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Myofibrillar (Desmin) Myopathy

Desmin   Aggregates   Caps   Myopathy (I402N)     5th decade     3rd decade   Myopathy (R454W)     AVSF     Ultrastructure ZASP

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Cytoplasmic aggregates   Eosinophilic   Homogeneous   H & E stain

H & E stain

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Gomori trichrome stain

Cytoplasmic aggregates
  Dark stained regions
  Irregular shapes
  May be several in each fiber

Gomori trichrome stain

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Sarcoplasmic membranes
  Absent from regions with desmin-containing cytoplasmic bodies.
  Irregular (moth-eaten) internal architecture is present in several muscle fibers

NADH stain

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Myofibrillar apparatus
  Absent from regions with desmin-containing cytoplasmic bodies
  Aggregates are in both fiber types

ATPase, pH 9.4

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Desmin aggregates   Cytoplasmic accumulations   Various shapes & sizes   Other desmin staining     Diffuse in regenerating fibers

Anti-desmin antibody

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Myofibrillar Myopathy: Desmin mutations

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I402N Desmin mutation: 46 year old patient

H&E stain

Fiber size: Varied, Large & Small
Necrosis: Few fibers
Internal nuclei
Endomysial connective tissue: Mildly increased

H&E stain

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Gomori trichrome stain

Internal nuclei
Internal architecture: Aggregates; Irregular

Gomori trichrome stain

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VvG stain

Internal architecture: Aggregates; Irregular

VvG stain

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HADH stain

Internal architecture: Irregular

HADH stain

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Congo red stain

Nuclei: Internal; Clustered; Irregular shapes; Large
Cytoplasm: Congophilic aggregates

Congo red stain

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Desmin stain

Desmin: Cytoplasmic aggregates

Desmin stain

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I402N Desmin mutation: 24 year old patient

H&E stain

Fiber size: Varied
Endomysial connective tissue: Mildly increased

H&E stain

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Gomori trichrome stain

Fiber size: Varied
Endomysial connective tissue: Mildly increased
Internal nuclei
Aggregates: Irregular; Dark stained

Gomori trichrome stain

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Congo red stain

Fiber size: Varied
Internal nuclei

Congo red stain

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NADH stain

Internal architecture: Mildly irregular

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Desmin stain

Desmin: Small or Irregular aggregates

Desmin stain

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Desmin Myopathies with Sarcolemmal Vacuoles

R454W Desmin tail domain mutation

Histochemistry Vacuoles with Sarcolemmal Features Ultrastructure

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H&E stain Myopathy   Multifocal pathology   Muscle fibers     Atrophy: Often in groups     Hypertrophy     Clear, irregular vacuoles   Endomysial connective tissue: Increased

H&E stain

H&E stain

H&E stain

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Gomori trichrome stain

Vacuoles   Irregular shapes   Contain red-staining material   Subsarcolemmal or Central

Invaginations   Branched   Extend deeply into muscle fibers   May contain capillaries

Gomori trichrome stain

Gomori trichrome stain

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Cytoplasmic bodies

Gomori trichrome stain

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Myopathy   Muscle fibers     Varied size     Internal architecture       Irregular       Aggregates       Vacuoles   Endomysium     Connective tissue       Increased

VvG stain

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Internal architecture: Irregular

NADH stain

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Congo red stain

Vacuoles: Contain basophilic granular debris
Splits & Invaginations: Extensive; Branched
Nuclei: Large; Irregular shapes; Some have clear centers

Congo red stain

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ATPase pH 9.4 stain Aggregates (Pale areas): In Type I & II fibers

ATPase pH 9.4 stain

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Type IIC fibers: Common ATPase pH 4.3 stain

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Caveolin-3 stain Invaginations & Vacuoles: Lined with Caveolin-3 on membrane

Caveolin-3 stain

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Dystrophin stain Invaginations & Vacuoles: Lined with Dystrophin on membrane

Dystrophin stain

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Aggregates: Stain for desmin Desmin stain

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Desmin Myopathy: Ultrastructure (R454W)

Aggregates   Filaments   Organelles Tubules Vacuoles Z-Disk

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From: R Schmidt

Desmin Myopathy: Filament Aggregates

From: R Schmidt

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Desmin Myopathy: Filament Aggregates
  Loose filament cluster with additional organelles & Z-Band-like material

From: R Schmidt

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Desmin Myopathy: Organelle Aggregates

From: R Schmidt

Subsarcolemmal Cluster of Organelles
  Membrane & Basal lamina invagination with Extracellular debris (Arrow)

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From: R Schmidt

Cluster of Organelles within muscle fiber
  Contents include Mitochondria, Vacuoles with irregular membranes & Droplets of abnormal lipid

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Desmin Myopathy: Z-Disk pathology

From: R Schmidt

From: R Schmidt

Z-Disk: Streaming
  General: Extension of Z-Disk material along long axis of muscle fiber
  Also see: Rod myopathy

From: R Schmidt

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Z-band Disruption

From: R Schmidt

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From: R Schmidt

Desmin Myopathy: Dark Tubules

From: R Schmidt

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Autophagic Vacuoles

From: R Schmidt

Desmin Myopathy
  Vacuoles: Have varied contents
  Aggregated material: May surround vacuoles

From: R Schmidt

Autophagic Vacuoles
  Contents: Varied
  May be surrounded by dark aggregated material

From: R Schmidt

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From: R Schmidt

Autophagic Vacuoles: Varied Contents

From: R Schmidt

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From: R Schmidt

Autophagic Vacuoles: Varied Contents

From: R Schmidt

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From: R Schmidt

Autophagic Vacuoles: Contain membranes & Membranous whorls

From: R Schmidt

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Sural nerve: Mildly reduced number of myelinated axons Toluidine blue stain

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Return to Myofibrillar/Desmin myopathies
Return to Muscle biopsies

4/20/2021