Neuro-Oncology
Central Nervous System Tumors and Neuropathology
I. Introduction
Location of CNS Tumors
Intracranial
Supratentorial
Infratentorial
Intraspinal
Extradural (e.g., epidural metastases, bone tumors)
Intradural
Intramedullary (e.g., ependymomas, astrocytomas, glioblastomas)
Extramedullary (e.g., schwannomas, meningiomas)
Seventy percent of tumors in children are found in the posterior fossa (e.g., cerebellar medulloblastomas, cerebellar astrocytomas, and fourth ventricle ependymomas).
Seventy percent of tumors in adults are found in the cerebral hemispheres (e.g., astrocytomas, glioblastomas, metastases, meningiomas).
Histogenesis of CNS Cells
The brain and spinal cord develop from the neural tube.
The neural tube is composed of neuroepithelium, which gives rise to all neurons and microglial cells (astrocytes, oligodendrocytes, ependymal cell, and epithelial cells of the choroid plexus).
The mesenchyme gives rise to the microglial cells.
Abnormal cellular proliferation (neoplasia) results from the following:
Loss of tumor suppressor genes
Examples:
GENE
CHROMOSOME
ASSOCIATED TUMOR
P53
17 p13.1
Glioblastoma
CDKN2
9 p21
Glioblastoma
RB1
13 q14
Retinoblastoma
NF1
17 q11.2
Pilocytic astrocytoma, neurofibroma
NF2
22 q12
Schwannoma/meningioma
MEN1
11 q13
Pituitary adenoma
11q, 14q, 17p
Neuroblastoma
21q
Choroid plexus carcinoma
5q, 9q, 11
Choroid plexus carcinoma
9p9
Malignant meningioma
1p36, 2p, 6q
Atypical meningioma
22q, 18, 1p3
Meningioma
17p, 6q, 16q
Medulloblastoma
9p or 13 q loss
Anaplastic ependymoma
22
Spinal low-grade ependymoma
Activation of protooncogenes (which encode for growth factors, growth factor receptors, and regulators of gene expression)
Examples:
GENE
CHROMOSOME
MECHANISM
EGFR
7 p12
Amplification/rearrangement
C-myc, N-myc
8 q24, 2 p23&24
Amplification
H-ras, N-ras
11 p15, 1 p13
Overexpansion/point mutation
Tumors associated with angiogenesis
Metastatic tumors
Benign brain tumors
Craniopharyngioma
Meningioma
Pituitary adenoma
Malignant brain tumors
Anaplastic astrocytoma and glioblastoma multiforme
Hemangioblastoma
Medulloblastoma
Pituitary carcinoma
II. Grading Systems for Astrocytic Tumors
Kernohan: based on cellularity, mitoses, pleomorphism, vascularity, and necrosis
Grade I: increased cellularity
Grade II: greater cellularity than grade I plus pleomorphism
Grade III: greater cellularity and pleomorphism than grade II plus vascular proliferation
Grade IV: all of the above, plus necrosis and pseuodopallisading
Three-tiered: also based on cellularity, mitosis, pleomorphism, vascularity, and necrosis
Astrocytoma
Anaplastic astrocytoma
Glioblastoma multiforme (GBM)—necrosis present
World Health Organization classification—1993
Grade I: pilocytic astrocytoma, subependymal giant cell astrocytoma
Grade II: low-grade astrocytoma—hypercellularity, nuclear atypia
Grade III: anaplastic astrocytoma—mitosis, endothelial proliferation
Grade IV: GBM—necrosis
III. Glial Tumors
Pilocytic astrocytoma
Epidemiology: mainly children and adolescents. Can be seen in NF.
Clinical features: cerebellar lesions produce symptoms secondary to obstruction of cerebrospinal fluid (CSF) flow (hydrocephalus) or cerebellar dysfunction.
Location: cerebellum (children)
Brainstem, optic nerve, thalamus, hypothalamus (young adults)
Radiology: cyst with mural nodule, which enhances on magnetic resonance imaging (MRI)
Pathologic findings: Rosenthal fibers (opaque, homogenous, eosinophilic bodies); long, slender “hairlike” cells (hence the name “pilocytic”); eosinophilic granular bodies
Treatment: surgically curable if gross resection possible. Also sensitive to chemotherapy (preferred in children) and x-ray therapy.
