Syndromes Flashcards
(200 cards)
1
Q
inheritance of malignant hyperthermia
A
auto dom
2
Q
most commonly implicated gene in malignant hyperthermia
A
ryanodine receptor gene 19q13
but really anything that encodes a voltage dependent Ca or Na channel
3
Q
what are ryanodine receptor mutations implicated in?
A
malignant hyperthermia
&
central core disease of muscle
4
Q
pattern of inheritance of Fahr’s disease
A
auto dom OR auto rec :)
if auto dom, 14q has been assoc
5
Q
what’s the other name for Wilson’s disease
A
hepatolenticular degeneration
6
Q
mode of inheritance of wilson’s disease
A
auto recessive
7
Q
gene in wilson’s disease
A
ATP7B on 13q14.3
8
Q
gene in Menke’s disease
A
ATP7A
9
Q
gene in aceruloplasminemia
A
ceruloplasmin gene on 3q23-24
10
Q
inheritance of aceruloplasminemia
A
auto dominant
11
Q
G-M2 gangliosidosis is a group of disorders that have XS normal ganglioside. what eponym goes with this
A
Tay-Sachs
&
Sandhoff
12
Q
what is the defect in Tay-Sachs
A
Beta-hexosaminidase subunit A deficiency
13
Q
mode of inheritance of G-M2 gangliosidosis
A
auto recessive
14
Q
Tay-Sachs looks like what microscopically?
A
Ballooned cortical neurons
FFPE is PAS- but LFB+ & sudan black+
Frozen tissue is PAS+
microglia will be PAS+ no matter what
EM: membranous cytoplasmic bodies
15
Q
what these
A
membranous cytoplasmic bodies in the gangliosidoses
16
Q
gross finding for G-M1 gangliosidosis
A
mild gyral atrophy
17
Q
mode of inheritance of galactosialidosis
A
auto recessive
18
Q
issue in galactosialidosis
(like sialidosis + Fabry)
A
defective PPCA (protective protein/cathepsin A) > combined deficiency in beta-galactosidase & neuraminidase > sialyloligosaccarides accumulate in lysosomes (& urine)
19
Q
gene in galactosialidosis
A
CTSA (gene encoding PPCA) on 20q13.1
20
Q
what non-CNS micro manifestations can you see in galactosialidosis?
A
foam cells in bone marrow
cytoplasmic vacuolation (lymphs, hepatocytes, Kupffer cells, Schwann cells, fibroblasts, endothelial cells)
21
Q
what is the way to dx neuronal ceroid lipofuscinosis?
A
suction rectal biopsy
cryostat sections
characteristic accumulation of autofluorescent ceroid lipofuscin
infantile is silvery, the rest are yellow
the ONE exception is CLN4/Kufs dz
22
Q
what’s the eponym for neuronal ceroid lipofuscinosis?
A
Batten’s disease
23
Q
which ceroid lipofuscinosis has the latest onset & survival?
A
CLN4/Kufs
24
Q
which ceroid lipofuscinosis has the earliest onset and worst survival?
A
CLN1
25
what diseases (prob not exhaustive) show granular osmiophilic deposits on EM?
CADASIL
neuronal ceroid lipofuscinosis type 1 (infant)
26
what diseases (prob not exhaustive) show curvilinear bodies on EM?
colchicine/hydroxychloroquine induced myopathy
neuronal ceroid lipofuscinoses 2 thru 8 (late infant thru adult)
27
what diseases (prob not exhaustive) show fingerprint profiles on EM?
ceroid lipofuscinoses 3 thru 7 (late infant & juvenile)
28
in which Niemann-Pick subtype do you NOT see CNS abnormalities?
type B (this is the "visceral only" group I subtype)
29
where do you find Niemann-Pick cells?
mononuclear phagocyte system (LMAO) & can fill alveoli
30
which disease has "sea-blue histiocytes"?
