Pathohistological Subtype Predicts Survival in Patients With Intraductal Papillary Mucinous Neoplasm (IPMN) of the Pancreas

Distler, Marius; Kersting, Stephan; Niedergethmann, Marco; Aust, Daniela E.; Franz, Melanie; Rückert, Felix; Ehehalt, Florian; Pilarsky, Christian; Post, Stefan; Saeger, Hans‐Detlev; Grützmann, Robert

doi:10.1097/sla.0b013e318287ab73

Cited by 128 publications

(123 citation statements)

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“…One previous study has reported that gastric-and intestinal-type intraductal papillary mucinous neoplasms demonstrate less malignant potential than pancreatobiliary-type intraductal papillary mucinous neoplasms. 47 Distler et al 48 have reported that pancreatobiliary-type intraductal papillary mucinous neoplasm is strongly associated with advanced tumor stage in comparison with intestinal-type intraductal papillary mucinous neoplasm. Moreover, pancreatobiliary-type intraductal papillary mucinous neoplasm demonstrates higher local recurrence and metastatic rates compared with other histological subtypes of intraductal papillary mucinous neoplasm, including intestinal, gastric, and oncocytic types.…”

Section: Discussionmentioning

confidence: 99%

“…In ampullary carcinoma, the pancreatobiliary type also demonstrates significantly deeper tumor invasion (that is, pT classification) and more frequent lymph nodal, perineural, duodenal, and pancreatic invasion than intestinal ampullary carcinomas. 13,49 In addition, intestinal type tumors demonstrate significantly better patient survival than pancreatobiliary type neoplasms from various gastrointestinal tract tumors, including intraductal papillary mucinous neoplasm 48 and ampullary 49 and gastric 50 carcinomas. In concordance with the results of previous studies on the prognostic implications of the morphologic and immunophenotypic classifications of other gastrointestinal tumors, the intestinal immunophenotype adenocarcinomas we examined in our present study were associated with significantly better patient survival outcomes than small intestinal adenocarcinomas of other immunophenotypes.…”

Section: Discussionmentioning

confidence: 99%

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Prognostic significance of CDX2 and mucin expression in small intestinal adenocarcinoma

et al. 2014

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The clinicopathological and prognostic significance of CDX2 and mucin expression have not been comprehensively evaluated in small intestinal adenocarcinoma. Immunohistochemical microarray analyses of CDX2, MUC1, MUC5AC, and MUC6 protein expressions in 189 surgically resected small intestinal adenocarcinoma cases were examined and compared with various clinicopathologic variables, including survival. CDX2, MUC1, MUC5AC, and MUC6 expressions were observed in 43.4% (82 patients), 37.6% (71), 31.7% (60), and 21.7% (41) of patients, respectively. Whereas CDX2 expression was found to be associated with lowgrade tumors (P ¼ 0.034), fewer nodal metastases (P ¼ 0.019), and less perineural invasion (P ¼ 0.049) in small intestinal adenocarcinoma patients, patients expressing MUC1 tended to demonstrate high-grade (P ¼ 0.021) and nodular or infiltrative (P ¼ 0.020) tumors. On the basis of the combined CDX2, MUC1, MUC5AC, and MUC6 expression patterns, small intestinal adenocarcinoma patients were further classified as intestinalAmong these immunophenotypes, intestinal-type patients demonstrated more frequent distal (jejunal or ileal; P ¼ 0.033), tubular (P ¼ 0.039), and low-grade tumors (P ¼ 0.004) and significantly better survival according to univariate (Po0.0001) and multivariate (P ¼ 0.001) analyses. In summary, intestinal immunophenotype adenocarcinomas are associated with distal (jejunal or ileal), tubular, and low-grade tumors and better survival outcomes. Hence, CDX2 and mucin immunohistochemical staining may provide better estimations of survival after surgical resection and intestinal immunophenotype could therefore be used as a better prognostic indicator of small intestinal adenocarcinoma. Modern Pathology (2014Pathology ( ) 27, 1364Pathology ( -1374 doi:10.1038/modpathol.2014 published online 7 March 2014 Keywords: adenocarcinoma; CDX2; immunohistochemistry; mucin; prognosis; small intestine Primary small intestinal adenocarcinomas account for only 5% of malignant neoplasms in the gastrointestinal tract despite the long length of the small intestine and the significant mucosal coverage over the entire gastrointestinal tract. 1 In 2013, it is estimated that 8810 Americans will be diagnosed with small intestinal adenocarcinoma. 1 Despite recent improvements in the detection of the small intestinal adenocarcinomas, including improved imaging techniques and endoscopic modalities, the diagnosis of small intestinal adenocarcinomas is usually made at an advanced clinical stage and the 5-year survival rate is only 41.2%. 2 Several clinicopathologic factors, including lymph node metastasis and the distal locations of these tumors (jejunum and ileum), are known as the most important independent prognostic factors. 2 Although several molecular alterations, including KRAS, TP53, and DPC4/SMAD4 mutations and the overexpression of cyclinD1, are known to be involved in small intestinal adenocarcinoma carcinogenesis, [3][4][5][6]

