VASCULITIS
VASCULITIC LESION: EARLY
- Inflammation around vessel wall
- Macrophage inflammation (acid phosphatase positive) in vessel endothelium
- Relatively intact structure of vessel wall
- ANCA+ vasculitis: Neutrophil-associated lesions
1
- Attachment of neutrophils to epineurial vascular endothelial cells
- Migration of neutrophils to extravascular space via the penetration of endothelial layer
- Release of neutrophil components into extracellular space
- Not present in NSVN
![](../pics/biopsy/vasculitis/vascearlyhe.jpg)
H&E stain
|
![](../pics/biopsy/vasculitis/vascearlyacp.jpg)
Acid phosphatase stain
|
![](../pics/biopsy/vasculitis/vascearlyhpacp.jpg)
Acid phosphatase stain
|
Histiocytic cells in vessel wall: Especially endothelial layer
FIBRINOID NECROSIS
Definition: Accumulation of Fibrin layer in Vessel (Below; Brown arrow)
Properties: Non-cellular
Location: On luminal side of vessel wall; Inside fibril layer
![](../pics/biopsy/vasculitis/vasculitisfibneche2a.jpg)
H&E stain
|
Fibrinoid Necrosis
- Eosinophilic, homogenous, & refractile staining in inner regions of vessel wall
- Endothelial components
- Can be seen inside the layer of fibrinoid necrosis
- Endothelial cell nuclei may be enlarged
- Inner ring of elastin is incomplete, damaged & irregular (VvG)
- Fibrin is deposited inside elastin ring (VvG)
Cells: In & around Damaged Vessel wall
- Eosinophils (Above; Black arrow)): Many, Scattered
![](../pics/biopsy/vasculitis/vasculitisfibneche.jpg)
H&E stain
|
![](../pics/biopsy/vasculitis/vasculitisfibnecvvg.jpg)
VvG stain
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Vasculitis
Fibrinoid Necrosis: Thick orange layer within lumenal side of vessel wall
Vessel wall
Thickness: Increased
Fibril layer: Irregular or Fibrils absent
Epineurial connective tissue
Neovascularization & Irregular structure: Surrounds vessel
![](../pics/biopsy/vasculitis/vasculitisfibnecvvg2.jpg)
VvG stain
|
![](../pics/biopsy/vasculitis/vasculitisgt.jpg)
Gomori trichrome stain
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Fibrinoid Necrosis
Inner layer of vessel wall
![](../pics/biopsy/vasculitis/vasculitisvvg2.jpg)
VvG stain
|
Vasculitis: Damaged Vessel Wall
Fibril layer (Above)
Thin, small, irregular fibrils
Abnormal layer within fibril layer
Lumen remains present at this level
Smooth Muscle Layer: Markedly & Irregularly reduced ATPase staining (Below; Arrow)
Lumen is lost at this section level: ATPase stains neo-vessels in area that was previously lumen
![](../pics/biopsy/vasculitis/vasculitisatp43.jpg)
ATPase pH 4.3 stain
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Vasculitis
Fibrinoid Necrosis: Thick, irregular layer within lumenal side of vessel wall
Vessel wall: Cellular; Reduced connective tissue
![](../pics/biopsy/vasculitis/vasculitisfibnectb.jpg)
Toluidine blue stain
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VASCULITIS: Connective Tissue (Perimysium or Epineurium) near, & far from, Vessels
![](../pics/biopsy/vasculitis/vascmusclealplp.jpg)
Alkaline phosphatase stain
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Connective tissue in Muscle Perimysium: Alkaline phosphatase staining
![](../pics/biopsy/vasculitis/vascmuscalp.jpg)
Alkaline phosphatase stain
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![](../pics/biopsy/vasculitis/vascnervealplp.jpg)
Alkaline phosphatase stain
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Connective tissue in Nerve Epineurial connective tissue: Alkaline phosphatase staining in Vasculitis
![](../pics/biopsy/vasculitis/vasnvcalpmp.jpg)
Alkaline phosphatase stain
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Connective tissue: Alkaline phosphatase staining around vessel
![](../pics/biopsy/vasculitis/vascmedalp.jpg)
Alkaline phosphatase stain