Niemann-Pick (older pts with type B)
31
what clinical feature unites all the Niemann-Picks subtypes?
hepatosplenomegaly
32
which Niemann-Pick subtype has tangles?
type C
33
main issue in Gaucher's disease
deficient activity of glucocerebrosidase aka glucosylceramidase (it’s the only gluco- one)
OR
a cofactor (saposin C)
34
chromosomes implicated in Gaucher's
GBA1 (glucocerebrosidase aka glucosylceramide) 1q21
Prosaposin 10q21
35
heterozygous mutations in GBA increase risk of what?
Parkinson's dz
dementia w/ Lewy bodies
(GBA = glucocerebrosidase aka glucosylceramidase = Gaucher's)
36
types 2 & 3 Gaucher's disease have a neuronopathic microscopic finding, which is what?
perivascular clusters of Gaucher cells in subcortical white matter and cerebellum
(Foamier than Krabbe’s globoid cells)
37
which mucopolysaccharidosis is NOT auto recessive?
Hunter syndrome (MPS II)
38
EM finding of mucopolysaccharidoses?
Zebra bodies (stacked stored material)
(not specific)
39
strikingly firm and white...white matter should make you think of what?
fucosidosis
40
in what 2 diseases can you see abundant Rosenthal fibers that cluster around blood vessels?
fucosidosis
&
Alexander disease
41
acid maltase deficiency is what eponym and what storage disease?
Pompe's disease
type II glycogenosis
(The lava in PompeII MALTing faces)
42
in what forms (ages) of Pompe's can you see neuronal glycogen storage? and where do you see it
infant & juvenile
NOT adult
anterior horn cells, motor cranial nerve nuclei
BG
GI tract plexuses
(It’s glycogen so it’s PAS+)
43
gene defect in Farber's disease
ASAH1 gene
8p22
44
what is the issue in Farber's disease
deficiency of acid ceramidase (ASAH)
45
micro & EM of Farber's disease
1. GI ganglion cell PAS+ material
2. birefringent in polarized light
3. EM zebra bodies & Farber bodies (bananas)
46
which syndrome has "iron fist in a velvet glove" due to firm centrum semiovale?
Krabbe's globoid cell leukodystrophy
47
EM of Krabbe's
globoid cells/macrophages contain curved or straight crystalloid tubular inclusions
48
what do the macrophages (or any other cell honestly) in metachromatic leukodystrophy look like on FROZEN SECTION?
PAS+, LFB+
brown metachromasia with acidified cresyl violet, toluidine blue, or thionine
49
what are the 3 types of EM inclusions in metachromatic leukodystrophy?
1. prismatic (“herringbone” on bottom)
2. tuffstone (looks like a mosaic)
3. laminated (looks like a child drew zebra bodies)
50
what is getting stored in metachromatic leukodystrophy?
sulfatide
51
what is Zellweger cerebrohepatorenal syndrome?
peroxisomal storage disorder in which the peroxisomes are too few (one of many disorders that have this issue)
52
issue in Krabbe's disease
galactocerebroside-beta-galactosidase deficiency
53
gene for krabbe's
GALC
14q31
54
issue in metachromatic leukodystrophy (& gene)
aryl sulfatase A deficiency
ARSA 22q13
55
EM finding in adrenoleukodystrophy
lipid deposits w/ very long chain fatty acids > needle-like trilaminar bodies
56
micro of adrenoleukodystrophy in brain
extensive myelin loss that SPARES U-fibers
&
PAS+ macrophages in large groups
older lesions have perivascular inflammation
57
adrenal gland in adrenoleukodystrophy?
severely atrophic
remaining adrenocortical cells are enlarged and have striations
58
"punched out" chronic lesions in cortex devoid of neurons, resembling old infarct should make you think of what syndrome?
MELAS
59
what does MELAS stand for?
mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes
60
mutation in MELAS
A3243G in mitochondrial tRNA (LeuUUR) gene
or T3271C in same gene
61
what part of the brain is most affected in MELAS?
occipital lobe
62
histo of muscle in MELAS?
ragged red fibers
+/- paracrystalline inclusions
too many mitochondria in endothelium & smooth muscle of BVs, so they show increased SDH (or tRNA if you have it) staining
63
what does MERRF stand for
myoclonic epilepsy with ragged red fibers
64
gene a/w MERRF
A8344G in mitochondrial tRNA(Lys)
65
all cases of MERRF have 2 things; what are they? Only SOME have a 3rd thing; why is that?
