Mucinous Pancreatic Cysts Research Articles

Testing cross-species and cross-organ stellate cells as model system for pancreatitis research

s / Pancreatology 13 (2013) e1–e94 e65 and 0.002). Kynurenine level had a diagnostic accuracy of 90% and 95%, respectively, in the two cohorts. Neither could differentiate pre-malignant from malignant cysts. Conclusion: Metabolomic profiling identified glucose and kynurenine to have clinical utility for classification of mucinous and non-mucinous pancreatic cysts. Further evaluation with this approach is warranted.

RNF43 is a tumour suppressor gene mutated in mucinous tumours of the ovary

Mucinous carcinomas represent a distinct morphological subtype which can arise from several organ sites, including the ovary, and their genetic characteristics are largely under-described. Exome sequencing of 12 primary mucinous ovarian tumours identified RNF43 as the most frequently somatically mutated novel gene, secondary to KRAS and mutated at a frequency equal to that of TP53 and BRAF. Further screening of RNF43 in a larger cohort of ovarian tumours identified additional mutations, with a total frequency of 2/22 (9%) in mucinous ovarian borderline tumours and 6/29 (21%) in mucinous ovarian carcinomas. Seven mutations were predicted to truncate the protein and one missense mutation was predicted to be deleterious by in silico analysis. Six tumours had allelic imbalance at the RNF43 locus, with loss of the wild-type allele. The mutation spectrum strongly suggests that RNF43 is an important tumour suppressor gene in mucinous ovarian tumours, similar to its reported role in mucinous pancreatic precancerous cysts.

Pancreatic stents with diclofenac reduce the incidence of post ERCP pancreatitis in patients undergoing molecular screening of pancreatic juice for pancreatic cancer

s / Pancreatology 13 (2013) e1–e94 e60 months (19.3-38.6) in localized disease; 11 months (10.2-11.7) in regional stage and 3 months (2.8-3.1) in distant stage disease. Younger age, localized disease, curative intent surgery, radiotherapy, more recent year of diagnosis (2002-2008 vs 1988-1994) [but not gender, race, geographic location] were associated with increased survival. Conclusions: Although there has been a decrease in the age-adjusted incidence rate and mortality from PMC in recent years, most patients are diagnosed at an advanced stage, and this tumor has a poor prognosis. Efforts to recognize malignancy in mucinous pancreatic cysts and earlier diagnosis are warranted.

PMD44 Evaluating Strategies for Using DNA Testing to Identify Mucinous Pancreatic Cysts

PMD44 Evaluating Strategies for Using DNA Testing to Identify Mucinous Pancreatic Cysts

Chemotherapy for Ablation and Resolution of Mucinous Pancreatic Cysts (CHARM) Trial: Initial Proof-of-concept Index Case for this Prospective, Randomized, Double-blinded, Single-center Study

Purpose: An initial report of the safety and feasibility of the recently opened CHARM trial, evaluating EUS-guided fine-needle infusion (EUS-FNI) of a chemotherapeutic cocktail, following ethanol or normal saline lavage, for mucinous pancreatic cyst ablation. We hypothesize that: 1) EUS-guided lavage of these premalignant pancreatic cysts with normal saline (rather than ethanol) will result in similar efficacy and a lower rate of complications; 2) EUS-FNI of a combination of paclitaxel and gemcitabine will be safe and more effective than previously used ablative agents (paclitaxel or ethanol alone) for the elimination of such lesions. Methods: Adult subjects with mucinous or indeterminate pancreatic cysts who meet inclusion criteria are randomized to undergo single-session EUS-guided lavage of the cyst with 80% ethanol followed by EUS-FNI of a chemotherapeutic cocktail of 3 mg/mL of paclitaxel and 19 mg/mL of gemcitabine (control group) or alternatively, EUS-guided normal saline lavage followed by EUS-FNI of the same chemotherapeutic agents (study group). Patients are then monitored for procedure-related complications, and the success of cyst ablation is assessed by follow-up CT or MRI at 3, 6, and 12 months post-procedure. We aim to enroll 78 subjects (39 in each arm) over a period of 4 years. Results: EUS-guided lavage of a pancreatic mucinous cyst followed by EUS-FNI chemoablation has been successfully performed in the initial patient enrolled in the CHARM trial (78-year-old male with coronary artery disease). The procedure required 21 minutes, and the patient developed no complications. A follow-up CT 3 months post-procedure showed a marked reduction of the lesion from 21 mm to 8 mm (Figure).Figure: [237]Conclusion: Ablation of mucinous pancreatic cysts using EUS-FNI with a chemotherapeutic cocktail of paclitaxel and gemcitabine (with or without ethanol lavage) may represent a safe and effective option in selected cases for elimination of these lesions. Furthermore, management of pancreatic mucinous cysts using EUS-FNI in selected cases offers a minimally invasive alternative to surgery. This initial case of the CHARM trial suggests that EUS-FNI ablation of pancreatic mucinous or indeterminate cysts using a combination of paclitaxel and gemcitabine is feasible and safe. Progress report of this trial will be presented at future meetings.

