SQSTM1: Distal Myopathy

SQSTM1: Distal Myopathy - Digenic - Welander Phenotype

Mutations: SQSTM1 c.1165 G>A; TIA1 N357S

Myopathy
Internal Architecture
Vacuoles
Aggregates
Other

H&E stain

Chronic myopathy
Fiber sizes
Varied from Small to Hypertrophic
Small fibers: clustered
Pyknotic nuclear clumps
Perimysium & Endomysium: Replaced by fat
No necrosis or regeneration
Vacuoles: In some smaller muscle fibers

Chronic myopathy, Late stage
Perimysium: Wide; Replaced by fat
No necrosis or regeneration

H&E stain

H&E stain

Small muscle fibers
May occur in clusters or groups
Some have
Basophilic cytoplasm & large nuclei
Vacuoles
Endomysial connective tissue
Increased between muscle fibers

H&E stain

Internal Architecture

NADH stain

Small muscle fibers
May occur in clusters or groups
Irregular internal architecture or Dark staining
Endomysial connective tissue
Increased between muscle fibers

VvG stain

Internal architecture
Irregular esterase-stained cytoplasm in scattered muscle fibers

Esterase stain

Vacuoles

VvG stain

Vacuoles: Black-stained rim on VvG

VvG stain

VvG stain

Gomori trichrome stain

Gomori trichrome stain

Vacuoles: Red-stained rim on Gomori trichrome stain

Gomori trichrome stain

Gomori trichrome stain

Vacuoles
Red staining material (Amyloid-like; Arrow) around edge of vacuoles

Congo red stain

Congo red stain

Vacuoles & Aggregates

Congo red stain

Aggregate: Cytoplasmic (Arrows)

Congo red stain

Nuclei: Aggregates & Vacuoles

Congo red stain

Aggregates: Intranuclear (Arrows)
Congo red: Red-Green, birefringent (Above)
Rhodamine positive (Below)
Cytoplasmic
Rhodamine-positive irregular aggregate surrounds large nucleus on left side of fiber