Although cystic neoplasms and lesions of the pancreas are rare, they have attracted a great deal of attention because of their potential curability. Since, in recent years, several new entities have been identified, the relative frequency of the tumors and their classification need to be reevaluated. In a series of 1454 tumorous lesions of the pancreas collected between 1971 and 2003 in our surgical pathology files and consultation files, all cystic pancreatic neoplasms and tumor-like lesions were identified and typed both histologically and immunohistochemically. There were 418 cases (29%) showing cysts with a diameter ranging between 0.5 cm and 27 cm. Most common were solid pseudopapillary neoplasms (21%) and intraductal papillary-mucinous neoplasms (18%). When only the cystic neoplasms and lesions that had been resected in a single institution were considered, intraductal papillary mucinous neoplasms were the most frequent cystic neoplasms, while solid pseudopapillary neoplasms took fifth place behind ductal adenocarcinomas with cystic features, serous cystic neoplasms and mucinous cystic neoplasms. The most frequent cystic tumor-like lesions were pancreatitis-associated pseudocysts. New and rare entities that have recently been identified are mucinous nonneoplastic cysts, acinar cell cystadenomas and cystic hamartomas. Bearing in mind that figures from referral centers such as ours may be biased regarding the relative frequency of lesions, we concluded from our data that intraductal papillary-mucinous neoplasms are the most frequently occurring pancreatic cystic neoplasms, rather than solid pseudopapillary neoplasms. It was possible to classify all cystic lesions encountered in our files or described in the literature in a new system that distinguishes between neoplastic and nonneoplastic lesions, with further subdivisions into epithelial (adenomas, borderline neoplasms and carcinomas) and nonepithelial tumors. This classification is easy to handle and enables a distinction on the basis of clinical behavior and prognosis.

S U M M A R YThe uptake of monoamines into the secretory granules of monoamine-storing neuroendocrine cells is mediated by vesicular monoamine transporter protein 1 or 2 (VMAT1 or VMAT2). This study analyzed the expression of VMAT1 and VMAT2 in endocrine cells of normal human and monkey pancreas. The expression of VMAT1 and VMAT2 was also examined in infants with hyperinsulinemic hypoglycemia and in adults with pancreatic endocrine tumors (PETs). Using immunohistochemistry (IHC) and in situ hybridization (ISH), we demonstrated the mutually exclusive expression of VMAT1 in endocrine cells of the duct system and of VMAT2 in many cells of the islets of Langerhans. By confocal laser scanning microscopy, VMAT1-positive cells were identified as enterochromaffin (EC) cells and VMAT2-positive cells as ␤ -cells. In PETs, VMAT1 was found exclusively in all serotonin-containing tumors. In contrast, VMAT2 expression was lost in many insulinomas, independent of their biological behavior. VMAT2 was expressed by some non-insulin-producing tumors. The mutually exclusive expression of VMAT1 in EC cells and of VMAT2 in ␤ -cells suggests that both cell types store monoamines. Monoamine storage mediated by VMAT1 in EC cells is apparently maintained in EC cell tumors. In contrast, many insulinomas appear to lose their ability to accumulate monoamines via VMAT2. (J Histochem

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 nonneoplastic changes, such as retention cysts and inflammatory pseudocysts.

Solid tumors of the pancreas are usually neoplastic. We report on two adult patients, each with a solid tumor of the pancreas that presented with an unusual histology and seemed to follow a benign course. The tumors, one located in the body and one in the tail, were well demarcated and composed of irregularly arranged but welldifferentiated acini and small intralobular and interlobular ducts embedded in predominantly hypocellular fibrotic tissue that contained fascicles of cytologically bland spindle cells. Islets were lacking, but immunohistochemical staining for chromogranin A and insulin revealed individual scattered insulin-producing cells distributed between acinar and ductal cells. The spindle cell component tissue showed coexpression of CD34, c-kit (CD117) and bcl-2. The follow-up (2 and 4 years) of the patients was uneventful. We propose to designate the tumors as 'cellular hamartoma resembling gastrointestinal stromal tumor.' Modern Pathology ( Keywords: pancreatic tumor; hamartoma; c-kit; CD34; bcl-2; differential diagnosis Well-demarcated tumor-like lesions in the pancreas are uncommon. They have been described under the term pseudotumor 1 or inflammatory pseudotumor. 2 Recently, we described a tumorous lesion that we termed pancreatic solid and cystic hamartoma. 3 Here we report on two further solid pancreatic tumors that have features in common with both hamartomas and gastrointestinal stromal tumors. Patients, materials and methodsThe cases were collected from the consultation files of the Department of Pathology of the University of Kiel, to which they had been submitted by the Department of Pathology in Dinslaken, Germany (case 1), and the Department of Pathology of the University of Coimbra, Portugal (case 2).In the first case, a 51-year-old man without clinical symptoms had a routine check-up, during which a mass, 3 cm in diameter, was detected by ultrasonography in the tail of the pancreas next to the splenic artery. This finding was confirmed by endosonography and CT. Laboratory tests were normal. As a result of the unclear nature of the tumor, abdominal surgery was performed with resection of the tumor.In the second case, a 54-year-old woman with slight abdominal discomfort was examined by ultrasonography, which revealed a well-demarcated tumor, 2 cm in diameter, in the body of the pancreas. A left-sided pancreatic resection was performed to remove the tumor. Both patients had an uncomplicated postoperative course and so far (2 and 4 years, respectively) have relapse-free follow-up.Representative 4 mm sections of formalin-fixed, paraffin-embedded tissue from both specimens were stained with hematoxylin and eosin (H&E) and periodic acid-Schiff. Immunohistochemical staining was performed using the standard avidinbiotin method against following antibodies: cytokeratin 8 (CAM 5

