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Background and Aims: The tissue acquisition and diagnostic yield of cyst fluid cytology is low-to-moderate and rarely provides a specific diagnosis. The aim of this study was to compare the tissue acquisition and diagnostic tissue yield of microforceps biopsy (MFB) with cyst fluid cytology., Methods: In this multicenter study, data of 42 patients who had cysts both aspirated by EUS-guided FNA (EUS-FNA) and biopsy specimens were then obtained with an MFB device, were collected. Cytology analysis of cyst fluid and histologic analysis of biopsy specimens were done. Acquisition yield was defined as percentage of patients with tissue present in the aspirate or biopsy. Diagnostic tissue yield was evaluated at 3 levels: the ability of differentiation between mucinous and/or nonmucinous cysts, detection of high risk for malignancy, and specific cyst type diagnosis., Results: The mean patient age was 69 years. Sixteen pancreatic cysts (38.1%) were located in the head, 17 (40.5%) in the body, and 9 (21.4%) in the tail. The mean cyst size was 28.2 mm (12-60 mm); 25 of 42 (60%) were septated. The EUS-FNA tissue (fluid) acquisition yield was 88.1% (37/42). The MFB tissue acquisition yield was 90.4% (38/42). The diagnostic cytology yield to differentiate between mucinous and/or nonmucinous cysts was 47.6% (20/42), and the MFB histologic yield to differentiate between mucinous and/or nonmucinous cysts was 61.9% (26/42) (P = .188). The percentage of cysts at high risk for malignancy by cytology was 54.7% (23/42), and MFB was 71.5% (30/42) (P = .113). However, the ability of MFB to provide a specific cyst type diagnosis was 35.7% (15/42), and that for cytology was 4.8% (2/42) (P = .001). Surgical histology was concordant with that of MFB in 6 of 7 patients (85%), and with that of cytology in 1 of 7 patients (15%)., Conclusion: The cyst tissue acquisition yield for MFBs was 90%. Although cytology of cyst fluid and MFB were comparable in distinguishing mucinous and nonmucinous cysts and detecting cysts at high risk for malignancy, MFB was far superior to cytology for providing a specific cyst diagnosis., (Published by Elsevier Inc.)

Background: Recent work has demonstrated early shedding of circulating epithelial cells (CECs) from premalignant intraductal papillary mucinous neoplasms (IPMNs). However, the potential use of CECs as a "liquid biopsy" for patients with IPMNs has been limited by antigen dependence of CEC isolation devices and the lack of robust detection biomarkers across CEC phenotypes., Materials and Methods: We utilized a negative depletion microfluidic platform to purify CECs from contaminating leukocytes and coupled this platform with immunofluorescence, RNA in situ hybridization, and RNA sequencing (RNA-seq) detection and enumeration., Results: Using established protein (EpCAM, cytokeratins) and novel noncoding RNA (HSATII, cytokeratins) biomarkers, we detected CECs in 88% of patients bearing IPMN lesions. RNA-seq analysis for MUC genes confirm the likely origin of these CECs from pancreatic lesions., Conclusion: Our findings increase the sensitivity of detection of these cells and therefore could have clinical implications for cancer risk stratification., Implications for Practice: This work describes a high-sensitivity platform for detection of epithelial cells shed from preneoplastic lesions at high risk of malignant transformation. Further research efforts are underway to define the transcriptional programs that might allow discrimination between circulating cells released from tumors that will become malignant and cells released from tumors that will not. After further refinement, this combination of technologies could be deployed for monitoring and early detection of patients at high risk for developing new or recurrent pancreatic malignancies., Competing Interests: Disclosures of potential conflicts of interest may be found at the end of this article., (© AlphaMed Press 2017.)

