Intraductal Papillary Mucinous Neoplasm: Clinical Surveillance and Management Decisions

https://doi.org/10.1016/j.semradonc.2013.11.005Get rights and content

Intraductal papillary mucinous neoplasm (IPMN) of the pancreas is a relatively rare cystic neoplasm. Although most IPMNs appear to be benign and may be managed by surveillance, all IPMNs are considered premalignant lesions with malignant potential. As such, current efforts are focused on identifying those neoplasms that are at high risk for malignancy to optimize treatment strategy and outcome. IPMNs with invasive carcinoma have clinical outcomes that approach those of conventional pancreatic ductal adenocarcinoma. Management guidelines recommend surgical resection for IPMNs with high-risk imaging or cytologic features. The role of adjuvant therapy is unclear, and we review the evidence for chemoradiation here. Some studies suggest adjuvant chemoradiation may have the greatest impact in malignant IPMNs with adverse histologic features, that is, lymph node metastasis at the time of diagnosis or positive surgical margins. As more IPMNs are recognized and treated, more evidence will accumulate to guide clinicians regarding appropriate use of radiotherapy in the management of IPMN.

Introduction

Various names have been used to describe intraductal papillary mucinous neoplasms (IPMNs) since Ohashi1 published 4 cases of mucinous neoplasms of the pancreas leading to ectasia of the pancreatic duct system in 1982. In 1996, the World Health Organization (WHO) classified cystic mucin-producing pancreatic neoplasms under intraductal papillary mucinous tumor (renamed neoplasm in 2006) and mucinous cystic neoplasm (MCN). IPMNs are defined as mucin-producing cystic pancreatic neoplasms with intraductal papillary projections of tall columnar epithelium, without subepithelial ovarian-type stroma, which distinguishes them from MCNs. Originally thought to be a rare tumor, IPMNs are now recognized to be more frequent entities based on autopsy and surgical series and currently constitute approximately 20%-50% of resected cystic pancreatic tumors.2, 3, 4 Likely, some of the apparent increase in IPMN incidence is because of increased incidental detection on imaging.5 It is estimated that at least 2% of the general population have pancreatic cysts, with a strong correlation to age; for example, in patients older than 80 years, 8.7% of patients had pancreatic cysts in an institutional series.6 Using magnetic resonance imaging (MRI), the prevalence of pancreatic cysts has been estimated to be as high as 13.5%.7

IPMNs range from premalignant intraductal lesions to malignant neoplasms with invasive carcinoma. Indeed, 20%-50% of resected IPMNs have an invasive component. Although 10-year disease-specific survival for resected, noninvasive IPMNs is greater than 95%, invasive cancers have a 5-year overall survival of 36%-70%.8, 9, 10, 11

Overall, patients with invasive IPMN appear to present at an earlier stage than those with classic pancreatic ductal adenocarcinoma, and this is likely a reflection of the natural history of the disease, in which larger cystic lesions may be apparent on imaging or cause clinical symptoms that prompt imaging.8, 12 In a series of resected IPMNs at the Massachusetts General Hospital (MGH), 30% of patients with invasive IPMN presented with nodal involvement compared with approximately 70% in patients with classic pancreatic ductal adenocarcinoma.4 Similarly, in a surgical series from Johns Hopkins University, 64% of patients presented with stage II disease.8 Although overall mortality for resected invasive IPMN is better than in conventional pancreatic ductal carcinoma (hazard ratio [HR] = 0.58, 95% CI: 0.39-0.86), it appears that among node-positive patients, there is no significant difference between clinical outcomes in invasive IPMN and ductal adenocarcinoma (HR = 0.89, 95% CI: 0.52-1.50).13 Therefore, at least some of the improved outcomes observed in IPMN compared with conventional adenocarcinoma may be because of earlier stage at presentation; that is, smaller size and a decreased incidence of nodal involvement.

Section snippets

Location

IPMNs are classified preoperatively by imaging according to the pancreatic ducts involved: the main duct (MD-IPMN), the branch ducts (BD-IPMN), or both (mixed or combined type). Identifying the type of IPMN has implications on prognosis and, therefore, management, as MD-IPMNs have a higher risk of malignancy. MD-IPMN typically leads to marked dilation that can often be seen by computed tomography (CT) imaging or by magnetic resonance cholangiopancreatography (MRCP). More invasive techniques,

Imaging

Cystic pancreatic lesions, including IPMNs, are found on imaging that is often performed for unrelated reasons. The location and degree of duct dilation can be seen on CT and, in our institution, a dedicated pancreatic protocol is used for improved detection of ductal abnormalities (Fig. 1). Mucinous globules are often seen and may appear as filling defects in the duct system. Serial sectioning of the entire pancreas by CT is useful for determining the full extent of the disease. Staging should

Management

The management guidelines for IPMN outlined by the 2005 and 2012 International Consensus Guidelines recommend resection of lesions that are at high risk for malignancy and for symptomatic management.14 Before the 1990s, surgical resection was recommended for all mucin-producing pancreatic neoplasms. The 2012 guidelines of multidisciplinary experts recognized the different propensities for malignancy of MD and mixed type IPMNs compared with the lower malignant potential of the BD-IPMN subtypes.

Role of Radiotherapy

Determining the optimal strategy following resection for invasive IPMN is subject to discussion, as is adjuvant therapy for pancreatic carcinomas in general. Because of the relative rarity of the disease, there is no randomized evidence regarding adjuvant therapy in malignant (invasive) IPMN. Most commonly, clinicians extend results from trials of pancreatic ductal adenocarcinoma to the management of invasive IPMNs, which may not be applicable. Complicating the discussion, is the relatively

Summary Recommendations

IPMNs are relatively new entities that are recognized with increasing frequency. Because of the limited number of cases, prospective clinical trials to identify optimal treatment would be difficult to achieve. Therefore, we are dependent on retrospective studies that have only recently been using similar guidelines regarding classification and histologic grading. In addition, surgical resection techniques, including whether lymph node dissections are performed, may vary across institutions,

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    The authors declare no conflict of interest.

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