Neuropathology Flashcards
A 3-year-old boy with transient repetitive episodes of right hemiplegia undergoes genetic testing. He is found to have a common mutation in RASA1 (RAS p21 protein activator [GTPase activating protein] 1). This patient is at increased risk for developing which of the following conditions?
A. Arteriovenous malformation
B. Glaucoma
C. Glioma
D. Liver failure
E. Hamartoma
Arteriovenous malformation
Capillary malformation-arteriovenous malformation (CM-AVM) syndrome is characterized by the presence of multiple small capillary malformations mostly localized on the face and limbs. Affected individuals have associated arteriovenous malformations (AVMs) and/or arteriovenous fistulas (AFVs). Symptoms from intracranial AVMs/AVFs appear to occur early in life. CM-AVM syndrome is an autosomal dominant inherited disorder that has been reported in association with heterozygous mutations in the RASA1 gene, which encodes the protein RASp21.
Glaucoma is more likely to occur with Sturge-Weber Syndrome, which has a mutation in GNAQ gene. There is no significant increased risk for development of glioma or hamartomas. Liver failure is associated with Alagille syndrome.
A photomicrograph (H & E stain) of a biopsy specimen of brain is shown. These findings are most consistent with which of the following diagnoses?
A. Lewy Body dementia
B. Viral encephalitis
C. Pick’s disease
D. Alzheimer’s disease
E. Anti-NMDA encephalitis
Viral encephalitis
The photomicrograph shows a babes nodule which is consistent to viral encephalitis. Anti-NMDA encephalitis would show an increase of immune cells. Amyloid beta plaques would be present for Alzheimer’s disease. Lewy bodies are present in Lewy body dementia. Pick’s bodies are present in Pick’s disease.
A histologic change commonly found as a result of hypoxemia is:
A. Microglia infiltration
B. Wallerian degeneration
C. Neuronal swelling with cytoplasmic pallor
D. Demyelination
E. Oligodendrocyte apoptosis
Neuronal swelling with cytoplasmic pallor
During hypoxic-ischemic events, neurons tend to be more selectively affected due to their high metabolic needs as compared to other cell types. As ATP becomes less available, sodium- potassium exchange pumps are no longer able to function, resulting in neuronal swelling due to osmotic shifts. This can appear histologically as cytoplasmic pallor. Other features include swelling of neuronal organelles, as well as shriveling and shrinkage of neurons undergoing apoptosis. Overall, this can result in a “spongy” appearance of the tissue on histology. As a result, the best answer is neuronal swelling.
Wallerian degeneration may occur at later stages of injury. Microglial infiltration would be seen during later stages of cerebral injury, as the dead neurons are phagocytosed. Neurons are typically considered more sensitive to hypoxia than oligodendrocytes.
A 67-year-old woman presents with a 30-mL cortically based left temporal lobe hemorrhage. The clot is removed, along with a small amount of adjacent brain. A representative section stained with Congo Red is shown. Which of the following is the most likely diagnosis?
A. Intracranial atherosclerosis
B. CNS neoplasm
C. Cerebral amyloid angiopathy
D. CNS vasculitis
E. Hypertensive hemorrhage
Cerebral amyloid angiopathy
Cerebral amyloid angiopathy (CAA) is characterized by the accumulation of amyloid fibrils in the walls of small to medium-sized arterial blood vessels and in capillaries of the CNS parenchyma and leptomeninges. CAA is a major cause of spontaneous intracerebral hemorrhage in elderly people and an important contributor to age-related cognitive decline. The most common clinical presentation of CAA is intracranial hemorrhage (ICH), which occurs predominantly in lobar sites.
Amyloid angiopathy-associated hemorrhages are most often solitary, but the natural history often progresses to include multifocal and recurrent hemorrhages. Compared with other causes of ICH, patients with CAA-associated hemorrhages have a lower mortality rate but an increased risk of recurrence. Unlike hypertensive arteriolar hemorrhages that occur in penetrating subcortical vessels, CAA-associated hemorrhages are more often superficial in location due to preferential involvement of vessels in the cerebral cortex and meninges. This makes them, at times, more surgically accessible. The photomicrograph above demonstrates amyloid laden blood vessels. H&E staining of affected tissues shows hyaline thickening in vessel walls with luminal narrowing. The presence of amyloid protein can be confirmed by multiple techniques but has traditionally been diagnosed by staining with Congo red. In the presence of polarized light, Congo red binds to amyloid fibrils and causes the classic finding of apple-green birefringence.
