Neuromuscular

Capillary Pathology: Muscle

General
  Analysis
ELS in BIM
Regional microvasculopathies
  Dermatomyopathy syndromes
Diffuse microvasculopathy
  SLE
    Minimal Myopathy
  Systemic Sclerosis
    Myopathy
    Capillary ultrastructure
  GvHD
Also see
  Pipestem capillaries
 		CTD Patients
  Endomysial capillary Δ
    CREST: 1; 2
    SLE
    Systemic Sclerosis
      Th/To antibody
      RUV B1/2 antibody
      + Myopathy
        Ro-52 antibody
  Myopathy
    Systemic Sclerosis
      Ro-52 antibody

Capillary Pathology with Minimal Myopathy: Systemic Sclerosis 1 & Other

Clinical associations Pathology: Endomysial Capillaries
Capillary Features: Stain Analysis
Basal Lamina Endothelium Immune
Morphology
  H&E
  GT/VvG
  Ultrastructure
Molecular
  Decorin/Col IV
  PAS: + or -
Pericytes
  PDGFRβ
 H&E: Morphology
Ulex: Distribution;
  #; Size; Stain intensity
ATPase pH 4.3: #+
Alkaline phosphatase: #+
NADH: + or -
 Humoral
  C5b-9
Cellular
  Acid phosphatase
  HAM56
Cell involvement
  Muscle: MHC I
  Capillary: MxA

Systemic Immune Disorders: Capillary ± Muscle Pathology

SLE

Patient Features
  38 yo female
  Clinical diagnoses: Systemic Lupus Erythematosis; ILD
  Serum Antibodies: Ro52; ANA 1:640, Speckled; ± NT5C1a, PL-12 & MGT-30
  Treatment: Prednisone

Capillary pathology
  Morphology: Basal lamina mildly to moderately thick
  Basal lamina: PAS+; Decorin mildly thick
  Endothelium: Ulex large & reduced #; Alkaline phosphatase -; ATPase +; NADH ++
  Immune: C5b-9 scattered capillaries; MxA & Acid phosphatase cells
Muscle: MHC1+
Endomysial Capillaries: Morphology

H&E stain
Endomysial Capillaries (Arrow)
  Moderately enlarged
Muscle fibers
  Fiber sizes: Moderately varied

H&E stain

Gomori trichrome stain
Endomysial Capillaries
  Moderately enlarged
  Some have thick basal lamina

Gomori trichrome stain
Endomysial Capillaries
  Moderately enlarged

Congo red stain

VvG stain
Endomysial Capillaries: Basal lamina
  PAS stains capillary basal lamina

PAS stain

Decorin stain
Endomysial Capillaries
  Moderately enlarged
  Basal lamina: Commonly thick

Decorin stain
Endomysial capillaries: Endothelium

UEA I stain

Alkaline phosphatase phosphatase stain

ATPase pH 4.3 stain
Endomysial Capillaries
  ATPase positive (Arrow)

ATPase pH 4.3 stain

NADH stain
Endomysial Capillaries
  NADH positive

NADH stain

NADH stain
Endomysial Capillaries: Immune

C5b-9 stain

MxA stain
MxA
  Stains cells in & around endomysial capillary walls

MxA stain

Acid phosphatase stain
Endomysial Capillaries: Immune
  Acid phosphatase: Stains cells in & around (Arrows) endomysial capillary walls

Acid phosphatase stain
Histiocyte neighbors Endomysial capillary
Muscle fiber pathology
  MHC I up regulated on muscle fibers

MHC Class I stain

Systemic Sclerosis: Capillary Pathology + Myopathy 2

Patient features
52 yo female
Clinical diagnosis: Systemic Sclerosis; ILD
Serum Antibodies: ANA 1:1280, Speckled; Ro52; AChR binding

Capillary pathology
  Morphology: Basal lamina very thick
  Basal lamina: PAS-; Decorin dark & moderately thick
  Endothelium: Ulex large & reduced #; Alkaline phosphatase -; ATPase +; NADH ++
  Immune: C5b-9 scattered capillaries; Acid phosphatase cells & endothelium
Muscle: MHC1+

H&E stain
Myopathy
  Muscle Fiber sizes: Varied
  Small, Immature fibers: Scattered
  Internal nuclei: Some muscle fibers
Endomysial Capillary Pathology
  Capillary sizes: Large
  Capillary basal lamina: Thick
  Endothelial cells: Large in enlarged capillaries

