T3 Nishiyama Cns Tumors

Front 1

What are the unique characteristics of tumors in the CNS?

Back 1

1. Hard to distinguish b/w benign & malignant
2. Hard to resect neoplasms w/o compromising neuro fxn
3. Location! of tumors can be lethal irrespective of histo type'
4. Malignant tumors of CNS seldom spread beyond CNS but are capable of seeding brain & sc.

Front 2

What are the four major classes of brain tumors?

Back 2

Gliomas, neuronal tumors, poorly differentiated neoplasms, & meningiomas.

Front 3

What three tumors are derived from glial cells.

Back 3

Astrocytomas, oligodendrogliom, ependymomas.

Front 4

Astocytomas/Glioblastomas: General Characteristics

Back 4

-80% of primary brain tumors
-Usually involve cerebral hemispheres.
-30-50 y/o

Front 5

Astrocytoma Morphology

Back 5

-Glios easy to see b/c of necrosis, hemorrhage.
-Low grade or well differentiated astros-->mild to moderate inc of glial cells, variable nuclear pleomorphism & network of fine GPAP + astorocytic processes, so fibrillary appearance.
-Indistinct transition from nl to neoplastic tissue
-Anaplastic astros more cellular w/ more nuclear polymorphism & mitotic figures.

Front 6

Whats the difference b/w glioblastomas morphology & apaplastic astros?

Back 6

Similar histo but 2 add'l features: areas of NECROSIS & vascular or endothelial proliferation. Glios cross midline.

Front 7

Whats the difference in molecular genetics b/w low and high grade astros?

Back 7

Low grade: inactivation of p53 & overexpression of PDGF-A & its receptor
Transition of higher grade: add'l disruption of tumor-suppressior genes, the RB gene; the p16/CKNZA gene.

Front 8

Whats the difference b/w a primary glioblastoma & a secondary glio?

Back 8

Primary: arose as glioblastoma de novo (rapid, progressive clinical course, older pts, assoc w/ amplification of EGRF gene)
Secondary: aroze from preexisting lower grade astro (shared p53 mutations found in low grade gliomas, 2 pathways to secondary glio: PDGF-A amplification or MCM2 overexpression; p16 deletion of PTEN mutation)

Front 9

Describe the clinical course of astrocytomas.

Back 9

-Get more anaplastic w/ time.
-well differentiated: >5 yr mean survival.
-More rapid course correlated w/ development of more anaplastic features & more rapid growth of tumors.
-Poor prognosis for glios w/ 8-10 month mean survival.

Front 10

What are the characteristics of Pilocytic (Low grade) Astros?

Back 10

-benign clinical condition.
-in kids, young adults
-usually site: cerebellum (floor of 3rd ventricle, optic nerves, cerebral hemispheres),
Morphology: cystic w/ nodule in wall of cyst (mural nodule)
-Grow very slowly.

Front 11

What are the general characteristics of oligodendrogliomas?

Back 11

-15-20% of gliomas.
-Age group: 30-40s
-Site: cerebral hemisphere w/ white matter preference.

Front 12

Which cells have perinuclear halos?

Back 12

oligodendroglia

Front 13

What are the molecular genetics of oligodendrogliomas?

Back 13

Most common: genetic alterations: loss of heterozygosity for chrom 1p & 19pq.
As tumors get more anaplastic: loss of 9p & 10q, mutation in CDKNZA.
-Tumors w/ loss of 1p & 19q respond better to tx (radiation, chemo)
-W/o loss of 1p & 19z, refractory to tx.

Front 14

What is the clinical course of oligodendrogliomas?

Back 14

better than astrocytomas, mean survival of 5-10 yrs.

Front 15

General characteristics of ependymomas.

Back 15

Location: ependyma-lined ventricular system, incl spinal cord.
In 1st 2 decades: usually arise near 4th ventricle.
-5-10% of primary brain tumors in aboce age group.
-In adults, spinal cord become the usual site.

Front 16

Describe the morphology of ependymomas.

Back 16

-perivascular pseudorosettes (central vessel w/ tumors cells radiating from it);
-close to vital centers in pons & medulla-->so hard to surgically remove.
-Tumors are GFAP positive.
-Most, well differentiated & behave accordingly.

Front 17

What is the molecular genetics of ependymomas?

Back 17

B/c they form part of NF type 2-->the NF2 gene on chromosome 22 has been investigated for spinal cord ependymomas only.

Front 18

Describe the clincal course of Ependymomas.

Back 18

-Often w/ hydrocephalus due to 4th ventricle obstruction.
-Poor prognosis b/c of tumor location, mean survival 4 years.

Front 19

Whats the most common poorly differentiated neoplasm?

Back 19

Medulloblastoma (20% of brain tumors in kids)

Front 20

Describe the general characteristics of medulloblastomas.

Back 20

kids, cerebellum exclusively;
neuronal & glial markers may be expressed, but tumor often largely undifferentiated.

Front 21

Morphology of Medulloblastomas

Back 21

Extremely cellular w/ sheets of anaplastic cells. Individual tumor cells are small, mitotic figures are abundant; markers of cellular proliferation, like Ki-67, found in high percentage of cells. May find neurosecretory granules & Homer Wright rosettes. Can have dissemination into sc. Can have 'drop mets: may spread to cauda equina thru most direct manner.

