Vasculitis: Rheumatoid Disorder/Cryoglobulinemia

Histiocytic Vasculopathy: Rheumatoid Disorder/IgMκ M-protein/Cryoglobulinemia

Histiocytic Arteriopathy

82 year old female with rapidly progressive mononeuritis multiplex & Multi-organ failure
Rheumatoid factor = 616; ANCA-; NfL 777; C4<4; IgMκ M-protein; Cryoglobulins, borderline

Vessel Pathology
Epineurium
Artery Occlusion & Damage
Also see: pANCA
Perimysium: Histiocytic Vasculitis
Focal Infarction: Nerve
Axon loss: Severe; Regional

Nerve: Occluded Artery; Focal infarction; Histiocytic/Few lymphocytes

Focal nerve infarction: Also see Behçet

Gomori trichrome stain

H&E stain

Epineurial Vessel (Artery): Chronic Pathology, Occlusion

Vessel Structure
Damaged wall
Elastin layer interrupted & irregular
Irregular ATPase stained smooth muscle
Endothelial cells: Acid phosphatase positive
Lumen: Absent or Contains large cells, possibly endothelium
Neovascularization
Abnormal staining for NCAM
Size: Large at some levels
Calcification: In some regions of vessels wall
Hemosiderin: Present in Epineurium
Epineurial connective tissue Surrounding vessel
Scattered histiocytes
Alkaline phosphatase stained

See: Epineurial vessels, control

VvG stain

VvG stain

Acid phosphatase stain

Acid phosphatase stain

Alkaline phosphatase stain

ATPase pH 4.3 stain

Cryoglobulin/Rheumatoid Vasculitis: Nerve Infarction

H&E stain

Perineurium: Pale in regions
Endoneurial vessels: Large size & lumen
Epineurium: Increased numbers of small vessels (Above)
Wallerian degeneration: Many Myelin sheaths are abnormally pale-stained (Below)

Gomori trichrome stain

Endoneurial Vessels: Enlarged with large lumen

Toluidine blue stain

Endoneurial vessels: Many are large (Also see below)
Histiocytes with Lipid droplets: Scattered in endoneurium
Myelin remnants (Ovoids): Scattered in endoneurium

Axon Loss

Myelinated Axons: Marked loss
Endoneurial Microvessels: Often large; Some dark stained

VvG stain

Axons, Large & Small: Nearly complete loss
Perineurium: Thick & Irregular structure

Neurofilament stain

Axons, Large & Small: Nearly complete loss in some regions

Neurofilament (Green) + NCAM (Red)

Schwann cells, Non-myelinating (Red): Reduced in regions of endoneurium
Axons: Complete loss in fascicles with loss of Schwann cells

Neurofilament (Green) + NCAM (Red)

Schwann cell & Myelin Degeneration

Histiocytic cells: Many; Scattered in endoneurium
Myelin sheaths: Abnormal, strong acid phosphatase stain

Acid phosphatase stain

Nerve Infarction: Schwann cell loss in focal regions

Schwann cells, Non-myelinating: Reduced in region of endoneurium

NCAM stain

Schwann cells (Green & Yellow)
Reduced numbers in region of endoneurium (Left)
Chronic pathology
"Denervated"" SC type: Büngner bands; Most SC co-stain for P0 & NCAM (Yellow)

NCAM (Green) + P0 (Red)

Endoneurial Damage: C_5b-9 staining of Endoneurium

C_5b-9 stains
Endoneurium: Cells & Connective tissue
Perineurium: Irregular structure; Thick

C_5b-9 stain

Endoneurial Damage: Hemorrhage

Toluidine blue stain

Endoneurial Cells after Axon loss

From: R Schmidt

Histiocytes
Schwann cells: With myelin & lipid debris
Mast cell
Fibroblast processes

Schwann cells
With Myelin & Lipid debris
Büngner bands

From: R Schmidt

Epineurial Damage

Alkaline phosphatase stain

Alkaline Phosphatase
Stains: Connective tissue around nerve; Epineurium

Alkaline phosphatase stain

Histiocytic Vasculopathy: Rheumatoid Disorder/IgMκ M-protein/Cryoglobulinemia in Muscle

Vessel Structure: Damaged

See: Perimysial vessels, control

H&E stain

Perimysial Vessels (Arteries)
Size: Very large
Wall Structure
Inner layer: Fibrinoid necrosis
Outer layer: Replaced by large, "palisaded" cells
Lumen: Large cells, possibly endothelium, adherent to inner wall

H&E stain

Gomori trichrome stain

Fibrinoid Necrosis: In central region of artery
Large cells: Replace wall structure

Congo red stain

AMPDA stain

Fibrinoid Necrosis: Inside fibril layer
Fibril layer of vessel wall: Irregular
Outer layer: Replaced by large cells

VvG stain

See: Perimysial vessels, control

Fibrinoid Necrosis: C_5b-9 stain

C_5b-9 stain

Histiocytic Arteritis

Acid phosphatase stain

Histiocytes (Acid phosphatase stained cells)
Replace vessel wall
Nearly all cells are stained

Acid phosphatase stain

Esterase stains
Clusters of cells in vessel wall
? Early granulomatous change

Esterase stain

Arterial Smooth Muscle Layer: Incomplete & Damaged

ATPase pH 4.3 stain

Perimysial Connective Tissue: Alkaline phosphatase stain around damaged artery

Alkaline phosphatase stain

Alkaline phosphatase stains
Perimysial connective around, & extending away from, damaged artery

Alkaline phosphatase stain

Vessel Endothelium Pathology
Strong endothelial stain by NADH
Also some endothelial cell staining on Esterase & Acid phosphatase

NADH stain

Vasculopathic Neuropathy with Endothelial Cell Pathology

83 year old female with asymmetric distal weakness & sensory loss in legs and arms progressive over 3 months.
Lab testing: Cryoglobulinemia type 2 (Mixed), CREST, IgMκ M-protein; Rheumatoid factor; NfL = 434.