CNS Tumors - Cochran

Question 1

Distinguish between the frequency and presentation of CNS tumors in adults and children.

Are metastases or primary tumors more common?

Answer 1

Adult tumors are generally supratentorial. Pediatric brain tumors are infratentorial and more common.

According to lecture, metastases are more common. According to Pathoma, they are equal.

Question 2

Why are even low-grade CNS tumors very dangerous?

How apt are the high-grade to spread to other sites?

Answer 2

The brain is enclosed, meaning any mass expansion could be catastrophic. Focal involvement can be serious and resection difficult.

Not very apt (Medulloblastoma is a key exception to this)

Question 3

What is the most common glioma?

What form is most common in adults?

In children?

Answer 3

Astrocytoma.

Glioblastoma multiforme

Pilocytic astrocytoma

Question 4

Pilocytic Astrocytoma

Who does it affect? Where does it manifest?

How does it appear on histology?

Prognosis?

Answer 4

Pilocytic Astrocytoma

Mostly children; hence it is found in the cerebellum (infratentorial!)

Biphasic pattern of fibrillary and microcystic areas. Generally loose and low-grade, with Rosenthal fibers (eosinophilic, astrocytic)

Good! Well-demarcated with slow growth. Pilocytic astrocytoma does not progress to grades II/III/IV astrocytoma.

Question 5

Contrast grade II astrocytoma with grade III.

Answer 5

In grade II astrocytoma, cellularity is moderate and nuclear atypia is only occasional.

In grade III astrocytoma, both features are worse, and mitoses can be found.

Question 6

What is grade 4 astrocytoma also known as?

How does it appear grossly?

On histology?

Answer 6

Glioblastoma multiforme.

Apt to cross the corpus callosum and cause subfalcine herniation. May seed the ventricles.

Pleomorphic with rich mitotic activity. Necrosis with pseudopalisading, and endothelial proliferation (“glomeruloid”).

Question 7

Oligodendroglioma

Adults or children?

Grades?

Prognosis?

Answer 7

Oligodendroglioma

Adults.

Unlike astrocytoma, only presents as grade II and III (anaplastic).

Better than astrocytomas.

Question 8

What genetic trait should be determined in an oligodendroglioma to direct treatment?

How does it appear on histology?

On radiology?

Answer 8

Loss of chromosomes 1p and 19q.

Sheets of cells with round nuclei (“Fried egg” appearance)

Well-defined lesion, maybe with calcification.

Question 9

Ependymoma

Adults or children?

Grades?

Where is it usually found, and what are the consequences of this?

Answer 9

Ependymoma

Children mostly, but also young adults.

Unlike astrocytoma (but like oligodendroglioma), only grades II and III (anaplastic).

Around the ventricles, may cause hydrocephalus.

Question 10

Ependymoma

How does it appear grossly?

On histology?

What factor do these stain positive for?

Answer 10

Ependymoma

Can be solid or cystic, prodrudes from ventricular lining.

Rosettes of columnar cells (sometimes perivascularly; “pseudorosettes”).

GFAP (recall that ependymal cells, like astrocytes, express this)

Question 11

Most gliomas are sporadic. Some can result from genetic mutations or environmental factors. Try to name 3-4 of these risk factors (for familial causes, give the syndrome name and associated tumors).

Answer 11

p53 mutation (Li-Fraumeni); Astrocytomas

DNA mismatch repair mutations (Turcot); Glioblastoma & Medulloblastoma

PTEN mutation (Cowden); Gangliocytoma

(NF1, NF2, Tuberous sclerosis, VHL)

Therapeutic radiation (such as for treating childhood ALL)

Question 12

Choroid plexus papillomas are not the same thing as ependymomas! Still, name their complications.

Are they benign or malignant?

Answer 12

Hydrocephalus again (obstruct outflow or overproduce)

Can be either; benign has good prognosis, while malignant has dismal (occurs in young children)

Question 13

Where can colloid cysts be found?

What condition will the patient complain of?

How do they appear on microscopy?

Answer 13

Usually at the roof of the 3rd ventricle, near the foramen of Monro.

Positional headache due to obstruction of the foramen.

A thin-walled cyst with cuboidal/columnar lining.

Question 14

Where can gangliogliomas be found?

What condition will the patient exhibit?

What is distinctive about the treatment of ganglioglioma?

Answer 14

Usually in the temporal lobe (note: CNS only!)

