Neuropathology Flashcards
What mutations do papillary craniopharyngiomas and adamantinomatous craniopharyngiomas have?
Adamantinomatous craniopharyngiomas have mutations in beta-catenin which may be recognized on immunostains by accumulation of stain in nuclei.
Papillary craniopharyngiomas have mutations in BRAF V600E.
What stain is a lymphoid marker that cross-reacts with myelin associated protein and has been used as a second tier marker for Schwann cells?
CD57
What stain can be done in muscle biopsies that if positive is diagnostic of dermatomyositis?
C5b-9 (MAC) It is diagnostic in muscle biopsies but only stains about 40% of the skin lesions and it must be a linear band along the DEJ to be positive
What are the consequences of an uncal herniation?
3rd nerve compression (dilated pupil)
Reticular formation (coma)
Duret hemorrhages (death)
Posterior cerebral artery compression (occipital lobe infarct)
Kernohan’s notch–contralateral cerebral peduncle compression, weakness opposite the side of the lesion
What mutation is a specific point mutation (R132H) in 50-80% of astrocytomas, oligodendrogliomas, and “mixed” gliomas? The mutation found in secondary GBM (NOT IN PRIMARY GBM) and is only rarely found in other cancers (10% of AML).
IDH-1 mutation
BQ! What is the mutation that pilocytic astrocytomas can have?
BRAF fusion
Tandem duplication on chromosome 7q34 leads to several KIAA1549:BRAF gene exon fusions in 50% to 70% of pilocytic astrocytomas. Cerebellar (80%), Optic pathway and hypothalamic (60%), Cerebral (15%)
What are the tumors seen in
1) Type I VHL
2) Type II VHL?
Type 1: Multiple hemangioblastomas in CNS & retina, renal cell carcinoma, cysts of pancreas and kidney
Type 2: plus pheochromocytoma, endolymphatic sac tumor
VHL gene on 3p25-26; encodes tumor suppressor protein
*not sure which type but the Quick Ref for SP says VHL also get clear cell variant of pancreatic endocrine neoplasm and papillary cystadenoma of epididymis and broad ligament
What variant of pilocytic astrocytoma is found in hypothalamus of young children and is Grade II?
Pilomyxoid variant of pilocytic astrocytoma
What brain tumors have mutations at BRAF at codon V600E?
- 66% of pleomorphic xanthoastrocytomas
- 20% of gangliogliomas
- 10% of pilocytic astrocytomas (usually of noncerebellar type)
Papillary craniopharyngiomas
They are two types of Turcot syndrome. What brain tumors are each associated with?
Type 1: GBM with hereditary non-polyposis colorectal carcinoma (HNPCC). Mutations of mismatch repair genes (Hpms2; 7p22)
Type 2: Medulloblastoma in patients with familial
adenomatous polyposis (FAP), Germline mutations in APC gene (5q21)
Name one good and one bad prognostic factor in medulloblastoma.
GOOD: Nuclear Beta catenein
BAD: MYC gene amplification, also Large cell/anaplastic variant
The cell shown is called a Creutzfeldt cell. What condition are these cells seen?
Demyelinating disease
What type of cerebral aneurysm is due to developemental defect in media and elastica (aneurysms that form over time)?
Saccular
These are the berry aneurysms
What disease causes this?
Syphilis
this is tabes dorsalis
What disease causes this?
B12 deficiency
combined posterior columns plus motor
What disease causes this?
ALS
motor affected
What organism causes this characteristic appears of organisms in perivascular spaces and this bubbly gross appearance?
Cryptococcosis
What is the most common cause of focal mass lesion in AIDS?
cerebral toxoplasmosis
Necrotizing lesion with free tachyzoites and encysted
bradyzoites at the lesion periphery.
What organism causes this appearance?
neurocysticercosis
What organism causes a mass like lesion and you see this structure?
Acanthamoeba/Balamuthia species
Almost exclusively in immunocompromised host
Differs from Naegleria which causes a progressive meningoencephalitis
What is this a gross photo of?
Multiple small lesions coalescing into one large one that relatively spares the grey matter
Progressive Multifocal Leukoencephalopathy
Caused by JC virus (a polyoma virus)
Pic is showing intranuclear oligodendroglial inclusion of the virus
What is immune reconstitution inflammatory syndrome (IRIS)?
When an HIV patient is developing PML and HAART therapy is introduced so the CD4 cells increase adn the viral load decreases but you see an inflammatory change to the usual changes seen in PML
If you see this “daisy plaque” (eosinophilic amyloid plaque with surrounding vacuoles), what is the diagnosis?
“New-variant” CJD
What is the sequence of microscopic changes seen in a cerebral infarction?
– 12 - 48 hrs: eosinophilic neurons; other cells (glia,etc) also die
– 3 - 7 days: macrophages enter - begins liquifaction
– 7 - 14 days: vascular proliferation; liquifaction
– weeks: resolving cavitation
What is this a gross image of?
