Neuromuscular

Immune Myopathy with Antibodies to Signal Recognition Particle

SRP pathology
  Early
  Intermediate
  Late, Severe
  Late, Mild
  Capillaries
  Complement deposition

General features
SRP: Early Pathology
Necrotic & Regenerating muscle fibers: Scattered

H&E stain
Necrotic & Regenerating (Arrow) muscle fibers: Scattered

H&E stain
Acid phosphatase stain
Acid phosphatase stain

H&E stain
Muscle fibers: Necrosis & Regeneration

Congo red stain

Acid phosphatase stain
Necrotic muscle fibers: Scattered
  Phagocytic cells: Stain for acid phosphatase
  Cytoplasm: Stains for C5b-9 complement

C5b-9 stain

NADH stain
Necrotic (pale) & Regenerating (dark) muscle fibers

NADH stain
MHC Class I
  Muscle fibers
    Generally not expressed
    Present in cytoplasm of regenerating muscle fibers
  Cells: Present on histiocytic cells associated with necrotic muscle fibers
  Vessels: Normally present on endomysial capillary & perimysial vessel endothelial cells

MHC Class I stain
SRP: INTERMEDIATE PATHOLOGY
Muscle fiber sizes: Varied; Small to Upper limit of normal; Bimodal distribution
Small muscle fibers: Rounded; Large nuclei; Basophilic cytoplasm, Clustered
Endomysial connective tissue: Increased, Mild to Moderate
Perimysial connective tissue: Irregular or fragmented
Pathology distribution: Patchy; Some regions with more small muscle fibers & Increased endomysial connective tissue

H&E stain
Muscle damage
  More severe, with increased endomysial connective tissue, in some regions

H&E stain

H&E stain
Muscle fiber sizes: Bimodal
Small muscle fibers: Rounded; Large nuclei
Endomysial connective tissue: Mildly increased
        
H&E stain

Gomori trichrome stain

Gomori trichrome stain
Immature muscle fibers with large myonuclei

Congo red stain
Muscle fiber internal architecture
  Some small muscle fibers stain dark
  One necrotic muscle fiber has pale cytoplasm (Arrow)
  Large fibers have coarse internal architecture

NADH stain

VvG stain
Fiber sizes: Varied; Small fibers round
Endomysial connective tissue: Increased
Muscle fiber necrosis: Few fibers with pale-stained cytoplasm

Congo red stain

Acid phosphatase stain
Necrotic muscle fibers
  Scattered
  Pale cytoplasm
  Associated histiocytic cells
Acid phosphatase stain
Acid phosphatase positive cells
  Scattered in endomysium

Acid phosphatase stain
Necrotic muscle fibers
  Scattered in muscle

C5b-9 stain
C5b-9 Deposition
  Necrotic muscle fibers
    Distribution: Scattered
    Cytoplasm: Diffuse C5b-9 stain
  Endomysial capillaries: Some patients

C5b-9 stain
SRP myopathy: Immature muscle fibers
  Many muscle fibers persist in immature states

Alkaline phosphatase stain
Muscle fiber immaturity
  Properties
    Many small immature muscle fibers stain for alkaline phosphatase
    Many small & large muscle fibers are type 2C (Below)
  Distribution in muscle: Immature, small fibers are often clustered

ATPtase pH 4.3 stain
Immature Muscle Fibers: Clustered

ATPtase pH 4.3 stain

H&E stain

Gomori trichrome stain
Small clusters of Immature muscle fibers

VvG stain

NADH stain
Small clusters of Immature muscle fibers

Alkaline phosphatase stain

Gomori trichrome stain
Focal Regions of Muscle fiber Damage

VvG stain
SRP Myopathy, Moderate
  Perimysial Pathology

Gomori trichrome stain
Perimysium
  Fragmented
  No cells

VvG stain

VvG stain
SRP Myopathy, Moderate
  Myofiber Basal Lamina Pathology

Laminin-α2 stain
SRP Muscle fiber basal lamina: Thickened & Irregular on large & small fibers
Control Muscle fiber basal lamina

Laminin-α2 stain
SRP: LATE, SEVERE PATHOLOGY, Months
Muscle fiber sizes: Varied; Small to Mildly large
Small muscle fibers: Rounded; Large nuclei; Basophilic cytoplasm
Endomysial connective tissue: Increased, Moderate to Marked
Pathology distribution: Patchy; Some regions with more endomysial connective tissue & only small rounded muscle fibers

H&E stain

H&E stain

Increased endomysial connective tissue
Hypertrophic and small muscle fibers
Gomori trichrome stain

Many small rounded muscle fibers
Increased endomysial connective tissue
H&E stain

Endomysial connective tissue: Marked increase
Disease course of only 6 months

H& E stain
Endomysial connective tissue
  Marked increase
  More in some fascicles than others

VvG stain

VvG stain
Endomysial connective tissue: Marked increase

Gomori trichrome stain

ATPase pH 4.3 stain
Many muscle fibers retain immature features
  Type 2C on ATPase pH 4.3 stain
  Cytoplasm stains for alkaline phosphatase

Alkaline phosphatase stain
Histiocytic (red stained) cells in endomysial connective tissue

Acid phosphatase stain
MHC Class I
  Normal on muscle fibers: No staining
  Present on endomysial cells

MHC Class I stain
SRP Myopathy, Severe
  Myofiber Basal Lamina Pathology

Laminin-α2 stain
Muscle Fiber Basal lamina: Thickened & Irregular (Above) vs control (Below)

Laminin-α2 stain
SRP: LATE, MILD PATHOLOGY, Months

H&E stain
Muscle fiber sizes: Varied; Small angular fibers, Scattered
Small muscle fibers: Angular; Basophilic cytoplasm
Endomysial connective tissue: Increased, Mild

H&E stain

VvG stain
Histiocytic cells: Scattered in endomysium

Acid phosphatase stain

ATPase pH 4.3 stain
Many muscle fibers retain immature features
  Type 2C on ATPase pH 4.3 stain
  Cytoplasm stains for alkaline phosphatase

Alkaline phosphatase stain

C5b-9 stain
Necrotic muscle fibers: Scattered (with C5b-9 stained cytoplasm)
MHC Class I: Not prominent on muscle fibers

MHC Class I stain
Neuromuscular junctions: Normal

Esterase stain
SRP MYOPATHY: CAPILLARY PATHOLOGY

Ulex europaeus agglutinin I stain
SRP myopathy
  Endomysial capillaries: Large & Mildly reduced in number
  Some muscle fibers have no adjacent capillary
Ulex europaeus agglutinin I stain
SRP myopathy
  Endomysial capillaries: Large
 
Ulex europaeus agglutinin I stain
Normal muscle
  Endomysial capillaries: Small
  All fibers have adjacent capillaries

Ulex europaeus agglutinin I stain
SRP MYOPATHY: MEMBRANE ATTACK COMPLEX (C5b-9)
  In cytoplasm of scattered necrotic muscle fiber
  On some capillaries

Antibody vs C5b-9
C5b-9
Deposition in endomysial capillaries and
  necrotic muscle fiber cytoplasm (Arrow)
Antibody vs C5b-9
C5b-9
Irregular deposition in endomysial capillaries (Arrows)
Return to Inflammatory myopathies
Return to SRP myopathy

4/26/2023