Patterns of inflammation

• Variation in muscle fiber size
• Small rounded fibers

• Mononuclear cell

• Cells invade non-necrotic muscle fiber
  • Commonly CD3+
  • CD8+ cells: 60%; Cytotoxic; Recognize antigens on surface membrane
  • Autoinvasive cells are oligoclonal: Express only few types of T-cell receptors (TCR Vβ families)
  • Macrophages: 20%
  • CD4+ cells: 10%; Do not penetrate muscle fibers
  • Monocyte chemoattractant protein-1 (MCP-1) chemokine expression¹
    • By CD3+ cells and macrophages invading non-necrotic muscle fibers
    • In response to TNF-α
    • During monocyte– endothelial cell interaction mediated by ICAM-1
• Remaining cytoplasm of muscle fiber appears relatively unaffected
• Invaded muscle fibers commonly
  • Express HLA-I (MHC-I)
  • Upregulate MMP-2 and MMP-9 on membrane
• Neighboring normal appearing muscle fibers often express MHC-I on surface membranes
• No binding of complement to muscle fiber (Not shown)
• Clinical correlations
  • Pathology commonly associated with steroid-resistant forms of inflammatory myopathy
  • Specific syndromes with prominent focal invasion of non-necrotic muscle fibers
    • Polymyositis with COX deficiency (P-COX);
    • IBM
    • Uncommon in typical steroid-responsive inflammatory myopathies

Necrotic Muscle Fibers

• Fiber is pale & enlarged.
• Internal nuclei may reflect
  invasion by macrophages.

• Fiber is invaded by macrophages.

• Often found in absence of C3 deposits
• Differential diagnosis
  • Inflammatory myopathy
  • Muscular dystrophy
    • LGMD 2B
    • Facioscapulohumeral dystrophy
    • Congenital muscular dystrophy: Merosin positive
• See: Patterns of complement deposition