Necrotizing pancreatitis due to simian adenovirus type 31 in a rhesus monkey.

Simian adenovirus type 31 was isolated from pancreatic tissue of an 8-year-old male rhesus monkey that died as the result of acute necrotizing pancreatitis. Histologically, the pancreas showed wide-spread necrosis, extensive infiltration of polymorphonuclear leukocytes, and nuclear inclusions in pancreatic acinar cells. Large numbers of adenovirus particles were demonstrable in the acinar cells by electron microscopy. This is the second case of adenovirus-associated pancreatitis we have found in rhesus monkeys and the first case in which we attempted to isolate the virus. Our data indicate that adenovirus pancreatitis is a distinct entity in rhesus monkeys and may occur with greater frequency than is generally believed.     

A new pathological scoring method for adrenal injury in rats with severe acute pancreatitis

These studies investigated the appearance and function of adrenal glands in rats with severe acute pancreatitis (SAP) and established a new histopathological score to evaluate adrenal histopathological changes. Severe acute pancreatitis relied on retrograde infusion of 5% sodium taurocholate into the bile-pancreatic duct. The damage of SAP was estimated by serum amylase, secretory phospholipase A₂ and pancreatic histopathology. Light and electron microscopy of adrenal gland, and the levels of serum corticosterone were investigated. These results showed that the generally ascending trend of adrenal pathological score was inversely proportional to the generally descending trend of serum corticosterone levels, but parallel with the changes of pancreatic histopathology. Herein, the new adrenal histopathological score was effective in the evaluation of adrenal injury following SAP. It may indirectly reflect the variation of serum cortisol levels and the severity of pancreatitis to a certain extent.     

Circumportal pancreas: a clinicoradiological and embryological review

Circumportal pancreas is a congenital fusion anomaly of the pancreas where the pancreatic tissue from the uncinate process, anomalously encases the portal vein and/or the superior mesenteric vein. Depending upon the level of the pancreatic annulus the variant can be classified into three subtypes—suprasplenic, infrasplenic or mixed; and each subtype exhibits either an anteportal or retroportal main pancreatic duct. Limited literature is available on this intriguing anomaly primarily because of its relatively low prevalence in humans (published prevalence rates vary from 0.2 to 2.5 %), probable lack of awareness among medical professionals and its generally symptomless course. In an attempt to appraise the embryological basis, clinicoradiological manifestations and potential surgical implications of circumportal pancreas, literature published in English was searched using PubMed and information collated so as to provide up-to-date information on this relatively understudied entity. The anomaly by itself remains innocuous but its preoperative recognition in those undergoing pancreatic resection bears decisive influence on planning and selecting apposite surgical resection planes as inadvertent duct injury can lead to pancreatic fistula.     

Intraductal papillary mucinous adenoma that arises from pancreatic heterotopia within a meckel diverticulum

Neoplasia is an unusual complication of Meckel diverticulum. Most tumors of Meckel diverticulum are neuroendocrine or mesenchymal in origin. Adenocarcinomas represent a minority of the tumors that arise in Meckel diverticulum and are generally thought to develop from either endogenous small intestinal epithelium or heterotopic gastric epithelium. Despite the presence of ectopic pancreas in a small fraction of Meckel diverticula, convincing evidence of tumors that arise from heterotopic pancreatic exocrine tissue has not been described in this setting. Intraductal papillary mucinous neoplasms are relatively uncommon tumors of pancreatic ductal epithelial cells that line the main pancreatic duct or its major side branches. We present an unusual case of an intraductal papillary mucinous neoplasm that arose in a heterotopic pancreas within a Meckel diverticulum.     

The arteries of the pancreas of the dog. An injection–corrosion and microangiographic study

The ramification of the pancreatic arteries, including the lobular vessels, was studied in 36 mongrel dogs by means of plastic injection and corrosion, as well as microangiography. The left pancreatic lobe receives the left cranial pancreatic artery and other smaller branches from the splenic artery, and two to four twigs from the gastroduodenal artery. In addition, it receives very often a branch from the common hepatic artery. Branches arising from the cranial mesenteric artery and from the first jejunal artery may also be found. The right cranial pancreatic artery and the right gastroepiploic artery give branches to the pancreatic angle. The arteries to the right pancreatic lobe arise from the cranial and from the caudal pancreaticoduodenal arteries. The interlobular arteries give origin to the intralobular arteries. The penetration and the distribution of the latter vessels differ in lobules of different shape. The intralobular course may be straight or curved. Branches arise generally at acute angles, forming Y or fork-like patterns, ending into bundles of arterioles.     

