NEMALINE RODS
Nemaline Rod: Muscle Pathology
- Light microscopy
- Rods best visualized with
- Gomori trichrome stain
- Toluidine blue stained plastic sections
- Phalloidin
- Dark blue structures
- Most in muscle fiber cytoplasm
- Often in regions with disrupted sarcomere structure
- Contain
- Z-line like material
- α-actinin, actin & tropomyosin ± desmin at the periphery
- Rods: 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
- NEB: Normal & Small size fibers; Globular in severe disease; Desmin cytoplasmic aggregates
- Patterns
- Rod anatomy
- Types of fibers
- Rod location in fibers
- Associated with Dense (desmin) cytoplasmic aggregates: NEB; TPM2
1
- Adult onset: SLONM
- Similar staining: Cytoplasmic bodies
- Rods & Cytoplasmic bodies: Mainly visible on Gomori trichrome & Toluidine blue
- Cytoplasmic bodies: Have a surrounding halo; Round shape; Large size
- Rods: No halo; More per each individual fiber; Higher frequency of involved fibers
- Also see: Rods or Cytoplasmic bodies in target fibers
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Nemaline rod myopathy: Infantile
![](../pics/biopsy/rods/rodsinfantlg.jpg)
Gomori trichrome
Nemaline rods in gastrocnemius muscle from 4 month old child
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![](../pics/biopsy/rods/rodnorodmp.jpg)
No nemaline rods in quadriceps muscle from same child biopsied at 2 months of age
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Nemaline rod myopathy, Infantile: Toluidine blue stains
Nemaline rod myopathy, Infantile: Other stains
![](../pics/biopsy/rods/rodhelp.jpg)
H&E stain
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Muscle fiber sizes: Varied
![](../pics/biopsy/rods/rodhemp.jpg)
H&E stain
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![](../pics/biopsy/rods/rodinfhe2.jpg)
H& E stain
Muscle fiber size: Varied
Refractile rods can be seen
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![](../pics/biopsy/rods/Rodinfatp94.jpg)
ATPase stain, pH 9.4
Type I muscle fiber predominance
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![](../pics/biopsy/rods/rod4mohe.jpg)
H& E stain
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Rods: Actin stain
![](../pics/biopsy/rods/rodphalloidin.jpg)
Phalloidin staining for actin
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Focal (bright green), large and small aggregates of actin are present in some muscle fibers |
![](../pics/biopsy/rods/rodphalloidinlong.jpg)
Phalloidin staining for actin
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Nemaline Rod Ultrastructure
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Infantile-onset Rod myopathy |
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![](../pics/biopsy/rods/rodem3m.jpg)
From: R Schmidt
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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
![](../pics/biopsy/rods/rod3mhp.jpg)
From: R Schmidt
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![](../pics/biopsy/rods/rodem3mhp2.jpg)
From: R Schmidt
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Nemaline Rods: Mouse Model
![](../pics/biopsy/rods/rodemsmv.jpg)
From E Hardeman
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Electron microscopy of rods from Z-lines in Met9Arg αTMslow mouse
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Nemaline rod myopathy, infant (8 months of age): Type 1 muscle fiber smallness
Rods: More prominent in smaller muscle fibers
![](../pics/biopsy/rods/rod8mogt.jpg)
Gomori trichrome
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![](../pics/biopsy/rods/rod8moatp94.jpg)
ATPase pH 9.4
Type 1 muscle fibers: Small (Pale)
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![](../pics/biopsy/rods/rod8mohe.jpg)
H&E
Muscle fiber sizes: Bimodal
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![](../pics/biopsy/rods/rod8monadh.jpg)
NADH
Internal architecture of muscle fibers: Irregular
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Rod Myopathy: Congenital + Arthrogryposis
![](../pics/biopsy/rods/rodscongenhe.jpg)
H&E stain
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Fiber sizes: Bimodal distribution
![](../pics/biopsy/rods/rodscongengt.jpg)
Gomori trichrome stain
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Rods
Dark-stained: Punctate or Clustered regions, Often sub-sarcolemmal
More common in smaller muscle fibers
![](../pics/biopsy/rods/rodscongengthp.jpg)
Gomori trichrome stain
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![](../pics/biopsy/rods/rodscongengtlong.jpg)
Gomori trichrome stain
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![](../pics/biopsy/rods/rodscongenatp94.jpg)
ATPase pH 9.4 stain
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Fiber types
Type 1 fibers: Usually small
Type 2 fibers: Larger; Abnormal intermediate staining (2C) at ATPase pH 4.3
![](../pics/biopsy/rods/rodscongenatp43.jpg)
ATPase pH 4.3 stain
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![](../pics/biopsy/rods/rodscongennadh.jpg)
NADH stain
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Rods: In clusters in muscle fibers
![](../pics/biopsy/rods/rodtbx.jpg)
Toluidine blue stain
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![](../pics/biopsy/rods/rodlongtb1.jpg)
Toluidine blue stain
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Nemaline rod myopathy, Childhood: 2 Different patterns
Rods: In smaller muscle fibers
![](../pics/biopsy/rods/rodchildgt.jpg)
GT stain
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![](../pics/biopsy/rods/Rodschildatp94.jpg)
ATPase stain, pH 9.4
Type I muscle fibers: Smaller than type II
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Rods: In small & large muscle fibers
![](../pics/biopsy/rods/rod664chgt.jpg)
GT stain
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Type I predominance
![](../pics/biopsy/rods/rod664chatp94.jpg)
