MYASTHENIA GRAVIS: Muscle Pathology

Neuromuscular Junctions: Myasthenia Gravis

Esterase stain

Small, pale neuromuscular junction from patient with congenital myasthenia gravis.

Esterase stain

Small, pale and multi-segmented neuromuscular junctions from patients with acquired myasthenia gravis.

Esterase stain

Neuromuscular junctions: Normal

Lymphorrhages

H&E stain

H&E stain

Lymphorrhages from patients with myasthenia gravis and thymoma.

Myasthenia Gravis: Muscle pathology ¹

• AChR Ab+
  • Muscle fiber atrophy: Type I & II
  • Pyknotic nuclear clumps: More without adequate treatment
  • Muscle fiber type grouping: Some patients
  • Internal architecture: Disordered; Minicores
  • Neuromuscular junctions: Small or multisegmented
    
• MuSK Ab+
  • COX- muscle fibers: Present in < 2% of fibers
  • Internal architecture: Disordered; Minicores

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, 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, 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 cells   Few cells stain for acid phosphatase (Below)

Acid phosphatase 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