Extra-adrenal Composite Paraganglioma with Ganglioneuroma Component Presenting as a Pancreatic Mass

Paragangliomas may have composite forms in which they combine features of a typical paraganglioma with those of a neural component consisting of either neuroblastoma, ganglioneuroblastoma, or ganglioneuroma. These variants are rare and generally located in the adrenal. Herein, we describe a retroperitoneal, extra-adrenal composite paraganglioma–ganglioneuroma of a 57-year-old woman. Radiological evaluation revealed a nodular mass with apparent pancreatic location, with findings suggestive of an endocrine tumor, yielding the diagnosis of a pancreatic endocrine tumor. At histology the neoplasm, strictly adhering to the external surface of the pancreatic gland but well demarcated, displayed a main central region with typical paraganglioma features and cells arranged in cords and in a nesting “zellballen” pattern, positive for neuroendocrine markers, and a distinct peripheral area consisting of dense bundles of wavy spindled Schwann cells, with scattered ganglionic cells.     

Histological and fine structural features of pancreatic ductal adenocarcinomas in relation to growth and prognosis: studies in xenografted tumours and clinico-histopathological correlation in a series of 75 cases

Histology and fine structure of pancreatic ductal adenocarcinomas were assessed with respect to their significance for tumour growth and prognosis. The histological parameters included glandular differentiation, nuclear anaplasia, nuclear size, and mitotic activity (number of mitoses per high power field). Using these criteria three grades of malignancy were distinguished. They correlated well with the growth kinetics of seven human pancreatic ductal adenocarcinomas transplanted into nude mice. The tumour doubling time of a G 3 carcinoma was about half that of a G 1 carcinoma. On electron microscopy the tumour grade was reflected in the degree of functional differentiation of the neoplastic duct cells. In an additional clinicopathological evaluation of 75 patients operated upon for ductal adenocarcinoma of the pancreatic head, a positive relationship was found between grade and duration of symptoms until diagnosis. Moreover, the G 1 tumours showed generally a lower stage symptoms until diagnosis. Moreover, the G 1 tumours showed generally a lower stage at the time of surgery than G 2 and G 3 carcinomas. Finally, the median survival times correlated significantly with the tumour grade. From the various parameters used nuclear grade proved to be the most significant prognostic criterion, since a separate morphometric study revealed a very close correlation between median nuclear size of the tumours and survival time.     

Clinical use of radioimmunological plasma insulin assessment

Summary The use of the measurement of plasma immunoreactive insulin levels is generally accepted for the diagnosis of insulin-secreting tumours. In diabetes, this determination is of major importance for the differentiation between the metabolic and pancreatic factors involved in the disease and it is helpful both for initiating therapy and following up cases over the years.     

Pancreatic enzyme secretion: nonspecific stimulation by duodenal mucosal extracts

Felber et al. (Lancet 2: 185-188, 1974) reported that duodenal extracts obtained from rats fed a given meal induced the specific secretion of related pancreatic enzymes. Such an observation challenges the generally accepted theory of parallel secretion of pancreatic enzymes. Although these experiments were faithfully reproduced, no induction of specific enzyme secretion could be obtained. Moreover, comparison of the secretagogue potency of different preparations of duodenal extract, both in vivo (anesthetized rat) and in vitro (pancreatic lobules), demonstrated that in the original extraction procedure most of the secretagogue activity was lost. Finally, even the fully active extract failed to induce specific enzyme secretion. It is therefore unlikely that duodenal extracts from rats fed a specific meal can induce selective secretion of the related enzyme.     

Somatostatin type 2A receptor immunoreactivity in human pancreatic adenocarcinomas