Cytology and CEA from Cystic Fluid Have Marginal Utility in the Management of Pancreatic Cystic Neoplasms

Context The management of patients with cystic lesion of the pancreas still remains controversial, mainly because traditional cross-sectional imaging have a limited ability to differentiate benign from premalignant or malignant pancreatic cysts. Endoscopic ultrasound (EUS) has been increasingly used in clinical practice, and the value of sample cyst fluid with fine-needle aspiration for cytology (FNAC) or fluid CEA concentration has been reported to be useful for risk assessment of malignancy in pancreatic mucinous cysts [1]. Objective The aim of this study was to determine whether EUS and cyst fluid analysis for cytology and CEA determination may be predictive of malignancy in a series of patients investigated for cystic neoplasms of the pancreas. Methods From January 2009 to June 2011, 51 patients underwent EUS in the preoperative work-up for suspected cystic tumor of the pancreas. Whenever possible, aspiration of cyst fluid for cytology and cyst fluid analysis for CEA, CA 19-9, amylase and lipase determination were performed. All patients underwent also abdominal MRI and whole-body PET/CT. Patients with symptoms or radiological or cytological suspicion of premalignant or frankly malignant lesion underwent surgical treatment. In the remaining patients validation of diagnosis was obtained by follow-up. Median follow-up was 23 months, range 12-41 months. Results There were 24 males and 27 females (mean age 52.7 years, range 34-81 years). The mean cyst size was 3.4 cm (range 2.0-12 cm). In all, 10 patients were symptomatic and 24 underwent surgery (47%). Diagnosis included: 29 IPMNs, 7 malignant mucinous cysts, 2 solid-pseudopapillary tumors, 2 mucinous cystadenomas, 8 serous cystadenomas, 1 endocrine tumor, and 2 pseudocysts. Ctytology and cyst fluid analysis were performed in 49 patients. Cytology was positive in 3/7 malignancies, 1/2 solid pseudopapillary tumors, doubtful in 1 IPMN, negative in 28 benign cysts, inconclusive in the remaining 11 patients. CEA was >200 ng/mL in 8 patients (>1,000 ng/mL in 5): only 2 patients proved to have malignant tumor. PET/CT was positive in 6/7 malignant tumors and false positive in 1 IPMN with low-grade dysplasia. Conclusion The correct evaluation of pancreatic cystsic neoplasms remains challenging. The decision to proceed with operative or non operative management should not be based on cytology or CEA levels in the cyst fluid aspirate.

Carcino Embryonic Antigen and long-term follow-up of mucinous pancreatic cysts including intraductal papillary mucinous neoplasm

Background and aimsThe utility of Carcino Embryonic Antigen (CEA) in differentiating malignant from benign pancreatic cysts is controversial. We sought to examine the role of CEA in differentiating benign from malignant cysts and its utility in progression of cyst size in follow-up. MethodsRetrospective chart review of patients who underwent Endoscopic Ultrasound with Fine Needle Aspiration for mucinous cysts between 1998 and 2010. CEA was measured in benign and malignant mucinous cysts. Coefficient of determination (R2) was used to measure the association between change in cyst size and CEA. Mann–Whitney test was used to compare the median values of CEA. Results143 patients (38.4% males) were included (mean age 68.9±0.8 years). 105 patients had intra-cystic CEA measured. 63 patients underwent surgery while 80 patients were in the follow-up group. In the surgical group, median CEA value for benign and malignant mucinous neoplasms was 796 and 438ng/ml, respectively (p=0.79). The median follow-up was 21 months. There was no correlation between CEA level and progression in cyst size in patients who had >6 months of follow-up, R2=0.0002. Malignant transformation was observed in 5 (5.9%) patients. ConclusionCEA level was not predictive of malignant cyst nor cyst size progression over follow-up.

