The normal pancreas shows absent to sparse inflammatory infiltrates, confined to the fibrous septa without involvement of septal structures. The fibrous septa are proportional to the size of the associated duct and vessels.

Focal active septal inflammation is present; however, the overall features do not fulfill the criteria for mild ACR

Active inflammation, including activated blastic lymphocytes and/or eosinophils, involving septal structures is present. This inflammatory infiltrate may be variable. Foci of venulitis are seen, which is characterized by circumferential lymphocytic/inflammatory accumulation in the subendothelium with associated endothelial injury (Figs. 8.1 and 8.2). Ductal injury (ductitis) should also be present and will show lymphocytic or eosinophilic inflammation within the ductal epithelium. As a result of the inflammatory infiltrate, the ductal epithelial cells often show irregular spacing of the nuclei, anisonucleosis, and reactive changes (Fig. 8.3). Denudation of the epithelial cells may also be seen. The presence of venulitis or ductitis is sufficient for the diagnosis of mild ACR. In the absence of venulitis and ductitis, mild ACR may be diagnosed by the presence of focal acinar inflammation, limited to no more than two inflammatory foci per lobule with absent to minimal acinar cellular injury or dropout (Fig. 8.4).

In addition to the histological findings of mild rejection, moderate ACR includes the finding of multifocal acinar inflammation (three or more foci per lobule) with individual acinar cell injury/dropout (Fig. 8.5). Alternatively, the diagnosis of moderate ACR may be defined by the presence of mild intimal arteritis, which is characterized by rare or occasional subendothelial inflammation by mononuclear cells without activation of or damage to the overlying arterial endothelium. The extent of the arteritis should compromise less than 25 % of the vessel lumen (Fig. 8.6).

Severe ACR is characterized by diffuse acinar inflammation (confluent) with associated focal or diffuse confluent acinar cell necrosis. Interstitial edema and hemorrhage are characteristic of severe tissue damage. There should be no significant acinar tissue present without inflammatory infiltrate. Severe ACR may also be diagnosed by moderate to severe intimal arteritis, in which mononuclear cells are seen within the intima of a muscular artery with evidence of injury. This injury can manifest as endothelial cell activation or sloughing, margination of neutrophils, macrophage activation, proliferation of myofibroblasts within the intima, and fibrin leakage. Greater than 25 % of the vessel lumen should be compromised by the injury. Necrotizing arteritis, with focal or circumferential fibrinoid necrosis, may be seen with or without transmural inflammation. This finding can also be seen in AMR and should raise this possibility.