ALL: neurosensory hearing loss and mt myopathy with ragged red fibers
likelihood of developing myoclonic epilepsy is related to proportion of mtDNA that has the mutation
66
what disease can you get from A8344G?
MERRF
67
how can you tell MERRF and Leigh syndrome apart?
MERRF has myoclonus, seizures, and ragged red fibers; shrunken, discolored dentate nucleus; gliotic putamen
Leigh syndrome has focal, bilateral, symmetric brain lesions in BG, thalamus, and brainstem
68
which 3 mitochondrial diseases result in degeneration of the retinal ganglion cell layer of the eye, with sparing of the photoreceptors and RPE?
Leber's hereditary optic neuropathy
Bilateral striatal necrosis
Multiple sclerosis-like mitochondrial disease
69
what is NARP (lol)
Neuropathy, ataxia, and retinitis pigmentosa
NO ragged reds; instead, lipid & glycogen in vacuoles in muscle cells
70
what is Kearns-Sayre syndrome? (we're gonna remember 3 things and 3 things only)
1. Prog external ophthalmoplegia + cardiac conduction issues
2. Vacuolation of white matter (myelin sheaths) in brainstem > cerebellum > cerebrum
3. Ragged red AND COX- fibers AND paracrystalline mt inclusions on EM!
remember K + S
Kardiac
eKSternal ophthalmoplegia
paraKrystalline inclusions/ragged reds
Sheaths (of myelin with vacuoles)
71
what is MNGIE?
myoneurogastrointestinal encephalopathy syndrome
72
what's another name for MNGIE?
polyneuropathy, ophthalmoplegia, leukoencephalopathy, and intestinal pseudo-obstruction (POLIP)
73
what organ (besides the brain) has characteristic changes in Alpers-Huttenlocher/progressive neuronal degen of childhood?
the Liver > essentially cirrhosis/fibrosis and microvesicular fatty or oncocytic change
74
if you see calcarine cortical lesions, what disease should you be thinking of?
Alpers-Huttenlocher/progressive neuronal degeneration of childhood
75
Micro findings of Alpers-Huttenlocher lesions
1. superficial cortical spongiosis
2. hypertrophic astrocytes
3. +++neutral fat
***predominantly affecting striate/visual cortex***
76
clinical Huntington's without the right genetic defect
Holotopistic striatal necrosis
aka
familial striatal degeneration
77
what is Hallervorden-Spatz dz?
neurodegeneration with brain iron accumulation-1
78
familial fatal insomnia
PRNP D178N w/ 129M polymorphism
79
the mnemonic is:
INAD 2PLA
(i need to play)
Infantile Neuro-Axonal Dystrophy
2PLA = the gene, PLA2G6
PLA also stands for Purkinjeloss + Lewytau + Axonalspheroids :)
80
the mnemonic is:
Leigh's SNEeze PDHC's symmetries
Leigh's SNEeze = Subacute Necrotizing Encephalomyelopathy
PDHC's = PDHC pyruvate dehydrogenase complex
symmetries = symmetrical gray-brown lesions (striatum + SN)
81
the mnemonic is:
Be Very Very Quiet
BVV = Brown-Vialetto-van Laere
Quiet = bilateral nerve deafness
82
what's DRPLA
Dentatorubral-pallidoluysian atrophy (spinocerebellar degen)
83
DRPLA inheritance
Auto DOM
84
DRPLA gene/issue
CAG repeat expansion > polyglutamine tract in the atrophin-1 protein (ATN1 on 12p)
85
DRPLA structures affected (use the letters)
Spinocerebellar tracts + posterior columns + superior cerebellar peduncles
neuronal apoptosis + astrocytosis in the dentatorubral and pallidoluysian systems (**GPe + red nucleus + dentate + subthalamic [body of Luys]**)
D = dentate
R = red nucleus
P = (sPine) Posterior columns + suPerior cerebellar Peduncles + sPinocerebellar tracts
L = Luys (subthaLamic)
A = Angry that GPe doesn't fit in this mnemonic
86
genetic issue in Huntington's
CAG repeat expansion within polyQ region of HTT (huntingtin) on chrom 4
87
thresholds of trinucleotide repeats and manifestations of Huntington's
<27 = normal (no dz)
27-35 = "intermediate" (no dz)
36-39 = "reduced penetrance" (+/- dz, later onset)
40+ = full penetrance (+ dz)
60+ = juvenile HD (Westphal, <20yo)
88
the mnemonic is:
HULKenlocher
Alpers-Huttenlocher
Green Hulk = liver manifestations
pole-dancing = POLG1 mutation
while shooting gamma rays out his eyes = polymerase gamma + calcarine cortex affected
and punching holes in the cortex = spongiosis
89
familial british dementia gene
ITM2B
90
micro of familial british dementia
Bri amyloid plaques + CAA (widespread) + NFTs/tau path around CAA vessels
91
clinical diffs between familial british and danish dementias
BOTH: ataxia + dementia
DANISH: cataracts + deafness
92
micro of familial danish dementia
ADan amyloid in vessels but NO PLAQUES!!!!!
