Pathology Flashcards
What is this
ALS - degeneration of corticospinal tracts with sparing of other tracts
What is this
Friedrich’s ataxia: tract degeneration - Dorsal columns, spinocerebellar tracts, lateral corticospinal tracts and DRG
Most common hereditary ataxia
AR, Chromosome 9, Triplet repeat GAA, Frataxin
50% hypertrophic cardiomyopathy, severe scoliosis
What is this?
B12 or HIV
What is this?
Subacute combined degereration of the cord
What is this?
Tabes Dorsalis
Tabes dorsalis, also known as syphilitic myelopathy, is a slow degeneration (specifically, demyelination) of the neural tracts primarily in the dorsal columns (posterior columns) of the spinal cord (the portion closest to the back of the body) & dorsal roots.
Name
Confusion, 70, autopsy - diagnosis?
Alzheimers Disease
This is an amyloid plaque. Look at the big, swollen black neurities! Those are filled with amyloid protein aggregates.
- Amyloid plaques are accumulation of beta amyloid between neurons. And neurofibrillary tangles are intracellular aggregates of tau protein. These are often associated with swollen neurities.
- Neuofibillary tangles also in Picks, supranuclear palsy, etc
Proximal weakness and pain- diagnosis?
Polymyositis – infiltration inflammation with muscle fiber destruction (left, H&E; right, trichrome). (not rimmed vacuoles like IBM, not perifasicular inflammation like dermatomyositis)
Other histologic features include type II atrophy, fiber type grouping. Usually presents with proximal weakness and pain.
Polymyositis is an idiopathic inflammatory myopathy that typically occurs between the ages of 40 and 50.
Symptoms: Proximal weakness and pain
CK >10x normal
Treatment: Steroids +/- steroid sparing agent
Proximal weakness -dx?
Dermatomyositis – as opposed to polymyositis, the inflammation and atrophy are largely perifascicular in dermatomyositis.
Dermatomyositis, but not polymyositis, has been associated with a higher degree of malignancy.
Other features of DM are a heliotrope rash, shaw sign and Gottron papules.
A 55 year old female presents with muscle pain and proximal weakness of several weeks duration. Her muscle biopsy is shown. Which of the following is the most likely diagnosis?
- Dysferlinopathy
- Polymyositis
- Inclusion body myositis
- Dermatomyositis
The constellation of findings is most consistent with polymyositis.
60, proximal weakness, Dx?
Inclusion Body Myositis – the hallmark of IBM is “rimmed vacuoles”, or vacuolations in the muscle fibers lined with an eosinophilic rim. Less inflammatory infiltrate.
Idiopathic inflammatory myopathy
Onset: >50 yo
Symptoms: Quadricep and deep finger flexor weakness. May be asymmetric.
CK normal to 10x normal. No treatment available.
Other conditions may give rise to rimmed vacuoles, such as chloroquine toxicity.
What is this?
Polymyositis
What do target fibers suggest in a muscle biopsy?
- Acute demyelination
- Target fibers appear as a centrally located dark staining patches on gomori’s modified trichrome and are best demonstrated by NADH-TR staining. There is a pale core with no NADH=TR activity surrounded by a dark ring and rimmed by a more normal staining peripheral zone.
- Histochemical and ultrastructural observations suggest that they are secondary to a disturbed tropic influence of the nervous system such as denervation
What is the pathological finding in muscle fibers associated with hypokalemic periodic paralysis?
•Vacuolar Dilatation of Sarcoplasmic reticulum is found in muscle biopsy of patients with hypokalemic periodic paralysi
Weak child, thin thighs, preserved calves
Duchenne Muscular Dystrophy – on the left is an H&E and the right a trichrome of Duchenne muscular dystrophy.
Rounded muscle fibers, variable fiber size, increased connective tissue, and fat.
The disease is caused by mutations in the gene for dystrophin (X-linked) which results in the absence of dystrophin form the muscle fiber surface.
What is this?
Discussion:
Myotonic dystrophy (MD) is characterized pathologically by predominance of small type I fibers and increased internal nuclei. Type I MD tends to display more numerous ring fibers and targetoid fibers than Type II MD.
type I
Name
Which glycogen storage disease affects only skeletal muscle?
Symptoms in glycogen storage diseases depend on the tissue distribution of the missing enzyme. McArdle disease, which is due to myophosphorylase deficiency, affects only skeletal muscle. Most of the other glycogen storage disease, including von Gierke disease, liver phosphorylase kinase deficiency, Forbes disease, and Pompe disease, also affect the liver.
Weakness, difficulty relaxing hand
Myotonic Dystrophy – on the left shows multiple internal nuclei characteristic of myotonic dystrophy.
This disease features more internal nuclei than any other muscle disorder.
The right longitudinal section shows that the interal nuclei within the muscle fibers also tend to line up. Note the increase in connective tissue.
Myotonic dystrophy results from a triplet repeat expansion of the myotonin gene on chromosome 19; more severe anticipation occurs with maternal inheritance
What is this
- Vasculitis:
- Discussion:
- The muscle biopsy specimen shows a necrotizing vasculitis with fibrinoid necrosis of the vessel walls, not amyloid angiopathy.
Vasculitis may be seen in amphetamine-induced vasculitis, polyarteritis nodosa, rheumatoid vasculitis, and Wegener granulomatosis, but not in polymyalgia rheumatica which is associated with temporal arteritis and usually type II fiber atrophy in the muscle biopsy, not vasculitis. Takayasu arteritis affects large blood vessels such as aortic arch, not small intramuscular vessels.
A 45 year old male presents with proximal muscle weakness that developed over the last year. His EMG shows a non-irritative proximal predominant myopathy. Muscle biopsy is shown. Use of which of the following drugs could be the cause of his symptoms?
- Statin
- Colchicine
- Prednisone
- Cocaine
Prednisolone
What is this?
Trichinosis – pictured is a cyst containing the larvae of Trichinella spiralis within muscle. Infection is initiated via ingestion of living larvae in raw or undercooked meat (usually pork) and results in eosinophilc fever and myalgias.
Myoclonus, seizures and blindness - diagnosis?
