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DYSTROPHINOPATHIES: Duchenne

Early age
  Mild
  Myopathic grouping
  Regeneration
  Severe
Later age
Dystrophin
Revertants

General description

Muscle biopsy: General features


DMD
  Muscle fibers
    Size: Varied
    Shape: Small fibers round or polygonal
    Internal nuclei
    Hypercontracted
    Necrosis
  Muscle fiber replacement
    Endomysial connective tissue: Increased
    Fat replacement

H&E stain

DMD
  Endomysial connective tissue increased

VvG stain


NADH stain
DMD: Immature muscle fibers
  Coarse internal architecture on NADH (Above)
  Intermediate staining on ATPase pH 4.3 (Below)

ATPase pH 4.3 stain

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



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

Acid phosphatase stain




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: Many

Myopathic group, Early DMD Alkaline phosphatase + immature muscle fibers Many 2C muscle fibers
Staining properties of immature muscle fibers includes:
  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: Severe at age 2 years


H&E stain
DMD
  Endomysial connective tissue: Increased
  Muscle fibers
    Necrosis & Regeneration
    Size: Varied

H&E stain
 
H&E stain
DMD
  Endomysial connective tissue: Increased
  Muscle fibers
    Necrosis & Regeneration
    Size: Varied


Gomori trichrome stain

Gomori trichrome stain

VvG stain

DMD
  Many intermediate-stained muscle fibers

ATPase pH 4.3 stain

Duchenne Muscular Dystrophy: Later Pathology (10 years)



H&E stain
DMD: Later pathology
  Fiber size: Varied
  Endomysial connective tissue: Increased
  Fat replacement of muscle: Prominent

H&E stain

VvG stain


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

Muscle fiber internal architecture: Coarse

NADH stain


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

Sudan stain

DMD late: Few necrotic muscle fibers

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: 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.

DMD: Ring Fibers

H&E stain

Gomori trichrome stain

NADH stain

NADH stain

Go to Becker muscular dystrophy pathology
Return to Dystrophinopathies.
Return to Neuromuscular syndromes
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9/1/2017