Background: The differential diagnosis of pancreatic cystic lesions (PCLs) is an increasingly common clinical challenge. Confocal laser endomicroscopy (CLE) may differentiate PCLs by imaging of the cyst wall. However, clinical experience is still limited, and better image definition and characterization of the cyst wall in a spectrum of cysts are needed. This experimental study aimed to expose detailed imaging characteristics of PCLs by CLE., Methods: Patients who underwent surgery of a PCL were enrolled. During surgery, intravenous fluorescein (2.5 ml of 10%) was injected just prior to the ligation of blood vessels supplying the pancreas. The freshly excised specimens were transected along the long axis to fully expose the luminal surface. A Gastroflex-UHD CLE probe (pCLE) was used manually to acquire images directly from the surface of cyst wall. The specimen subsequently underwent cross-sectional histology. All recorded data were analyzed by two investigators for predefined and original image findings of PCLs., Results: Ten cases were recruited into the study. All patients underwent surgery because of a mucinous cyst with worrisome features or a symptomatic PCL. Imaging was successful in all patients and differently shaped papillary projections (PP) were visualized in eight patients. Pathological examination of those patients confirmed 6 cases with Intraductal Papillary Mucinous Neoplasm (IPMN) and 2 cases with Mucinous Cystic Neoplasm (MCN). In two patients with serous cystadenoma, typical vascular network was visualized in one patient, and microcystic structures in the other. Three of the IPMNs were malignant. The loss of papillary margin integrity and significant fragmentation together with irregularity was detected in malignant IPMNs by CLE., Conclusions: Pancreatic cyst epithelial wall can be visualized successfully by pCLE in ex vivo surgical specimens. Different papillary projections have been seen in all cases of IPMNs and MCNs. CLE has potential for identifying IPMN subtypes and for grading dysplasia.

Background & Aims: Little is known about the development of branch duct intraductal papillary mucinous neoplasms (BD-IPMNs). We evaluated long-term outcomes of a large cohort of patients with BD-IPMNs to determine risk of malignancy and define a subset of low-risk BD-IPMNs., Methods: We performed a retrospective analysis of data from 577 patients with suspected or presumed BD-IPMN under surveillance at the Massachusetts General Hospital. Patients underwent cross-sectional imaging analysis at 3 months or later after their initial diagnosis. The diagnosis of BD-IPMN was based on the presence of unilocular or multilocular cysts of the pancreas and a non-dilated main pancreatic duct (<5 mm). We collected demographic, clinical, and pathology data. Cysts were characterized at the time of diagnosis and during the follow-up period. Follow-up duration was time between initial cyst diagnosis and date of last visit or death for patients without development of pancreatic cancer, date of surgery for patients with histologically confirmed malignancy, or date of first discovery of malignancy by imaging analysis for patients with unresectable tumors or who underwent neoadjuvant treatment before surgery. The primary outcome was risk of malignancy, with a focus on patients followed for 5 years or more, compared with that of the US population, based on standardized incidence ratio., Results: Of the 577 patients studied, 479 (83%) were asymptomatic at diagnosis and 363 (63%) underwent endoscopic ultrasound at least once. The median follow-up time was 82 months (range, 6-329 months) for the entire study cohort; 363 patients (63%) underwent surveillance for more than 5 years, and 121 (21%) for more than 10 years. Malignancies (high-grade dysplasia or invasive neoplasm) developed after 5 years in 20 of 363 patients (5.5%), and invasive cancer developed in 16 of 363 patients (4.4%). The standardized incidence ratio for patients with BD-IPMNs without worrisome features of malignancy at 5 years was 18.8 (95% confidence interval, 9.7-32.8; P < .001). One hundred and eight patients had cysts ≤1.5 cm for more than 5 years of follow-up; only 1 of these patients (0.9%) developed a distinct ductal adenocarcinoma. By contrast, among the 255 patients with cysts >1.5 cm, 19 (7.5%) developed malignancy (P = .01)., Conclusions: In a retrospective analysis of patients with BD-IPMNs under surveillance, their overall risk of malignancy, almost 8%, lasted for 10 years or more, supporting continued surveillance after 5 years. Cysts that remain ≤1.5 cm for more than 5 years might be considered low-risk for progression to malignancy., (Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background and Aim: Molecular analysis of pancreatic cyst fluid (PCF) has been proposed as a novel method for differentiating pancreatic cystic lesions (PCL). The present study aimed to investigate the value of GNAS testing when added to KRAS and carcinoembryonic antigen (CEA) testing of PCF for the diagnosis of intraductal papillary mucinous neoplasms (IPMN)., Methods: Prospectively collected endoscopic ultrasonography fine-needle aspiration (EUS-FNA) data were analyzed retrospectively for GNAS and KRAS mutations and CEA results. IPMN were histologically confirmed or supported by imaging and EUS-FNA findings (KRAS, CEA, cytology). Performance characteristics of GNAS added to KRAS and CEA for the diagnosis of IPMN were calculated., Results: The study population consisted of 197 patients with cyst fluid test results. Cysts were histologically classified in 33 patients and by clinical criteria in 164 patients. The IPMN group included 108 patients and the non-IPMN group included 89 patients. GNAS was positive in 51 patients (47.2%) with IPMN. Forty-two of these patients (82.3%) also had a KRAS mutation. Adding GNAS to KRAS increased the diagnostic accuracy from 76.6% to 79.1% (P > 0.05). Adding GNAS to CEA increased the diagnostic accuracy from 66.4% to 80.7 % (P < 0.05), but did not achieve a diagnostic superiority to KRAS testing alone (80.7% vs 76.6%, P > 0.05). The diagnostic accuracy of the triple combination was significantly better than all single tests (P < 0.05)., Conclusion: GNAS mutation is a highly specific test for IPMN. When GNAS testing is added to CEA and KRAS, a significantly greater overall accuracy (86.2%) is achieved., (© 2016 Japan Gastroenterological Endoscopy Society.)