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![](../pics/biopsy/vasculitis/vascocclalp.jpg)
Alkaline phosphatase stain
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Connective tissue: Acid phosphatase stain
Most cells in epineurium & vessel walls are histiocytes
![](../pics/biopsy/vasculitis/vasculitisnvacp2.jpg)
Acid phosphatase stain
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Hemosiderin
![](../pics/biopsy/vasculitis/hemosidnadh.jpg)
NADH stain
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Perimysial vessels: Surrounded by hemosiderin deposits in connective tissue
![](../pics/biopsy/vasculitis/vaschemosidcr.jpg)
Congo red stain
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Epineurium: Hemosiderin deposits; Neovascularization
![](../pics/biopsy/vasculitis/vasculophemosidcr.jpg)
Congo red stain
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Vasculitis: Hemorrhage, Old
Hemosiderin: Brown granules in connective tissue around vessel
![](../pics/biopsy/vasculitis/epineurvessvascab.jpg)
Alcian blue/Nuclear fast red
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VASCULITIS: Occluded Vessels & Lumen pathology
![](../pics/biopsy/vasculitis/vascparaflp.jpg)
H & E stain
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![](../pics/biopsy/vasculitis/vascparafhe.jpg)
H & E stain
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- Lumen is replaced by
- Vessel wall: Thick; Cellular
- Inflammation may remain surrounding vessel
- Macrophages (acid phosphatase staining cells) are relatively scarce
- Alkaline phosphatase staining
- Present around vessels in connective tissue
- No endothelial structures stained
![](../pics/biopsy/vasculitis/vascocclhe2.jpg)
H & E stain
|
![](../pics/biopsy/vasculitis/vascocclhpvvg.jpg)
VvG stain
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![](../pics/biopsy/vasculitis/vascocclacp.jpg)
Acid phosphatase stain
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![](../pics/biopsy/vasculitis/vasculitisnvgtlpar.jpg)
Gomori trichrome stain
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Arteries: Varied degrees of occlusion
Histiocytic Cells (
Acid phosphatase positive)
Locations: Artery wall & Surrounding connective tissue
Lymphocytes: Less common
Fibrinoid deposition (Arrow)
Connective tissue surrounding vessels
Damaged & Rarified
Contains histiocytic cells
Arterial Damage
Lumen: Occluded
Fibril (elastin) layer: Damaged, Irregular (Arrow)
![](../pics/biopsy/vasculitis/vasculitisnvvvg.jpg)
VvG stain
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Perimysial arteriole: Occluded, Early neovascularization
![](../pics/biopsy/vasculitis/vascperimysvess.jpg)
VvG stain
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Perimysial vessel: Occluded, Early neovascularization
![](../pics/biopsy/vasculitis/vasculitisoccvessgt.jpg)
Gomori trichrome stain
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Vessel wall: Thickened around area of occlusion
![](../pics/biopsy/vasculitis/vascoccltb.jpg)
Toluidine blue stain
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![](../pics/biopsy/vasculitis/vascocchptb.jpg)
Toluidine blue stain
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VASCULITIS (Chronic): Neovascularization; Multiply recanalized Vessels
- Several small lumens surrounded by cells appear in center of intermediate-sized vessel
- New vessels also appear in connective tissue surrounding vessel intermediate-sized
- Alkaline phosphatase stains endothelium of new vessels
![](../pics/biopsy/vasculitis/recanvessvvgh.jpg)
VvG stain
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![](../pics/biopsy/vasculitis/recanvessgt2h2.jpg)
Gomori trichrome stain
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![](../pics/biopsy/vasculitis/vascrecanheh.jpg)
H & E stain