Lafora body disease
Autosomal recessive
Intractable progressive myoclonic and generalized seizures, dementia, and cortical blindness
Age: 11-18 yo at onset; Total disability in 5-8 years
Dx: Biopsy of skin, liver, muscle or brain with pathognomonic polyglucosan inclusions
Tx: Limited to treatment of seizures
Progressive confusion- autopsy - diagnosis?
•CJD
•
Spongiform degeneration is characteristic of Creutzfeldt-Jacob disease. Most cases are sporadic and occur in patients between 50 and 70 years of age. Iatrogenic transmission can occur but is rare. Startle myoclonus is commonly seen. Although patients may have elevated protein 14-3-3 levels in CSF, this is a non-specific finding which may be seen in other neurologic disorders
CJD is caused by protein particles known as prions they are innocuous proteins but become pathological when transformed into their beta sheet rich isoforms
Headache - diagnosis?
Giant cell arteritis
Sections demonstrate inflammation with giant cells centered on the internal elastic lamina of the temporal artery, characteristic of giant cell arteritis. Although primary angiitis of the CNS may have overlapping histologic features, it affects primarily leptomeningeal blood vessels and presents clinically with multifocal infarcts rather than headache or jaw claudication. Polyarteritis nodosa is characterized histologically by fibrinoid necrosis, and vessels in Moyamoya syndrome have fibrointimal proliferation. Amyloid angiopathy is characterized by Congo red-positive deposits within vessel walls
What is the histopathological finding of Moya Moya?
•Intimal Fibroplasia
•
- Moya Moya is characterised by intimal thickening in the walls of the terminal portions of the internal carotid vessels bilaterally
- Proliferating intima may contain lipid deposits.
•
Confusion - diagnosis?
Lewy body disease (large number)
Multiple systems atrophy (within glia), Parkinsons disease dementia or LBD
Intraventricular hemorrhage in the preterm infant vs term infant usually originates from which of the following structures?
- Germinal matrix (preterm infant)
- Choriod plexus is the source of intraventricular hemorrhage in the term infant
Confusion - diagnosis?
- These are senile plaques
- Dx Alzheimer’s Dementia
- Consist of – amyloid deposits surrounded by numerous astrocytic processes, neuron terminals, and swollen neurites.
- Tau protein is the main component of neurofibrillary tangles, but is not seen in senile plaques
Encephalitis then death - diagnosis?
The characteristic inclusion body of rabies (Negri body) is classically seen in large pyramidal neurons of the hippocampus and is located in the cytoplasm.
Bats, raccoons, skunks and foxes
Highest case fatality rate of any infectious disease (30-70,000 deaths/yr worldwide) - Encephalitic: hydrophobia, aerophobia, and hyperactivity
Paraylitic: Quadriparesis with sphincter involvement, may mimic GBS (but persistent fever and normal sensation except at inoculation site)
Confusion - diagnosis?
Hirano bodies are nonspecific, highly eosinophilic inclusions, located primarily in the cells of the subiculum and the CA1 region of the hippocampus.
Large numbers, suggest Alzheimer’s
Diagnosis?
Pick bodies - on a tau stain
40 progressive dementia, abnormal limb movements
Huntington’s disease – atrophy of the caudate nucleus bilaterally suggestive of HD
Triplet repeat of CAG , AD
Which chromosome???
- 4
HIV
•Human immunodeficiency virus (HIV) related cognitive change is frequently accompanied by neurologic dysfunction sometime during the course of the infection. This may be from opportunistic infections and/or primary involvement of white matter in the brain by HIV resulting in a subcortical dementia-like picture. Macrophages and multinucleate giant cells infected with the virus are seen in perivascular spaces in white matter.
- Measles
- Discussion:Subacute sclerosing panencephalitis (SSPE) is a rare and chronic form of progressive brain inflammation caused by a persistent infection with measles virus (which can be a result of a mutation of the virus itself). The condition primarily affects children and young adults.
- SSPE is caused by defective measles virus replication secondary to natural measles virus infection before the age of two. Having become rare, it may increase again with the recent decrease in vaccination rates. Intranuclear eosinophilic inclusions and demyelination are seen histologically. Pre-morten diagnosis can be made by serum or CSF virus-specific IgG.
- Gross pathology of the brain in SSPE discloses gliotic (hard brain)
- Intracellular (type A) and intracytoplasmic neuronal and glial inclusion are usually found on microscopic examination
- Adult onset leukoencephalopathy with neuraxoanl spheroids
Discussion:
Adult-onset leukoencephalopathy with neuroaxonal spheroids is a rare adult-onset leukodystrophy, often misdiagnosed as MS or small vessel disease. Symptoms typically develop starting in the early 40s. He may have a mutation in the CSF-1R gene. Although autosomal dominant there may be no family history of the disease. Symptoms are variable and can include dementia, psychiatric problems, parkinsonism, seizures, and other neurological deficits. The spheroids are the histologic hallmark.
62, cortex, rapidly progressive dementia and hallucinations, seizures, jerks. Dx?
CJD:
CJD: spongiform (multiple lacunae causing sponge like appearance) = prion disease
What pathologic abnormality correlates with severity of cognitive loss in HIV dementia? What CSF finding correlates with dementia severity? What cells does the AIDS virus infect and replicate in?
- Neuronal dendritic los
- In HIV dementia – the pathologic feature that best correlates with severity of dementia is the grade of neuronal dentritic loss.
- Number of multinucleated giant cells has no correlation with severity of dementia
- On CSF levels of p24 antigen, beta 2 microglobulin, TNF alpha and antimyelin basic protein are shown to correlate with severity of HIV dementia. CSF tryptophan, serotonin metabolites and quinolinic acid level have recently been considered as marker of dementia severity in HIV
- HIV virus infects and replicates in microglial cels – actively synthesize viral RNA and produce progeny virions. HIV can also infect oligodendrocytes and astrocytes but doesn’t replicate in these cells
HIV, low grade fever, diagnosis?
Cerebral toxoplasmosis is the most common opportunistic CNS infection in AIDS patients and occurs in 15-50% of cases
Commonly a focal mass lesion involving the basal ganglia.
characterized by microglial nodules with associated encysted bradyzoites (obligate intracellular parasite in cellular stage).