Gomori trichrome stain
Systemic Sclerosis
  Endomysial capillaries: Large

VvG stain
Myopathy
  Muscle Fiber sizes: Varied
  Small, Immature fibers: Scattered
Endomysial Capillary Pathology
  Capillary sizes: Large
  Capillary basal lamina: Thick
  Endothelial cells: Large in enlarged capillaries

VvG stain

VvG stain
Endomysial Capillary Pathology
  Capillary sizes: Large
  Capillary basal lamina: Thick
  Endothelial cells: Large in enlarged capillaries

Congo red stain
Capillary pathology: Basal lamina

PAS stain

Decorin stain
Capillary pathology: Endothelium

UEA I stain
Endomysial Capillaries
  Number: Reduced; Many fibers with no adjacent capillary
  Endothelial cells
    Location: Inside thick basal lamina
    Size: Large

UEA I stain

UEA I stain
Endomysial Capillaries
  Size: Often large
  Endothelial cells
    Stain for UEAI & MHC I
    Location: Inside thick basal lamina
    Size: Large
  Basal lamina (Unstained): Thick

MHC I stain
Endomysial Capillaries
  Size: Often large
  Endothelial cells
    Stain for MHC Class I
    Enlarged inside thick basal lamina
  Basal lamina (Unstained): Thick

MHC I stain

Alkaline phosphatase stain
Endomysial capillaries: Normal numbers stained

NADH stain
Endomysial Capillary Pathology
  Capillary sizes: Large
  Capillary basal lamina: Thick
  Endothelial cells: Large; NADH positive

ATPase pH 4.3 stain
Systemic Sclerosis
Endomysial Capillaries: Large (Arrows)

ATPase pH 4.3 stain
Endomysial Capillaries
  Endothelial cells: ATPase positive
  Capillary basal lamina: Often thick around endothelial cells

ATPase pH 4.3 stain

ATPase pH 4.3 stain
C5b-9 stain: Endomysial Capillaries

C5b-9 stain
Endomysial Capillaries
  Endothelial cells: Acid phosphatase positive

Acid phosphatase stain
Systemic Sclerosis: Myopathy

MHC Class I stain
Systemic Sclerosis: Myopathy
  Muscle fibers
    Varied sizes
    MHC1: Patchy upregulation

MHC Class I stain

LC3 stain
Systemic Sclerosis
  Clusters of muscle fibers have multiple, irregular collectons of LC3 aggregates

LC3 stain

Systemic Sclerosis: Myopathy ± Capillary Pathology

Patient features
Clinical diagnosis: Systemic Sclerosis
Serum Antibodies: ANA high; Ro; NT5C1a

Capillary pathology
  Morphology: Some capillaries large
  Basal lamina: PAS-; Decorin mildly thick walls
  Endothelium: Ulex large; Alkaline phosphatase -; ATPase +; NADH -
  Immune: C5b-9 scattered capillaries; Acid phosphatase cells & endothelium
Muscle: MHC1+; Endomysial inflammation; Sarcoplasmic pads; Atrophy; LC3 -
Systemic Sclerosis Myopathy: Morphology

H&E stain
Endomysial Capillaries
  Mildly large
  Often diffficult to visualize
Muscle fibers
  Sizes: Bimodal distribution
    All fibers are small
    Some fibers: Very small, Round, Large nuclei

H&E stain

GT stain
Endomysial Capillaries
  Mildly large
  Often diffficult to visualize
Muscle fibers
  Sizes: Bimodal distribution
    All fibers are small
    Some fibers: Very small, Round, Large nuclei

VvG stain

PAS stain
PAS: Endomysial capillaries not well stained
Decorin: Endomysial capillaries have thick walls

Decorin stain

UEA I stain
UEA I: Endomysial capillary endothelium large vs vs control (Below)
Control

UEA I stain

Alkaline Phosphatase stain
Alkaline Phosphatase: No increase in capillary staining
ATPase pH 4.3: Stains larger endomysial capillaries

ATPase pH 4.3 stain

NADH stain
NADH
  Capillaries: No prominent staining
  Muscle fibers
    Internal architecture: Coarse
    Scattered fibers: Rings or Sarcoplasmic pads