Primary CNS vasculitis demonstrates transmural inflammation with vessel wall injury on pathologic examination.
Longstanding hypertension produces degeneration of the intima media, breakage of the elastic lamina, and fragmentation of arterial smooth muscle. Lipohyalinosis, fibrinoid necrosis of the subendothelium, microaneurysms, and focal dilatations are seen in the arterioles.
In atherosclerosis, larger vessels demonstrate plaques, hyalinization, thickening, narrowing, and stiffness. It is a disease of arterial intima membrane.
There is no evidence of malignancy or tumor neovascularization on the microscopic slide.
The pathology in the photomicrograph shown is associated with which of the following?
A. Amyloid angiopathy
B. Vasculitis
C. Atherosclerosis
D. Hypertension
E. Tumor neovascularization
Amyloid angiopathy
Cerebral amyloid angiopathy (CAA) is characterized by the accumulation of amyloid fibrils in the walls of small to medium-sized arterial blood vessels and in capillaries of the CNS parenchyma and leptomeninges. CAA is a major cause of spontaneous intracerebral hemorrhage in elderly people and an important contributor to age-related cognitive decline. The most common clinical presentation of CAA is intracranial hemorrhage (ICH), which occurs predominantly in lobar sites.
Amyloid angiopathy-associated hemorrhages are most often solitary, but the natural history often progresses to include multifocal and recurrent hemorrhages. Compared with other causes of ICH, patients with CAA-associated hemorrhages have a lower mortality rate but an increased risk of recurrence. Unlike hypertensive arteriolar hemorrhages that occur in penetrating subcortical vessels, CAA-associated hemorrhages are more often superficial in location due to preferential involvement of vessels in the cerebral cortex and meninges. This makes them, at times, more surgically accessible. The photomicrograph above demonstrates amyloid laden blood vessels. H&E staining of affected tissues shows hyaline thickening in vessel walls with luminal narrowing. The presence of amyloid protein can be confirmed by multiple techniques but has traditionally been diagnosed by staining with Congo red. In the presence of polarized light, Congo red binds to amyloid fibrils and causes the classic finding of apple-green birefringence (Figure 1).
Longstanding hypertension produces degeneration of the intima media, breakage of the elastic lamina, and fragmentation of arterial smooth muscle. Lipohyalinosis, fibrinoid necrosis of the subendothelium, microaneurysms, and focal dilatations are seen in the arterioles.
Primary CNS vasculitis demonstrates transmural inflammation with vessel wall injury on pathologic examination.
Tumor neovascularization would demonstrate endothelial cell proliferation and migration.
In atherosclerosis, larger vessels demonstrate plaques, hyalinization, thickening, narrowing, and stiffness. It is a disease of arterial intima membrane.
A 62-year-old man with chronic alcoholism develops progressive global confusion. Examination of the eyes shows nystagmus and disconjugate gaze. His gait is broad-based and ataxic. A CT scan of the head shows atrophy of the cerebellar vermis. In addition to cerebellar cell loss, which of the following findings is most likely on postmortem examination of the brain?
A. Deposit in globus pallidus
B. Putamen appears brown and shrunken
C. Hemorrhages in the pallidum
D. Hemorrhages in mammillary bodies
E. Calcification in basal ganglia
Hemorrhages in mammillary bodies
The patient describe is suffering from Wernicke encephalopathy which on postmortem examination may show hemorrhage in the mammillary bodies. Hemorrhages in the pallidum are often seen with carbon dioxide poisoning. Wilson disease is an autosomal recessive disorder caused by mutations in a copper transport gene (ATP7B). The protein is expressed most strongly in the liver and brain and is necessary for the export of copper from the cell. The putamen appears brown and shrunken. In iron toxicity there is usually a deposit of iron seen in the globus pallidus. Calcifications can often been seen in Fahr disease in bilateral basal ganglia. Fahr disease can be secondary to SLC20A2 gene mutations which encodes sodium-dependent phosphate transporter 2 (PiT2) or XPR1 gene mutations that encodes for a retroviral receptor with phosphate export function.
The cortical lesion shown is most commonly encountered at autopsy in patients presenting with which of the following conditions?
