Intraductal Papillary Mucinous Adenoma Research Articles

Pancreatic Intraductal Papillary Mucinous Neoplasms: Role of CT in Predicting Pathologic Subtypes

The objective of our study was to evaluate whether CT can be used to predict the pathologic subtypes of pancreatic intraductal papillary mucinous neoplasms (IPMNs). Three radiologists, blinded to the pathologic IPMN subtype, retrospectively and independently reviewed the preoperative CT scans of 38 patients with surgically resected pancreatic IPMN: 11 intraductal papillary mucinous adenomas, 11 intraductal papillary mucinous carcinomas, and 16 intraductal papillary mucinous carcinomas with invasion. The patients, 16 women and 22 men, ranged in age from 38 to 80 years (mean age, 64.3 years). CT findings were correlated with each pathologic subtype using the chi-square (two-sided) test and analysis of variance. Interobserver agreement of the CT diagnosis of pathologic subtype and agreement between the CT diagnosis and pathologic subtype were also studied (kappa statistic). Predominant main pancreatic duct (MPD) involvement (p = 0.04) and a wide (> 1 cm) connection of a side-branch lesion with the MPD (p = 0.03) correlated with intraductal papillary mucinous carcinoma with invasion. Tumor size, MPD diameter, number of tumors per patient, number of pseudoseptations per tumor, common bile duct dilatation, enlarged lymph nodes, intraductal calcifications, papillary bulging, and presence and size of a solid mass yielded no statistically significant relationship with pathologic subtype. Both interobserver agreement of CT diagnosis (range, 0.004-0.359) and agreement between CT diagnosis and pathologic subtype (range, 0.046-0.317) ranged from slight to fair. Prediction of the pathologic subtypes of pancreatic IPMNs by CT is limited. Predominant MPD involvement and a wide connection of a side-branch lesion with the MPD are the only CT findings that can be used to predict the pathologic subtype of pancreatic IPMN.

Synchronous and Metachronous Extrapancreatic Malignant Neoplasms in Patients with Intraductal Papillary-Mucinous Neoplasm of the Pancreas

Background/Aims: Patients with intraductal papillary-mucinous neoplasm (IPMN) of the pancreas are likely to have a better prognosis than those with conventional pancreatic ductal adenocarcinoma. Recently there have been some reports on extrapancreatic malignant neoplasms (EPM) occurring in patients with IPMN. The purpose of this study was to discover the characteristic features of IPMN with EPM compared with IPMN without EPM. Methods: 61 patients with IPMN who underwent surgery at Tohoku University Hospital between 1988 and 2006 were retrospectively analyzed. Results: The 61 patients with IPMN in this study comprised 25 with intraductal papillary-mucinous adenomas (IPMA) and 36 with intraductal papillary-mucinous carcinomas (IPMC) including 6 with invasive carcinomas. Synchronous and metachronous EPM were observed in 15 out of the 61 patients (24.6%). Three of these patients, including 2 with IPMA and 1 with invasive carcinoma associated with IPMC, died of the EPM. None of the features, including sex, age, smoking, family history, macroscopic types (main duct type or branch duct type), histological types (gastric, intestinal, pancreatobiliary or oncocytic), and aberrant expression of molecules including CDKN2A, TP53, SMAD4 and DUSP6, except for the histological diagnoses were associated with the occurrence of EPM, i.e., the EPM occurred more often in patients with IPMA (10 out of 25) than in those with IPMC (5 out of 36) in our series (p = 0.0199 by the χ2 test, p = 0.0330 by Fisher's exact probability test, p = 0.0422 by Yates' correction). Conclusion: Patients with IPMA were more likely to have EPM than those with IPMC. Patients with IPMA are usually expected to have a fair prognosis but EPM could be fatal in some of them, so it must be noted during follow-up.

