3/23/99

Pathology II

 

Neoplasms of the Central Nervous System

·        1° neoplasms even if benign may cause death, due to compression of vital structures

·        although brain is a common site for dissemination from other tumors, 1° brain neoplasms rarely metastasize

 

1° Neuroglial Tumors (Gliomas)

Astrocytomas

·        most common group of 1° CNS tumors

·        two major classifications:  Fibrillary and Pilocytic

 

Fibrillary Astrocytic neoplasms (diffuse astrocytomas)

·        infiltrative growth pattern-usually in cerebral hemispheres

·        adults

·        histological grade is important predictor of behavior

a)      well-differentiated—astrocytoma

b)      intermediate grade—anaplastic

c)      most aggressive-glioblastoma

·        glioblastoma multiforme

·        infiltrative lesions w/irregular areas of hemorrhage, necrosis and cystic change

·        rapidly moving

·        moves through brain

·        doesn't  metastasis

 

Pilocytic Astrocytomas

·        more common in children

·        common sites—cerebellum, 3^rd ventricle, optic nerves

 

Oligodendrogliomas

·        most common  in adults, usually cerebral hemisphere

·        soft gelatinous and better circumscribed that infiltrating astrocytoma

·        calcification is common

·        satellitosis—neoplastic cells tend to cluster around native neurons

·        prognosis—less predictable

 

Ependymomas

·        may occur at any age

·        arise in ventricles or central canal of spinal cord

·        intracranial lesions common in young (0-20 yrs)

·        most commonly affects 4^th ventricle, may cause hydrocephalus

·        intraspinal lesions predominate in adults

·        perivascular "pseudorosettes"—elongated tumor cell processes radiate around blood vessels, or around the lumen, ependymal rosettes

·        Clinical features depend on location, particularly if intracranial.  Increased intracranial pressure effects.

 

Primitive Neuroectodermal Tumor

·        Group of neoplasms composed of embryonal small cells

·        Includes medulloblastomas (most common), Ewings' tumor

 

Medulloblastoma

 

Meningiomas

·        Adults

·        Cranial vault or spinal cord sites

·        Female esp in spinal cord

·        Due to presence of progesterone receptors on meningothelial cells

·        Neurofibromatosis type 2

·        Firm lobulated lesions

·        Psammonma bodies—concentrically laminated calcified granules

·        Increased intracranial pressure, seizures, focal neurologic deficits

·        Prognosis related to size, location, surgical accessibility, histologic grade

 

Metastatic Neoplasms

·        Common site: lung, breast, malignant melanomas

·        Increased intracranial pressure, variable focal neurologic

 

1° Diseases of Myelin

·        Acquired demyelinated—MS

 

Multiple Sclerosis

·        Temperate climate

·        Most common demyelinating disease

·        European extraction

·        18-40

·        waxing and waning neurologic abnormalities involving different regions of CNS over a period of years

·        not well understood-probably autoimmune disease in which T cells react against myelin components

·        possible exposure to environmental agent early in life

·        if migrate from high-risk to low risk area before age 15, individual assumes low risk

·        Plaques—areas of demyelination.  May occur anywhere in the brain or spinal cord

·        periventricular white matter, optic nerves, spinal cord

·        acute lesions are soft and pink

·        older lesions are firm, pearly gray to pink

·        PNS is not affected

·        Clinical

·        Unpredictable

·        Some patients die w/in wks to months of onset

·        Some patients have normal life w/few sequela

·        Typically—multiple exacerbations and remissions w/cumulative neurologic deficits

 

Leukodystrophies

·        Demyelination disease

·        Hard to produce myelin

·        Genetic disorder

·        Childhood

·        Relentless progressive course

·        Lose in brain and spinal cord

 

Nutritional Diseases

·        Thyamine and vit B12

·        Wernicke-Korsafoff

·        Thyamine and alcoholism

·        Wernicke's encephalopathy—rapid onset of confusion, paralysis of extraocular mm (LR)

·        Korsakoff's psychosis—permanent memory loss w/untreated Wernicke's.  Inability to ether form new memories or retrieve old one, often accompanied by confabulation (creation of ready answers or fantasy responses to fill in memory gaps—organic brain disorders)

·        Alcoholic cerebellar degeneration—atrophy of superior vemis

·        Vitamin B12

·        Results in pernicious anemia

·        Nervous system response—subacute combined degeneration of spinal cord

·        Myelin vacuolation in dorsal and lateral white matter columns of cord

·        Motor and sensory abnormalities—including spasticity, weakness, loss of proprioception

·        May produce confusional state-"megoloblastic madness"

 

Acquired Metabolic Disorders

·        Hepatic failure

·        Altered levels of consciousness

·        Asterixis—characteristic flapping tremor

·        Astroytic changes due to high level of ammonia

 

Degenerative Diseases

Alzheimer's Disease

·        Most common cause of dementia in the elderly

·        Ocucurs after age 50, w/progressive increase w/age

·        Formerly termed senile dementia and presenile dementia

·        Seen in almost all Down's Syndrome after age 40

·        Cause is unknown:  factors involved include:

1. genetic—familial cases—mutation chromosome 14.  No single defect is likely
2. deposit of amyloid from breakdown of amyloid precursor protein (APP), b-amyloid, may be secondary
3. abnormal expression of apoprotein E (apoE).  May be involved in transprot/processing of b-amyloid

·        brain atrophy—frontal, temporal or parietal

·        cerebral ventricles are dilated (hydrocephalus ex vacuo), compensatory to loss of parenchyma

·        progressive impairment of memory and other cognitive functions

·        subtle at first—easily confused w/depression

·        cognitive impairment continues over 5-15 yrs

·        complete disorientation, loss of language

·        death from bronchopneumonia or other infection

 

Parkinsonism

·        disturbance in motor function characterized by rigidity, expressionless face, stooped posture, gait disturbances, slowing of voluntary movements, and characteristic "pill-rolling" tremor

·        not a single disease—disturbance in dopaminergic pathways connecting substantia nigra to basal ganglia

·        also occurs w/trauma, toxic agents, vascular disease, encephalitis

·        best known form:  idiophatic parkinsonism—paralysis agitans

·        disease of adulthood—manifest by sixth decade

·        depigmentation in substantia nigra

·        lewy bodies

·        insidious onset w/steady progression over 10 yrs

·        motor disturbances, dementia in some cases

·        death from incurrent infection or traumas due to falls

 

Huntington's Disease

·        hereditary, progressive fatal disorder involving the "extrapyramidal" motor system, characterized by involuntary movements (chorea) and dementia

·        autosomal dominate trait w/complete penetrance

·        gene is on chromosome 4-huntingtin abnormal protein appear to bind/inactive other normal proteins

·        excessive CAG sequence

·        atrophy of caudate nucleus, putamen, globus pallidus

·        cortical neuonal loss produces dementia

·        onset during 40's &50's

·        initially—choreiform movements (involuntary and writhing)

·        seizures, ridigidy, depression, cognitive impairment

·        symptoms progress over 15 to 20 yrs

·        death-suicide or intercurrent infections