Duct-acinar-islet cell tumor of the pancreas

A case of a rare pancreatic tumor, duct-acinar-islet cell tumor is presented. The tumor was incidentally found in the pancreatic body on computed tomography of a 21 year old male suffering from mumps. It was well demarcated from surrounding pancreas, and spherical in shape, measured 2.5 cm in diameter. Histologic and immunohistochemical examinations showed the tumor to consist of three distinct cell populations: duct, acinar and islet cells. Small cell nests consisting of these cellular components, either solely of one cell type or mixed of the three cell types, were separated by broad desmoplastic stroma. Islet (endocrine) cells, which were most predominant, were arranged in a tra-becular pattern or small cell nests. Most of them were positive for glucagon, and a few cells expressed insulin, somatostatin, serotonin or pancreatic polypeptide. These cells were distributed randomly within the cell nests. Ducts, some of which contained goblet cells, were found among the endocrine cell nests. Duct-islet complexes were also observed. The acinar cells were the least conspicuous component. They expressed pancreatic α-amylase. An electron microscopic examination revealed duct cells with intercellular attachments and interdigitations, endocrine cells containing secretory granules, and acinar cells with zymogen granules. No definite evidence suggesting malignancy could be obtained.     

Duct-islet cell tumor of the pancreas. A case report with immunohistochemical and electron microscopic findings

A case of pancreatic tumor with features of both duct and islet cell components was found incidentally at autopsy in a 76-year-old male who had died of intrahepatic cholangiocarcinoma. The tumor, measuring about 1.0 cm in diameter, was located in the pancreatic tail. The tumor was composed of two distinct cell populations, islet cells and duct cells. Immunocytochemically, nearly all of the former cells were positive for insulin but negative for cytokeratin, carcinoembryonic antigen (CEA) and mucin, while the latter were positive for cytokeratin, CEA and mucin but negative for insulin. Additionally, a majority of the tumor cells that had formed islet-like structures were positive for neuron-specific enolase (NSE), whereas NSE-positive cells were found only rarely in duct components. Electron microscopy confirmed the presence of two cell populations. Simultaneous occurrence of duct and islet cell components in a single pancreatic tumor indicates an intimate histogenetic relationship between pancreatic endocrine and duct cells.     

Duct-Islet Cell Tumor of the Pancreas. A Case Report with Immunohistochemical and Electron Microscopic Findings

A case of pancreatic tumor with features of both duct and islet cell components was found incidentally at autopsy in a 76 year old male who had died of intrahepatic cholan-giocarcinoma. The tumor, measuring about l.0cm in diameter, was located in the pancreatic tail. The tumor was composed of two distinct cell populations, islet cells and duct cells. Immunocytochemically, nearly all of the former cells were positive for insulin but negative for cytokeratin, carcinoembryonic antigen (CEA) and mucin, while the latter were positive for cytokeratin, CEA and mucin but negative for insulin. Additionally, a majority of the tumor cells that had formed islet-like structures were positive for neuron specific enolase (NSE), whereas NSE-positive cells were found only rarely in duct components. Electron microscopy confirmed the presence of two cell populations. Simultaneous occurrence of duct and islet cell components in a single pancreatic tumor indicates an intimate histogenetic relationship between pancreatic endocrine and duct cells. Acta Pathol Jpn 39: 328 335, 1989.     

Filamentous Inclusions in Acinar Cell Carcinoma of the Pancreas

Acinar cell carcinoma of the pancreas exhibits a spectrum of histologic appearances. Some tumors can be readily identified by light microscopy, but others resemble endocrine/neuroen-docrine neoplasms. Ultrastructurally, though large zymogen granules of acinar cells are usually distinctive, the zymogen granules of neoplastic acinar cells are sometimes abnormally small, overlapping in size with the granules of endocrine/neu-roendocrine neoplasms. Six cases of acinar cell carcinoma, two with a typical histologic appearance and four that resembled endocrine/neuroendocrine tumors, were studied ultrastructurally. In addition to zymogen granules and abundant rough endoplasmic reticulum, all cases of acinar cell carcinoma exhibited pleomorphic, membrane bound inclusions that contained filaments. Similar inclusions were not identified in islet cell or carcinoid tumors, and several findings indicate that the inclusions represent deranged zymogen granules. In the ultrastructural study of a pancreatic neoplasm with granules, these inclusions may provide a clue for the diagnosis of acinar cell carcinoma.     