Somatostatin and its analogs have been included in experimental treatment protocols for advanced pancreatic adenocarcinoma based on their known antisecretory and antiproliferative properties. Somatostatin receptor type 2 (sstr2A) mediates antiproliferative actions of somatostatin and has the strongest affinity to the therapeutically used somatostatin analog—octreotide. We investigated localization of sstr2A in 27 pancreatic adenocarcinomas in relation to tumor histological features and neuroendocrine differentiation confirmed by immunoreactivity for chromogranin A (CgA), chromogranin B (CgB), or somatostatin. Immunoreactivity for sstr2A generally coincided with tumor neuroendocrine differentiation demonstrated by staining for CgA and was present on the cell membranes of pancreatic islet cells and endocrine cells occasionally present in the wall of normal pancreatic ducts. Thirteen pancreatic adenocarcinomas contained cells immunoreactive for sstr2A in numbers ranging from occasional single cells, cell clusters, or carcinoma duct segments. In two cases, cells immunoreactive for sstr2A and CgA represented more than 30 and 10% of the total tumor cell population (case 1 and 15, respectively). Case 1 fulfills the diagnostic criteria of mixed ductal endocrine carcinoma. We conclude that immunohistochemical staining for a generic neuroendocrine marker such as CgA would facilitate identification of a subgroup of pancreatic adenocarcinomas expressing sstr2A receptors. Future studies need to evaluate the responsiveness of these tumors to somatostatin analogue treatment.     

Fine structure and immunocytochemistry of cells within the endocrine pancreas of larval and adult sea lampreys,Petromyzon marinus L.

Immunocytochemistry with protein A-gold and routine electron microscopy were used to identify cell types within the endocrine pancreas of larvae, juvenile adults, and upstream-migrant adults of the sea lamprey, Petromyzon marinus. The larval pancreatic islets are composed only of insulin-immunoreactive B-cells, which are uniform in their fine structure. The cranial and caudal pancreatic tissue in both adult periods contains three cell types: B-cells, somatostatin-immunoreactive D-cells, and a third cell type of unknown content. No glucagon-immunoreactive cells are present in lampreys, but B-and D-cells exist in equal numbers in the pancreatic tissue of adults. The B-cells of adults have a fine structure similar to those in larvae. D-cells have secretory granules that are distinctly different from those both in B-cells and in the third cell type. Although B- and D-cells in lamprey pancreatic tissues have a basic morphological similarity to these cells in other vertebrates, their granules are generally of smaller dimensions. The inclusion of granules within large pleomorphic bodies in many D-cells indicates that granule turnover is common. Immunocytochemistry will be a useful tool for showing the relationship between the cells in the degenerating bile ducts and those of the developing adult pancreas.     

Effect of intraduodenal HCl and soybean extract on pancreatic juice secretion during atropinization and cold vagal blockade in calves.

In order to elucidate the mechanisms by which intraduodenal hydrochloric acid (HCl) and soybean extract influence exocrine pancreatic secretion in the young ruminant, we conducted experiments repeatedly on six conscious calves with and without blockade of the extrinsic and intrinsic neural pathways. In the absence of blockade, each of the two stimuli increased the juice volume, the HCl effect being far stronger than that of soybean extract. Intrinsic cholinergic blockade by atropinization blocked the stimulatory work of soybean extract on pancreatic secretion and on HCl-stimulated protein but had a weak effect on the amount of juice evoked by HCl. Temporary vagal blockade by chilling virtually abolished the excitatory effects of both soybean extract and HCl. With or without blockade, duodenal HCl resulted in a noteworthy increase in plasmal secretin and a slight increase in cholecystokinin (CCK). With alimentary proteins, acidification of the duodenum was responsible for both the composition and secretion of pancreatic juice in young calves, generally via neural pathways. Atropine-sensitive nerves of the pancreas totally regulate the intestinal phase of pancreatic juice secretion allied with intraduodenal protein, whereas HCl-dependent excitation of the exocrine pancreas takes place partly via atropine-resistant nerves. However, as hardly any pancreatic juice was secreted independently of the vagi, the vagi are deemed to govern all the postprandial regulatory mechanisms of the exocrine pancreas in the young calf.     

Expression of L1CAM,COX‐2, EGFR,c‐KIT and Her2/neu in anaplastic pancreatic cancer: putative therapeutic targets?

