MUSCLE BIOPSY RESULTS: Differential diagnosis

• Atrophy (H&E; ATPase): Also see Fiber type disorders
  • Small rounded fibers: Myopathy; Type I smallness
  • Small angular fibers: Neuropathy; Type 2 atrophy
  • Grouped: Neuropathy with denervation
    • Multiple small groups: Most commonly associated with ALS
    • Large groups: Chronic denervation; Motor neuron disease
    • Rule out: Myopathic grouping
  • Perifascicular: Dermatomyositis
• Muscle fiber damage
  • Necrosis
  • Regeneration
  • Focal invasion
    • Inclusion body myositis
    • Polymyositis with cytochrome oxidase muscle fibers
• Nuclear pathology (H&E)
  • Pyknotic clumps: Chronic denervation without reinnervation
  • Internal nuclei
    • Most abundant & > 60% of fibers: Chronic myotonic dystrophy
    • Single, centrally placed: Centronuclear myopathy
    • 10% to 30% of fibers: Chronic neuropathic or myopathic process
  • Abnormal nuclei: Inclusion body myositis
  • Large nuclei: Regenerating muscle fibers; Myosin-loss myopathy
• Inflammation (H&E; Congo red; Acid phosphatase; Esterase; Immunocytochemistry)
  • Immune myopathies: T-cells > Macrophages focally invading muscle fibers
  • Vasculitis: T-cells > Macrophages
  • Fasciitis: Macrophages > T-cells
  • FSH dystrophy: T-cells
  • Sarcoid: Macrophages & histiocytes in center of granulomatous inflammation
  • Fiber necrosis: Macrophages in muscle fibers
  • Lymphorrhages (myasthenia): T-cells
• Endomysial fibrosis (H&E; GT & VvG)
  • Diffuse & abundant: Dystrophy or endstage muscle
  • Patchy: Acquired myopathy
  • Increased endomysial connective tissue between muscle fibers is normal in regions with NMJs
• Abnormal internal fiber architecture (NADH stain)
  • Targets: Denervation & reinnervation; Tenotomy
  • Cores: Central core syndromes
  • Coarse: Immature or regenerating fibers
  • Rods (GT stain): Rod myopathy; Reinnervation with targets
  • Tubular aggregates
  • Moth-eaten fibers: Systemic connective tissue disorders; Chronic dystrophy
  • Rings
• Fiber type disorders (ATPases pH 9.4, 4.6 & 4.3)
  • Absent staining at all pHs: Myosin deficiency myopathies
  • All type 1: Central core; Large fiber type grouping; Demyelinating neuropathies
  • Smaller type 1 fibers:
    • Dystrophy: Emery-Dreifuss: ?Myotonic
    • Congenital myopathies: Centronuclear; Nemaline rod; Fiber type disproportion
    • Exercise training
  • Small type 2 fibers: Disuse; Aging; Weight loss; Systemic disease; Paraneoplastic
  • Type grouping: Chronic denervation with reinnervation or collateral sprouting
• Mitochondrial (SDH & Cytochrome oxidase)
• Glycogen storage (PAS)
• Lipid storage (Sudan black or Oil red O)
  • Carnitine deficiency
  • Malnutrition
• Vacuoles
  • Lysosomal: Acid maltase deficiency; Batten's disease
  • Autophagic
    • 2° lysosome: Stains + for acid phosphatase
    • Acid maltase; Toxic; Inflammatory myopathy; Hypokalemic myopathy;
      X-linked myopathy with excessive autophagia
  • Peroxisomes: Lafora disease
  • Rimmed: Inclusion body myositis; OPD; Distal myopathies;
    Hereditary inclusion body myopathy; LGMD 2G
  • Subsarcolemmal: Phosphorylase deficiency
  • Other: Periodic paralysis; Glycogen storage; Lipid storage; Centronuclear myopathy;
    Lipofuscin (aging); Freezing artifact; Desmin storage
• Amyloid (Congo red)