MG Pathology

MYASTHENIA GRAVIS: Muscle Pathology

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

Esterase stain

Congenital MG
AChR deficiency
Small, pale NMJ

Neuromuscular junctions: Normal

Esterase stain

Neuromuscular Junctions: Myasthenia Gravis, Acquired

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

H&E stain

H&E stain

H&E stain

Myasthenia Gravis, Immune: 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, 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