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Published in: Annals of Surgical Oncology 11/2013

01-10-2013 | Pancreatic Tumors

Incidentally Discovered Pancreatic Intraepithelial Neoplasia: What Is Its Clinical Significance?

Authors: Ioannis T. Konstantinidis, MD, Eduardo F. Vinuela, MD, Laura H. Tang, MD, David S. Klimstra, MD, Michael I. D’Angelica, MD, Ronald P. DeMatteo, MD, T. Peter Kingham, MD, Yuman Fong, MD, William R. Jarnagin, MD, Peter J. Allen, MD

Published in: Annals of Surgical Oncology | Issue 11/2013

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Abstract

Purpose

Pancreatic intraepithelial neoplasia (PanIN) is a presumed precursor of pancreatic ductal adenocarcinoma (PDAC). We assessed the relationship between incidental PanIN after resection of non-adenocarcinoma lesions and the development of metachronous PDAC in the remnant.

Methods

We retrospectively reviewed the clinicopathologic data of patients who underwent pancreatectomy for non-PDAC from January 2000 to January 2010. Intraductal papillary mucinous lesions were excluded. All available postoperative imaging and clinical follow-up data were reviewed; the risk of developing PDAC was assessed in patients with a minimum follow-up time of 6 months and with imaging studies available for review.

Results

A total of 584 patients were analyzed. Median age was 59 years (range 10–85 years), and 338 (58 %) were female. The most common lesions for which resection was performed were serous cystic neoplasms (17 %), pancreatic neuroendocrine tumors (38 %), metastatic tumors (9 %), and mucinous cystic neoplasms (7 %). PanIN was identified in 153 (26 %) patients. The majority of these patients had PanIN-1 or -2 (50 and 41 %, respectively), whereas 13 (8 %) had PanIN-3. Of the 506 (87 %) patients with adequate follow-up (median 3.7 years, range 0.5–12.6 years), 1 patient (0.2 %) with PanIN identified at the time of initial resection developed cancer in the remnant. This occurred 4.4 years after a distal pancreatectomy in the setting of PanIN-1B. No patient with PanIN-3 developed cancer during follow-up.

