Muscles Flashcards
If you see perifascicular necrosis, what should you pick?
antisynthetase syndrome myositis
What feature is distinctive between antisynthetase syndrome myositis and dermatomyositis?
intranuclear actin aggregates
Pompe/type II glycogenosis hallmark
vacuolar degeneration in skeletal muscle fibers (worse in infants)
general concept behind dystroglycanopathies
Not actually a mutation in the DAG gene
usually abnormal glycosylation of alpha-dystroglycan
what gene has “the common mutation” in dystroglycanopathy?
FKRP1
what’s the stain for glycosylated alpha dystroglycan?
IIH6
what cell type has glycosylated alpha dystroglycan in peripheral nerve?
Schwann cells
(they think it’s the entry point for mycobacterium leprae)
where in the cell does dysferlin live?
sarcolemma (plasma membrane)
what is the function of dysferlin?
membrane repair
what are the 2 clinical syndromes/presentations for dysferlinopathies?
- limb-girdle-esque (LGMD 2B/R2)
- Miyoshi myopathy (distal)
Constellation of histopath findings for dysferlinopathy?
- total loss of Hamlet staining
- complement deposition (C5b-9)
- amyloid
gene & inheritance for dysferlinopathy?
DYSF gene
auto recessive
what is the antibody for dysferlin?
Hamlet
will be TOTALLY NEGATIVE if dz present (nonspecific sarcoplasmic staining can happen, not diagnostic of dz)
(because LGMD 2B [or not 2B])
what is the inflammatory component of dysferlinopathies?
Complement deposition (C5b-9) in myofibers
NOT increased inflammatory cells
You can see 2 of the dysferlinopathy histo findings in other entities. what are they?
- complement: ANO5 and LMNA
- amyloid: ANO5
ANO5 = anoctaminopathy
LMNA = laminopathy
if you have a pt presenting with chronic progressive external ophthalmoplegia (CPEO), what should your FIRST thought be?
mitochondrial myopathy
what step in the mitochondrial respiratory chain does the SDH stain rely on, and what does that tell you?
activity of complex II
entirely encoded by nuclear genome
so it only tells you about mitochondria quantity, NOT quality/fxn!
what step in the mitochondrial respiratory chain does COX rely on?
complex IV
some subunits are encoded by mtDNA > loss of staining
name 2 findings you can have on EM in mitochondrial myopathies
paracrystalline/parking lot inclusions
hyperbranching mitochondria
what is THE disorder of lysosomal glycogen degradation?
Pompe disease
aka
acid alpha-glucosidase (acid maltase) deficiency
aka
GSD II
main diff btwn infantile & late onset Pompe dz
infantile: <1% enzyme activity
late: up to 30% enzyme activity
what is the main difference in clinical presentation between Pompe and the rest of the glycogen storage myopathies?
Pompe presents with weakness
Others present with exercise intolerance
most common non-Pompe glycogen storage myopathy
myophosphorylase deficiency
aka
GSD V
aka
McArdle dz
what is the classic histo finding for Duchenne muscular dystrophy?
revertant fiber
most fibers will be negative for dystrophin, then there will be one that has expression (it’s reverted)
what is the issue with immunostaining for Becker muscular dystrophy?
the stains for dystrophin (DYS1, 2, 3) do not include exons 46-50, and that is where MOST mutations causing Becker are
how do you dx McArdle’s/myophosphorylase deficiency with IHC?
Loss of phosphorylase staining (duh)
what is the structure of autophagosomes?
double membrane vacuoles (induction membrane)
these are delivered to lysosomes for degradation
what are the 2 components of autophagic vacuole formation that you can stain for?
LC3-PE (LC3-II) > bound to membrane on inside
autophagy receptor (p62) > links cargo to LC3-PE (it’s an inductor)
how does the autophagosome fuse with the lysosome?
moves along microtubule (from + to - end) to get to the center of the cell
True or false: the autophagosome requires an alkaline pH inside of it to degrade things
FALSE
it requires an ACIDIC pH
(chloroquine raises the pH and impairs digestion in a lysosome)
how do the multisystem proteinopathies manifest clinically?
- IBM
- ALS/FTD
- Paget disease of bone
what are the protein aggregates in multisystem proteinopathies (MSP) positive for?
TDP-43
p62
ubiquitin
(cause it manifests as an IBM)
What gene should you think of if you are talking about multisystem proteinopathy (MSP)?
VCP
myofibrillar myopathies & their clinical issues result from disintegration of what?
sarcomeric Z-disc and myofibrils > abnoraml ectopic accumulation of their components (desmin, alpha B-crystallin, dystrophin, myotilin)
what two structures NORMALLY have nemaline rods?
myotendinous jxn
extraocular muscle
MC clinical thing in nemaline myopathy
respiratory muscle involvement
what (VERY general) pathology has myonecrosis & regeneration with prominent satellite cells?
dystrophies
what stains do you use for regenerating fibers?
embryonic myosin heavy chain
N-CAM/CD56
besides total loss of dystrophin (DYS1, 2, 3) staining, what 2 other stains can help diagnose Duchenne?
Utrophin > upregulated, not specific
nNOS > loss (this binds to fxnal dystrophin)
what is the mechanism of colchicine myopathy?
colchicine prevents microtubule polymerization, which blocks autophagosome maturation bc the autophagosome can’t get to its correct place via the microtubule tracks
diagnostic options for this EM finding
curvilinear bodies
either hydroxy/chloroquine-induced or neuronal ceroid lipofuscinosis
what is this
z-band streaming
can see in colchicine/vincristine toxicity, some myofibrillar myopathies, some nemaline myopathies
