Necrosis Patterns
Scattered Necrosis
  Necrosis & Rhabdomyolysis
    Early patterns
      Metabolic damage
      Sarcolemmal membrane damage
      Macrophage activation
      Fixed muscle, Paraffin sections
    Later features
      Phagocytosis & Regeneration
      HMGCR myopathy
      Macrophage activation
      SRP myopathy
    Phosphorylase deficiency
    Statin toxicity
Clustered or Regional Necrosis
    Regional Ischemic Immune
  Myopathic grouping

Necrosis: Types & Features
  Metabolic failure
  Membrane damage

Muscle fibers: Segmental Necrosis, Varied stages

General features 1

Cell & Metabolic
  Metabolic failure
  Membrane damage

Muscle Fiber Necrosis (Rhabdomyolysis episode): Morphology

Segmental necrosis: Scattered necrotic & hypercontracted muscle fibers

H & E Stain
Normal muscle fiber
Necrotic muscle fiber: Pale; Little phagocytosis
Necrotic muscle fiber: Phagocytosis by macrophages
Hypercontracted necrotic muscle fiber

Necrosis: Early; Metabolic failure
Pale muscle fibers with loss of cytoplasmic structures & staining

H&E stain
Necrotic muscle fibers: Pale; Little phagocytosis (Arrows)

Gomori trichrome stain

Necrotic muscle fiber, Early
  • Fiber is pale & enlarged.
  • Internal nuclei may reflect
    invasion by macrophages.

Necrotic muscle fibers: Internal architecture has lost NADH staining (Arrow)

NADH stain

Necrosis: Early; Membrane damage, Statin toxicity
Varied internal structure: Hypercontracted material & Palor in different areas of single fibers

H&E stain

Membrane damage at several regions of individual fibers: Associated with clear regions in cytoplasm

H&E stain

Membrane damage in a focal region of individual muscle fiber: Produces a "C"- or "Delta"-lesion

H&E stain

Necrotic muscle fibers: Phagocytosis (Arrows)

H&E stain
Necrotic muscle fibers: Phagocytosis (Arrows)

Gomori trichrome stain

NADH stain
Phagocytic cells within pale necrotic muscle fibers: Mild NADH staining

Acid phosphatase stain
Necrosis: Stages
  Early: Pale stained muscle fibers
  Later: Muscle fibers progressively replaced by acid phosphatase + cells

Esterase stain
Necrotic muscle fiber, Late
Muscle fiber is invaded and
  replaced by phagocytes.

MHC Class I stain
MHC Class I: Stains capillaries & cells phagocytsing muscle fibers; No staining of most muscle fibers

Alkaline phosphatase stain
Necrosis: Alkaline phosphatase stains around the rim of muscle fibers

Toluidine blue stain
Necrotic muscle fiber (Longitudinal section)
  Invaded by cells

Toluidine blue stain
Necrotic muscle fiber (Cross-section)
  Invaded by cells

Toluidine blue stain
Necrotic muscle fiber
  Invaded by cells

Toluidine blue stain
Cells in necrotic fiber

Toluidine blue stain
Non-necrotic, abnormal muscle fiber (Left): Dilated SR

Necrotic muscle fibers: Complement C5b-9 (MAC) deposition

Stain: C5b-9 components of complement (Membrane attack complex (MAC))
Necrosis: C5b-9 deposition diffusely within muscle fiber cytoplasm

Rhabdomyolysis: PAS stain is pale in small & large muscle fibers

Necrosis: Ongoing

Necrosis: Early stage
  Pale muscle fiber cytoplasm
  Lipid droplets
  Two other muscle fibers have large lipid droplets but are not pale & necrotic

H&E stain

H&E stain
Necrosis: Phagocytosis of varying degrees

H&E stain

H&E stain
Necrosis & Regeneration associated with eosinophils
  Unusual: Eosinophils may be a component of cells replacing necrotic muscle fibers
    Reported with LGMD 2A (Calpain-3 mutations)

H&E stain

Also see: Regional Ischemic Immune Myopathy

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1. Cell Death Differ 2016 Feb 12