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Pathology- Retinoblastoma
A tumor suppressor gene called RB found on chromosome 13 is deleted in both alleles, resulting in a tumor originating from neuroepithelial cells in the retina. Can be hereditary or random. The familial form is inherited as an autosomal dominant characteristic, requiring homozygosity for disease manifestation. Over 90% of those who are heterozygous carriers ultimately get the condition.
The retina consists of circular cells with darkly stained nuclei and little cytoplasm organized in Flexner-Wintersteiner rosettes (cuboidal cells surrounding a central lumen).
Can spread to the brain, spinal cord, bone, or lymph nodes.
Medical Typically seen in young children (familial form) who display reduced visual acuity, eye discomfort, strabismus, intraocular mass on funduscopic examination, and white cat's eye pupillary reflex.
Individuals with familial disease are prone to getting retinoblastoma in both eyes and have a heightened susceptibility to other malignancies such as osteosarcoma.
Surgical excision of tumor or eye if required, followed by radiation therapy.
A tumor becomes lethal after it has metastasized beyond the eye.
Notes Knudson's two-hit hypothesis prototype: Two mutations are necessary for the disease to occur. Deletion can be either hereditary (familial) or sporadic. The second mutation arises sporadically in both familial and sporadic instances.
A tumor suppressor gene called RB found on chromosome 13 is deleted in both alleles, resulting in a tumor originating from neuroepithelial cells in the retina. Can be hereditary or random. The familial form is inherited as an autosomal dominant characteristic, requiring homozygosity for disease manifestation. Over 90% of those who are heterozygous carriers ultimately get the condition.
The retina consists of circular cells with darkly stained nuclei and little cytoplasm organized in Flexner-Wintersteiner rosettes (cuboidal cells surrounding a central lumen).
Can spread to the brain, spinal cord, bone, or lymph nodes.
Medical Typically seen in young children (familial form) who display reduced visual acuity, eye discomfort, strabismus, intraocular mass on funduscopic examination, and white cat's eye pupillary reflex.
Individuals with familial disease are prone to getting retinoblastoma in both eyes and have a heightened susceptibility to other malignancies such as osteosarcoma.
Surgical excision of tumor or eye if required, followed by radiation therapy.
A tumor becomes lethal after it has metastasized beyond the eye.
Notes Knudson's two-hit hypothesis prototype: Two mutations are necessary for the disease to occur. Deletion can be either hereditary (familial) or sporadic. The second mutation arises sporadically in both familial and sporadic instances.
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Pathology - Glioblastoma Multiforme
Linked to genetic alterations in many oncogenes and tumor suppressor genes, such as p53 and the RB gene.
Most prevalent primary brain tumor.
Most commonly found in individuals aged 40 to 60.
Pathology: Irregular, unconfined lesion located in the cerebral hemisphere.
Microscopic examination reveals a high-grade astrocytoma originating from astrocytes. Central regions show necrosis and bleeding surrounding by many tumor cells grouped in a pseudopalisading pattern, displaying a high level of anaplasia.
Symptoms and signs
Seizures, headaches, nausea, vomiting, and other symptoms indicating elevated intracranial pressure.
Imaging shows mass effect and cerebral edema caused by a tumor.
Treatments: Surgical excision along with chemotherapy and radiation therapy.
The prognosis is very grim, with the majority of patients succumbing within a year of being diagnosed.
Benign low-grade astrocytomas, particularly pilocytic astrocytomas, are slow-growing tumors seen in the cerebellum of children. Rosenthal fibers, which are eosinophilic corkscrew fibers, are observed on histological examination.
Linked to genetic alterations in many oncogenes and tumor suppressor genes, such as p53 and the RB gene.
Most prevalent primary brain tumor.
Most commonly found in individuals aged 40 to 60.
Pathology: Irregular, unconfined lesion located in the cerebral hemisphere.
