Download 7. 8. Brain Tumors

7. 8. Brain Tumors
Neurons are the principal functional unit of brain tumors  There are multiple different types with
different properties, sizes, and structures.
Astrocytes  branching multipolar cytoplasmic processes containing glial fibrillary acidic protein
(GFAP); Gliosis is the most imp histopathologic indicator of CNS injury, and is characterized by both
hypertrophy and hyperplasia
Microglia  macrophage system of the CNS with monocytes/macrophages (e.g. CD68) surface markers.
Following an injury microglia cells aggregates about small foci of tissue necrosis (microglial nodules)
Ependyma  Ciliated columnar epithelial cells lining the ventricles; do not have specific patterns of rxn
Oligodendrocytes  dark round nuclei and a perinuclear “halo” (whereas astrocytes are larger, less
dense, oval)
Meninges  form focal nests of arachnoid cells (meningothelial cells) over arachnoid villa and in adults
they form whorls w/central psammoma bodies
CNS TUMORS: Dx of these tumors depend upon locations. Typically does’t metastasize (dependent on
unique features of each tumor):
 Glioma – most common & rarely metastasizes outside CNS (Grades I-IV according to biologic
behavior - based on WHO grading scheme)
o Astrocytoma
o Oligodendroglioma
o Ependymomas
 Glial tumors w/benign histo features – may infiltrate large brain areas  poor prognosis (not
feasible to resect these tumors w/o compromising neuro functions)
 Prognosis of tumors in CNS depends on location
 Through the CSF, the subarachnoid space provides a pathway for spread
Meningioma
Infiltrating Astrocytoma,
Oligodendroglioma
Pilocytic Astrocytoma,
Medulloblastoma
Ependymomas
and periventricular lesions
Ganglioglioma
Glioma  Astrocytomas
Diffuse Astrocytoma
(Fibrillary Astrocytoma)
Etiology/Characteristics
Grade II
- Infiltrative
Anaplastic Astrocytoma
Grade III
- Infiltrative
Glioblastoma
(Glioblastoma multiform)
- Infiltrative
* Most malignant form of
astrocytoma and the most
common primary brain
tumor
Pilocytic Astrocytoma
- Non-infiltrating
* Most common
astrocytoma
Grade IV
Lower grade: p53 and α(PDGF-A)
w/receptor
Higher grade: RB and p16/CDKNaA
Older pts will typically have
primary form
Younger pts will typically have
secondary form
- Both leads to ↑tyrosine kinase
receptor activity and the
activation of the RAS and PI-3
kinase pathways
Grade I/IV
Typically in children and young
adults
* Occurrence in presence of NF1
shows functional loss of
neurofibromin
Histo
- Network of fine GFAP +
astrocytic processes that give a
fibrillary appearance
- Cellular lesion w/sworling
fibrillary appearance
- Hard to differentiate btwn
normal and neoplastic cells
- Densely cellular
- Gemistocytic astrocytoma used
if bright eosinophilic cell body
seen
- Similar to anaplastic
astrocytoma
- Necrosis (in hypercellular areas
- serpentine pattern)
- Endothelial/vascular cell
proliferation (tufts of piled up
cells)
- Thin "hairlike" GFAP + processes
that form dense fibrillary
meshworks
- Rosenthal fibers
- Often biphasic
Gross
Poorly defined, gray,
infiltrative tumor (goes past
the midline)
Clinical Info & Dx & Tx
Usually @ cerebral
hemispheres
Sxms - Seizures, HA, and
focal neurologic deficits
relative to the anatomic
site
Varies
* Gliomatosis cerebri:
Affects multiple regions…
sometimes the entire brain;
Grade III
Piloid (hair-like) processes
and are characterized by a
relatively circumscribed
growth pattern
Dx - High-grade
astrocytomas have
abnormal vessels that are
"leaky" and therefore
demonstrate contrast
enhancement on imaging
studies
Tx - Poor prognosis
Benign (relative to others)
& slow growth
Tx – resection
Dx – histo  rarity of p53
mutation or other genetic
Δ compared to others
Other Gliomas
Oligodendroglioma
Etiology/Characteristics
Grade II
@ cerebral hemispheres
Slow growing, low grade
malignant tumor
Genetic - Loss of heterozygosity
for chromosomes 1p and 19q
Histo
- Surrounded by a clear halo of
cytoplasm
- Anastomosing capillaries
- Calcification
- Perineural satellitosis
- Anaplastic
Oligodendroglioma
Grade III
↑ cell density, nuclear anaplasia,
and ↑ mitotic activity
Ependymoma
Grade II
Typically @ 4th ventricle
Spinal ones are associated w/ NF2
- Resembles embryologic
ependymal canal
- Perivascular pseudorosettes
- GFAP + in most
Solid or papillary mass;
Well demarcated from
adjacent brain
Mixture of astrocytic, and
ependymal cell clusters
surrounded by their fibers
Nodules protruding into the
lateral/4th ventricle
Sxms – normally
asymptomatic; may cause
hydrocephalus
Papillary growths
recapitulate the structure of
the normal choroid plexus
Clinically presents with
hydrocephalus
- Paraventricular Lesions
Subependymoma
Benign to low grade lesions
Slow growing
- Choroid plexus papilloma