Still has NFTs/tau path around CAA vessels!
93
gene in familial danish dementia
ITM2B (not same mut as British)
94
Familial encephalopathy with neuroserpin inclusion bodies GENE
Serpin1
Ser49Pro = later onset
Ser52Arg = young, seizures
95
what disease has Collins bodies?
familial encephalopathy with neuroserpin inclusion bodies (FENIB)
96
what type of Tau do you get in Pick's disease?
3R
97
gene in FAMILIAL Pick's dz
MAPT
(but most cases are sporadic!)
98
what do Pick bodies stain with?
silver, phospho tau (3R), ubiquitin, tubulin, and chromogranin-A
99
Huntington von Sattel grading
caudate & GP
Grade 0-1 = grossly normal
Grade 2= visible atrophy
Grade 3 = flat
Grade 4 = concave
100
nucleus affected in ballismus/hemiballismus?
subthalamic nucleus
101
gene in Friedreich's Ataxia
FXN (9q)
GAA trinucleotide repeat expansion (mitochondrial iron)
very rarely d/t point mutation (auto recessive)
102
what are the thresholds for Friedreich's ataxia
normal: 6-34 rpts
mild: ~500
severe: ~1000
103
4 sx of Friedreich's ataxia
1. Cardiomyopathy
2. Proprioceptive ataxia
3. Dysarthria
4. Areflexia
bonus: diabetes (beta cells)
104
Friedreich's ataxia has 4 MAIN affected structures (and then specific things within those). what are the 4 MAIN ones?
1. Cerebellum
2. Medulla
3. Spinal cord
4. Peripheral nerves
105
Friedreich: what 3 parts of the SC are affected?
they're a circuit
(peripheral) > afferent >
1. **posterior columns** (gracile > cuneate)
2. **Clarke's column** loses neurons
3. distal degen of **pyramidal and spinocerebellar tracts**
106
Friedreich: what 3 things in the medulla are affected?
1. Accessory cuneate/gracile nuclei (tract degen/neuron loss)
2. Vestibular/cochlear nuclei (balance)
3. Superior olives (inferior olives are usu normal)
107
Friedreich: what 2 main things in the cerebellum are affected?
1. Dentate (severe cell loss)
2. Superior cerebellar peduncle (atrophy)
108
Friedreich: what 2 things are affected in peripheral nerves?
1. DRG ganglion cell loss
2. Depletion of large myelinated axons (posterior roots & sensory nerves) (same thing happens in optic nerves/tracts but less severe)
109
which disease looks like Friedreich's clinically but has an alpha-tocopherol transfer protein defect?
cerebellar ataxia with isolated vitamin E deficiency
110
gene: mitochondrial recessive ataxia syndrome
POLG
nuclear-encoded mitochondrial DNA polymerase gamma
(POLG1 is also the gene in Alpers-Huttenlocher)
111
what 2 tissue types does mitochondrial recessive ataxia syndrome affect?
peripheral nerve
skeletal muscle
(mtDNA depletion)
112
what are the 2 clinical mitochondrial recessive ataxia syndromes?