Conclusions

PanIN was identified in 26 % of patients who underwent resection for histopathology other than PDAC. The presence of PanIN of any grade did not result in an appreciable cancer risk in the pancreatic remnant after short-term follow-up.
Literature
2.
go back to reference Hruban RH, Takaori K, Klimstra DS, et al. An illustrated consensus on the classification of pancreatic intraepithelial neoplasia and intraductal papillary mucinous neoplasms. Am J Surg Pathol. 2004;28:977–87.PubMedCrossRef Hruban RH, Takaori K, Klimstra DS, et al. An illustrated consensus on the classification of pancreatic intraepithelial neoplasia and intraductal papillary mucinous neoplasms. Am J Surg Pathol. 2004;28:977–87.PubMedCrossRef
3.
go back to reference Hruban RH, Adsay NV, Albores-Saavedra J, et al. Pancreatic intraepithelial neoplasia: a new nomenclature and classification system for pancreatic duct lesions. Am J Surg Pathol. 2001;25:579–86.PubMedCrossRef Hruban RH, Adsay NV, Albores-Saavedra J, et al. Pancreatic intraepithelial neoplasia: a new nomenclature and classification system for pancreatic duct lesions. Am J Surg Pathol. 2001;25:579–86.PubMedCrossRef
4.
go back to reference Iacobuzio-Donahue CA. Genetic evolution of pancreatic cancer: lessons learnt from the pancreatic cancer genome sequencing project. Gut. 2012;61:1085–94.PubMedCrossRef Iacobuzio-Donahue CA. Genetic evolution of pancreatic cancer: lessons learnt from the pancreatic cancer genome sequencing project. Gut. 2012;61:1085–94.PubMedCrossRef
5.
go back to reference Hruban RH, Goggins M, Parsons J, et al. Progression model for pancreatic cancer. Clin Cancer Res. 2000;6:2969–72.PubMed Hruban RH, Goggins M, Parsons J, et al. Progression model for pancreatic cancer. Clin Cancer Res. 2000;6:2969–72.PubMed
6.
go back to reference Stelow EB, Adams RB, Moskaluk CA. The prevalence of pancreatic intraepithelial neoplasia in pancreata with uncommon types of primary neoplasms. Am J Surg Pathol. 2006;30:36–41.PubMedCrossRef Stelow EB, Adams RB, Moskaluk CA. The prevalence of pancreatic intraepithelial neoplasia in pancreata with uncommon types of primary neoplasms. Am J Surg Pathol. 2006;30:36–41.PubMedCrossRef
7.
go back to reference Andea A, Sarkar F, Adsay VN. Clinicopathological correlates of pancreatic intraepithelial neoplasia: a comparative analysis of 82 cases with and 152 cases without pancreatic ductal adenocarcinoma. Mod Pathol. 2003;16:996–1006.PubMedCrossRef Andea A, Sarkar F, Adsay VN. Clinicopathological correlates of pancreatic intraepithelial neoplasia: a comparative analysis of 82 cases with and 152 cases without pancreatic ductal adenocarcinoma. Mod Pathol. 2003;16:996–1006.PubMedCrossRef
8.
go back to reference Brat DJ, Lillemoe KD, Yeo CJ, et al. Progression of pancreatic intraductal neoplasias to infiltrating adenocarcinoma of the pancreas. Am J Surg Pathol. 1998;22:163–9.PubMedCrossRef Brat DJ, Lillemoe KD, Yeo CJ, et al. Progression of pancreatic intraductal neoplasias to infiltrating adenocarcinoma of the pancreas. Am J Surg Pathol. 1998;22:163–9.PubMedCrossRef
9.
go back to reference Brockie E, Anand A, Albores-Saavedra J. Progression of atypical ductal hyperplasia/carcinoma in situ of the pancreas to invasive adenocarcinoma. Ann Diagn Pathol. 1998;2:286–92.PubMedCrossRef Brockie E, Anand A, Albores-Saavedra J. Progression of atypical ductal hyperplasia/carcinoma in situ of the pancreas to invasive adenocarcinoma. Ann Diagn Pathol. 1998;2:286–92.PubMedCrossRef
10.
go back to reference Takaori K, Matsusue S, Fujikawa T, et al. Carcinoma in situ of the pancreas associated with localized fibrosis: a clue to early detection of neoplastic lesions arising from pancreatic ducts. Pancreas. 1998;17:102–5.PubMedCrossRef Takaori K, Matsusue S, Fujikawa T, et al. Carcinoma in situ of the pancreas associated with localized fibrosis: a clue to early detection of neoplastic lesions arising from pancreatic ducts. Pancreas. 1998;17:102–5.PubMedCrossRef
11.
go back to reference Almoguera C, Shibata D, Forrester K, et al. Most human carcinomas of the exocrine pancreas contain mutant c-K-ras genes. Cell. 1988;53:549–54.PubMedCrossRef Almoguera C, Shibata D, Forrester K, et al. Most human carcinomas of the exocrine pancreas contain mutant c-K-ras genes. Cell. 1988;53:549–54.PubMedCrossRef
12.
go back to reference Hu YX, Watanabe H, Ohtsubo K, et al. Frequent loss of p16 expression and its correlation with clinicopathological parameters in pancreatic carcinoma. Clin Cancer Res. 1997;3:1473–7.PubMed Hu YX, Watanabe H, Ohtsubo K, et al. Frequent loss of p16 expression and its correlation with clinicopathological parameters in pancreatic carcinoma. Clin Cancer Res. 1997;3:1473–7.PubMed
13.
go back to reference Ruggeri B, Zhang SY, Caamano J, et al. Human pancreatic carcinomas and cell lines reveal frequent and multiple alterations in the p53 and Rb-1 tumor-suppressor genes. Oncogene. 1992;7:1503–11.PubMed Ruggeri B, Zhang SY, Caamano J, et al. Human pancreatic carcinomas and cell lines reveal frequent and multiple alterations in the p53 and Rb-1 tumor-suppressor genes. Oncogene. 1992;7:1503–11.PubMed
14.