NADH stain

C5b-9 stain

C5b-9 stain

Acid phosphatase stain

Acid phosphatase stain

Acid phosphatase stain

Esterase stain

MxA stain

MHC I stain

MHC I stain

H&E stain

H&E stain

H&E stain

Systemic Sclerosis

Serum Antibody: Th/To

Capillary pathology
  Morphology: Capillary sizes normal to slightly large
  Basal lamina: PAS-; Decorin small size, dark staining & moderately thick
  Endothelium: Ulex & MHC I reduced intensity of staining; Alkaline phosphatase +; ATPase +; NADH -
  Immune: C5b-9 -; Acid phosphatase minor staining of few endomysial capillaries; MxA -
Muscle: MHC1-

H&E stain
Systemic sclerosis, Th/To antibody
  Muscle fibers: Scattered intermediate sized fibers
  Capillaries: Normal to Mildly large sizes

H&E stain
Systemic sclerosis + Th/To: Basal Lamina

PAS stain
Capillary Basal lamina: No PAS staining

Decorin stain
Capillary Basal lamina: Small size endomysial capillaries with mildly thick, dark-stained walls
Systemic sclerosis + Th/To: Endomysial Capillary Endothelium

UEA I stain
Endothelium: Reduced intensity of UEA I staining (Above) compared to control (Below)

UEA I stain

MHC Class I stain
Capillaries: Very pale staining for MHC Class I (Above) compared to controls (Below)
Muscle: No upregulation of MHC class I

MHC Class I stain

Alkaline phosphatase stain
Endomysial capillaries: Increased # stained by alkaline phosphatase

>Alkaline phosphatase stain

ATPase pH 4.3 stain
Endomysial capillaries: Increased # stained by ATPase pH 4.3

NADH stain
Endomysial capillaries: No staining by NADH
Systemic sclerosis + Th/To: Immune

Acid phosphatase stain
Endomysial capillaries: Mild staining of a few endomysial capillaries by acid phosphatase

Acid phosphatase stain

MxA stain

Systemic Sclerosis

Serum Antibody: RUV B1/2

Capillary pathology
  Morphology: Capillary sizes mildly large
  Basal lamina: PAS-; Decorin capillaries moderately thick wall, Normal size to slightly large
  Endothelium: Ulex mildly large capillaries; Alkaline phosphatase -; ATPase +- few capillaries; NADH mild +
  Immune: C5b-9 no capillary staining; Acid phosphatase +; MxA +-
Muscle: MHC1-; C5b-9 on endomysium; UEA I on muscle fiber surfaces
Systemic Sclerosis + RUV B1/2: Morphology

H&E stain

H&E stain

Gomori trichrome stain

VvG stain
Systemic Sclerosis + RUV B1/2: Endomysial Capillary Basal Lamina

PAS stain
Endomysial capillaries: No PAS staining

Decorin stain
Endomysial capillaries: Decorin thick walls; Smaller sizes
Systemic Sclerosis + RUV B1/2: Capillary endothelium

UEA I stain
Endomysial capillary endothelium: UEA I stain
  Moderately large sizes
  Borderline reduced #: Scattered small muscle fibers with no associated capillary
Muscle fibers: UEA I stain on fiber surfaces

UEA I stain

MHC class I stain
Endomysial capillary endothelium: MHC I stain
  Pale (Above) compared to
  Control (Below)
Muscle fibers: Mostly Normal

MHC class I stain

Alkaline phosphatase stain
Endomysial capillaries: Normal stain

ATPase pH 4.3 stain
Endomysial capillaries: Minor scattered staining

NADH stain
Endomysial capillaries: Mild staining of most vessels
Systemic Sclerosis + RUV B1/2: Immune features

C5b-9 stain
C5b-9
  Endomysial capillaries: No staining
  Muscle fiber surface membranes: Patchy beaded staining

Acid phosphatase stain
Acid phosphatase
  Stains capillary endothelial cells & few neighboring histiocytes

MxA stain
MxA
  Stains capillary endothelial cells & few neighboring histiocytes

CREST

 Patient 1 features
75 yo female
Clinical Diagnosis: CREST
Serum antibodies: Ro-52; Tif1γ; NT5C1a