1. SpinoCerebellar Ataxia with Epilepsy (SCAE)
2. Sensory Ataxia linked to peripheral Neuropathy with Dysarthria and Ophthalmoplegia (SANDO)
113
what's the main diff btwn SCAE and SANDO
SCAE is in kids
SANDO is in adults
(cause I didn't like sandwiches as a kid)
114
Gene & mode of inheritance: ataxia telangiectasia
ATM (DNA breakage repair deficiency)
auto recessive
115
clinical features of ataxia telangiectasia (5)
1. Cerebellar ataxia
2. oculocutaneous telangiectasias
3. recurrent infxn (cell & humoral immunity)
4. increased risk of leukemia/lymphoma
5. increased sensitivity to ionizing radiation
116
gene: autosomal dominant cerebellar ataxia (SCA)
ataxin CAG repeats
(same thing as Huntington's)
the repeats are part of an exon
117
how can you use IHC to identify DRPLA?
ubiquitin or an antibody to expanded polyglutamine stretches
neurons in pons, dentate, Luys/subthalamic, and cortex will have intranuclear or cytoplasmic (skein-like) inclusions (i guess it's atrophin?)
118
how many repeats of the triplet repeat expansion manifest in DRPLA?
CAG triplet repeat expansion in ATN1
normal: 7-23
dz: 49-75
119
clinical DRPLA
1. ataxia
2. chorea
3. epilepsy (myoclonic)
4. dementia (AD)
120
gene: fragile-X tremor/ataxia syndrome
CGG trinucleotide repeat in FMR1 on X resulting in LoF of FMRP
(> methylation > silenced)
rarely can be FMRP del or point mutation
121
how many repeats of the triplet repeat expansion manifest in fragile-x tremor/ataxia syndrome?
normal: <45
late: 55-200 (most common)
childhood: >200
122
inheritance: fragile-X tremor/ataxia syndrome
X-linked dominant
women are less commonly affected, but may instead get fragile-x assoc primary ovarian insuff (FXPOI) bc they have the other X to compensate
123
clinical features (big 2) of fragile-x tremor/ataxia syndrome
1. intention tremor
2. ataxia (gait)
and like, all the fragile X facies
124
radiological hallmark of fragile x tremor/ataxia syndrome
increased T2 FLAIR in middle cerebellar peduncles (or in women, splenium of CC)
125
1 gross and 2 histo findings in fragile x tremor/ataxia syndrome
Gross: focal white matter lesions (tiny)
Histo: ubiquitinated intranuclear inclusion bodies (cortex, BG, thalamus, midbrain, medulla) & XS iron
126
what's the sporadic ataxia syndrome that is a dx of exclusion and is stupid?
sporadic adult-onset ataxia of unknown etiology aka midline cerebellar syndrome
no inclusions :)
thanks, i hate it
127
gene in neuroacanthocytosis
there's 2
VPS13A (choreo-acanthocytosis)
XK (X-linked, Kell)
128
what's the clinical of McLeod neuroacanthocytosis?
Kell variant Kx
Striatal degeneration
Myopathy
129
inheritance of McLeod neuroacanthocytosis?
X-linked
130
gene in primary torsion dystonia
torsin A
131
gene in X-linked dystonia-parkinsonism/Lubag
TAF1 (X)
132
gene in segawa syndrome
GTP cyclohydrolase I
133
inheritance of primary torsion dystonia & population
auto dom
Ashkenazi
134
population of x-linked dystonia-parkinsonism
filipino
135
inheritance of segawa syndrome
auto dom
136
population & presentation for pure thalamic atrophy
pop: young adults
behavioral disturb, memory issues, akinetic rigidity/ataxia/chorea
137
chordoid meningioma is a/w what disease?
