Pathology Flashcards
1
Q
THE hallmark of all the neurodegenerative diseases
A
Loss of neurons
2
Q
- Expanded ventricles (“hydrocephalus ex vacuo”)
- Narrow gyri and wide sulci
- Widespread neuronal loss, worst in the hippocampus**
- Generalized cortical atrophy
A
Alzheimer’s
3
Q
TAU (gene MAPT) is a component of ____________.
A
microtubules
4
Q
Taupathies involving neurons and their processes only: (2)
A
- Alzheimer’s dz / old age
- Chronic traumatic encephalopathy (boxer’s dementia)
5
Q
Taupathies involving both neurons and oligodendroglia: (5)
A
- Classic Pick’s dz (i.e., with real tau-based Pick bodies)
- Progressive supranuclear palsy
- Corticobasal degeneration
- The Pick’s-plus-Parkinsonism (FTDP-17) from mutated tau
- Argyrophilic grain dz
6
Q
Alpha-synuclein (gene SNCA) pentamers are located in (pre/post)synaptic terminals.
A
PREsynaptic
7
Q
Synucleinopathies involving neurons: (3)
A
- Classic Parkinson’s dz
- Cortical Lewy body dementia
- Parkinson’s with mutated synuclein
8
Q
Synucleinopathies involving both neurons and oligodendroglia: (1)
A
Multiple systems atrophy (*Papp-Lantos inclusions)
9
Q
Amyloid precursor protein may be degraded abnormally to form _______ ____, which is central to 4 major diseases.
A
amyloid beta
10
Q
Amyloid beta diseases of neurons and vessels: (2)
A
- Alzheimer’s dz
- Chronic traumatic encephalopathy
11
Q
Amyloid beta diseases of vessels only: (1)
A
-Some versions of congophilic angiopathy
12
Q
Amyloid beta diseases of skeletal muscle: (1)
A
-Inclusion body myositis
13
Q
Diseases of neurons involving TDP-43 (TAR DNA binding protein, TARDBP): (2)
A
- TDP-related frontotemporal dementia
- Many cases of amyotrophic lateral sclerosis (ALS)
14
Q
Many (but not all) pts with TDP-43 inclusion-related dz have mutations of: (3)
A
- TDP-43
- Progranulin (frontotemporal dementia only)
- C9orf72
15
Q
FUS (“Fused in Sarcoma”) diseases involving neurons: (2)
A
- FUS-related frontotemporal dementia
- FUS-related cases of amyotrophic lateral sclerosis
16
Q
Polyglutamine inclusions are seen in the nucleus in dz’s caused by genes with long polyglutamine-coding trinucleotide repeat regions: (3)
A
- Huntington’s chorea
- Several of the spinocerebellar ataxias
- Kennedy’s spinobulbar muscular atrophy
17
Q
- MC dementia
- Incidence increases with age
A
Alzheimer’s dz
18
Q
Certain mutations in ___ produce a more amyloidogenic product. The protein is on chr.21 and perhaps this is why Down’s adults usually get Alzheimer’s in their 40’s.
A
APP
19
Q
Senile plaques are masses of A-beta amyloid in the neuropil, surrounded by neurites containing tau. Seen in:
A
Alzheimer’s
20
Q
TQ: _______________ _______ stain with silver (binds to the phosphate). In tall neurons, they can look like flames. Seen in:
A
Neurofibrillary tangles
-Alzheimer’s
21
Q
TQ: Neurofibrillary tangles and neuritic plaques. Silver stain. You think…
A
Alzheimer’s
22
Q
Granulovacuolar degeneration. You think…
A
Alzheimer’s
23
Q
Amyloid (congophilic) angiopathy. Almost all pts have amyloid in vessels and bleeding can occur. You think…
A
Alzheimer’s
24
Q
Tomorrow’s tests for Alzheimer’s dz: (2)
A
- Diffusion tensor imaging (DTI)
- Serum clusterin
25
In addition to the selective atrophy of frontal and anterior temporal lobes (sparing of superior temporal gyrus), microscopy often shows balloon neurons.
