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TUBULAR AGGREGATES

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Tubular aggregates   Differential Diagnosis   Pathology Location: Cytoplasm Origin: Sarcoplasmic reticulum Histochemistry: Similar to Cylindrical spirals H & E Irregular, internal regions, slits or lakes May be clear, or contain pink material Gomori trichrome Contain red material Location: Central or sub-sarcolemmal VvG stain: Gray NADH: Stain strongly ATPase: Often in type II > I muscle fibers Sudan: Tubular aggregates contain lipid AMPDA: Stain strongly No reaction Mitochondrial stains: COX & SDH Acid & Alkaline phosphatase Protein contents 1 DHPR: T-tubules RyR1: Terminal cisternae; Sarcoplasmic reticulum SERCA1: Longitudial sarcoplasmic reticulum Other: In some patients SERCA2: Longitudial sarcoplasmic reticuilum SAR1 : Endoplasmic exit sites Dysferlin CASQ1 Ultrastructure: 3 types

H & E stain

Muscle fibers
  Pink cytoplasmic areas: May contain nuclei
  Irregular-shaped clear regions

H & E stain

Congo red stain

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Gomori trichrome stain Tubular aggregates   Stain red on Gomori trichrome

Gomori trichrome stain

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Gomori trichrome stain

Tubular aggregates: May have elongated or rounded shapes

Gomori trichrome stain

Gomori trichrome stain

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VvG stain Tubular aggregates   Stain gray-black on VvG

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NADH-TR reductase (NADH) stain Tubular aggregates:   Stain dark on NADH

NADH stain

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AMPDA stain

Tubular aggregates: Contain AMPDA

AMPDA stain

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ATPase pH 9.4 stain

Tubular aggregates (Pale regions): Are often more common in type 2 muscle fibers

ATPase pH 4.3 stain

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Sudan black stain

Tubular aggregates: Stain for lipid on Sudan black

Sudan black stain

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Tubular aggregates
  May have mild or patchy staining for Acid Phosphatase

Acid Phosphatase stain

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Tubular aggregates: Ultrastructure ²

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Tubules: 3 types

• I: 50 to 70 nm diameter tubules with 20 to 40 nm inner central tubule
• II: 70 to 400 nm tubules with moderately dense material in center
• III: 130 to 400 nm diameter tubules containing several 25 to 40 nm tubules

Tubular Aggregates: Constituents & Patterns

• Ordered Tubules
  • Tubule contents: Varied
    • Inner smaller tubule (Double-walled)
    • Flocculent, granular materal
  • Tubule sizes: Similar for most; May contain scattered moderately larger tubules
  • May be surrounded by larger sarcoplasmic reticulum vacuoles
• Clustered/Disordered Tubules
  • Tubule sizes: Varied
  • Tubule variants
  • Locations
    • Entire tubular aggregates
    • Similar regions may surround ordered tubular aggregates
• Associated Structures
  • Cylindrical Spirals

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From: R Schmidt

Tubular aggregates: Ordered
  Arrays of 50 nm tubules: May range from to 80 nm
  Single-walled
  Contents: Clear or Granular; May contain 20 to 30 nm inner tubules
  Locations
    Often sub sarcolemmal
    May be in central regions of muscle fibers
    Some are peri-nuclear
  Associations
    May connect with lateral cisternae of Sarcoplasmic reticulum
    May be surrounded by dilated SR sacs
  Variants: Irregular clusters of varied sized tubules
  Common syndrome associations: Periodic paralysis; Congenital MG syndromes; Cramp/Myalgia syndromes

From: R Schmidt

From: R Schmidt

Tubular aggregates
  Arrays of 20 to 50 nm tubules
  Single-walled
  Some larger 150 to 500 nm sacs are intermixed within the tubular aggregates

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From: R Schmidt

Tubular aggregates: Longitudinal sections
  Long parallel membranes
  General contents: Granular; Moderately dark-stained
  Interruptions: Contain pale rounded swellings in regions along their length

From: R Schmidt

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Tubular aggregates: Regional associations

From: R Schmidt

Tubular aggregates: 2 in one muscle fiber
  Locations: 1 subsarcolemmal; 1 in central region of fiber
  Fiber type: Likely type 2 with fewer mitochondria & paler Z-bands than type 1 fiber at upper left
  Nucleus is within subsarcolemmal region of tubular aggregates

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From: R Schmidt

Well formed Tubular aggregate surrounded by irregularly distributed larger tubules

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From: R Schmidt

Tubular aggregate: Perinuclear

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From: R Schmidt

Clustered vesicles/tubules with varied sizes surrounded by irregularly distributed larger tubules

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From: R Schmidt

Regions of loosely aggregated tubules
  Tubule sizes vary widely
  Larger tubules: Contents are often pale-stained
  Small tubules: Contents are often darker-stained
  Lipopigment may be scattered in these areas
  Tubules may be located between sarcomeres

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Tubular Aggregates: Unordered

From: R Schmidt

Regions of aggregated tubules
  Tubule sizes vary widely
  Larger tubules
    Some have thick walls
    Contents are often pale-stained
  Small tubules: Contents are often darker-stained

From: R Schmidt

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Tubule Variants

From: R Schmidt

Tubule variants: May have
  Thick walls
  Layered walls
  Dark-stained internal regions
  Thin membrane contents
  Cylindrical Spirals
  Large size

From: R Schmidt

From: R Schmidt

Tubule variants: May have
  Thick walls
  Layered walls
  Dark-stained internal regions
  Thin membrane contents
  Cylindrical Spirals
  Large size

From: R Schmidt

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From: Tahseen Mozaffar

Tubular Aggregates: Ultrastructure

From: Oliver Ni

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Tubular Aggregates: Mouse Muscle

From: Andrew Findlay

From: Andrew Findlay

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Mair & Tome

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Return to Myopathies with tubular aggregates

References
1. J Neuropathol Exp Neurol 2016;75:1171-1178
2. Gen Physiol Biophys 2003;22:425-40

7/19/2026