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MITOCHONDRIAL DISEASE PATHOLOGY

Distinctive features   Biopsy differential diagnosis   Cytochrome oxidase   Ragged red fibers   SDH   Ultrastructure

Syndromes   AZT   CFC1   Coenzyme Q10 deficient   COX deficient   IRIS   Kearns-Sayre   Megaconial   MELAS     Brain     Muscle   PEO     Autosomal Dominant     Sporadic     Other     Extraocular Muscle   SURF1   Ultrastructure

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MITOCHONDRIAL PROLIFERATION

Ragged Red Muscle Fibers (Gomori trichrome stain)
SDH stain: More sensitive for detecting mitochondrial proliferation

Gomori trichrome stain

Mitochondrial proliferation, Mild to Moderate: In muscle fibers
(Red rim & Irregular sarcoplasm)

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Gomori trichrome stain

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

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Mitochondrial Proliferation

Muscle fibers with mitochondrial proliferation: Increased SDH staining

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.

Succinic dehydrogenase (SDH) stain

Mitochondrial Proliferation in Muscle fibers

Succinic dehydrogenase (SDH) stain

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Other stains

H & E stain

H & E stain

Myofibers with mitochondrial proliferation: May have
  Clear, or stained, external rim on H & E stain (Above)
  Increased lipid: Many small lipid droplets (Below)

Sudan stain

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Gomori trichrome stain

VvG stain

ATPase pH 4.3 stain

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CYTOCHROME OXIDASE (COX)

Adult
  Scattered COX- muscle fibers

Cytochrome oxidase (COX) stain

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.

Cytochrome oxidase (COX) stain

Cytochrome oxidase (COX) Negative muscle fibers
  COX staining is markedly reduced
  Punctate mitochondria are reduced or not visible

Cytochrome oxidase (COX) stain

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Reduced COX staining is often segmental: Other areas along the length of the muscle fiber may be normal

Cytochrome oxidase (COX) stain

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Adult: COX + SDH stain

COX + SDH stain

Cytochrome oxidase (COX) negative muscle fibers
  Stain varying shades of blue

COX + SDH stain

COX + SDH stain

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Child
  COX deficiency in all muscle fibers

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

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Progressive External Ophthalmoplegia (PEO)

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PEO: Single large mitochondrial DNA deletion

Biopsy from muscle with normal strength

H & E stain	SDH stain	Cytochrome oxidase (COX) stain
Scattered intermediate sized polygonal muscle fibers	Muscle fibers with excessive SDH staining (left) have reduced or absent COX (right) staining (arrows)

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PEO: Autosomal Dominant

Biopsy from weak muscle

Gomori Trichrome stain	SDH stain	Cytochrome oxidase (COX) stain
Varied muscle fiber size: Small fibers are rounded Increased endomysial connective tissue	Muscle fibers with excessive SDH staining (left): COX is present in all fibers (right)

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

8/25/2022