Download LECTURE 7-8 BRAIN TUMORS Functional Cells of CNS Astrocytes

LECTURE 7-8 BRAIN TUMORS
Functional Cells of CNS
1. Astrocytes
a. Gliosis  proliferation of astrocytes in damaged areas of the central nervous system
i. Most important histopathological indicator of CNS injury!
ii. See hypertrophy and hyperplasia
2. Microglia
a. Macrophage system of CNS
b. Share many surface markers with peripheral monocytes/macrophages (such as CD68)
c. With injury  form microglial nodules  aggregates about small foci of tissue necrosis
3. Ependyma
4. Oligodendrocytes
a. Have a dark round nuclei and a perinuclear “halo”
5. Meninges
a. Focal nests of arachnoid cells (meningothelial cells)
b. often form whorls with central psammoma bodies
***Note: Brain tumors (primary!) do not generally metastasize  other
cancers though metastasize to the brain though
Tumors
•
75% of childhood CNS tumors arise within the posterior fossa
•
75% of adult CNS tumors arise within the cerebral hemispheres above the tentorium
Major Classes of Primary Brain Tumor
Gliomas
Different Types
**Most common group of primary brain tumors
• Astrocytomas
• Infiltrating
• Non-infiltrating
• Oligodendrogliomas
• Ependymomas
Neuronal Tumor
Most common tumor containing mature-appearing
neurons  ganglioglioma
-
Dysembryoplastic neuroepithelial tumor
Central neurocytoma
Most of these tumors are slow growing but glial
component occasionally become anaplastic
Often present as seizure disorder
Surgical resection is often effective in controlling
seizures
Astrocytomas
Infiltrating Astrocytomas
Non-Infiltrating Astrocytomas
Usually in the CEREBRAL HEMISPHERE
Usually in the CEREBELLUM
1. Diffuse astrocytoma (grade II/IV)
2. Anaplastic astrocytoma (grade III/IV)
3. Glioblastoma (grade IV/IV)
• MOST MALIGNANT
• MOST COMMON primary brain tumor
MOST COMMON ASTROCYTOMA!
•
A condition: Gliomatosis cerebri
• Multiple regions of the brain
(sometimes the entire brain) are
infiltrated by neoplastic astrocytes
• AGGRESSIVE!
• grade III/IV lesion-independent of the
appearance of the individual tumor
cells
•
Pilocytic astrocytoma (grade I/IV)
Relatively Benign with piloid (hair-like) processes
and are characterized by a relatively circumscribed
growth pattern
Grow very slow!!
Treated with resection!
Molecular Genetics:
Molecular Genetics:
Low Grade
- mutations affecting p53
- overexpression of platelet-derived growth
factor α (PDGF-A) and its receptor
High Grade
- disruption in RB and p16/CDKNaA
Glioblastomas occur in two settings:
- Primary glioblastoma (new onset disease)
- Secondary glioblastoma (previous low grade)
o BOTH stimulate RAS and PI-3 Kinase
pathways  stimulate growth and
survival of tumor cells!
-
NF1 show functional loss of neurofibromin
P53 mutation is rare
Clinical Features
- Depend on location and growth rate
- Mass effect
- High grade  abnormal vessels that are
“leaky” and will show contrast enhancement
- Glioblastoma pts  poor prognosis
Diffuse Astrocytoma
Microscopic Examination
-
Network of fine, GFAP positive astrocytic
processes that give the background a fibrillary
appearance
-
Anaplastic Astrocytoma
Microscopic Examination
-
Glioblastoma
cellular lesion with a sworling fibrillary
appearance to many of the cells
Transition between neoplastic and normal
tissue is indistinct
More densely cellular
Gemistocytic Astrocytoma
o neoplastic astrocyte shows a brightly
eosinophilic cell body from which
emanate abundant processes
Microscopic Examination (similar to above but
additional features)
-
-
necrosis and vascular or endothelial cell
proliferation
Necrosis in glioblastoma often occurs in a
serpentine pattern in areas of hypercellularity
(pseudopalisading)
Vascular cell proliferation is characterized by
tufts of piled-up cells that bulge into the lumen
Pilocytic Astrocytoma (non-infiltrating)
Macroscopic  well circumscribed
Microscopic Examination
-
thin "hairlike" processes that are GFAP-positive
and form dense fibrillary meshworks
Rosenthal fibers
often biphasic
narrow infiltrative border with the surrounding
brain
Oligodendroglioma
About
1.
2.
3.
4.
Patients usually have several years of neurological complaints
Lesions found mostly in CEREBRAL HEMISPHERES
Slow growing – well circumscribed – LOW grade malignant tumors
BEST over all prognosis!!
Gross Examination
1. Well-circumscribed, gelatinous, gray masses,
often with cysts, focal hemorrhage, and
calcification
Microscopic Examination
1.
2.
3.
4.
Surrounded by a clear halo of cytoplasm
Delicate network of anastomosing capillaries
Calcification
Perineuronal satellitosis  secondary structures
often seen with tumor cells
5. WHO grade II/IV lesions
Molecular Genetics
1. loss of heterozygosity for chromosomes 1p and 19q
2. Consideration in treatment
a. Tumors with loss of 1p and 19q, but without other alterations have consistent, long-lasting
responses to chemotherapy and radiation
b. Those without loss of 1p and 19q seem to be resistant to therapy
Anaplastic Oligodendroglioma
1. WHO grade III/IV
2. Microscopic Examination: increased cell density, nuclear anaplasia, and increased mitotic activity
Ependymoma and Paraventricular Mass Lesions
–
In the first two decades of life they typically occur near the fourth ventricle
–
Frequent in the setting of neurofibromatosis type 2
Ependymoma
Gross Morphology:
-
Solid or papillary mass extending from the
floor of the ventricle
Usually makes complete excision impossible
Microscopic Examination
- rosettes, canals) that resemble the
embryologic ependymal canal
- perivascular pseudorosettes
- GFAP expression
Molecular Genetics
- NF2 gene of chromosome 22
Clinical Features – Posterior Fossa
- Hydrocephalus
- CSF dissemination is a common occurrence
and portends a poor prognosis
- Posterior fossa lesions have the worst overall
outcome
- clinical outcome for completely resected
supratentorial and spinal ependymomas is
better
Periventricular Lesions
General Information:
- are usually benign to low-grade lesions
- location may cause clinical problems
Subependymomas
-
Choroid Plexus Papillomas
-
Slow growing nodules attached to ventricular
lining protruding into the ventricle
Incidental Finding
Cause hydrocephalus
Most often in LATERAL and FOURTH ventricle
Mixture of astrocytic, and ependymal cell
clusters surrounded by their fibers
-
Most common in children
o Seen in LATERAL ventricles
In adults
o Seen in FOURTH ventricles
Papillary growths almost exactly recapitulate
the structure of the normal choroid plexus
Cause hydrocephalus
-
Most common in TEMPORAL LOBE
-
Neuronal Tumors
Ganglioglioma
-
Glial component of these lesions usually
resembles a low-grade astrocytoma