AVM
What vasular brain lesion can be from an autosomal dominant inheritance in some Hispanic families with mutation of CCM1 gene (7q) (Encodes KRIT1; interacts with RAS family of GTPases)?
Cavernous angiomas
BQ! What neuro disease shows migraine with aura may be initial symptom, presenting most commonly in third decade, ischemic attacks peak between 40-50 years of age and dementia?
CADASIL
Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy
Point mutations or small deletions on Notch 3 gene (chromosome 19p13). Notch 3 protein is expressed in vascular smooth muscle cells and may promote survival. Granular vascular material is reactive for Notch 3 protein.
What neuro disease has aquaporin 4 antibodies in 70-75% of patients?
NMO (Devic’s disease)
Aquaporin 4 water channel is located on astrocyte foot processes – may have role in the blood-brain barrier (BBB).
What chromosome has the amyloid precursor protein?
Chr 21
*why Down’s kids get it by 40!
Plaques are made from Aß amyloid
What protein(s) is/are affected in:
1) Alzeheimer’s
2) Frontotemporal degenerations (Pick’s, Corticobasal degeneration, progressive supranuclear palsy, FTDP-17)
3) Idiopathic Parkinson’s, Dementia with Lewy Bodies and Multiple System Atrophy
1) Beta-amyloid (plaques) and Tau
2) Tau
3) alpha-synuclein
What was recently identified as the major disease protein in FTLD-U and ALS?
TDP-43 (Transactive response (TAR)-DNA-binding protein with a molecular weight of 43 kDa)
Mutation in what gene is associated with holoprosencephaly?
SHH gene (sonic hedgehog)
What inflammatory cells predominate in:
1) dermatomyositis
2) polymyositis
1) CD4 positive T cells often perivascular
2) CD8 positive T cells
What is the mutation in Alexander’s disease?
This is a rare demyelinating disease with numerous Rosenthal fibers that is caused by a mutation in the GFAP gene
This lesion was found in the cerebellum of a 22 yr old. What syndrome is this associated with?
Cowden syndrome
This is showing a dysplastic cerebellar gangliocytoma and this lesion is known as Lhermitte-Duclos disease which is associated with Cowden syndrome (PTEN mutation)
What are the different grades for germinal matrix bleeds?
Grade I: hemorrhage limited to the germinal matrix zone
Grade II: rupture of blood from the germinal matrix into the ventricles, without ventricular expansion
Grade III: intraventricular hemorrhage with ventricular enlargement
Grade IV: intraventricular hemorrhage and hemorrhage into the hemispheric parenchyma
What syndrome is associated with meningiomatosis?
Neurofibromatosis Type 2
What disorder is X linked and caused by a defect in the adenosine-5’-triphosphate binding cassette transporter (ABCD1) gene, resulting in accumulation of long-chain fatty acids?
Adrenoleukodystrophy
X linked peroxisomal disorder of myelin and myelin-producing cells
Here there is relative sparing of the frontal lobes in contrast to metachromatic leukodystrophy that preferentially involves the frontal lobes.
What disorder is autosomal recessive and results in accumulation of sulfatide due to a deficiency of the lysosomal enzyme arylsulfastase A and because of this results in a loss of myelin and axonal degeneration?
Metachromatic leukodystrophy
The adult form usually presents between 20-30 years old with psychiatric and behavioral disturbances or psychosis.
The lesions are usually bilateral, symmetrically distributed and generally spare the subcortical U fibers. The frontal lobes are preferentially involved by the disorder in contrast to adrenoleukodystrophy where there is relative sparing of the frontal lobes.
In neurofibrillary tangle dementia, a high density of neurofibrilary tangles are found in all of the following EXCEPT:
1) Amygdala
2) Basal ganglia
3) CA1 region of the hippocampus
4) Entorhinal cortex
5) Subiculum
2) BASAL GANGLIA
Mutations in all of the following genes are associated with familiar cases of Parkinson disease EXCEPT:
1) Alpha-synuclein
2) Parkin
3) PINK1
4) Tau
5) UCHL1
4) Tau
Tau mutations are associated with ceratin forms of frontotemporal dementia (FTDP-17).
Parkinson genes: Alpha-synuclein, parkin, UCHL1, PINK1, DJ1, LRRK2, ATP13A2 and Omi/HtrA2
What is the most common type of frontotemporal lobe dementia?
FTLD-U
Characterized by ubiquitin immunoreactive structures that are tau, neurofilament, alpha-synuclein and prion negative.
A subset of patients demonstrate a mutation in CHMP2B
What neuro disorder is associated with diabetes mellitus, gait ataxia, hypertrophic cardiomyopathy, scoliosis and sensorineural hearing loss?