Microscopic examination reveals a high-grade astrocytoma originating from astrocytes. Central regions show necrosis and bleeding surrounding by many tumor cells grouped in a pseudopalisading pattern, displaying a high level of anaplasia.
Symptoms and signs
Seizures, headaches, nausea, vomiting, and other symptoms indicating elevated intracranial pressure.
Imaging shows mass effect and cerebral edema caused by a tumor.
Treatments: Surgical excision along with chemotherapy and radiation therapy.
The prognosis is very grim, with the majority of patients succumbing within a year of being diagnosed.
Benign low-grade astrocytomas, particularly pilocytic astrocytomas, are slow-growing tumors seen in the cerebellum of children. Rosenthal fibers, which are eosinophilic corkscrew fibers, are observed on histological examination.
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Pathology - Meningioma
Benign tumor originating from meningothelial cells of the arachnoid, located outside the brain.
Most prevalent among women over the age of 30.
Pathology: Typically a spherical encapsulated mass with a dural base, commonly found in the convexities of the cerebral hemispheres or the parasagittal area, and normally does not invade the brain.
Microscopic examination reveals a tightly packed whorled pattern of tumor cells together with psammoma masses with laminated calcifications.
Symptoms related to the compression of the underlying brain, such as seizures, headaches, nausea, vomiting, and other indications of elevated intracranial pressure.
Surgically remove the tumor if it causes symptoms.
The prognosis is favorable.
Meningiomas rank as the second most prevalent primary brain tumors.
Patients with neurofibromatosis type 2 may have several meningiomas.
Benign tumor originating from meningothelial cells of the arachnoid, located outside the brain.
Most prevalent among women over the age of 30.
Pathology: Typically a spherical encapsulated mass with a dural base, commonly found in the convexities of the cerebral hemispheres or the parasagittal area, and normally does not invade the brain.
Microscopic examination reveals a tightly packed whorled pattern of tumor cells together with psammoma masses with laminated calcifications.
Symptoms related to the compression of the underlying brain, such as seizures, headaches, nausea, vomiting, and other indications of elevated intracranial pressure.
Surgically remove the tumor if it causes symptoms.
The prognosis is favorable.
Meningiomas rank as the second most prevalent primary brain tumors.
Patients with neurofibromatosis type 2 may have several meningiomas.
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Pathology - Ischemic Stroke
Possible causes are thrombosis, embolism, dissection, vasculitis, or hypotension.
Risk factors including tobacco use, hypertension, atrial fibrillation, hyperlipidemia, and diabetes.
Cerebral infarction is linked to thrombosis or embolism and results in ischemic neuronal changes such as nuclear pyknosis and eosinophilic cytoplasm within 12 hours. Microglia and monocyte infiltration occur within 2 days, followed by liquefactive necrosis leading to a fluid-filled cavity and reactive astrocytes within 1-3 weeks. Gliosis, which is scar formation, can occur after several months and the infarction may progress to hemorrhagic infarction.
Watershed infarction is linked to low blood pressure and manifests as a wedge-shaped infarction at the border of the artery's supply area, typically found between the distribution of the anterior cerebral artery (ACA) and middle cerebral artery (MCA).
Lacunar infarcts are linked to high blood pressure and blockage of small blood vessels due to blood clots, resulting in small empty spaces surrounded by scar tissue in the brain.
It varies based on the location of reduced blood flow and the degree of alternative blood supply.
Anterior Cerebral Artery (ACA): Contralateral leg weakness and sensory loss.
Middle Cerebral Artery (MCA) presents with contralateral paralysis, sensory loss, contralateral hemianopia, and aphasias.
Proximal Cerebral Artery (PCA) symptoms include contralateral sensory disruption and homonymous hemianopia, with or without macular-sparing.
Damage to the lateral striate arteries results in contralateral paralysis.
Administer thrombolytic therapy after 4.5 hours of symptom onset if no signs of hemorrhage. Use antiplatelet medication such as aspirin and dipyridamole. Modify risk factors by treating hypertension and hyperlipidemia.