Laparoscopic spleen-preserving distal pancreatectomy with conservation of the splenic artery and vein: Report of three cases

Between March 2003 and March 2007, three patients with benign pancreatic tumors underwent a planned laparoscopic spleen-preserving distal pancreatectomy with conservation of the splenic artery and vein. Four trocars were placed, and an endoscopic linear stapler was used to transect of the pancreas. The perioperative data and surgical outcomes were examined. This procedure was successfully completed in three patients. The mean operative time was 158.3 min, with mean blood loss of 14.7 ml. The postoperative pathological diagnoses included one insulinoma, one solid pseudopapillary tumor, and one intraductal papillary-mucinous adenoma. The mean size of the tumors was 29.3 mm. Oral intake was initiated on day 1.7, and the length of postoperative hospital stay was 8.7 days on average. No morbidity or mortality was observed. A laparoscopic spleen-preserving distal pancreatectomy with conservation of the splenic artery and vein is a safe and feasible treatment option without compromising the splenic function for benign or borderline malignant tumors in the distal pancreas.

Indikationen zur chirurgischen Therapie benigner Pankreastumoren

Benign pancreatic tumors should undergo surgical resection when they are symptomatic or--in the case of incidental discovery--bear malignant potential. This is the case for the majority of benign pancreatic tumors, especially for intraductal papillary mucinous neoplasms or mucinous cystic adenomas. In addition, resection is indicated for all tumors where preoperative diagnostic fails to provide an exact classification.Several different operative techniques are available. The treatment of choice depends on the localization of the tumor, its size and on whether there is evidence of malignant transformation. Partial duodenopancreatectomy is the oncological treatment of choice for tumors of the pancreatic head whereas for tumors of the pancreatic tail a left-sided pancreatectomy is appropriate. Middle pancreatectomy or duodenum-preserving resection of the pancreatic head is not a radical oncologic procedure. They should only be performed in cases of tumors without malignant potential.

偶発的に発見され初期像からの経過を観察し得た膵頭部膵管内乳頭粘液性腺腫の1切除例

偶発的に発見され初期像からの経過を観察し得た膵頭部膵管内乳頭粘液性腺腫の1切除例

Growth process of small pancreatic carcinoma: A case report with imaging observation for 22 months

This report describes serial observations of the growth process of a small invasive ductal carcinoma (IDC) of the pancreas from imaging studies. Histopathological studies showed IDC with macroscopic retention cysts proximal to an intraductal papillary-mucinous adenoma with mild atypia of the branch duct type in the pancreatic body, with no relation between the two lesions. IDC was demonstrated as an extremely low-echoic mass resembling a cyst with an unclear margin on the initial endoscopic ultrasonography. We misinterpreted the low-echoic mass as a benign intraductal mucinous-papillary neoplasm (IPMN) based on findings of other imaging studies, and the patient was followed-up. The mass increased from 7 mm to 13 mm in diameter over 22 mo, and remained smaller than 10 mm in diameter for about 420 d. The tumor volume doubling time was 252 d. The Ki67 labeling index was 15.9%, similar to that described in previous reports. Hence, IDC may grow slowly while remaining small.

Main-duct intraductal papillary mucinous adenoma of the pancreas with a large mural nodule

Intraductal papillary mucinous neoplasm (IPMN) is an increasingly recognized entity representing a spectrum of benign and malignant neoplasms of the pancreas. Preoperative distinction between benign and malignant IPMNs remains difficult. Reported predictive factors for malignancy are size of the main pancreatic duct, cystic neoplasm, and mural nodule. We report herein the case of a 50-year-old woman in whom a large mural nodule (30 mm) in the dilated main pancreatic duct (16 mm in diameter) was detected by ultrasonography, computed tomography, and endoscopic retrograde cholangiopancreatography. Because the large mural nodule and dilatation of the main pancreatic duct were also detected by endoscopic ultrasonography (EUS) and intraductal ultrasonography (IDUS), the main-duct IPMN was considered to have malignant potential. Thus, pylorus-preserving pancreaticoduodenectomy with lymph node dissection was performed. The resected intraductal tumor appeared polypoid with a broad stalk and comprised a proliferation of mucin-containing columnar epithelial cells with papillary structures without malignant features. The final diagnosis was intraductal papillary mucinous adenoma of the pancreas. The size of the mural nodule and the final diagnosis in this case suggest that the introduction of a novel molecular-biological approach might be necessary for the precise preoperative diagnosis of main-duct IPMN and adequate surgical treatment.