go back to reference Schutte M, Hruban RH, Hedrick L, et al. DPC4 gene in various tumor types. Cancer Res. 1996;56:2527–30.PubMed Schutte M, Hruban RH, Hedrick L, et al. DPC4 gene in various tumor types. Cancer Res. 1996;56:2527–30.PubMed
15.
go back to reference Mazur PK, Einwachter H, Lee M, et al. Notch2 is required for progression of pancreatic intraepithelial neoplasia and development of pancreatic ductal adenocarcinoma. Proc Natl Acad Sci USA. 2010;107:13438–43.PubMedCrossRef Mazur PK, Einwachter H, Lee M, et al. Notch2 is required for progression of pancreatic intraepithelial neoplasia and development of pancreatic ductal adenocarcinoma. Proc Natl Acad Sci USA. 2010;107:13438–43.PubMedCrossRef
16.
go back to reference Recavarren C, Labow DM, Liang J, et al. Histologic characteristics of pancreatic intraepithelial neoplasia associated with different pancreatic lesions. Hum Pathol. 2011;42:18–24.PubMedCrossRef Recavarren C, Labow DM, Liang J, et al. Histologic characteristics of pancreatic intraepithelial neoplasia associated with different pancreatic lesions. Hum Pathol. 2011;42:18–24.PubMedCrossRef
17.
go back to reference Shi C, Klein AP, Goggins M, et al. Increased prevalence of precursor lesions in familial pancreatic cancer patients. Clin Cancer Res. 2009;15:7737–43.PubMedCrossRef Shi C, Klein AP, Goggins M, et al. Increased prevalence of precursor lesions in familial pancreatic cancer patients. Clin Cancer Res. 2009;15:7737–43.PubMedCrossRef
18.
go back to reference McCarthy DM, Brat DJ, Wilentz RE, et al. Pancreatic intraepithelial neoplasia and infiltrating adenocarcinoma: analysis of progression and recurrence by DPC4 immunohistochemical labeling. Hum Pathol. 2001;32:638–42.PubMedCrossRef McCarthy DM, Brat DJ, Wilentz RE, et al. Pancreatic intraepithelial neoplasia and infiltrating adenocarcinoma: analysis of progression and recurrence by DPC4 immunohistochemical labeling. Hum Pathol. 2001;32:638–42.PubMedCrossRef
19.
go back to reference Matthaei H, Hong SM, Mayo SC, et al. Presence of pancreatic intraepithelial neoplasia in the pancreatic transection margin does not influence outcome in patients with R0 resected pancreatic cancer. Ann Surg Oncol. 2011;18:3493–9.PubMedCrossRef Matthaei H, Hong SM, Mayo SC, et al. Presence of pancreatic intraepithelial neoplasia in the pancreatic transection margin does not influence outcome in patients with R0 resected pancreatic cancer. Ann Surg Oncol. 2011;18:3493–9.PubMedCrossRef
20.
go back to reference Kim J, Reber HA, Dry SM, et al. Unfavourable prognosis associated with K-ras gene mutation in pancreatic cancer surgical margins. Gut. 2006;55:1598–605.PubMedCrossRef Kim J, Reber HA, Dry SM, et al. Unfavourable prognosis associated with K-ras gene mutation in pancreatic cancer surgical margins. Gut. 2006;55:1598–605.PubMedCrossRef
21.
go back to reference Ferrone CR, Tang LH, Tomlinson J, et al. Determining prognosis in patients with pancreatic endocrine neoplasms: can the WHO classification system be simplified? J Clin Oncol. 2007;25:5609–15.PubMedCrossRef Ferrone CR, Tang LH, Tomlinson J, et al. Determining prognosis in patients with pancreatic endocrine neoplasms: can the WHO classification system be simplified? J Clin Oncol. 2007;25:5609–15.PubMedCrossRef
22.
go back to reference Sakorafas GH, Smyrniotis V, Reid-Lombardo KM, Sarr MG. Primary pancreatic cystic neoplasms revisited. Part I: serous cystic neoplasms. Surg Oncol. 2011;20:e84–92PubMedCrossRef Sakorafas GH, Smyrniotis V, Reid-Lombardo KM, Sarr MG. Primary pancreatic cystic neoplasms revisited. Part I: serous cystic neoplasms. Surg Oncol. 2011;20:e84–92PubMedCrossRef
23.
go back to reference Agoff SN, Crispin DA, Bronner MP, et al. Neoplasms of the ampulla of Vater with concurrent pancreatic intraductal neoplasia: a histological and molecular study. Mod Pathol. 2001;14:139–46.PubMedCrossRef Agoff SN, Crispin DA, Bronner MP, et al. Neoplasms of the ampulla of Vater with concurrent pancreatic intraductal neoplasia: a histological and molecular study. Mod Pathol. 2001;14:139–46.PubMedCrossRef
24.
go back to reference Canto MI, Hruban RH, Fishman EK, et al. Frequent detection of pancreatic lesions in asymptomatic high-risk individuals. Gastroenterology. 2012;142:796–804.PubMedCrossRef Canto MI, Hruban RH, Fishman EK, et al. Frequent detection of pancreatic lesions in asymptomatic high-risk individuals. Gastroenterology. 2012;142:796–804.PubMedCrossRef
25.
go back to reference Kelly KA, Bardeesy N, Anbazhagan R, et al. Targeted nanoparticles for imaging incipient pancreatic ductal adenocarcinoma. PLoS Med. 2008;5:e85.PubMedCrossRef Kelly KA, Bardeesy N, Anbazhagan R, et al. Targeted nanoparticles for imaging incipient pancreatic ductal adenocarcinoma. PLoS Med. 2008;5:e85.PubMedCrossRef
Metadata
Title
Incidentally Discovered Pancreatic Intraepithelial Neoplasia: What Is Its Clinical Significance?
Authors
Ioannis T. Konstantinidis, MD
Eduardo F. Vinuela, MD
Laura H. Tang, MD
David S. Klimstra, MD
Michael I. D’Angelica, MD
Ronald P. DeMatteo, MD
T. Peter Kingham, MD
Yuman Fong, MD
William R. Jarnagin, MD
Peter J. Allen, MD
Publication date
01-10-2013
Publisher
Springer US
Published in
Annals of Surgical Oncology / Issue 11/2013
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-013-3042-2

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