Neuromuscular

Myofibrillar (Desmin) Myopathy

Aggregates
Desmin
  Myopathy
    5th decade
    3rd decade
    AVSF
  Caps
ZASP

Cytoplasmic aggregates
  Eosinophilic
  Homogeneous


 

H & E stain

H & E stain


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

Gomori trichrome stain

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

NADH stain

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

ATPase, pH 9.4

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

 


Anti-desmin antibody

Myofibrillar Myopathy: Desmin mutations


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


Gomori trichrome stain
Internal nuclei
Internal architecture: Aggregates; Irregular

Gomori trichrome stain


VvG stain
Internal architecture: Aggregates; Irregular

VvG stain


HADH stain
Internal architecture: Irregular

HADH stain


Congo red stain
Nuclei: Internal; Clustered; Irregular shapes; Large
Cytoplasm: Congophilic aggregates

Congo red stain


Desmin stain
Desmin: Cytoplasmic aggregates

Desmin stain

I402N Desmin mutation: 24 year old patient

H&E stain
Fiber size: Varied
Endomysial connective tissue: Mildly increased

H&E stain


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

Gomori trichrome stain


Congo red stain
Fiber size: Varied
Internal nuclei

Congo red stain


NADH stain
Internal architecture: Mildly irregular


Desmin stain
Desmin: Small or Irregular aggregates

Desmin stain

Desmin Myopathies with Sarcolemmal Vacuoles

R454W Desmin tail domain mutation
Histochemistry
Vacuoles with Sarcolemmal Features
Ultrastructure


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

H&E stain

H&E stain

H&E stain


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

Cytoplasmic bodies

Gomori trichrome stain

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

VvG stain

Internal architecture: Irregular

NADH stain


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

Congo red stain


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

ATPase pH 9.4 stain

Type IIC fibers: Common

ATPase pH 4.3 stain


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

Caveolin-3 stain


Dystrophin stain
Invaginations & Vacuoles: Lined with Dystrophin on membrane

Dystrophin stain

Aggregates: Stain for desmin

Desmin stain

Desmin Myopathy: Ultrastructure
Aggregates
  Filaments
  Organelles
Tubules
Vacuoles
Z-Disk


From: R Schmidt
Desmin Myopathy: Filament Aggregates

From: R Schmidt

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

From: R Schmidt

Desmin Myopathy: Organelle Aggregates

From: R Schmidt
Subsarcolemmal Cluster of Organelles
  Membrane & Basal lamina invagination with Extracellular debris (Arrow)


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

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

Z-band Disruption

From: R Schmidt


From: R Schmidt
Desmin Myopathy: Dark Tubules

From: R Schmidt


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


From: R Schmidt
Autophagic Vacuoles: Varied Contents

From: R Schmidt


From: R Schmidt
Autophagic Vacuoles: Varied Contents

From: R Schmidt


From: R Schmidt
Autophagic Vacuoles: Contain membranes & Membranous whorls

From: R Schmidt

Sural nerve: Mildly reduced number of myelinated axons

Toluidine blue stain

Return to Myofibrillar/Desmin myopathies
Return to Muscle biopsies

4/20/2021