A transient ischemic attack is a temporary episode of neurological symptoms resulting from reduced blood flow to the brain, which typically lasts less than 24 hours and indicates a high risk of a future stroke.
Possible causes are thrombosis, embolism, dissection, vasculitis, or hypotension.
Risk factors including tobacco use, hypertension, atrial fibrillation, hyperlipidemia, and diabetes.
Cerebral infarction is linked to thrombosis or embolism and results in ischemic neuronal changes such as nuclear pyknosis and eosinophilic cytoplasm within 12 hours. Microglia and monocyte infiltration occur within 2 days, followed by liquefactive necrosis leading to a fluid-filled cavity and reactive astrocytes within 1-3 weeks. Gliosis, which is scar formation, can occur after several months and the infarction may progress to hemorrhagic infarction.
Watershed infarction is linked to low blood pressure and manifests as a wedge-shaped infarction at the border of the artery's supply area, typically found between the distribution of the anterior cerebral artery (ACA) and middle cerebral artery (MCA).
Lacunar infarcts are linked to high blood pressure and blockage of small blood vessels due to blood clots, resulting in small empty spaces surrounded by scar tissue in the brain.
It varies based on the location of reduced blood flow and the degree of alternative blood supply.
Anterior Cerebral Artery (ACA): Contralateral leg weakness and sensory loss.
Middle Cerebral Artery (MCA) presents with contralateral paralysis, sensory loss, contralateral hemianopia, and aphasias.
Proximal Cerebral Artery (PCA) symptoms include contralateral sensory disruption and homonymous hemianopia, with or without macular-sparing.
Damage to the lateral striate arteries results in contralateral paralysis.
Administer thrombolytic therapy after 4.5 hours of symptom onset if no signs of hemorrhage. Use antiplatelet medication such as aspirin and dipyridamole. Modify risk factors by treating hypertension and hyperlipidemia.
A transient ischemic attack is a temporary episode of neurological symptoms resulting from reduced blood flow to the brain, which typically lasts less than 24 hours and indicates a high risk of a future stroke.
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Pathology - Hemorrhagic Stroke
Primarily caused by hypertension, other factors may include bleeding disorders, anticoagulant medication use, arteriovenous malformations, brain tumors, or amyloid angiopathy.
Pathophysiology: Chronic hypertension is linked to Charcot-Bouchard microaneurysms, typically seen in the basal ganglia. The bursting of these aneurysms may directly lead to bleeding.
Brain hemorrhage typically occurs in the basal ganglia or thalamus, with a core patch of blood surrounded by swollen brain tissue leading to edema resolution. Reactive astrocytes and macrophages then form around the injury's edge, resulting in gliosis.
Clinical Symptoms and Signs
Symptoms include altered awareness, nausea, vomiting, headache, and neurological abnormalities such as weakness on one side of the body, sensory disturbances on one side, and vision field loss.
Therapy
Treat any blood clotting disorders; closely monitor blood pressure; consider surgical decompression for significant cerebral bleeding.
Primarily caused by hypertension, other factors may include bleeding disorders, anticoagulant medication use, arteriovenous malformations, brain tumors, or amyloid angiopathy.
Pathophysiology: Chronic hypertension is linked to Charcot-Bouchard microaneurysms, typically seen in the basal ganglia. The bursting of these aneurysms may directly lead to bleeding.
Brain hemorrhage typically occurs in the basal ganglia or thalamus, with a core patch of blood surrounded by swollen brain tissue leading to edema resolution. Reactive astrocytes and macrophages then form around the injury's edge, resulting in gliosis.
Clinical Symptoms and Signs
Symptoms include altered awareness, nausea, vomiting, headache, and neurological abnormalities such as weakness on one side of the body, sensory disturbances on one side, and vision field loss.
Therapy
Treat any blood clotting disorders; closely monitor blood pressure; consider surgical decompression for significant cerebral bleeding.
