Neuromuscular

AMYLOID: PATHOLOGY

Muscle
  Dysferlin
  IM-VAMP
Nerve
Vessels
  1° Amyloid
  LGMD 2B
Mutations
  Val30Met
  Thr60Ala
  Dysferlin

MUSCLE


Amyloid myopathy

  • Amyloid (red): Extracellular; Deposited along muscle fiber surfaces & in Perimysium
  • Apple green birefringence of amyloid
  • Amyloid Components
    • Hereditary
      • Apolipoprotein A1, Apolipoprotein A4, Apolipoprotein E, Serum amyloid P component
      • No Anoctamin-5 or Dysferlin
    • Acquired: Amyloidogenic proteins (AL & SSA)
  • Amyloid in IM-VAMP (IBM)

Congo red

Congo red (Polarized light)

Congo red (Fluorescence)
Amyloid surrounding, and on, muscle fibers

Congo red

Congo red (Polarized light)

Congo red (Fluorescence)


Congo red

Congo red
Muscle fiber pathology in amyloid myopathy

Congo red

Congo red stain

Congo red stain

Congo red stain (Polarized light)

Congo red, polarized light


Congo red

Amyloid Fibers
  Muscle fiber pathology in amyloidosis

H&E stain

H&E stain

Gomori trichrome

Gomori trichrome

VvG

ATPase pH 9.4

ATPase pH 9.4

NADH


Dystrophin
Surface membrane (Above) & Basal lamina (Below): Thickened & reduplicated around muscle fibers

α2-Laminin

IgAκ M-protein: Amyloid


Congo red
Amyloid deposits in perimysium and along the perimysial surface of muscle fibers

Congo red

NERVE: Amyloid

Patterns of axon loss Amyloid deposition in nerve may be
Severe Axon Loss
Markedly reduced numbers of large and small axons

Neurofilament stain

Neurofilament stain

Moderate axon loss
Differential fascicular loss: More axon loss in some areas than others

Neurofilament stain

Moderate axon loss

VvG stain
More loss of small, than large, axons

Neurofilament stain
Large axons: Moderate loss
Small axons: Severe loss

Neurofilament stain


NCAM stain
Non-myelinating Schwann cells
Normal or Increased Numbers

NCAM stain


Toluidine blue stain
Moderate axon loss
  More loss of small, than large, myelinated axons
  Subperineurial edema in some fascicles



Toluidine blue stain

Toluidine blue stain

Toluidine blue stain

Amyloid Deposition

Capillary walls: Thick
Sub-Perineurial edema

H&E stain


Congo red stain
Capillary walls
  Contain red-stained amyloid
  Amyloid is birefringent

Congo red stain

Endoneurial amyloid, Multifocal, often near endoneurial vessels (Arrow)

Congo red stain


Congo red stain
Amyloid: Amorphous deposits surround endoneurial microvessels

Congo red stain

Toluidine blue stain
Amyloid: Amorphous deposits around endoneurial microvessels

Toluidine blue stain

Endoneurial amyloid, Diffuse

Congo red stain

Congo red stain

Toluidine blue stain
Amyloid: Amorphous deposits in endoneurium

Toluidine blue stain

SUBPERINEURIAL AMYLOID (Arrow)

Congo red stain

Moderate sized vessels: Amyloid

Vessels in Perimysium & Epineurium: May have amyloid deposits

Congo red stain
Amyloid birefringence
Congo red stain (± Polarized light)

Congo red stain (Polarized light)
Amyloid in vessel walls
  Red-Stained
Birefrengence ± Polarization
Amyloid in vessel wall
  Apple green
    with polarized light.

Amyloid: Artery

Congo red stain
Amyloid: Vein + Perimysium

Congo red stain

Amyloid: TTR Val30Met mutation

Nerve

H&E stain
Amyloid: Amorphous clusters in endoneurium

H&E stain

H&E stain
Amyloid: Amorphous, rounded clusters in endoneurium

Gomori trichrome stain

VvG stain

Toluidine blue stain
Amyloid
  Amorphous, rounded clusters in endoneurium
  Amyloid surrounded by pale cell-free regions

Toluidine blue stain

Congo red stain
Amyloid
  Amorphous, rounded clusters in endoneurium
  Perineurial deposition, scattered

Congo red stain

Amyloid
  Surrounds endoneurial microvessel

Congo red stain

Amyloid (TTR Val30Met): Muscle

H& E stain
Chronic denervation & Reinnervation, Progressive
  Grouped atrophy
  Larger muscle fibers are hypertrophied

VvG stain

ATPase pH 9.4 stain
Chronic denervation & Reinnervation, Progressive
  Fiber type grouping

ATPase pH 4.3 stain

ATPase pH 4.3 stain
Chronic denervation & Reinnervation, Progressive
  Muscle fibers in region of grouped atrophy
    Varied degrees of immaturity (Type 2C)
    Esterase positive cytoplasm

Esterase stain

Congo red stain
Amyloid deposits
  Most prominent in smaller perimysial vessels

Congo red stain

Amyloid (TTR Thr60Ala): Muscle

H&E stain

Congo red stain
Amyloid deposits
  Most prominent in connective tisue & around muscle fibers

Congo red stain

Congo red stain

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5/16/2017