Objectives: Pancreatic ductal adenocarcinoma (PDAC) has not experienced a meaningful mortality improvement for the past few decades. Successful screening is difficult to accomplish because most PDACs present late in their natural history, and current interventions have not provided significant benefit. Our goal was to identify determinants of survival for early PDAC to help inform future screening strategies., Methods: Early PDACs from the National Cancer Institute's Surveillance, Epidemiology, and End Results Program database (2000-2010) were analyzed. We stratified by size and included carcinomas in situ (Tis). Overall cancer-specific survival was calculated. A Cox proportional hazards model was developed and the significance of key covariates for survival prediction was evaluated., Results: A Kaplan-Meier plot demonstrated significant differences in survival by size at diagnosis; these survival benefits persisted after adjustment for key covariates in the Cox proportional hazards analysis. In addition, relatively weaker predictors of worse survival included older age, male sex, black race, nodal involvement, tumor location within the head of the pancreas, and no surgery or radiotherapy., Conclusions: For early PDAC, we found tumor size to be the strongest predictor of survival, even after adjustment for other patient characteristics. Our findings suggest that early PDAC detection can have clinical benefit, which has positive implications for future screening strategies.

Background and Aims: The value of next-generation sequencing (NGS) of pancreatic cyst fluid relative to the clinical and imaging impression has not been well-studied. The aim of this study was to assess the impact of NGS on the clinical diagnosis from imaging and carcinoembryonic antigen (CEA) and thus the management of pancreatic cysts., Methods: Ninety-two pancreatic cyst fluids from 86 patients were analyzed by cytology, CEA, and targeted NGS. Cysts were classified by imaging as nonmucinous, mucinous, or not specified. NGS results were compared with the imaging impression stratified by CEA and cytology., Results: NGS impacted the clinical diagnosis by defining a cyst as mucinous in 48% of cysts without elevated CEA levels. The VHL gene in 2 intraductal papillary mucinous neoplasms (IPMNs) supported a serous cystadenoma. Twenty percent of cysts that were nonmucinous by imaging were mucinous by NGS. Of the 14 not-specific cysts, CEA levels were not elevated in 12 (86%), and NGS established a mucinous etiology in 3 (25%). A KRAS or GNAS mutation supported an IPMN with nonmucinous CEA in 71%. A KRAS mutation reclassified 19% of nonneoplastic cysts with nonmucinous CEA as mucinous. Seven cyst fluids (8%) had either a TP53 mutation or loss of CDKN2A or SMAD4 in addition to KRAS and/or GNAS mutations; 5 of 7 (71%) were clinically malignant, and high-grade cytology was detected in all 5. Overall, CEA was more specific for a mucinous etiology (100%), but NGS was more sensitive (86% vs 57%)., Conclusions: NGS of pancreatic cyst fluid impacts clinical diagnosis and patient management by defining, supporting, or changing the clinical diagnosis based on imaging and CEA. NGS was most valuable in identifying mucinous cysts with nonmucinous CEA. An added benefit is the potential to detect mutations late in the progression to malignancy that may increase the risk classification of the cyst based on imaging and cytology., (Copyright © 2016 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Background & Aims: Intraductal papillary mucinous neoplasms (IPMNs) of the pancreas occur mostly in older individuals. Individual life expectancy and risk of death from other factors must be carefully considered in analyzing the risks that IPMNs pose. We investigated whether there is a subset of patients with IPMNs and a high risk of dying from other causes who would not benefit from pancreatic surgery., Methods: We collected data from 725 patients at Massachusetts General Hospital who underwent resection or have been under observation for IPMNs from 1992 through 2012. Comorbidities were classified according to the age-adjusted Charlson comorbidity index (CACI). Causes of death were recorded, and survival data were analyzed by the Kaplan-Meier method., Results: The patients' median CACI score was 3; 10% of patients had CACI of 7 or more. Of the entire cohort, 55% underwent resection, and the remaining 45% have been under observation. After a median follow-up period of 5 years, 177 patients died (24%, 55% of deaths