Clinicopathological characteristics and molecular analyses of multifocal intraductal papillary mucinous neoplasms of the pancreas

Hanno Matthaei, Alexis L. Norris, Athanasios C. Tsiatis, Kelly Olino, Seung Mo Hong, Marco Dal Molin, Michael G. Goggins, Marcia Canto, Karen M. Horton, Keith D. Jackson, Paola Capelli, Giuseppe Zamboni, Laura Bortesi, Toru Furukawa, Shinichi Egawa, Masaharu Ishida, Shigeru Ottomo, Michiaki Unno, Fuyuhiko Motoi, Christopher L. Wolfgang & 6 others Barish H. Edil, John L. Cameron, James R. Eshleman, Richard D. Schulick, Anirban Maitra, Ralph H. Hruban

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Abstract

Objective: To examine the clinicopathologic features and clonal relationship of multifocal intraductal papillary mucinous neoplasms (IPMNs) of the pancreas. Background: Intraductal papillary mucinous neoplasms are increasingly diagnosed cystic precursor lesions of pancreatic cancer. Intraductal papillary mucinous neoplasms can be multifocal and a potential cause of recurrence after partial pancreatectomy. Methods: Thirty four patients with histologically documented multifocal IPMNs were collected and their clinicopathologic features catalogued. In addition, thirty multifocal IPMNs arising in 13 patients from 3 hospitals were subjected to laser microdissection followed by KRAS pyrosequencing and loss of heterozygosity (LOH) analysis on chromosomes 6q and 17p. Finally, we sought to assess the clonal relationships among multifocal IPMNs. Results: We identified 34 patients with histologically documented multifocal IPMNs. Synchronous IPMNs were present in 29 patients (85%), whereas 5 (15%) developed clinically significant metachronous IPMNs. Six patients (18%) had a history of familial pancreatic cancer. A majority of multifocal IPMNs (86% synchronous, 100% metachronous) were composed of branch duct lesions, and typically demonstrated a gastric-foveolar subtype epithelium with low or intermediate grades of dysplasia. Three synchronous IPMNs (10%) had an associated invasive cancer. Molecular analysis of multiple IPMNs from 13 patients demonstrated nonoverlapping KRAS gene mutations in 8 patients (62%) and discordant LOH profiles in 7 patients (54%); independent genetic alterations were established in 9 of the 13 patients (69%). Conclusions: The majority of multifocal IPMNs arise independently and exhibit a gastric-foveolar subtype, with low to intermediate dysplasia. These findings underscore the importance of life-long follow-up after resection for an IPMN.

Original languageEnglish (US)
Pages (from-to)326-333
Number of pages8
JournalAnnals of Surgery
Volume255
Issue number2
DOIs
StatePublished - Feb 2012
Externally publishedYes

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Pancreatic Neoplasms
Neoplasms
Loss of Heterozygosity
Stomach
Multiple Primary Neoplasms
Microdissection
Pancreatectomy
Lasers
Epithelium
Chromosomes

ASJC Scopus subject areas

  • Surgery

Cite this

Matthaei, H., Norris, A. L., Tsiatis, A. C., Olino, K., Hong, S. M., Dal Molin, M., ... Hruban, R. H. (2012). Clinicopathological characteristics and molecular analyses of multifocal intraductal papillary mucinous neoplasms of the pancreas. Annals of Surgery, 255(2), 326-333. https://doi.org/10.1097/SLA.0b013e3182378a18

Clinicopathological characteristics and molecular analyses of multifocal intraductal papillary mucinous neoplasms of the pancreas. / Matthaei, Hanno; Norris, Alexis L.; Tsiatis, Athanasios C.; Olino, Kelly; Hong, Seung Mo; Dal Molin, Marco; Goggins, Michael G.; Canto, Marcia; Horton, Karen M.; Jackson, Keith D.; Capelli, Paola; Zamboni, Giuseppe; Bortesi, Laura; Furukawa, Toru; Egawa, Shinichi; Ishida, Masaharu; Ottomo, Shigeru; Unno, Michiaki; Motoi, Fuyuhiko; Wolfgang, Christopher L.; Edil, Barish H.; Cameron, John L.; Eshleman, James R.; Schulick, Richard D.; Maitra, Anirban; Hruban, Ralph H.

