A neoplasm with pancreatic and hepatocellular differentiation presenting with subcutaneous fat necrosis

A neoplasm demonstrating both pancreatic and hepatic phenotypes is described. The tumor, from a 53-year-old woman with the syndrome of subcutaneous fat necrosis and arthropathy, was studied histologically, immunohistochemically, ultrastructurally, and biochemically. The clinical features of this case can be explained by the production of large amounts of lipase by the tumor. The hepatocellular properties of the tumor included characteristic morphology and the synthesis of catalase. The pancreatic properties of the tumor included the production of pancreatic lipase. This neoplasm would appear to be analogous to animal models in which the transdifferentiation of pancreatic acinar cells and hepatocytes has been demonstrated. Although the bulk of the tumor was present in the liver, the authors believe the tumor arose from the pancreas. The distinction between differentiation and site of origin of tumors is discussed.     

Pancreatic acinar cell carcinoma extending into the common bile and main pancreatic ducts

Acinar cell carcinoma (ACC) of the pancreas is relatively rare, accounting for only approximately 1% of all exocrine pancreatic tumors. A 69-year-old man was found to have a mass lesion measuring approximately 4 cm in diameter in the pancreatic head on ultrasound, abdominal dynamic CT, and percutaneous transhepatic cholangiography. Magnetic resonance cholangiopancreatography showed defect of the lower common bile duct (CBD) due to obstruction by the tumor cast. Histopathologically, the pancreatic head tumor invaded the main pancreatic duct (MPD) and CBD with extension into the CBD in a form of tumor cast. The tumor cells consisted of a solid proliferation with abundant eosinophilic cytoplasm and round nuclei in an acinar and trabecular fashion. A 55-year-old man with upper abdominal pain and nausea, had a cystic lesion approximately 3 cm in size in the pancreatic tail on CT. Histopathologically, the tumor was encapsulated by fibrous capsule and had extensive central necrosis with solid areas in the tumor periphery, and invaded with extension into the MPD in a form of tumor cast. The tumor cells resembled acinar cells in solid growths. Two resected cases of ACC with unusual tumor extension into the CBD and the MPD, respectively, are reported.     

Perivascular epithelioid cell tumor (PEComa) of the pancreas: Immunoelectron microscopy and review of the literature

A perivascular epithelioid tumor (PEComa) is a rare tumor probably arising from the perivascular epithelioid cells. Only three cases of pancreatic PEComa have been reported in the English-language literature. The present report describes an extremely rare case of pancreatic PEComa. A 47-year-old Japanese woman complained of lower abdominal pain and a well-demarcated solid tumor was found in the pancreatic head. There was no history of tuberous sclerosis complexes. Pylorus-preserving pancreaticoduodenectomy was thus performed. There was a well-demarcated, solid tumor measuring 17 mm in the pancreatic head. The tumor was composed of a diffuse proliferation of epithelioid tumor cells with many blood vessels but no adipose tissue. The tumor cells expressed HMB45 and α-smooth muscle actin. Ultrastructurally, the tumor cells possessed many membrane-bound granules that were positive for HMB45 on immunoelectron microscopy. The results of immunoelectron microscopy show that some PEComas possess not only typical melanosomes or premelanosomes but also aberrant melanosomes.     

Multiple endocrine neoplasia type 1‐associated cystic pancreatic endocrine neoplasia and multifocal cholesterol granulomas

A novel combination of tumors was found in a 68 year‐old female with Multiple Endocrine Neoplasia type‐1 (MEN 1) that included a cystic pancreatic endocrine neoplasm (CPEN), a pituitary adenoma, and multifocal cholesterol granulomas (MCGs) in the breast, pleura, and the extremities. The pancreatic tumor displayed a single central locule surrounded by a thin rim of neoplastic parenchyma. The tumor showed heterogeneity in the architecture that included glandular, trabecular and solid patterns. The tumor cells of the pancreas were immunohistochemically positive for both endocrine and pancreatic acinar markers including chromogranin A, synaptophysin, glucagon, lipase, and reg protein. Electron microscopy revealed that there were numerous smaller dense‐cored neurosecretory granules, larger zymogen‐like granules and microvilli on the apical side of the tumor cells. The pancreatic tumor was diagnosed as CPEN with acinar cell features. Analysis of the DNA extracted from the tissues revealed that there is a MEN1 germline mutation in exon 10 codon 527, and somatic mutation in exon 2 codon 32 in the pancreatic tumor, and one base pair deletion in exon 2 codon 79 in the pituitary adenoma. Here, we report the case and discuss possible pathogenesis of CPEN and MCGs in a patient with MEN 1.     