A. Hypoxic ischemic encephalopathy
B. Sturge–Weber syndrome
C. Focal cortical dysplasia epilepsy
D. Lissencephaly
E. Tuberous sclerosis
Hypoxic ischemic encephalopathy
The H&E image shows pseudolaminar necrosis which can be seen in hypoxic ischemic encephalopathy. Focal cortical dysplasia is seen in patients that have epilepsy. Lissencephaly Is a thick cortex with 4 layers instead of 6. Sturge–Weber syndrome has pseudolaminar calcification of the neocortex and cortical atrophy underneath leptomenigeal angiomatosis. Tuberous sclerosis is associated with cortical tubers. Cortical tubers can cause thickened, raised, and occasionally dimpled gyrus with giant cells, dysmorphic neurons, gliosis, calcifications as well prominent cell loss in all cortical layers and lamination.
When the odontoid is fractured, serious spinal cord injury is often avoided because of the integrity of which of the following?
A. C2 pars interarticularis
B. Alar ligament
C. C1 lateral mass
D. Transverse ligament
E. C2 transverse process
Transverse ligament
Odontoid fractures are generally classified into 3 types. Type 1 encompasses an avulsion fracture of the odontoid tip. Type 2 involves a fracture through the odontoid waist, and Type 3 includes fractures that extend into the body of C2. The transverse ligament attaches to the lateral masses of C1 on either side and runs behind the odontoid process. As a result, it plays a key role in C1-C2 stability and prevents anterior translation, thus preventing spinal cord injury. Type 2 fractures that involve a disruption of the transverse ligament may be at higher risk of non-union.
The alar ligament is involved in Type 1 odontoid fractures, as there is an avulsion at the odontoid tip where the alar ligament inserts. These fractures are typically considered mechanically stable and managed with orthoses. The C2 pars interarticularis is involved in Hangman’s fractures. Fractures of the C2 transverse process are typically considered mechanically stable.
The most characteristic pathologic feature of the spinal cord four weeks after blunt trauma is
A. Wallerian degeneration
B. Disruption of blood-spinal cord barrier
C. Release of oxygen free radicals
D. Gray matter ischemia
E. Rupture of intramedullary vessels
Wallerian degeneration
Spinal cord injury may be divided into acute, subacute, intermediate, and chronic phases. During the acute phase of spinal cord injury, there are features such as axon disruption, hemorrhage, compromised vascular supply that leads to ischemia, and disruption of the blood-spinal cord barrier. This subsequently moves to the subacute phase, which is characterized by infiltration of inflammatory cells and release of free radicals. At 4 weeks after traumatic spinal cord injury, the patient would be in the next, intermediate phase. This is characterized by axon degeneration and scar formation. Maturation of scar and restricted regrowth and remyelination would be seen in the final, chronic phase. As a result, the best answer is Wallerian degeneration.
Rupture of intramedullary vessels, gray matter ischemia, disruption of the blood-spinal cord barrier would be seen in the acute phase of spinal cord injury. Release of oxygen free radicals would be seen in the subacute phase.
Which of the following areas of the brain is most likely to show petechiae when death is caused by closed head trauma?
A. Fornix
B. Gray-white junction
C. Brainstem
D. Corpus callosum
E. Anterior commissure
Brainstem
Diffuse axonal injury can be graded from 1 to 3, based on the Adams classification. Grade 1 is characterized by microscopic axonal damage of the subcortical cerebral white matter. Grade 2 is defined by white matter axonal damage with additional focal lesions involving the corpus callosum. Finally, Grade 3 additionally shows focal lesions indicative of axonal injury that involves the brainstem. MRI reporting often may use an adapted Gentry grading, in which grade 1 is defined by white matter lesions in the cerebral hemispheres.
Higher grade diffuse axonal injury has been associated with worse long-term outcome. As a result, evidence of petechiae in the brainstem would suggest grade 3 diffuse axonal injury. Recent work has further suggested that lesions in the substantia nigra and tegmentum may be even more specific markers of poor outcome.
Which of the following is most specifically related to progressive supranuclear palsy?
A. Bradykinesia and stiffness of the trunk muscles
B. Dementia
C. MAPT mutation to chromosome 17
D. The accumulation of tau protein
E. Supranuclear gaze palsy
Supranuclear gaze palsy
One of the differentiating clinical manifestations of PSP are the oculomotor findings. The oculomotor signs include impairment of vertical saccades, loss of optokinetic nystagmus, or loss of convergence.