Picture on right is RITE 2014
Pyrimethamine is used to treat toxoplasmosis.
It should be distinguished from opportunistic fungal infections, which often produce granulomatous inflammation, and from CNS lymphomas, which are characterized by large lymphoid cells which typically surround blood vessels.
What is it?
Coccidiodes- endospore
Coccidioidomycosis meningitis is endemic to the southwestern United States and northwestern Mexico.
flu-like syndrome or a limited pulmonary infection.
Meningitis most typically presents with a subacute unremitting headache.
Definitive diagnosis is made by a positive CSF fungal culture but most relied upon diagnostic study is a positive CSF cocci IgG antibody in CSG, which is highly specific.
Mature fungi in tissue are endospores, such as the one pictured, which are round and have a refractile wall.
What is it?
Aspergillosis produces gray irregular necrotic masses.
The gross photograph showed hemorrhages characteristic of vasoinvasive fungi such as Aspergillus. The photomicrograph shows a silver stain, identifying multiple septate fungi with invasion of a blood vessel in the brain, characteristic of Aspergillus species. The other organisms listed would not have this typical microscopic appearance or strong predilection for angioinvasive behavior.
The brain is second only to the lung as a site of visceral involvement, and frequently manifests as hemorrhagic infarctions.
•Alpha synuclein
•
Dementia with Lewy bodies is an example of a so-called synucleinopathy and is considered to be the second most common neurodegenerative dementia syndrome in the elderly. It is characterized clinically by fluctuating cognitive function, visual hallucinations, and mild parkinsonism. Histologically, the characteristic feature is the presence of both cortical and brainstem Lewy bodies that show immunoreactivity for alpha synuclein.
- Alzheimer’s
- Discussion:
- Neuritic plaques consist of an amyloid core and dystrophic neurites, with reactive astrocytes and microglia. They are a classic finding in Alzheimer’s disease; in the commonly used CERAD grading system, neuritic plaque counts are used as histologic criteria for making the diagnosis of Alzheimer’s disease. They are not characteristic of the other diseases listed.
Which chromosome codes for the prion protein?
- Chromosome 20
- The prion protein (PrnP) gene encodes the prion protein
- Implicated in several transmissible neurodegenerative spongiform encephalopathies
- Approximatedly 15% of cases are inherited and associated with coding mutations in the PrnP gene
Which karyotype is associated with increased meningiomas
Monosomy 22
What is this?
Desmoplastic infantile gangliogliomas
Large solid and cystic tumours with dense collagen and spindled fascicular cells
Mass from the clivus, on MRI it was hypointense on T1 and hyperintense on T2 - diagnosis?
- Chordoma:
- Rare tumour that arises from the notochord. Commonly occur at the sacrococcygeal region or at the spheno-occipital region (mostly at the clivus)
- Microscopically chordomas are composed of uniform cells with small round/oval eccentric nuclei with variably sized vacuoles located in the cell cytoplasm of the so called physalipherous cells (bubble bearing cells).
•
- Subependymal giant cell astrocytoma
- Discussion:
- Subependymal giant cell astrocytomas (SEGAs) occur almost exclusively in patients with tuberous sclerosis, which is due to the mutation or loss of a tumor suppressor gene on either chromosome 9q34 (TSC1) or chromosome 16p (TSC2). Other common manifestations of this autosomal dominant syndrome include cortical tubers, subependymal glial nodules, cutaneous angiofibromas, cardiac rhabdomyomas, pulmonary lymphangioleiomyomatosis, and renal angiomyolipomas.
•
•
Conus medullaris of a 50 year old - diagnosis?
•Myxopapillary ependymoma – subtype of ependymoma that occurs almost exclusively in the conus medullaris / cauda equina region and is thought to arise from the ependymal cells of the filum terminale. Histologically, cuboidal tumor cells arranged around vascularized stromal cors. Microcystic areas can also be found
•
What tumour is this?
The photomicrographs show classic perivascular pseudorosettes characteristic of ependymoma.
What is this
Ganglioma
The image shows a typical ganglioglioma with numerous dysmorphic ganglion cells, including binucleated forms. These tumors most frequently arise in children within the temporal lobes (often with cyst with mural nodule configuration on neuroimaging studies), and often produce seizures. The abnormal ganglion cells stain with neuronal markers, not GFAP (though the glial component would be positive for this marker). Dysmorphic ganglion cells are generally not a feature of pilocytic astrocytoma, nor are they seen in the other tumors listed. Glioblastoma and medulloblastoma are both high grade malignant neoplasms, the former glial and the later primitive embryonal (small blue cell tumor). Central neurocytoma is “neurocytic” by morphology and may closely resemble oligodendroglioma.
Langerhan’s histiocytosis
Discussion:
Langerhans cell histiocytoses may be isolated (so-called eosinophilic granuloma) or multifocal. Bone lesions in the cranium are
lytic with beveled edges. Typically sellar involvement includes a thickened enhancing infundibulum and absent posterior pituitary bright spot, which was not seen in this patient. A mixed inflammatory infiltrate of macrophages, lymphocytes, plasma cells, eosinophils and Langerhans cells is seen. Langerhans cells have a large, convoluted nucleus and are CD1a immunopositive.
28 - headache and diplopia - suprastella mass
- Craniopharyngioma – an epithelial-squamous cystic tumour arising from remnants of the craniopharyngeal duct or Rathke cleft
- Basaloid epithelium and keratin nests are characteristic
Resected ring enhancing tumour from 50 year old– what is it?
Glioblastoma multiforme – astrocytic neoplasm. Necrosis with pseudopalisading and microvascular proliferation. High cellularity and marked nuclear atypia
55, headache and personality change - diagnosis?
Glioblastoma multiforme.
Less than 3 months symptoms
Frontal , variegated appareance, hemorrhage and necrosis within it. Some mass effect
Palisading or pseudopalisading – can be seen histologically
what is this?
Myxopapillary ependymoma
Most Ependymomas (85%) are benign myxopapillary ependymomas - slow growing, low - grade tumors.
