CNS Malformations & Tumors Flashcards
Neurulation
- Days 17-27 after fertilization
- NOTOCHORD induces overlying ectoderm to differentiate into NERUOECTODERM –> forms NEURAL PLATE
NEURAL PLATE –> NEURAL GROOVE –> NEURAL TUBE + NEURAL CREST CELLS
Neuropore = site of tube closure
- Anterior Neuropore: site of cephalic closure
- Posterior Neuropore: site of caudal closure
Anencephaly
vs.
Encephalocele
Anencephaly: occurs before 24 days gestation
- Rostral closure defect, with absence of Brain and skull
- frog-like appearance of fetus
- Maternal polyhydramnios due to impairment of fetal swallowing of amniotic fluid
- Clinical finding: increased AFP
Encephalocele: occurs before 26 days
- defective closure of rostral tube
- outpouching of brain tissue, mostly OCCIPITAL
Spina Bifida Occulta
- Occurs before 26 days of gestation
- Failure of bony spinal canal to close, but no structural hernation (Dura is intact)
- presents as a dimple or patch of hair overlying vertebral defect
- Clinical finding: increased AFP
Spina Bifida
- Meningocele
- Meningomyelocele
Meningocele: meninges, but not the spinal cord, herniate through the spinal canal defect
Meningomyelocele: Meninges AND spinal cord herniate through the spinal canal defect
- Clinical finding: increased AFP
Arnold-Chiari Malformation (Type II)
- Significant cerebellar tonsillar and vermian herniation through the foramen magnum
- midbrain roof deformed
- results in aqueductal stenosis and hydrocephalus due to blockage of the 4th ventricle
- often occurs with meningomyelocele & syringomyelia (syrinx expansion into anterior white commissure)
Dandy-Walker Malformation
- Agenesis of CEREBELLAR VERMIS (failed hindbrain development)
- presents as cystic enlargement of 4th ventricle with absent cerebellum
- associated with hydrocephalus and spina bifida
The Types of Glial Cells
- Astrocytes: Physical support, maintaining BBB
- Oligodendroglia: Myelinate CNS neurons
- Ependyma: Embryologic inner lining of the neural tube
- Choroid Plexus Epithelium: produces CSF
- Microglia (by convention, but are mesodermal in origin): CNS phagocytes
Components of Meninges
Pachymenix: Dura Mater
Leptomeninges:
- Arachnoid
- Pia mater
CNS Tumor Principles
Most common in incidence:
- Gliomas
- Meningioma
- Metastases
- Pituitary Adenoma
- Schwannoma
- Adult primary tumors: usually supratentorial
- Pediatric primary tumors: usually infratentorial
- Morbidity/Mortality: Correlates best with surgical respectability
- Primary CNS tumors rarely metastasize beyond CNS
- CNS tumors act as space-occupying masses: results in increased intracranial pressure & brain herniations
Pediatric Primary CNS Tumors
- 70 percent located bellow tentorium cerebelli (infratentorial)
- 60-70 percent derived from primitive CNS
precursor celllls or glia
Common Pediatric Tumors:
- Medulloblastoma: Cerebellar vermis
– Diffuse astrocytoma: Brainstem astrocytoma: Low-grade astrocytoma (Astrocytoma, Grade II); Glioblastoma multiforme (Astrocytoma, Grade IV)
– Circumscribed astrocytoma: Pilocytic astrocytoma (Astrocytoma, Grade I)
- Ependymoma: IV ventricle
- Craniopharyngioma: Region above sella turcica (suprasellar)
- Germ cell tumors: Region of pineal gland (posterior III ventricle)
Subfalcine/Cingulate Herniation
- Cingulate gyrus pushed under falx cerebri by expanding frontal/parietal mass
- May compress branches of anterior cerebral
artery (ACA) with infarction in ACA distribution
Transtentorial/Uncal/Hippocampal Herniation
- Medial-most part of temporal lobe (uncus) pushed out over edge of tentorium and wedged into cleft between tentorium and cerebral peduncle of midbrain
- Compresses ocullomotor nerve (CN III), resulting in fixed dilated pupil
- May push midbrain against contralateral tentorium, resulting in IPSILATERAL hemiparesis from peduncular compression - Compresses posterior cerebral artery (PCA) with infarction in PCA distribution
Cerebellar Tonsillar Herniation
