Prognostic relevance of morphological types of intraductal papillary mucinous neoplasms of the pancreas

Furukawa, Toru; Hatori, Takashi; Fujita, Izumi; Yamamoto, Masakazu; Kobayashi, Makio; Ohike, Nobuyuki; Morohoshi, Toshio; Egawa, Shinichi; Unno, Michiaki; Takao, Sonshin; Osako, Masahiko; Yonezawa, Suguru; Mino‐Kenudson, Mari; Lauwers, Gregory Y.; Yamaguchi, Hiroshi; Ban, Shinichi; Shimizu, Michio

doi:10.1136/gut.2010.210567

Cited by 289 publications

(222 citation statements)

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“…Previous studies also demonstrate the greater prevalence of gastric and intestinal IPMN subtypes. 7,8,27 The mixed subtype may have been difficult to assess due to the limited examination of the specimen by all the gastrointestinal pathologists, which is reflected in the poor interobserver agreement for this subtype. Nonetheless, the entirety of each case was seen by a gastrointestinal pathologist at his or her respective institution and the selected slide from each case should be considered representative of the overall lesion.…”

Section: Discussionmentioning

confidence: 99%

“…Gastric and pancreatobiliary subtypes are more often associated with invasive tubular adenocarcinoma versus intestinal subtype, which is frequently associated with invasive colloid carcinoma. [5][6][7][8] Furthermore, studies have reported conflicting evidence on whether the histologic IPMN subtype has prognostic significance. [8][9][10][11][12] The Verona consensus meeting in 2013 recently led to the publication of guidelines for pathologic reporting of IPMN with the recommendation that pathologists provide a histologic subtype.…”

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confidence: 99%

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Interobserver variability in intraductal papillary mucinous neoplasm subtypes and application of their mucin immunoprofiles

et al. 2016

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Intraductal papillary mucinous neoplasm is considered a precursor lesion to pancreatic adenocarcinoma. These are further classified into four histologic subtypes: gastric, intestinal, pancreatobiliary, and oncocytic. The first aim of this study was to assess the interobserver variability among five gastrointestinal pathologists in diagnosing intraductal papillary mucinous neoplasm subtypes by morphology alone. The second aim of the study was to compare intraductal papillary mucinous neoplasm subtypes, which received consensus diagnoses (≥80% agreement) with their respective mucin immunoprofiles (MUC1, MUC2, MUC5AC, MUC6, and CDX2). A consensus histologic subtype was reached in 58% of cases (29/50) among the five gastrointestinal pathologists. Overall there was moderate agreement (κ = 0.41, Po 0.01) in subtyping intraductal papillary mucinous neoplasms without the use of immunohistochemistry. The histologic subtype with the best interobserver agreement was intestinal type (κ = 0.56, Po 0.01) followed by pancreatobiliary, gastric, mixed, and oncocytic types (κ = 0.43, Po 0.01; κ = 0.38, Po 0.01; κ = 0.17, Po 0.01; κ = 0.08, Po 0.04, respectively). Both kappa values for mixed and oncocytic subtypes were likely artificially low due to the underrepresentation of these subtypes in this study and not a true indication of poor interobserver agreement. Following an intradepartmental consensus meeting between two gastrointestinal pathologists, 68% of cases (34/50) received a consensus intraductal papillary mucinous neoplasm subtype. Sixty-nine percent of cases (11/16) that did not receive a consensus intraductal papillary mucinous neoplasm subtype could be classified based on their respective immunoprofiles. Standardizing the use of immunohistochemistry with a mucin immunopanel (MUC1, MUC2, MUC5AC, and MUC6) may improve the agreement of diagnosing intraductal papillary mucinous neoplasm histologic subtypes.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Interobserver variability in intraductal papillary mucinous neoplasm subtypes and application of their mucin immunoprofiles

et al. 2016

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“…2,5 Concerning pancreatic intraductal papillary mucinous neoplasm, the existence of four different subtypes (intestinal, gastric, pancreato-biliary and oncocytic) is well established, 6 and prognostic differences among subtypes have been described. [7][8][9][10] In addition, several studies performed on human and transgenic mice revealed a number of genetic changes in key molecular pathways during intraductal papillary mucinous neoplasm development. [11][12][13][14][15][16] In contrast to the more common pancreatic intraductal papillary mucinous neoplasms, intraductal papillary neoplasms of the bile duct have not been well characterized so far, either from the clinical or from the molecular point of view.…”

