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Inflammatory Myopathies with Vacuoles, Aggregates & Mitochondrial Pathology (IM-VAMP)

Myositis with mitochondrial pathology (PM-Mito) subtype

Inflammation   Endomysial   Focal invasion of muscle fibers Myopathic changes Mitochondrial disorders Other Variant syndromes   IBM   IM-VAMP + HIV   Granulomatous myopathies

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PM-Mito: Muscle pathology

• Muscle fibers
  • Myopathy: Fiber sizes vary from small to hypertrophic
  • Mitochondrial pathology: 2% to 27% of muscle fibers
    • Cytochrome oxidase negative muscle fibers
    • SDH positive muscle fibers
    • Also see: Mitochondrial pathology
  • MHC class I: Upregulated on all fibers
  • mtDNA deletions (90%): Multiple
  • Aggregates: LC-3; αB-crystallin ⁵⁸
  • No: Vacuoles or SMI-31 aggregates; Necrosis
• Inflammation
  • Endomysial: CD8 & CD4 lymphocytes
  • Focal invasion of muscle fibers by inflammatory cells
  • Molecular: Less expression of
    • IFN-induced guanylate-binding protein (GBP)6
    • T-cell function–related KLRG1

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PM-Mito: Myopathy, Inflammatory

VvG stain

Muscle fibers
  Sizes: Varied; Largest fibers hypertrophied
  Internal nuclei
  Immature
    Small, Darker stained cytoplasm, Large nuclei
    Distribution: Scattered
Connective tissue, endomysial
  Increased, mild to moderate
Inflammation
  Endomysial lymphocytes
  Some focal invasion of muscle fibers

H&E stain

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Gomori trichrome stain

PM-Mito: Myopathy, Inflammatory

H&E stain

Gomori trichrome stain

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PM-Mito: INFLAMMATION

H&E stain

Cell foci: Predominantly Endomysial

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Focal invasion of muscle fibers by immune cells

H&E stain

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Cell foci contain: Lymphocytes & Histiocytes (Acid phosphatase positive)

Acid phosphatase stain

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IM-VAMP: Mitochondrial Pathology

Cytochrome oxidase stain

Cytochrome oxidase (COX) negative muscle fibers
  COX- muscle fibers: Scattered in muscle
  Normal fibers have: Dark (Type 1) or Intermediate (Type2) stain

Cytochrome oxidase stain

Cytochrome oxidase (COX) stain: Negative muscle fibers
  COX staining absent or severely reduced
  Normal fibers have: Dark (Type 1) or Intermediate (Type2) stain

Cytochrome oxidase stain

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Mitochondrial Proliferation: Succinate Dehydrogenase (SDH) positive Muscle fibers

SDH stain

Succiniate Dehydrogenase (SDH) stain
  Scattered large & small muscle fibers are abnormally dark
  Normal fibers have: Intermediate (Type 1) or Moderately pale (Type2) stain

SDH stain

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PM-Mito: MHC 1 upregulation

MHC-I Upregulation on sarcolemma: Diffuse

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LC-3 aggregates in muscle fibers
  Varied shapes: Diffuse, punctate, or irregular, dark aggregates

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PM-Mito: Capillary & Vessel pathology

Capillary sizes: Some are large
Endothelial cells: May stain for acid phosphatase (Dark arrow)
Neighboring histiocytic cells (White arrow)

Acid phosphatase stain

Perivascular Inflammation (Arrow)

H&E stain

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Return to Inflammatory myopathies
Return to Polymyositis with mitochondrial disorders

12/12/2024