low-grade neuronal neoplasm
most commonly the lateral or third ventricles
uniform nuclei and often islands of neuropil
Cells resemble oligodendroglioma, but
ultrastructural and immunohistochemical
studies reveal the neuronal lineage of the
tumor cells
Central neurocytoma
Poorly Differentiated Neoplasms
-
express few phenotypic markers of mature cells of the nervous system and are described as poorly
differentiated, or embryonal
Medulloblastoma
Predominantly in CHILDREN!
MOST COMMON
Exclusively in the CEREBELLUM!!
Neuronal and glial markers may be expressed, but
the tumor is often largely undifferentiated
Causes Hydrocephalus
Usually well circumscribed
Metastases to the cauda equina are sometimes
termed drop metastases
Molecular Genetics:
- loss of material from 17p with an abnormal
chromosome isochromosome 17q or i(17q)
- Signals poor prognosis
Clinical Features
- HIGHLY malignant
- Very radiosensitive!
CNS supratentorial primitive neuroectodermal
tumors (CNS PNET)
Atypical Teratoid/Rhabdoid Tumor
•
Tumors of similar histology and poor
differentiation, resembling medulloblastomas,
found in the cerebral hemispheres
•
Can lead to confusion with the peripheral
neuroectodermal tumor, that shares a genetic
alteration with Ewing sarcoma
Highly malignant tumor of young CHILDREN
Occurs equally in the posterior fossa and
supratentorial compartments
Presence of rhabdoid cells
Molecular Genetics:
- genetic alterations in chromosome 22
- hSNF5/INI1 gene
o Deletions of the locus and loss of
nuclear staining for INI1 protein are
seen in the majority of tumors
Clinical Features
- highly aggressive tumors of the very young,
usually before the age of 5
- Most patients live less than a year after
diagnosis
Other Parenchymal Tumors
Primary CNS Lymphoma

