Classification of types of intraductal papillary-mucinous neoplasm of the pancreas: A consensus study

Graduate School of Medical and Dental Sciences, Kagoshima University, Kagosima, Kagoshima, Japan
Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin (Impact Factor: 2.65). 12/2005; 447(5):794-9. DOI: 10.1007/s00428-005-0039-7
Source: PubMed


Now that more than two decades have passed since the first reports of intraductal papillary-mucinous neoplasms (IPMNs), it has become clear that IPMN consists of a spectrum of neoplasms with both morphological and immunohistochemical variations. At a meeting of international experts on pancreatic precursor lesions held in 2003, it was agreed that a consensus classification of IPMN subtypes should be established to enable a more detailed analysis of the clinicopathological significance of the variations. Based on our experience and on information from the literature, we selected representative histological examples of IPMNs and defined a consensus nomenclature and criteria for classifying variants as distinctive IPMN subtypes including gastric type, intestinal type, pancreatobiliary type, and oncocytic type. These definitions can be used for further analyses of the clinicopathological significance of the variations of IPMN.

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Available from: Akira Horii, Feb 02, 2014
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    • "Mucin-producing cystic neoplasms of the pancreas are divided into two separate entities: intraductal papillary mucinous neoplasia (IPMN) and mucinous cystic neoplasia. IPMN is a well-described entity characterized by papillary proliferation of mucin-producing neoplastic epithelium, which causes cystic dilatation of the pancreatic duct system [1] [6] [7]. IPMN is a condition with a malignant potential comprising a spectrum of dysplastic epithelial lesions with varying severity of dysplastic changes that eventually progress to invasive carcinoma [8] [9]. "
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    ABSTRACT: Background and objective Even when advanced cross-sectional imaging modalities have been employed, endoscopic evaluation of intraductal papillary mucinous neoplasms (IPMN) is often required in order to assess the final character and extent of lesions. The current study addresses the use of SpyGlass single-operator peroral pancreatoscopy in suspected IPMN. Design A prospective, non-randomized exploratory cohort study. Setting Single-center. Patients and intervention A prospective study-cohort of 44 consecutive patients in a single tertiary referral center who underwent ERCP and peroral pancreatoscopy, was prospectively collected between July 2007 and March 2013 because of a radiological signs of IPMN. These IPMN-findings were discovered incidentally in 44% of the cases. Main outcome measurements Diagnostic accuracy (specificity & sensitivity) and complications. Results The targeted region of the pancreatic duct was reached with the SpyGlass system in 41 patients (median age 65 years, 41% female). Three patients were excluded from analysis because of failed deep cannulation of the pancreatic duct. Brush cytology was taken in 88% and direct biopsies in 41%. IPMN with intermediate or high-grade dysplasia was the main final diagnosis (76%) in 22 patients who had surgery. Out of the 17 patients with a final diagnosis of MD-IPMN, 76% were correctly identified by pancreatoscopy. Of the 9 patients with a final diagnosis of BD-IPMN, the pancreatoscopy identified 78% of the cases correctly.The incidence of post-ERCP pancreatitis was 17%. Pancreatoscopy was found to have provided additional diagnostic information in the vast majority of the cases and to affect clinical decision-making in 76%. Limitations Single-center study. Conclusions Single-operator peroral pancreatoscopy contributed to the clinical evaluation of IPMN lesions and influenced decision-making concerning their clinical management. The problem of post-procedural pancreatitis needs further attention.
    Full-text · Article · Sep 2014 · Pancreatology
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    • "Based on the degree of MUC2 expression, IPMNs (other than pancreatobiliary type and oncocytic type) are subdivided into three types: gastric, intestinal and mixed gastric and intestinal type. Pathological characteristics of IPMNs and the surrounding parenchyma of IPMNs of gastric and intestinal types defined in this study correspond to previously described gastric and intestinal type IPMNs [2, 3, 10, 14, 36, 39]. In keeping with previous reports [1, 13, 26, 42], MUC2 expression is a reliable marker for discriminating between the gastric type IPMN with foveola-pyloric gland and flat structures and intestinal type IPMN with the villous-crypt and low papillary structures. "