Intraductal papillary-mucinous adenocarcinoma in the remnant pancreas after pancreatoduodenectomy for cancer of Vater's papilla associated with intraductal papillary-mucinous adenoma

A 72-year-old woman, who had undergone pylorus-preserving pancreatoduodenectomy 3 years before for cancer of Vater's papilla associated with a branch-type intraductal papillary-mucinous adenoma (IPMA), developed dilatation of the main duct and a nodular lesion in the remnant pancreas. Total pancreatectomy was performed, which revealed that the lesion was intraductal papillary-mucinous adenocarcinoma (IPMC) with minimal invasion, suggesting the metachronous multicentric occurrence of this intraductal papillary-mucinous neoplasm (IPMN). Because there were no malignant cells at the pancreaticojejunostomy, and because the histological appearance of the main-duct IPMC was different from that of the IPMA in the primary specimen, the main-duct IPMC was thought to be of different origin from the IPMA. These findings suggest that careful surveillance of the gastrointestinal tract and careful follow up are necessary for IPMN, because an IPMN could be associated with other gastrointestinal tract malignancies.

Surgical Outcome of Intraductal Papillary Mucinous Neoplasms of the Pancreas

An increasing number of intraductal papillary mucinous neoplasms of the pancreas have been reported in recent years. However, the clinicopathologic features and surgical outcome of this neoplasm are not fully understood because of the limited number of cases. The objective of this study is to clarify the clinicopathologic features of intraductal papillary mucinous neoplasm of the pancreas and evaluate prognostic factors influencing survival. Eighty-two patients with intraductal papillary mucinous neoplasm undergoing surgical resection at the National Cancer Center Hospital East between April 1994 and October 2006 were retrospectively analyzed. There were 31 patients with adenoma and 51 patients with carcinoma. Carcinomas were subdivided into noninvasive carcinoma (n = 14), minimally invasive carcinoma (n = 6), and invasive carcinoma (n = 31). The postoperative mortality rate was 0%. The 5-year survival rate for patients with intraductal papillary mucinous adenoma, noninvasive carcinoma, minimally invasive carcinoma, and invasive carcinoma was 80%, 78%, 83%, and 24%, respectively. Regardless of the margin status, no patient with adenoma developed recurrent disease. There were significant differences in survival between noninvasive carcinoma and invasive carcinoma (P = .016) and between minimally invasive carcinoma and invasive carcinoma (P = .030). Multivariate analysis confirmed that lymph node metastasis (P = .004) and age (P = .015) were significant prognostic factors after surgical resection of these neoplasms. Patients with intraductal papillary mucinous adenoma, noninvasive carcinoma, and minimally invasive carcinoma showed favorable survival. In contrast, invasive intraductal papillary mucinous carcinoma was associated with poor survival regardless of the margin status. Nodal involvement was the strongest predictor of poor survival.