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Prognostic significance of CDX2 and mucin expression in small intestinal adenocarcinoma

et al. 2014

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“…[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. 13 Although most previous studies used morphology and immunohistochemistry to designate the IPMN subtype, this is not necessarily implemented as standard practice.…”

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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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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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“…Epithelial subtyping helps to explain this well documented survival advantage through the observation that each has a distinct path and rate of progression to a specific form of pancreatic cancer. Subtype analysis of these specific cancers reveals that much of the overall survival advantage is due to the more favorable prognoses of colloid and oncocytic carcinoma compared to tubular adenocarcinoma, which has a similar overall survival to classic PDAC [8,10,11] .…”

Section: Clinicopathological Features Of Ipmnmentioning

confidence: 99%

“…IPMN are classified further into 4 epithelial subtypes based upon mucin expression and morphology: gastric, intestinal, pancreatobiliary and oncocytic [8][9][10] . The gastric subtype is the most common overall and is generally found in the periphery of the pancreas in the form of BD-IPMN.…”

Section: Clinicopathological Features Of Ipmnmentioning

confidence: 99%

Is It Time to Expand the Role of Total Pancreatectomy for IPMN?

Griffin

Poruk

Wolfgang³

2016

Dig Surg

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Intraductal papillary mucinous neoplasms (IPMN) are cystic precursors to pancreatic cancer believed to arise within a widespread neoplastic field defect. The tendency for some patients to present with multifocal disease and/or develop additional lesions over time argues in favor of a field defect and complicates surgical management decisions. Surgery usually consists of partial pancreatic resection, which leaves behind a pancreatic remnant at risk for recurrent disease and progression to cancer. As an alternative, total pancreatectomy (TP) provides the most complete oncologic resection, but postoperative morbidity and quality of life (QoL) issues have generally limited its use to only the highest risk patients. Significant progress has been made in the management of the post-TP apancreatic state and studies now show less morbidity with acceptable QoL comparable to type 1 diabetic and post-pancreaticoduodenectomy patients. These improvements do not yet justify the routine use of TP, but they have opened the door for expansion to additional subsets of non-invasive IPMN. Here, we have identified several groups of patients that we believe would benefit from TP over partial resection based on the most current literature.

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Pathohistological Subtype Predicts Survival in Patients With Intraductal Papillary Mucinous Neoplasm (IPMN) of the Pancreas

Abstract: Evaluation of IPMN subtypes supports postoperative patient prognosis prediction. Therefore, subtype differentiation could lead to improvements in clinical management. Potentially identifying subgroups with the need for adjuvant therapy may be possible.

Cited by 128 publications

References 24 publications

Prognostic significance of CDX2 and mucin expression in small intestinal adenocarcinoma

Prognostic significance of CDX2 and mucin expression in small intestinal adenocarcinoma

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

Is It Time to Expand the Role of Total Pancreatectomy for IPMN?

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