Prognosis: >90% 10-year survival for cerebellar lesions after total resection
Subependymal giant-cell astrocytoma
Epidemiology: nearly always associated with tuberous sclerosis
Clinical features: produces symptoms by obstructing CSF flow at the foramen of Monro
Location: wall of lateral ventricle
Radiology: intraventricular enhancing mass on MRI
Pathology: aiant astrocytes without significant anaplasia
Treatment: surgical debulking for obstructive symptoms
Prognosis: slow-growing and benign, rare malignant degeneration
Pleomorphic xanthoastrocytoma
Epidemiology: most common in second decade of life
Clinical features: frequently long history of seizures
Location: predilection for superficial temporal lobes
Radiology: superficial meningocerebral nodule often associated with a cyst
Pathologic findings: lipid-laden astrocytes, extreme pleomorphism, cellular atypia, multinucleated giant cells. NO NECROSIS (often mistaken for GBM)
Treatment: surgical resection
Prognosis: good with resection. Occasional recurrence, rare malignant degeneration
Low-grade astrocytoma
Epidemiology: 25% to 30% of all cerebral gliomas. Chiefly in young adults ages 30 to 50 years.
Clinical features: seizures are more common than functional deficits, which depend on location.
Location: most commonly cerebral hemispheres (adults), but may also occur in the cerebellum, hypothalamus, optic nerve/chiasm, and brainstem (children)
Radiology: low density on computed tomography (CT) without enhancement. Low density on T1-weighted and high density on T2-weighted MR images (also without enhancement)
Pathologic findings: hypercellular, well-differentiated astrocytes; can be cystic; may be fibrillary (most common) or protoplasmic
Treatment: surgical resection with or without x-ray therapy (XRT) for hemispheric lesions
Prognosis: median survival, 5 to 6 years with treatment
Anaplastic astrocytoma
Epidemiology: chiefly in adults ages 30 to 50 years (as with low-grade astrocytoma)
Clinical features: sepends on location
Location: most commonly cerebral hemispheres (adults), but may occur in the cerebellum, hypothalamus, optic nerve/chiasm, and brainstem (children)
Radiology: enhancement usually present, but is of variable degree
Pathologic findings: endothelial proliferation, mitosis, nuclear atypia, hyperchromatic nuclei
No necrosis. Gemistocytic subtype frequently (80%) transforms into GBM.
Treatment: surgical resection, XRT, chemotherapy
Prognosis: 50% 2-year survival rate. Frequent transformation into GBM
Mean survival is 18 to 36 months.
GBM
Epidemiology: peak age 45 to 55 years. Male to female ratio is 2:1. Comprises 20% of all intracranial tumors, 50% to 55% of all cerebral gliomas
Clinical features: focal neurologic deficits common and depend on location
Location: predominantly cerebral hemispheres (particularly frontal and temporal lobes), but may also occur in brainstem, cerebellum, and spinal cord
Radiology: ringlike/annular enhancement around central necrosis on CT and MRI with vasogenic edema. Frequently tracks along white matter pathways. When it tracks along the corpus callosum into other hemisphere, this is known as “butterfly” GBM.
Pathologic findings
Gross: poorly demarcated variegated lesion with areas of necrosis and hemorrhage
Micro: pseudopallisading around areas of necrosis and endothelial proliferation are hallmarks. May look “glomeruloid” because it makes its own blood supply
Treatment: surgical debulking, XRT, chemotherapy
Prognosis: poor, mean 95% mortality in 2 years even with treatment. Age is the most important prognostic indicator, with worse survival in older persons.
Oligodendroglioma
Epidemiology: ages 30 to 50 years. Comprise 5% of intracranial gliomas
Clinical features: frequently long history of seizures
Location: cerebral hemispheres (frontal and temporal lobes most common)
Radiology: calcification in 50% to 90%; minimal edema and enhancement (may have wispy “chicken wire” enhancement)
Pathologic findings
Gross: tracks along white matter
Micro: “fried-egg” cells (artifact of fixation), delicate vessels (most common primary tumor to bleed) and calcification, geometric patterns, round nuclei with stippled chromatin
Variants
“Intraventricular oligo”—really a neuronal cell tumor and should be called a central neurocytoma (see section VI, “Neuronal Cell Tumors”).
Mixed oligoastrocytoma—oligodendroglial and astrocytic components both occur in significant or roughly equal amounts.
Anaplastic oligodendroglioma—increased mitotic rate and pleomorphism. May transform into GBM. Responds to chemotherapy.
Treatment: surgical resection and chemotherapy (usually good response to chemotherapy)
Prognosis: median survival 5 years
Ependymoma
Epidemiology: most frequent in childhood and adolescence, peak age 10 to 15 years
Comprise 6% of intracranial gliomas, 60% of spinal cord gliomas
Most common spinal cord glioma
Clinical features: symptoms secondary to obstruction of CSF flow
Location: infratentorial in 60% of cases, supratentorial in 40%. Most frequently in region of fourth ventricle; also common in the lumbosacral spinal cord and filum terminale
Radiology: intraventricular mass with contrast enhancement and frequent calcification. Obstructive hydrocephalus may be seen.
