Glial Tumors

Incidence 18000/yr in US (=8/100000 adults/yr) for malignant tumors

incidence is same for benign tumors
mets 10x as common
Incidence by Histology

GBM 21%
gliomas 42% of all tumors, 77% of malignant
meningioma 29%

Circumscribed

Juvenile pilocytic astrocytoma – 1/3 of pediatric tumors, 10% of all gliomas

Most common CNS tumor of childhood and the most benign of the astrocytic tumors
Peak incidence is in 1^st decade
Often associated with cyst and mural nodule
Mostly found in cerebellum, brain stem, optic tract, infundibulum
Biphasic with loose cells and microcysts; dense elongated tapering hairlike cellular processes with Rosenthal fibers
Leptomeningeal invasion, nuclear atypia, multinucleated cells, and vascular proliferation are not adverse prognostic indicators
Distinct from adult pilocytic astrocytoma (not encapsulated, poorer prognosis)
Radiology: Hemispheric cystic lesion with region of nodular enhancement
Treatment: Surgical excision
Prognosis: Many long-term survivors

Pleomorphic Xanthoastrocytoma (PXA)

7-25 years, often presents with seizures
usually superficial temporal lobe (cortex/meninges, not dural)
cystic with mural nodule
bizarre pleomorphic astrocytes, xanthomatous cells, spindle cells, multinucleated cells
mitoses, calcium, reticulin frequently found
no necrosis
good prognosis
pathologically appears like GBM but without necrosis or microvascular proliferation

Subependymal Giant Cell Astrocytoma (SEGA)

Found at foramen of monro
Enhancing, calcified, cystic, lobulated, well-demarcated, large multinucleated cells
Found in 25% of tuberous sclerosis cases
Mitoses rare
heavily calcified tumors with spindle and ganglionoid cells

Diffuse

Grade I-II Astrocytoma – 15% of astrocytomas

30 years, M>F
usually frontal, in fibrillary white matter
gray, homogenous, indistinct borders, expands white matter
Radiology: Low density lesion crossing gray/white matter junction, usually with minimal enhancement and mass effect
no mitosis, rare hemorrhage, 15% calcify
genetically unstable and may develop malignant degeneration
no good data about surgery for low-grade gliomas

radiation increases progression-free survival but not overall survival (no data on quality of life)
chemotherapy - early for oligos (1p/19q)

Pathologically resembles reactive astrocytosis, except patternless, violate gray-white junction, contain microcysts, microcalcification, nuclear atypia/pleomorphism
hypercellularity without mitoses, calcification, or pleomorphism
25% survive 5 years (increases to 38% if resected) so treatment is surgical excision
Prognosis: Follows one of 2 paths – remains benign with long-term survival or undergoes malignant transformation to anaplastic astrocytoma or glioblastoma multiforme

Grade III Astrocytomas – 30% of astrocytomas

40-60 years, M>F
Hypercellularity
Radiology: Mixed density lesion crossing gray/white matter junction with enhancement and mass effect
pleomorphic cells with angulated nuclei
no necrosis, rare calcification
secondary structures of Scherer around neurons in gray matter, also subpial and subependymal
usually treated the same as GBM (surgical excision)
median survival 3 years
Prognosis: 2 year mean survival

Grade IV Astrocytomas (Glioblastoma) – 50% of astrocytomas, 20% of all brain tumors

Many have EGFr (chromosome 7)
Necrosis, endothelial proliferation
Most frequently located in frontal lobe and corpus callosum
3% multicentric
patients in their 50's and 60's
mitotic figures, microvascular proliferation, necrosis
primary vs. secondary: paths are mutually exclusive but prognosis not different

primary (EGFr amplified, p53 normal) – EGFR amplification with LOH at 10p and 19q, PTEN mutation prior to transformation to GBM
secondary (progression from lower-grade astrocytoma; p53 mutations, EGFr normal) – p53 mutation or inactivation to produce low-grade astrocytoma, LOH at 19q and RB attenuation to produce anaplastic astrocytoma, LOH 10q/PTEN mutation/PDGFR amplification to produce GBM

Radiology: Mixed density lesion, occasionally crossing the corpus callosum, usualy ring-enhancing with marked surrounding cerebral edema and mass effect
Prognosis: Almost all patients die within one year of diagnosisradiation doubles life expectancy
chemotherapy - temazolamide (may only work on a subpopulation of GBM) – increase life 2 months