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.     

Usefulness of immunohistochemical staining for MUC5AC in differentiating primary pancreatic cancer from pancreatic metastasis of breast cancer

Diagnosis of pancreatic ductal adenocarcinoma (PDAC) and its differentiation from metastases to the pancreas from other organs remains challenging. We report a case in which immunohistochemical staining for MUC5AC was useful in distinguishing primary pancreatic cancer from breast cancer metastasis. A 51‐year‐old Japanese woman who underwent curative resection of her breast cancer was referred to our hospital with a pancreatic head tumor. Although we surmised her pancreatic tumor to be metastatic breast cancer based on her past history and imaging studies, she was subsequently diagnosed with PDAC on the basis of immunohistochemical staining for MUC5AC using specimens obtained by endoscopic ultrasound‐fine‐needle aspiration. Thus, MUC5AC may be a useful diagnostic marker for discriminating PDAC from a secondary malignancy.     

Choriocarcinoma involving the pancreas as first manifestation of a metastatic regressing mixed testicular germ cell tumor.

We describe an unusual case of metastatic choriocarcinoma of the pancreas arising from a regressing testicular mixed germ cell tumor that clinically mimicked a primary pancreatic tumor. A 54-year-old male presented with a 2-month history of progressive upper abdominal pain, weight loss, and jaundice. He also had a history of recurrent epididymitis associated with the presence of a right testicular mass shown to be cystic by ultrasound and stable for at least 10 years. A computed tomography scan showed an isolated 6 cm mass in the head of the pancreas. A pancreaticoduodenectomy was performed. Upon histological examination, the pancreatic tumor showed extensive hemorrhage and necrosis. In the viable area, the tumor was composed of an intimate mixture of mononuclear cytotrophoblast cells and multinucleated syncytiotrophoblasts with vascular invasion. These characteristic features led to the correct diagnosis on frozen section. The cytology of the tumor was nonspecific and suggested undifferentiated carcinoma of the pancreas. The trophoblastic origin of the tumor cells was confirmed by immunohistochemistry staining. The testicular mass showed a regressed mixed germ cell tumor of predominantly seminoma with focal teratoma but without a choriocarcinoma component. In conclusion, we present a rare and unusual case of a regressing testicular mixed germ cell tumor that presented as a primary pancreatic tumor. Cytological features of the pancreatic mass were not specific and raised the possibility of a primary undifferentiated carcinoma of the pancreas. Characteristic histological features of choriocarcinoma led to the correct diagnosis on frozen section. Subsequent resection of the testicular mass confirmed the presence of a cystic and scarring (regressing) mixed germ cell tumor but without evidence of choriocarcinoma.     

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.     

Intraductal Pancreatic Neuroendocrine Tumor

Intraductal lesions of the pancreas are usually due to intraductal papillary mucinous neoplasms and the less common intraductal tubular adenoma. Cases of acinar cell carcinoma within intraductal location have also been encountered recently. Pancreatic neuroendocrine tumors are rarely encountered within the main pancreatic duct. A 74-year-old male presented with non-specific abdominal symptoms and was found to have an obstructive lesion in the main pancreatic duct with associated chronic pancreatitis. A distal pancreatectomy was performed which revealed a solid and cystic tumor measuring 6 × 3 × 2 cm situated wholly within the main pancreatic duct. It formed an obstructing intraluminal polypoid lesion that resulted in surrounding chronic pancreatitis. Microscopic evaluation of the mass showed it to be a well-differentiated pancreatic neuroendocrine tumor with entrapped, non-malignant tubules. Intraductal pancreatic neuroendocrine tumors may occur in two settings. Firstly, and more commonly, there is a parenchymal-based tumor that then encroaches on and pushes into the main pancreatic duct. The less common scenario is of a primary intraductal location without a pancreatic parenchymal lesion. While an intraductal location of a pancreatic neuroendocrine tumor is rare, it should be borne in mind when confronted by an intraductal lesion in the pancreas.     

