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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

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Patterns of inflammation

Perivascular Lymphocyte 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

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Focal invasion of non-necrotic muscle fibers by inflammatory cells

Morphology Endomysial inflammation Histiocytes MHC Class I General features Ultrastructure

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H&E stain

Focal invasion of muscle fibers
  Mononuclear cells
    Present in: Endomysium; Focal invasion of muscle fibers
    Cell Types: Lymphocytes; Histiocytes
    Cell Molecular markers: KLRG1; CD8 ³
  Muscle fiber cytoplasm: Normal color & structure
  Common in
    IM-VAMP syndromes: Inclusion body myositis & PM-Mito

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H&E stain

Mononuclear cells
  Present in: Endomysium & Focally invading muscle fibers

H&E stain

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Focal invasion of muscle fibers: Stages

H&E stain

H&E stain

H&E stain

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Gomori trichrome stain

IBM: Focal Invasion of Muscle fibers by Cells

Gomori trichrome stain

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Focal invasion of muscle fibers: Histiocytic cells Acid phosphatase stain

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Focal invasion of muscle fibers in IM-VAMP: Histiocytic cells
  Histiocytic cells invade muscle fiber (Arrow)

Acid phosphatase stain

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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

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Features of focal invasion of muscle fibers Cells invade non-necrotic muscle fiber Commonly CD3+ CD8+ cells 60% of population Cytotoxic Recognize antigens on surface membrane May also stain for CD57 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 expression 1 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 Many normal appearing muscle fibers in same biopsy 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 IBM syndromes Polymyositis with COX deficiency (P-COX); Uncommon, but may occur, in steroid-responsive immune myopathies 2

Necrotic Muscle Fibers

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

Esterase stain Necrosis, Late   Fiber replaced by macrophages.

Also see   Muscle fiber necrosis   Regional Ischemic Immune Myopathy (RIIM)

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

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

General features

• Normal muscle
  • MHC-I is expressed on capillaries but not muscle fibers
• Inflammatory myopathies & MHC-I
  • Upregulation: Expressed by
    • Muscle fibers on surface & cytoplasm
    • Inflammatory cells
  • Inclusion body myositis, Sporadic
    • Diffuse expression by all muscle fibers: > 95% of patients
    • Expressed by histologically normal muscle fibers
  • Dermatomyositis & IMPP: Patterns of muscle fiber expression
    • Diffuse: Expression on all fibers
    • Selective: Muscle fibers near perimysium (perifascicular)
  • SRP & HMGCR antibody myopathies
    • Usually have expression mainly by regenerating muscle fibers
• Hereditary myopathies
  • Usual: MHC-I is expressed on capillaries & scattered regenerating muscle fibers
  • Up-regulation by muscle fibers common
    • FSH dystrophy
    • LGMD 1A

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Normal MHC-I on small vessels but not muscle fibers	Necrosis MHC-I on phagocytic cells in a muscle fiber
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)

MHC Class I stain

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References
1. Neurology 2002;58:1779–1785
2. Neurology 2017 Aug 9
3. Brain 2019;142:2590-2604

7/3/2021