within 5 years of diagnosis); 78% of deaths were not related to IPMNs. The median survival time for all patients with CACI score of 7 or more was 43 months. Multivariate regression analysis revealed that the chance of non-IPMN-related death within 3 years of diagnosis is 11-fold higher for patients with CACI score of 7 or more than for patients with lower scores., Conclusions: The CACI can be used to identify patients with a high risk of death from factors other than IPMNs within a few years after diagnosis. These patients are therefore not likely to benefit from further IPMN observation or pancreatic resection., (Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Objective: Intraductal papillary mucinous neoplasm (IPMN) consists of four epithelial subtypes that correlate with histological grades and risks for malignant transformation. mAb Das-1 is a monoclonal antibody against a colonic epithelial phenotype that is reactive to premalignant conditions of the upper GI tract. We sought to assess the ability of mAb Das-1 to identify IPMN with high risk of malignant transformation., Design: mAb Das-1 reactivity was evaluated in 94 patients with IPMNs by immunohistochemistry. Lesional fluid from 38 separate patients with IPMN (n=27), low-grade non-mucinous cystic neoplasms (n=7) and pseudocysts (n=4) was analysed by ELISA and western blot., Results: Immunohistochemistry-Normal pancreatic ducts were non-reactive and low-grade gastric-type IPMN (IPMN-G) (1/17) and intermediate-grade IPMN-G (1/23) were minimally reactive with mAb Das-1. In contrast, mAb Das-1 reactivity was significantly higher in high-risk/malignant lesions (p<0.0001) including: intestinal-type IPMN with intermediate-grade dysplasia (9/10); high-grade dysplasia of gastric (4/7), intestinal (12/12), oncocytic (2/2) and pancreatobiliary types (2/2); and invasive tubular (8/12), colloid (7/7) and oncocytic (2/2) carcinoma. The sensitivity and specificity of mAb Das-1 for high-risk/malignant IPMNs were 85% and 95%, respectively. Lesional fluid-Samples from low- and intermediate-grade IPMN-G (n=9), and other low-grade/benign non-mucinous lesions demonstrated little reactivity with mAb Das-1. Conversely, cyst fluid from high-risk/malignant IPMNs (n=18) expressed significantly higher reactivity (p<0.0001). The sensitivity and specificity of mAbDas-1 in detecting high-risk/malignant IPMNs were 89% and 100%, respectively., Conclusions: mAb Das-1 reacts with high specificity to tissue and cyst fluid from high-risk/malignant IPMNs and thus may help in preoperative clinical risk stratification., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Background: The malignant potential of intraductal mucinous neoplasm of the pancreas (IPMN) is associated closely with main pancreatic duct (MPD) involvement. Because mixed-type IPMN is thought to have the same malignant potential as that of main-duct (MD)-IPMN, resection is recommended; however, the biological nature of mixed-type IPMN with only minimal involvement of MPD (min-mix-IPMN) may be different., Methods: A prospective database of 404 resected IPMNs was re-reviewed to subclassify mixed-type IPMNs. We defined min-mix-IPMN as absence of gross abnormalities (except for dilatation) of MPD and noncircumferential microscopic involvement of MPD limited to few sections., Results: We identified 46 min-mix-IPMNs, 163 IPMNs with extensive involvement of MPD (ex-mix-IPMN), 175 branch-duct (BD)-IPMNs, and 20 MD-IPMNs. The majority of min-mix-IPMNs were found incidentally and increased cyst size on surveillance was the leading operative indication. The median diameter of MPD was 2 mm in min-mix-IPMN versus 9 mm in ex-mix-IPMN (P < .0001), and cysts ≥10 mm were present in 62% of ex-mix-IPMNs versus 93% of min-mix-IPMNs (P < .0001). Most importantly, the vast majority of min-mix-IPMNs exhibited gastric-type epithelium, similar to BD-IPMNs, whereas intestinal-type epithelium was present in half of ex-mix-IPMNs, similar to MD-IPMNs. The prevalence of high-grade lesions was less in min-mix-IPMN than ex-mix-IPMN (P < .0001). These differences were reflected in better disease-specific outcomes of min-mix-IPMN compared with ex-mix-IPMN (P = .046)., Conclusion: Min-mix-IPMN often presents with no MPD dilation and is an incidental finding by microscopic examination. min-mix-IPMN shares the pathologic features and less aggressive biology with BD-IPMN. We propose that min-mix-IPMN be categorized differently than ex-mix-IPMN., (Copyright © 2014 Mosby, Inc. All rights reserved.)

