Muscle Neuropathology
What You'll Learn
- To separate neurogenic from myopathic change on muscle biopsy
- The muscular dystrophies and their membrane-protein defects
- The inflammatory myopathies — DM, PM, IBM, and immune-mediated necrotizing myopathy — by their distinct immunopathology
- Metabolic, mitochondrial and congenital myopathies and the histochemical stains that reveal them
The neuropathology view of muscle biopsy. Clinical myopathy workup lives in the Neuromuscular notes.
- Neurogenic = grouped (angular) atrophy + fiber-type grouping; myopathic = rounded fiber-size variation, internal nuclei, degeneration/regeneration, endomysial fibrosis.
- Dermatomyositis = perifascicular atrophy + capillary MAC (C5b-9) deposition + perifascicular MxA / MHC-I; perivascular/perimysial CD4 & plasmacytoid DCs (humoral, vessel-directed).
- Polymyositis / IBM = endomysial CD8+ T-cells invading non-necrotic MHC-I+ fibers; IBM adds rimmed vacuoles + congophilic/TDP-43 inclusions.
- Immune-mediated necrotizing myopathy = scattered necrotic/regenerating fibers with scant inflammation (anti-SRP / anti-HMGCR, statin-associated).
- Ragged-red fibers (Gomori trichrome) + COX-negative fibers = mitochondrial myopathy.
Reaction Patterns
| Pattern | Histology | Stain clue |
|---|
| Neurogenic (denervation) | Grouped atrophy, small angular fibers, target fibers; reinnervation → fiber-type grouping | ATPase / NADH shows type grouping; esterase+ angular fibers |
| Myopathic | Rounded fiber-size variation, internal nuclei, split fibers, necrosis/regeneration, endomysial fibrosis & fatty replacement | — |
Muscular Dystrophies
| Dystrophy | Pathology | Defect |
|---|
| Duchenne / Becker | Necrosis-regeneration, opaque hypercontracted fibers, marked fibrosis/fat; DMD = absent, BMD = reduced/patchy | Dystrophin IHC (X-linked) |
| Limb-girdle (LGMD) | Dystrophic pattern; sarcoglycan/dysferlin/calpain loss on IHC/immunoblot | Sarcoglycans, dysferlin, etc. |
| Myotonic dystrophy | Central nuclei (chains), ring fibers, sarcoplasmic masses, type 1 fiber atrophy | DMPK CTG (DM1) |
| FSHD | Myopathic + scattered inflammation | D4Z4 contraction (chr 4q35) |
Inflammatory Myopathies
| Myopathy | Immunopathology | Signature |
|---|
| Dermatomyositis | Humoral, complement-mediated microangiopathy: capillary MAC (C5b-9), capillary dropout, perivascular CD4/plasmacytoid DCs | Perifascicular atrophy + perifascicular MxA / MHC-I |
| Polymyositis | Endomysial CD8+ T-cells surrounding & invading non-necrotic MHC-I+ fibers | No perifascicular atrophy; diffuse MHC-I upregulation |
| Inclusion body myositis | Endomysial CD8 invasion + rimmed vacuoles, congophilic/p62/TDP-43 inclusions, ragged-red/COX-negative fibers | Older, asymmetric; treatment-resistant |
| Immune-mediated necrotizing myopathy | Scattered necrotic & regenerating fibers, scant inflammation, sarcolemmal MAC | Anti-SRP / anti-HMGCR (statin) |
Metabolic & Mitochondrial
| Myopathy | Pathology | Stain |
|---|
| Mitochondrial | Ragged-red fibers (subsarcolemmal mito aggregates), COX-negative fibers, paracrystalline inclusions (EM) | Gomori trichrome; COX/SDH; “blue” ragged fibers on SDH |
| Pompe (acid maltase, GSD II) | Vacuolar myopathy with glycogen-filled vacuoles, high acid phosphatase | PAS+; acid phosphatase+ |
| McArdle (myophosphorylase, GSD V) | Subsarcolemmal glycogen blebs; absent phosphorylase histochemistry | PAS+; phosphorylase-negative |
| Lipid storage (CPT2/carnitine) | Lipid droplets, type 1 fiber vacuolation | Oil-red-O |
Congenital Myopathies
| Myopathy | Pathology | Gene / clue |
|---|
| Central core | Central cores lacking oxidative enzyme (NADH/SDH pale) | RYR1; malignant hyperthermia risk |
| Nemaline (rod) | Red rods on Gomori trichrome (Z-disc material), type 1 predominance | ACTA1/NEB |
| Centronuclear / myotubular | Central nuclei in most fibers (myotube-like) | MTM1 (X-linked) |
Biopsy Tools
- Fresh-frozen (not formalin) muscle: H&E, Gomori trichrome (ragged-red, rods, rimmed vacuoles), NADH/SDH/COX (oxidative, cores, mito), ATPase (fiber typing/grouping), PAS (glycogen), oil-red-O (lipid), acid phosphatase, esterase (denervation).
- Immunostains: dystrophin/sarcoglycans/dysferlin, MHC-I, C5b-9 (MAC), MxA, CD4/CD8/CD68.
| Finding | Diagnosis |
|---|
| Grouped atrophy + fiber-type grouping | Neurogenic (denervation/reinnervation) |
| Absent dystrophin | Duchenne |
| Perifascicular atrophy + capillary MAC / MxA | Dermatomyositis |
| CD8 invading non-necrotic MHC-I+ fibers | Polymyositis |
| Rimmed vacuoles + congophilic inclusions | Inclusion body myositis |
| Necrosis with scant inflammation | Immune-mediated necrotizing myopathy |
| Ragged-red / COX-negative fibers | Mitochondrial myopathy |
| Cores lacking NADH | Central core disease (RYR1) |
References
- Dubowitz V, Sewry CA, Oldfors A. Muscle Biopsy: A Practical Approach. 5th ed.
- Love S, et al. Greenfield's Neuropathology. 9th ed. 2015.
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