Classic Pick's dz
| Frontotemporal dementia
26
- MC illness among a group in which cells are lost from the nigrostriatal system
- resting tremor ("pill rolling"), rigidity, mask-like face, cogwheel rigidity
- Alpha-synuclein-rich Lew bodies are found in the substantia nigra and locus ceruleus
Parkinson's dz
27
Lewy bodies in substantia nigra with only a few neurons remaining. You think...
Parkinson's dz
28
Clinically, parkinsonism and/or bizarre behavior. Pathologists look for NFT's.
Parkinson's Variant: Dementia Pugilistica / Chronic Traumatic Encephalopathy
29
A taupathy involving primarily the substantia nigra and other subcortical structures. Look for globose neurofibrillary tangles.
Progressive Supranuclear Palsy (PSP)
30
A taupathy with tau-containing inclusions in both brainstem and cortex
Corticobasal Degeneration
31
- Alpha-synuclein inclusions in the glia (esp oligodendroglia) and more damage to the white matter
- "Hot cross bun" sign on T2 results from selective loss of the pontine raphe nuclei
Multiple System Atrophy (MSA)
32
- Cerebral cortex tends to be spared
- Pts have trouble moving their eyes, especially looking down
- Trucal rigidity and falls are more of a problem than tremor
Progressive Supranuclear Palsy (PSP)
33
"Globose" neurofibrillary tangles in the substantia nigra
PSP
34
Tau "smoke puffs" around an astrocyte - the pathognomonic "astroglial plaque"
Corticobasal Degeneration
35
Tau coils next to neuron nuclei
Corticobasal Degeneration
36
- Same pathology as striatonigral degeneration with the addition of damage to some autonomic neurons in the cord
- Cause of orthostatic hypotension
Shy-Drager (MSA type A)
37
Tiny basis pontis
MSA-C
38
- Relatively common dz that mimics Alzheimer's but with a faster course, visual hallucinations and paranoia
- Lewy bodies are seldom numerous, and it's through that the damage is done by small aggregates of alpha-synuclein
Lewy body dementia
39
- Autosomal dominant, full-penetrant dz with genetic anticipation
- Caused by a CAG trinucleotide-repeat mutation at HTT (huntingtin)
- The polyglutamine protein accumulates in the nucleus and causes loss of neurons, esp in the caudate**
- Pts present with emotional changes, a curious dance-like movement disorder, and eventually dementia
Huntington's dz
40
- The neurons of portions of the hippocampus die off and are replaced by glia
- Not treatable
- Younger patients tend to have a history of seizures
Hippocampal Sclerosis
41
- Striatonigral degeneration
| - Putamen takes the worst damage
MSA type P
42
- Flattening / loss of head of caudate
| - Polyglutamine in the nucleus
Huntington's dz
43
- Develops around age 10
| - Mutation in Torsin A (DYT-1)
Dystonia Musculorum Deformans / Torsion Dystonia
44
- Caused by mutated frataxin, which allows iron overload within mitochondria
- Posterior columns and corticospinal tracts are gone
Friedreich's Ataxia
45
- Autosomal recessive dz caused by defective ATM (11q22-q23), involved in the repair of DNA breaks and more
- Purkinje and granular cells are lost from the cerebellum during childhood, esp the vermis
- Hypoplastic thymus with defective T-cell immunity
- Prominent arteries ("telangiectasias") esp on eye surfaces
Ataxia-Telangiectasia
| "Louis-Bar dz"
46
- Involves disappearance of both UMNs and LMNs
- Fasciculations in the tongue
- Best-known gene SOD1 - superoxide dismutase
- Pyramidal motor cells gone
- Hypoglossal nucleus gone
- Anterior horns and corticospinal tracts lost
- Bunina bodies present
- Many but not all of these pts have mutated germline FUS and an early onset
Amyotrophic Lateral Sclerosis
| "Motor Neuron dz"
47
- X-linked recessive dz with genetic anticipation and polyglutamine causing a toxic product
- Lesion is in the androgen receptor
- Both UMN and LMN lost
- Milder than ALS
