Neuromuscular

Immune Myopathy with Antibodies to HMGCR

HMGCR pathology
  Active myopathy
    Perimysium
    Lipid
    Nuclear pathology
    Immune pathology
    Mild pathology
  Early onset, Chronic


ACTIVE MYOPATHY
  Muscle fibers: Necrosis & Regeneration
  Perimysial Damage

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 have no staining (Dark arrow).
Regenerating muscle fibers (Small) are dark stained (White arrow)


NADH stain

Necrotic muscle fibers are infiltrated by histiocytic (red) cells


Acid phosphatase stain

Acid phosphatase stain

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

ATPase pH 4.3 stain

Necrotic & Regenerating muscle fibers are often near the perimysium
C5b-9 stains the cytoplasm of necrotic fibers near the perimysium

C5b-9 stain
NADH stains smaller fibers near the perimysium

NADH stain

HMGCR MYOPATHY: Perimysium


Perimysial structure: Fragmented & Irregular


Gomori trichrome stain

Abnormal staining of perimysium with alkaline phosphatase

Alkaline phosphatase stains: Perimysial connective tissue & Cytoplasm of 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

5/9/2017