The Tauopathies, a group of disorders associated with the accumulation of tau, includes progressive supranuclear palsy (PSP), Alzheimer’s disease, corticobasal degeneration. Patients with PSP often suffer from bradykinesia, but this symptom is also seen with Parkinson’s. While patients with PSP may suffer from dementia, this is also seen in those with Alzheimer’s and Parkinson’s patients. A mutation of MAPT on chromosome 17 is associated with frontal lobe dysfunction, parkinsonism, and frontotemporal dementia. These are seen in PSP but also Alzheimer’s and Parkinson’s disease.
Which of the following types of brain cells are most resistant to hypoxia and ischemia?
A. Pyramidal Cells of CA1
B. Pyramidal Cells of CA3
C. Neurons of Locus Ceruleus
D. Neurons of forsal Nucleus Tractus Solitarius
E. Neurons of Trigeminal Mesencephalic Nucleus
Pyramidal Cells of CA3
The brain regions most sensitive to this type of injury are parts of the hippocampus (CA1), the dorsolateral caudate nucleus and the reticular nucleus of thalamus. Cerebellar purkinje cells (PCs) are known to exhibit a selective vulnerability to naturally occurring and experimental hypoxic/ischemic insults. However, cells of the hypothalamus and brainstem are resistant to hypoxia as is CA3 of hippocampus.
Which of the following diseases is most likely to predispose an individual to the condition disclosed in the pathologic cross section of the spinal cord shown?
A. Mutation in Survival Motor Neuron 1 B. Mutation in Frataxin
C. Poliovirus
D. Crohn disease
E. Syphillis
Crohn disease
The image shows an H&E of a patient that had subacute combined degeneration, which is due B12 deficiency. Patients with Crohn disease are B12 deficient. Tables dorsalis occurs secondary to syphilis. Friedreich’s ataxia occurs in patients with mutations in frataxin. Mutations in Survival Motor Neuron 1 result in Spinal Muscular atrophy which is an anterior horn cell disease in infancy or early childhood. Poliovirus is the virus to cause polio which results in anterior horn cell disease.
The most likely source of hemorrhage in the patient from whom the specimens shown were obtained is
A. Arteriovenous malformation
B. MCA aneurysm rupture
C. Hypertension
D. Hemorrhagic conversion of ischemic stroke
E. Neoplasm
Hypertension
Hypertension is the most common cause of hemorrhagic stroke. Longstanding hypertension produces degeneration of the intima media, breakage of the elastic lamina, and fragmentation of arterial smooth muscle. Lipohyalinosis, fibrinoid necrosis of the subendothelium, microaneurysms, and focal dilatations are seen in the arterioles. The microaneurysms are called Charcot-Bouchard aneurysms. Most common locations are the basal ganglia (especially putamen), thalamus, pons, and cerebellum. The image above is demonstrating most likely a putaminal hypertensive hemorrhage. Given the location and extent of bleed, there is unlikely to be an underlying neoplasm or vascular malformation. This is also an unlikely location for an ischemic stroke and thus, hemorrhagic conversion. MCA aneurysmal rupture would more likely present with subarachnoid hemorrhage.
Which of the following histologic findings is most likely to be seen in the plaques of multiple sclerosis?
A. Hyperplasia
B. Demyelination
C. Vacuolation
D. Perivascular necrosis
E. Axon retraction
Demyelination
The pathologic hallmark of multiple sclerosis is multiple focal areas of myelin loss within the CNS called plaques or lesions. Demyelination is accompanied by variable gliosis and inflammation and by relative axonal preservation.
Perivascular necrosis can be seen in hypoxic regions of the brain following a period of hypoxia or a disease state that results in regions of hypoxia i.e. glioblastoma multiforme. Vacuolation can be seen in multiple disorders in which there is an accumulation of a protein or dysregulation of transportation of proteins in the cell. Axonal retraction can be seen following trauma, including diffuse axonal injury. Hyperplasia is the enlargement of an entity, usually in this case referring to the size of a particular cell. Perivascular necrosis, vacuolation, axon retraction and hyperplasia do not occur in multiple sclerosis.
The gross autopsy specimen shown demonstrates a lesion that contains which of the following?