In: Annals of Surgery, Vol. 255, No. 2, 02.2012, p. 326-333.

Research output: Contribution to journalArticle

Matthaei, H, Norris, AL, Tsiatis, AC, Olino, K, Hong, SM, Dal Molin, M, Goggins, MG, Canto, M, Horton, KM, Jackson, KD, Capelli, P, Zamboni, G, Bortesi, L, Furukawa, T, Egawa, S, Ishida, M, Ottomo, S, Unno, M, Motoi, F, Wolfgang, CL, Edil, BH, Cameron, JL, Eshleman, JR, Schulick, RD, Maitra, A & Hruban, RH 2012, 'Clinicopathological characteristics and molecular analyses of multifocal intraductal papillary mucinous neoplasms of the pancreas', Annals of Surgery, vol. 255, no. 2, pp. 326-333. https://doi.org/10.1097/SLA.0b013e3182378a18
Matthaei, Hanno ; Norris, Alexis L. ; Tsiatis, Athanasios C. ; Olino, Kelly ; Hong, Seung Mo ; Dal Molin, Marco ; Goggins, Michael G. ; Canto, Marcia ; Horton, Karen M. ; Jackson, Keith D. ; Capelli, Paola ; Zamboni, Giuseppe ; Bortesi, Laura ; Furukawa, Toru ; Egawa, Shinichi ; Ishida, Masaharu ; Ottomo, Shigeru ; Unno, Michiaki ; Motoi, Fuyuhiko ; Wolfgang, Christopher L. ; Edil, Barish H. ; Cameron, John L. ; Eshleman, James R. ; Schulick, Richard D. ; Maitra, Anirban ; Hruban, Ralph H. / Clinicopathological characteristics and molecular analyses of multifocal intraductal papillary mucinous neoplasms of the pancreas. In: Annals of Surgery. 2012 ; Vol. 255, No. 2. pp. 326-333.
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abstract = "Objective: To examine the clinicopathologic features and clonal relationship of multifocal intraductal papillary mucinous neoplasms (IPMNs) of the pancreas. Background: Intraductal papillary mucinous neoplasms are increasingly diagnosed cystic precursor lesions of pancreatic cancer. Intraductal papillary mucinous neoplasms can be multifocal and a potential cause of recurrence after partial pancreatectomy. Methods: Thirty four patients with histologically documented multifocal IPMNs were collected and their clinicopathologic features catalogued. In addition, thirty multifocal IPMNs arising in 13 patients from 3 hospitals were subjected to laser microdissection followed by KRAS pyrosequencing and loss of heterozygosity (LOH) analysis on chromosomes 6q and 17p. Finally, we sought to assess the clonal relationships among multifocal IPMNs. Results: We identified 34 patients with histologically documented multifocal IPMNs. Synchronous IPMNs were present in 29 patients (85{\%}), whereas 5 (15{\%}) developed clinically significant metachronous IPMNs. Six patients (18{\%}) had a history of familial pancreatic cancer. A majority of multifocal IPMNs (86{\%} synchronous, 100{\%} metachronous) were composed of branch duct lesions, and typically demonstrated a gastric-foveolar subtype epithelium with low or intermediate grades of dysplasia. Three synchronous IPMNs (10{\%}) had an associated invasive cancer. Molecular analysis of multiple IPMNs from 13 patients demonstrated nonoverlapping KRAS gene mutations in 8 patients (62{\%}) and discordant LOH profiles in 7 patients (54{\%}); independent genetic alterations were established in 9 of the 13 patients (69{\%}). Conclusions: The majority of multifocal IPMNs arise independently and exhibit a gastric-foveolar subtype, with low to intermediate dysplasia. These findings underscore the importance of life-long follow-up after resection for an IPMN.",
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AU - Matthaei, Hanno

AU - Norris, Alexis L.

AU - Tsiatis, Athanasios C.

AU - Olino, Kelly

AU - Hong, Seung Mo

AU - Dal Molin, Marco

AU - Goggins, Michael G.

AU - Canto, Marcia

AU - Horton, Karen M.