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Recanalization (Multiple lumens surrounded by endothelium) within intermediate-sized vessels with no elastin lamina
![](../pics/biopsy/vasculitis/neovaschsatp43.jpg)
ATPase pH 4.3 stain
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![](../pics/biopsy/vasculitis/neovascgt.jpg)
Gomori trichrome stain
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![](../pics/biopsy/vasculitis/neovascncam.jpg)
NCAM stain
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Elastin layer & fibrils: VvG stain
![](../pics/biopsy/vasculitis/vasculitischronvvg.jpg)
VvG stain
Artery: Damage
Connective tissue & Neovascularization: Proliferation inside elastin layer
Elastin layer: Incomplete in a region of vessel wall
|
![](../pics/biopsy/vasculitis/vein.jpg)
VvG stain
A neighboring vein has normal wall structure
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![](../pics/biopsy/vasculitis/neovasc.jpg)
VvG stain
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Occluded Artery
Surrounding Connective Tissue: Irregular & Rarified (Above)
Structure
Elastin fibrils (Arrow): Reduced in number
Central Connective tissue: Proliferation & Recanalization inside elastin layer
![](../pics/biopsy/vasculitis/neovascvvg.jpg)
VvG stain
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![](../pics/biopsy/vasculitis/neovascalp3.jpg)
Alkaline phosphatase stain
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![](../pics/biopsy/vasculitis/vascrecanhpalph.jpg)
Alkaline phosphatase stain
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Neovascularization
New, small vessels within previous large vessel
Endothelium of new vessels stains for alkaline phosphatase
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![](../pics/biopsy/vasculitis/neovascalp.jpg)
Alkaline phosphatase stain
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![](../pics/biopsy/vasculitis/neovascacp.jpg)
Acid phosphatase stain
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Neovascularized vessel: Surrounded by scattered Hemosiderin globules (Arrow)
![](../pics/biopsy/vasculitis/neovaschsnf.jpg)
Neurofilament + Trichrome stain
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VASCULITIS (Chronic & Ongoing): Epineurial Neovascularization
Differential diagnosis
![](../pics/biopsy/vasculitis/vasculitisnvhelp.jpg)
H&E stain
Neovascularization: New small vessels in pale, hypercellular epineurial connective tissue around large vessels
Fibrinoid necrosis: Wide-stained region around vessel lumen
|
![](../pics/biopsy/vasculitis/vasculitisnvvvglp.jpg)
VvG stain
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Epineurial Neovascularization
![](../pics/biopsy/vasculitis/vasculitisepineogt.jpg)
Gomori trichrome stain
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![](../pics/biopsy/vasculitis/vasculitisneovasccr.jpg)
Congo Red stain
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Epineurial connective tissue: Reorganized in region of neovascularization
![](../pics/biopsy/vasculitis/vasculitisneovascvvg.jpg)
VvG stain
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![](../pics/biopsy/vasculitis/vasculitisnvacp.jpg)
Acid Phosphatase stain
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Histiocytic cells: In Epineurium & Vessel walls
![](../pics/biopsy/vasculitis/vasculitisnvalplp.jpg)
Alkaline Phosphatase stain
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Epineurial Vessels & Connective tissue
Vasculitic process involves connective tissue around vessel
Alkaline phosphatase: Stains connective tissue around, & distant from, abnormal vessel
![](../pics/biopsy/vasculitis/vasculitisnvneovascgt.jpg)
Gomori trichrome stain
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Epineurial neovascularization
Proliferation of small vessels in epineurium near larger vessel (Above)