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Pathology - Subarachnoid Hemorrhage and Berry Aneurysm
Subarachnoid bleeding can be caused by the rupture of a berry aneurysm, trauma, or arteriovenous malformation.
Berry aneurysms typically happen randomly, however variables that increase the risk include hypertension, smoking, aortic coarctation, APKD, connective tissue disorders, and neurofibromatosis type I.
Berry aneurysms are more likely to rupture in women and individuals over the age of 40.
Subarachnoid hemorrhage is the presence of blood in the subarachnoid space. Fibrosis, which might occur after the blood is cleared, may cause obstruction of cerebrospinal fluid.
Berry aneurysm typically develops at the junctions of arteries in the circle of Willis. It involves a bulging of the artery wall due to thickening of the inner layer and thinning of the middle layer at the neck of the aneurysm, with the middle layer being absent in the sac wall.
Clinical presentation of subarachnoid hemorrhage includes severe headache, nausea, vomiting, loss of consciousness, possible fever, and nuchal stiffness. It can be life-threatening.
Laboratory results: Blood is found in the cerebrospinal fluid after a lumbar puncture.
Imaging: CT scan shows blood in basal cisterns.
Therapy
Treatment options include surgical repair, coil embolization, and supportive care, with the therapeutic method determined by cerebral angiography.
Arteriovenous malformations are vascular anomalies present from birth in the cerebrum, typically seen in the subarachnoid space but can also extend into brain tissue. The symptoms typically appear in young people as seizures or cerebral bleeding.
Subarachnoid bleeding can be caused by the rupture of a berry aneurysm, trauma, or arteriovenous malformation.
Berry aneurysms typically happen randomly, however variables that increase the risk include hypertension, smoking, aortic coarctation, APKD, connective tissue disorders, and neurofibromatosis type I.
Berry aneurysms are more likely to rupture in women and individuals over the age of 40.
Subarachnoid hemorrhage is the presence of blood in the subarachnoid space. Fibrosis, which might occur after the blood is cleared, may cause obstruction of cerebrospinal fluid.
Berry aneurysm typically develops at the junctions of arteries in the circle of Willis. It involves a bulging of the artery wall due to thickening of the inner layer and thinning of the middle layer at the neck of the aneurysm, with the middle layer being absent in the sac wall.
Clinical presentation of subarachnoid hemorrhage includes severe headache, nausea, vomiting, loss of consciousness, possible fever, and nuchal stiffness. It can be life-threatening.
Laboratory results: Blood is found in the cerebrospinal fluid after a lumbar puncture.
Imaging: CT scan shows blood in basal cisterns.
Therapy
Treatment options include surgical repair, coil embolization, and supportive care, with the therapeutic method determined by cerebral angiography.
Arteriovenous malformations are vascular anomalies present from birth in the cerebrum, typically seen in the subarachnoid space but can also extend into brain tissue. The symptoms typically appear in young people as seizures or cerebral bleeding.
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Pathology - Alzheimer Disease
The cause is uncertain, however hypotheses including aberrant amyloid gene expression leading to elevated Alpha beta protein, choline acetyltransferase deficiency causing reduced acetylcholine levels, or atrophy of the nucleus basalis of Meynert. Familial Alzheimer's disease is caused by mutations in the amyloid precursor protein (APP) gene on chromosome 21, mutations in presenilin genes on chromosomes 1 and 14, and the beta 4 allele of apolipoprotein E on chromosome 19.
Impacts half of those over the age of 85.
Gross Pathology : Brain cortical atrophy with expansion of sulci and ventricles.
Microscopic pathology features include neurofibrillary tangles made of tau protein displacing the nucleus in the cytoplasm, neuritic plaques with an alpha beta protein core surrounded by astrocytes, amyloid angiopathy, Hirano bodies in hippocampal cells, and granulovacuolar degeneration with cytoplasmic vacuoles in hippocampal cells.
