Intraductal papillary mucinous neoplasms of the pancreas: an increasingly recognized clinicopathologic entity

Abstract

Objective: To assess the authors' experience with intraductal papillary mucinous neoplasms of the pancreas (IPMNs).

Summary background data: Intraductal papillary mucinous neoplasms of the pancreas are being recognized with increasing frequency.

Methods: All 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.

Results: In 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 +/- 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 = 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 = 60) was 57%.

Conclusion: Intraductal 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.

Figure 1. (A) Noninvasive intraductal papillary mucinous neoplasm of the pancreas (IPMN). Note the tall, columnar, mucin-filled epithelium and the papillary proliferations extensively involving the main pancreatic duct (main PD). The basement membrane is intact. The ampulla of Vater is shown. (B) IPMN with associated infiltrating adenocarcinoma. Note the noninvasive component at the right and the infiltrating component at the left, characterized by dissecting pools of mucin in which neoplastic glandular cells are embedded. (C) Infiltrating ductal adenocarcinoma of the pancreas. The tumor consists of cuboidal epithelial cells with irregular nuclei. Note the striking desmoplastic response typical of pancreatic ductal adenocarcinoma. (D) Dpc4 protein staining of an IPMN with associated infiltrating adenocarcinoma. The noninvasive component is strongly positive for Dpc4, whereas the infiltrating component no longer expresses the Dpc4 protein (Dpc4 negative).

Figure 2. Histogram representing the number per year of pancreaticoduodenal resections for pancreatic ductal adenocarcinoma, resections for intraductal papillary mucinous neoplasms (IPMNs), and pancreaticoduodenal resections for mucinous cystadenomas/cystadenocarcinomas.

Figure 3. The Kaplan-Meier actuarial survival for the entire cohort of 60 patients with resected intraductal papillary mucinous neoplasms (IPMNs) of the pancreas. The survival rates were 82% at 1 year, 67% at 3 years, and 57% at 5 years.

Figure 4. The Kaplan-Meier actuarial survival curves comparing patients with noninvasive intraductal papillary mucinous neoplasms (IPMNs) (n = 38) and patients with IPMNs with an infiltrating adenocarcinoma component (n = 22, P = .87). Patients with noninvasive IPMNs had 1-, 2-, and 4-year survival rates of 87%, 71%, and 64%; patients with IPMNs with an associated infiltrating adenocarcinoma had survival rates of 73%, 73%, and 62%.

Figure 5. The Kaplan-Meier actuarial survival curves comparing patients with intraductal papillary mucinous neoplasms (IPMNs) with an infiltrating adenocarcinoma component (n = 22) and patients with infiltrating ductal adenocarcinoma of the pancreas without an associated IPMN (n = 698, P = .01). IPMN patients had 1-, 3-, and 5-year survival rates of 73%, 73%, and 62%; patients with pancreatic ductal adenocarcinoma had corresponding rates of 63%, 27%, and 19%.