Many epineurial capillaries with endothelium stained by UEA-I (Below)
![](../pics/biopsy/vasculitis/vasculitisnvulex.jpg)
Ulex (UEA-I) stain
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![](../pics/biopsy/vasculitis/neovasctb.jpg)
Toluidine blue stain
Epineurium
Vessel: Abnormal structure
Connective tissue: Neovascularization & Irregular structure
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Endoneurial Microvessel Proliferation
Unusual feature of vasculopathic neuropathies
![](../pics/biopsy/vasculitis/vasculitisendoneurneovasctb.jpg)
Toluidine blue stain
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Epineurial Vessel: Intimal Proliferation
![](../pics/biopsy/vasculitis/vasculopintprolifhe.jpg)
H&E stain
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Artery
Lumen: Connective tissue proliferation
![](../pics/biopsy/vasculitis/vasculopintprolifcr.jpg)
Congo red stain
|
![](../pics/biopsy/vasculitis/vasculopintprolifnf.jpg)
Neurofilament stain
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Artery
Lumen: Connective tissue proliferation
Elastic lamina: Damaged & Interrupted
![](../pics/biopsy/vasculitis/vasculopintprolifncam.jpg)
NCAM stain
|
![](../pics/biopsy/vasculitis/vasculopintprolifacp.jpg)
Acid phosphatase stain
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Artery: Intimal proliferation
![](../pics/biopsy/vasculitis/vasculopintprolifgt.jpg)
Gomori trichrome stain
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![](../pics/biopsy/vasculitis/vasculopintprolifvvg.jpg)
VvG stain
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Vasculitis
Damaged Artery Walls: Abnormal fibril layer in
Larger artery near nerve (Dark Arrow)
Smaller epineurial artery (White Arrow)
Axons
Myelinated axons: Severe loss
Unmyelinated, small axons: Relative preservation
![](../pics/biopsy/vasculitis/vascvvglp.jpg)
VvG stain
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Vasculitis: Larger artery
Discontinuous fibril layer
Intima proliferation
![](../pics/biopsy/vasculitis/vasculitisepintvessvvg.jpg)
VvG stain
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Vasculitis: Epineurial artery
Abnormal fibril layer
Intima proliferation
![](../pics/biopsy/vasculitis/vasculitisvvgepvesshp.jpg)
VvG stain
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Vasculopathy: Larger artery with abnormal wall
Fibril layer: Reduced number of fibrils
Intima proliferation, Mild
![](../pics/biopsy/vasculitis/artwallredfibrilsvvg.jpg)
VvG stain
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Vasculitis: Axon loss
Large axons: Near complete loss
Small, unmyelinated axons: Relatively preserved
![](../pics/biopsy/vasculitis/vasculitisnf.jpg)
Neurofilament stain
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Vasculitis
Vessel wall: Contains blue mucinoid material inside elastin layer
![](../pics/biopsy/vasculitis/epineurvessvascab2.jpg)
Alcian blue/Nuclear fast red
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Perivascular Inflammation
![](../pics/biopsy/vasculitis/pvinf1.jpg)
H&E stain
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Vaaculitis: Inflammatory Cells
Mixture of lymphocytes & histiocytes surrounds vessels
![](../pics/biopsy/vasculitis/pvinf2.jpg)
H&E stain
|
![](../pics/biopsy/vasculitis/vasculitispvcellshe.jpg)
H&E stain
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VASCULITIS: Other Inflammatory features
![](../pics/biopsy/vasculitis/vascparafhphe.jpg)
H & E stain
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![](../pics/biopsy/vasculitis/vascvhphe.jpg)
H & E stain
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Inflammation patterns
- Giant cells (Above Left; Arrow) or Granulomas may be present
- Inflammatory cells in vessel wall may be fragmented (Above Right)
