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Immune Myopathy with Serum IgG vs HMGCR

HMGCR pathology   Active myopathy     Muscle fibers       Immature fibers       Lipid       Necrosis       Nuclear pathology       Vacuoles: 1; 2     Connective tissue       Perimysium       Epimysium     Immune pathology     Mild pathology   Chronic myopathy     Younger onset

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Active Myopathy with Perimysial Pathology (IMPP)

H&E stain

Common Features
  Muscle fibers
    Necrosis & Regeneration: Scattered or at Edge of fascicles
    MHC1 upregulation: Diffuse or Perifascicular
  Perimysium
    Structure: Damaged
    Histiocytic cells
    Alkaline Phosphatase stain

VvG stain

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Alkaline Phosphatase stain

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C5b-9 stain

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MHC Class 1 stain

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Myopathy, Ongoing

H&E stain

Necrotic (Arrows) & Regenerating muscle fibers: Scattered
H&E stain	H&E stain

H&E stain

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Necrosis & Regeneration

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Variable Damage: Region with small muscle fibers & increased endomysial connnective tissue

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Necrotic muscle fibers are pale and infiltrated by cells (Arrow) Congo red stain

Necrotic muscle fibers: No or Pale staining (Dark arrow). Immature muscle fibers (Small): Dark stained (White arrow) NADH stain

Acid phosphatase stain Necrotic muscle fibers   Replaced, or infiltrated, by histiocytic (red) cells

Acid phosphatase stain

Acid phosphatase stain

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Necrotic Muscle Fibers

C5b-9 stains: Cytoplasm of necrotic fibers near perimysium C5b-9 stain

NADH stains: Smaller fibers near perimysium NADH stain

Myopathy: Necrotic, C_5b-9-stained, muscle fibers often neighbor the perimysium

C5b-9 stain

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Vacuoles: Myopathy with HMGCR antibodies

H&E stain

Gomori trichrome stain

VvG stain

NADH stain

ATPase pH 9.4 stain

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ATPase pH 4.3 stain

Immature, type 2C, muscle fibers: Scattered small, intermediate-staining

ATPase pH 4.3 stain

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HMGCR MYOPATHY: Perimysium

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Gomori trichrome stain

Perimysial structure

  Fragmented & Irregular
  Scattered, Large, Acid phosphatase+ cells: Present in some regions

Gomori trichrome stain

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Perimysium: Stains for alkaline phosphatase

Alkaline phosphatase stains:
  Perimysial connective tissue (Arrows)
  Cytoplasm of immature, or regenerating, muscle fibers

Alkaline phosphatase stain

Alkaline phosphatase stain

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Perimysial cells & Scattered necrotic muscle fibers H&E stain

H&E stain

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Acid phosphatase stain

Perimysial cells:   Histiocytic & Acid phosphatase positive (Red) Acid phosphatase stain

Acid phosphatase stain

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Perimysial Cells: Large & Irregular shapes Esterase stain

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CD4 cells

Immune cells: Epimysial (Arrow) & Endomysial

CD4 stain

Also see: Epimysial & Perimysial staining by alkaline phosphatase

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Immune Cells: Perimysial (Arrow), Endomysial & Associated with Necrotic muscle fibers

CD4 stain

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Lipid

Sudan Black stain

Lipid
  Normal in most muscle fibers (Above)
  May be increased in scattered Muscle fibers (Below)

Sudan Black stain

Sudan Black stain

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H&E stain MYONUCLEAR PATHOLOGY: Enlargement, Irregular shapes & Clusters

Congo red stain Myonuclei (Abnormal) in intact muscle fibers   Large   Irregular shapes (Arrows)   Clustered   May contain inclusions

H&E stain

H&E stain

H&E stain

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Congo red stain

Congo red stain

IMMUNE PATHOLOGY MHC Class I expression: Variable   Mostly on muscle fibers in more severely affected regions (Left)     Also present on cells invading necrotic muscle fibers   Less prominent, or absent, in mildly affected regions (Right) MHC Class I stain

C5b-9 Deposition: In cytoplasm of scattered necrotic muscle fibers (Arrow) C5b-9 stain

CD4 Cells: In Necrotic muscle fibers & Near endomysial capillaries CD4 stain

Ulex stained capillaries: Normal numbers Ulex (UEA1) stain

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HMGCR MYOPATHY: EARLY or MILD PATHOLOGY

Occasional Necrotic Muscle Fiber (Arrow) H&E stain

Large or Irregular Nuclei (Arrow) Congo red stain

Large Nuclei (2nd patient) H&E stain

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HMGCR Antibody: Chronic Myopathy, Young onset, Poor response to treatment

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H&E stain

Gomori Trichrome stain

VvG stain

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VvG stain

Myopathic features
  Muscle fibers
    Internal architecture: May have aggregates
    Size: Varied
  Regenerating muscle fibers: Scattered
  Endomysial connective tissue: Increased
  Severity of pathology: May vary among fascicles

VvG stain

Myopathic features   Muscle fibers     Size: Varied; Hypertrophy & Atrophy   Endomysial connective tissue: Increased VvG stain

H&E stain

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Gomori trichrome stain

Myopathic features: Muscle fiber morphology
  Inclusions & Vacuoles: Red stained

Gomori trichrome stain

Inclusions & Vacuoles: Red stained

Gomori trichrome stain

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VvG stain

Muscle fiber pathology
  Necrosis (Left, Above)
  Vacuoles (Right, Above)
  Aggregates & Abnormal internal architecture (Below)

VvG stain

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Muscle fiber pathology   Vacuoles   Aggregates   Basophilic granular debris

Congo red stain

Congo red stain

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PAS stain

Muscle fiber pathology: Internal architecture
  Aggregated glycogen
  Internal architecture: Coarse or Dark
  Necrosis: Some fibers have very pale-stained cytoplasm (Below)

NADH stain

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Immature muscle fibers (Intermediate staining)
  Abundant
  Scattered

ATPase pH 4.3 stain

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Perimysial Pathology
  Perimysial staining by Alkaline phosphatase
  Immature muscle fibers: Cytoplasm is Alkaline phosphatase +

Alkaline phosphatase stain

Histiocytic cells (Red)   Scattered in perimysium   Necrotic muscle fiber: Replaced by histiocytic cells Acid phosphatase stain

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Return to Inflammatory myopathies
Return to HMGCR myopathy

3/7/2024