MGT - enzyme that protects cells against chemotherapy; methylation of MGT promotor blocks MGT production

Giant Cell GBM – multinucleated, increased reticulin, better prognosis (no division)
Gliomatosis cerebri – younger, 20-30 years
Gliosarcoma (Feign tumor) – 2% glioblastoma

40-60 years
temporal lobe with dural invasion
lobulated with spindle cells (silver stain), astrocytoma cells (GFAP
15-30% metastasize intracranially or extracranially
origin: vascular structures in GBM or leptomeningeal fibroblasts

Gemistocytic – 20%; worse prognosis
Optic Glioma

3-5 years, F>M
20% malignant
associated with NF1
resect to chiasm only (preserve vision on other side)

Brainstem Gliomas – 20% of intracranial tumors in children; unresectable unless exophytic

Peak incidence is in 1^st decade
Pons is most frequent site
Presentation: Cranial nerve palsies, gait instability, long tract signs; Hydrocephalus is rare and late finding
Radiology: Variably dense lesion with variable enhancement enlarging brainstem
Treatment: XRT
Prognosis: 2-3 year mean survival

Oligodendrogliomas – 10% of gliomas

35-40 years old, M=F
usually mixed with astrocytoma elements (pure form rare)
more likely to hemorrhage than astrocytomas
often present with seizures
start in white matter, can involve cortex; tend to be located in the frontal lobes
hypercellular but monomorphic with round cells, scant cytoplasm, chicken-wire vasculature, serpentine configuration, Indian-file lineup in white matter, satellitosis in gray matter
can form band-like calcification in the cortex
mini-gemistocytes – small, round nucleus with inclusion-like cytoplasm
fried-egg nuclei (perinuclear halo) on frozen section – artifact found mostly with oligodendrogliomas
GFAP+, S100+
presence of 1p deletion makes them more sensitive to chemo
1p and 19q deletions are associated with lower grade and better prognosis (esp response to chemo)
cortical permeation with perineuronal satellites, subpial accumulation
Radiology: Low density lesion with dense calcifications usually in a curvilinear distribution corresponding to gyri
Treatment:

3/4 demonstrate response to radiation or chemotherapy
1p deletion predicts sensitivity to adjuvant therapy
19q deletion in 2/3 of 1p deleted patients
adjuvant therapy increases progression-free survival but not overall survival (radiation usually reserved for recurrance)

Prognosis: Many long-term survivors
anaplastic oligodendroglioma

mitotic activity with vascular proliferation and necrosis
1p, 19q mutations indicate better response to therapy
1p intact, p53 mutation or EGFr amplification has worse response (more similar to GBM)

Oligodendroglioma look-alikes

central neurocytoma – usually intraventricular, may be heavily calcified

cell-free patches of fibrillary matrix (neuropil)
synaptophysin +

DNET – multinodular; have "glioneuronal element" as well as “oligodendrocyte-like element”

lack perineuronal satellitosis

clear-cell ependymoma – rare supratentorial tumor in children

have cilia/microvilli, often have areas of typical ependymomatous differentiation
GFAP +

clear-cell meningioma – can be located in CPA or cauda equina

found in young females (especially the spinal tumors)
looks benign but behaves aggressively
"blocky" collagen matrix
EMA +, cytoplasm is PAS+

Mixed Gliomas

Ganglioglioma – neoplastic neurons and neoplastic glia

Usually found in temporal lobe causing seizures
Well-circumscribed
Cystic with mural nodule
Calcified
Usually enhance
Perivascular inflammatory cells, reticulin, glia, binucleated neurons
Stains for neurofilament, synaptophysin, neurosecretory granules, GFAP

Gangliocytoma – neoplastic neurons, reactive glia (may represent dysplastic brain rather than true neoplasm)
Desmoplastic infantile ganglioglioma

Usually <18 month
Massive frontal tumor adherent to dura
Enhancing, cystic
Similar to meningioma pathologically, but GFAP+, EMA-

Dysembryoplastic neuroepithelial tumor (DNT) – normal neurons, dysplastic glia

1-19 years
temporal lobe (seizures)
circumscribed, cystic, multinodular, superficial cortex
resection causes cure