The role of GNAS mutation in diagnosis of mucinous pancreatic cysts.

e21048 Background: Pancreatic cysts pose a challenge in patient management primarily due to difficulties distinguishing non-mucinous cysts from potentially pre-malignant mucinous ones, and in determining the malignant potential of mucinous cysts. Mutations to the GNAS gene have been identified as a marker for intraductal papillary mucinous neoplasm (IPMN). [1,2] We evaluated the significance of GNAS mutation in diagnosis of pancreatic cysts. Methods: We retrieved archival DNA from 237 cyst fluids. 200 specimens were chosen with 100 KRAS mutant and 100 KRAS wild type in a range of CEA values. 37 specimens were chosen with a molecular diagnosis of aggressive biological behavior, to enrich for malignant IPMNs. We sequenced each fluid’s DNA from for codon 201 of GNAS. Molecular criteria for mucinous cysts included KRAS mutation, elevated DNA, or ≥2 high clonality LOH mutations. Results: Of the 237 specimens, 25 were not amplifiable due to degraded DNA, 52 (25%) had a GNAS mutation, and 160 had no GNAS mutation. Of the 52 GNAS mutated specimens, 5 were diagnosed as biologically aggressive based on significant associated mutations, 28 as statistically indolent based on associated molecular changes, and 19 as benign (no accompanying mutations). The proportion of GNAS mutations decreased with increasing molecular changes linked to malignancy. Data from [1] shows no statistical difference in frequency of GNAS mutation in side branch vs. main vs. mixed IPMNs (p= 0.46). Similarly, in our cohort, 6 cases had clear imaging features of a side branch IPMN, and of these 2 (33%) had a mutation in GNAS. Using molecular criteria for identification of mucinous cysts, 166 were mucinous and 71 non-mucinous. Incorporation of GNAS into the molecular determination of mucinous etiology identified 13 additional cases (7%). Conclusions: Use of GNAS increases sensitivity for detection of mucinous lesions. GNAS does not appear to correlate with molecular measures of biological aggressiveness. These findings confirm those in [1], that GNAS should be used in conjunction with a panel of molecular markers for evaluating the malignant potential of pancreatic cystic lesions.

Very high CEA level in a large pancreatic cyst: Is it a surgical indication by itself?

BackgroundPancreatic mucinous cystic lesions might develop malignancy if untreated, or could harbor malignancy at the time of the diagnosis. Many reports stated that cyst fluid carcinoembryonic antigen is an accurate diagnostic marker of pancreatic mucinous cysts. MethodsA man with a incidental pancretic cystic lesion of 35 mm in diameter was admitted to our Department. CT and EUS did not reveal solid components, main duct was not dilated and cyst fluid CEA was very high (1445 ng/ml). ResultsThe patient underwent a pancreatoduodenectomy and the surgical specimen showed a pseudocyst with columnar mucinous epithelium, consistent with low-grade PanIN. ConclusionsIs it possible that the mucinous epithelium of panIN was responsible for the unexpectedly high CEA value?Clinicians should be aware of the usefulness of the CEA level in cystic fluid but even a very high CEA value should not be considered by itself to be evidence of a mucinous lesion.

