Muscle Capillary Pathology

Capillary Pathology: Muscle

General
Analysis
ELS in BIM
Regional microvasculopathies
Dermatomyopathy syndromes
Diffuse microvasculopathy
SLE
Minimal Myopathy
Systemic Sclerosis
Myopathy
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

Muscle
- Less weakness
- Serum CK: High but lower than myopathy patients
Systemic: Less frequent
- Pulmonary: Interstitial lung disease; Arterial hypertension
- Renal crises
- Skin: Diffuse involvement

Pathology: Endomysial Capillaries

Histochemistry
- Size: Large
- Stains: NADH; ATPase pH 4.3; Acid phosphatase; PAS
- Neighboring cells: Pericytes & Histiocytes
Ultrastructure
- Basement membrane: Thick & Reduplicated
- Endothelium: Activation
- Pericytes (PDGFR-β stain): Proliferation

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 C_5b-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: C_5b-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

C_5b-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

Muscle fiber pathology
MHC I up regulated on muscle fibers

MHC Class I stain

Systemic Sclerosis: Capillary Pathology + Myopathy

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: C_5b-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

C_5b-9 stain: Endomysial Capillaries

C_5b-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: C_5b-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

C_5b-9 stain

C_5b-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: C_5b-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: C_5b-9 no capillary staining; Acid phosphatase +; MxA +-
Muscle: MHC1-; C_5b-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

C_5b-9 stain

C_5b-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: C_5b-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
C_5b-9 staining
Capillaries: Present on many endomysial capillaries
Muscle fibers: Punctate on some fiber surfaces

C_5b-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: C_5b-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)