AU - Jackson, Keith D.

AU - Capelli, Paola

AU - Zamboni, Giuseppe

AU - Bortesi, Laura

AU - Furukawa, Toru

AU - Egawa, Shinichi

AU - Ishida, Masaharu

AU - Ottomo, Shigeru

AU - Unno, Michiaki

AU - Motoi, Fuyuhiko

AU - Wolfgang, Christopher L.

AU - Edil, Barish H.

AU - Cameron, John L.

AU - Eshleman, James R.

AU - Schulick, Richard D.

AU - Maitra, Anirban

AU - Hruban, Ralph H.

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N2 - Objective: To examine the clinicopathologic features and clonal relationship of multifocal intraductal papillary mucinous neoplasms (IPMNs) of the pancreas. Background: Intraductal papillary mucinous neoplasms are increasingly diagnosed cystic precursor lesions of pancreatic cancer. Intraductal papillary mucinous neoplasms can be multifocal and a potential cause of recurrence after partial pancreatectomy. Methods: Thirty four patients with histologically documented multifocal IPMNs were collected and their clinicopathologic features catalogued. In addition, thirty multifocal IPMNs arising in 13 patients from 3 hospitals were subjected to laser microdissection followed by KRAS pyrosequencing and loss of heterozygosity (LOH) analysis on chromosomes 6q and 17p. Finally, we sought to assess the clonal relationships among multifocal IPMNs. Results: We identified 34 patients with histologically documented multifocal IPMNs. Synchronous IPMNs were present in 29 patients (85%), whereas 5 (15%) developed clinically significant metachronous IPMNs. Six patients (18%) had a history of familial pancreatic cancer. A majority of multifocal IPMNs (86% synchronous, 100% metachronous) were composed of branch duct lesions, and typically demonstrated a gastric-foveolar subtype epithelium with low or intermediate grades of dysplasia. Three synchronous IPMNs (10%) had an associated invasive cancer. Molecular analysis of multiple IPMNs from 13 patients demonstrated nonoverlapping KRAS gene mutations in 8 patients (62%) and discordant LOH profiles in 7 patients (54%); independent genetic alterations were established in 9 of the 13 patients (69%). Conclusions: The majority of multifocal IPMNs arise independently and exhibit a gastric-foveolar subtype, with low to intermediate dysplasia. These findings underscore the importance of life-long follow-up after resection for an IPMN.

AB - Objective: To examine the clinicopathologic features and clonal relationship of multifocal intraductal papillary mucinous neoplasms (IPMNs) of the pancreas. Background: Intraductal papillary mucinous neoplasms are increasingly diagnosed cystic precursor lesions of pancreatic cancer. Intraductal papillary mucinous neoplasms can be multifocal and a potential cause of recurrence after partial pancreatectomy. Methods: Thirty four patients with histologically documented multifocal IPMNs were collected and their clinicopathologic features catalogued. In addition, thirty multifocal IPMNs arising in 13 patients from 3 hospitals were subjected to laser microdissection followed by KRAS pyrosequencing and loss of heterozygosity (LOH) analysis on chromosomes 6q and 17p. Finally, we sought to assess the clonal relationships among multifocal IPMNs. Results: We identified 34 patients with histologically documented multifocal IPMNs. Synchronous IPMNs were present in 29 patients (85%), whereas 5 (15%) developed clinically significant metachronous IPMNs. Six patients (18%) had a history of familial pancreatic cancer. A majority of multifocal IPMNs (86% synchronous, 100% metachronous) were composed of branch duct lesions, and typically demonstrated a gastric-foveolar subtype epithelium with low or intermediate grades of dysplasia. Three synchronous IPMNs (10%) had an associated invasive cancer. Molecular analysis of multiple IPMNs from 13 patients demonstrated nonoverlapping KRAS gene mutations in 8 patients (62%) and discordant LOH profiles in 7 patients (54%); independent genetic alterations were established in 9 of the 13 patients (69%). Conclusions: The majority of multifocal IPMNs arise independently and exhibit a gastric-foveolar subtype, with low to intermediate dysplasia. These findings underscore the importance of life-long follow-up after resection for an IPMN.

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