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1/10. Pancreatic duct cell carcinoma with positive 111In octreotide uptake.

    Duct cell adenocarcinomas may produce neuroendocrine markers such as pancreatic polypeptide, gastrin and gastrin releasing hormones. A 53 year old patient, with a history of insulin dependent diabetes, was found to have a pancreatic mass which was later pathologically demonstrated to be a duct cell adenocarcinoma. The tumor produced elevated circulating neuroendocrine markers specifically gastrin and pancreatic polypeptides. An 111In octreotide imaging showed definite uptake of octreotide by the tumor. The patient was subsequently treated with somatostatin analog which resulted in the reduction of some of the circulating endocrine markers. The patient had essentially six months of asymptomatic clinical remission but then she relapsed. octreotide scanning could be useful for selected patients with pathologic diagnosis of duct cell adenocarcinoma, because some tumors may have neuroendocrine features and can be imaged, and might even respond to somatostatin analog therapy.
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ranking = 1
keywords = endocrine
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2/10. 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.
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ranking = 0.75
keywords = endocrine
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3/10. 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.
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ranking = 2
keywords = endocrine
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4/10. Mixed ductal-pancreatic polypeptide-cell carcinoma of the pancreas.

    AIMS: Mixed ductal-endocrine carcinomas of the pancreas are rare tumours with 10 cases reported in the English literature. We report the first case with a polypeptide-cell component. methods AND RESULTS: : The tumour was fortuitously discovered in a 72-year-old woman during the exploration of an endometrial adenocarcinoma. It measured 100 mm and was located in the tail of the pancreas. On microscopic examination two intermingled endocrine and exocrine components were present. The endocrine component consisted of trabeculae and solid nests composed of cells immunoreactive for chromogranin a, synaptophysin and pancreatic polypeptide, but negative for p53 and Bcl-2 proteins. The exocrine component was composed of tubules lined by atypical cylindrical cells immunoreactive for CK19, CEA, p53 and Bcl-2. The stroma of the endocrine component contained amyloid deposits. CONCLUSION: Mixed ductal-endocrine carcinomas of the pancreas are often described in middle-aged patients. The tumours are usually large and located in the head of the pancreas. An endocrine syndrome is rare and the prognosis is often unfavourable. We report the first case of mixed endocrine-exocrine carcinoma of the pancreas with a pancreatic polypeptide-cell component. The histogenesis of mixed carcinoma of the pancreas is still uncertain but the over-expression of p53 and Bcl-2 could play a major role in the neoplastic progression of the ductal component.
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ranking = 1.75
keywords = endocrine
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5/10. Solid adenoma with exclusive hepatocellular differentiation: a new variant among pancreatic benign neoplasms?

    We report a unique, previously unreported pancreatic tumor with hepatoid differentiation associated with serous microcystic adenoma in a 70-year-old man. These two lesions localized, respectively, at the body and the tail of the pancreas, were found incidentally on abdominal ultrasonography. serum alpha-fetoprotein was not increased and no hepatic lesion was displayed on computed tomography. A subtotal pancreatectomy with splenectomy was performed. The patient is alive and well 12 months after resection. Pathological examination showed a very unusual encapsulated solid tumor with hepatocytic differentiation, bile production and immunoreactivity for hepatocyte paraffin-1 antibody. The tumor cells were negative for endocrine (neuron-specific enolase, chromogranin a, synaptophysin) and acinar (amylase, trypsin) markers. Ultrastructurally, zymogen and neurosecretory granules were absent. The features of the tumor were almost indistinguishable from those of hepatocellular adenoma; therefore, we believe that this solid hepatoid tumor may represent a variant of pancreatic adenoma. Recognition of this entity is important because the only reported pancreatic hepatoid tumors to date have been malignant. The main differential diagnoses include hepatoid ductal adenocarcinoma, hepatoid acinar cell carcinoma, primitive hepatoid endocrine tumor, and metastatic hepatocellular carcinoma.
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ranking = 0.5
keywords = endocrine
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6/10. Mixed ductal-endocrine carcinomas of the pancreas and ductal adenocarcinomas with scattered endocrine cells: characterization of the endocrine cells.