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    ABSTRACT: Pancreatic intraductal papillary mucinous neoplasms (IPMNs) are mucin-producing neoplasms of the main and/or branch pancreatic ducts. To assess differences between various IPMN subtypes, immunohistochemical markers of gastric surface mucous cells (MUC5AC), gastric gland mucous cells (MUC6 and GlcNAcα1→4Galβ→R), gastric pyloric and duodenal epithelial cells (PDX1), intestinal cells (MUC2 and CDX2), small intestinal cells (CPS1) and large intestinal cells (SATB2) were evaluated in 33 surgically treated IPMNs. MUC2 expression classified IPMNs into gastric (n=17), intestinal (n=8) and mixed gastric and intestinal type (collision=7, composite=1). No differences in age or sex were observed among these types. MUC5AC and PDX1 were expressed in all IPMNs. MUC6 expression was higher in gastric and mixed types than in intestinal type. GlcNAcα1→4Galβ→R was detected in gastric and mixed type, but not in intestinal type. MUC2 and CDX2 expression were higher in intestinal type than gastric and mixed type. CPS1 expression was higher in intestinal type than gastric type. SATB2 was not observed in any IPMNs. Frequent abrupt transition between the two IPMN types in mixed-type IPMNs was observed. Gastric pyloric and small intestinal differentiation are characteristic of gastric and intestinal type IPMN, respectively, and these two IPMN types may have distinct pathogenesis.
    Preview · Article · May 2014 · Acta histochemica et cytochemica official journal of the Japan Society of Histochemistry and Cytochemistry
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    • "Among the transfected cells studied, PK-8 cells exhibited the most consistent upregulation of mucin genes, including MUC2, MUC5B, MUC6, MUC15, and MUC20. Among these genes, MUC2, MUC5B, and MUC6 encode secreted mucins and are known to be expressed abundantly in IPMNs [31], [32]. MUC1, which is commonly expressed in PDACs but relatively rarely in IPMNs [33], [34], was upregulated in PCI-35 and MIA PaCa-2 cells but was downregulated in the PK-8 cells. "
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    ABSTRACT: GNAS, a gene encoding G protein stimulating α subunit, is frequently mutated in intraductal papillary mucinous neoplasms (IPMNs), which are indolent and slow-growing pancreatic tumors that secrete abundant mucin. The GNAS mutation is not observed in conventional ductal adenocarcinomas of the pancreas. To determine the functional significance of the GNAS mutation in pancreatic ductal lineage cells, we examined in vitro phenotypes of cells of pancreatic ductal lineage, HPDE, PK-8, PCI-35, and MIA PaCa-2, with exogenous expression of either wild-type or mutated (R201H) GNAS. We found that exogenous GNAS upregulated intracellular cyclic adenine monophosphate (cAMP), particularly in mutated GNAS transfectants, and upregulated expression of MUC2 and MUC5AC in HPDE and PK-8 cells. By contrast, exogenous GNAS inhibited expression of mucin genes in PCI-35 and MIA PaCa-2 cells, despite upregulation of cAMP. We examined global gene expression profiles of some of the cells transfected with exogenous mutated GNAS (PK-8, PCI-35, and MIA PaCa-2), and found that PK-8 cells exhibited drastic alterations of the gene expression profile, which contrasted with modest alterations in PCI-35 and MIA PaCa-2 cells. To identify a cause of these different effects of exogenous mutated GNAS on phenotypes of the cells, we examined effects of interactions of the signaling pathways of G protein-coupled receptor (GPCR), mitogen-activated protein kinase (MAPK), and phosphatidylinositol 3-kinase (PI3K) on expression of mucin genes. The MAPK and PI3K pathways significantly influenced the expression of mucin genes. Exogenous GNAS did not promote cell growth but suppressed it in some of the cells. In conclusion, mutated GNAS found in IPMNs may extensively alter gene expression profiles, including expression of mucin genes, through the interaction with MAPK and PI3K pathways in pancreatic ductal cells; these changes may determine the characteristic phenotype of IPMN. PK-8 cells expressing exogenous mutated GNAS may be an ideal in vitro model of IPMN.
    Full-text · Article · Feb 2014 · PLoS ONE
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