Background and Study Aims: There have been concerns about peritoneal seeding after endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) of mucinous pancreatic cystic lesions. The aims of this study were to determine the frequency of postoperative peritoneal seeding in patients with intraductal papillary mucinous neoplasm (IPMN) who had undergone pre-operative EUS-FNA and to compare it with that of patients with IPMN who had surgery with no pre-operative tissue sampling., Patients and Methods: A total of 175 patients who had undergone resection of IPMNs with pre-operative EUS-FNA (EUS-FNA group) were analyzed and compared with 68 patients who had undergone resection with no pre-operative tissue sampling (No Sampling group). Patient characteristics, pathology, and frequency of peritoneal seeding after surgery were analyzed and compared. Peritoneal seeding was diagnosed based on pathology or image findings., Results: The two groups were comparable with respect to sex, age, follow-up duration, involvement of the pancreatic head, involvement of the main duct, grade of dysplasia, and size of histologically proven branch-duct IPMNs. Four patients (2.3 %) with invasive IPMN developed peritoneal seeding in the EUS-FNA group, whereas three (4.4 %, two with invasive IPMN and one with high-grade dysplasia) developed peritoneal seeding in the No Sampling group (P  = 0.403). No peritoneal seeding was noted during surgery in these cases. Except for one patient in the EUS-FNA group, no spillage occurred during resection in these patients., Conclusions: In this cohort of patients undergoing resection of IPMN, the difference in the frequency of peritoneal seeding in the EUS-FNA group and the No Sampling group was not significant., (© Georg Thieme Verlag KG Stuttgart · New York.)

Background: The recognition of epithelial cells with high-grade atypia (HGA) in the cyst fluid of an intraductal papillary mucinous neoplasm (IPMN) identifies a cyst at high risk of invasive carcinoma. To the best of the authors' knowledge, the cytological features of HGA have not been systematically analyzed to define diagnostic criteria., Methods: Cell groups from patients with histologically confirmed branch-duct IPMNs were evaluated by 2 cytopathologists with expertise in pancreatic cytology. A consensus interpretation categorized the cell groups as having either low-grade (LG) or high-grade (HG) morphology. Characteristics regarding cell size and architecture, nuclear and cytoplasmic features, and background necrosis were analyzed. Performance characteristics were assessed using the Fisher exact test at 95% confidence intervals., Results: Sixty cell groups yielded 27 LG and 25 HG morphological groups. No consensus was reached for 8 groups, which were excluded from statistical analysis. Five features that were found to be significantly different between the LG and HG groups included: 1) cell size <  a 12-μm duodenal enterocyte for HG and size equal for LG; 2) an increased nuclear-to-cytoplasmic (N/C) ratio; 3) marked nuclear membrane abnormalities; 4) abnormal chromatin pattern; and 5) background necrosis. The 3 most accurate features for the identification of HGA were background necrosis (88%), abnormal chromatin pattern (84%), and an increased N/C ratio (82%)., Conclusions: IPMN cyst fluid at high-risk of malignancy can be recognized most accurately by the presence of epithelial cells with HGA showing an increased N/C ratio, an abnormal chromatin pattern, and background necrosis., (© 2013 American Cancer Society.)

