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Muscle: Chronic Partial Denervation

Muscle   Capillaries   Fibers     Atrophy       Ultrastructure     Grouped atrophy     Nuclei       Internal       Pyknotic clumps     Necrosis       Regeneration, Clustered     Split     Types       Grouped       Patterns   Chronic Features     Moderate     Severe: Pseudomyopathic     Endstage Nerve   Regenerating axon clusters

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Groups (Size): Hypertrophic & Atrophic Muscle fibers

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H & E stain

Large Muscle Fibers
  Distribution: Clustered
  Size: Often hypertrophied
Small Muscle Fibers
  Shape: Polygonal, Rounded or Nuclear Clumps
Endomysial connective tissue in regions of grouped muscle fiber atrophy
  Distribution: Clustered or Grouped
  Normal (Above) or Increased (Below)

H & E stain

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Clusters, or groups, of large, intermediate & small sized muscle fibers

H & E stain

Grouped atrophy: Increased space between tiny muscle fibers

Gomori trichrome stain

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VvG stain

Internal architecture: Hypertrophic muscle fibers have Irregular clear centers or Targets

NADH stain

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Chronic Partial Denervation: Fiber type abnormalities
  Large fibers are commonly a single type: May be Type 1, 2, or Abnormal

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ATPase pH 9.4 stain

Large muscle fibers: All type 1

ATPase pH 4.3 stain

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Large muscle fibers: All type 2

ATPase pH 4.3 stain

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ATPase pH 4.6 stain

Large, Type 2-like muscle fibers: Abnormal fiber types
  Type 2 with varied degrees of intermediate staining on ATPase pH 4.6 stain (Above)
  Incomplete fiber type switch: Type 1 properties on COX stain (Below)

COX stain

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Atrophic Muscle fibers

H&E stain

H&E stain

Gomori trichrome stain

Congo Red stain

Esterase stain

NADH stain

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PYKNOTIC NUCLEAR CLUMPS

• Definition: End product of severe muscle fiber atrophy
• Nosology
  • Nuclear clumps
  • Pyknotic
    • Term used to denote dark color
    • Scientific definition (karyopyknosis with chromatin condensation): Not applicable
  • Syncytial knots
• Clumps of myonuclei
  • Larger (More nuclei) in muscles with previous fiber hypertrophy
  • Lipofuscin: May also be present; In Older patients
• The remainder of the myofiber largely disappears
  • Contractile apparatus
  • Cytoplasm
• Pyknotic nuclear clump distributions
  • Singular: May occur alone
  • Clusters: Part of regions of grouped muscle fiber atrophy
• Disease associations
  • Denervation without reinnervation
  • Myasthenia gravis: Late stage, untreated
  • Myopathies: Myotonic dystrophy 2; IBM3
• Histochemical staining
  • Nuclei: Basophilic on H & E
  • Muscle fiber: Dark on NADH & Esterase
• Ultrastructure: 1; 2

Also see

• Fiber type grouping
• Grouped atrophy: Large
• Ongoing denervation
• Regenerating axon clusters

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Pyknotic nuclear clumps: Morphology

H & E stain

H & E stain

H&E stain

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Congo red stain

Congo red stain

Pyknotic nuclear clumps: High magnification
  Clusters of myonuclei with no, Lipofuscin or little, visible cytoplasm
  May also contain clustered lipofuscin

H&E stain

Congo red stain

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H&E stain

Pyknotic nuclear clumps: Grouped
  Late outcome of grouped muscle fiber atrophy

H&E stain

Congo red stain

Pyknotic nuclear clumps: Grouped
  Nuclear clusters: Some are associated with lipofuscin

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Pyknotic nuclear clumps: Stain dark with esterase & NADH

NADH stain

Esterase stain

Esterase stain

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Pyknotic nuclear clumps: With lipofuscin

Acid phosphatase stain

Acid phosphatase stain

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Pyknotic nuclear clumps: Ultrastructure

From: R Schmidt

From: R Schmidt

Also see: PNC

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Chronic Partial Denervation: Pseudo-Myopathic Changes

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H& E stain

"Myopathic"-like changes

• Endomysial connective tissue: Increased
• Internal nuclei: One or several in muscle fibers
• Muscle fiber sizes
  • General: Widely varied
  • Hypertrophic muscle fibers: Common
  • Small fibers
    • May be round or angular
    • Pyknotic nuclear clumps: Common
  • Grouped atrophy of muscle fibers
    • Atrophic groups: Less well demarcated than in ongoing denervation
    • Endomysial connective tissue: More prominent in these regions
• Perimysium: Replaced by fat

H& E stain

H&E stain

Gomori Trichrome stain

Gomori Trichrome stain

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Large Muscle Fibers: Hypertrophy & Abnormal Internal Architecture

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Split (Partially fused) Muscle Fibers (White arrows) ¹

• Common features
  • Very large (Hypertrophic)
  • Have internal nuclei
• Probably result from: Partial fusion of regenerating fibers
• Associated with: Skeletal muscle fiber branching

H&E stain NADH stain

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Internal Nuclei

H&E stain

Internal Nuclei
  Several myonuclei are scattered internally in cytoplasm of some muscle fibers
  Normal muscle fibers have all myonuclei in subsarcolemmal regions

H&E stain

H&E stain

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Necrotic large muscle fibers → Clustered regeneration

• Hypertrophied muscle fibers may become necrotic (left)
• Several different muscle fibers regenerate in its place & cluster within old basal lamina of large fiber

Muscle Fiber Necrosis H&E stain   Large necrotic muscle fiber     Invaded by many histiocytes

Clustered Regeneration (Arrows) H&E stain

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Clustered Regeneration

H&E stain

Hypertrophic muscle fibers: Undergo necrosis & are replaced by multiple smaller, partially-fused fibers
  Areas of grouped atrophy are also present in this image

NADH stain

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Hypertrophic Muscle Fibers: Abnormal Internal Architecture

VvG stain

Gomori Trichrome stain

VvG stain

Gomori Trichrome stain

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Chronic Denervation: Capillary Pathology

UEA I stain

Capillaries: Chronic Partial Denervation
  Abnormal orientation: Some become circumferential around muscle fibers
  Increased numbers of capillaries adjacent to each muscle fiber

UEA I stain

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References
1. Skelet Muscle 2023;13:13

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8/14/2023