involved in the CNS, the familial syndromes of peripheral nervous system is in Ch22 which we obv don’t have to know)

Question 30

What is tuberous sclerosis?

Answer 30

Tuberous sclerosis is an autosomal dominant syndrome characterized by the development of hamartomas and benign neoplasms involving the brain and other tissues. CNS hamartomas variously consist of cortical tubers and subependymal hamartomas, including a larger tumefactive form known as subependymal giant cell astrocytoma.