Neuromuscular

CENTRONUCLEAR (MYOTUBULAR) MYOPATHY

General features
Infantile
Childhood
Juvenile
  Necklace fibers
  Abnormal fiber types
  Punctate, Small fibers
  DNM2 mutations: Myopathic

General

Centronuclear myopathy: Infantile

A single central nucleus in many muscle fibers

   
From: T Mozaffar


H&E stain

H&E stain

H&E stain

H&E stain

Toluidine blue stain
Central nuclei & abnormal internal architecture



Toluidine blue stain

Toluidine blue stain

Toluidine blue stain

Electron microscopy from T Mozaffar


Type I (light) muscle fibers tend to be smaller than type II.
Clear regions occur in center of some fibers.


ATPase stain, pH 9.4

ATPase stain, pH 9.4


Internal architecture: Small muscle fibers.
  Darker staining: Central regions
  Clear rim around edge


NADH stain

NADH stain




NADH stain

Centronuclear myopathy: Childhood


H&E stain

H&E stain

NADH stain

ATPase stain, pH 9.4
Some smaller muscle fibers
  Central nuclei
Other muscle fibers
  Central regions are basophilic.
Abnormal internal architecture.
  Central dark staining.
  Coarse
  Radial strands
Type I (light) muscle fibers
  Smaller than type II
  Clear central regions

Muscle fibers with abnormal internal architecture, including "radial" strands and necklace fibers
NADH stain

Centronuclear myopathy: Juvenile with Necklace fibers



H&E stain
H+E
H&E stain
Muscle fiber sizes: Bimodal distribution
Central nuclei: Especially in smaller fibers
Clefts: In center of other muscle fibers


H&E stain


Gomori trichrome stain
Central nuclei: Especially in smaller fibers
Clefts: In center of other muscle fibers
Rings (Necklaces): In some muscle fibers


Gomori trichrome stain

Necklace fibers
  Dark fibers: Rings
  Light fibers: Irregular internal architecture

NADH stain

NADH stain

  ATPase, pH 9.4
ATPase pH 9.4 stain
Small muscle fibers
  Most are type 1
  Contain central clear regions


ATPase pH 4.3 stain


Esterase stain

Centronuclear myopathy: Juvenile with many Central nuclei & Type 2C fibers


H&E stain
Many muscle fibers have single central nuclei


H&E stain


VvG stain


NADH stain
Abnormal internal architecture around central nuclei


ATPase pH 9.4 stain


ATPase pH 4.3 stain
Many abnormal, intermediate-staining (type 2C), muscle fibers

Centronuclear myopathy: Juvenile with Small muscle fibers & Punctate central NADH stain



H&E stain
Many muscle fibers have single central nuclei


H&E stain stain


NADH stain
Punctate central staining in many muscle fibers


ATPase pH 9.4 stain
Type 1 muscle fibers are smaller than type 2


ATPase pH 4.3 stain

Centronuclear myopathy: Teenage, DNM2 mutation


H&E stain
Myopathic muscle
Central nuclei: Single; In most muscle fibers
Endomysial connective tissue: Increased between muscle fibers
Fat: Replaces perimysium and some muscle


Gomori trichrome stain

H&E stain

NADH stain
Abnormal internal architecture
Muscle fibers may have radial strands, necklace formations or central "dots"

NADH stain

NADH stain

ATPase pH 4.3 stain
Fiber types: All type I

Acid phosphatase stain

Cytochrome oxidase stain
Central abnormalities in internal architecture
Lysosomal (Acid phosphatase positive; Above)
Mitochondrial (COX positive; Left)
Endoplasmic reticulum (Caveolin-3 positive; Below)




Caveolin-3 stain

Cytoplasmic abnormalities: Dystrophin & Desmin staining


Dystrophin stain

Desmin stain

Nuclei: Large central nuclei with irregular emerin

Emerin stain

Also see: Congenital fiber type size disproportion
Return to Centronuclear myopathy

4/1/2014