Acinar cell carcinoma of the pancreas

Four cases of acinar cell carcinoma of the pancreas are reported. An acinar cell carcinoma can resemble an islet cell tumor by routine light microscopy but the two differ considerably in their fine structure and immunostaining properties. Although cells of both tumors contain numerous dense-core granules, their size ranges are different, and atypical forms occur in the acinar cell tumors, including elongated bodies filled with filaments. Many mitochondria-rough endoplasmic reticulum complexes were present in one tumor. In a liver metastasis, nests of endocrine cells were discovered amid the groups of acinar cells, and some of the endocrine granules contained rectangular cores.     

Acinar Cell Carcinoma of the Pancreas

Four cases of acinar cell carcinoma of the pancreas are reported. An acinar cell carcinoma can resemble an islet cell tumor by routine light microscopy but the two differ considerably in their fine structure and immunostaining properties. Although cells of both tumors contain numerous dense-core granules, their size ranges are different, and atypical forms occur in the acinar cell tumors, including elongated bodies filled with filaments. Many mitochondria-rough endoplasmic reticulum complexes were present in one tumor. In a liver metastasis, nests of endocrine cells were discovered amid the groups of acinar cells, and some of the endocrine granules contained rectangular cores.     

Pancreatic endocrine tumor with partial acinar cell differentiation

We examined a 70-year-old woman in whom a pancreatic endocrine tumor with partial acinar cell differentiation had been diagnosed. She had neither endocrine nor exocrine symptoms. The tumor was located in the pancreatic tail and measured 12.5 x 9.5 x 8 cm. It had a capsule, was composed of multiple adhesion nodules, and was elastically soft, medullary, and yellowish white. The neoplastic cells had large, irregular, oval nuclei; prominent eosinophilic nucleoli; and abundant eosinophilic cytoplasm with many fine granules. The cells had proliferated in islet-like solid medullary, trabecular, acinar, and papillary patterns. Most neoplastic cells were strongly positive for synaptophysin. 10 to 25% of the neoplastic cells were positive for alpha1-antitrypsin. Neuroendocrine and zymogen granules were simultaneously observed in the cytoplasm of the same neoplastic cells at the ultrastructural level. The tumor may be considered an amphicrine tumor.     

Heterotopic pancreatic tissue associated with intra- and extrahepatic choledochal cysts

A case report of heterotopic pancreas in intra- and extrahepatic biliary tracts in a 36-year-old female who suffered from intra- and extrahepatic choledochal cysts with an anomalous pancreatobiliary duct system. Histologic examination of the resected specimen showed pancreatic tissues located along the wall of the biliary tract with choledochal cysts. The pancreatic tissue consisted of acinar cells and duct elements without Langerhans' islets; the acinar cells were positive immunohistochemically for alpha-amylase and negative for endocrine hormones. Ultrastructural study revealed zymogen granules in the acinar cells. In the present case the heterotopic exocrine pancreatic tissue seems to be etiologically related to choledochal cysts as well as to the anomalous arrangement of the pancreatobiliary duct.     

Primary pancreatic carcinoma in childhood. Pancreatoblastoma

A case of primary pancreatic carcinoma confirmed by postmortem examination in a 15-year-old girl is presented. The tumor was studied by light and electron microscopy and an indirect immunoperoxidase technique. Some of the tumor cells contained eosinophilic, PAS-positive, diastase-resistant granules. Electron microscopy revealed large electron-dense granules resembling zymogen granules. The granules seen in the islet cell tumors were not demonstrated by electron microscopy and immunoperoxidase technique. These findings suggest that the tumor is of duct cell origin with some differentiation toward the acinar cells. The tumor appears to belong to the so-called "pancreatoblastoma".     