Most common CNS neoplasm seen in
immunocompromised patients

Usually of B-cell origin

Cells involved are usually infected with EBV

Often mutifocal

Aggressive and poor response to
Morphology:
- Often involve deep gray matter as well as
white matter and cortex
- Periventricular spread is common
- often show extensive areas of central necrosis
- accumulate around blood vessels
- B-cell markers, markers of Epstein-Barr viral
infection can be used as an aid in diagnosis
chemotherapy
Germ Cell Tumors
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•
•
•
occur along the midline
0.2% to 1% of brain tumors in people of
European descent but up to 10% in Japanese
people
tumors of the young, with 90% occurring
during the first two decades
tumors in the pineal region show a strong
male predominance
-
-
tumors share many features with their
counterparts in the gonads
metastasis of a gonadal germ cell tumor to the
CNS is not uncommon
– presence of a non-CNS primary
tumor must be excluded before a
diagnosis of primary germ cell
tumor is made
CSF levels of tumor markers including αfetoprotein and β-human chorionic
gonadotropin can be used to aid
Meningioma
General Informaiton
1. benign tumors of adults
2. attached to the dura, that arise from the meningothelial cell of the arachnoid
3. Prior radiation therapy
Morphology
1. Usually rounded masses with well-defined dural bases
compress underlying brain, but are easily separated
2. encapsulated with thin, fibrous tissue and may have
polypoid appearance
3. psammoma bodies
that
Histology
1. Syncytial ("meningothelial"), appropriately named
the whorled clusters of cells that sit in tight
groups without visible cell membranes
for
2.
3.
4.
5.
6.
7.
8.
Fibroblastic,
Transitional,
Psammomatous,
Secretory
Microcystic
Most meningiomas are easily separable from the brain
commonly immunoreactive for epithelial membrane antigen
Molecular Genetics
1. loss of chromosome 22, especially the long arm (22q)
2. deletions include the region of 22q12 that harbors the NF2 gene, which encodes the protein merlin
Clinical Features
1.
2.
3.
4.
5.
6.
7.
8.
Slow-growing
compression of underlying brain
Common sites of involvement include the parasagittal aspect of the brain conv
uncommon in children
moderate female predominance
usually solitary
diagnosis of NF2 should be considered
Meningiomas often express progesterone receptors
Atypical Meningiomas
1. Higher rate of recurrence and more aggressive local growth
a. mitotic index of four or more mitoses per 10 high power fields or at least three atypical features
Anaplastic Meningioma
1. Highly aggressive tumor, retaining some histologic evidence of meningothelial origin
2. Mitotic rates are often extremely high
Metastatic Tumors
1. Mostly carcinomas
2. Morphology
1. Intraparenchymal metastases form sharply demarcated masses, often at the junction of gray matter
and white matter, usually surrounded by a zone of edema
Paraneoplastic Syndromes
1. Major underlying mechanism
2.
3.
4.
5.
a. development of an immune response against tumor antigens that cross-react with antigens in
the central or peripheral nervous systems
Subacute cerebellar degeneration
a. Destruction of Purkinje cells
Limbic encephalitis
a. Subacute dementia
b. most evident in the anterior and medial portions of the temporal lobe
Eye movement disorders
a. Most commonly opsoclonus (uncontrolled eye movement),
b. often in association with other evidence of cerebellar and brainstem dysfunction
The peripheral nervous system can also be affected
a. Subacute sensory neuropathy
i. Loss of sensory neurons from dorsal root gangli
b. Lambert-Eaton myasthenic syndrome