Seizures, usually.

Surgery alone is usually curative!

Question 15

Gangliogliomas are (well-circumscribed/poorly-differentiated).

On histology both neuronal and glial components will be found. Which is actually neoplastic?

Answer 15

Well-circumscribed.

The glial component (this should be intuitive; neurons have little proliferative potential)

Question 16

Medulloblastoma is a (neuronal/glial) tumor of (adults/children). It is generally found in ______, causing the symptoms of ______. It has a (favorable/dismal) prognosis.

Answer 16

Neuronal (actually neuroectodermal), in children. Posterior fossa, look for cerebellar defects (ataxia). Dismal prognosis.

Question 17

Describe the treatment for medulloblastoma.

Why might an adjuvant treatment be needed?

Answer 17

Surgical resection followed by craniospinal radiation.

The radiation is for treatment of “drop metastases” in the lower spine.

Question 18

Does medulloblastoma appear highly irregular or typical on histology?

What factor, stainable in IHC, affirms medulloblastoma’s neuroectodermal origin?

What eponymous finding is seen on histology?

Answer 18

Highly irregular! Recall that most medulloblastoma is grade IV.

Synaptophysin.

Homer-Wright rosettes.

Question 19

What is the classic etiology of a primary CNS lymphoma?

What is it’s outlook?

Histology?

Answer 19

EBV-associated, seen often in immunocompromised hosts (some immunocompetent as well)

Dismal, most die within 1 year.

Periventricular and perivascular expansions.

Question 20

Who is the classic meningioma patient?

What are some classic sites?

What is its etiology & known associations?

Answer 20

An older woman.

Parafalcine, orbitofrontal, on the sphenoid ridge, etc. Anywhere there’s dura, really…

Unknown, though these are generally ER/PR+. Associated with radiotherapy and NF2 gene mutation.

Question 21

What histologic findings are seen in low-grade meningioma?

On high-grade?

Which is more common?

Answer 21

Whorls of cells, psammoma bodies.

As above, plus the usual bad signs (necrosis, mitoses)

Low-grade (90% are Grade I).

Question 22

Name five sources of metastases to the CNS.

How do they appear on imaging?

Histology?

Answer 22

Lung & Breast >> Kidney, Skin, and GI tract.

Multiple & well-demarcated.

Resembles the tissue of origin.

Question 23

Some tumors have a particular predilection for CNS metastasis.

What metastases can spread through/along the meninges?

What metastases target the lumbar spine, potentially causing cord compression?

Answer 23

Breast cancer is prone to this (Meningeal carcinomatosis)

Prostatic adenocarcinoma spreads to lower spine (remember? Batson venous plexus?)

Question 24

Are schwannomas benign or malignant? In adults or children?

What is the most classic site of appearance?

Any genetic associations?

Answer 24

Benign, more commonly in adults.

The cerebellopontine angle, where CN VIII emerges (note deafness/tinnitis, facial numbness)

Neurofibromatosis type 2.

Question 25

Schwannomas can have a couple of distinct histologic morphologies.

Distinguish between Antoni A and Antoni B.

Answer 25

Antoni A: Compact spindle cells.

Antoni B: Loose spongy areas, full of small cells with round nuclei.

Question 26

What are neurofibromas comprised of?

Describe the cutaneous form.

How is neurofibroma morphology different than that of schwannoma?

Answer 26

Schwann cells, fibroblasts, and perineural cells.

Usually solitary, presumably sporadic.

Neoplasm is generally infiltrative (schwannoma causes peripheral expansion around the nerve)

Question 27

Describe the histologic appearance of a neurofibroma

What distinguishes a plexiform neurofibroma from a cutaneous one?

Answer 27

Elongated spindle cells with wavy nuclei. “Loose”

Plexiform tends to involve multiple nerves or whole plexi. More likely to be malignant, and stronger NF1 association.

Question 28

What are the four neurophakomatoses? Name the mutation associated with each of them.

Answer 28

Neurofibromatosis Type 1 - NF1 (neurofibromin, suppresses proliferation)

Neurofibromatosis Type 2 - NF2 (merlin, promotes cell junctions)

VHL disease - VHL (regulates growth factor expression)

Tuberous Sclerosis - TSC1 (hamartin) or TSC2 (tuberin) inhibit mTOR.

Question 29

Besides neurofibromas, what findings are seen in NF1?

What mutation and chromosome are involved?

