Neuromuscular

MYASTHENIA GRAVIS: Muscle Pathology

NMJs
  Normal
    Limb muscles
    EOM
  Proteins
Myasthenia gravis
  NMJs: Abnormal
  Congenital
    AChE deficiency
    AChR mutation
    Agrin mutations
  Immune
    Chronic, Undertreated
    Diagram
    Lymphorrhages
    Rippling muscles & Thymoma
  Pathological features
  Pathophysiology
NMJ Congenital MG
Esterase stain
Congenital MG
AChR deficiency
Small, pale NMJ

Neuromuscular junctions: Normal

Normal NMJ  
Esterase stain

Neuromuscular Junctions: Myasthenia Gravis, Acquired

NMJ MG    
 



Esterase stain
Small, pale and multi-segmented neuromuscular junctions from patients with acquired myasthenia gravis.
Myasthenia Gravis, AChR antibody positive

Esterase stain

Esterase stain

Esterase stain

Lymphorrhages

Lymphorrhages
  From patients with myasthenia gravis & thymoma.
  Foci of lymphocytes with dark nuclei & little cytoplasm
Lymphorrhage
H&E stain


H&E stain


H&E stain


Myasthenia Gravis, Immune: Muscle pathology 1


NEUROMUSCULAR JUNCTION ANATOMY: NORMAL & MYASTHENIA GRAVIS


From Drachman

Myasthenia gravis: Chronic, Undertreated



H&E stain
Varied muscle fiber size: Atrophy & Hypertrophy
Pyknotic nuclear clumps

H&E stain


Esterase stain
Neuromuscular Junctions: Small, Irregular & Pale stained

Esterase stain


ATP pH 9.4 stain
Fiber types
  Type 2 predominance
  Small are type 2
  Large are type 1 (Above) or 2 (Below)

ATP pH 9.4 stain

Fiber types: Scattered type 2C fibers (Intermediate staining) are present

ATP pH 4.3 stain

Myasthenia gravis, Thymoma & Rippling muscle syndrome


H&E stain
Muscle fibers: Occasional area with regenerating muscle fibers (Above)
Normal muscle fibers: In most areas (Below)

H&E stain

Perimysial vessel: Associated inflammation extending into the endomysium

H&E stain


VvG stain
Inflammation around intermediate-sized vessels
  Mostly mononuclear (probably with B-cells)
  Few cells stain for esterase (Below)
  Vessel endothelium: Stains for esterase

Esterase stain


Esterase stain
Neuromuscular Junctions
  Size: Small or Elongated
  Intensity of staining: Normal

Esterase stain

Caveolin-3
  Variably reduced or normal on muscle fiber surfaces

Caveolin-3 stain

MHC, Class I
  Abnormally upregulated on muscle fiber surfaces & cytoplasm in some regions

MHC Class I stain

Myasthenia gravis, Congenital: AChE deficiency



H&E stain
Muscle, Motor points (Areas with NMJs; Above = Top left & Bottom right near spindle)
  Endomysium: Mildly increased
  Muscle fibers: Enlarged nuclei (Below right)

H&E stain


Gomori trichrome stain
Muscle, Motor points
  Endomysium: Mildly increased
  Muscle fibers: Coarse internal architecture (Above)
  Intramuscular nerves: Normal (Below)

VvG stain

Fiber types: Type 1 (pale) muscle fiber predominance

ATP pH 9.4 stain


Esterase stain
Neuromuscular Junctions
  Very Pale stained (Above; Arrows)
  Some of the palest NMJs have neighboring acid phosphatase staining (Below; Arrows)

Acid phosphatase stain

Myasthenia gravis, Congenital: AChR deficiency ε-Subunit mutations


Young adult
Motor Point in Muscle
Intramuscular Nerves: Normal
  Present in perimysium
  Myelinated axons: Normal numbers
Endomysium: Increased space between muscle fibers compared to other areas of muscle.
Muscle fibers
Fiber sizes
  Bimodal distribution
  Smaller fibers are often angular

VvG stain


Gomori trichrome stain
Motor Point in Muscle
Intramuscular Nerves
  Small branches: Present in endomysium
  Myelinated axons: Red stained (Above)
Muscle fibers
  Increased space between fibers compared to other areas of muscle.
  Small fibers are often angular

H&E stain

Muscle Spindle: Normal

Gomori trichrome stain

Muscle Fibers: Internal architecture
  Normal distribution
  Small muscle fibers: Pale stained (Probably mostly type 2)

NADH stain

Congenital MG: Neuromuscular Junctions

Esterase stain
NMJs: Abnormal
  Pale stained
  Small
  May be multi-segmented (Above Right)
See: Control

Esterase stain

2 yo Child: AChR ε subunit mutation
Muscle morphology

H&E stain
Muscle Fibers
Size Distribution: Bimodal
Small fiber shapes: Polygonal or Round

H&E stain

Gomori trichrome stain


NADH stain
Samll fibers are most often pale (Type 2)


ATPase pH 9.4 stain
Type 2 Fiber (Dark) atrophy

ATPase pH 9.4 stain

ATPase pH 9.4 stain


ATPase pH 4.3 stain
Immature fibers (Intermediate stain; Type 2C): scattered in biopsy


ATPase pH 4.6 stain
Small fibers are Types 2A & 2B

References
1. Neuropathology and Applied Neurobiology 2009;35:103110

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7/12/2022