- Inferior-most parts of cerebellar hemispheres (tonsils) pushed into foramen magnum, compressing respiratory centers of medulla
- may result from spinal tap in patient with intracranial pressure (ICP); Check for papilledema, obtain CT and/or MRI
before tapping patient with suspected ICP
Pilocytic Astrocytoma
- Well Circumscribed Astrocytoma
- MOST COMMON CNS TUMOR IN CHILDREN, usually in cerebellum (infratentorial)
- Cystic lesion (empty space) with MURAL NODULE (solid tumor nidus in cyst wall)
- Biphasic microscopic pattern:
- Piloid cells: dense, fascicles of elongated spindle cells
- microcystic zones: loose
- ROSENTHAL FIBERS: eosinophilic, corkscrew processes of astrocytes
- GFAP POSITIVE
- amenable to resection
Diffuse Astrocytoma: Grade II
– Poor demarcation from surrounding brain with deep extension into neighboring tissue
– Complete surgical resection often not possible; late recurrence common
– Progression of Grade II lesions to Grades III/IV
- CT/MRI: Hypodense lesion without contrast enhancement; minimal/absent edema
- Gross: Gray-white poorly demarcated mass expanding or effacing normal architecture; NO HEMORRHAGE OR NECROSIS
- Micro: Hypercellularity (increased astrocytes) with nuclear pleomorphism; NO MITOSES, VASCULAR PROLIFERATION OR NECROSIS
Anaplastic Astrocytoma
- Grade III astrocytoma
– Cerebral hemispheric white matter in adult 40-50 - CT/MRI: Low density lesion with irregular contrast enhancement, ± edema (greater contrast than grade II)
- Microscopic: Hypercellularity, pleomorphism, MITOSES
– Recurrence after surgery in 12-24 months
Gioblastoma Multiforme (Grade IV Astrocytoma)
- Most common primary brain tumor in adults
- Malignant, high grade tumor of astrocytes, with < 1 year life expectancy
- found in cerebral hemispheres, usually crossing the corpus callosum (BUTTERFLY LESION)
- CT/MRI: Heterogeneous, hyperdense lesion, with Peripheral rim of contrast enhancement (“ringenhancing”); Significant peritumoral edema and “mass effect”
- Gross: Hemorrhage, necrosis; can cause FUNGUS CEREBRI appearance
- Microscopic: Hypercellularity, pleomorphism, mitoses,
GLOMERULOID vascular proliferation, necrosis surrounded by PSEUDOPALISADING viable tumor cells - GFAP STAIN POSITIVE
Ependymoma
- Malignant pediatric tumor of ependymal cells
- Children: most common in 4th ventricle (presents with hydrocephalus)
- Adults: most common in spinal cord
Gross: Solid/papillary intraventricular tumor; Relatively circumscribed - Microscopic: Glial tumor with PERIVASCULAR PSEUDOROSSETTES, ±
ependymal canals
Perivascular Pseudorosette
- characteristic histological finding in ependymoma
- Characteristic 3 ring target:
1. blood vessel
2. cytoplasmic processes: attach themselves to blood vessels
3. nuclei: congregate in a stripe outside the pink processes
Medulloblastoma
- highly malignant, pediatric cerebellar tumor (primitive neuroectoderm), which can compress 4th ventricle (hydrocephalus)
- “Drop metastasis”: spread to spinal cord
- CT/MRI: Hyperdense contrast enhancing lesion
- Gross: Variable circumscription, gray-white to hemorrhagic
- Microscopic: “Small round blue-cell tumor”
Cells with very high nuclear:cyttoplasmic ratio
– HOMER WRIGHT ROSETTES: small round blue cells wrap around neuritic processes
– High mitotic activity, apoptosis, pleomorphism - TX: Surgery plus radiation/chemo
Oligodendroglioma
- malignant tumor of oligodendrocytes, found in cerebral hemispheric white matter, commonly involving FRONTAL LOBE, of adults
- clinical: presents with seizures
- CT: calcified tumor
- Gross: Gray-pink mass with cysts, calcification, hemorrhage
- Miicroscopic: Uniform cells with clear cytoplasm and central nuclei (“fried eggs”); follows acutely branching capillary stroma (“chicken wire vasculature”)
- Variable survival, but somewhat better than
astrocytomas (5-10 years)
Meningioma
- 2nd most common primary brain tumor (F>M; tumor expresses estrogen receptor)
- benign tumor of arachnoid cells, with dural tail, located over cerebral convexity
