Neuromuscular

Immune Myopathy with Serum IgG vs HMGCR

HMGCR pathology
  Active myopathy
    Perimysium
    Muscle fibers
      Immature fibers
      Lipid
      Necrosis
      Nuclear pathology
      Vacuoles: 1; 2
    Immune pathology
    Mild pathology
  Early onset, Chronic

ACTIVE MYOPATHY
  Muscle fibers: Necrosis & Regeneration
  Perimysium: Damaged structure; Histiocytic cells


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

H&E stain

H&E stain

H&E stain

Necrosis & Regeneration

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

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

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, C5b-9-stained, muscle fibers often neighbor the perimysium

C5b-9 stain

Vacuoles: Myopathy with HMGCR antibodies

H&E stain

Gomori trichrome stain

VvG stain

NADH stain

ATPase pH 9.4 stain


ATPase pH 4.3 stain
Immature, type 2C, muscle fibers: Scattered small, intermediate-staining

ATPase pH 4.3 stain

HMGCR MYOPATHY: Perimysium



Gomori trichrome stain

Perimysial structure

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

Gomori trichrome stain

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

Perimysial cells & Scattered necrotic muscle fibers


H&E stain

H&E stain


Acid phosphatase stain

Perimysial cells:
  Histiocytic & Acid phosphatase positive (Red)



Acid phosphatase stain

Acid phosphatase stain

Perimysial Cells: Large & Irregular shapes


Esterase stain

CD4 cells

Epimysial immune cells (Arrow)


CD4 stain

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


CD4 stain

Lipid


Sudan Black stain
Lipid: Normal in muscle fibers.


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


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

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

HMGCR Antibody: Chronic Myopathy, Young onset


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


Gomori trichrome stain
Myopathic features: Muscle fiber morphology
  Inclusions & Vacuoles: Red stained

Gomori trichrome stain
Inclusions & Vacuoles: Red stained

Gomori trichrome stain


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

VvG stain

Muscle fiber pathology
  Vacuoles
  Aggregates
  Basophilic granular debris

Congo red stain

Congo red stain


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

Immature muscle fibers (Intermediate staining)
  Abundant
  Scattered

ATPase pH 4.3 stain

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

Return to Inflammatory myopathies
Return to HMGCR myopathy

6/20/2019