Clinical Symptoms and Signs
Dementia manifests as a steady decline in memory, disorientation, language difficulties, visuospatial impairments, loss of motor function, or incontinence.
Administer Donepezil, an acetylcholinesterase inhibitor, or memantine, an NMDA receptor antagonist, to slow down disease progression.
Chronic illness with no remedy.
The cause is uncertain, however hypotheses including aberrant amyloid gene expression leading to elevated Alpha beta protein, choline acetyltransferase deficiency causing reduced acetylcholine levels, or atrophy of the nucleus basalis of Meynert. Familial Alzheimer's disease is caused by mutations in the amyloid precursor protein (APP) gene on chromosome 21, mutations in presenilin genes on chromosomes 1 and 14, and the beta 4 allele of apolipoprotein E on chromosome 19.
Impacts half of those over the age of 85.
Gross Pathology : Brain cortical atrophy with expansion of sulci and ventricles.
Microscopic pathology features include neurofibrillary tangles made of tau protein displacing the nucleus in the cytoplasm, neuritic plaques with an alpha beta protein core surrounded by astrocytes, amyloid angiopathy, Hirano bodies in hippocampal cells, and granulovacuolar degeneration with cytoplasmic vacuoles in hippocampal cells.
Clinical Symptoms and Signs
Dementia manifests as a steady decline in memory, disorientation, language difficulties, visuospatial impairments, loss of motor function, or incontinence.
Administer Donepezil, an acetylcholinesterase inhibitor, or memantine, an NMDA receptor antagonist, to slow down disease progression.
Chronic illness with no remedy.
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Pathology - Pick Disease
The cause is unidentified, but there is evidence suggesting that mutations on chromosomes 3, 9, and 17 are inherited in an autosomal dominant manner in up to 50% of cases.
Pathology: Uneven shrinkage of the frontal and temporal lobes of the brain.
Microscopic examination reveals the presence of Pick cells, which are enlarged neurons, or Pick bodies, which are spherical, silver-staining, neurofilamentous entities present in the cytoplasm within neurons.
Symptoms and signs
Dementia manifests with predominant personality changes, atypical behavioral patterns, and speech problems.
Therapies
Address symptoms; handle behavioral issues.
Chronic illness with no remedy.
Dementia with Lewy bodies is a progressive form of dementia characterized by parkinsonism and hallucinations. Histologically, it is identified by the presence of Lewy bodies, which are eosinophilic inclusion bodies found in the cytoplasm of substantia nigra cells.
The cause is unidentified, but there is evidence suggesting that mutations on chromosomes 3, 9, and 17 are inherited in an autosomal dominant manner in up to 50% of cases.
Pathology: Uneven shrinkage of the frontal and temporal lobes of the brain.
Microscopic examination reveals the presence of Pick cells, which are enlarged neurons, or Pick bodies, which are spherical, silver-staining, neurofilamentous entities present in the cytoplasm within neurons.
Symptoms and signs
Dementia manifests with predominant personality changes, atypical behavioral patterns, and speech problems.
Therapies
Address symptoms; handle behavioral issues.
Chronic illness with no remedy.
Dementia with Lewy bodies is a progressive form of dementia characterized by parkinsonism and hallucinations. Histologically, it is identified by the presence of Lewy bodies, which are eosinophilic inclusion bodies found in the cytoplasm of substantia nigra cells.
Pick Disease / Frontotemporal Dementia
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Pathology - Huntington Disease
Huntington's disease is an autosomal dominant disorder caused by an excessive number of CAG repeats in the Huntington disease gene located on chromosome 4.
Typically appears between the ages of 30 and 50.
Study of diseases
Findings: Degeneration of caudate nucleus and putamen, possible atrophy of globus pallidus and frontal lobe, and enlargement of lateral and third ventricles.
Microscopic findings include the loss of GABAergic neurons in the striatum and the presence of fibrillary gliosis.