Histopathology is characterized by well differentiated cuboidal / elongaged cells without atypical / low mitotic activity arranged around papillations having a myxoid connective tissue
Eosinophilic granular bodies are found in tissue preparations of which conditions?
- Low grade gliomas
- Brightly eosinophilic round bodies in hematoxylin and eosin-prepared sections.
- Immunocytochemically some EGB are positive for antibodies against ubiquitin, Bcrystallin and glial fibrillary acidic protein.
- EGB are membrane bound round bodies of different diameters
- Generally identified in low grade gliomas
This is taken from an intraventricular tumour from a 19 year old. What is the dx.
Ependymoma. Ependymomas are composed of small cells with regular, round nuclei. Tumor cells typically form perivascular “pseudorosettes” in which cells are arranged radially around vessels with a clear region consisting of thin ependymal processes directed towards the vessel wall.
- Headaches and bitemporal hemianopia. Surgically resected tumor which is cystic with the cystic lesions containing yellow fluid and calcified areas- diagnosis?
- Craniopharyngioma – benign tumor commonly located in the suprasellar region
- Calcifications and uni-multiloculated cysts containing yellow fluid
30 yr old right temporal mass
Oligodendryoma
Fried egg appearance is characteristic – pericellular halo is a fixation artifact – but very helpful to identify oligodendrocytes.
What is this tumour?
low grade oligodendroglioma; the calcifications and “fried-egg cells” are characteristic of oligodendroglioma.
present in patients in their 30s or 40s.
Due to the high tendency of these tumors to invade the overlying cortex, seizures (often of one to five years duration) are one of the most frequent clinical presentations.
Pineal tumour taken from a 19 yr old. What is it?
Germoma. Mostly located in the pineal region or suprasellar region. Composed of neoplastic cells that have abundant clear cytoplasm (rich in glycogen) and are arranged in nests. Other cell populations generally found in germinomas are composed of small reactive T lymphocytes.
Discussion:
The microscopic findings together with immunohistochemistry is characteristic of germinoma. None of the listed alternate answers would show positivity for PLAP and CD117. Pituicytoma and granular cell tumor would both be expected to be positive for S100, the former often with positivity for GFAP also. Craniopharyngiomas should show cytokeratin staining, and look microscopically quite different from a germinoma. Pituitary adenoma may be negative for all pituitary hormone stains, but most
typically will at least show some positivity for chromogranin.
What is this tumour?
Pilocytic astrocytoma
Rosenthal fibers, slender “hairlike” cells, eosinophilic granular bodies
What is this tumour?
Medulloblastoma - Sheets of blue cells, some forming Homer-Wright rosettes, likes midline cerebellum vermis and spreads outward
What is this tumour?
Schwannoma - Stacked nuclei alternating with fibrillar zones, called Verocay bodies
The photo shows a well-demarcated mass at the cerebellopontine angle. The most common tumor at this site is a schwannoma of the vestibular branch of the 8th cranial nerve.
What is this tumour?
Meningioma -Whorled pattern, Calcified whorls are Psammoma bodies
Similar picture on RITE 2015
What is this?
Colloid Cyst –
Developmental malformation
Most in anterior third ventricle
Can block foramen of monroe – “ball valve”
Positional headaches, drop attacks and papilledema, sudden death
Treated surgically
RITE 2014 differential: Hypothalamic hamartoma would be within the hypothalamus, not the third ventricle. Lipomas classically are seen near the corpus callosum. Subependymomas only occur rarely in the third ventricle.
What is specific for Dx variant CJD? RITE 2017
- Tonsil biopsy is a highly sensitive and specific method to diagnose variant CJD;
- follicular dendritic cells with be PrPSc- immunoreactive in a positive case.
- Unlike sporadic CJD which presents as a “rapidly progressive dementia”, cerebellar dysfunction is typical of vCJD. The illness is fairly short in duration (year to 16 months), and it characterized histologically by florid plaques (multicentric plaques are typical of GSS).
- vCJD is not thought to be heritable.
•
What is this?
This muscle biopsy shows a predominance of tiny rounded atrophic fibers with few hypertrophic fibers, typical of SMA.
What disease is this?
(a) Coronal slice of the brain. Wilson’s disease shows bilaterally symmetrical putaminal (P) softening (arrows) extending laterally up to the external capsule
(a) Luxol Fast Blue shows relative preservation of internal capsule and pale and softened neuropil in the putamen (P, arrow).
(a) Softened area in the putamen has bizarre astrocytes with vesicular lobulated nuclei (arrow) with inset showing Alzheimer type 2 astrocytes in the neuropil (arrow). H&E
(a) Large opalski cell characteristic of Wilson’s disease has irregular eosinophilic cytoplasm and small peripherally placed pyknotic nucleus. H&E
What is this?
- Neurofibromatosis Type II
- Bilateral cerebello-pontine angle mass lesions.
- Most common bilateral CP mass lesions are bilateral acoustic neuromas.
- Neurofibromatosis Type II is a condition that frequently presents with bilateral acoustic neuromas – transmitted via autosomal dominant inheritance (gene encodes for Merlin, chromosome 22).
- 2 acoustic neruomas, age 20s, chromosome 22, NF type 2
•
What is this?
Formation of onion bulbs results from repeated episodes of demyelination and remyelination.
Onion bulbs are especially conspicuous in hypertrophic Charcot-Marie-Tooth disease and Dejerine-Sottas disease (hereditary motor and sensory polyneuropathy type 3.
In addition, approximately one half of the cases of chronic inflammatory demyelinative polyneuropathy show substantial numbers of onion bulbs.
CMT, type 1A, is associated with a duplication in the PMP22 gene.
28-year-old woman with acute onset of confusion and disorientation, presenting with tonic-clonic seizures. On admission she is afebrile with no evidence of papilledema.
Negative tox screening
CT scan showed a 3 cm recent hemorrhage in left temporal lobe
CSF show few mononuclear cells with normal glucose – dx?
HSV
75-year-old lady with forgetfulness, difficulties with ADL such as keeping her checkbook, paying bills etc, with multiple TIA episodes.