Localisation of hyaluronate (HA) in primary tumors and nude mouse xenografts of human pancreatic carcinomas using a biotinylated HA-binding protein

A biotinylated hyaluronate (HA)-binding protein isolated from bovine cartilage was used to analyze the distribution of HA in nude mouse xenografts derived from human pancreatic adenocarcinoma cell lines as well as in primary human pancreatic adenocarcinomas. The most reproducible results for the localisation of HA were obtained using cryostat sections. When the biotinylated HA-binding protein was applied to histological sections of nude mouse xenografts, the specific staining found could be inhibited by preincubating the HA-binding protein with an excess of HA or by hyaluronidase treatment of the tissue before staining. The highest HA concentration was found at the tumor boundaries, while in the central part of the tumor staining was slight or absent. In cryostat sections of primary tumors HA was found predominantly in the connective tissue immediately around tumor cells or at the border between the tumor and normal pancreatic tissue.     

Stepwise progression of centrosome defects associated with local tumor growth and metastatic process of human pancreatic carcinoma cells transplanted orthotopically into nude mice.

Recent evidence indicates that loss of centrosome integrity may be a major cause of genetic instability underlying various human cancers. The aim of this study was to define the role of centrosome defects during the in vivo tumor progression of pancreatic carcinoma using an orthotopic implantation model. Injection of Suit-2 human pancreatic cancer cells into the pancreata of nude mice reproduced the pattern of local tumor growth and distant metastasis observed in humans. Pancreatic xenografts, peritoneal disseminations, and hepatic metastases were harvested, and tumor cells were examined for centrosomes by immunofluorescence microscopy. Centrosome abnormalities, characterized by increased numbers of centrosomes, were detected in only a small fraction of parental Suit-2 cells in culture, whereas the frequency was markedly increased in cells isolated from the pancreatic xenografts. Abnormal centrosome numbers were found at higher frequencies in metastatic foci than in pancreatic xenografts. A significant positive correlation existed between the fraction of cells with multiple centrosomes and that with multipolar mitotic spindles, suggesting a functional involvement of aberrant centrosomes in spindle disorganization and chromosome missegregation. In addition, the increased frequency of abnormal centrosomes was associated with an enhanced degree of chromosomal instability. These findings suggest a novel model of pancreatic tumor progression whereby a stepwise increase in the magnitude of centrosomal abnormalities confers an increased chance for aberrant mitotic events, thus accelerating genetic instability and causing the tumor to progress to a more advanced stage.     

一株人胰腺癌细胞系的建立及其特性

人胰腺癌是很难建系的癌细胞之一,特别是从原发瘤建立的细胞系。我们成功地从一个胰腺癌组织建立了一株人胰腺癌细胞系,命名为PC-3。PC-3细胞呈上皮样,贴壁生长,经过四年连续培养,细胞系稳定。通过免疫组化、电镜观察、染色体及DNA含量分析,细胞集落形成及裸鼠移植,生长因子对瘤细胞生长的影响和癌基因的表达证实PC-3细胞系为人胰腺癌细胞系。PC-3细胞系的建立进一步丰富了人胰腺癌细胞库,对深入了解人胰腺癌细胞生物学及分子生物学特性提供了有力的物质基础。     

