Neuromuscular

MYOPATHIES WITH MYOSIN LOSS

Clinical
Histochemistry patterns: Myosin loss in
  Small muscle fibers
    Myosin loss in fibers
    Abnormal myonuclei
  Intermediate- & Larger-sized muscle fibers
  Severe muscle fiber atrophy
  Cushing disease
Ultrastructure


Myosin loss: Small muscle fiber pathology

Small muscle fibers
  Shape: Angular
  Cytoplasm: Basophiic
  Nuclei: Large

H&E stain

Myosin loss ("Critical illness") myopathy
  Intramuscular nerves
    Normal numbers of myelinated axons
  Muscle fibers
    Small
    Angular
    Cytoplasm: Loss of internal architecture

VvG stain


Gomori trichrome stain
Small, angular muscle fibers: Dark stained on Gomori trichrome & NADH

Gomori trichrome stain

NADH stain
Small muscle fibers: Aggregated internal architecture

NADH stain

Myosin loss, Moderately Severe: Occurs in many small muscle fibers
  Many small muscle fibers have staining that is less than in Type I fibers

ATPase pH 9.4 stain
Myosin loss, Moderately Severe: Occurs in many small muscle fibers
  Many small muscle fibers have staining that is less than in Type I fibers

ATPase pH 9.4 stain

 
Muscle fibers with myosin loss:
  Less staining than type I muscle fibers on ATPase pH 9.4 stain.
  Varying degrees of severity of loss among fibers

ATPase pH 9.4 stain

Myosin Loss: Varied degrees of severity in different muscles

ATPase pH 9.4 stain
Many small muscle fibers with myosin loss

ATPase pH 9.4 stain
Few intermediate-sized fibers with myosin loss

Comparison of ATPase pH 9.4 (Left) & 4.3 (Right) in serial sections
Type I fibers (1): Darker staining at pH 4.3 than 9.4
Type II fibers (2): Darker staining at pH 9.4 than 4.3
Myosin loss fibers (0 or arrows): No staining at both pH 9.4 and pH 4.3

ATPase pH 9.4 stain

ATPase pH 4.3 stain

Autophagy marker (LC3): Increased in cytoplasm of many small muscle fibers

LC3 stain



H&E stain
Nuclei in small muscle fibers
  Large
  Irregular shapes

H&E stain


H&E stain
Nuclei in small muscle fibers
  Large
  Irregular shapes

Congo red stain

Myosin loss: In intermediate- and large-sized muscle fibers



ATPase pH 9.4 stain

ATPase pH 9.4 stain
Myosin loss may be diffuse, or patchy, within a muscle fiber cross-section.

ATPase pH 4.3 stain

Gomori trichrome stain

Gomori trichrome stain
Myosin loss: Patchy reduction of staining in scattered muscle fibers

NADH stain

H&E stain

Myosin loss: LC3 expression in scattered muscle fibers

LC3 stain

LC3 stain
LC3 may be peresnt in regions, or more diffusely, in muscle fiber cytoplasm

LC3 stain

Myosin loss: Severe with diffuse muscle fiber atrophy


H&E stain
Muscle fibers:
  Severe atrophy
  Large nuclei in small fibers

VvG stain

Gomori trichrome stain
Muscle fibers:
  Severe atrophy
  Large nuclei in small fibers


ATPase pH 9.4 stain
Myosin loss: May occur in large or small muscle fibers

ATPase pH 4.3 stain
Myosin loss: No staining in muscle fibers; Retained staining in an intermediate-sized vessel

Myosin Loss: Anti-myosin antibody



Reduced myosin in many small
  muscle fibers

H & E stain

 

 

Myosin ATPase, pH 9.4 stain
A focal pattern of myosin loss may also occur in muscle fibers.
  Focal regions of myosin loss in type I and II muscle fibers.
  These regions appear basophilic on H & E stain.
  Myosin loss may occur in large as well as small fibers

Myosin loss: Ultrastructure


From: R Schmidt
Thick filament loss: Relative preservation of thin filaments & Z-lines

Thick filament loss: Can involve some regions within muscle fibers but not others


Myosin Loss: Cushings disease


Fiber size: Varied
Nuclei: Large; Irregular shapes

Fiber cytoplasm: Irregular, mildly basophilic regions


Muscle fibers
  Shape: Varied shape; Some are small and angular
  Internal architecture: Irregular


Small, angular muscle fibers: Clustered internal architecture



Myosin loss
  Small angular fibers: Lost in whole fiber crossection
  Larger fibers: Patchy loss
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1/16/2017