PRIMARY PANCREATIC CARCINOMA IN CHILDHOOD

A case of primary pancreatic carcinoma confirmed by postmortem examination in a 15-year-old girl is presented. The tumor was studied by light and electron microscopy and an indirect immunoperoxidase technique. Some of the tumor cells contained eosinophilic, PAS-positive, diastase-resistant granules. Electron microscopy revealed large electron-dense granules resembling zymogen granules. The granules seen in the islet cell tumors were not demonstrated by electron microscopy and immunoperoxidase technique. These findings suggest that the tumor is of duct cell origin with some differentiation toward the acinar cells. The tumor appears to belong to the so-called "pancreatoblastoma".     

Histidine decarboxylase expression in pancreatic endocrine cells and related tumors

Histidine decarboxylase (HDC) is an enzyme for decarboxylating l-histidine to histamine and is expressed in various types of cells including neuroendocrine tumors. Recent findings have demonstrated a high percentage of HDC immunoreactivity in many neuroendocrine tumors, including carcinoid tumors, small cell carcinomas of the lung, pheochromocytomas, and medullary carcinomas of the thyroid. HDC immunostaining was applied to pancreatic islet cells and related tumors to explore possible expression of HDC as a wide spectrum marker for neuroendocrine differentiation. A total of 24 cases (22 pancreatic endocrine neoplasms, one small cell carcinoma of the pancreas, and one mixed exocrine-endocrine carcinoma) along with normal pancreatic tissue were immunostained with the anti-HDC antibody. In a normal pancreas, a double immunostaining revealed possible colocalization of HDC with glucagon- or insulin-positive cells in the islets. Seventeen of 22 pancreatic endocrine neoplasms (77%) were found to be positive for HDC, and no distinct relation to hormonal activity was observed. One small cell carcinoma was strongly positive to HDC. One non-functional tumor with mixed exocrine and endocrine components showed a diffuse positive immunostaining for HDC, and some neoplastic glucagon- or somatostatin (SRIF)-positive cells coexpressed HDC. In conclusion, we demonstrated that the majority of pancreatic endocrine tumors expressed HDC, and we suggest that HDC is a wider new marker for neuroendocrine differentiation.     

Intraductal acinar cell carcinoma of the pancreas

We describe a purely intraductal acinar cell carcinoma involving branch ducts of the pancreas in a 74-year-old man, which presented as recurrent episodes of acute pancreatitis. Endoscopic ultrasound examination revealed an intraductal mass bulging into the main pancreatic duct suggesting, pre-operatively, an intraductal mucinous papillary tumour. Gross examination showed several dilated branch ducts that contained haemorrhagic tumour material without any solid or true cystic formation within the pancreatic parenchyma. Using histology, a purely intraductal acinar cell carcinoma was observed, involving branch ducts only, associated with foci of carcinoma in situ in adjacent exocrine parenchyma. The main pancreatic duct was free of disease except for its communication with a cancerous branch duct. A concomitant neuroendocrine microadenoma was incidentally found during slide screening. Immunohistochemistry performed on the intraductal proliferation confirmed zymogen secretion with positive staining for alpha-1 anti-chymotrypsin and anti-trypsin and the persistence of diastase-periodic acid-Schiff positive granules in the apical pole of the tumour cells. Neuroendocrine markers were negative in the acinar cell carcinoma and positive in the neuroendocrine microadenoma. To our knowledge, this is the first report of an intraductal acinar cell carcinoma of the pancreas involving branch ducts and sparing the main pancreatic duct.     

Mixed exocrine-endocrine tumors of the pancreas

Neoplasms of the pancreas usually show either ductal, acinar, or endocrine differentiation. Mixed exocrine-endocrine pancreatic neoplasms, in which the endocrine component is significant and comprises one-third to one-half of the tumor tissue, are rare. Truly mixed tumors have to be distinguished from exocrine neoplasms with scattered endocrine cells. In ductal adenocarcinomas, the scattered endocrine cells seem to be nonneoplastic. In other malignancies such as acinar cell carcinoma and pancreatoblastoma, scattered endocrine cells most likely represent an integral component of the tumor.     