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confidence: 99%

Intraductal papillary neoplasms of the bile duct: stepwise progression to carcinoma involves common molecular pathways

Schlitter

Born

Bettstetter³

et al. 2014

Modern Pathology

135

131

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Intraductal papillary neoplasms of the bile duct are still poorly characterized regarding (1) their molecular alterations during the development to invasive carcinomas, (2) their subtype stratification and (3) their biological behavior. We performed a multicenter study that analyzed these issues in a large European cohort. Intraductal papillary neoplasms of the bile duct from 45 patients were graded and subtyped using mucin markers and CDX2. In addition, tumors were analyzed for common oncogenic pathways, and the findings were correlated with subtype and grade. Data were compared with those from 22 extra-and intrahepatic cholangiocarcinomas. Intraductal papillary neoplasms showed a development from preinvasive low-to highgrade intraepithelial neoplasia to invasive carcinoma. Molecular and immunohistochemical analysis revealed mutated KRAS, overexpression of TP53 and loss of p16 in low-grade intraepithelial neoplasia, whereas loss of SMAD4 was found in late phases of tumor development. Alterations of HER2, EGFR, b-catenin and GNAS were rare events. Among the subtypes, pancreato-biliary (36%) and intestinal (29%) were the most common, followed by gastric (18%) and oncocytic (13%) subtypes. Patients with intraductal papillary neoplasm of the bile duct showed a slightly better overall survival than patients with cholangiocarcinoma (hazard ratio (cholangiocarcinoma versus intraductal papillary neoplasm of the bile duct): 1.40; 95% confidence interval: 0.46-4.30; P ¼ 0.552). The development of biliary intraductal papillary neoplasms of the bile duct follows an adenomacarcinoma sequence that correlates with the stepwise activation of common oncogenic pathways. Further large trials are needed to investigate and verify the finding of a better prognosis of intraductal papillary neoplasms compared with conventional cholangiocarcinoma.

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“…According to histological features (architecture and cytology), four types of IPMNs, such as gastric, intestinal, pancreatobiliary, and oncocystic, have been described. Gastric-type epithelium is frequent in side branches type with better prognosis (malignant potential 28%); intestinal-type and pancreatobiliary-type epithelia are more frequent in main duct type with bad prognosis (malignant potential 60%) [30]. Several patients can be symptomatic with non-specific symptoms.…”

Section: Intraductal Papillary Mucinous Neoplasms (Ipmns)mentioning

confidence: 99%

Management of Pancreatic Cystic Lesions

Neri¹

2017

Challenges in Pancreatic Pathology

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Objectives: In the last several decades, the knowledge of the cystic neoplasms has enlarged and the management has changed. The wide adoption in the diagnostic procedures of routine and advanced imaging has become the cornerstone of the diagnosis.Methods: Pancreatic cystic tumors comprise neoplasms with a wide range of malignant potential. The most common include serous cystic neoplasm, mucinous cystic neoplasms (MCNs), intraductal papillary mucinous neoplasms (IPMNs), solid pseudopapillary neoplasms (SPPNs), and cystic pancreatic endocrine neoplasms (CPENs). Other cystic lesions are acute postnecrotic pseudocysts and chronic pseudocysts. Finally, the indeterminate cystic lesions have been presented. Results:The epidemiology, pathological features, imaging characteristics, clinical evolution, and therapeutic choices of the most frequent lesions as well as less frequent forms are described. This study can be completed with the presentation of some cases of cystic pancreatic neoplasms treated in our service. Conclusion:The improvement of imaging, endoscopic modalities, and cyst fluid studies allows now accurate and reliable diagnosis of pancreatic cystic lesions. Moreover, the enlarged knowledge of valuable pathological studies established the potential for malignant transformation of these lesions identifying higher-risk neoplasms. Finally, the management options should be based on the assessment of each type of cystic neoplasms and the distinction of pancreatic cystic neoplasms (PCNs) from other cystic lesions.

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Prognostic relevance of morphological types of intraductal papillary mucinous neoplasms of the pancreas

Abstract: In this multicentre retrospective analysis, the morphological type of IPMN appears to be an independent predictor of patient prognosis.

Cited by 289 publications

References 22 publications

Interobserver variability in intraductal papillary mucinous neoplasm subtypes and application of their mucin immunoprofiles

Interobserver variability in intraductal papillary mucinous neoplasm subtypes and application of their mucin immunoprofiles

Intraductal papillary neoplasms of the bile duct: stepwise progression to carcinoma involves common molecular pathways

Management of Pancreatic Cystic Lesions

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