- extra-axial (external to brain parenchyma); well circumscribed
- my present with seizures and focal signs (compresses, but does not invade cortex)
- Histo: Whorled pattern; psammoma bodies (calcified whorled spindle cells) present; minimal pleomorphism and mitotic activity
- prognosis: easy to resect
Schwannoma
- 3rd most common primary brain tumor
- Benign tumor of Schwann cells (extra-axial)
- Locations: Vestibular Schwannoma: at Cerebellopontine angle with
hearing loss (CN VIII) - Gross: Well circumscribed, encapsulated, attached to nerve root; May show degenerative changes (cysts,
hemorrhage) - Microscopic: Biphasic with dense (Antoni A) and loose (Antoni B) zones; Spindle Cells (long, flat nuclei); Alignment of nuclei in palisades/zebra-stripe pattern (VEROCAY BODIES); Parent nerve pushed to one side
- surgically curable
Neurofibromatosis type 2
- bilateral acoustic schwannoma, especially at cerebellopointine angle
Neurofibroma
– Tumor in Spinal canal, attached to nerve root (usually dorsal) with nerve root compression
- Gross: Unencapsulated, diffuse fusiform expansion of nerve; Soft with shiny gelatinous cut surface
- Microscopic: Loose myxoid background with small wavy or comma shaped schwann cell nuclei; Axons of parent nerve embedded in, and separated by, tumor
Neurofibromatosis type 1 (NF1) (von Recklinghousen’s Disease)
- Multiple neurofibromas
- Autosomal dominant, with 100% penetrance, variable expression
- cafe-au-lait spots
- Lisch nodules (pigmented iris hamartomas)
Metastatic Tumors
- characteristically present as multiple, well-circumscribed lesions at the watershed gray-white junction
- Primary tumors include: Lung carcinoma; Breast carcinoma; Malignant melanoma; Renal cell carcinoma; Gastrointestinal tract carcinomas
- CT/MRI: Multiple heterogeneous masses with contrast enhancement and surrounding edema (ring-enhanced lesion)
- Gross: Circumscribed tumors with necrosis, hemorrhage
- Microscopic: Histology matches primary neoplasm
Craniopharyngioma
- Pediatric supratentorial brain tumor, involving cerebrum
- benign Rathke’s pouch tumor with cholesterol crystals & calcification
- May compress optic chiasm –> bitemporal hemianopsia
Holoprosencephaly
- Occurs at 5-6 weeks (disorder of ventral induction)
- Failure of segmentation and cleavage into paired brain hemispheres
- Usually sporadic, but can be associated with Patau Syndrome (Trisomy 13), Edward Syndrome (Trisomy 18), and Sonic Hedgehog gene mutation
Microcephaly Vera
- Autosomal recessive disorder of nerve cell proliferation; brain doesn’t grow
- Occurs around 2-4 months
- causes severe mental retardation
E.g., Down Syndrome: too few neurons in certain areas of the brain
Marcocephaly
- autosomal dominant or recessive disorder in nerve proliferation, where you have too much nerve proliferation
- occurs ~2-4 months of gestation
- frequently associated with HETEROTOPIAS (misplaced gray matter)
Disorders of Nerve Cell Migration
Occur during 3-5 months
- Agenesis of Corpus Collosum
- Lissencephaly: smooth cortex; POLYHYDRAMNIOS IN PREGNANCY
- Pachygyria: Thick wide gyri; heterotopic neurons
- Polymicrogyria: small, multiple gyri, with cobblestone appearance; assoc w/ Zellwegger syndrome
- Schizencephaly: a congenital split or cleft in the brain; usually early in brain development
- Fetal Alcohol Syndrome: Microcephaly, motor disorders, MR, dysmorphisms
Myelination
- Final process in brain development, occuring at 5 months gestation
- Usually completed at 18 months of age
- Direction:
- Inferior to superior
- Posterior to anterior
Hydraencephaly
- Destructive prenatal lesion
- Almost complete absence of the hemispheres
- Damage is along distribution of internal carotid arteries
- Clinically normal until 3-4 months
Porencephaly
- Destrutive prenatal lesion
- Cavitary defect in the brain, often extending from the surface of hemisphere to the ventricle
- Predilection for parietoccipal region