Castleman disease
138
4R tauopathies
PSP
CBD
GGT
AGD
FTLD-tau-4R
mostly 3 letter acronyms
139
3R tauopathies
FTLD
Pick
all 4 letter
140
CADASIL gene
NOTCH3 (chr 19)
Cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy
141
CARASIL gene
HTRA1 (chr 10)
Cerebral autosomal-recessive arteriopathy with subcortical infarcts and leukoencephalopathy
142
CARASIL clinical
backache
baldness
brain attack (stepwise cognitive decline d/t infarcts)
143
oculopharyngeal muscular dystrophy genetic issue
GCG trinucleotide repeat in PABP1 gene
AUTO DOM!!!
144
Hereditary sensory neuropathy type 1
Part of sphingolipid metabolism
Storage material
Defect
Gene
Synthesis
None
Serine palmitoyl CoA Transferase 1
SPTLC1
145
Hereditary sensory and autonomic neuropathy type 1
Part of sphingolipid metabolism
Storage material
Defect
Gene
Synthesis
None
Serine palmitoyl-CoA transferase 2
SPTCL2
146
Spastic paraplegia
Part of sphingolipid metabolism
Storage material
Defect
Gene
Synthesis
None
Fatty acid 2 hydroxylase
FA2H
147
Myoclonic epilepsy
Part of sphingolipid metabolism
Storage material
Defect
Gene
Synthesis
None
Ceramide synthase 1
CERS1
148
Salt & pepper developmental regression syndrome
Part of sphingolipid metabolism
Storage material
Defect
Gene
Synthesis
None
GM3 synthase
ST3GALS
149
Spastic paraplegia but later in the pathway
Part of sphingolipid metabolism
Storage material
Defect
Gene
Synthesis
None
GM2 synthase
B4GALNT1
150
GM1 gangliosidosis
Part of sphingolipid metabolism
Storage material
Defect
Gene
Catabolism
GM1 ganglioside
Beta-galactosidase
GLB1
151
GM2 gangliosidosis/Tay-Sachs
Part of sphingolipid metabolism
Storage material
Defect
Gene
Catabolism
GM2 ganglioside
Beta-hexosaminidase subunit alpha
HEXA
152
GM2 gangliosidosis/Sandhoff
Part of sphingolipid metabolism
Storage material
Defect
Gene
Catabolism
GM2 ganglioside
Beta-hexosaminidase subunit beta
HEXB
153
Sialidosis
Part of sphingolipid metabolism
Storage material
Defect
Gene
Catabolism
Sialic acid storage material (lol)
N-acetyl-alpha-neuraminidase-1
NEU1
154
Fabry
Part of sphingolipid metabolism
Storage material
Defect
Gene
Catabolism
Gb3, LysoGb3
Alpha-galactosidase A
GLA
155
Gaucher
Part of sphingolipid metabolism
Storage material
Defect
Gene
Catabolism
Glucosylceramide + glucosylsphingosine
Glucosylceramidase
GBA1
156
Metachromatic leukodystrophy
Part of sphingolipid metabolism
Storage material
Defect
Gene
Catabolism
Sulfatide
Arylsulfatase A
ARSA
157
Krabbe/globoid cell leukodystrophy
Part of sphingolipid metabolism
Storage material
Defect
Gene
Catabolism
Galactosylceramide + galactosylsphingosine
Galactosylceramidase
GALC
158
Niemann-Pick (type A and/or B)
Part of sphingolipid metabolism
Storage material
Defect
Gene
Catabolism
Sphingomyelin
Sphingomyelinase
SMPD1
159
Farber disease
Part of sphingolipid metabolism
Storage material
Defect
Gene
Catabolism
Ceramide
Acid ceramidase
ASAH
160
Leigh syndrome gene
MT-ATP6
161
NF1 vs NF2
which one has neurofibromas
NF1
162
NF1 gene
NF1 on chr 17
163
2 main types of neoplasms in NF1
dermal neurofibromas (acquired)
plexiform neurofibromas (congenital: week 2 of gestation)
164
what are the eye manifestations of NF1
1. optic glioma
2. Lisch nodules (melanocytic iris hamartomas)
3. choroidal plaques (dendritic melanocytes)
165
what disease shares cutaneous manifestations with NF1 and complicates diagnosis sometimes?
