Neuromuscular

MUSCLE FIBER NECROSIS

General features
  Necrosis & Rhabdomyolysis
  Stages
    Early Features
      Metabolic damage
      Sarcolemmal membrane damage
      Macrophage activation
      Fixed muscle, Paraffin sections
    Later features
      Phagocytosis & Regeneration
      Myofiber collapse
      Eosinophils
  Distribution of Necrotic fibers
    Clustered
      Immune (Vascular)
        Regional Ischemic Immune
        NXP-2
      Hereditary (Stretch-induced)
        Myopathic grouping
    Perifascicular: IMPP
    Scattered
  Necrosis: Types & Features
    Muscle Fiber Patterns
      Membrane damage
        Delta lesions
      Metabolic failure, Diffuse
      Peripheral, Histiocyte-related
  Etiologies
    Differential Diagnosis
      Necrosis
      Necrosis, Immune
    Immune
      Antibody-related
        HMGCR
        Mi-2
        NXP-2
        SRP
        BCIM
      LHIM
      Macrophage activation
      RIIM
    Phosphorylase deficiency
    Statin toxicity

Segmental Necrosis of Muscle fibers: Varied stages

Necrosis: General features & Stages 1

Cell & Metabolic
Morphology
  Metabolic failure
  Membrane damage
  Variant
  Phagocytosis
Early Stages

Myofiber Necrosis
  Metabolic
    Muscle Fiber cytoplasm: Pale
    Myonuclei: Lose staining

Myofiber Necrosis
  Sarcolemmal Membrane
    Muscle Fiber Cytoplasm
      "C" or Δ Lesion
      Regional Hypercontraction
Later Stages

Myofiber Necrosis
  Phagocytic
  Late
    Muscle Fiber:
      Replaced by macrophages.

Myofiber Necrosis
  Collapse
  Very Late
    Muscle Fiber space: Collapse,
      Few remaining histiocytes
    Macrophages have migrated away


Differential Diagnosis: Myofiber Necrosis in Immune Myopathies

Syndrome Myofiber
Pathology
Pathology
  Other Tissues
Immune cells/
  Location
Antibody (Serum) IIM Clinical
  Syndromes
LHIM Necrosis, Scattered None Histiocytes/
  Near myofibers
No Necrotic Myopathy
IMPP Necrosis, Perifascicular Perimysium Histiocytes/
  Perimysium
tRNA synthetase (Jo-1)
HMGCR
DM/PM/NM/ILD
Necrotic myopathy
SRP Necrosis, Scattered
Regeneration, Incomplete
Endomysium &
  Perimysium
No Signal Recognition
  Particle
(SRP)
Necrotic myopathy
RIIM Necrosis, Clustered
  Borderzone
Vein damage No No DM/PM/
  Paraneoplastic
BCIM Necrosis, Scattered
Focal invasion
Endomysium
  C5b-9 deposition
B-lymphocyte foci/
  EGC (ELS)
ANA Polymyositis/
Other immune


Myopathies with Abundant Muscle Fiber Necrosis: Comparative Pathology

Myopathy Type Myopathy: Examples
Necrotic Muscle Fibers
Distribution           
in Muscle
Course            Fiber
Cytoplasm
Damage
Tissue Pathology
  Other
Hereditary
Sarcolemma
  Disorders
Dystrophin
Dysferlin
Scattered
Myopathic Groups
Ongoing Δ lesion, or
Diffuse
Endomysium
  Increased
Rhabdomyolysis
  Metabolic &
  Membrane
    Disorders
Phosphorylase
Malignant Hyperthermia
  Membrane disorders
Scattered Monophasic
  ± Ongoing
Diffuse No
Toxic
Rhabdomyolysis Statin, acute Scattered Monophasic Δ lesion, or
Diffuse
No
Immune
IMPP Synthetase &
  Jo-1 Antibody
Perifascicular
  Predominant
Ongoing Diffuse Perimysium Damage
SRP antibody SRP Myopathy Scattered Ongoing Diffuse Endomysial Proliferation
Perimysial damage
RIIM Paraneoplastic
  Myopathy
Clustered: Vessel
  Borderzone areas
Ongoing Diffuse Vessel: Veins & Capillaries
Connective tissue
LHIM   Scattered Ongoing Peripheral Histiocytes:
  Surround Myofibers
NXP-2 antibody Paraneoplastic Clustered Ongoing Diffuse Vessels
Mi-2 antibody Dermatomyopathy Scattered &
  Perifasciular
Ongoing Diffuse  
Focal
Toxic Injections
Venoms
Clustered Monophasic Diffuse, or
  Δ lesion
 
Ischemia Vascular Disease Clustered Monophasic Diffuse Endomysium: Edema
Freeze   Clustered Monophasic
Slow recovery
Diffuse Satellite cells
  Number reduced


Muscle Fiber Necrosis (Rhabdomyolysis episode): Morphology


Segmental necrosis: Scattered necrotic & hypercontracted muscle fibers


H & E Stain
← Normal muscle fiber
Necrotic muscle fiber: Pale; Little phagocytosis
Necrotic muscle fiber: Phagocytosis by macrophages
← Hypercontracted necrotic muscle fiber
← Perimysium

