Neuromuscular

MITOCHONDRIAL DISEASE PATHOLOGY

Distinctive features
  Biopsy differential diagnosis
  Cytochrome oxidase
  Ragged red fibers
  SDH
  Ultrastructure
Syndromes
  MELAS
    Brain
    Muscle
  Kearns-Sayre
  PEO
    Autosomal Dominant
    Sporadic
  Coenzyme Q10 deficiency
  COX deficiency


RAGGED RED MUSCLE FIBERS


Gomori trichrome stain

Muscle fibers have mild to moderate mitochondrial proliferation
(Red rim & speckled sarcoplasm)


Gomori trichrome stain

Marked mitochondrial proliferation. Mitochondria have replaced
      most other structures in one of the muscle fibers

Mitochondrial Proliferation

Increased SDH staining in muscle fibers with mitochondrial proliferation

Adult

Succinic dehydrogenase (SDH) stain

Child

Succinic dehydrogenase (SDH) stain
Mitochondrial disorder

Succinic dehydrogenase (SDH) stain
Normal

Muscle fibers with mitochondrial proliferation stain darkly for succinic dehydrogenase (SDH).
SDH is the most sensitive stain for detecting mitochondrial proliferation.

Other stains



H & E stain

Muscle fibers with mitochondrial proliferation
may have a clear external rim on H & E stain

Sudan stain

Ragged red fibers often have increased lipid
 

CYTOCHROME OXIDASE (COX)

Scattered COX- muscle fibers: Adult

Cytochrome oxidase (COX) stain
  • Type I fibers stain more darkly than type II.
  • Several fibers have no staining for cytochrome oxidase (COX).
  • On SDH, COX- muscle fibers may be normal or have increased staining
  • In normal biopsies virtually all fibers have staining for COX.


COX deficiency: Child
Cytochrome oxidase (COX) stain
Cytochrome oxidase (COX) stain
Mitochondrial disorder

Cytochrome oxidase (COX) stain
Normal
  • Cytochrome oxidase (COX) levels are reduced in all muscle fibers (Left)
  • Normal muscle (Right) has COX staining in all muscle fibers: More in type I than type II



Progressive External Ophthalmoplegia (PEO)


PEO: Single large mitochondrial DNA deletion

Biopsy from muscle with normal strength

H & E stain

Scattered intermediate sized polygonal muscle fibers

SDH stain

Cytochrome oxidase (COX) stain

Muscle fibers with excessive SDH staining (left) have reduced or absent COX (right) staining (arrows)


PEO: Autosomal Dominant

Biopsy from weak muscle

Gomori Trichrome stain

Variable fiber size: Small fibers are rounded
Increased endomysial connective tissue



SDH stain

Cytochrome oxidase (COX) stain

Muscle fibers with excessive SDH staining (left): COX is present in all fibers (right)


Return to Mitochondrial Ultrastructure
Return to Mitochondrial syndromes
Return to Muscle biopsies

7/22/2005