Intracellular amyloidosis in peripheral nerve and skeletal muscle.

Amyloidosis is an etiologically heterogeneous group of disorders pathologically characterized by the extracellular deposition of amyloid fibrils, leading to tissue damage. It commonly affects the peripheral nervous system and occasionally involves skeletal muscle. The pathogenic mechanisms driving cellular injury in amyloidosis remain elusive. In this study, we examined 3 sural nerve and 5 skeletal muscle biopsies from patients with amyloidosis to localize the deposition of amyloid fibrils. Histologically, the nerve biopsies showed axonal degeneration and Schwann cell (SC) changes; muscle biopsies demonstrated variable myopathic and neurogenic features with multifocal amyloid deposition, including within intramuscular nerves. Electron microscopy identified both intracellular and extracellular amyloid deposition in all 8 biopsies. The ultrastructural localization of amyloid fibrils included the nerve and muscle extracellular matrix, as well as the SC processes, peri-/sub-sarcolemmal region of non-necrotic myofibers, and endoneurial and endomysial/perimysial blood vessel cells. Notably, SC processes, particularly bands of Büngner, formed amyloid-related complex inclusions in all 3 nerve cases. These findings suggest that intracellular amyloid deposition is common in peripheral nerve and skeletal muscle and may play a significant role in cellular injury and degeneration, and ultimately the progression of neuropathy and myopathy.