A. Irregular venous-type channels lined by flat endothelium and surrounded by scant smooth muscle
B. Necrotic astrocytes and reactive astrocytosis in the penumbra
C. Tortuous arteries and large, thick-walled veins
D. Lobules of curved capillaries and venules separated by edematous stroma with inflammatory cells
E. Lobules of capillaries in cannonball shapes with spindled endothelial cells
Tortuous arteries and large, thick-walled veins
Arteriovenous malformations (AVMs) are high-flow vascular malformations which allow direct connections between cerebral arteries and veins. They can cause significant morbidity and mortality from intracranial hemorrhage.
Macroscopically, AVMs are tangles of abnormally enlarged vessels which directly shunt blood from the arterial system to the venous system due to a lack of an intervening capillary bed. Histologically, these abnormal vessels resemble capillaries despite their diameter, which is multiple times larger than that of a capillary. The lack of a normal capillary bed causes abnormally high flow through these nidal vessels due to the subsequent lack of normal capillary bed resistance. Since blood vessels adapt to changes in flow through flow-induced vessel wall remodeling, this abnormally high flow often causes ectatic remodeling of the veins draining the AVM or of the arteries feeding it. In addition to causing enlargement of the vessel caliber, this may lead to formation of venous ectasias, intranidal aneurysms, or aneurysms of the feeding arteries. The gross specimen demonstrates a large parietal AVM.
Tortuous arteries and veins with overgrowth of fibromyxoid and adipose tissue are seen with PTEN hamartomas of soft tissues, which can often be misdiagnosed as an AVM.
Lobules of capillaries in cannonball shapes with spindled endothelial cells are seen in tufted angiomas.
Irregular venous-type channels lined by flat endothelium and surrounded by scant smooth muscle are seen in venous malformations/cavernous angiomas.
Lobules of curved capillaries and venules separated by edematous stroma with inflammatory cells are seen in pyogenic granulomas.
A 35-year-old man with HIV and multiple brain lesions has the histopathologic findings shown in the photomicrograph. Which of the following is the most likely diagnosis?
A. JC Virus
B. Myobacterium tuberculosis
C. Cytomegalovirus
D. Cryptococcus neoformans
E. Toxoplasma gondii
Toxoplasma gondii
The photomicrograph shows several cells with tachyzoites. The tachyzoite is lunate and are seen during the proliferative stage of Toxoplasma gondii, a common CNS infection seen in patients with
HIV. JC Virus causes Progressive Multifocal Leukoencephalopathy (PML). PML can usually be identified by the characteristic tissue cytopathology, including oligodendrocytes with intranuclear inclusions, bizarre astrocytes, and lipid-laden macrophages, with identification of JCV or cross reacting polyoma virus by immunohistochemistry, in situ nucleic acid hybridization, or electron microscopy.
Myobacterium tuberculosis are acid fast bacilli on microscopy. Cryptococcus neoformans like other fungal infections, typically shows granuloma formation with or without associated central necrosis. Cytomegalovirus is a double stranded DNA virus belonging to the herpesvirus group, microscopy shows cytomegalic cells with basophilic intranuclear inclusions.
A 19-year-old man dies three days after sustaining multiple injuries in a motor vehicle collision. He had a fractured femur and had been in a coma; Glasgow Coma Scale score had been 5 since admission. CT scan of the head showed small hemorrhages in the corpus callosum and midbrain. The light microscopic appearance of H & E (Figure 1) and Bielschowsky (Figure 2) stains of the brain tissue obtained at autopsy is shown. Which of the following is the most likely cause of his coma?
A. Chronic traumatic encephalopathy
B. Left middle cerebral artery infarction
C. Diffuse axonal injury
D. Hypoxia
E. Creutzfeldt-Jakob Disease
Diffuse axonal injury
The clinical vignette suggests high grade diffuse axonal injury. Presence of microhemorrhages in the corpus callosum and midbrain are indicative of grade 3 injury, which is additionally consistent with the poor Glasgow Coma Scale score. The hematoxylin-eosin stain demonstrates axonal injury by the presence of axonal swellings. Bielschowsky’s silver stain is used to visualize nerve fibers including axons, and this again shows axonal injury, with evidence of axonal retraction bulb formation. Other histopathological characteristics of diffuse axonal injury include axons that appear varicose, with a “beading” appearance.
Hypoxia is typically seen histopathologically with cytoplasmic pallor and neuronal swelling. Chronic traumatic encephalopathy is a tauopathy and perivascular tau deposits can be visualized. Creutzfeldt-Jakob disease is a prion disease that on histology appears as spongy tissue.