Brain autopsy: Brain weight 1050grams with diffuse atrophy involving frontal temporal and parietal lobes
Alzheimer’s Disease
A 64 year old woman presents during the first week of winter with AMS, nausea, vomiting, malaise and nonspecific dizziness.
She had an episode at home, prior to presentation, that may have been consistent with seizure versus syncope.
She had a cherry-red appearance to her lips.
Bilateral necrosis of the globus pallidus is often due to carbon monoxide intoxication. However, contrary to popular opinion, CO poisoning does NOT just affect the globu pallidus. It has widespread effects.
CO affinity for hemoglobin is 200x stronger than that for oxygen. Pulse ox is normal as it does not differentiate carboxyhemaglobin and oxyhemoglobin. Diagnosis is made clinically and with a blood gas with elevated carboxyhemoglobin. Levels are typically 3% in nonsmokers but can be as high as 15% in smokers.
73 yo alcoholic found stumbling and confused in his room. He was unkempt, disoriented, had right cranial nerve VI palsy and wide based gait.
A coronal section of the brain at autopsy shows mammillary bodies that are congested and discolored, which is a characteristic finding in thiamine deficiency manifesting as Wernicke’s encephalopathy.
Cerebellar vermal atrophy from alcoholic cerebellar degeneration
Vitamin B1 deficiency
Clinical triad: confusion, eye movement abnormalities, and gait ataxia
Nystagmus > lateral rectus palsy > conjugate gaze palsy
Demyelination of medial thalamus and atrophy/hemorrhage of mamillary bodies is common
MRI: symmetric hyperintensities around third ventricle, aqueduct and fourth ventricle
Txt: IV thiamine
Diagnosis?
Wernicke’s encephalopathy
Discussion:
Wernicke’s encephalopathy is clinically characterized by the triad of eye abnormalities, ataxia and mental status symptoms.
Classically seen in alcoholics, it is a thiamine deficiency which can be seen in many malnourished states such as after gastric
bypass. It is underdiagnosed in HIV patients. Acute lesions can be detected by MRI. Lesions affect the grey matter around the
third and fourth ventricle and aqueduct, the colliculi, and mammillary bodies. Histopathology consists of capillary proliferation, congestion, and pericapillary hemorrhages acutely, with neuron loss and gliosis chronically.
- Alcoholic. Car accident. What is shown
Marchiafava Bignami Disease
This myelin stain makes the myelinated white matter appear black. There is demyelination demonstrated in the corpus callosum which is consistent with Marchiafava bignami disease
disease of alcoholism, characterized by corpus callosum demyelination and necrosis and subsequent atroph
- Died high speed MCA. Brain stem with b-amyloid stain. What does it show?
Diffuse axonal injury – rotational forces produce focal alterations of the axoplasmic membrane, results in impairment of axoplasmic transport and axoplasmic swelling and formation of so called “axonal spheroids”
What is this?
Meningioma
The photomicrograph depicts a meningioma with typical whorled architecture. Multiplicity of meningiomas should prompt workup for neurofibromatosis Type 2. It’s likely the current patient has a unilateral vestibular schwannoma as well, given the history of hearing loss. None of the other listed heritable syndromes exhibit meningioma multiplicity
What is this?
Bilateral, nearly symmetric, parasagittal, cortical and basal ganglia venous infarctions due to thrombosis of the superior sagittal sinus and deep cerebral veins.
Disease pathology?
Demyelination
Discussion:
Multiple periventricular areas of demyelination are characteristically seen in multiple sclerosis. These plaques have a grey hue because of the loss of myelin that normally confers a glistening white appearance to the white matter.
What is shown?
1.Chronic infarct
●
Discussion:
The lesion shown in this image is a remote infarct. The preservation of the outer layer of the cortex would argue against a remote contusion. An old hematoma cavity would be smoother, and would not necessarily be confined to the vascular distribution territory of a branch of the middle cerebral artery as this lesion is. Both an abscess and metastatic carcinoma would be accompanied by brain swelling rather than shrinkage; note the lack of mass effect on the ventricular system.
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25, unconscious, cherry red skin colour, high CO. What will MRI show day 3
- Bilateral globus pallidus lesions – common in hypoxic injury including carbon monoxide poisoning.
- Medium spiny neurons in the basal ganglia fire rapidly and have a higher O2 requirement and thus more susceptible to hypoxic injury
•
Stem: bilateral rigidity and alien hand. Pathology?
- CBD: TAU positive astrocytic plaques.
- On autopsy – Ballooned neurons and glial abnromalities (astrocytic plaques) with tau immunoreactivity are seen.
•
- Cheat remembering – if the pathology is above the midbrain it is usually a tau opathy – progressive supranuclear palsy, alzheimers, pick, FTD, corticobasilar
- If it is below the midbrain it is ususally alpha-synucleinopathy (parkinson’s MSA) Dementia with LB is a dementia however affecting the supratentorial regions caused by an aloha synucleinopathy
Which parkinson’s plus is this?
MSA: Glial intracytoplasmic inclusions (particularly in oligodendroglia) are seen in multiple system atrophy (seen .
The midsagittal section of the brain of a patient with MSA-P (A) is unremarkable, except for mild dilation of the fourth ventricle. Inset in (A) shows transverse section of the midbrain with marked loss of neuromelanin pigment in the ventrolateral region (arrow). Coronal sections of the cerebral hemisphere (B) shows marked atrophy and discoloration in the lateral putamen (arrow).
The clinical history and gross brain features are typical of multiple system atrophy (MSA). This disorder is characterized by neuronal loss, gliosis, and glial cytoplasmic inclusions (containing alpha-synuclein). Neuritic plaques are found in Alzheimer Disease, globose neurofibrillary tangles are seen in PSP, Lewy bodies in Parkinson Disease, and tufted astrocytes are also a feature of PSP.
Which parkinson’s plus is this?
Progressive supranuclear palsy
The clinical constellation of hypokinesis, gait instability and vertical gaze palsy without tremor coupled with the gross neuropathological findings of midbrain atrophy are strongly suggestive of progressive supranuclear palsy.
Globose neurofibrillary tangles are seen in the residual neurons of the brainstem and basal ganglia.
Weakness, T2 lesions, this pathology - what is it?