Insulinoma of the pancreas with insular-ductular differentiation in its liver metastasis--indication of a common stem-cell origin of the exocrine and endocrine components

We describe an insulinoma of the pancreas in a 56-year-old patient, which showed insular-ductular differentiation in its liver metastasis. Although the primary tumor was uniformly endocrine in nature with insulin production, the metastasis contained two distinct cell types in organoid arrangement. One cell type was insulin-positive and was arranged in islet-like structures; the other was insulin-negative but distinctly pan-cytokeratin and cytokeratin 7 positive and arranged in ducts. In the primary tumor and the metastasis, the tumor cells were surrounded by a desmoplastic stroma. As to the histogenesis of the tumor and its metastasis, we discuss the following possibilities: (1) the tumor cells might derive from a common stem cell that matures into two phenotypically different cell lines, resembling the situation in embryogenesis and (2) one tumor cell type originates from the other by transdifferentiation (metaplasia). We conclude that the parallel occurrence of endocrine and ductal differentiation supports the concept that, under certain conditions, islet cells and ductular cells may also originate from islets and that mixed endocrine/exocrine pancreatic tumors do not necessarily arise from totipotent duct cells but might also have a primary endocrine cell origin.     

Serotonin immunoreactivity in pancreatic endocrine neoplasms (carcinoid tumors).

Primary serotonin secreting pancreatic endocrine neoplasms (carcinoid tumors) are extremely rare and may be associated with manifestations of the carcinoid syndrome. Two cases of primary carcinoid tumor of the pancreas with liver metastases showed clinical and biochemical features of the carcinoid syndrome. Both cases demonstrated strong positive immunoreactivity for serotonin within the tumor cells. In an attempt to determine the relationship between pancreatic carcinoid tumors and other pancreatic endocrine neoplasms, immunostains for serotonin were performed on 11 additional islet cell tumors and on non-neoplastic pancreatic tissues. These cases showed serotonin immunoreactivity within islet cell tumors (36%). In addition, focal staining for serotonin was present in non-neoplastic ducts and ductules (88%), acini (22%), and islets of Langerhans (33%). Based on these observations, specific criteria are suggested for the diagnosis of primary pancreatic carcinoid tumor.     

The physiology of a local renin–angiotensin system in the pancreas

The systemic renin–angiotensin system (RAS) plays an important role in regulating blood pressure, electrolyte and fluid homeostasis. However, local RASs also exist in diverse tissues and organs, where they play a multitude of autocrine, paracrine and intracrine physiological roles. The existence of a local RAS is now recognized in pancreatic acinar, islet, duct, endothelial and stellate cells, the expression of which is modulated in response to physiological and pathophysiological stimuli such as hypoxia, pancreatitis, islet transplantation, hyperglycaemia, and diabetes mellitus. This pancreatic RAS has been proposed to have important endocrine and exocrine roles in the pancreas, regulating local blood flow, duct cell sodium bicarbonate secretion, acinar cell digestive enzyme secretion, islet beta-cell (pro)insulin biosynthesis, and thus, glucose-stimulated insulin release, delta-cell somatostatin secretion, and pancreatic cell proliferation and differentiation. It may further mediate oxidative stress-induced cell inflammation, apoptosis and fibrosis. Further exploration of this system would probably offer new insights into the pathogenesis of pancreatitis, diabetes, cystic fibrosis and pancreatic cancer formation. New therapeutic targets and strategies might thus be suggested.     

