CNS Tumors (Gianani)

Question 1

TUMORS OF NEUROGLIAL CELLS

Answer 1

A. Tumors of Glial Cells:

Astrocytic tumors:

Astrocytoma
Glioblastoma multiforme

Oligodendroglioma

Ependymoma - choroid plexus papilloma

B. Neuronal Tumors
Ganglioglioma
Gangliocytoma
Central neurocytoma

C. Embryonal Tumors
Medulloblastoma

Question 2

Most common tumor in the brain

Answer 2

metastatic

Question 3

tumor that most often metastasizes to the brain

Answer 3

melanoma

Question 4

glioblastoma multiforme is another name for

Answer 4

astrocytoma grade 4

Question 5

Ependymoma

Answer 5

choroid plexus papilloma

Question 6

GERM CELL TUMORS

Answer 6

Teratoma

Craniopharyngioma

Question 7

TUMORS OF CRANIAL

AND SPINAL NERVES

Answer 7

Schwannoma
Neurofibroma

can occur peripherally too

Question 8

The terms “intra-axial” and “extra-axial,”

Answer 8

used in radiological descriptions, mean “in brain or spinal cord tissue” and “extrinsic to brain” respectively.

For instance, astrocytoma and oligodendroglioma are intra-axial; meningioma and Schwannoma are extra-axial.

The term anaplasia describes the cellular atypia and loss of differentiation that are associated with malignant tumors.

Question 9

OLIGODENDROGLIOMA: genetic alteration

Answer 9

1p and 19q codeletion

Question 10

ATYPICAL TERATOID-RHABDOID TUMOR genetic alteration

Answer 10

Loss of 22q

particularly bad prognosis- see it in infants

Question 11

MENINGIOMA: genetic alteration

Answer 11

Loss of 22q

Question 12

NF1

Answer 12

NF1/17q

NS tumors: Plexiform neurofibroma, MPNST, optic and other gliomas

Other tumors: Pheochromocytoma, GIST

cafe au lait spots

Question 13

NF2

Answer 13

NF2/22q- the gene is merlin

Vestibular and PN shwannoma, meningioma, other brain tumors
(*acoustic schwannoma)

not associated with other tumors

Question 14

Li- Fraumeni

Answer 14

TP53/17p

Astrocytoma

Breast carcinoma, bone and soft tissue sarcoma

Question 15

tuberosclerosis

Answer 15

SEGA

Renal AMLs, lung LAM, ** cardiac rhabdomyoma

Question 16

VHL

Answer 16

VHL/3p

Hemangioblastoma

Renal cell carcinoma, pheochromocytoma

Question 17

Von Recklinghausen neurofibromatosis (VRNF - Neurofibromatosis type 1-NF1)

Answer 17

one of the most common genetic disorders, is autosomal dominant and is caused by mutations of a gene on chromosome 17q that encodes a protein called neurofibromin.

Neurofibromin is involved in control of cell proliferation and acts as a tumor supressor.

• have a variety of tumors, including * bilateral optic nerve astrocytomas, and plexiform neurofibromas and malignant peripheral nerve tumors.
• café au lait spots of the skin, axillary and inguinal freckles, dysplasia of the sphenoid wing and other skeletal abnormalities, fibromuscular dysplasia of arteries, and other lesions.

Question 18

DDx of intracranial mass lesion

Answer 18

Infections

• Cerebral abscess
• Toxoplasmosis
• Tuberculosis

Hemorrhage

• Hematoma
• Hemorrhagic metastasis

Neoplasms

• Primary
• Metastatic

Question 19

Classification- grades of tumors, etc.

Answer 19

Astrocytic Tumors

• Pilocytic Astrocytoma, WHO Grade I
• Diffuse Astrocytoma, Grades II, III, IV
• Other (PXA, SEGA)

Oligodendroglial Tumors can have a variety of grades

Ependymal Tumors can have a variety of grades

Choroid Plexus Tumors
- Papilloma, Carcinoma

Neuronal and Glioneuronal Tumors
- Neurocytoma, Ganglioneurocytoma, Ganglioglioma

Question 20

3 tumors in the embryonal category

Answer 20

medulloblastoma, PNET, atypical TERATOID-RHABDOID TUMOR

Question 21

Meningioma

Answer 21

gets a big chunk of the brain tumor pie (MOST COMMON primary non-malignant tumor of CNS)

Dural-based, extra-axial tumor in adults…complete excision…cure
~25 to 30% of CNS tumors.
Arise from meningothelial cells of arachnoid.
More common in women
Most common genetic abnormality…loss of chromosome 22 (22q)…loss of function of protein merlin.
Multiple in NF2 and post radiation
50% sporadic tumors have mutation of NF2 gene
Majority have good prognosis
>90% WHO I (~5% II, ~2% III)
Many histologic types

Question 22

meningiomas and invasion

Answer 22

Meningiomas can be seen to invade bone and even muscle…does not mean it is malignant

majority are benign but that some can look and behave malignant.

Question 23

how meningiomas look on histology

Answer 23

In transitional meningiomas, tumor cells are arranged in whorls with hyalinized and calcified centers that are called psammoma (sand) bodies because they resemble tiny grains of sand.

Question 24

Gliomas

Answer 24

fairly common group of primary brain tumors, include astrocytomas, oligodendrogliomas, and ependymomas.