The Role of the DNA Damage Checkpoint Pathway in Intraductal Papillary Mucinous Neoplasms of the Pancreas

Intraductal papillary mucinous neoplasms (IPMN) are known to show a transition from adenoma to carcinoma accompanied by several molecular abnormalities. ATM-Chk2-p53 DNA damage checkpoint activation, which is involved in prevention of the progression of several tumors, was analyzed to evaluate the role of the DNA damage checkpoint in the progression of IPMNs. One hundred and twenty-eight IPMNs were classified into four groups (intraductal papillary mucinous adenoma, borderline IPMN, noninvasive intraductal papillary mucinous carcinoma, and invasive intraductal papillary mucinous carcinoma) and stained immunohistochemically using antibody for Thr(68)-phosphorylated Chk2. Expression of ATM, Chk2, and p21(WAF1) and accumulation of p53 were also analyzed. Chk2 phosphorylation was shown in all adenomas and showed a significant decreasing trend with the progression of atypia (P < 0.0001 by the Cochran-Armitage test for trend). Expression of p21(WAF1) also exhibited a decreasing tendency (P < 0.0001), reflecting DNA damage checkpoint inactivation. p53 accumulation was mostly detected in malignant IPMNs. It was suggested that the DNA damage checkpoint provides a selective pressure for p53 mutation. Our findings indicate that DNA damage checkpoint activation occurs in the early stage of IPMNs and prevents their progression. It is suggested that disturbance of the DNA damage checkpoint pathway due to Chk2 inactivation or p53 mutation contributes to the carcinogenesis of IPMNs.

Nuclear Expression of STAT5 in Intraductal Papillary Mucinous Neoplasms of the Pancreas

Intraductal papillary mucinous neoplasms (IPMNs) are noninvasive lesions of the pancreas and classified as intraductal papillary mucinous adenomas (IPMAs), borderline IPMNs, and intraductal papillary mucinous carcinomas (IPMCs). Expression patterns of the specific genes alter during IPMN progression. Based on the evidence that signal transducers and activators of transcription (STAT) 5 play important roles in tumor development, we tested STAT5 expression in IPMAs, borderline IPMNs, and IPMCs by immunohistochemical method. STAT5 frequently expressed in the nuclei of tumor cells of borderline IPMNs or IPMCs but was not observed in those of IPMAs. Nuclear expression of STAT5 protein correlated to the Ki-67 labeling index of the examined IPMNs. STAT5 protein could contribute to the progression and proliferation of IPMNs.

A Case of Pancreatic Heterotopy of Duodenal Wall, Intraductal Papillary Mucinous Tumor and Intraepithelial Neoplasm of Pancreas, Papillary Carcinoma of Kidney in a Single Patient

We report a case of the contemporaneous presence of two histologically different pancreatic neoplasms, one renal cancer and one embryogenic duodenal anomaly in a single patient. A 66-year-old man underwent ultrasound examination because of urinary disorders; a solid neoformation within the inferior pole of the left kidney was observed. Computed tomography confirmed the renal lesion, but also a heterogeneous mass within the pancreatic head appeared without bile ducts dilatation. Abdominal magnetic resonance revealed a multiloculated cystic component of the pancreatic mass. A second CT scan confirmed the renal and biliary findings, but it revealed a modest enlargement of the pancreatic asymptomatic mass. A resection of the left kidney inferior pole and a pylorus-preserving pancreaticoduodenectomy were performed. Histopathologic analysis of the surgical specimen revealed mild differentiated papillary renal carcinoma, intraductal papillary mucinous adenoma of the pancreatic head, foci of intraepithelial pancreatic neoplasm and pancreatic heterotopy of duodenal muscular and submucosal layers. The coexistence of several primaries and anomalies in one patient led us to suppose a genetic predisposition to different lesions, even in the absence of known familial genetic syndromes. The study of such cases may help to improve the investigation of molecular correlations and etiological factors of different solid tumors. Nowadays, surgery is the only effective cure.

