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Intraductal Papillary Mucinous Neoplasms of the Pancreas With Distinct Pancreatic Ductal Adenocarcinomas Are Frequently of Gastric Subtype

Ideno, Noboru MD*; Ohtsuka, Takao MD, PhD*; Kono, Hiroshi MD*; Fujiwara, Kenji MD*; Oda, Yasunori MD; Aishima, Shinichi MD, PhD; Ito, Tetsuhide MD, PhD; Ishigami, Kousei MD, PhD§; Tokunaga, Shoji PhD; Ohuchida, Kenoki MD, PhD*; Takahata, Shunichi MD, PhD*; Nakamura, Masafumi MD, PhD; Mizumoto, Kazuhiro MD, PhD*; Tanaka, Masao MD, PhD, FACS*

doi: 10.1097/SLA.0b013e31828cd008
Original Articles

Objective: To identify a high-risk group of patients with pancreatic ductal adenocarcinoma (PDAC), independently arising in the pancreas with intraductal papillary mucinous neoplasm (IPMN), using histopathologic subtypes.

Background: Pathologic features of IPMN with distinct PDAC, including histopathologic subtypes of IPMN and PDAC phenotypes, have not been well characterized. Mucin expression patterns and the mutational status of GNAS and KRAS are useful to explore the relationship between these 2 lesion types.

Methods: Clinicopathologic data of 179 resected IPMNs and 180 resected PDACs without IPMNs as a control group were reviewed. IPMNs were classified into 4 grades (low-grade, intermediate-grade, high-grade dysplasia, and an associated invasive carcinoma) and 4 subtypes (gastric, intestinal, pancreatobiliary, and oncocytic). The expression of MUC1, MUC2, MUC5AC, MUC6, and CDX2 was investigated by immunohistochemistry in IPMNs and PDACs with and without IPMNs. The mutational status of GNAS and KRAS was evaluated by cycle sequencing in PDACs and pre-/coexisting IPMNs.

Results: Twenty-six synchronous or metachronous PDACs were identified in 20 patients (11.2%) with IPMNs. Occurrence of concomitant PDACs was more frequently observed in gastric-type IPMNs (18/110, 16.4%) compared with intestinal (1/49, 2.0%), pancreatobiliary (1/17, 5.9%), or oncocytic-type (0/3, 0%) (P = 0.047). Both PDACs with and without IPMNs were frequently positive for MUC1, MUC5AC, and MUC6 expression, as assessed by immunohistochemistry, but were negative for MUC2 and CDX2. The mucin-staining patterns were similar to those of invasive tubular adenocarcinoma arising from gastric-type IPMNs. Mutation of GNAS within codon 201 was not detected in PDACs and gastric-type IPMNs, whereas most of these exhibited KRAS mutations. However, the R201H GNAS mutation was detected in 1 intestinal-type IPMN with distinct PDAC.

Conclusions: Mucin expression patterns demonstrate that PDAC without GNAS mutations of an aggressive phenotype frequently arise in the pancreas with benign gastric-type IPMN in the absence of GNAS mutations.

Supplemental Digital Content is Available in the Text.A review of the histopathologic grade and subtypes of 179 intraductal papillary mucinous neoplasms of the pancreas revealed that those with distinct pancreatic ductal adenocarcinomas represented a high-risk group. This study demonstrated that concomitant pancreatic ductal adenocarcinomas are highly associated with gastric-type intraductal papillary mucinous neoplasms.

Departments of *Surgery and Oncology,

Anatomic Pathology,

Medicine and Bioregulatory Science, and,

§Clinical Radiology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan,

Medical Information Center, Kyushu University Hospital, Fukuoka, Japan

Department of Gastrointestinal Surgery, Kawasaki Medical School, Okayama, Japan.

Reprints: Masao Tanaka, MD, PhD, FACS, Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan. E-mail: masaotan@med.kyushu-u.ac.jp.

Supported in part by a Grant-in-Aid from the Ministry of Education, Culture, Sports, Science and Technology of Japan.

Disclosure: The authors declare no conflicts of interest.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Web site (www.annalsofsurgery.com).

© 2013 by Lippincott Williams & Wilkins.