Tu1734 Cost Analysis of Molecular (DNA) Markers of Suspected Mucinous Pancreatic Cysts (MPCs)

Tu1734 Cost Analysis of Molecular (DNA) Markers of Suspected Mucinous Pancreatic Cysts (MPCs)

Clinical Implications of Mucinous Nonneoplastic Cysts of the Pancreas

An undercharacterized subclass of pancreatic mucinous cysts without histologic characteristics of neoplasia is emerging. This article aimed to highlight the clinical characteristics and implications of this new subset of pancreatic cystic lesions. The clinical, radiologic, and pathologic features of all cysts that underwent operative resection at a tertiary referral pancreatic disease center from February 2005 to June 2009 were reviewed. Immunohistochemistry for mucinous peptide antigens was selectively performed. Of 104 operations, a pathologic examination revealed 52 intraductal papillary mucinous neoplasms, 9 mucinous cystadenomas, 17 serous cystadenomas, 9 pseudocysts, 5 solid pseudopapillary tumors, 2 carcinomas, 1 cystic pancreatic endocrine tumor, and 2 other cystic lesions. Seven mucinous cysts without neoplastic features were identified, representing 2% of all pancreatic resections, 6.7% of all resected cysts, and 10.3% of the 68 mucinous cysts. There was no evidence of cytologic atypia, papillary growth, or ovarian-type stroma in any of the cases. MUC1, MUC2, and MUC5AC were expressed in 83%, 0%, and 100%, respectively. There has been no recurrence with a mean follow-up of 44 months. This underappreciated entity belongs to the family of mucinous pancreatic cysts. However, unifying clinical characteristics that would prevent unnecessary resections in patients harboring these seemingly benign lesions are currently lacking.

Diagnostic accuracy of cyst fluid amphiregulin in pancreatic cysts

BackgroundAccurate tests to diagnose adenocarcinoma and high-grade dysplasia among mucinous pancreatic cysts are clinically needed. This study evaluated the diagnostic utility of amphiregulin (AREG) as a pancreatic cyst fluid biomarker to differentiate non-mucinous, benign mucinous, and malignant mucinous cysts.MethodsA single-center retrospective study to evaluate AREG levels in pancreatic cyst fluid by ELISA from 33 patients with a histological gold standard was performed.ResultsAmong the cyst fluid samples, the median (IQR) AREG levels for non-mucinous (n = 6), benign mucinous (n = 15), and cancerous cysts (n = 15) were 85 pg/ml (47-168), 63 pg/ml (30-847), and 986 pg/ml (417-3160), respectively. A significant difference between benign mucinous and malignant mucinous cysts was observed (p = 0.025). AREG levels greater than 300 pg/ml possessed a diagnostic accuracy for cancer or high-grade dysplasia of 78% (sensitivity 83%, specificity 73%).ConclusionCyst fluid AREG levels are significantly higher in cancerous and high-grade dysplastic cysts compared to benign mucinous cysts. Thus AREG exhibits potential clinical utility in the evaluation of pancreatic cysts.

Cytology Adds Value to Imaging Studies for Risk Assessment of Malignancy in Pancreatic Mucinous Cysts

Evaluate the value of cytology relative to imaging features in risk assessment for malignancy as defined in the Sendai Guidelines. 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. 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. 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. Cytology adds value to the radiological assessment of predicting malignancy in mucinous cysts, particularly in small BD IPMN.

Current status on the diagnosis and management of pancreatic cysts in the Asia–Pacific region: Role of endoscopic ultrasound

Endoscopic ultrasound (EUS) and EUS-guided fine-needle aspiration (EUS-FNA) play increasingly prominent roles in the diagnosis and management of pancreatic cysts. The Asian Consortium of Endoscopic Ultrasound was recently formed to conduct collaborative research in this area. This is a review of literature on true pancreatic cysts. Due to the lack of systematic studies, there are no robust data on the true incidence of pancreatic cystic lesions in Asia and any change in over the recent decades. Certain EUS morphological features have been used to predict particular types of pancreatic cysts. Pancreatic cyst fluid viscosity, cytology, pancreatic enzymes, and tumor markers, in particular carcinoembryonic antigen, can aid in the diagnosis of pancreatic cysts. Hemorrhage and infection are the most common complications of EUS-FNA of pancreatic cysts. Pancreatic cysts can either be observed or resected depending on the benign or malignant nature, or malignant potential of the lesions. Guidelines from an international consensus did not require positive cytological findings to be present in their recommendation for resection, which included all mucinous cystic neoplasms, all main-duct intraductal papillary mucinous neoplasms (IPMN), all mixed IPMN, symptomatic side-branch IPMN, and side-branch IPMN larger than 3 cm. In patients with poor surgical risks, EUS-guided cyst ablation of mucinous pancreatic cysts is an alternative. As long-term prospective data on pancreatic cysts are still not available in Asia, management strategies are largely based on risk stratification by surgical risk and malignant potential. Gene expression profiling of pancreatic cyst fluid and confocal laser endomicroscopic examination of pancreatic cysts are novel techniques currently being studied.

