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INFLAMMATORY MYOPATHIES: PATTERNS OF PATHOLOGY

Focal inflammation
Focal invasion of muscle fiber
Granuloma
Perimysial (IMPP)
MHC-I expression
Muscle fiber necrosis
Myositis
Also see:
  Dermatomyositis
  Inclusion body myositis
  Inflammation: Cellular Patterns
  Lymphorrhages
  Trichinosis: Acute; Chronic
  Vasculitis: Small & Large vessel


Patterns of inflammation

Perivascular
Lymphocyte inflammation

Polymyositis Mononuclear cell inflammation
H&E
Lymphocytes:
  Perivascular
  May extend into perimysium
  Common in BCIM
Endomysial
  inflammation


H&E
Lymphocytes:
  Often associated with
    focal invasion of
    muscle fibers
  Common in IM-VAMP
Perimysial
inflammation


Histiocytes
  Location: Perimysium
  Stain for acid phosphatase
  Common in IMPP
Granulomatous
inflammation


Histiocytes
  Focal clusters
  Endomysium or Perimysium
  Granulomatous disorders

Focal invasion of non-necrotic muscle fibers by inflammatory cells

H & E stain
Acid phosphatase stain
General features

Progressive focal invasion of muscle fibers: H & E stain




H&E stain

Progressive focal invasion of muscle fibers: Acid phosphatase stain

 


Focal Invasion of Muscle fibers: MHC Class I
  Up-regulated by muscle fibers
  Strongly expresed by mononuclear cells invading muscle fibers

MHC Class I stain

Features of focal invasion of muscle fibers
  • 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

Necrotic Muscle Fibers


H&E
Necrosis, Early (Left)
  Fiber is pale & enlarged
  Internal nuclei
    Invading macrophages

Esterase stain
Necrosis, Late
  Fiber replaced by macrophages.
Also see: Muscle fiber necrosis; Paraneoplastic necrotizing myopathy


Membrane attack complex deposition on muscle fiber surface


Stain: C5b-9 components of complement (Membrane attack complex (MAC))

C5b-9 deposition without muscle fiber necrosis


Major Histocompatibility Complex-1 (MHC-I) Expression in Muscle

General features
Normal: MHC-I on small vessels

Normal
MHC-I on small vessels but not muscle fibers
Necrosis: MHC-I on phagocytic cells

Necrosis
MHC-I on phagocytic cells in a muscle fiber

IBM IBM

Inclusion Body Myositis
MHC-I on surface of most or all muscle fiber
MHC-I increased in cytoplasm of regenerating muscle fibers
MHC-I also stains mononuclear cells in infiltrate (Right)


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References
1. Neurology 2002;58:1779–1785

7/30/2016