Clinical Symptoms
A progressive disorder characterized by chorea (involuntary jerky movements), cognitive decline, and mood disorders.
Ultimately advances to profound dementia.
Treatment aimed at alleviating symptoms of dyskinesia and mood disorders.
Typically results in death after 15-20 years of being diagnosed.
Huntington disease, fragile X syndrome, and myotonic dystrophy exhibit anticipation, where the number of repeats grows in each generation, leading to progressively severe disease symptoms.
Huntington's disease is an autosomal dominant disorder caused by an excessive number of CAG repeats in the Huntington disease gene located on chromosome 4.
Typically appears between the ages of 30 and 50.
Study of diseases
Findings: Degeneration of caudate nucleus and putamen, possible atrophy of globus pallidus and frontal lobe, and enlargement of lateral and third ventricles.
Microscopic findings include the loss of GABAergic neurons in the striatum and the presence of fibrillary gliosis.
Clinical Symptoms
A progressive disorder characterized by chorea (involuntary jerky movements), cognitive decline, and mood disorders.
Ultimately advances to profound dementia.
Treatment aimed at alleviating symptoms of dyskinesia and mood disorders.
Typically results in death after 15-20 years of being diagnosed.
Huntington disease, fragile X syndrome, and myotonic dystrophy exhibit anticipation, where the number of repeats grows in each generation, leading to progressively severe disease symptoms.
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Pathology - Parkinson Disease
Cause unclear.
Typically occurs in those over the age of 50.
Pathology: The substantia nigra and locus ceruleus seem pale upon examination.
Microscopic examination reveals the absence of pigmented dopaminergic neurons in the substantia nigra along with gliosis. Additionally, Lewy bodies, which are eosinophilic intracytoplasmic inclusion bodies, are present in the neurons of the substantia nigra.
Pathophysiology: Decreased dopaminergic input to the striatum causes reduced activation of the basal ganglia motor circuit, resulting in bradykinesia.
Clinical Symptoms
Cluster of symptoms including pill-rolling tremor, bradykinesia, shuffling gait, rigidity with cogwheeling of extremities upon passive motion, postural instability, and expressionless facies, collectively referred to as parkinsonism.
10%-15% of individuals with Parkinson's disease experience dementia.
Treatment involves pharmacologic therapy using medications such as amantadine, anticholinergics, levodopa, dopamine agonists, and MAO-B inhibitors.
Additional factors leading to parkinsonism are recurrent head injuries (common in boxers), some medications (such as MPTP), parkinsonism following encephalitis (seen after the influenza outbreak in the early 1900s), and Shy-Drager syndrome (parkinsonism accompanied by orthostatic hypotension and autonomic dysfunction).
Cause unclear.
Typically occurs in those over the age of 50.
Pathology: The substantia nigra and locus ceruleus seem pale upon examination.
Microscopic examination reveals the absence of pigmented dopaminergic neurons in the substantia nigra along with gliosis. Additionally, Lewy bodies, which are eosinophilic intracytoplasmic inclusion bodies, are present in the neurons of the substantia nigra.
Pathophysiology: Decreased dopaminergic input to the striatum causes reduced activation of the basal ganglia motor circuit, resulting in bradykinesia.
Clinical Symptoms
Cluster of symptoms including pill-rolling tremor, bradykinesia, shuffling gait, rigidity with cogwheeling of extremities upon passive motion, postural instability, and expressionless facies, collectively referred to as parkinsonism.
10%-15% of individuals with Parkinson's disease experience dementia.
Treatment involves pharmacologic therapy using medications such as amantadine, anticholinergics, levodopa, dopamine agonists, and MAO-B inhibitors.
Additional factors leading to parkinsonism are recurrent head injuries (common in boxers), some medications (such as MPTP), parkinsonism following encephalitis (seen after the influenza outbreak in the early 1900s), and Shy-Drager syndrome (parkinsonism accompanied by orthostatic hypotension and autonomic dysfunction).