Histologic and Imaging Features of Mural Nodules in Mucinous Pancreatic Cysts

Mural nodules predict malignancy within pancreatic cysts, but it is not clear whether endoscopic ultrasound (EUS) and computed tomography (CT) accurately identify nodules. We assessed images and the histology of mural nodules in branch duct intraductal papillary mucinous neoplasms (BD-IPMNs) and mucinous cystic neoplasms (MCNs) and identified criteria to distinguish mural nodules from mucus. We reviewed pathology specimens and EUS and CT images from consecutive patients with resected BD-IPMNs or MCNs. A blinded interobserver study of the EUS images was then conducted to identify features that distinguished nodules from mucus. After education about these features, the raters interpreted the EUS images again. On the basis of histologic analysis, 22 of 57 cases had epithelial nodules. Cancer or high-grade dysplasia was found in 23% of cysts with nodules versus 3% without nodules (P = .02). On the basis of reports, EUS detected epithelial nodules with 75% sensitivity and 83% specificity, whereas these values were 24% and 100%, respectively, for CT. Mucus accounted for 65% of intracystic lesions detected by EUS and was often diagnosed by using change in body position and fine-needle aspiration. Interobserver analysis identified 3 features that were detected by EUS (echogenicity, edge, and rim) that distinguished mucus from epithelial nodules. The diagnostic accuracy of the raters improved from a mean of 57% to 79% after education about these features (P = .004); accuracy was 90% when all 3 features of mucus were present. Malignancy is associated with epithelial nodules in BD-IPMNs and MCNs, but most echogenic lesions detected in cysts by EUS are mucus. Knowledge of features that discriminate mucus from mural nodules improves the diagnostic accuracy of EUS.

Cyst Fluid Carcinoembryonic Antigen Is an Accurate Diagnostic Marker of Pancreatic Mucinous Cysts

Endoscopic ultrasound (EUS) may offer a diagnostic tool through the combination of imaging and guided fine-needle aspiration of pancreatic cysts. The purpose of this investigation was to determine the most accurate test for differentiating mucinous from nonmucinous cysts. The results of EUS imaging, cytology, and cyst fluid biochemical markers were prospectively collected and compared in a large single-center study (776 patients) using histology or malignant cytology as the final diagnostic standard in 198 patients. The mean cyst fluid carcinoembryonic antigen (CEA) was greater in mucinous cysts (4703.0 ng/mL) compared with nonmucinous cysts (25.8 ng/mL) (P = 0.008). When using the optimal cutoff value of 109.9 ng/mL, the CEA was more accurate (86%, receiver operating characteristic area = 0.928) than EUS imaging (48%) and cytology (58%) in predicting a mucinous cyst (P < 0.0001). Malignant cysts had a mean cyst fluid CEA value (2558.2 ng/mL) similar to benign cysts (4700.2 ng/mL). Cytology (75%) more accurately diagnosed malignant cysts than EUS (66%) and CEA (62%) (P < 0.05). Cyst fluid CEA concentration provides a highly accurate test for the diagnosis of a mucinous cyst, but does not distinguish benign from malignant cysts. Cytology is the most accurate test for the diagnosis of a malignant cyst.

The value of cyst fluid analysis in the pre-operative evaluation of pancreatic cysts.

Like any clinical diagnostic test, analysis of pancreatic cyst fluid should add value in the decision making process of patient management. Pancreatic cysts are a complex group of benign, malignant and premalignant lesions with diverse clinical, radiological and pathological features (1). No longer are the vast majority of pancreatic cysts thought to be pseudocysts, inclusion cysts or benign neoplastic cysts that do not require follow-up. Our knowledge and understanding of neoplastic pancreatic cysts in general and mucinous pancreatic cysts in particular has grown exponentially since the recognition of intraductal papillary mucinous neoplasm (IPMN) as a distinct entity from mucinous cystic neoplasm (MCN) (2). Our realization that all neoplastic mucinous cysts have malignant potential has led to intensive evaluation of patients with both symptomatic and asymptomatic pancreatic cysts to determine the nature of the cyst, and thus the possible need for resection (3).

