PMC5678613_01
A low-power view demonstrates widespread proximal tubular degenerative changes and interstitial edema. (a) A glomerulus appears unremarkable (hematoxylin and eosin, original magnification x200). (b) At higher magnification, many proximal tubular cells are distended by numerous small intracytoplasmic PAS+ granules (arrow; periodic acid-Schiff, original magnification x400). (c) Immunohistochemial staining for lysozyme shows intense granular reactivity in the distribution of proximal tubular cell cytoplasm (immunoperoxidase, original magnification x100). (d) No significant staining is seen in a paired negative control obtained from an allograft postreperfusion biopsy (immunoperoxidase, original magnification x100). (e) On ultrastructural evaluation, proximal tubular cells contain abundant membrane-bound vacuoles (arrow; original magnification x8000). (f) On closer inspection, the vacuoles in proximal tubules contain clumped, degenerating organellar debris, consistent with autophagolysosomes (arrow; original magnification x25,000). (g) In rare cells, the autophagolysomes appear to form larger, membrane-bound aggregates (arrow; original magnification x6,000), corresponding to the (h) scattered large round eosinophilic inclusions seen in a minority of cells (arrow; hematoxylin and eosin, original magnification x600).
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The predominant abnormalities involved proximal tubular epithelial cells, which exhibited widespread degenerative changes including luminal ectasia, cytoplasmic simplification and vacuolization, irregular luminal profiles, loss of brush border, enlarged nuclei with prominent nucleoli, and focal apoptotic figures (Figure 1a). Many proximal tubular cells had hypereosinophilic granular cytoplasm owing to the presence of abundant intracytoplasmic, PAS-positive granules (Figure 1b). Scattered larger rounded, eosinophilic inclusions that were moderately periodic acid-Schiff positive and nonargyrophilic with the Jones methenamine silver stain were also seen (Figure 1h). Immunohistochemical staining for lysozyme (Lysozyme EP134; RabMAb, Rocklin, CA) revealed strong positivity in the distribution of the proximal tubular cell cytoplasm (Figure 1c, d). The most distinctive finding was abundant membrane-bound cytoplasmic vacuoles containing clumped, electron-dense, degenerating cellular organellar debris, consistent with autophagolysosomes (Figure 1e, f). The autophagolysosomes were diffusely distributed in proximal tubular epithelia and in some instances formed larger, membrane-bound aggregates that approached the size of the nucleus (Figure 1g).