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Immune Checkpoint Inhibitors

Immune Neuropathies   Endoneurial Microvessel Inflammation   Perineuritis/Epineuritis Immune Myopathies, Multifocal   Cell foci, Mild fiber necrosis   Cell foci, Clustered fiber necrosis

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Polyradiculoneuropathy + Endoneurial Inflammatory Vasculopathy (Ipilimumab)

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MRI: Root enhancement

MRI: Meningeal enhancement

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Endoneurial Microvessels: Perivascular inflammation

H&E stain

CD163 stain

Inflammation: Endoneurial; Perivascular

H&E stain

CD3 stain

CD163 stain

Acid phosphatase stain

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Toluidine blue stain

Toluidine blue stain

Subperineurial Edema

VvG stain

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Perineuritis/Epineuritis/Vasculopathy: ICI-related

H&E stain

Perineurium
  Pale & Wide around most fascicles
Epineurium
  Structure: Irregular & Pale

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MHC Class I stain

MHC Class I
  Abnormally & Diffusely expressed in Epineurial connective tissue

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H&E stain

Perineurium
  Pale & Wide around most fascicles
Epineurium
  Structure: Irregular & Pale
Endoneurium
  Wallerian Degeneration: Myelin irregularly stained, may be pale

VvG stain

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Loss of large axons

Neurofilament stain

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Perineurial Pathology

H&E stain

Perineurium
  Pale & Wide
  Some areas have increased cells

H&E stain

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Perineurium
  Pale & Wide
Endoneurium
  Wallerian Degeneration: Myelin irregularly stained & may be pale

VvG stain

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ICI Perineuriopathy: C_5b-9 stain
  Perineurium: Loss of C_5b-9 stain
  Endoneurium: C_5b-9 stains cells associated with Wallerian degeneration
  Epineurium: C_5b-9 stains scattered cells

C5b-9 stain

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Control Nerve
  Perineurium: Strong C_5b-9 stain

C5b-9 stain

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Toluidine blue stain

Perineurium
  Pale & Wide
Endoneurium
  Loss of most myelinated axons: Varied between fascicles

Toluidine blue stain

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Epineurium
  Structure: Irregular & Pale

H&E stain

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CD4 stain

Epineurial Cells
  Scattered
  Stain for CD4 & CD8
Perineurial Cells
  Mostly CD8

CD8 stain

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Epineurial & Endoneurial Cells
  Many Histiocytes

HAM56 stain

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ICI Myopathy, Multifocal

Immune ICI Myopathies, Multifocal   Perimysial Cell foci, Mild fiber necrosis   Cell foci, Clustered fiber necrosis

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ICI Myopathy, Multifocal 1

Cells
  Histiocyte foci, Perimysial
Muscle fibers   Necrosis, Mild
  MHC Class I: Increased in clusters of fibers

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H&E stain

Perimysial Connective Tissue
  Widened: focal regions
  Cellular, Histiocytes
Muscle fibers
  Perifascicular pathology
  Scattered, small fibers at edge of some fascicles, near perimysial damage

H&E stain

Acid phosphase stain

Histiocytic cell clusters in widened Perimysium

Esterase stain

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Alkaline Phosphatase stains
  Perimysium
  Endomysial capillaries

Alkaline Phosphatase stain

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Multifocal involvement of Muscle fibers

MHC I stain

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Necrotic muscle fibers: C_5b-9 stained

C5b-9 stain

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ICI Myopathy, Multifocal 2

Cells
  Histiocyte Foci
Muscle Fibers   Necrosis, Clustered
  MHC Class I: Increased in clusters of fibers

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Congo red stain

Multifocal Myopathy
  Regions of: Necrotic fibers; Cell clusters

NADH stain

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C5b-9 stain

Multifocal Myopathy
  Regions of: Necrotic or Damaged muscle fibers

MHC Class 1 stain

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C5b-9 stain

Necrotic muscle fibers: In Clusters

NADH stain

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H&E stain

Cell Foci: Large; Histiocytic

Congo Red stain

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Alkaline phosphatase stain

Cell Foci
  Stain for alkaline phosphatase
  Contain many capillaries

UEA I stain

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H&E stain

Cell Foci
  Contain mostly histiocytes

HAM56 stain

CD4 stain

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Necrotic muscle fibers: clustered

NADH stain

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VvG stain

Cell clusters: contain vessel-like strudtures

Esterase stain

Cell clusters: Contain many histiocytes

Acid phosphatase stain

Acid phosphatase stain

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ICI Myopathy, Multifocal 3

Muscle Fiber Morphology
  Necrosis, Clustered, Small Region
  Most fibers: Normal morphology
  MHC Class I: Increased in clusters of fibers

Congo red stain

MHC Class I stain

H&E stain

H&E stain

stain

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4/16/2024