MS lesion
The photomicrograph is showing sheets of macrophages, typical of a demyelinating lesion. Given the presentation of this patient with a solitary mass lesion, the diagnosis is consistent with Tumefactive demyelinating lesion, thought to represent a form of multiple sclerosis. The neuroimaging findings are an important clue, as an incomplete ring is most typically seen with demyelinative lesions whereas a complete ring may be seen with glioblastoma or brain absess, among others. Although the cells here may superficially resemble oligodendroglioma or renal cell carcinoma, these macrophages in fact have foamy cytoplasm containing phagocytosed myelin debris. No neoplastic cells are present, nor are there neutrophils typical of brain abscess.
RITE 2017: what is found on most temporal lobe biopsies for epilepsy?
•While balloon, giant, immature and individual heterotopic neurons can all been seen in temporal lobectomy specimens for seizures, the most common structural abnormality in most series is hippocampal sclerosis.
RITE 2017
What disease is characterised by accumulation of sphingolipids in the PNS?
- Metachromatic Leukodystrophy, Fabry’s and Krabbe
- Deficient metabolism of sphingolipids and their accumulation in lysosomes leads to development of Krabbe disease and metachromatic leukodystrophy
63 – headaches (not migraines), confusion, MRI – multiple infarcts of varying ages – Diagnosis?
- Primary CNS angiitis
- Primary Angiitis of the CNS affects middle aged men
- Presents with headache and encephalopathy, multifocal strokes
- Often mild anaemia, elevated WCC, elevated ESR
- CSF – elevated protein, and lymphocytisis
- Angiogram abnormal in 50-80% (with beading) of the small intracranial arteries
A young child presents with new onset seizures. Imaging shows lesions with an enhancing mural nodule and a cyst. Pathology is shown. What is the lesion?
- Pilocytic astrocytoma
- Medulloblastoma
- Neurocytoma
- Ganglioglioma
Ganglioglioma
The image shows a typical ganglioglioma with numerous dysmorphic ganglion cells, including binucleated forms. These tumors most frequently arise in children within the temporal lobes (often with cyst with mural nodule configuration on neuroimaging studies), and often produce seizures. The abnormal ganglion cells stain with neuronal markers, not GFAP (though the glial component would be positive for this marker). Dysmorphic ganglion cells are generally not a feature of pilocytic astrocytoma, nor are they seen in the other tumors listed. Glioblastoma and medulloblastoma are both high grade malignant neoplasms, the
former glial and the later primitive embryonal (small blue cell tumor). Central neurocytoma is “neurocytic” by morphology and may closely resemble oligodendroglioma
What is the common pathological finding of Rasmussen’s Encephalopathy?
- Rasmussen’s encephalitis is a chronic inflammatory disease affecting only one hemisphere of the brain
- Occurs in children less than 10
- Frequent seizures, loss of motor skills, encephalitis, hemiparesis
- Hemispherectomy is the standard treatment
- CA4 and CA3 sector neurons of the hippocampus seem to be particularly affected
- holoprosencephaly. Discussion:
The findings of cyclopia with proboscis-like structure would be seen to accompany holoprosencephaly (“face predicts the
severity of brain abnormalities”)
Hydranencephaly is caused by loss of blood flow through what?
- Internal carotid arteries
- Hydranencephaly is near total or total absence of the cerebral cortex and basal ganglia
- Thalami, pons, cerebral peduncles and cerebellum are usually present
A 35 year old female with medically intractable epilepsy has the following imaging findings. Her lesions depicted on MRI is resected with resulting reduction in her seizure frequency. Her histology from the resection cavity is shown . What is her diagnosis?
- Focal cortical sclerosis
- Subependymal giant cell astrocytoma
- Focal cortical dysplasia type 1
- Focal cortical dysplasia type 2b
ANSWER: 2B: Balloned neurons characteristic of focal cortical dysplasia type 2b
Aberrant microcolumns (Type IA),
loss of individual cortical layers (Type IB),
or both (Type IC) represent cortical architecture abnormalities of FCD Type 1.
Dysmorphic neurons are found in FCD Type IIA and B,
however balloon cells are only found in FCD Type IIB.
What is the prognosis of desmoplastic infantile ganglioglioma?
- Desmoplastic infantile ganglioglioma and desmoplastic infantile astrocytoma are rare neoplasms usually affecting children less than three years of age.
- Massive, partially cystic, invariably occur supratentorial location
- Multiple lobes
- Abundant and dense desmoplasia
- Prognosis following surgical ressection of DIG and DIA is favourable.
What is this?
Chiari II
Discussion:
Elongation of the cerebellar vermis and medulla, with kinking of the upper cervical cord and beaking of the quadrigeminal plate are components of the Chiari type II (Arnold-Chiari) malformation.
What is this?
1.Mitochondrial myopathy with ragged red fibers
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Discussion:
Ragged red fibers are typically seen in the setting of mitochondrial myopathies. Other findings in this setting include increased subsarcolemmal staining on succinate dehydrogenase (SDH) stains (ragged blue fibers) and cytochrome oxidase-negative
myofibers.
what does electron micrograph show in CADASIL
•Electron micrograph shows numerous accumulations of granular osmiophilic material
The clinical, histologic, and ultrastructural findings presented are diagnostic of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). The electron micrograph shows numerous accumulations of granular osmiophilic material (GOM) in the basal lamina of a small cutaneous arteriole. Similar findings would be present in CNS arteries. This CNS vascular disease is associated with mutations of the NOTCH3 gene.
- Falling. Increased paraspinal muscle tone, stiff and rigid legs. Normal strength, lordotic stance. What Antibody?
- Anti GAD antibody
- STIFF PERSON SYNDROME
- 40
- Stiff gait, paraspinal muscle stiffness
- Lung mass with brain lesion. Biopsy of lung mass shows large anaplastic lymphocytes that infiltrate the walls of the blood vessels and surrounding areas, with intravascular occlusions. Dx? What order of most common cancer metastases to brain?
- Intravascular lymphoma
- Systemic disease with prominent pulmonary, dermal and lymph node changes and CNS involvement
- Accumulation of large anaplastic lymphocytes that infiltrate the walls of blood vessels and surrounding areas, with occasional intravascular occlusion.