Answer 29

Notably: Cafe-au-lait pigmentation, lisch nodules (iris), optic gliomas, axillary freckling

And many others (rhabdomyosarcomas, pheochromocytomas, carcinoid tumors)

Neurofibromin (chromosome 17)

Question 30

What tumors result from NF2 mutation?

Is it more or less common than NF1?

What mutation chromosome is involved?

Answer 30

Bilateral vestibular schwannoma, meningiomas, gliomas, NON-plexiform neurofibromas!

Less common.

Merlin; Chromosome 22.

Question 31

What tumors result from von-Hippel Lindau disease?

What is the mutation and chromosome involved?

Answer 31

RCC, pheochromocytoma, retinal angiomas, but especially **cerebellar hemangioblastomas **(cerebellar, well-defined, treated with resection)

VHL on chromosome 3.

Question 32

What tumors result form tuberous sclerosis? Are these benign or malignant?

What mutations & chromsomes are involved?

Answer 32

Cutaneous angiofibromas, cortical hamartomas, subependymal nodules & giant cell astrocytoma (beware hydrocephalus). These are generally benign.

TSC1 (hamartin on chr 9), TSC2 (tuberin in chr 16)

Question 33

What malignancies are apt to cause paraneoplastic syndromes?

Is there a gender prevalence?

What is the pathophysiology of paraneoplastic syndrome?

Answer 33

Small cell carcinoma, lymphomas, neuroblastoma, gynecologic and testicular cancer.

Seems to have a female predominance.

Effect of ectopic hormone production, usually. This is not necessarily the case in neurologic paraneopalstic syndromes.

Question 34

There are many possible neurologic paraneoplastic syndromes.

Is the underlying malignancy generally mild or severe? Why is this?

How are neurologic syndromes different than other paraneoplastic syndromes?

Answer 34

Malignancies causing neurologic paraneoplastic syndromes are generally limited due to an anti-tumor immune response. Antibodies against tumor antigens can be isolated.

These syndromes may result from cross-reaction by anti-tumor antibodies to neuronal antigens.

Question 35

There are many possible neurologic paraneoplastic syndromes.

Describe subacute cerebellar ataxia (symptoms, associated cancers, and serologic findings)

Do the same for LEMS.

Answer 35

Subacute cerebellar ataxia: Progressive ataxia, dysarthria, nystagmus, vertigo, diplopia, titubation. Ovarian and Breast cancers. Antibody against purkinje cells (PCA-1 or Anti-Yo)

LEMS: Eye-sparing muscle weakness that improves with use. Small cell lung cancer. Antibodies to voltage-gated calcium channels.

Question 36

Recap:

Is ependymoma a tumor of the young or old?

Medulloblastoma?

Oligodendroglioma?

Answer 36

Ependymoma: Young

Medulloblastoma: Young

Oligodendroglioma: Old

Question 37

Since everyone loves pathologic eponyms, name the corresponding tumor:

Rosenthal fibers

Homer Wright rosettes

Antoni A/B tissue

Answer 37

Rosenthal fibers: Astrocytoma (generally low-grade, eg Pilocytic)

Homer Wright rosettes: Medulloblastoma

Antoni A/B tissue: Schwannoma

Question 38

Since everyone also loves immunohistochemistry, name the tumors that would stain positively for these:

GFAP

Synaptophysin

S-100

Answer 38

GFAP: Astrocytomas and ependymomas

Synaptophysin: Medulloblastoma

S-100: Schwannoma

Question 39

Which tumor is probably found deep in white matter?

Which is most likely to produce spinal metastases?

Which is associated with NF1? NF2?

Answer 39

Oligodendrogliomas (this is intuitive; oligodendrocytes are responsible for myelination)

Medulloblastoma (“drop mets”)

NF1 - Plexiform neurofibromas; NF2 - (bilateral) Schwannoma

Question 40

Name the tumor as its histology is here described.

1. Whorls and psammoma bodies.
2. Sheets of “Fried egg” cells with round nuclei.
3. Necrosis with pseudopalisading
4. Round, small blue cells arranged in rosettes.
5. Thin-walled cyst walled by cuboid/columnar epithelium
6. Compact bundles of spindle cells

Answer 40

1. Meningioma
2. Oligodendroglioma
3. Glioblastoma multiforme
4. Medulloblastoma
5. Colloid cyst
6. Schwannoma (“Antoni A”)