The current definition of gastrointestinal tumors (GIST) as CD117-positive mesenchymal tumors of uncertain malignant potential fails to include a number of cases with similar histology. In an attempt to improve the classification of these neoplasms, we conducted an immunohistochemical analysis of 244 mesenchymal tumors with histological features of GIST. According to their immunophenotype, the tumors were classified as GISTs, which are characterized by CD117 (c-kit) expression; gastrointestinal CD117-negative CD34 positive stromal tumors (GINST); alpha-smooth muscle actin and/or desmin positive gastrointestinal leiomyogenic tumors (GILT); S-100 and glial fibrillary acidic protein positive gastrointestinal glial/schwannian tumors (GIGT); gastrointestinal neuronal/glial tumors (GINT), which are positive for S-100/glial fibrillary acidic protein plus neuronal/glial markers; and gastrointestinal fibrous tumors (GIFT), which are only vimentin positive. The most common type of tumors were GIST, followed in order of frequency by GINST, GILT, GIGT, GIFT, and GINT. GISTs did not show any preferential location, whereas GINSTs occurred almost exclusively in the stomach and duodenum, and GILTs preferentially in the large intestine. Over a median follow-up period of 71 months, malignant behavior, i.e., metastatic spread, was observed in all tumor types except GINTs. Malignancy was associated with distal gut location, high mitotic activity, large tumor size, and nuclear pleomorphism, though none of these criteria alone discriminated between benign and malignant. Kaplan-Meier analysis of disease-specific survival showed significant differences in the long-term outcome of the newly defined subgroups. We conclude that, despite strong morphological similarities, gastrointestinal mesenchymal tumors are heterogeneous in their immunophenotype and biology.

Nonneoplastic tumor-like lesions ("pseudotumors") of the pancreas include cystic and noncystic varieties. We report on a solid and cystic tumor-like lesion of the pancreas that occurred in 2 adult patients. The lesions, located in the head and neck of the gland, respectively, were well demarcated and composed of cystic ductal structures embedded in focally inflamed stromal tissue. In addition, one of the lesions showed irregularly arranged but well-differentiated acini and small intralobular and interlobular ducts embedded in hypocellular, fibrotic tissue. Discrete islets were lacking, but immunohistochemical staining for chromogranin A revealed individual scattered endocrine cells evenly distributed between acinar and ductal cells. The surrounding pancreatic parenchyma did not show significant chronic pancreatitis. After tumor removal, the follow-up of the patients was uneventful. Because of the irregular arrangement of otherwise mature tissue components of the pancreas, the lesions were considered solid and cystic hamartomas. Their pathogenesis is so far unknown.

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Cystic tumors and tumor-like lesions of the pancreas are rare, but have attracted a great deal of attention because they are easily recognized with new imaging methods and, in contrast to ductal adenocarcinoma, they can usually be cured surgically. The increasing resection rate in recent years has also increased our knowledge of cystic pancreatic tumors by conspicuously enlarging their morphological spectrum. Known entities have been better characterized (i.e. solid pseudopapillary neoplasm, intraductal papillary mucinous neoplasm) and new ones described (serous oligocystic adenoma, mucinous non-neoplastic cyst, acinar cell cystadenoma and cystic hamartoma). This review discusses the most important cystic tumors and tumor-like lesions, presents a new classification, and summarizes the immunohistochemical differential diagnosis.