Kennedy's spinobulbar muscular atrophy
48
TQ:
- Autoimmune inflammation and demyelination of CNS
- Pts can present with optic neuritis
- Essential lesion = "yellow/jaune plaque"
- Relapsing and remitting course
- Most often affects women in their 20s and 30s, more common in whites
- Periventricular plaques **
- Link to HLA-B15 and DQ6 **
- Myelin destroyed, axons spared
Multiple Sclerosis (MS)
49
- Immunity against myelin that tends to follow viral illness
- Myelin loss is widespread and diffuse
- "T-cell rampage"
Acute disseminated encephalomyelitis
50
- Immune attack on brain's myelin and blood vessels
- Neutrophils ARE involved
- Outcome is usually death or severe disability
Acute necrotizing hemorrhagic leukoencephalitis
51
-Caused by antibodies against glutamic acid decarboxylase
Stiff person syndrome
52
- "Duck foot Purkinje cells"
- Zebra bodies
- Deposits in the intima
Hurler's
53
TQ:
- Lysosomal storage dz, MC due to arylsulfatase A deficiency
- Accumulation of sulfatides leads to impaired production of myelin sheath
- Acid cresyl violet stain - stains sulfatides (in histiocytes) brown
Metachromatic leukodystrophy
54
- Myelin gone from white matter
- Lysosomal storage dz due to deficiency in galactosylceramide
- Causes accumulation of abnormal lipids within myelin
- Peripheral neuropathy, developmental delay, optic atrophy, "globoid histiocytes"
Krabbe's leukodystrophy
55
-Can't break down GFAP
Alexander's
56
-Loss of EIF2B complex, which prevents cell death from minor stress
Vanishing white matter dz
57
- Aspartoacylase deficiency...
- Causes accumulation of aspartic acid in white matter of the brain, esp right under the cortex...
- Pulls water in by osmosis, unraveling the myelin and making a bubbly appearance
Canavan's dz
58
- X-linked genetic disorder typically affecting males
- Disrupts metabolism of very-long-chain fatty acids...
- Leads to buildup in nervous system, adrenal gland, and testes
- Lack gene ABCD1
Adrenoleukodystrophy
59
- Portions of brain are affected by accum of lactic acid, and there is a mild mitochondrial myopathy
- Little strokes may result
MELAS
| Mitochondrial Encephalopathy, Lactic Acidosis and Stroke-like episodes
60
-Mitochondrially inherited, often with a tRNA synthetase
MERRF
| Myoclonic Epilepsy and Ragged Red Fibers
61
- Result of mutations that prevent proper oxidative phosphorylation
- Symmetric, widespread destruction of the brain results
Leigh's subacute necrotizing encephalopathy
62
Bleeds in mammillary bodies
Wernicke's (acute)
63
TQ: Shrunken, discolored mammillary bodies.
Wernicke's (old)
64
Hemorrhagic necrosis of the putamen
Methanol toxicity
65
Necrosis of the globus
Carbon monoxide toxicity
66
- Miners and foundry workers
- A movement disorder which combines Parkinson-like symptoms and dystonia
- Unlike true Parkinson's dz, the major damage is probably to the globus pallidus
Manganese toxicity
67
- Garlic breath
- Symmetric CNS necrosis
- Necrosis of GI epithelium
- Stocking and glove neuropathy
Arsenic poisoning (acute)
68
- Garlic breath
- Pigment (neck, armpits, nipples)
- Muscle weakness
- Increased keratin on palms
- Mee's lines (after 6 weeks)
- Numbness, worst in legs
Arsenic poisoning (chronic)
69
Copper in basal ganglia
Wilson's
70
Caused by pantothenate kinase deficiency
Brain iron accumulation type I
71
Indirect bilirubin can cross the newborn's brain and high levels can cause damage
Kernicterus
72
Methotrexate increases the risk of:
Radiation necrosis
73
Carboplatin and anti-Hu may cause a ______________ - dorsal root ganglion cells are killed.
neuronopathy
74
- Loss of proprioception and vibration
| - "Fall in the dark"
Large fiber neuropathies
75
-Loss of pain and temperature, perhaps paresthesias / pain
Small fiber neuropathies
76
Mononeuritis multiplex. Think...
