General features
  Necrosis & Rhabdomyolysis
    Early Features
      Metabolic damage
      Sarcolemmal membrane damage
      Macrophage activation
      Fixed muscle, Paraffin sections
    Later features
      Phagocytosis & Regeneration
      Myofiber collapse
      HMGCR myopathy
      Macrophage activation
      SRP myopathy
    Phosphorylase deficiency
    Statin toxicity
      Immune (Vascular)
        Regional Ischemic Immune
      Hereditary (Stretch-induced)
        Myopathic grouping
    Perifascicular: IMPP
Necrosis: Types & Features
  Metabolic failure
  Membrane damage

Segmental Necrosis of Muscle fibers: Varied stages

Necrosis: General features & Stages 1

Cell & Metabolic
  Metabolic failure
  Membrane damage

Myofiber Necrosis
  Early stage
    Muscle Fiber cytoplasm: Pale
    Myonuclei: Lose staining

Myofiber Necrosis
  Sarcolemmal Membrane
  Early stage
    Muscle Fiber Cytoplasm
      "C" or Δ Lesion
      Regional Hypercontraction

Myofiber Necrosis
  Later stage
    Muscle Fiber:
      Replaced by macrophages.

Myofiber Necrosis
  Very Late stage
    Muscle Fiber: Collapse
    Macrophages have migrated away

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.
Necrosis: Early; "Metabolic" pattern
  Muscle fiber cytoplasm: Pale
  Nuclear staining: Absent

Gomori trichrome stain

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

Phagocytosis: Earlier stages
  Histiocytic cells invade & replace muscle fibers

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

Gomori trichrome stain

Necrotic muscle fiber
  Largely replaced by cells
  Some remaining debris

Phagocytic cells within pale necrotic muscle fibers
  Phagocytic cells: Have mild NADH staining
  Necrotic muscle fibers: Cytoplasm has little, or no, staining

NADH stain

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

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

Phagocytosis: Late
  Phagocytic cells move out of necrotic muscle fiber
  Space occupied by necrotic muscle fibers "Collapses"

H&E stain

H&E stain
Collapsed muscle fibers
  Some remaining histiocytes

Acid phosphatase stain

MHC Class I stain
Very late stage necrosis: MHC Class I
  Stains remaining cells phagocytsing collapsed muscle fibers
  Stains capillaries (Normal)
  No staining of most muscle fibers (Normal)

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

Necrosis 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

H&E stain

Gomori trichrome stain

H&E stain

H&E stain

H&E stain

Necrosis: Scattered Muscle fibers

H&E stain
Necrotic Muscle Fibers: Scattered
  Ongoing: Muscle fibers in varied stages of necrosis & regeneration
  Also see: Scattered necrosis, Severe

H&E stain

Necrotic Muscle Fibers: Scattered
  Monophasic: Scattered muscle fibers in early stage of necrosis
    Cytoplasm of Necrotic Muscle fibers stains diffusely for C5b-9

C5b-9 stain stain

Also see: Regional Ischemic Immune Myopathy

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1. Cell Death Differ 2016 Feb 12