- Most commonly in children –
lateral ventricles
- Adults – 4th ventricle
Gross
Well-circumscribed,
gelatinous, gray masses,
often with cysts, focal
hemorrhage, and
calcification
Clinical Info & Dx & Tx
Sxms – Multiple years of
neuro complaints
Best prognosis among
gliomas
Tx – In tumors w/loss of
1p & 19q genes  longlasting response to chemo
In tumors w/o loss of
these genes  resistant
Sxms – CSF dissemination,
2ndary hydrocephalus
Tx – Complete excision
(good prognosis); if CSF
dissemination-poor
prognosis and if posterior
fossa lesion-worst
outcome)
Neuronal Tumors  Gangliocytomas – entirely neuronal tumors
Tumors
Ganglioglioma
Etiology/Characteristics
Contains mature-appearing
neurons (ganglions) – usually
admixed glial neoplasm
Mostly slow growing, but the glial
comp becomes anaplastic
Histo
- Bi-nucleate forms are frequent;
- Glial component resembles
astrocytoma
Gross
Commonly @ temporal lobe
Clinical Info & Dx & Tx
Lesions containing
mixtures of neuronal and
glial elements present as a
seizure disorder
Tx – surgical resection
Central neurocytoma
@ lateral or 4th ventricle
Low grade neuronal neoplasm
- uniform nuclei and often islands
of neurophil
- Resembles oligodendroglioma
Medulloblastoma
Commonly in children (near
vermis, whereas in adults more
lateral)
Genes – loss of material from 17p
 poor prognosis
- May express neuronal and glial
markers
CNS supratentorial
primitive neuroectodermal
tumors (CNS PNET)
Can lead to confusion with the
peripheral neuroectodermal
tumor, that shares a genetic
alteration with Ewing sarcoma
Similar histology and poor differentiation, resembling
medulloblastomas, found in the cerebral hemispheres
Atypical
Teratoid/Rhabdoid Tumor
Genes – alterations in
chromosome 22 (>90%) or
hSNF5/INI1 gene
Presence of rhabdoid cells
(resembles rhabdomyosarcoma)
* Drop metastases =
metastasis to cauda equina
Dx - ultrastructural and
immunohistochemical
studies reveal the
neuronal lineage
Poorly differentiated or
embryonal
Exclusively in cerebellum
@ posterior fossa and
supratentorial
compartments
May lead to
hydrocephalus
Highly malignant, but
radiosensitive
Highly malignant tumor of
young CHILDREN, usually
before the age of 5
Prognosis – most live less
than a yr
Brain Parenchymal tumors:
Tumors
Primary CNS Lymphoma
(2ndary CNS lymphoma is
very rare – occasionally by
CSF/nerve roots)
Germ Cell Tumors
Meningioma
Atypical Meningioma
Anaplastic Meningioma
Etiology/Characteristics
Arises from B-cells, often
multifocal (rarely involves
structures outside CNS)
Periventricular spread is common
0.2% to 1% of brain tumors in
Europeans but 10% in Japanese.
90% affected by 20yo.
If tumor @ pineal region – male
predominance
May metastasize from gonadal
germ cell tumor
Grade I
Predominantly benign tumors of
adults
Arises from the meningothelial
cell of the arachnoid
Risk factor:
- Prior radiation therapy
- Loss of chromosome 22 (esp.
22q)  NF2 gene  merlin
protein loss
Grade II
Higher rate of recurrence
Grade III
Histo
Malignant cells accumulate
around blood vessels
Patterns observed:
Numerous calcified psammoma
bodies
Syncytial – whorled cluster of cell
Fibroblastic – collagen deposits
Transitional – btwn above 2
Secretory
Microcystic
Gross
Often involves deep gray
matter as well as white
matter and cortex
Well defined, but not as
discrete as metastases and
often show extensive areas
of central necrosis
Clinical Info & Dx & Tx
Common in
immunosuppressed pt
(Epstein-Barr virus)
- Poor response to chemo
Occurs along the midline
Dx – 1st-exclude non-CNS
primary tumor
2nd-α-fetoprotein and βhuman chorionic
gonadotropin markers
Attached to the dura;
Rounded mass, well-defined
dural base - compressing
underlying brain;
Surface of mass –
encapsulated by thin,
fibrous tissue w/polypoid
appearance
Sxms – Slow growing,
normally parasagittal
aspect of the brain
convexity; usually solitary;
Dx - B-cell markers or
Epstein-Barr markers
Tx – Surgery - easily
separable from the brain
Dx – Immunoreactive for
epithelial membrane Ag
Mitotic index of four or more
mitoses per 10 high power fields
or at least three atypical features
More aggressive local
growth
Histo evidence of meningothelial
origin
Mitotic rates - extremely high
Highly aggressive
Metastatic Tumors:
 Mostly carcinomas
 Morphology: 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  Immune response against tumor Ag that cross-react with Ag in the CNS or PNS
 In CNS
a. Subacute cerebellar degeneration  Destruction of Purkinje cells
b. Limbic encephalitis  Subacute dementia, commonly @ temporal lobe
c. Eye movement disorders  opsoclonus, may be associate w/evidence of cerebellar and brainstem dysfunction
 In PNS:
a. Subacute sensory neuropathy  Loss of sensory neurons from dorsal root gangli
b. Lambert-Eaton myasthenic syndrome