Necrosis: Early; Metabolic failure
Pale muscle fibers with loss of cytoplasmic structures & staining

H&E stain
Necrotic muscle fibers: Pale; Little phagocytosis (Arrows)

Gomori trichrome stain

H&E
Necrotic muscle fiber, Early
  • Fiber is pale & enlarged.
  • Internal nuclei may reflect
    invasion by macrophages.
Necrosis: Early; "Metabolic" pattern
  Muscle fiber cytoplasm: Pale
  Nuclear staining: Absent

Gomori trichrome stain


Necrotic muscle fibers: Internal architecture has lost NADH staining (Arrow)

NADH stain

Rhabdomyolysis
  Some non-necrotic muscle fibers have increased lipid (Left)
  Phagocytic cells have only minor staining of their cytoplasm (Right)

Sudan black stain

Necrosis: Early; Membrane damage, Statin toxicity
Varied internal structure: Hypercontracted material & Palor in different areas of single fibers

H&E stain

Membrane damage at several regions of individual fibers: Associated with clear regions in cytoplasm

H&E stain


H&E stain
"C"- or "Delta"-lesions
  Membrane & Neighboring cytoplasm damage in a focal region of individual muscle fibers: Pale staining
  Cytoplasm around focal lesion stains dark

H&E stain

NADH stain
"C"- or "Delta"-lesions
  Cytoplasm around focal lesion stains pale

NADH stain

Congo red stain

Phagocytosis of Muscle fibers
  Histiocytic cells invade & replace muscle fibers

H&E stain
Necrotic muscle fibers: Phagocytosis (Arrows)

Gomori trichrome stain

Necrotic muscle fiber
  Largely replaced by cells
  Some remaining debris

H&E stain


NADH stain
Phagocytic cells within pale necrotic muscle fibers
  Phagocytic cells have
    Mild NADH staining
    Strong esterase staining
  Necrotic muscle fibers: Cytoplasm has little, or no, staining

Esterase stain


Acid phosphatase stain
Necrosis: Varied Stages
  Early: Pale stained muscle fibers
  Later: Muscle fibers progressively replaced by acid phosphatase + cells (Right)

Acid phosphatasae stain

Esterase stain
Necrotic muscle fiber, Late
Muscle fiber is invaded and
  replaced by phagocytes.

Esterase stain

Necrosis & Phagocytosis: Late

H&E stain
Phagocytic cells
  Replace necrotic muscle fibers
  Move out of necrotic muscle fiber areas

Acid phosphatasae stain


H&E stain
Collapsed, phagocytosed muscle fibers
  Space occupied by necrotic muscle fibers "Collapses"
  Some histiocytes remain

Acid phosphatase stain

MHC Class I stain
Very late stage necrosis: MHC Class I
  Stains remaining cells phagocytsing collapsed muscle fibers
  Stains capillaries (Normal)
  No staining of most muscle fibers (Normal)


Alkaline phosphatase stain
Necrosis: Alkaline phosphatase stains around the rim of muscle fibers


Toluidine blue stain
Necrotic muscle fiber (Longitudinal section)
  Pale
  Invaded by cells


Toluidine blue stain
Necrotic muscle fiber (Cross-section)
  Pale
  Invaded by cells

Toluidine blue stain
Necrotic muscle fiber
  Pale
  Invaded by cells


Toluidine blue stain
Cells in necrotic fiber

Toluidine blue stain
Non-necrotic, abnormal muscle fiber (Left): Dilated SR

Necrotic muscle fibers: Complement C5b-9 (MAC) deposition


Stain: C5b-9 components of complement (Membrane attack complex (MAC))
Necrosis: C5b-9 deposition diffusely within muscle fiber cytoplasm

Rhabdomyolysis: PAS stain is pale in small & large muscle fibers

Necrosis: Ongoing


Necrosis: Early stage
  Pale muscle fiber cytoplasm
  Lipid droplets
  Two other muscle fibers have large lipid droplets but are not pale & necrotic

H&E stain


H&E stain
Necrosis: Phagocytosis of varying degrees

H&E stain

Necrosis associated with Eosinophils

  Unusual: Eosinophils may be a component of cells replacing necrotic muscle fibers
    Reported with LGMD 2A (Calpain-3 mutations)


H&E stain

H&E stain

Gomori trichrome stain

H&E stain

H&E stain

H&E stain

Necrosis: Scattered Muscle fibers


H&E stain
Necrotic Muscle Fibers: Scattered
  Ongoing: Muscle fibers in varied stages of necrosis & regeneration
  Also see: Scattered necrosis, Severe

H&E stain

Necrotic Muscle Fibers: Scattered
  Monophasic: Scattered muscle fibers in early stage of necrosis
    Cytoplasm of Necrotic Muscle fibers stains diffusely for C5b-9

C5b-9 stain stain

Also see: Regional Ischemic Immune Myopathy

Return to Neuromuscular Home Page

References
1. Cell Death Differ 2016 Feb 12

5/14/2019