    We compared the histological and immunohistochemical features of mixed ductal-endocrine carcinomas of the pancreas with those of ductal adenocarcinomas (DACs) containing scattered tumor-associated endocrine cells (SECs). Three pancreatic neoplasms fulfilled the WHO criteria for mixed ductal-endocrine carcinomas. Two of them showed moderately to poorly differentiated glandular structures composed of both mucin producing and neuroendocrine cells. The third mixed ductal-endocrine carcinoma was of the composite type showing DAC structures and a solid component with small epithelial cells, most of them of neuroendocrine nature. In 32 of 34 cases of DAC located in the head (30 cases) and body to tail (4 cases) of the pancreas and showing lymph-node metastases, SECs were found, but they were few in number and irregularly distributed in the tumors. In three DACs a few SECs were also detected in lymph-node metastases. Double staining for chromogranin a and the proliferation marker Ki-S5 revealed that all SECs that were not intimately integrated into the neoplastic glandular epithelium failed to show proliferative activity and changes of the expression of tumor suppressor genes (p53 and DPC 4). These findings suggest that only those SECs that belong to the proliferative cell fraction may be of neoplastic origin, while the majority of SECs probably constitute a tumor-associated but non-neoplastic cell population. These features contrast with those of mixed ductal-endocrine carcinomas, in which all endocrine cells are a component of the neoplasm.
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ranking = 5
keywords = endocrine
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7/10. 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.
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ranking = 2.25
keywords = endocrine
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8/10. A new indication for pancreas transplantation: high grade pancreatic dysplasia.

    A 42-yr-old male presented with a family history of pancreatic carcinoma inherited an autosomal dominant pattern. The development of endocrine and exocrine pancreatic insufficiency served as early markers for neoplastic transformation. Screening endoscopic ultrasound and ERCP showed abnormalities suggestive of pancreatic dysplasia. Total pancreatectomy was performed and pathology confirmed carcinoma in situ, also known as high-grade pancreatic ductal dysplasia or Pan IN-3. The patient's post-operative course was complicated by life threatening, brittle diabetes. pancreas transplantation was successfully performed. One year following transplantation, the patient has excellent pancreas graft function. He remains insulin free and has no signs of malignancy. Total pancreatectomy followed by pancreas transplantation is a viable therapeutic option for patients in the dysplastic but still pre-malignant phase of familial pancreatic adenocarcinoma who develop hypoglycemic unawareness following total pancreatectomy.
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ranking = 0.25
keywords = endocrine
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9/10. Clear cell ductal adenocarcinoma of pancreas: a case report and review of the literature.

    We present a unique carcinoma of the pancreas with predominantly clear cell morphology (>95% clear cells). Mucicarmine stain revealed abundant intraluminal and intracytoplasmic mucin. Immunohistochemically, the cells were positive for the epithelial markers cytokeratin 7 and CAM 5.2, and were focally positive for cytokeratin 20. These cells also expressed monoclonal carcinoembryonic antigen. Stains for the neuroendocrine markers synaptophysin and chromogranin were negative, as were stains for vimentin, p53, HMB-45, and CD10. An additional outstanding feature was the presence of dense intraluminal and intracytoplasmic hyaline globules, which were immunohistochemically positive for alpha1-antitrypsin. Sequencing of the K-ras oncogene revealed a point mutation in codon 12, providing molecular evidence of ductal origin. In the proper morphologic context supported by immunohistochemistry, clear cell carcinoma can be regarded as a rare variant of ductal adenocarcinoma.
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ranking = 0.25
keywords = endocrine
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10/10. Mixed exocrine-endocrine tumor of the pancreas.

    CONTEXT: Neoplasms of the pancreas usually show ductal, acinar or endocrine differentiation. Tumors with mixed exocrine and endocrine components are unusual. We herein describe a case of a mixed ductal-endocrine tumor. CASE REPORT: A 65-year-old woman was referred to our department with a diagnosis of carcinoma of the tail of the pancreas. The patient had a short history of upper abdominal pain, nausea and melena. Upper gastrointestinal endoscopy revealed gastric fundus varices and CT scan demonstrated an inhomogeneous tumor located in the tail of the pancreas infiltrating the spleen and the splenic vein. The patient underwent distal pancreatectomy and splenectomy, and had an uneventful recovery. Pathological examination revealed a mixed ductal-endocrine tumor. The endocrine component was immunoreactive for glucagon, gastrin and somatostatin, and non-reactive for insulin. CONCLUSIONS: Because of the rarity and unpredictable biologic behavior of these tumors, the need for adjuvant therapy has not yet been well-defined. The patient has had a follow-up CT scan every six months, and one and a half years later remains disease free.
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ranking = 2.25
keywords = endocrine
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