Vasculitis or vasculopathy
| -Lupus, Sjogrens*, and hep C can all produce either a vasculitis or a polyneuropathy
77
- Autoimmune condition that destroys Schwann cells
- Causes inflammation and demyelination of peripheral nerves and motor fibers
- Illness is often preceded by an infection, famously CMV, campylobacter, H. flu
Guillain-Barre Acute Inflammatory Demyelinating Polyneuropathy
78
- Bacteria grow inside the Schwann cells
- Loss of pain/temp
- Tendency not to notice injuries is famous
- Tuberculoid form more likely to see anesthetic, hypopigmented patches*
Leprosy (Hansen's dz)
79
-Produces an axonal neuropathy by molecular mimicry between the microbe and an axonal protein
Lyme dz
80
- MC and most complex of the peripheral neuropathies
- Attributed to products of non-enzymatic glycosylation but not fully understood
- Axons, myelin, and vessels are all involved
- Symmetric sensorimotor neuropathy
- Starts distally
Diabetic neuropathy
81
- Family of variously-inherited dz's in which the longest nerve fibers die off first, either from failure of the myelin or the axons
- Mutations in the essential proteins of myelin
Charcot Marie Tooth
82
TQ:
- In children, most often found in posterior fossa (e.g., cerebellum)
- Risk factor = neurofibromatosis type I (NF1)
- Usually feature mutated BRAF
- Contain Rosenthal fibers
- GFAP(+)
- Benign, good prognosis
Pilocytic astrocytoma
| grade I astrocytoma
83
TQ:
- Common, highly malignant primary brain tumor
- Found in cerebral hemispheres
- Pts usually present with headaches, personality changes and/or seizures
- 1-year median survival
- "Pseudopalisading" pleomorphic tumor cells around area of necrosis
Glioblastoma multiforme
| grade IV astrocytoma
84
____ is amplified or point-mutated in about 50% of primary glioblastomas.
EGFR
| epidermal growth factor receptor
85
The big new discovery is that most gliomas (90% of glioblastomas) bear a point mutation in __________ ____________.
isocitrate dehydrogenase
| -Leads to production of 2-hydroxyglutarate, which alters epigenetic controls
86
The MC change in both primary and secondary glioblastomas is loss of heterozygosity on:
10q (PTEN)
87
TQ:
- Most often affects younger adults
- Grade II tumor
- Pts with NF1, NF2 or Li Fraumeni are at extra risk
- Tame-looking cells, lots of fibers
- These tumors often bear TP53 mutations and/or loss of 17p
Diffuse astrocytoma
88
What gene, if knocked out, makes the glioblastoma more vulnerable to the alkylating agent temozolomide?
MGMT
| methylguanine methyl transferase
89
TQ:
- Grade III tumors of astrocytes
- Distinguished by increased cellularity, nuclear atypia, and mitotic activity
- Risk factors same as diffuse astrocytomas, many have 9p loss
- Majority of these tumors transform into glioblastoma within two years
Anaplastic astrocytoma
90
TQ:
- Relatively rare, slow growing
- Grade II tumors
- Most often in frontal lobes, but usually in cerebral hemisphere (headache, seizure, personality change)
- "Fried egg" cells**
- Often calcified
- Only known risk factor = old radiation
- Loss of 1p and 19q
Oligodendroglioma
91
TQ:
- Grade II tumors
- MC primary tumor of spinal cord, but most commonly found in 4th ventricle*
- Most pts are children and young adults
- Characteristic perivascular rosettes
- Rod-shaped blepharoplasts (basal ciliary bodies) found near nucleus
Ependymoma
92
- Grade I tumors
- On the cortex
- Seizures
- BRAF V600E
- Surgery is curative
Ganglioglioma
93
- Grade I tumors
- Children with seizures
- Surgery is curative
Dysembryoplastic neuroepithelial tumors
94
- Grade II tumors
| - Walls of ventricles
Central neurocytoma
95
TQ:
- Highly malignant cerebellar (vermis) tumor
- Grade IV tumor
- MC aggressive childhood brain tumor (peak age 7 yo)
- A form of primitive neuroectodermal tumor
- Can compress 4th ventricle, causing hydrocephalus
- Can send "drop metastases" to spinal cord, encases spinal cord*
- Homer-Wright rosettes
- Solid, small blue cells on histo
- Molecular target is sonic hedgehog pathway
Medulloblastoma
96
TQ:
- Grade I tumor
- Common, typically benign primary brain tumor
- Most often occurs in convexities of hemispheres (near surfaces of brain) and parasagittal region
- Arises from arachnoid cells
- Headache, personality change, seizures
- Spindle cells concentrically arranged in a whorling pattern
- Psammoma bodies
Meningioma
97
Increased mitotic figures** in a meningioma increases the grade from Grade I to Grade __, and is called ________ __________.