- Eosinophils may be present in cellularity around vessel (Below)
|
![](../pics/biopsy/vasculitis/vasculitisfibneceos.jpg)
H&E stain
Fibrinoid necrosis: In vessel wall
Eosinophils: In perivascular inflammation
|
Differential fascicular involvement of nerve
- Some fascicles have fewer axons than the others
![](../pics/biopsy/vasculitis/vascdiffascicgt.jpg)
Gomori trichrome stain
Different loss of myelinated axons in Different fascicles
|
![](../pics/biopsy/vasculitis/vasculitisdiffascicvvg.jpg)
VvG stain
Vessel fibril layer damage (Bottom Right)
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Vasculitis: Wallerian Degeneration
Gomori Trichrome stain
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Wallerian Degeneration
Myelin on many axons has lost red staining properties
Vasculopathy: Larger vessels
![](../pics/biopsy/vasculitis/vasculitisvvg.jpg)
VvG stain
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Vessel Wall Damage
Elastin fibril lamina: Interrupted
Intimal proliferation: Increased tissue inside fibril layer (See:
Normal)
![](../pics/biopsy/vasculitis/vascchronvvg.jpg)
VvG stain
|
![](../pics/biopsy/vesselsm/hiemnvvess.jpg)
VvG stain
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Vessel wall: Contains Histiocytic cells
![](../pics/biopsy/vasculitis/vasculitisacp.jpg)
Acid phosphatase stain
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Vasculitis: Endoneurium
ATPase stain reduced except onendoneurial vessels
![](../pics/biopsy/vasculitis/vasculopatp43.jpg)
ATPase pH 4.3 stain
|
Vessels: Intermediate-Sized
Normal Vessels
Nerve: Epineurial Veins & Arteries
Artery (Black arrow): Linear fibrils near lumen; Thick wall
Vein (White arrow): Interlaced, thin fibrils around outside of vessel; Thin wall
![](../pics/biopsy/vasculitis/vessintnv.jpg)
VvG stain
|
Artery: Linear fibrils near lumen
![](../pics/biopsy/vesselsm/nvvess1.jpg)
VvG stain
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Epineurial Artery: Normal
![](../pics/biopsy/vasculitis/arteryalblue.jpg)
Alcian blue stain
|
Epineurial Vein: Normal
Vein wall contains less mucopolysaccharide than artery
![](../pics/biopsy/vasculitis/veinalblue.jpg)
Alcian blue stain
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Muscle: Perimysial Vein & Artery
Endothelial cell markers
6
Artery: SEMA3G, PCSK5, VWF
Vein: LRRC1, ACKR1, VWF
Capillary: ADGRF5, BTNL9, VWF
Artery (Top right): Linear fibrils near lumen; Thick wall
Vein (Bottom left): Interlaced, thin fibrils around outside of vessel; Thin wall
![](../pics/biopsy/vasculitis/vessperimys.jpg)
VvG stain
|
Muscle: Perimysial structural variations
Vascular Perimysium: Contains intermediate sized arteries & veins
Avascular Perimysium: Contains connective tissue & fibrils, but no vessels
DM-VP: Muscle fiber atrophy is most often near avascular perimysium
Elastin
Forms a continuous ring inside the smooth muscle layer: Most prominent in artery
Is present in a network outside the smooth muscle layer: Artery & Vein
Vein (Bottom left) & Artery (Top right)
![](../pics/biopsy/vasculitis/nlvesssmagrnelastinred.jpg)
Smooth muscle actin (SMA) (Green) & Elastin (Red) stains
|
PECAM (Endothelium marker)
Fibrils inside the smooth muscle layer: Most prominent in artery
Vein (Left) & Artery (Right)
![](../pics/biopsy/vasculitis/avpcmgrsmard2sm.jpg)
Smooth muscle actin (SMA) (Red) & PECAM (Green) stains
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Epineurial Artery & Vein
Artery is mildly abnormal: Small cluster of connective tissue inside fibril layer
![](../pics/biopsy/vesselsm/nvvess2.jpg)
VvG stain
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Syphilitic arteritis
![](../pics/people/syphart.jpg)
Oppenheim 1894
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Vasculitis
References
1.
Neuropathology 2022 Jun 15
10/18/2023