Fig 3. Histopathological features of NSVN.

Digital photomicrographs of sural nerve biopsies from patients with NSVN show classic histopathological features. Axial paraffin-embedded Hematoxylin and Eosin-stained thick sections demonstrate lymphocytic and macrophagic infiltration of an epineurial medium diameter vessel (a) with higher magnification images demonstrating epineurial vasculitis with transmural vasonecrosis with luminal occlusion (b; white arrow and c; black arrow, white asterisk indicates expected location of lumen). A longitudinal paraffin-embedded Hematoxylin and Eosin-stained thick section depicts the less commonly observed endoneurial microvasculitis (d; black arrow). Indirect immunohistochemistry of frozen axial thick sections counterstained with Hematoxylin demonstrates predominantly CD3+ T lymphocyte infiltration of the media and adventitia of an epineurial medium diameter vessel (e, black arrow) without involvement of an adjacent epineurial small diameter vessel (e, red arrow). In acute and severe cases, marked endoneurial ischemia occurs with active Wallerian degeneration with diffuse myelin debris and ovoids, as demonstrated in the Toluidine Blue/ Basic Fuchsin-stained, plastic-embedded semi-thin section (f; black arrows). Endomysial microvasculitis with vasonecrosis and luminal occlusion (g; black arrow) with focal inflammatory cell infiltration into muscle fibers and the surrounding endomysium associated with myonecrosis (h) are demonstrated in Hematoxylin and Eosin-stained frozen axial thick sections of a quadriceps muscle biopsy of a patient with NSVN. Magnification bars: a, d, e, f, g = 100 μm; b = 50 μm; c and h = 200 μm