Capillary pathology
  Morphology: Basal lamina normal; Lymphocytes surround small vessels
  Basal lamina: PAS+; Decorin small size, dark staining & moderately thick
  Endothelium: Ulex large & reduced #; Alkaline phosphatase +; ATPase +; NADH -
  Immune: C5b-9 most capillaries; Acid phosphatase cells & endothelium, scattered; MxA +
Muscle: MHC1+
CREST: Endomysial Capillary Morphology

H&E stain
Endomysial capillaries
  Morphology: Normal to Slightly large size
  Lymphocytes: Surround a small vessel

H&E stain

Gomori trichrome stain
CREST: Endomysial Capillary Basal Lamina

PAS stain
Basal Lamina
  PAS: Mild staining

Decorin stain
Basal Lamina
  Decorin: Dark stained walls
CREST: Endomysial Capillary Endothelium

UEA I (Ulex) stain
Capillaries
  Reduced numbers: Many muscle fibers have no adjacent capillary

Alkaline phosphatase stain
Endomysial Capillaries
  Alkaline phosphatase stain: Increased numbers, especially large capillaries, are positive (Above)
  ATPase pH 4.3 stain: Larger capillaries are positive (Below)

ATPase pH 4.3 stain
Endomysial Capillaries: No NADH stain

NADH stain
CREST capillaries: Immune
C5b-9 staining
  Capillaries: Present on many endomysial capillaries
  Muscle fibers: Punctate on some fiber surfaces

C5b-9 stain
Endomysial Capillaries
  MxA stained cells are present near endomysial capillaries & in perimysium

MxA stain
Endomysial Capillaries
  Endothelial cells & some surrounding cells: Acid phosphatase positive

Acid phosphatase stain
CREST: Muscle fibers

MHC Class I stain
CREST: Myopathy
  Muscle fibers
    Varied sizes
    MHC1: Patchy upregulation, especially by fibers with
      Small size
      Location near perimysium
  Capillaries: Reduced numbers in some regions

MHC Class I stain
CREST
Patient 2 features
30 yo Male
Clinical Diagnosis: CREST
Serum antibodies: Sm; ANA 1:2560

Capillary pathology
  Morphology: Basal lamina normal to mildly thick
  Basal lamina: PAS +-; Decorin large, dark staining & moderately thick
  Endothelium: Ulex large & reduced #; Alkaline phosphatase +; ATPase +; NADH -
  Immune: C5b-9 few capillaries; Acid phosphatase cells & endothelium, scattered; MxA ++
Muscle: MHC1 -

H&E stain
Endomysial capillaries
  Morphology
    Size: Large
    Basal lamina: Mildly thick

H&E stain

Gomori trichrome stain
Endomysial capillaries
  Morphology
    Size: Large
    Basal lamina: Mildly thick

VvG stain
CREST: Endomysial Capillary Basal Lamina

PAS stain
Basal Lamina
  PAS: Mild staining of larger vessels

Decorin stain
Basal Lamina
  Decorin: Dark stained walls; Large size

Decorin stain

UEA1 stain
Capillaries
  Reduced numbers
  Many muscle fibers have no adjacent capillary

UEA1 stain
Capillaries (Control)
  All muscle fibers have adjacent capillary
  Endomysial capillary size: Mildly large

UEA1 stain

Alkaline phosphatase stain
Endomysial Capillaries
  Alkaline phosphatase stain: Increased numbers, especially large capillaries, are positive (Above)
  ATPase pH 4.3 stain: Larger capillaries are positive (Below)

ATPase pH 4.3 stain
Endomysial Capillaries: NADH stains endothelium in larger capillaries

NADH stain

C5b-9 stain
CREST capillaries: Immune
C5b-9 staining
  Capillaries: Present on a few, scattered endomysial capillaries

MxA stain
Endomysial Capillaries
  MxA stains endothelial cells & cells around endomysial capillaries

MxA stain

Acid phosphatase stain
Endomysial Capillaries
  Endothelial cells & some surrounding cells: Acid phosphatase positive

Acid phosphatase stain
CREST: Muscle fibers

MHC Class I stain
MHC Class I: No staining on muscle fiber surfaces
Endomysial Capillaries: Basal Lamina
  Irregular increase in basal lamina layers around capillaries (Arrows)
Capillary Basal Lamina: Multiple circumferential layers
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References
1. Acta Neuropathol 2021;141:917-927
2. Rheumatology (Oxford) 2023;62(SI):SI82-SI90, Curr Opin Rheumatol. 2023 Aug 23

12/9/2023