REMM

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: Pathology predominantly in Small muscle fibers

H&E stain

Small muscle fibers
Shape: Angular
Cytoplasm: Basophiic
Nuclei: Large & Irregular shaped

H&E stain

H&E stain

Small muscle fibers
Shape: Angular
Cytoplasm: Basophiic
Nuclei: Large & Irregular shaped

Congo red 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

NADH stain

Small muscle fibers: Internal architecture with clumped, or reduced, sarcoplasmic reticulum

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

Myosin Loss: Myonuclei

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: Variant pantology

In intermediate- and large-sized muscle fibers
Varied degrees of loss in individual 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 changes 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