A 67-year-old woman presents with a 30-mL cortically based left temporal lobe hemorrhage. The clot is removed along with a small amount of adjacent brain. A representative section stained with H & E is shown. Which of the following is the most likely diagnosis?
A. Capillary teleangiectasia
B. Venous angioma
C. Cavernoma
D. Hemangioblastoma
E. Arteriovenous malformation
Cavernoma
The correct answer is cavernoma. These vascular lesions are defined by vessels back-to- back/little intervening parenchyma. Arteriovenous malformations contain large vessels with eccentric wall thickening. Venous angioma have thin walled, dilated vascular channels. Capillary teleangiectasia have many small, thin-walled capillaries surrounded by normal brain but no associated hemorrhage. Hemangioblastomas contain capillaries with variable sized, closely packed, thin-walled vessels and large neoplastic stromal cells with pink to clear foamy cytoplasm with fine vacuoles containing PAS+ lipid.
Which of the following is the most appropriate management of the lesion shown in this Masson trichrome-stained immunohistochemical block?
A. Temozolomide
B. BCNU
C. Biopsy
D. Surgical resection
E. Endovascular embolization
Surgical resection
The image demonstrates closely packed vascular sinuses with thin walls, with evidence of surrounding gliosis, suggestive of a cavernous malformation. Management options for cavernous malformation include observation, surgical resection, and radiosurgery, and selection of a treatment option depends on accessibility, eloquence of the surrounding area, symptomaticity, and evidence of hemorrhage. Surgical resection may be considered in cases of solitary, symptomatic cavernous malformations, particularly if located in non-eloquent areas.
Endovascular embolization and biopsy are not typically used to treat cavernous malformations. Temozolomide and BCNU are chemotherapeutic agents that are used to treat gliomas
Histopathologic features of the lesion in the axial T2/FLAIR MR image shown most likely include which of the following?
A. Tau neurofibrillary tangles
B. Vascular walls with smooth muscle elements
C. Vascular sinusoids lined by endothelial cells
D. Rosenthal fibers
E. Beta amyloid
Vascular sinusoids lined by endothelial cells
The image shows an axial slice from a T2-weighted MRI and reveals a cavernous malformation, which typically includes a hypointense rim. Histopathological features of cavernous malformations include sinusoid vessels with a single layer of endothelium. These characteristically do not have smooth muscle cells.
Vessels with smooth muscle elements are seen in arteriovenous malformations. Beta amyloid deposits are seen in cerebral amyloid angiopathy. Rosenthal fibers are eosinophilic inclusions that can be found in gliosis and pilocytic astrocytomas. Tau neurofibrillary tangles are seen in Alzheimer disease.
Ten years after returning from battle, a 45-year-old soldier presents with confusion and slurred speech. Shortly after presentation, he dies suddenly in his sleep. Autopsy specimen of the frontal cortex on staining for tau proteins is shown. Which of the following is the most likely diagnosis?
A. Alzheimer disease
B. Parkinson disease
C. Chronic traumatic encephalopathy
D. Creutzfeldt-Jakob disease
E. Diffuse axonal injury
Chronic traumatic encephalopathy
Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease that is within the family of tauopathies. Seen in patients who have history of repeated concussive injuries, including football players, wrestlers, and veterans, CTE symptoms include cognitive deficits, dementia, mood changes, and executive dysfunction. Histopathologically, other than tau deposits, there may also be evidence of gliosis and dystrophic axons. Microglia may also be seen. Cortical regions that tend to be affected in veterans include the frontal and temporal lobes. The image here shows perivascular tau labeling in cortex, which is a hallmark of CTE.
Creutzfeldt-Jakob disease is a prion disease that on pathology demonstrates sponge-like holes. The clinical vignette described would be less consistent with Alzheimer or Parkinson’s disease. Diffuse axonal injury would be characterized by microhemorrhages and axonal injury.
The pathology specimen shown was removed from the surface of the cerebellar hemisphere during evacuation of a posterior fossa hematoma. Which of the following is the most likely cause of this patient’s hemorrhage?
A. Arteriovenous malformation
B. Hypertension
C. Amyloid angiopathy
D. Cavernous angioma
E. Vasculitis
Arteriovenous malformation
Arteriovenous malformations (AVMs) are high-flow vascular malformations which allow direct connections between cerebral arteries and veins. They can cause significant morbidity and mortality from intracranial hemorrhage.