Bergmann F, Moldenhauer G, Herpel E, Gaida M M, Strobel O, Werner J, Esposito I, Sebens Müerköster S, Schirmacher P & Kern M A
(2010) Histopathology 56 , 440–448
Expression of L1CAM, COX‐2, EGFR, c‐KIT and Her2/neu in anaplastic pancreatic cancer: putative therapeutic targets? Aims: Undifferentiated (anaplastic) pancreatic cancer and undifferentiated pancreatic carcinoma with osteoclast‐like giant cells (giant cell tumour) are rare variants of pancreatic ductal adenocarcinoma. Representing biologically highly aggressive neoplasms, they are frequently diagnosed at an advanced stage. The response to established chemo‐ or radiochemotherapeutic treatment regimens is poor, and undifferentiated pancreatic cancer generally has a dismal prognosis. As additional therapeutic options have not yet been investigated in undifferentiated pancreatic cancer, the aim was to analyse the expression of putative therapeutic targets that have shown promising results in various other neoplasms. Methods and results: Fifteen cases of undifferentiated pancreatic cancer (seven containing osteoclast‐like giant cells) were investigated clinicopathologically and immunohistochemically for putative therapeutic targets. Whereas L1CAM, cyclooxygenase (COX)‐2 and epidermal growth factor receptor (EGFR) were found to be significantly expressed in 80%, 93% and 87% of the investigated tumours, respectively, there was no substantial expression of c‐kit (CD117) and there was no detectable expression of Her2/neu. Conclusions: The expression of L1CAM, COX‐2 and EGFR in the majority of undifferentiated pancreatic carcinomas suggests that they might represent targets for adjuvant therapy in anaplastic pancreatic cancer. On the other hand, c‐kit and Her2/neu seem to have no relevance for the therapy of these tumours.     

Maspin is useful in the distinction of pancreatic adenocarcinoma from chronic pancreatitis: a tissue microarray based study.

Maspin, a member of the serpin family of serine protease inhibitors, has been shown to limit invasion and metastases in breast and prostate carcinomas. Maspin gene expression is up-regulated in pancreatic cancer, but not in normal pancreatic tissue. Maspin expression has been documented using immunohistochemical studies in pancreatic adenocarcinoma and high-grade intraductal dysplasia. We studied pancreatic ductal adenocarcinomas and chronic pancreatitis utilizing tissue microarray technology to determine the utility of maspin in differentiating these lesions. Immunohistochemistry was performed on tissue microarrays made from 72 cases of pancreatic ductal adenocarcinoma and 24 cases of chronic pancreatitis. Carcinomas were graded as well, moderately, or poorly differentiated using the WHO criteria. The primary antibody used was monoclonal antimaspin antibody (clone G167-70, 1:800, PharMingen, San Diego, CA). Nuclear and/or cytoplasmic staining for maspin was qualitatively scored from 1 + to 3 + based on intensity. Cases were considered positive if one or more cores demonstrated staining. Cases of chronic pancreatitis showed focal, weak (1 + to 2 +) staining within occasional benign ductal epithelial cells in 29% of cases (7/24). Diffuse and intense (3 +) staining was present in ducts with squamous metaplasia (3 cases). The majority of ducts showed no staining. Ductal adenocarcinomas showed diffuse staining in 91% (66/72) of cases with generally more intense staining than cases of chronic pancreatitis. Maspin may be helpful in differentiating ductal adenocarcinoma from chronic pancreatitis, once squamous metaplasia is ruled out.     

Solid-pseudopapillary tumor of the pancreas: a typically cystic carcinoma of low malignant potential

Solid-pseudopapillary tumors are uncommon neoplasms of low malignant potential generally occurring in young women. They often cause few symptoms and may reach a large size by the time they are detected. Degenerative cystic changes are common, and the clinical presentation is often that of a cystic pancreatic tumor. Pathological features include solid, cellular, hypervascular regions without gland formation, and degenerative pseudopapillae. The cells contain eosinophilic granules rich in alpha-1-antitrypsin and the nuclei are typically grooved. Despite its characteristic microscopic appearance, the immunophenotype (positive for vimentin, alpha-1-antitrypsin, and neuron specific enolase) is not specific and does not define a line of differentiation corresponding to any normal pancreatic cell type. Ultrastructural studies have also failed to identify specific differentiated features. Nonetheless, the biological behavior of solid-pseudopapillary tumor is well established. The tumor is indolent, with infrequent metastases to liver or peritoneum and usually long survival, even in the presence of disseminated disease.     

Pancreatic frozen section nightmares

Pancreatic resections have steadily increased over the past few decades and as a consequence so have the number of pancreatic specimens submitted for intraoperative frozen section consultation. Frozen section evaluation of the pancreas is generally performed for tumour confirmation and the assessment of margin status. An accurate and prompt diagnosis is therefore critical in guiding surgical management. However, pancreatic frozen sections are among the most challenging specimens submitted to the pathologist. While the main diagnostic dilemma is between adenocarcinoma and chronic pancreatitis, the spectrum of reactive changes, preinvasive neoplasms, neoadjuvant treatment effect and incidental lesions can further confound this assessment. The purpose of this review is to briefly discuss practical guidelines in specimen handling, common tissue artifacts, non-neoplastic and neoplastic frozen section histology, and challenging scenarios. In addition, it is our hope that this review will serve to facilitate better communication between the surgeon and pathologist to enhance patient care.     