- Lung > Breast > melanoma > renal
- 4 year old boy evaluated for blindness, seizures, myoclonus,
- Turkish decent
- No motor or sensory problems
- Electroretinogram shows very low amplitude response
- Diagnosis?
- Neuronal ceroid lipofuscinosis
- The lipofuscinosis are common neurdegenerative diseases of infancy and childhood.
- Four types: Santavuori – Haltia type (infancy) Jansky Bielschowsky (early childhood) Vogt-spielmeyer (juvenile) Kufs (adult). Seizures, myoclonic jerks, visual loss,
Atypical teratoid/rhabdoid tumours are associated with mutations on which chromosome?
- Chromosome 22
- Atypical teratoid/rhabdoid tumour are associated with mutations (most commonly deletions) of the INI1 gene on chromosome 22
- Smoker with hypertension
Progressive headache over 2 days then dies
If she had come in for treatment what could have been done?
Cerebral venous thrombosis – thrombosed cortical veins with superficial hemorrhage – treat with volume expansion and anticoagulation (unfractionated heparin initially)
Anterior commissure
Discussion:
The structure indicated by the arrow is the anterior commissure, which connects the temporal lobes and also contains fibers from
the amygdala and the olfactory system.
What is this structure?
Anterior commisure in the spinal cord
What is this structure
The tract indicated by the arrow is the anterior corticospinal tract which carries fibers arising from the ipsilateral precentral gyrus. It is the uncrossed component of the pyramidal tract
- Migraines. FHx dementia and sudden death. MRI – subacute infarcts. Dx?
- CADASIL
- NOTCH3 gene mutation
- Migraines, CVA disease, Dementia
- Diffuse white matter lesions and subcortical infarcts
- Skin biopsy: electron dense granules in the media of arterioles that can also be seen by electron microscopic evaluation of skin biopsies
Diagnosis?
Neurofibromatosis: Cauda equina segment with 2 large tumours. Common cauda equina tumours are meningiomas and ependymomas
82, died from ICH, parietal cortex + silver stain, cause of haemorrhage?
Cerebral amyloid angiopathy – it is secondary to the deposition of beta amyloid protein in the media and adventitia of cortical and leptomeningeal arteries.
What is it?
AVMs are the most likely vascular malformation in the CNS to have catastrophic consequences for patients. They are characterized by large abnormal arteries and thick-walled veins in brain. The arteries demonstrate fragmentation and reduplication of the elastic layer, while the thick-walled veins show little elastic. The intervening brain tissue is gliotic.
What is it?
1.Amyloid angiitis:
Discussion:
Amyloid related angiitis is most often associated with dementia and/or seizures unlike amyloid angiopathy which is associated with hemorrhages of various sizes. Both involve amyloid in small cortical and leptomeningeal arteries, with a female predominance. The inflammation (or lack thereof) affects the presentation.
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•Young – developmental delay and seizure.
Massive accumulation of Rosenthal fibers is typical of Alexander Disease, and this disorder has as its underlying genetic abnormality a gain of function mutation involving the GFAP gene.
The clinical, histologic, and ultrastructural findings presented are diagnostic of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). The electron micrograph shows numerous accumulations of granular
osmiophilic material (GOM) in the basal lamina of a small cutaneous arteriole. Similar findings would be present in CNS arteries. This CNS vascular disease is associated with mutations of the NOTCH3 gene.
What is this?
Dandy walker malformation
What structure is shown here
Substantia Nigra
Discussion:
The structure is the substantia nigra, which projects to and receives fibers predominantly from the caudate and putamen. Degeneration of this structure is seen in idiopathic Parkinson’s disease.
6mnths, failure to thrive. MRI – increased signal intensity that surrounds the aqueduct of sylvius and the tectum of the midbrain – symmetric, involves midbrain, caudate, putamen, globus pallidus, substantia nigra but spares mammillary bodies and red nuclei. Dies 48hrsDx?
- Leigh’s disease
- Subacute necrotizing encephalomyelopathy
- Brainstem
- Mitochondrial DNA mutation or deficiencies of pyruvate dehydrogenase
Zellweger syndrome – what do you see?
- Polymicrogryia and periventricular pseudocysts
- Zellweger syndrome is a peroxisomal disorder that affects not only the brain but also the liver and kidneys (cerebro – hepato-renal syndrome). The most common features are hepatomegaly, elevated serum levels or iron and copper, hypotonia, renal insufficiency and vision disturbance.
- Some affected infants may show prenatal growth failure
- Facial features: high forehead, underdeveloped eyebrow ridges, deformed ear lobes
- Cortical dyral patterns of polymicrogyria and polygria, impaired myelination and periventricular pseudocysts
ASPIRIN
Discussion:
This patient has non-arteritic anterior ischemic optic neuropathy (NAION) resulting in optic nerve head ischemia. This is usually due to vascular occlusive disease of the posterior ciliary arteries which supply the optic nerve. Embolism from cardiac or large artery sources underlie few if any cases of NAION. In contrast to retinal ischemia, NAION is not associated with carotid occlusive disease. The primary risk factors are hypertension and diabetes mellitus. Most patients awaken with painless monocular visual loss presumably because of nocturnal hypotension. Corticosteroids, hyperbaric oxygen, and anticoagulation are not beneficial for this condition. Abrupt lowering of blood pressure may aggravate the ischemia. No treatment has been shown to
improve clinical outcome in these patients but fortunately most will improve or stabilize over several weeks. Aspirin therapy is appropriate as it reduces the patient’s future risk of cardiovascular and cerebrovascular disease. Vasculitic anterior ischemic optic
35 neuropathy, a common presentation of giant cell arteritis, usually produces severe monocular or binocular visual loss. It often occurs in association with headache, systemic symptoms and elevated ESR.
Tuberous sclerosis
Discussion:
Tuberous sclerosis (TS) is characterized by skin lesions including depigmented macules (so called “ash leaf spots”), shagreen patches, periungual fibromas, and facial lesions termed adenoma sebaceum. Cardiac rhabdomyomas are seen prenatally and at birth but generally regress. About 50% of patients with TS are mentally retarded, but 50% are normal intellectually. Although the gene is transmitted as an autosomal dominant, over 25% represent new mutations. MRI should be done at diagnosis then periodically. Lesions at the foramen of Monro may progress but generally do so very slowly. Infantile spasms are quite common as a presenting feature of TS, and TS is said to be the most common single identifiable cause of symptomatic infantile spasms.
