Neuromuscular

Immune Checkpoint Inhibitors

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

Polyradiculoneuropathy + Endoneurial Inflammatory Vasculopathy (Ipilimumab)

MRI: Root enhancement
 MRI: Meningeal enhancement

Endoneurial Microvessels: Perivascular inflammation


H&E stain
CD163 stain
Inflammation: Endoneurial; Perivascular

H&E stain
CD3 stain
CD163 stain
Acid phosphatase stain

Toluidine blue stain
Toluidine blue stain
Subperineurial Edema

VvG stain

Perineuritis/Epineuritis/Vasculopathy: ICI-related


H&E stain
Perineurium
  Pale & Wide around most fascicles
Epineurium
  Structure: Irregular & Pale

MHC Class I stain
MHC Class I
  Abnormally & Diffusely expressed in Epineurial connective tissue

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

VvG stain
Loss of large axons

Neurofilament stain

Perineurial Pathology


H&E stain
Perineurium
  Pale & Wide
  Some areas have increased cells

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

VvG stain
ICI Perineuriopathy: C5b-9 stain
  Perineurium: Loss of C5b-9 stain
  Endoneurium: C5b-9 stains cells associated with Wallerian degeneration
  Epineurium: C5b-9 stains scattered cells

C5b-9 stain
Control Nerve
  Perineurium: Strong C5b-9 stain

C5b-9 stain

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

Toluidine blue stain
Epineurium
  Structure: Irregular & Pale

H&E stain

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

CD8 stain
Epineurial & Endoneurial Cells
  Many Histiocytes

HAM56 stain

ICI Myopathy, Multifocal

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

ICI Myopathy, Multifocal 1

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

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
Alkaline Phosphatase stains
  Perimysium
  Endomysial capillaries

Alkaline Phosphatase stain
Multifocal involvement of Muscle fibers

MHC I stain
Necrotic muscle fibers: C5b-9 stained

C5b-9 stain

ICI Myopathy, Multifocal 2

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

Congo red stain
Multifocal Myopathy
  Regions of: Necrotic fibers; Cell clusters

NADH stain

C5b-9 stain
Multifocal Myopathy
  Regions of: Necrotic or Damaged muscle fibers

MHC Class 1 stain

C5b-9 stain
Necrotic muscle fibers: In Clusters

NADH stain

H&E stain
Cell Foci: Large; Histiocytic

Congo Red stain

Alkaline phosphatase stain
Cell Foci
  Stain for alkaline phosphatase
  Contain many capillaries

UEA I stain

H&E stain
Cell Foci
  Contain mostly histiocytes

HAM56 stain

CD4 stain
Necrotic muscle fibers: clustered

NADH stain

VvG stain
Cell clusters: contain vessel-like strudtures

Esterase stain
Cell clusters: Contain many histiocytes

Acid phosphatase stain

Acid phosphatase stain

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