Objective: Invasive cancers arising from intraductal papillary mucinous neoplasm (IPMN) are recognised as a morphologically and biologically heterogeneous group of neoplasms. Less is known about the epithelial subtypes of the precursor IPMN from which these lesions arise. The authors investigate the clinicopathological characteristics and the impact on survival of both the invasive component and its background IPMN., Design and Patients: The study cohort comprised 61 patients with invasive IPMN (study group) and 570 patients with pancreatic ductal adenocarcinoma (PDAC, control group) resected at a single institution. Multivariate analyses were performed using a stage-matched Cox proportional hazard model., Results: The histology of invasive components of the IPMN cohort was tubular in 38 (62%), colloid in 16 (26%), and oncocytic in seven (12%). Compared with PDAC, invasive IPMNs were associated with a lower incidence of adverse pathological features and improved mortality by multivariate analysis (HR 0.58; 95% CI 0.39 to 0.86). In subtype analysis, this favourable outcome remained only for colloid and oncocytic carcinomas, while tubular adenocarcinoma was associated with worse overall survival, not significantly different from that of PDAC (HR 0.85; 95% CI 0.53 to 1.36). Colloid and oncocytic carcinomas arose only from intestinal- and oncocytic-type IPMNs, respectively, and were mostly of the main-duct type, whereas tubular adenocarcinomas primarily originated in the gastric background, which was often associated with branch-duct IPMN. Overall survival of patients with invasive adenocarcinomas arising from gastric-type IPMN was significantly worse than that of patients with non-gastric-type IPMN (p=0.016)., Conclusions: Tubular, colloid and oncocytic invasive IPMNs have varying prognosis, and arise from different epithelial subtypes. Colloid and oncocytic types have markedly improved biology, whereas the tubular type has a course that resembles PDAC. Analysis of these subtypes indicates that the background epithelium plays an equally, if not more, important role in defining the biology and prognosis of invasive IPMNs.

Objective: Evaluate the value of cytology relative to imaging features in risk assessment for malignancy as defined in the Sendai Guidelines., Background: The Sendai Guidelines list symptoms, cyst size >30 mm, dilated main pancreatic duct (MPD) >6 mm, mural nodule (MN) and "positive" cytology as high risk stigmata for malignancy warranting surgical triage., Methods: We reviewed clinical, radiological and cytological data of 112 patients with histologically confirmed mucinous cysts of the pancreas evaluated in a single tertiary medical center. Cytology slides were blindly re-reviewed and epithelial cells grouped as either benign or high-grade atypia (HGA) [≥high-grade dysplasia]. Histologically, neoplasms were grouped as benign (low-grade and moderate dysplasia) and malignant (in situ and invasive carcinoma). Performance characteristics of cytology relative to other risk factors were evaluated., Results: Dilated MPD, MN, and HGA were independent predictors of malignancy (p < 0.0001), but not symptoms (p = 0.29) or cyst size >30 mm (p = 0.51). HGA was the most sensitive predictor of malignancy in all cysts (72%) and in small (≤30 mm) branch-duct intraductal papillary mucinous neoplasm (BD IPMN; 67%), whereas also being specific (85 and 88%, respectively). MN and dilated MPD were highly specific (>90%), but insensitive (39%-44%). Cytology detected 30% more cancers in small cysts than dilated MPD or MN and half of the cancers without either of these high-risk imaging features., Conclusions: Cytology adds value to the radiological assessment of predicting malignancy in mucinous cysts, particularly in small BD IPMN.

Objective: To define how patients with pancreatic cysts are being diagnosed and treated., Design: Retrospective case series., Setting: University-affiliated tertiary care center., Patients: Four hundred one patients evaluated in the Department of Surgery between January 2004 and December 2007., Main Outcome Measures: Clinical management, histological diagnosis, and results of surveillance., Results: Pancreatic cysts were incidentally discovered in 71% (284 of 401) of patients. There was no statistically significant difference in age (60.4 vs 63.1 years; P = .10), cyst size (31 vs 27 mm; P = .12), or histological diagnosis between symptomatic patients and patients with incidentally discovered cysts. Whereas the majority of symptomatic patients had their cystic neoplasms resected on diagnosis, 50% (142 of 284) of incidentally discovered cysts were initially managed nonoperatively. Of the patients who were managed with surveillance, 13 (8%) subsequently underwent resection after a median of 2.1 years because of an increase in cyst size, development of symptoms, increasing tumor markers, worrisome endoscopic ultrasonography findings, or patient anxiety. The most common diagnosis among resected lesions was either main-duct intraductal papillary mucinous neoplasm (25%) or branch-duct intraductal papillary mucinous neoplasm (23%). Invasive cancer was found in 29 of 256 (11%) resected cystic neoplasms, 9 of which were incidentally discovered, and in 7% (1 of 13) of patients who underwent watchful waiting prior to resection., Conclusions: Incidentally discovered pancreatic cystic neoplasms composed 71% of our series, of which 50% were immediately resected. Subsequent morphologic changes or development of symptoms prompted an operation in 8% of patients after a period of surveillance. Invasive malignancy was present in 11% of all resected specimens but in 38% of main-duct intraductal papillary mucinous neoplasms.