Intraductal papillary mucinous neoplasms of the pancreas: an analysis of protein expression and clinical features

The molecular pathology of intraductal papillary mucinous neoplasms (IPMNs) of the pancreas has not been well characterized, and there are no reliable markers to predict the presence of associated invasive carcinoma in patients with IPMNs. We investigated the clinicopathologic characteristics of 37 IPMNs and the immunohistochemical findings of these tumors to investigate the malignancy of IPMNs. Between May 1992 and September 2003, 37 patients with IPMNs, 24 with adenoma and 13 with carcinoma, underwent pancreatic resections at Sapporo Medical University Hospital, Japan. In tumor specimens from these patients, we immunohistochemically analyzed the expression of p53 protein, proliferating-cell nuclear antigen (PCNA), vascular endothelial growth factor (VEGF), matrix metalloproteinase-7 (MMP-7), and E-cadherin. Clinical features and follow-up after resection were recorded. Aberrant expression of the proteins examined was frequently observed. Namely, there were significant differences in the expression of MMP-7 according to clinicopathological characteristics. Positive expression of MMP-7 was found in all of nine patients with infiltrating ductal pancreatic adenocarcinoma (IDC) and in all of seven patients with invasive intraductal papillary mucinous adenocarcinoma (IC-IPMC); however, 33.3% of patients with noninvasive IPMA, 58.3% of patients with intraductal papillary mucinous adenoma (IPMA), and all normal pancreatic tissues were negative for MMP-7; differences which were statistically significant (P < 0.05). Our current results indicate that MMP-7 may play a significant role in the progression of noninvasive to invasive IPMC.

Human pancreatic mucinous cystadenoma is characterized by distinct mucin, cytokeratin and CD10 expression compared with intraductal papillary‐mucinous adenoma

To examine cytokeratin, epithelial glycoprotein (mucin) and glycoprotein CD10 expression in benign mucinous cystdenomas (MCAs) in comparison with intraductal papillary mucinous adenomas (IPMAs). Thirty MCAs of the pancreas were analysed for immunohistochemical expression of cytokeratin (CK) 7, CK20, MUC1, MUC2, MUC5AC and CD10 and were compared with 16 IPMAs. CK7 was expressed in all neoplasms. CK20 was significantly more frequent in MCAs compared with IPMAs (56.66% versus 18.75%, P = 0.027). MUC1 was more frequent in MCAs (40% versus 12.5%, P = 0.0915), whereas MUC5AC was significantly less frequent in MCAs (33.33% versus 100%). MUC2 was expressed in goblet cells of seven MCAs. In MCAs, CD10 was observed both in epithelial cells and in the ovarian-type stromal cells (24/30). Epithelial expression of CD10 was significantly lower in IPMAs (66.66% versus 6.25%, p = 0.0001). MCA is characterized by a significantly greater frequency of expression of CK20 and CD10 when compared with IPMA, which preferentially expresses MUC5AC.

Inferior branch–preserving superior head resection of the pancreas with gastric wall–covering method for intraductal papillary mucinous adenoma

Intraductal papillary mucinous neoplasm (IPMN) of the pancreas showed significantly less aggressive pathologic features compared with common pancreatic cancer. Therefore, several organ-preserving techniques, including duodenum-preserving pancreatic head resection, have been advocated in surgical procedures for IPMN. We describe a surgical technique of superior head resection of the pancreas with inferior branch preservation followed by a gastric wall–covering method for the prevention of pancreatic leakage in patients with IPMN of the pancreas head.

Endoscopic naso-pancreatic stent-guided single-branch resection of the pancreas for multiple intraductal papillary mucinous adenomas

In benign or low-grade malignant pancreatic tumors, complete removal of the lesion is sufficient for a cure, and thus minimal resection techniques with preservation of the pancreatic functional reserve have advantages over more extended pancreatic resections. However, a high incidence of postoperative pancreatic fistula in such procedures has been reported. Moreover, branch-type intraductal papillary mucinous neoplasms of the pancreas tend to locate in the head of the pancreas, and show less malignant potential. We describe an endoscopic naso-pancreatic stent-guided single-branch resection of the pancreas for branch-type multiple intraductal papillary mucinous adenomas, along with a gastric wall-covering method for the prevention of pancreatic leakage.