- Grade II
| - Atypical meningioma
98
-Meningioma featuring obvious anaplasia and/or 20+ mitoses per 10 high power fields
Anaplastic meningioma
| Grade III
99
TQ:
- Grade I tumors composed of curious blood vessels that arise sporadically in the cerebellum*
- Associated with von Hippel Landau syndrome*
- Can produce erythropoietin leading to secondary polycythemia*
- Odd vessels, surrounded by big pale benign clear (lipid-filled) cells
Hemangioblastoma
100
- Most hated of all "benign" tumors
- Arise from notochord remnants on clivus or sacrum
- "Bubble cells"
Chordoma
101
TQ:
- Benign childhood tumor, may be confused with pituitary adenoma (both can cause bitemporal hemianopia
- MC childhood supratentorial tumor
- Derived from remnant of Rathke pouch*
- Calcification is common* (tooth enamel-like)
Craniopharyngioma
102
TQ:
- Grade I benign subtype of craniopharyngioma, seen in adults*
- Tumor arises in or just above the sella turcica*
- Derived from remnant of Rathke pouch*
- Pts present with visual and/or endocrine and/or emotional disturbances
- Regions of tumor filled with "machine oil" rich in cholesterol
- Benign squamous cells, no columnar cells or calcification
- Mutated BRAF
Papillary craniopharyngioma
103
TQ:
- Most familiar subtype of craniopharyngioma
- Age peaks among children age 5-15 and adults ages 45-60
- Rare in US, common in Nigeria and Japan
- Calcification is common
- Feature columnar cells bordering more squamous regions, as in a developing tooth
- Mutated beta-catenin (CTNNB1)
Adamantinomatous craniopharyngioma
104
- Benign (Grade I) brain tumors
| - Produce huge amounts of CSF, causing hydrocephalus
Choroid plexus papillomas
105
- Affect 3rd ventricle and are benign but contain mucus
- Obstruct the foramen of Munro
- Positional headaches
Colloid cysts
106
- Tumor often seen in young people
- Present as precocious puberty*
- Tumors that mimic testicular germ cell cancers are common here for some reason (esp seminoma)
- Grade 1 and Grade IV varieties
Pineocytoma (Grade I)
| Pineoblastoma (Grade IV)
107
MC cancer in the CNS
Metastatic cancer
108
MC source of metastatic cancer
Lung, especially oat/small cell and adenocarcinoma
109
Where do mets begin in the brain?
Gray-white junction
| where spreading cancer cell gets stuck in a blood vessel
110
TQ:
- Usually found at cerebellopontine angle
- Areas with nuclei arranged as zebra stripes ("Verocay bodies")
- Often localized to CN VIII
Schwannoma
| "acoustic schwannoma"
111
TQ:
Genes for tuberous sclerosis: (2)
-Angiomyolipoma of kidney
-Adenoma sebaceum on face
- Hamartin (TSC1)
| - Tuberin (TSC2)
112
```
TQ:
Gene for von Hippel-Lindau:
-Strange vessels on back of eye
-Hemangioblastoma in cerebellum
-Renal cell carcinoma
```
VHL (Chr. 3)
113
```
TQ:
Gene for neurofibromatosis type I:
-Cafe-au-lait spots
-Lisch nodules on iris
-Bilateral optic nerve gliomas
```
NF1, neurofibromin (Chr. 17)
114
```
TQ:
Gene for neurofibromatosis type II:
-Bilateral acoustic schwannomas ("neuromas")
-Juvenile cataracts
-Meningiomas and ependymomas
```
NF2, merlin (Chr. 2)
115
- anti-Yo, anti-PCA-1
- Destroys Purkinje cells
- Ataxia and then no movement at all
- Mostly breast, ovary, uterus cancer
Cerebellar degeneration
116
- anti-Hu, anti-NMDA, others
- Can destroy amygdala
- Appalling behavioral changes
Limbic encephalitis
117
The 5 MC cerebral paraneoplastic syndromes caused by immunity directed against tumors:
- Cerebellar degeneration
- Limbic encephalitis
- Opsoclonus
- subacute sensory neuropathy
- Eaton-Lambert myasthenia