Oncocytic non-functioning endocrine tumor of the pancreas

Herein is presented the case of a malignant non-functioning endocrine tumor of the pancreas with oncocytic features, and a discussion on the high incidence of malignancy in oncocytic endocrine pancreatic tumors. The patient was a 65-year-old woman who showed no paraneoplastic symptoms produced by functioning pancreatic endocrine tumors. The primary tumor was located in the body and tail of the pancreas, and had metastasized to the liver. Tumor cells were arranged in a ribbon-like or trabecular pattern and had an abundant eosinophilic cytoplasm containing numerous mitochondria and neurosecretory granules. The cytoplasm of the tumor cells was intensely stained with an antimitochondrial antigen antibody. Most tumor cells stained positively with Grimelius stain and for chromogranin A. Some tumor cells also stained for synaptophysin. However, the tumor cells negatively stained for hormones such as insulin, glucagon, somatostatin, gastrin, vasoactive intestinal peptide and pancreatic polypeptide, for serotonin, and for pancreatic enzymes such as amylase and trypsin. Analysis of 18 oncocytic pancreatic endocrine tumors, consisting of those reported previously and that in the present case, suggests that the high incidence of malignancy in oncocytic endocrine tumors is associated with the high incidence of non-functioning endocrine tumors among them, most of which are malignant.     

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.     

Anaplastic carcinoma of the pancreas with rhabdoid features

The malignant rhabdoid tumor (MRT) is histologically characterized by the invasive proliferation of polygonal to ovoid cells with abundant eosinophilic cytoplasm and eccentric vesicular nuclei with a prominent nucleolus. MRT frequently occurs in the kidney, but may also arise in other organs. However, MRT should be strictly distinguished from carcinomas with rhabdoid features. A post-mortem examination of a 68-year-old woman found an anaplastic carcinoma of the pancreas with rhabdoid features displaying extensive invasion into the neighboring tissues. To the best of our knowledge, this is the first case of a pancreatic tumor with rhabdoid features. Pathologists should consider that carcinomas showing rhabdoid features may also appear in the pancreas. As pancreatic tumors with rhabdoid features have characteristic histopathological features and poor prognosis compared to other pancreatic tumors, careful histopathological differential diagnosis is important.     

An Immunoglobulin M (IgM) Antibody to Carcinoembryonic Antigen (CEA)-like Antigen in Human Pancreatic Cancer

An immunoglobulin M (IgM) antibody to a carcinoembryonic antigen (CEA)-like antigen was isolated from the ascites fluid of a patient with pancreatic cancer by ammonium sulfate precipitation (25–55% saturation) and subsequent purification by gel filtrations on Sephadex G-200 and Sepharose 6B followed by protein A-Sepharose CL-4B chromatography. The IgM antibody was found to be in complex with a CEA-like antigen as revealed by the multiple precipitin lines obtained on immunoelectrophoresis and double diffusion with a mixture of antihuman IgM and anti-CEA. Dissociation of the complex with 0.2M glycine HCl buffer pH 2.5 and further chromatography on Sepharose CL-6B. followed by Sepharose 6B separated the IgM antibody from the CEA-like antigen. The IgM antibody formed an immunoprecipitate upon double diffusion with a homologous CEA cross-reactive antigen isolated from the liver metastasis of another patient with pancreatic cancer. The antigen (molecular weight 70,000 ± 15,000 daltons) which reacted with the IgM antibody was purified by Con A Sepharose affinity chromatography followed by gel filtration on BioGel A 1.5M. The IgM antibody reacted with tumor antigens from pancreatic cancer only. These results suggest that the human IgM antibody response to antigens may be specific to the tumor type involved.     

Watery diarrhea, hypokalemia and achlorhydria syndrome. Morphological and immunohistological study

A case of WDHA syndrome accompanied by a pancreatic tumor in a 44-year-old Japanese male is presented, the 6th case in Japan. Clinically, the patient suffered from unremitting watery diarrhea, hypokalemia and achlorhydria with marked anemia and jaundice. The patient died of emaciation, dehydration and bronchopenumonia, and an autopsy was performed. Autopsy examination revealed a hen's egg-sized tumor in the tail of the pancreas with metastases in liver, lungs and lymph nodes. In addition, bronchopneumonia and diabetic nephrosclerosis were present. Histologically, the tumor had the characteristics of an islet cell tumor, and histochemically the tumor cells were positive to Grimelius' stain which revealed non-B-islet cell features. Electron-microscopically, the tumor cells had electron dense round membrane-bounded granules resembling non-B-granules of pancreatic islet cells. With the immunoperoxidase procedure (PAP method), tumor cells nearly almost reacted to anti-vasoactive intestinal polypeptide (VIP) serum, which suggested that the tumor of the present case had the capability to produce VIP.     

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.