Intraductal papillary mucinous adenoma of the pancreas presenting with lobular panniculitis

Sir, Recently a 67-year-old woman presented at our dermatological department with relapsing subcutaneous tender nodules on both lower legs with yellow fluid discharge for 10 weeks (Fig. 1). Histology of a skin biopsy revealed a pancreatic panniculitis with pathognomic “ghost cells,” calcified anucleated adipocytes with thickened walls. Abdominal examination was without pathological findings. A pancreatic panniculitis develops in 2–3% of patients with pancreatic diseases. Mainly acute and chronic pancreatitis causes a pancreatic panniculitis; less commonly, a pancreatic carcinoma is detected. Further associations with pancreas divisum, pancreatic pseudocysts, vaculopancreatic fistula and pancreatitis secondary to sulindac intake are described [1]. For evaluation of the pancreas, contrast-enhanced multi-slice computed tomography, magnetic resonance cholangiopancreatography (MRCP) and endoscopic retrograde cholangiopancreatography (ERCP) were performed, which showed typical features of intraductal papillary mucinous neoplasms (IPMN) such as radiographically visible duct dilatation, extensive production of mucus, bulging ampulla seen in ERCP and the formation of intraductal papillary structures causing filling defects in ERCP and signal extinction on MRCP (Fig. 2). Presenting symptoms of IPMNs include abdominal pain, weight loss, jaundice, acute pancreatitis and deterioration of diabetes [2], while about one third of the patients are asymptomatic. So far, only one case of an association of IPMN with pancreatic panniculitis has been reported [3]. The pathophysiology behind the association of pancreatic disorders and the development of lobular panniculitis is still unknown, but possibly pancreatic enzymes such as trypsin elevate the permeability of the microcirculation, and lipase or amylase then cause the subcutaneous fat necrosis [3]. IPMNs of the pancreas are usually first suspected by CT scans, which show the dilatation of pancreatic ducts and filling defects after i.v. contrast caused by gaping papillae or mucus in the ducts. ERCP used to be the gold standard for the evaluation of IPMNs, showing the characteristic bulging of the ampulla and the extensive production of mucus. Now, MRI is considered superior to ERCP, especially in showing the full extent of duct involvement, size of the pancreatic mass and diagnosing associated pathologies such as metastatic spread or inflammatory changes. According to the WHO, IPMNs are classified as adenoma, borderline, carcinoma in situ and invasive carcinoma. In this case, the histology revealed an adenoma. Patients with malignant IPMNs were found to be 5–6 years older than patients with benign IPMNs, supporting the theory of oncogenic transformation [2]. With tumor progression, the life expectancy for 5 years decreases markedly, and once the disease has reached the stage of lymph node involvement, the survival rate is very poor. As performed in this case, the treatment of choice is a partial pancreatectomy with frozen section N. Gahr (*) . N. Ghanem Department of Diagnostic Radiology of the Hospital of the Albert-LudwigsUniversity Freiburg, Hugstetter Strasse 55, 79106 Freiburg, Germany e-mail: gahr@mrs1.ukl.uni-freiburg.de Tel.: +49-761-2703802 Fax: +49-761-2703956