Pathologic findings
Gross: well circumscribed, grow by local extension, and may spread in the CSF pathways
Micro: ependymal tubules, perivascular pseudorosettes
Variant
Subependymoma—intraventricular, benign, also causes symptoms from obstruction of CSF flow
Treatment: surgical resection followed by XRT with or without full spinal axis radiation
Prognosis: 87% 5-year survival rate after resection
Gliomatosis cerebri
Epidemiology: peak incidence in first and second decades of age; range 6 to 60 years of age
Clinical features: impairment of intellect, headache, seizures, and papilledema are common.
Location: diffusely infiltrating without discrete tumor mass. Arises deep (in thalamus and basal ganglia) and grows along scaffolding of normal brain.
Radiology: homogeneous, hypodensities, loss of grey-white junction, swollen hemispheres on CT. Diffuse increase in T2 signal on MRI. Enhances minimally if at all.
Pathologic findings
Gross: diffusely enlarged brain.
Micro: extensive grey and white matter infiltration by undifferentiated cells with foci of neoplastic astrocytes. Generally falls into the anaplastic astrocytoma subcategory.
Treatment: none proven effective
Prognosis: poor; survival is months to years.
IV. Primitive Neuroectodermal Tumors (PNET)
“Small blue cell tumors” resembling germinal matrix. Identified by the suffix “blastoma,” with the exception of GBM.
Medulloblastoma
Epidemiology: most common PNET. Occurs in first decade of life with a second peak in the 20- to 30-year age category. Accounts for about one third of all pediatric posterior fossa tumors.
Clinical features: present with cerebellar dysfunction and symptoms secondary to obstruction of CSF flow
Location: predilection for midline cerebellum (inferior vermis). Tends to infiltrate the cerebellar hemispheres and spread within the neuraxis via CSF pathways (“drop metastases”).
Radiology: contrast-enhancing, rare calcification
Pathology: Homer-Wright rosettes (sheets of cells forming rosettes around a central area filled with neuritic processes). These can be seen in any PNET.
Variants
Desmoplastic—abundant reticulin, more lateral in the cerebellar hemispheres, older children, better prognosis
Medullomyoblastoma—very rare, contains immature muscle cells, very malignant
Treatment: surgical resection followed by craniospinal XRT (sensitive) with or without chemotherapy
Prognosis: >50% 5-year survival rate with treatment. Recurrence, CSF seeding, and distant metastases are not uncommon.
Retinoblastoma
Epidemiology: children <3 years of age. Is the most common potentially fatal intraocular neoplasm of childhood. Sporadic (60%) or autosomal dominant (40%). Hereditary form tends to be bilateral with early onset. Increased incidence with chromosome 13 deletion (deletion of Rb supressor gene).
Clinical features: presenting symptoms include leukocoria (white pupil), squint (strabismus), red and painful eye, and secondary glaucoma.
Location: eye, with intracranial extension via optic nerve. Bone marrow is common site of blood-borne mets.
“Trilateral tumor” = bilateral retinoblastomas + pineoblastoma
Pathologic findings: Homer-Wright rosettes and Flexner-Wintersteiner rosettes (sheets of cells forming rosettes around an empty lumen—recall that Homer-Wright rosettes have neuritic processes filling this central area).
Treatment: surgical resection
Prognosis: high survival rate (90%) with early treatment
Neuroblastoma
Epidemiology: first decade of life; two thirds of cases occur before the age of 5 years.
Clinical features: can present with myoclonic encephalopathy neuroblastoma syndrome = opsoclonus, myoclonus, and encephalopathy. May be idiopathic or secondary to an occult neuroblastoma.
Location: most commonly arises from the sympathetic chain. Cerebral form is uncommon.
Radiology: large, discrete, contrast-enhancing lesions with calcification and cysts
Pathology: Homer-Wright rosettes, dense sheets of tumor cells. May secrete dopamine and catecholamines, which can be measured in urine (vanilmandelic acid, homovanillic acid). Amplification of N-myc oncogene present in more than one third of cases, and degree of amplification correlates with advanced stage and poor prognosis.
Treatment: surgical resection with tumor bed XRT with or without full neuraxis radiation
Prognosis: recurrence is frequent.
Esthesioblastoma—olfactory neuroblastoma
Epidemiology: bimodal age distribution with larger peak in late adulthood
Location: olfactory neuroepithelium with involvement of the cribriform plate
Radiology: enhancing, dumbbell-shaped mass centered on the cribriform plate
Pathologic findings: rare Homer-Wright rosettes, rare olfactory rosettes
Treatment: surgical resection
Prognosis: favorable with total resection
Pineoblastoma
Epidemiology: occurs most commonly in children
Clinical features: may present with Parinaud syndrome (see section VII, “Pineal Region Tumors”).Stay updated, free articles. Join our Telegram channel
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