Pathological Findings

Macroscopic Findings

Macroscopic recognition of pancreatic ischemia depends on the severity or size of ischemia, and the presence of complicated lesions, such as hemorrhages or fat necrosis. Some authors have described that the pancreatic necrotic area can be pale and yellowish with red congested margins [2]. In our experienced case, examination by the naked eye was not able to reveal significant changes in pancreatic ischemia caused by cholesterol, but on histological examination geographic or lobular ischemic necrosis was confirmed.

Histological Findings

The representative histological features of fresh ischemia are coagulative necrosis of the pancreatic tissues [2, 7]. The size of the necrosis can vary from case to case depending on the severity of the ischemia, and extensive pancreatic necrosis can occur. Pancreatic ischemia associated with DIC is characterized by well-demarcated patchy or geographic foci composed of degenerating cells with deeply eosinophilic cytoplasm and pyknotic or disappearing nuclei, indicating coagulative necrosis of affected acinar cells (figs. 1 and 2) [5]. These patchy lesions are an early or localized form of pancreatic infarct, and are referred to as primary acinar necrosis. Similar lesions can be recognized in pan-creata with cholesterol emboli [6]. Rarely, cancerous venous permeation causes

Fig. 1. Patchy ischemic lesion composed of primary acinar necrosis, associated with DIC. Fibrin thrombus is present in the interlobular artery close to the ischemic lesion (arrow) (original magnification X70).

focal ischemia of the pancreas (fig. 3). There are relatively clearly defined borders between the ischemic lesions and surrounding normal acinar cells. The presence of these clear borders could be useful for distinguishing ischemia from postmortem autolysis.

On the basis of the pathogenetic findings, ischemic lesions can be distinguished from fat necrosis [1]. Fat necrosis is tryptic or enzymic necrosis, resulting from autodigestion of pancreatic tissues caused by extravasated pancreatic juice containing various activated enzymes [1, 8]. Therefore, fat necrosis is secondary necrosis, and fundamentally differs from the ischemic necrosis referred to as primary acinar necrosis. However, peripheral or large ischemic necrosis may induce fat necrosis and/or hemorrhage (fig. 4) [2]. There is hence a correlation between pancreatic ischemia and acute pancreatitis [2, 7].

Some authors have noted selective ischemic changes of the islets of Langerhans in newborns or infants with various forms of shock [9, 10]. These findings may indicate the vulnerability of the islets to shock-related injury in newborns or infants [10]. The patchy ischemic lesions caused by DIC or cholesterol emboli infrequently involve the islets [5, 6]. Rarely, however, focal pancreatic ischemia focusing on the islets is found in DIC cases [5]. Figure 5 shows focal and segmental ischemia of the pancreatic islets, and figure 6 shows focal necrosis involving islets and surrounding acinar cells. This

Fig. 2. Fresh ischemic lesion. a Low magnification of patchy ischemic lesions composed of degenerating acinar cells (arrow heads) (original magnification X70). b High magnification of patchy ischemic lesions showing degenerating acinar cells with deeply eosinophilic cytoplasm and pyknotic nuclei. Intralobular ductules which have avoided the ischemic changes are present (arrow) (original magnification X400).

Fig. 2. Fresh ischemic lesion. a Low magnification of patchy ischemic lesions composed of degenerating acinar cells (arrow heads) (original magnification X70). b High magnification of patchy ischemic lesions showing degenerating acinar cells with deeply eosinophilic cytoplasm and pyknotic nuclei. Intralobular ductules which have avoided the ischemic changes are present (arrow) (original magnification X400).

morphological variety of ischemic lesions could be attributed to the size and/or location of the arteriolar lesions causing the ischemia. Using a correlation with the form of the pancreatic microvasculature, Takahashi et al. established three types of pancreatic ischemic injuries: (1) 'peripheral necrosis', chiefly occurring in the peripheral areas of the pancreatic lobules and not involving the islets; (2) 'central necrosis', representing a microinfarction of acinar cells and the islets, and (3) 'peripheral atrophy', characterized by the thinner and more degranulated pattern of acinar cells in the peripheral areas of the pancreatic lobules [11, 12]. According to this classification, selective ischemia of the islets could be referred to as central necrosis, and patchy acinar necrosis as peripheral necrosis. In fact, detailed examination revealed minute thrombi in the dilated vessels of the islets in cases showing central necrosis, and multifocal thrombi in the interlobular arteries of cases of peripheral necrosis [5].

Another interesting feature of the patchy ischemic lesions, as a localized or early form of pancreatic ischemia, is that intralobular ductular cells are apt to

Fig. 3. Small ischemic lesions (arrow heads) associated with cancerous emboli (arrow) (original magnification X70).
Fig. 4. Patchy ischemic lesions located on the peripheral portion of the pancreatic lobule, accompanying hemorrhage. Surrounded lobules showing interstitial edema (original magnification X70).
Fig. 5. Segmental ischemic lesions involving the islets of Langerhans (arrow heads) (original magnification X200).
Fig. 6. Focal pancreatic ischemia (arrow heads) centrally involving the islets of Langerhans (arrows). These findings correspond to those of central necrosis (original magnification X100).

Fig. 7. Patchy fibrotic foci corresponding to the subsequent features of pancreatic ischemic lesions. a Patchy fibrotic focus with slightly retracted appearance in the pancreatic lobule (original magnification X70). b High magnification of patchy fibrotic focus containing numerous small ductules. These ductules coud be intralobular ductules that avoided previous ischemic damage (original magnification X400).

Fig. 7. Patchy fibrotic foci corresponding to the subsequent features of pancreatic ischemic lesions. a Patchy fibrotic focus with slightly retracted appearance in the pancreatic lobule (original magnification X70). b High magnification of patchy fibrotic focus containing numerous small ductules. These ductules coud be intralobular ductules that avoided previous ischemic damage (original magnification X400).

escape the ischemic damage (fig. 2b). These findings suggest that intralobular ductular cells are more resistant to ischemic damage than acinar cells [6], the latter being the most differentiated and most vulnerable cells in pancreatic tissues. Moreover, these findings may be the diagnostic clue to identifying the

Fig. 8. Cholesterol embolus and associated patchy fibrotic focus (original magnification X70).

subsequent or chronic lesions of the pancreatic ischemia; the presence of the undamaged intralobular ductules could be the histological hallmark of chronic ischemia, differentiating it from non-specific fibrosis [6]. Our study proposed putative sequential changes of the small pancreatic ischemia [6]. After the earliest ischemic change, the ischemic area may show interstitial edema, mild neu-trophilic infiltration, and phagocytic removal of the necrotic acinar cells. Intralobular ductules are usually inconspicuous in normal pancreatic tissue, but become apparent in ischemic lesions. Patchy edematous foci with remnant ductules, acinar cell depletion and mild neutrophilic infiltrates can be referred to as 'subacute ischemic lesions'. These foci can be replaced by fibrosis and show relatively retracted features (fig. 7). Moreover, remnant ductules can be found in these fibrotic lesions. In our investigation, such lesions, suggesting chronic ischemic lesions, were found in five of the 17 postmortem pancreata with cholesterol emboli [6] (fig. 8). Unfortunately, however, the subsequent histological features of extensively involved ischemic lesions have not been elucidated.

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