Neuromuscular

PHOSPHORYLASE DEFICIENCY (McArdle Disease)

Vacuoles
No vacuoles
Rhabdomyolysis
  Muscle fibers: Dark necrosis
Post-Rhabdomyolysis
Ultrastructure

McArdle Disease: Vacuoles
  Often subsarcolemmal


H&E stain
Subsarcolemmal cytoplasmic vacuoles (Blebs)
  Most contain diffuse pale-staining material
  May contain myonuclei
 

H & E stain
 

 

 

 

VvG stain
Sub-sarcolemmal blebs
  Pale staining of contents on Gomori trichrome
  May contain myonuclei

Gomori trichrome stain

NADH stain
Subsarcolemmal vacuoles


NADH stain

NADH stain
PAS: May stain contents of sub-sarcolemmal blebs, or be diffusely increased in sarcoplasm

PAS stain

Phosphorylase stain
McArdle disease: Phosphorylase deficiency
  Absent in muscle fibers
  May be residual activity in vessels

Phosphorylase stain
Normal
  Phosphorylase in muscle fiber cytoplasm
  More in type II muscle fibers

PAS stain

McArdle disease: Muscle fibers in regions with few blebs


H&E stain
Linear "cracks" in muscle fibers

NADH stain
Linearized pattern of internal architecture: Type 2 > Type 1


Phosphorylase Deficiency
  Internal nuclei: some muscle fibers
  Prominent internal architecture

VvG stain

Phosphorylase stain     From: S Moore

Phosphorylase stains
McArdle disease
Some phosphorylase staining is present in vessels &
  regenerating muscle fibers

Phosphorylase stain: Normal

Type II fibers: Darker than type I  

Phosphorylase stain: McArdle disease

Myophosphorylase deficiency
Muscle fibers stain yellow

PAS stain: McArdle disease
McArdle disease: Glycogen increased (metachromatic blue) in muscle fiber cytoplasm

PAS stain: McArdle disease
Glycogen: PAS stain
  Increased: Diffusely in cytoplasm
  Slightly metachromatic blue color in some areas
  May also stain contents of blebs
PAS stain: McArdle's disease

PAS stain: McArdle's disease
Fiber types

Vacuoles: May be in type I or type II muscle fibers


ATPase pH 9.4 stain

ATPase pH 4.3 stain
Immature (Type 2C) muscle fibers are common

ATPase pH 4.3 stain

Phosphorylase Deficiency: Rhabdomyolysis


H&E stain
Necrotic Muscle fibers: Scattered; Stain Dark
Contrast: Pale necrotic fibers with Alcohol toxicity

Gomori trichrome stain
Phosphorylase deficiency: Necrotic muscle fibers
Pale on NADH: Despite dark stain on H&E & Gomori trichrome (Above)

NADH stain
Necrotic Muscle Fibers: Varied stages
  Dark
  Pale: Few fibers
  Replaced by histiocytic cells

H&E stain

Gomori trichrome stain
Necrotic Muscle Fibers: Varied stages
Cytoplasm
  Early
    Most necrotic fibers: Diffusely Dark stained; ? Hyper-contracted
  Intermediate
    Disintegrated fibers (Dark Arrow): Pale with irregular cytoplasm remnenats
  Late
    Replaced by histiocytic cells (White Arrow)

Gomori trichrome stain

NADH stain
Necrotic Muscle Fibers
  Pale: Reduced NADH staiining of cytoplasm
  Replaced by histiocytic cells: NADH+ cells in cytoplasm
  Hyper-contracted: Dark-stained cytoplasm

NADH stain
Glycogen in muscle fibers
  Reduced or absent during rhabdomyolysis

PAS stain

Acid phosphatase stain
Histiocytic cells
  Acid phosphatase positive cells invading or replacing scattered muscle fibers
  A few necrotic muscle fibers with pale cytoplasm are not invaded by histiocytes

Acid phosphatase stain
Necrotic muscle fibers: Characteristic pattern of irregular alkaline phosphatase stain around fibers

Alkaline phosphatase stain

ATPase pH 4.3 stain
Scattered small muscle fibers with intermediate staining

Phosphorylase stain
Phosphorylase
  Absent in large regions of muscle (Above)
  Other isozymes upregulated in scattered muscle fibers (Below)

Phosphorylase stain

Phosphorylase Deficiency, Early Rhabdomyolysis: Dark Necrosis of Muscle Fibers


Gomori Trichrome stain
Dark Necrosis
  Scattered muscle fibers have feature-less dark-stained cytoplasm

Alkaline phosphatase stain
Dark necrotic muscle fibers
  Surrounded by alkaline phosphatase stain

H&E stain
Dark necrotic muscle fibers
  Cytoplasm is diffusely dark stained

H&E stain

Gomori Trichrome stain
Dark necrotic muscle fibers
  Cytoplasm is diffusely dark stained

Gomori Trichrome stain

VvG stain
Dark necrotic muscle fibers
  Cytoplasm is diffusely dark stained

VvG stain

Acid Phosphatase stain
Dark necrotic muscle fibers
  May be surounded by histiocytes

Acid Phosphatase stain

NADH stain
Dark necrotic muscle fibers
  Pale stain on NADH: Typical of all types of muscle fiber necrosis

NADH stain

H&E stain
Dark necrotic muscle fibers: Slightly later stage
  Dark necrotic fibers may become
    Invaded by histiocytes (Above & Below)
    Degenerated with pale, fragmented cytoplasm but no associated histiocytes

Gomori trichrome stain
Dark necrotic muscle fibers: Slightly later stage
  Dark necrotic fibers may become
    Invaded by histiocytes

H&E stain

Phosphorylase Deficiency: Post-Rhabdomyolysis


H&E stain
Smaller or Immature Muscle fibers: Scattered
Internal architecture: Cracks & Clefts

H&E stain
Subsarcolemmal Blebs

NADH stain
Post Necrosis
  Residual histiocytic, Acid phosphatase-positive, cells scattered in endomysium

Acid phosphatase stain
Glycogen: PAS positive areas in muscle fiber cytoplasm

PAS stain
Immaturity: Many intermediate-stained (Type 2C) fibers

ATPase pH 4.3 stain
Phosphorylase: Many immature or small muscle fibers express an immature form of phosphorylase

Phosphorylase stain

Phosphorylase Deficiency: Fixed muscle & Ultrastructure


Toluidine blue-stained plastic section
From: Mari Perez-Rosendahl

From: S Moore
Blebs: Subsarcolemmal
  Contain Glycogen granules

From: Chunyu Cai
Blebs: Subsarcolemmal
  Some contain Glycogen granules (Arrow)
  Others have no contents (below)

From: Chunyu Cai
Glycogen granules in Bleb

From: Chunyu Cai
Phosphorylase Deficiency: Spindle

H&E stain
Also see: Acid maltase deficiency: Adult; Child
Return to Glycogen storage disorders
Return to Muscle biopsies
Return to Pathology images

11/7/2022