Intraductal papillary mucinous neoplasms have gained recognition in recent years as premalignant precursors to pancreatic cancer that enable early detection and often are found incidentally at imaging. Accurate diagnosis and optimal, finely tuned management of these lesions are important and require collaboration across various disciplines, including radiology, endoscopy, surgery, and pathology. Several imaging modalities can visualize these lesions adequately, each with specific advantages and disadvantages. Multidetector computed tomography and magnetic resonance cholangiopancreatography are generally the first-line imaging modalities; endoscopic imaging such as endoscopic ultrasound and endoscopic retrograde cholangiopancreatography are beneficial when the former 2 modalities are equivocal. Surgical candidates generally include patients with main duct lesions or branch duct lesions greater than 3 cm or any possessing a solid component. A management algorithm indicating when surgery should be pursued is proposed. For nonsurgical and postsurgical patients, follow-up management is important to monitor growth and recurrence, and risks from repeated radiation exposure should be taken into account. Furthermore, issues of multifocality and increased predisposition of the pancreas to ductal adenocarcinoma must be addressed at follow-up evaluation. A follow-up management algorithm also is proposed in this review.

Background: Intraductal papillary mucinous neoplasm (IPMN) is an increasingly recognized cystic neoplasm of the pancreas, histologically classified by the degree of epithelial atypia and by the presence or absence of invasion of the cyst wall. To the authors' knowledge, the cytologic features of this neoplasm are poorly characterized, especially with respect to tumor grade., Methods: Thirty-three endoscopic ultrasound (EUS)-guided pancreatic fine-needle aspiration biopsy (FNAB) samples and 1 pancreatic duct brush specimen from 25 patients with a histologically confirmed IPMN were retrospectively reviewed. Blinded to tumor grade, background mucin, inflammation, necrosis, overall cellularity, the presence of gastrointestinal-contaminating epithelium, architecture of cell clusters, and nuclear and cellular morphology were evaluated. In cases in which special stains for mucin were performed, the diagnostic utility of these stains was assessed. These cytologic features were subsequently correlated with the histologic diagnosis., Results: The 34 cytology samples represented 4 adenomas, 15 IPMN-moderate dysplasias, 7 intraductal carcinomas, and 8 IPMNs with invasive carcinoma. Extracellular mucin was present in 97% of all cases; 53% had thick, viscous, "colloid-like" mucin. Special stains for mucin were positive in 6 of 11 cases (54%), helping to identify thin mucin in only 2 cases. Gastrointestinal contamination did not appear to create diagnostic difficulty due to an apparent dual (dysplastic-nondysplastic) epithelial population, but only 4 adenomas were evaluated in this study. Necrosis distinguished IPMN with carcinoma from IPMN-adenomas and IPMN with moderate dysplasia (P < .00001), and was more often observed with invasion than IPMN-carcinoma in situ (P < .05). Tight epithelial cell clusters with hyperchromatic nuclei and a high nuclear to cytoplasmic ratio was more significant in IPMN of at least moderate dysplasia (P = .03). Pale nuclei with parachromatin clearing was found to be a nuclear feature that was suspicious for at least carcinoma in situ (P < .001). In addition, significant background inflammation (neutrophils and histiocytes) was found to be more characteristic of IPMN with at least carcinoma in situ (P = .002)., Conclusions: The presence of thick, "colloid-like" mucin is noted in half of the IPMN cases, but was not found to be specific to grade. The absence of such mucin does not exclude an IPMN. The presence of tight epithelial cell clusters is consistent with a neoplasm of at least moderate dysplasia, and abundant background inflammation and parachromatin clearing correlated with the presence of at least carcinoma in situ. Necrosis was the only feature found to be strongly suggestive of invasion.