胰岛肿瘤及胰岛增生的免疫组化研究

应用免疫组化ＡＢＣ及ＬＳＡＢ法，对２７例胰岛肿瘤和３例胰岛增生进行Ｉｎｓ，Ｇａｓ，Ｇｌｕ，Ｓｏｍ，Ｓｅｒ，ＶＩＰ，ＰＰ，ＮＳＥ，ＣＨＧ，ＳＹＰ，ｈＣＧ，ＥＭＡ，Ｋ及ＣＫ的研究。结果显示：胰岛素瘤及胰岛增生Ｉｎｓ均阳性，Ｉｎｓ阳性程度与临床症状的轻重无关。胰岛素肿瘤多数为混合性的，而增生基本上是单一的，免疫反应强度与细胞分化程度有关，而与组织学类型无关；无功能性肿瘤仅表现个别激素的弱阳性。ＮＳＥ，ＣＨＧ及ＳＹＰ均是胰岛肿瘤的良好标记，它们与ＥＭＡ及Ｋ（ＣＫ）联合使用，有助于胰岛内分泌肿瘤与外分泌肿瘤的鉴别；ｈＣＧ有助于鉴别胰岛素肿瘤的良恶性。     

Minute mixed ductal-endocrine carcinoma of the pancreas with predominant intraductal growth

We report a rare case of minute (5 mm x 4 mm) mixed ductal-endocrine carcinoma of the pancreas with predominant intraductal growth. A 34-year-old Japanese man was admitted because of elevated serum pancreatic enzymes. Endoscopic retrograde pancreatography revealed an unidentified material of 18 mm within the main pancreatic duct. Stone or parasite with acute pancreatitis was suspected clinically, and the biopsy revealed malignant cells positive for CA19-9, carcinoembryonic antigen (CEA) and synaptophysin. No apparent tumor was identified in the pancreas by various imaging techniques. Resection of pancreatic body and tail was performed. Grossly, the main pancreatic duct in the pancreatic body was occluded by as much as 20 mm. The pancreas had minute carcinoma of 5 mm x 4 mm just around the occluded main pancreatic duct. The tumor cells invaded the main pancreatic duct and spread within it as long as 20 mm. Histologically, the carcinoma had biphasic pattern; one was ductal carcinoma with tubular formations and another was carcinoma with neuroendocrine features. These two elements were admixed, and the ductal element comprised 30% while the endocrine element comprised 70%. The ductal element was immunoreactive for cytokeratins, CEA and CA19-9, while the endocrine element was immunoreactive for chromogranin A and synaptophysin. No immunoreactivity for pancreatic enzymes was noted. Ultrastructural observations showed dense core granules and no zymogen granules. Our case is unique clinically in that the tumor manifested as an intraductal material and no apparent tumor was found by imaging modalities, and pathologically in that the tumor was rare mixed ductal-endocrine carcinoma and the tumor was very small and mainly grew within the main pancreatic duct.     

Rat pancreatic islet is formed by unification of multiple endocrine cell clusters.

The organogenesis of islets in rat pancreas was studied by three-dimensional reconstructions from serial section micrographs. On embryonic day (E) 12, an endocrine cluster consisting mainly of glucagon-expressing cells maintained connection with the pancreatic endoderm at several regions. On E15-E17, the cluster enlarged by fusion of newly formed buds. Although the proportion of insulin-expressing cells increased, they were located in the periphery of the cluster. On the day of birth, insulin-expressing cell clusters enlarged and fused to form several cores within the islet. The glucagon-expressing cell mass expanded to form a thin mantle covering the cores. During islet organogenesis, proliferation activity was high in the exocrine duct system. Moreover, the endocrine cell clusters maintained contact with the duct epithelium throughout. We conclude that the pancreatic islet is generated by the unification of multiple endocrine clusters originated from separate regions of the duct system. The mechanism of mantle-core formation is discussed.     

Insulinoma with Fibrillar Inclusions and Acinar Cell Elements

Islet cell tumors associated with exocrine elements are rare. An insulinoma was removed from the head of the pancreas of a 33 -year-old woman. Ultrastructural and immunohistochemical studies demonstrated that, in addition to the endocrine cells, the tumor had a small population of cells with an acinar cell morphology. Rare cells exhibiting both endocrine and exocrine features (amphicrine cells) were also identified. Another unusual finding in this case was the presence of a large number of intracytoplasmic filamentous inclusions that, even though they have been observed in other neoplasms, have not previously been reported in endocrine tumors of the pancreas. The demonstration of cells with mixed endocrine features supports the concept that both the endocrine and exocrine portions of the components of the pancreas have a common embryologic origin.