Small vessel vasculopathy

Small Vessel Pathology (Capillaries or Endoneurial Microvessels) ²

Capillaries
Muscle: Normal
Endoneurial Microvessels
Capillary pathology
Microvasculopathy
C_5b-9 Deposits
HIEM (Nerve)
Muscle
Enlargement
Pipestem
SRP Myopathy
TS-HDS neuropathy
Hemosiderin
Endoneurial inflammation
Ipilimumab
Perineuritis
Loss
DM-VP
GvHD
Systemic Sclerosis
Minimal myopathy
Ultrastructure
Myopathy + Capillary Δ
Subperineurial edema
Thick vessel walls
ELS vessels

Endomysial Capillary: Normal

ENDOMYSIAL CAPILLARIES: NORMAL

Capillary: Normal
Endothelial cell = E: Inside basal lamina
Pericyte = P: Within basal lamina

Capillary Structure

Basement membrane
Around & outside endothelial cell layer
May be homogeneous or layered
Contains pericytes (P)
Composition
Collagen IV
Laminin
Glycoproteins: Fibronectin, Nidogen-1, Nidogen-2 (Entactin)
Proteoglycans (as HSPG): Perlecan, Agrin
Thickening: Differential diagnosis

Endothelial cells (E)
Surround lumen
Stains: Ulex Europaeus Agglutinin I (UEAI); CD31
Pericytes (P)
Location: Within basal lamina of vessel wall
Contractile
Frequency vs Endothelial cells: 1:10 to 1:100
Stain: PDGRFβ
Smooth muscle
Stain: Smooth muscle actin

Muscle Capillaries: Features

Anatomy

Adult: Normal
- Numbers: All muscle fibers have adjacent capillaries
- Orientation: Capillaries usually run along length of muscle fibers
Child (< 2 years)
- Numbers: Many muscle fibers have no adjacent capillary

Plasticity

Increased Capillary Numbers
- Muscle activity: Exercise; Electrical stimulation
- Denervation
- Anti-angiogenic thrombospondin-1 (TSP-1): Deletion
Reduced Capillary Numbers
- Disuse: Bedrest; Spaceflight
- Muscle-specific VEGF-A deletion
- TSP-1 induction
- Perifascicular loss: Dermatomyositis with Vascular Pathology

Endomysial Capillaries: Normal

UEA I stain

Endomysial capillaries: Normal
Normal number: Every muscle fiber has at least one adjacent capillary
Orientation: Run parallel to muscle fiber length; Cut in cross-section

UEA I stain

All muscle fibers have at least one adjacent capillary

UEA I stain

There are few or no capillaries immediately adjacent to the perimysium

UEA I stain

Endomysial Capillaries: Reduced numbers

Some muscle fibers have no adjacent capillary

UEA I stain

Endomysial Capillaries: Partial Denervation

UEA I stain

Endomysial capillaries
Orientation: May be circumferential around muscle fibers (Above); Cut in cross-section
Number: Every muscle fiber has several adjacent capillaries

UEA I stain

Endomysial Capillaries: Dermatomyositis with Vascular pathology (DM-VP)

Endomysial capillaries
Orientation: Normal
Number: Reduced or absent Endothelium (Ulex stain) in regions with small muscle fibers (Arrow)
Endothelium is lost but basal lamina is still present
& may have C_5b-9 deposition
Size: Increased in regions neighboring muscle fiber atrophy

UEA I stain

Endomysial Capillaries: Enlarged

UEA I stain

UEA I stain

Patient history: Cardiac failure & Interstitial lung disease

NERVE: Endoneurial Microvessels

H&E stain
Endoneurial Microvessel (Arrow)
Orientation: Along length of nerve

Toluidine blue stain

Endoneurial Microvessel

Endomysial & Endoneurial Capillaries: Thickened Walls

Ultrastructure: From Robert E Schmidt MD	Ultrastructure: From Robert E Schmidt MD
Diabetes Endoneurial vessel in Nerve Basal lamina: Multiple layers	Non-diagnostic muscle Endomysial vessel in Muscle Thickened wall: Homogeneous

From: Chunyu Cai


Basal lamina of Endoneurial microvessels Thickened; Homogeneous (Arrows) Capillary walls thick: Differential diagnosis ¹ Increased age Gastrocnemius muscle Diabetes Chronic idiopathic axonal neuropathies CMT I Hypoxia M-protein related neuropathy TS-HDS antibody-related polyneuropathy: Pathology Amyloid		Basal lamina of Endoneurial microvessel Normal (Arrow)

Capillaries: Walls have varied thickness

Capillaries with homogeneous thick walls

Humoral Immune Endoneurial Microvasculopathy (HIEM) ²⁸

Microvessels
C_5b-9 deposition on Microvessels
C_5b-9 around Endotheial cells
Endoneurial Microvascular Endothelial cells: Large
Nerve
Histology
Axon loss
Varied: Toluidine blue
Large > Small

Associated Clinical Syndrome

Confluent Asymmetric Neuropathy (HIEM)

C_5b-9 stain
HIEM Nerve
C_5b-9 Stains Most Endoneurial Microvessels

Disease Control Nerve
C_5b-9 Stains Perineurium & Epineurial vessels but not Endoneurial microvessels

C_5b-9 stain

HIEM Nerve
C_5b-9 Stains Endoneurial Microvessels

C_5b-9 stain

C_5b-9 stain

Endoneurial Microvasculopathy
HIEM: C_5b-9 stains Endoneurial microvessels

C_5b-9 stain

Disease Control Nerve
C_5b-9 does not stain Endoneurial microvessels

C_5b-9 stain

C_5b-9 (Green) + UEAI (Red) stain

HIEM: C_5b-9 stain (Green) around Endoneurial Microvessel endothelium (Red)

C_5b-9 (Green) + UEAI (Red) stain

C_5b-9 (Green) + UEAI (Red) stain

Toluidine blue stain

Endoneurial Microvessel Pathology
Vessel size: Normal or Large
Vessel wall: Thick
Endothelial cells: Large
Basal lamina: Multi-layered

Toluidine blue stain

Endothelial cells in HIEM Microvessels: Multiple, Large

Toluidine blue stain From R Schmidt

HIEM: Nerve anatomic pathology

H&E stain
HIEM nerve: No lymphocytic inflammation

VvG stain

HIEM: Differential fascicular involvement
Myelinated axon loss: Varied (Above)
Endoneurial ATPase stain: Varied (Below)

ATPase pH 4.3 stain

Toluidine blue stain

HIEM sural nerve
Moderate loss of large & small myelinated axons
Regeneration: Clusters of small myelinated axons
Endoneurial microvessels
Basal lamina: Thick
Endothelial cells: Large