Intraductal Tubular Adenoma of the Pancreas, Pyloric Gland Type

The intraductal tubular adenoma (ITA), pyloric gland type, of the pancreas is an uncommon benign tumor, akin to the pyloric gland type adenoma of the gallbladder. We report 6 cases of ITA of the pancreas: 3 male and 3 female aged 50 to 79 years (mean, 63.5 years; median, 65 years); all were examined clinicopathologically. Four patients showed no symptoms, but appetite loss and/or general fatigue presented in two. Grossly, all tumors formed a localized polypoid mass protruding into the lumen of the dilated pancreatic duct. Five of the six tumors were found within the main duct, and the other arose within the branch duct of the pancreas. Microscopically, the tumors were composed of closely packed tubular glands resembling pyloric type glands. They were lined by columnar or cuboidal epithelial cells with foci of mild to moderate dysplastic change. In 2 cases, the adjacent pancreas showed foci of intraductal papillary-mucinous adenoma. Histochemically, the tumors largely showed neutral mucin with a lesser amount of acidic mucin made up mainly of sialomucin. Endocrine cells were found in five tumors. Immunohistochemically, all tumors were labeled with M-GGMC-1 and MUC6, whereas MUC1 and MUC2 stains were negative. Pepsinogen II was positive in 5 tumors; thus, the results displayed a pattern of differentiation similar to those of ordinary gastric pyloric or metaplastic pyloric glands. DPC4 expression was maintained in all tumors and p53-positive nuclei were hardly encountered. All patients are alive with no evidence of disease 3 to 10.5 years after surgical resection.

Intraductal papillary-mucinous adenoma developed in the ventral pancreas in a patient with pancreas divisum

A 34-year-old man was admitted to our hospital with the chief complaints of back pain and epigastralgia. The physical examinations on admission disclosed no abdominal tumor. The serum concentration of total bilirubin was 1.4 mg/dl. The serum elastase-1 level was elevated to 526 ng/dl. Computed tomography showed a cystic lesion, 1 cm in diameter, in the head of the pancreas, without dilatation of the main pancreatic duct. Endoscopic retrograde cholangiopancreatography via the papilla of Vater and the accessory papilla revealed an enlarged ventral pancreatic duct and pancreas divisum. The preoperative diagnosis was mucin-producing pancreatic tumor in the ventral pancreas of a patient with pancreas divisum. A pylorus-preserving pancreatoduodenectomy was performed. The gross findings of the cut surface of the resected specimen disclosed mural nodules in the dilated duct of the ventral pancreas. A histological examination of the mural nodules in the ventral pancreas revealed mucin and intraductal papillary adenoma. Benign tumors associated with pancreas divisum are rare; to the best of our knowledge, only three cases have been reported. Although in these three patients the tumor developed in the dorsal pancreas, the tumor developed in the ventral pancreas in our patient.

Marker profile of pancreatic intraepithelial neoplasia (PanIN) in intraductal papillary mucinous neoplasms of the pancreas: by-standers or forerunners?

Anti-tumor immunity changes over the course of tumor progression; it is not clear how or when the developing tumor overcomes immune surveillance. Intraductal papillary mucinous neoplasm (IPMN) is an intraepithelial precursor lesion of pancreatic cancer that progresses from adenoma to carcinoma. We investigated when and how the human anti-tumor immune reaction changes during pancreatic tumor development.Using immunohistochemical analysis of cells isolated from patients with IPMN, the numbers of tumor-infiltrating lymphocytes and dendritic cells and the maturation state of dendritic cells in the regional lymph nodes were investigated during tumor progression. Gene expression profiles were compared among epithelial neoplastic cells at each stage of tumor development. Biological functions of the selected gene products were analyzed using syngeneic mouse models.The anti-tumor immune reaction changed from an immune response to immune tolerance between the stages of intraductal papillary mucinous adenoma (IPMA) and intraductal papillary mucinous carcinoma (IPMC). Chemokine (C-X-C motif) ligand 17 (CXCL17) and intercellular adhesion molecule 2 (ICAM2) were involved in immune surveillance during tumor development—their expression levels were up-regulated exclusively in IPMA and disappeared from IPMC. CXCL17 and ICAM2 induced infiltration and accumulation of the tumor epithelial layer by immature myeloid dendritic cells. This was followed by a cellular immune reaction and ICAM2 simultaneously promoted the susceptibility of the tumor cells to cytotoxic T-cell−mediated cytolysis. These processes had a synergistic effect to increase the anti-tumor immune response.Immune surveillance occurs during the early intraepithelial stages of human pancreatic carcinogenesis and is mediated by expression of CXCL17 and ICAM2.