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DYSTROPHINOPATHIES: Duchenne

Muscle biopsy: General features


Duchenne Muscular Dystrophy: Early Pathology



H & E stain
Muscle fiber size: Varied; Small fibers are rounded or polygonal; Occasional hypertrophic fiber
  Myopathic groups of small necrotic (Black arrow) & regenerating (White arrow) muscle fibers
Internal nuclei: Occasional
Endomysial connective tissue: Normal to mildly increased
Perimysium: Early replacement by fat

Myopathic grouping: Necrotic muscle fibers, clustered



Phagocytosis of muscle fibers by macrophages

Acid phosphatase + cells
 


Necrotic muscle fibers are pale on NADH stain

Myopathic grouping: Clusters of very small regenerating muscle fibers & histiocytic cells


H & E stain

ATPase, pH 4.3

NADH
Clusters of small cells
  Some stain for Acid phosphatase or NADH



Acid phosphatase

Acid phosphatase

Myopathic grouping: Intermediate-sized immature muscle fibers in clusters


H & E stain
Immature fibers are small & basophilic
 

ATPase, pH 4.3
Immature fibers are small & 2C
(Intermediate staining)

Alkaline phosphatase
Immature small fibers have
  cytoplasmic staining


NADH
Immature fibers have coarse cytoplasmic staining

NADH
 


VvG
Immature small fibers have coarse cytoplasmic staining

Immature muscle fibers: Numerous

Myopathic group, Early DMD Alkaline phosphatase + immature muscle fibers Many 2C muscle fibers
Staining properties of immature muscle fibers include:
  1. H & E (left): Basophilic fibers
  2. Alkaline phosphatase positive (center)
  3. 2C fibers: Intermediate staining on ATPase pH 4.3 (right)



Duchenne Muscular Dystrophy: Later Pathology


H&E stain
Endomysial connective tissue: Increased
Fiber size: Variable
Small fibers: Rounded
Large or hypercontracted muscle fibers: Scattered
Necrotic fibers (Arrow): Scattered

DMD: 5 yrs
H&E stain
DMD: 10 yrs

Endomysial connective tissue
  Increased between fibers

Muscle fiber size: Varied
Small & Large fibers: May be are either type (I = Dark; II = Light)
Many type IIC fibers: Smaller size; Intermediate stain

ATPase pH 4.3 stain

Replacement of Muscle fibers & Perimysial connective tissue by Fat (Dark black)

Sudan stain


Acid phosphatase stain
Acid phosphatase + cells
Endomysium: Small Scattered cells
Necrotic muscle fibers: Clusters of phagocytic cells

Acid phosphatase stain





Dystrophin staining

Normal
Normal dystrophin
Duchenne Muscular Dystrophy:
Absent dystrophin Absent dystrophin; 1 revertant
Normal dystrophin staining
around the rim of muscle fibers.
Absent dystrophin: Duchenne muscular dystrophy
Left: No staining around the rim of any muscle fibers
Right: No staining of most muscle fibers
  One "revertant" fiber with dystrophin staining.
  Revertant fibers reflect a somatic mutation allowing dystrophin expression

Normal: Dystrophin present near surface of muscle fibers

Dys1 stain
Duchenne MD: Dystrophin absent from surface of muscle fibers

Dys1 stain

Muscle from Duchenne MD male with large area of revertant muscle fibers

Muscle histology (Above): One fascicle has normal muscle fibers & connective tissue amid otherwise myopathic muscle
Dystrophin staining (Below): Muscle fibers in preserved fascicle are revertants with dystrophin present around their rim
    Some revertant muscle fibers are present in myopathic regions as well.

Western blot of dystrophin from dystrophinopathies

     
      from Novocastra

Lane 1: Becker dystrophy; Dystrophin has reduced abundance but normal size.
Lane 2: Becker dystrophy; Dystrophin has reduced size and abundance.
Lane 3: Normal; Dystrophin has normal size and amount.
Lane 4: Duchenne dystrophy; Almost no protein is present.
Lane 5: Duchenne outlier; Dystrophin has severely reduced abundance.



Go to Becker muscular dystrophy pathology
Return to Dystrophinopathies.
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8/13/2013