ATPase stain, pH 9.4
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Fiber size variation: Bimodal distribution
![](../pics/biopsy/rods/rod664chhe.jpg)
H&E stain
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Rods: Adult nemaline myopathy
Several patterns
Rods: Larger & Aggregated
![](../pics/biopsy/rods/Rodsadultgthp.jpg)
Gomori trichrome
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Rods: May cluster near myonuclei (Arrow)
![](../pics/biopsy/rods/rodpngt.jpg)
Gomori trichrome
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Rods: Small & Diffusely distributed in some muscle fibers
Myopathic features: Varied muscle fiber size; Internal nuclei; Endomysial connective tissue increased
![](../pics/biopsy/rods/rod512adgt1.jpg)
Gomori trichrome
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![](../pics/biopsy/rods/rod512adgt2.jpg)
Gomori trichrome
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![](../pics/biopsy/rods/roddif.jpg)
Gomori trichrome
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![](../pics/biopsy/rods/roddif2.jpg)
Gomori trichrome
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![](../pics/biopsy/rods/rod512adhe.jpg)
H&E stain
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Rods: Atypical
![](../pics/biopsy/rods/agggt.jpg)
Gomori trichrome stain
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Rod-like Aggregates
Stain dark on Gomori trichrome
Near myotendinous junctions
Gomori trichrome stain
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![](../pics/biopsy/rods/aggtb.jpg)
Toluidine blue stain
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Rod-like Aggregates: Rod shape in fixed sections
Rod-like Aggregates (Ultrastructure)
Dark stained
Internal structure: Amorphous
Shape: Irregular; Polygonal
Halo: Contains linear structures
Rods: ACTA1 mutation (M46T)
13 yo male with Rod myopathy
No rods in muscle biopsy of same patient at
1 year old
![](../pics/biopsy/rods/acta1/rodacta1he.jpg)
H&E stain
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Fiber Sizes
Small
Mild variation
Myonuclei
Mildly large
Shapes: Irregular
![](../pics/biopsy/rods/acta1/rodacta1he2.jpg)
H&E stain
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![](../pics/biopsy/rods/acta1/nemmyopnuccr.jpg)
Congo red stain
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Rod Myopathy (ACTA1): Myonuclei
Abundant
Shapes: Irregular
Sizes: Large
![](../pics/biopsy/rods/acta1/nemmyopnuccr2.jpg)
Congo red stain
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![](../pics/biopsy/rods/acta1/rodacta1atp43.jpg)
ATPase pH 4.3 stain
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Type I muscle fiber predominance
![](../pics/biopsy/rods/acta1/rodacta1gt.jpg)
Gomori trichrome stain
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Rods
Irregular shaped clusters of dark stained material in myofiber cytoplasm
![](../pics/biopsy/rods/acta1/rodacta1gt2.jpg)
Gomori trichrome stain
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![](../pics/biopsy/rods/acta1/rodacta1gt3.jpg)
Gomori trichrome stain
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![](../pics/biopsy/rods/acta1/rodphal3ar.jpg)
Phalloidin stain for Actin
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Actin aggregates in Rod myopathy (Arrows)
Clustered in regions of muscle fiber cytoplasm
![](../pics/biopsy/rods/acta1/rodphal1ar.jpg)
Phalloidin stain for Actin
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![](../pics/biopsy/rods/acta1/rodacta1tb4.jpg)
Toluidine blue stain
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![](../pics/biopsy/rods/acta1/rodacta1tb1.jpg)
Toluidine blue stain
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Rods
Morphology: Dark-stained rod-shaped inclusions
Distribution: Clustered or scattered in myofiber cytoplasm
![](../pics/biopsy/rods/acta1/rodacta1tb2.jpg)
Toluidine blue stain
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![](../pics/biopsy/rods/acta1/rodacta1tb3.jpg)
Toluidine blue stain
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Rods
Dark-stained rod-shaped inclusions: Often aligned along Z-bands
Rods
Rods occuring in a subsarcolemmal cluster
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 sections: Lattice structure like Z disk
Thin filaments: May be in continuity with rods
Rod Myopathy: Same patient as
above at 1 year old
No rods
Type 1 muscle fibers: Small
![](../pics/biopsy/rods/acta1/rodnegacta1he.jpg)
H&E stain
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Mucle fiber sizes: Varied
![](../pics/biopsy/rods/acta1/rodnegacta1gtmp.jpg)
Gomori trichrome stain
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No rods are visible on Gomori trichrome stain
![](../pics/biopsy/rods/acta1/rodnegacta1gthp.jpg)
Gomori trichrome stain
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![](../pics/biopsy/rods/acta1/rodnegacta1cr.jpg)
Congo red stain
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Nuclear shapes: Irregular
Mucle fiber sizes: Varied
![](../pics/biopsy/rods/acta1/rodnegacta1nadh.jpg)
NADH stain
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![](../pics/biopsy/rods/acta1/rodnegacta1atp94.jpg)
ATPase pH 9.4 stain
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Type I muscle fibers: Small
![](../pics/biopsy/rods/acta1/rodnegacta1atp43.jpg)
ATPase pH 4.3 stain
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Z-Disk: Streaming & Other disorders
Z-Disk: Streaming
- Z-Streaming Definition: Dense Z-band material extends from Z-Disk
- Into sarcomere
- May reach adjacent Z-Disk
- More common: In areas without mitochondria
- Anatomical Association: Loss of thick filaments, or of entire sarcomere
- Z-Streaming: Associations
- Other Z-line disorders
Z-disk Streaming
Crosses up to 2 sarcomeres
Return to
Rod myopathies
References
1.
J Neuropathol Exp Neurol 2022;81:304-307
10/26/2022