Legius syndrome (SPRED1)
166
NF1 vs NF2
which one has schwannomas
NF2
167
NF1 vs NF2
which one has meningiomas
NF2
168
NF1 vs NF2
which one has ependymomas
NF2
169
NF1 vs NF2
which one has gliomas
NF1
170
what are the eye manifestations of NF2
1. posterior cataract
2. retinal hamartomas
3. epiretinal membrane
171
what is the PATHOGNOMONIC histo finding for NF2?
glial micro hamartomas
172
what finding can be seen in BOTH NF1 and NF2?
cafe au lait spots
(ALSO constitutional mismatch repair defect)
173
NF1 vs NF2
which one has cutaneous plexiform schwannomas
NF2
(NOT plexiform neurofibromas! those are in NF1!)
174
what is the clinical feature that can be helpful in differentiating NF2 from schwannomatosis?
schwannomatosis is a/w PAIN
175
genes a/w schwannomatosis
1. SMARCB1 (22q)
2. LZTR1 (22q)
3. Loss of heterozygosity of 22q (mutation unknown)
176
what's the 4 hit hypothesis?
schwannomatosis
1. germline SCHW gene mutation
2. LoH of 22q which results in #3
3. Loss of 2nd SCHW allele + loss of NF2
4. somatic mutation of remaining 2nd NF2 allele
***NOT an NF2 germline mutation! bc that's NF2!***
177
which collision/combo tumor is NOT a/w NF?
schwannoma/perineurioma
178
if you see a choroid plexus carcinoma, what syndrome should you think of?
Li Fraumeni
179
If you see childhood adrenocortical carcinoma, what syndrome should you think of?
Li Fraumeni
180
if you see medulloblastoma, SHH-activated & TP53-mut, what syndrome should you think of?
Li Fraumeni
181
if you see a brain tumor with a "bunch of grapes" appearance on radiology, what should you think of?
desmoplastic nodular medulloblastoma
182
SHH-activated medulloblastoma has what IHC positivity?
GAB1+
YAP1+
no nuclear beta-catenin
183
WNT-activated medulloblastoma has what IHC positivity?
nuclear beta-catenin+
GAB1-
YAP1+
184
non-wnt/non-shh medulloblastoma has what IHC positivity?
GAB1-
YAP1-
no nuclear beta-catenin
185
what type of medulloblastoma is a/w Gorlin/nevoid BCC syndrome?
"extensively nodular"/desmoplastic
SHH-activated & TP53-wt
186
what is the gene a/w medullo in Gorlin?
germline SUFU mutation
PTCH1 is more common overall, but SUFU more frequently gets medullo
187
what is the tumor syndrome a/w ATRT?
rhabdoid tumor predisposition syndrome (RTPS)
188
what is the IHC surrogate for RTPS1?
INI1
(SMARCB1)
189
What is the IHC surrogate for RTPS2?
BRG1
(SMARCA4)
190
what is the gene a/w Carney complex?
PRKAR1A
191
what syndromes is primary intracranial sarcoma a/w?
DICER1 syndrome
NF1
192
in what ways does DICER1-associated sarcoma mimic astrocytic neoplasms?
1. ATRX loss
2. p53 overexpression
3. H3K27me3 loss
4. focal infiltration
193
what is the MOST COMMON CNS manifestation of DICER1 syndrome?
metastatic pleuropulmonary blastoma
194
if you see a high-grade giant cell neoplasm in a kid, what stains should you order?
(besides regular astrocytoma stains)
mismatch repair proteins
PMS2/MLH1/MSH2/MSH6
195
what stain should you use if you think something is choroid plexus-related?
transthyretin
196
if your ddx is ANNUBP vs MPNST and you order an H3K27me3 stain, what should you call it if H3K27me3 is LOST?
MPNST
197
what is the familial genetic association w/ clear cell meningiomas?
SMARCE1 (homozygous inactivation)
so IHC will be NEG if SMARCE1 is inactivated
198
what is the typical presentation of the familial syndrome a/w clear cell meningiomas?
multiple spinal meningiomas (SMARCE1)
199
200
What are these
Büngner bands
Schwann cells without an axon