Front 22

What is the clincal course for medulloblastoma.

Back 22

W/ total excision & radiation, 5 yr survuval rate may be as high as 75%.
-Tumor is exquisitely sensitive to radiation.

Front 23

General characteristics of meningiomas.

Back 23

benign tumors of adults;
attached to dura & arise from meningothelial cells of arachnoid;
-low risk of recurrence or aggressive growth.
-aggressive tumors may occur.
-various histo patterns that have no influence on prognosis.

Front 24

What are the most common locations of meningiomas?

Back 24

Common involvement areas: parasagittal area, wing of sphenoid, olfactory groove, sella turcica, foramen magnum.
Usually solitary lesions.
-Often carry progesterone receptors, so rapid growth during pregnancy has been reported.

Front 25

What is the most common tumor in immunosuppressed patients?

Back 25

Primary CNS lymphoma

Front 26

Which tumors account for approximately 25-50% of intracranial tumors in hospitalized patients?

Back 26

Metastatic tumors

Front 27

What are the top 3 places that metastatic CNS tumors metastasize from?

Back 27

lung, breast, melanoma

Front 28

Which tumors almost never metastasize to brain?

Back 28

prostate CA

Front 29

What is a common site of involvement for metastatic tumors?

Back 29

meninges

Front 30

Describe the morphology of metastatic tumors

Back 30

Sharply demarcated from brain parenchyma, Site: jxn of gray and white matter. Meningeal carcinomatosis: tumor involves brain surface & spinal cord & intradural nerve roots assoc w/ small CA of lung & CA of brest.

Front 31

What is the most common clinical cause of neuropathy?

Back 31

Diabetes.

Front 32

What is the most common inherited cause of neuropathy?

Back 32

Charcot-Marie-Tooth Disease

Front 33

What are some of the principal causes of peripheral neuropathy?

Back 33

Autoimmunity, vasculitis, systemic illness, CA, infections, dysproteinemia, nutritional deficiencies, alcoholism, compression, trauma, industrial agents, drugs, inherited neuropathies.

Front 34

What are immune-mediated neuropathies?

Back 34

Immune disorders, antibodies react w/ antigens on peripheral N, elicit response & macrophage rxn, destroying myelin & axons.

Front 35

What are the 2 main groups of immune-mediate neuropathies?

Back 35

Guillan-Barre syndrome, chronic inflammatory demyelinative neuropathy.

Front 36

What are the clinical findings of Guillain Barre syndrome?

Back 36

parasthesias, toes, & fingertips. Rapidly advancing weakness & areflexia. Plateau in 4 weeks, recovery begins. Some cases fulminant, evolve in 1-2 days. Follows upper respiratory infection, usually post-viral (Camp Jejuni).

Front 37

What is the tx for GBS?

Back 37

Plasma exchange treatment of choice (exchange transfusion)

Front 38

What is the outcome for GBS?

Back 38

5% die of respiratory paralysis, cardiac arrest, other complications;
10% recover w/ residual weakness
-Key lab abnormalities: Dec nerve conduction velocity or conduction block.
-CSF: elevated protein, relatively few cells (albuminocytologic dissociation)

Front 39

Describe Charcot-Marie-Tooth Disease

Back 39

-Most common inherited peripheral neuropathy,
-Involves 1/2500, AD.
-Wkness, atrophy of distal muscles, specifically those innervated by peroneal nerve ('stork leg')
-begins in childhood or adolescence, progresses slowly, involves other nerves.
-Dec conduction velocity in nerves.

Front 40

What do you see on a nerve biopsy in Charcot Marie Tooth disease?

Back 40

demyelination, myelin regeneration (thin myelin), axonal loss, onion bulbs.

Front 41

Whats the most common form of CMT, type 1?

Back 41

Dup of chro 17, contains gene for myelin protein, PMP22. CMT-1 pts, 3 copies of normal gene, produce 1.5 x as much PMP22 as normals do.

Front 42

What are the best tissues for diagnosis of vasculitis?

Back 42

sural nerve biopsy & muscle biopsy-->nerve biopsy is diagnostic, over 50% of pts w/ systemic vasculitis & clinical neuropathy.(yield inc w/ muscle biopsy too)

Front 43

What is the development of peripheral nerve sheath tumors?

Back 43

Arise from Schwann cells, perineural cells & fibroblasts.
-Peripheral nerve: axon w/ Schwann cells plus myelin sheath.
-Schwann cells envelopes, isolates variable numbers of unmyelinated fibers.

Front 44

Describe the origin and morphology of a Schwannoma (Neurilemmoma)

Back 44

Origin: Schwann cells, arise from neural crest, assoc w/ NF-type 2.
Morphology: Antoni type A and Type B.

Front 45

What are the clinical features of a Schwannoma?

Back 45

acoustic neuroma (8th nerve), deafness, vertigo., trigeminal nerve (trigeminal neuralgia)

Front 46

What are the 2 types of neurofibromas?

Back 46

1. Cutaneous form
2. Peripheral nerve (solitary neurofibroma)q

Front 47

Describe a neurogenous sarcoma.

Back 47

Highly malignant, frequent recurrences, eventual metastases.
-Frequently mutliple-->from neurofibroma.
-may follow radiation therapy.
-assoc w/ NF type 1.