Neuromuscular

DYSTROPHINOPATHIES: Becker 1

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

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

Myopathic Grouping


Gomori trichrome stain
Necrosis: Neighboring muscle fibers (Biopsy from child (7 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 Antibodies
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)

Becker MD (Exon 45 to 47 Deletion): NMJ Pathology


RNS from: Robert Bucelli
Repetitive Nerve Stimulation
  Decrement: Ramp-like
NMJ features
  Multi-segmented
  May be small (Below)

Esterase stain
Go to Duchenne muscular dystrophy pathology
Return to Dystrophinopathies.
Return to Neuromuscular syndromes
Return to Neuromuscular home page

References
1. Acta Neuropathol Commun 2022;10:48
2. J Cell Mol Med 2022;26:4678-4685
3. Brain Research 1999;839:298–304, Neurosci Lett 2020;737:135304
12/2/2023