Macroscopically, AVMs are tangles of abnormally enlarged vessels which directly shunt blood from the arterial system to the venous system due to a lack of an intervening capillary bed. Histologically, these abnormal vessels resemble capillaries despite their diameter, which is multiple times larger than that of a capillary. The lack of a normal capillary bed causes abnormally high flow through these nidal vessels due to the subsequent lack of normal capillary bed resistance. Since blood vessels adapt to changes in flow through flow-induced vessel wall remodeling, this abnormally high flow often causes ectatic remodeling of the veins draining the AVM or of the arteries feeding it. In addition to causing enlargement of the vessel caliber, this may lead to formation of venous ectasias, intranidal aneurysms, or aneurysms of the feeding arteries. This is demonstrated in the above microscopic section.
Cerebral amyloid angiopathy is characterized by the accumulation of amyloid fibrils in the walls of small to medium-sized arterial blood vessels.
Hypertension produces degeneration of the intima media, breakage of the elastic lamina, and fragmentation of arterial smooth muscle. Lipohyalinosis, fibrinoid necrosis of the subendothelium, microaneurysms, and focal dilatations are seen in the arterioles.
Primary CNS vasculitis demonstrates transmural inflammation with vessel wall injury on pathologic examination.
Irregular venous-type channels lined by flat endothelium and surrounded by scant smooth muscle are seen in venous malformations/cavernous angiomas.
The lesion shown is most commonly initiated by which of the following?
A. Leukocyte recruitment and increased inflammation
B. Macrophage infiltration of fibroatheroma
C. Fibroatheroma formation with necrotic core
D. Arterial endothelial cell injury from lipid retention
E. Layers of smooth muscle cells causing intimal thickening
Arterial endothelial cell injury from lipid retention
The pathogenesis of atherosclerosis involves a complex series of events, similar to a chronic inflammatory process, with the formation of atherosclerotic plaque as the end result. Injury to the endothelial cell of the artery, resulting in endothelial cell dysfunction, is the first step in the process. Activated endothelial cells attract leukocytes and vascular smooth muscle cells which accumulate and proliferate in the arterial wall. These cellular components produce an excessive amount of connective tissue matrix. The ultimate end point is the formation of a mature fibrous plaque. Lipid retention, oxidation, and modification provokes chronic inflammation at susceptible sites in the walls of all major conduit arteries.
Atherosclerosis begins with fatty streak, an accumulation of lipid laden foam cells in the intimal layer of the artery. Lipid retention is the first step in the pathogenesis of atherosclerosis which is followed by chronic inflammation at susceptible sites in the walls of the major arteries lead to fatty streaks, which then progress to fibroatheromas which are fibrous in nature. Symptoms occur when advanced lesions are complicated by plaque rupture, hemorrhage into the plaque, emboli, or thrombosis. Main classical risk factors for atherosclerosis include dyslipoproteinemia, diabetes, cigarette smoking, hypertension, and genetic abnormalities.
The other answers represent subsequent steps in atherosclerosis.
A 67-year-old woman is evaluated because of back pain and point tenderness over the spinous processes at the thoracolumbar junction. Temperature is 38.0°C (100.5°F). T1-weighted MR images of the spine without and with contrast are shown. Based on the MR images and the photomicrographs (H & E stain) shown, which of the following is the most likely diagnosis?
A. Ewing sarcoma
B. Lymphoma
C. Osteosarcoma
D. Osteomyelitis
E. Metastasis
Osteomyelitis
The images are consistent with osteomyelitis. In the H&E images lymphocytes and plasma cells with bone necrosis and reactive new bone formation are seen as well as capillary proliferation and fibrosis. In metastatic disease, there would be epithelial cells in clumps or glands in a fibrous stroma of bone. Ewing sarcoma is made up of uniform small round cells that are 1 - 2 times the size of lymphocytes with round inconspicuous nuclei and finely stippled chromatin. Osteosarcomas are composed of sarcomatous tumor cells that produce malignant bone or osteoid. The tumor cells may have densely eosinophilic cytoplasm resembling osteoblasts but often are larger than normal osteoblasts and vary in size with nuclear atypia. Lymphoma pathology would show a diffuse infiltration by large lymphoid cells.
