Neuromuscular

NEMALINE RODS

General description
Infant
  Diffuse
  Type 1 small
  Ultrastructure
  Congenital
Child
Adult
DDx
Atypical

Nemaline Rod Pathology

  • Light microscopy
    • Rods best visualized with
      • Gomori trichrome stain
      • Toluidine blue stained plastic sections
    • Dark blue structures
    • Most in muscle fiber cytoplasm
  • Contain
    • Z-line like material
    • α-actinin, actin & tropomyosin ± desmin at the periphery
  • Located in sarcoplasm: Often in regions with disrupted sarcomere structure
  • Occur in
    • Congenital myopathies
      • TPM3: Rods, Preferentially in type 1 fibers; Type 1 fiber predominance
      • ACTA1: Rods, Numerous, Most in small fibers, Cytoplasmic & Nuclear; Clusters of glycogen & actin filaments
      • TNNT1: Rods, Central in muscle fibers; Type 1 fibers small
      • KBTBD13: Rods, Diffusely distributed, All fibers; Type 1 fibers Predominant & Large
      • KLHL40: Rods, Many small; No normal myofibers
      • LMOD3: Rods Surrounded by "thin filament fringe"; Thickened Z disks;
    • Adult onset nemaline myopathies
  • Similar appearance & staining to: Cytoplasmic bodies
  • Also see: Rods or Cytoplasmic bodies in target fibers

Nemaline rod myopathy: Infantile

 
Gomori trichrome
Nemaline rods in gastrocnemius muscle from 4 month old child



No nemaline rods in quadriceps muscle from same child biopsied at 2 months of age

Nemaline rod myopathy, Infantile: Toluidine blue stains








Nemaline rod myopathy, Infantile: Other stains


H&E stain
Muscle fiber sizes: Varied

H&E stain


H& E stain
Muscle fiber size: Varied
Refractile rods can be seen

ATPase stain, pH 9.4
Type I muscle fiber predominance


H& E stain

Rods: Actin stain


Phalloidin staining for actin
Focal (bright green), large and small aggregates of actin are present in some muscle fibers

Phalloidin staining for actin



Nemaline Rod Ultrastructure


Infantile-onset Rod myopathy

From: R Schmidt
 

Nemaline Rods

  • Electron dense
  • Sizes: Length 1-7 μm; Width 0.3-2 μm
  • Long axis: Parallel to muscle fiber
  • Longitudinal section: Striations parallel & perpendicular to long axis
  • Transverse section: Lattice structure like Z disk
  • Thin filaments: In continuity with rods

From: R Schmidt

From: R Schmidt


From E Hardeman
Electron microscopy of rods from Z-lines in Met9Arg αTMslow mouse

Nemaline rod myopathy, infant (8 months of age): Type 1 muscle fiber smallness

Rods: More prominent in smaller muscle fibers

Gomori trichrome


ATPase pH 9.4
Type 1 muscle fibers: Small (Pale)

H&E
Muscle fiber sizes: Bimodal

NADH
Internal architecture of muscle fibers: Irregular

Rod Myopathy: Congenital + Arthrogryposis


H&E stain
Fiber sizes: Bimodal distribution

Gomori trichrome stain
Rods
  Dark-stained: Punctate or Clustered regions, Often sub-sarcolemmal
  More common in smaller muscle fibers

Gomori trichrome stain

Gomori trichrome stain

ATPase pH 9.4 stain
Fiber types
  Type 1 fibers: Usually small
  Type 2 fibers: Larger; Abnormal intermediate staining (2C) at ATPase pH 4.3

ATPase pH 4.3 stain

NADH stain

Rods: In clusters in muscle fibers

Toluidine blue stain

Toluidine blue stain


Nemaline rod myopathy, Childhood: 2 Different patterns


Rods: In smaller muscle fibers

GT stain
 

ATPase stain, pH 9.4
Type I muscle fibers: Smaller than type II

Rods: In small & large muscle fibers

GT stain
Type I predominance

ATPase stain, pH 9.4
Fiber size variation: Bimodal distribution

H&E stain

Rods: Adult nemaline myopathy
  Several patterns

Rods: Larger & Aggregated
 
Gomori trichrome
Rods: May cluster near myonuclei (Arrow)

Gomori trichrome

Rods: Small & Diffusely distributed in some muscle fibers
  Myopathic features: Varied muscle fiber size; Internal nuclei; Endomysial connective tissue increased

Gomori trichrome

Gomori trichrome

Gomori trichrome

Gomori trichrome


H&E stain

Rods: Atypical


Gomori trichrome stain
Rod-like Aggregates
  Stain dark on Gomori trichrome
  Near myotendinous junctions

Gomori trichrome stain


Toluidine blue stain
Rod-like Aggregates: Rod shape in fixed sections

Rod-like Aggregates (Ultrastructure)
  Dark stained
  Internal structure: Amorphous
  Shape: Irregular; Polygonal
  Halo: Contains linear structures

Return to Rod myopathies

12/2/2018