PYKNOTIC NUCLEAR CLUMPS: Denervation of muscle fibers without reinnervation

• Clumps of myonuclei
  • End product of denervation atrophy
  • Larger in muscles with fiber hypertrophy
• The remainder of the myofiber largely disappears
  • Contractile apparatus
  • Cytoplasm
• Pyknotic nuclear clump distribution
  • May occur alone (Left)
  • Part of a region of grouped muscle fiber atrophy (Center)
• Pyknotic nuclear clumps often stain for esterase (Right)
• Disease associations
  • Denervation without reinnervation
  • Late stage muscle in myasthenia gravis
  • Myotonic dystrophy 2

TARGET FIBERS

• Often seen with acute denervation & reinnervation.
• Histochemistry
  • Best visualized on NADH stain
  • May have clear, dark, or loculated centers.
  • Central clear regions with mitochondrial stains
  • Cytoplasmic bodies or Rods may occur within, or around, targets
• Especially common in: Gastrocnemius muscle
• Molecular components
  • Filamin C
  • hsp 27
  • aB-crystallin
  • Desmin
  • Caveolin

GROUPED ATROPHY OF MUSCLE FIBERS

• Small angular muscle fibers in clusters:
  • Often basophilic on H&E stain (Top left)
  • Stain darkly with NADH (Top right) and esterase (Bottom right).
  • May also stain with desmin, spectrin & Leu-19 (myoblast & satellite cell related antigen)
• Atrophic groups are small and contain angular fibers early in denervation.
• Small rounded fibers in groups may be seen with chronic denervation.
• Denervation in ALS (middle & right): Grouped atrophy with little type grouping
  • Numerous esterase positive small angular fibers
  • Numerous small regions of grouped atrophy
  • Both type I & type II atrophic fibers occur in a single group
• Denervation in SMA
  • Larger atrophic groups
  • Small fibers are often rounded.