Neuromuscular

DYSTROPHINOPATHIES: Becker 1

Patients
  < 10 years
    Myopathic grouping
  Young adult: Moderate severity
  Older adult: Late stage
Dystrophin staining patterns

Becker MD: 7 year old male

Muscle Fibers
  Sizes: Varied
  Internal nuclei: Few
  Myopathic groups
    Early: Clusters of muscle fibers in similar stages of necrosis or regeneration (Black arrow)
    Late: Focal regions with small muscle fibers & increased endomysial connective tissue (White arrow)
Endomysial Connective Tissue: Increased in some areas

H&E stain

Myopathic Grouping

  • Definition
    • Clusters of neighboring necrotic, regenerating, or immature muscle fibers all at similar pathologic stage
    • Probably caused by: Eccentric contraction involving muscle fibers with abnormal (fragile) sarcolemma
  • Most prominent
    • Becker MD: Patients aged < 12 years
    • Other LGMD: May be present with milder pathology & less endomysial connective tissue into later adulthood
    • hIBM
  • Stages
  • Differential diagnosis of causes
    • Dystrophinopathy: Duchenne MD; Becker MD
      • Most distinctive myopathic change in histochemistry of Becker's muscular dystrophy.
    • LGMD: 2A; 2B; 2D
Necrosis: Neighboring muscle fibers (Biopsy from child (< 10 years))

Gomori trichrome stain
ATPase pH 9.4 stain
Myopathic Groups

NADH stain
Esterase stain
Myopathic Groups: After muscle fiber necrosis

H & E stain
Esterase stain
Post-Phagocytosis (Biopsy from BMD child (< 10 years)
  Clusters of cells (esterase positive) replacing necrotic muscle fibers
  Cells may include: Histiocytes; Muscle fiber precursors


H & E stain

Gomori trichrome stain
Post-Phagocytosis (Biopsy from BMD child (< 10 years)
  Clusters of cells replacing group of neighboring necrotic muscle fibers
  Cells may include: Histiocytes; Muscle fiber precursors

ATPase pH 4.3 stain
Myopathic Groups: Clusters of Muscle Fibers all in same stage of Regeneration

H & E stain
Regeneration of muscle fibers in Myopthic groups
  Many small, immature muscle fibers with large nuclei

Gomori trichrome stain

H & E stain
H & E stain
NADH stain
Regenerating muscle fibers: Grouped (Biopsy from child (< 10 years))
  • Size: Small
  • Cytoplasm
    • Basophilic
    • NADH: Dark, irregularly stained
    • ATPase pH 4.3: Stains small muscle fibers
  • Nuclei: Large
  • Also see: Muscle fiber regeneration

Gomori trichrome stain
ATPase pH 4.3 stain

NADH stain

H&E stain
NADH stain
Regeneration: Grouped muscle fibers

ATPase pH 4.3 stain
Dys-2 (Dystrophin C-terminus) stain

Esterase stain 		Clusters of regenerated muscle fibers
  Fiber cytoplasm often has increased esterase staining


Esterase stain
Post-Regeneration
  • Fiber size: Moderately varied
  • Muscle fiber Cytoplasm: Some fibers with coarse stain on NADH
  • Internal nuclei: Occasional muscle fibers
  • Fiber types: Many 2C
    • Clustered
    • Varied frequencies in different fascicles
  • Endomysial connective tissue: Mildly increased in some areas

H&E stain
Gomori trichrome stain

ATPase pH 4.3 stain
NADH stain
Distribution of fiber types: Non-random
NADH stain: Mildly coarse structure of internal architecture

ATPase pH 4.3 stain
Becker Muscular Dystrophy: Biopsy from young adult male

H&E stain
H&E stain

Becker Muscular Dystrophy: Biopsy from adult male

H&E stain
H&E stain
Muscle fibers
  Sizes: Varied
  Hypercontracted: Scattered
Endomysial connective tissue
  Increased

H&E stain
H&E stain

VvG stain
Endomysial connective tissue: Increased
ATPase pH 4.3 stain
Many scattered 2C fibers

Sudan black stain
Endomysium & Perimysium replaced by fat
PAS stain
Normal glycogen

Becker Muscular Dystrophy: Dystrophin staining

Dystrophin gene: Large deletion
Normal control on left panels; Patient on right panels

Dys-3 stain
N-terminus: Staining is present but reduced
Dys-1 stain
Rod domain: Staining is present but reduced
Dys-2 stain
C-terminus: Staining is absent except on a revertant muscle fiber
Dystrophin gene: Leaky stop mutation
Normal control on left panels; Patient on right panels

Dys-3 stain
N-terminus: Staining is present but very reduced
Dys-1 stain
Rod domain: Staining is present but reduced
Dys-2 stain
C-terminus: Staining is present but very reduced
Dystrophin gene: Rod domain deletion

Normal                                                                 Becker MD 		Dystrophin: Sarcolemmal staining
  Rod region (d): Absent
  N- (b) & C-terminus (f): Reduced but Present
 Normal control on left; Becker MD patient on right
N-terminal region of dystrophin: (a & b; Dys-3 antibody)
Rod region of dystrophin (c & d; Dys-1 antibody)
C-terminal region of dystrophin (e & f; Dys-2 antibody)

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Return to Dystrophinopathies.
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References 1. Acta Neuropathol Commun 2022;10:48
2. J Cell Mol Med 2022;26:4678-4685
10/5/2022