Intraductal Papillary Mucinous Neoplasms of the Pancreas: An Increasingly Recognized Clinicopathologic Entity

Abstract

ObjectiveTo assess the authors' experience with intraductal papillary mucinous neoplasms of the pancreas (IPMNs). Summary Background DataIntraductal papillary mucinous neoplasms of the pancreas are being recognized with increasing frequency. MethodsAll patients who underwent pancreatic resection for an IPMN at the Johns Hopkins Hospital between January 1987 and December 2000 were studied. The data were compared with those of 702 concurrent patients with infiltrating ductal adenocarcinoma of the pancreas not associated with an IPMN resected by pancreaticoduodenectomy. ResultsIn the 13-year time period, 60 patients underwent pancreatic resection for IPMNs, with 40 patients undergoing resection in the past 3 years. Mean age at presentation was 67.4 Ϯ 1.4 years. The most common presenting symptom in patients with IPMNs was abdominal pain (59%). Most IPMNs were in the head of the pancreas or diffusely involved the gland, with 70% being resected via pancreaticoduodenectomy, 22% via total pancreatectomy, and 8% via distal pancreatectomy. Twenty-two patients (37%) had IPMNs with an associated infiltrating adenocarcinoma. In a subset of IPMNs immunohistochemically stained for the Dpc4 protein (n ϭ 50), all of the intraductal or noninvasive components strongly expressed Dpc4, whereas 84% of associated infiltrating cancers expressed Dpc4. The 5-year survival rate for all patients with IPMNs (n ϭ 60) was 57%. ConclusionIntraductal papillary mucinous neoplasms represent a distinct clinicopathologic entity being recognized with increasing frequency. IPMNs are clinically, histologically, and genetically disparate from pancreatic ductal adenocarcinomas. The distinct clinical features, the presumably long in situ or noninvasive phase, and the good long-term survival of patients with IPMNs offer a unique opportunity for early diagnosis, curative resection, and further studies of the molecular genetics and natural history of these unusual neoplasms.

Clinicopathologic and Molecular Features of Pancreatic Adenocarcinoma Associated with Peutz-Jeghers Syndrome

“…Pancreatic tumors in PJS patients are generally diagnosed at an early age (mean 46.3 year-old), as compared to patients with sporadic pancreatic ductal adenocarcinomas (mean 64.6 year-old). 49 The early age onset is consistent with the notion that PJS predisposes to pancreatic malignancies. There is a strong male preponderance for PJS patients with pancreatic tumors (75%), in contrast to patients with sporadic pancreatic ductal adenocarcinomas (54%).…”

“…There is a strong male preponderance for PJS patients with pancreatic tumors (75%), in contrast to patients with sporadic pancreatic ductal adenocarcinomas (54%). 49 Considering the patient's…”

Stromal responses to carcinomas of the pancreas: Juxtatumoral gene expression conforms to the infiltrating pattern and not the biologic subtype

“…Intraductal papillary mucinous neoplasms (IPMNs) are one such distinct neoplasm that arises within the main pancreatic duct system, in contrast to conventional ductal adenocarcinomas that are believed to arise from a genetic progression involving the duct epithelium lining smaller ducts of the pancreas (known as pancreatic intraepithelial neoplasia, PanIN). [7][8][9][10][11][12][13] Invasive carcinomas arising in an IPMN are separately categorized into colloid (mucinous noncystic carcinomas) or tubular (resembling usual ductal adenocarcinomas) types 11,14,15 (Fig. 1).…”

Hypermethylation-mediated reduction of WWOX expression in intraductal papillary mucinous neoplasms of the pancreas

“…Histologically, intraductal components of IPMN are classified into adenoma (intraductal papillary mucinous adenoma, IPMA) and carcinoma in situ (intraductal papillary mucinous carcinoma, IPMC). Interestingly, some patients occasionally have IDC derived from IPMN, suggesting that IPMN corresponds to a precursor lesion, which may potentially progress to IDC (Yamao et al, 2000;Sohn et al, 2001). Genetic alterations in IPMN have been identified, including mutations in the K-RAS (Z'Graggen et al, 1997; Schönleben et al, 2007), SMAD4 (Hruban et al, 2004), TP53 (Sessa et al, 1994) and PIK3CA genes (Schönleben et al, 2006), and have been shown to activate the mitogen-activated protein kinase and phosphatidylinositol-3 kinase pathways (Sessa et al, 1994;Semba et al, 2003).…”