Polymicrogyria and congenital hydrocephalus
Hemorrhagic metastases in cerebellum (likely renal cell, melanoma, or breast CA)
Down Syndrome (box-shaped brain) with polymicrogyria
Colloid cyst
Immature brain with germinal matric hemorrhage
epidural haematoma
Arteriovenous malformation
Arteriovenous malformation - arteriolized veins
Post-traumatic contusions – petechial hemorrhages in bilateral fronto-orbital cortex
Old contusions - fronto-orbital
Trauma - gliding contusion from shear injury at grey white junction
Old pontine lacune
Meningitis
4th cranial nerve
The structure indicated by the arrow is the trochlear (fourth) nerve which completely decussates before it exits from the dorsal aspect of the brainstem. After it exists the brainstem, the trochlear nerve innervates the superior oblique muscle and results in depression and intorsion of the ipsilateral eye.
Hydrocephalus – can’t tell if it’s obstructive without seeing 4th ventricle in brainstem
Cortical tuber - in tuberous sclerosis
Cerebellar vermal atrophy from alcoholic cerebellar degeneration
Large ventricles secondary to cortical atrophy (“hydrocephalus ex vacuo”). In this case from Alzheimer disease
A periventricular MS plaque
Low grade infiltrative tumor, indistinct margins, cystic changes
Metastatic tumor at grey-white junction, well-demarcated
Meningioma
The potential for invasion of mesenchymal tissues, including the dura (and superior sagittal sinus), cranial bones, muscles and scalp, is an intrinsic property that is frequently seen to a greater or lesser extent in many ordinary (WHO grade I) meningiomas. Invasion of these mesenchymal tissues may complicate surgical resection but does not constitute a criterion for upgrading to atypical (WHO grade II) or anaplastic (WHO grade III) meningioma. Brain invasion, in contrast, is much less commonly seen and its presence in the absence of prior surgical procedures warrants a diagnosis of atypical (WHO grade II) meningioma in the new 2007 WHO classification. Highly vascular meningiomas are sometimes referred to as angiomatous and have no association with aggressive behavior. The older term “angioblastic meningioma” encompassed a heterogeneous group of vascular dural- based tumors that included angiomatous meningioma, hemangiopericytoma and hemangioblastoma; it is an imprecise and obsolete term that should be avoided. Four histologic subtypes merit upgrading based on their potential for early recurrence and/or aggressive clinical behavior: clear cell (WHO grade II), chordoid (WHO grade II), rhabdoid (WHO grade III), and papillary (WHO grade III). In contrast, the remaining nine WHO-recognized meningioma subtypes are classified as low grade (WHO grade I): meningothelial, fibrous, transitional, psammomatous, angiomatous, microcystic, secretory, lymphoplasmacyte- rich, and metaplastic.
The structure indicated by the arrow is the lateral geniculate body which may be recognized by its convex shape (some say it looks like Napoleon’s hat) and proximity to the thalamus. The tail of the caudate is lateral to the LGB. The amygdala and hippocampus would be in the mesial temporal lobe. The juxtarestiform body lies next to the inferior cerebellar peduncle in the medulla
Central pontine myelinolysis (CPM) has been most closely associated with the too-rapid correction of profound hyponatremia.
Pantothenate kinase-associated neurodegeneration (formerly known as Hallervorden-Spatz disease) is a progressive neurodegenerative disease with neuroaxonal dystrophy, rust-brown discoloration of globus pallidus and pars reticularis of substantia nigra due to accumulation of iron-containing pigment, and an onset usually before age 15 years. These changes are due to mutations in a novel pantothenate kinase gene, PANK2. The other choices would not show the characteristic gross pathology seen in the image
Bone fractures are associated with release of fatty bone marrow into the systemic circulation. Pulmonary circulation may be compromised, and emboli may travel to the brain leading to ball hemorrhages around small vessels. The symptoms described in this patient also fit best with fat embolism rather than diffuse axonal injury which would result in immediate loss of consciousness
Bridging veins – can be torn and cause subdural hematoma
Alobar holoprosencephaly
Acoustic shwannoma
Abscess in occipital lobe. Thick-wall.
Polymicrogyria
Transtentorial hernation compressing the midbrain. You can see Kernohan’s notch on the side.
RITE 2017A 75 year old male presents with acute loss of consciousness and quickly dies. Gross pathology is shown. What is the most likely cause of death?
- Duret hemorrhage
- AVM
- Amyloid angiopathy
- Hypertensive hemorrhage
HYPERTENSIVE HEMORRHAGE
Of the choices provided, an acute hypertensive hemorrhage of the basis pontis is most likely. Autopsy also revealed hyalinization of basal ganglia arteries, left ventricular cardiac hypertrophy, and arteriolonephrosclerosis, which are all related to chronic hypertension. There is no history of a preceding event, which may have led to brainstem herniation and secondary (Duret) hemorrhage. Cerebral amyloid angiopathy does not typically involve the brainstem. Neoplasms and vascular malformations areuncommon causes of acute pontine hemorrhage.
This case demonstrates lobar holoprosencephaly. Holoprosencephaly is a forebrain defect with associated midline facial anomalies. The changes in the brain range from minimal (absence of the olfactory bulbs and tracts) to severe (alobar with failure of separation of the cerebral hemispheres). Maternal factors such as diabetes have been associated with this sequence, but many cases have a genetic cause. The most common nonrandom chromosomal abnormality is trisomy 13. Also reported have been trisomy 18 and other chromosomal anomalies involving chromosomes 13, 15 and 18
Old wedge-shaped stroke
Chiari II malformation
The photomicrograph shows a coronal section of the corpus callosum and cingulate gyri. The arrows identify the indusium griseum. The indusium (also called the supracallosal gyrus) is a direct continuation of the hippocampal formation located dorsal to the corpus callosum