The cytological spectrum of chronic pancreatitis

Chronic pancreatitis (CP) refers to a spectrum of changes generally seen after repeated injury that ranges histologically from mild fibrosis to extensive fibroinflammatory replacement of acinar tissue with accumulation of calcific debris. Because CP can share clinical and radiological features with malignancy, it often is sampled by fine-needle aspiration (FNA). The cytology files at Hennepin County Medical Center (HCMC) were searched for 20 consecutive cases of CP sampled by FNA. Clinical data and cytological findings were recorded. A spectrum of cytological findings typifies aspirates of CP. In most cases, mixed inflammation with debris and calcific material is present. Often, ductal cells are present and at most show mild atypia but generally appear organized. Often, fibrotic acinar tissue also is present while definitive islets are identified only rarely. Although these cytological findings were consistent with CP, 3 of 17 patients with follow-up were found to have pancreatic ductal adenocarcinoma.     

Pancreatic ductal adenocarcinomas with cystic features: neither rare nor uniform.

Cystic tumors of the pancreas are uncommon but important because of their diverse pathology and biology. Their wide spectrum also includes cystic variants of otherwise solid tumors, such as cystic endocrine tumors, cystic acinar cell carcinomas and ductal adenocarcinomas with cystic changes. In this study, we screened pancreatic ductal adenocarcinomas and their variants for macrocystic changes and determined the nature of the cysts (neoplastic vs non-neoplastic). Of 483 tumors 38 (8%) had cystic features. The largest group consisted of 24 pancreatic ductal adenocarcinomas showing a large-gland pattern with small cysts whose diameter varied between 0.5 and 1.8 cm. The epithelial lining of these cysts was generally positive for CEA (83%) and/or MUC1 (71%) and MUC5AC (74%). p53 was positive in 57% of the cases. The second group of cystic tumors (8/483) showed degenerative cystic cavities with diameters ranging between 1 and 6 cm. This group consisted of poorly differentiated pancreatic ductal adenocarcinomas, undifferentiated carcinomas with or without osteoclast-like giant cells and one adenosquamous carcinoma. In the third group of cystic tumors there were four pancreatic ductal adenocarcinomas containing tumor-related retention cysts. Their epithelial cells were positive for MUC5AC, but negative for CEA, MUC1 and p53. The fourth group consisted of two pancreatic ductal adenocarcinomas showing closely attached pseudocysts caused by tumor-associated pancreatitis. The results indicate that a considerable number of pancreatic ductal adenocarcinomas and their variants display cystic features and must therefore be considered in the differential diagnosis of cystic neoplasms of the pancreas. Moreover, not all of the cystic structures we observed were neoplastic in nature. They may also represent non-neoplastic changes, such as retention cysts and inflammatory pseudocysts.     

Morphometric image analysis of pancreatic disease by ThinPrep liquid-based cytology

Liquid‐based cytology preparations are being increasingly used in nongynecologic specimens. The aim of this study is to objectively evaluate pancreatic disease by ThinPrep (TP) liquid‐based cytology using morphometric image analysis. In all, 30 patients undergoing preoperative evaluation of pancreatic disease by TP were investigated from January to April 2009. We analyzed cytological features, such as cluster area, cluster circularity, and nucleus area, using morphometric image analysis software and further investigated the cytological findings of TP to determine which are useful for detecting malignancy. Pancreatic cytological findings of TP showed small clusters and loss of cluster irregularity in malignant cells. The patients were diagnostically categorized as inadequate, normal or benign, indeterminate, suspected malignancy, and malignant in 6.6% (2), 46.7% (14), 13.3% (4), 13.3% (4), and 20.0% (6) of the cases, respectively. Morphometric image analysis of 28 patients by TP,excluding two inadequate patients, showed no statistical difference in cluster area or cluster circularity among these cytological categories. In contrast, nucleus area in the normal or benign, indeterminate, suspected malignancy, and malignant categories was 17.6, 57.2, 67.4, and 68.0 μm², respectively, and was associated with diagnostic category (P < 0.05). Pancreatic cytological findings of TP preparations generally show small, round cluster shapes in pancreatic disease; however, nucleus size is a more important criteria for detecting malignancy by TP in pancreatic disease. Diagn. Cytopathol. 2012. © 2011 Wiley Periodicals, Inc.