These tumor types have characteristic histologic features that form the basis for the classification.

• It is no longer thought that these tumors derive from their specific, mature cell types (astrocytes, oligodendrocytes, and ependymal), but rather that they arise from a progenitor cell that preferentially differentiates down one of the cellular lineages.

Many of the tumors typically occur in certain anatomic regions within the brain, with characteristic age distribution and clinical course.

Question 25

grade 3 meningioma example

Answer 25

anaplastic meningioma

Question 26

The two major categories of astrocytic tumors are:

Answer 26

1. infiltrating astrocytomas - diffuse astrocytoma (grade II / IV) - anaplastic astrocytoma (grade III / IV) - glioblastoma (grade IV / IV) 2) more localized astrocytomas, of which the most common are the pilocytic astrocytomas. (BETTER PROGNOSIS)

Question 27

Pilocytic Astrocytoma, WHO I

Answer 27

Most frequent glial tumor in children Cerebellum - Thalamus, hypothalamus, * optic nerve Well circumscribed Solid and cystic Increased intracranial pressure, cerebellar signs Slow growth Overall good prognosis

Question 28

Diffuse Astrocytoma, WHO II

Answer 28

``` Ill-defined, infiltrating Any site in CNS > supratentorial (F,T) Seizures, headaches or focal signs Tendency to progress to higher grade Survival ~5-7 years ```

Question 29

Glioblastoma (GBM) WHO IV

Answer 29

``` Most frequent glial tumor in adults Highly malignant Seizures, headaches, focal deficits Supratentorial Survival ~1 year ```

Question 30

primary vs 2ndary glioblastoma

Answer 30

can arise denovo or secondary to astrocytomas

Question 31

best prognosis for glioblastoma

Answer 31

None of the genetic characteristics have specific prognostic significance except for IDH mutations (proneural type tumors)…better prognosis

Question 32

Oligodendroglioma

Answer 32

``` Ill-defined, infiltrating Supratentorial, cortical and white matter Frontal in 50-65% Most common in 4th-5th decades Long history of headaches, seizures Frequently calcified WHO II or III Prognosis 6 years II (better prognosis than other gliomas) ```

Question 33

histological look of glioblastoma

Answer 33

foci of necrosis with pseudo-palisading of malignant nuclei and endothelial cell proliferation

Question 34

Oligodendroglioma gene mutations and prognosis

Answer 34

IDH1/IDH2 gene mutations in 90% and portend a better prognosis. Deletions of chromosome 1p, together with * 19q seen in 80%...with these deletions, patients have consistent long lasting response to chemo and radiation…not so for the others.

Question 35

oligodengroglioma histologic appearance

Answer 35

fried egg positive for GFAP protein

Question 36

Medulloblastoma, WHO IV

Answer 36

Malignant tumor of children 70% under 15 years of age Posterior fossa, 75% in the vermis Ataxia and signs of > IP WHO IV Tendency to disseminate along subarachnoid space Prognosis - 50-70% at 5 years - (30% in the 1960’)

Question 37

Medulloblastomas are thought to arise from

Answer 37

stem cells located in the subependymal matrix and the external granular layer (EGL) of the cerebellum.

Question 38

Medulloblastoma histology

Answer 38

Classic medulloblastoma (the majority) is a highly cellular tumor composed of diffuse masses of small, undifferentiated oval or round cells. Wright rosettes- groups of tumor cells arranged in a circle around a fibrillary center

Question 39

Medulloblastoma and malignancy

Answer 39

* highly malignant tumor. It infiltrates and destroys brain tissue and tends to seed the subarachnoid space and spread along the walls of the ventricles. Leptomeningeal dissemination occurs more frequently in medullablastoma than any other BT The CSF shows high protein and low glucose, and contains tumor cells. CSF cytology is used to monitor the spread of the tumor. Extracranial metastases occur rarely, usually after operation or shunting. Treatment combines resection, to reduce the tumor mass and decompress the fourth ventricle, shunting of the lateral ventricles, radiation of the tumor bed and the entire neuraxis, and intrathecal chemotherapy.

Question 40

Primary CNS Lymphoma-PCNSL

Answer 40

PCNSL is typically a diffuse large B-cell lymphoma (DLBCL). The tumors that arise in immunocompromised patients are EBV-positive. peripheral Meningeal spread is very common, and some PCNSLs arise in the subarachnoid space. Corticosteroids induce apoptosis in PCNSL cells that may be so profound that the tumors disappear (vanishing lymphoma).

Question 41

METASTATIC TUMORS to BRAIN

Answer 41

majority men- most commonly primary carcinoma of the lung women- carcinoma of the breast highest rate of metastasis- melanoma

Question 42

Ependymoma

Answer 42

Slow growing tumors, children and young adults Hydrocephalus, >IP, ataxia 3-9% of CNS tumors Intraventricular, spinal cord Well circumscribed, but can disseminate WHO I, II and III Prognosis 60%(5y) and 48% (10y) II 55%(5y) and 26% (10y) III

Question 43

tumors that form rosettes in the brain

Answer 43

retinoblastoma ependymoma medulloblastoma

Question 44

Schwannoma

Answer 44

Other names in books: Neurilemoma, neurinoma, Vestibular or Acoustic Schwannoma >> in Peripheral nerves, but in CNS > Vestibular branch of 8th 4-6 decades Solitary (sporadic) Bilateral in NF2 Benign