Friedreich ataxia
What neuro conditions is a rare group of disorders that result in prominent iron accumulation in the brain particularly in the basal ganglia region? They are associated with mutation in the PANK2 gene on chr 20 (pantothenate kinase 2) and the entity is marked by axonal spheroids, neuronal loss and gliosis predominantly in the medial globus pallidus and substantia nigra. Glial cytoplasmic inclusions which are tau and alpha-synuclein positive may be seen in involved areas.
Hallervorden-Spatz disease
(or neurodegeneration with brain iron accumulation)
What variant of glioblastoma characteristically overexpresses EGFR?
Small cell glioblastoma
Brachyury is a relatively new stain that is positive in what TWO tumors?
Chordoma
Hemangioblastoma
Cathepsin-K is a stain which normally stains osteoclasts but it is positive in 3 other tumors, what are they?
Xp11 translocation RCC (both Xp11 and 6;11)
PEComas
Chordoma
What syndrome is associated with pilocytic astrocytomas of the optic nerve?
NF Type 1 (30% of patients with this tumor have NF1)
Name this tumor in the lateral ventricle.
Central neurocytoma
makes you think of ependymoma immediately but there are not true perivascular pseudorosettes, only areas of neuropil
What is this?
AVM
What is this?
Lacunar infarct
What is this?
Remote infarct
What is this?
Bleed likely secondary to hypertension
What is this?
Amyloid angiopathy
What is this?
Uncal herniation
What is this?
Duret hemorrhage
What is this?
Subfalcine herniation
What is this?
Epidural bleed
What is this?
Subdural bleed
What is this?
Contusion
What is this?
Diffuse axonal injury
What is this?
Fat emboli
What is this?
Anencephaly
What is this?
Encephalocele
What is this?
syringoBULBIA
*this is symantics. Notice the olivary nuclei next to the cystic dilation which tells you that you’re in the medulla (brainstem) whereas syringomyelia shown here is a cystic dilation of the spinal cord
What is this?
Hydromelia
An abnormal widening of the central canal of the spinal cord
What is this?
Holoprosencephaly
What is this?
Chiari malformation
downward displacement of the cerebellar tonsils through the foramen magnum (the opening at the base of the skull), sometimes causing non-communicating hydrocephalus
What is this?
Dandy Walker Malformation
congenital human brain malformation involving the cerebellum and the fluid-filled spaces around it. A key feature of this syndrome is the complete absence of the part of the brain located between the two cerebellar hemispheres (cerebellar vermis).[
What is this?
Polymicrogyria
condition that affects the development of the human brain by multiple small gyri creating excessive folding of the brain leading to an abnormally thick cortex. This abnormality can affect either one region of the brain or multiple regions.
What is this?
Partial agenesis of the corpus callosum
What is this?
Cavum septum pellucidum
a persistence of the embryological fluid-filled space between the leaflets of the septum pellucidum and is a common anatomical variant.
What is this?
Plexiform neurofibroma
Diagnostic of NF1
What syndrome does this patient have and how can you tell?
NF2
Pic is showing bilateral acoustic schwannomas on CNVIII
What is this?
Progressive Multufocal Leukoencephalopathy
note the viral inclusions (JC virus)
What is this?
Central pontine myelinolysis
result of rapid correction of hyponatremia
What are the cells shown and what disease is this associated with?
Pick Cells and the pic here is showing Pick bodies
These are associated with Pick’s disease (frontotemporal dementia) and the bodies are thought to be neurofilaments and microtubules
What is this?
Abscess
What is this?
Cryptococcus
What is subacute sclerosing panencephalitis (SSPE)?
- Fatal, measles virus
- Under age 12 years
- Months – few years course
- Progressive dementia, myoclonus, seizures, ataxia, dystonia
- Pathology: - Gray matter subacute encephalitis, eosinophilic nuclear and cytoplasmic inclusions, neuron loss, microglia, perivascular inflammation
- Demyelination, oligodendroglial inclusions, reactive astrocytosis
- Cerebral atrophy – old cases
What disease has this EM appearance?
Zebra bodies of Tay Sachs disease (also seen in Niemann-Pick)
- GM2-gangliosidoses
- Autosomal recessive, Ashkenazi Jewish population
- Hexosaminidase A deficiency so accumulation of GM2 ganglioside
- Brain weight normal or decreased/increased
- Balloon neurons with cytoplasmic vacuoles
- EM: whorled membranes or zebra bodies
- Cherry red spot in macula
- Death age 2-3 years
BQ!
Luxol fast blue stain–name this entity.
Primary Multifocal Leukoencephalopathy (PML)
BQ! Picture of gel showing what Apo E2/E4, E3/E4
would look like and 5 unknowns. Which
unknown is associated with loss of memory?
Know Apo E4 associated with Alzheimer’s and pick appropriate gel showing homozygous
E4.