Fluid analysis prior to surgical resection of suspected mucinous pancreatic cysts. A single centre experience.

EUS-FNA cytology and fluid analysis are frequently utilized to evaluate pancreatic cysts. Elevated cyst fluid CEA is usually indicative of a mucinous pancreatic cyst but whether CEA or amylase values can subclassify various mucinous cysts is unknown. The purpose of this study is to determine whether cyst fluid CEA and amylase obtained by EUS-FNA can differentiate between mucinous cystic neoplasms (MCNs) and intraductal papillary mucinous neoplasms (IPMNs). Using our prospective hospital EUS and surgical databases, we identified all patients who underwent EUS of a pancreatic cyst prior to surgical resection, in the last 10 years. Cysts were pathologically sub-classified as MCNs or IPMNs; all other cysts were considered non-mucinous. Values of cyst fluid CEA and amylase were correlated to corresponding surgical histopathology and compared between the two groups. 134 patients underwent surgery for pancreatic cysts including 82 (63%) that also had preoperative EUS. EUS-FNA was performed in 61/82 (74%) and cyst fluid analysis in 35/61 (57%) including CEA and amylase in 35 and 33 patients, respectively. Histopathology in these 35 cysts demonstrated nonmucinous cysts in 10 and mucinous cysts in 25 including: MCNs (n=9) and IPMNs (n=16). Cyst fluid CEA (p=0.19) and amylase (p=0.64) between all IPMNs and MCNs were similar. Between branched duct IPMNs and MCNs alone, cyst fluid CEA (p=0.34) and amylase (p=0.92) were also similar. In this single center study, pancreatic cyst fluid amylase and CEA levels appeared to be of limited value to influence the differential of mucinous pancreatic cysts. Larger studies are recommended to evaluate this role further.

High‐grade atypical epithelial cells in pancreatic mucinous cysts are a more accurate predictor of malignancy than “positive” cytology

The Sendai guidelines for risk assessment of malignancy in patients with mucinous cysts lists "positive" cytology as a high-risk feature. In the current study, the authors hypothesized that a cytological threshold of high-grade atypical epithelial cells (AEC) is a more accurate predictor of malignancy. The clinical, radiological, and cytological data of 112 patients with histologically confirmed mucinous cysts of the pancreas were reviewed. Cytology slides were blindly reviewed and cells were classified as benign, AEC, or malignant. On histology, neoplasms were grouped as benign (low-grade and moderate dysplasia) and malignant (high-grade dysplasia/carcinoma in situ and invasive carcinoma). There were 92 patients with an intraductal papillary mucinous neoplasm (IPMN) and 20 with a mucinous cystic neoplasm; 39 were malignant and 73 were benign (42 with low-grade dysplasia and 31 with moderate dysplasia). Only 28% (11 of 39) of the malignant cysts were cytologically malignant with a sensitivity of 29%, a specificity of 100%, and an accuracy of 75%. AEC detected 17 additional cancers (44% of all malignant cysts; 16% more than detected on the basis of "positive" cytology). By using AEC as a surgical triage threshold, the sensitivity was 72%, the specificity was 85%, and the accuracy was 80%, with similar values for small (≤ 3 cm) branch duct IPMN. Nine of 73 (12%) benign cysts were identified with AEC, 4 of which had moderate dysplasia. AEC had a positive predictive value of 87% for the detection of a mucinous cyst with moderate dysplasia or worse. AEC are a more accurate predictor of malignancy than "positive" cytology in aspirates of pancreatic mucinous cysts, including small branch duct IPMN. AEC warrant a "suspicious" interpretation for appropriate surgical triage.

Comparison of Preoperative Cytopathology, Tumor Markers and Molecular Analysis for the Diagnosis of Mucinous Pancreatic Cysts in Patients Undergoing Surgical Resection: 2010 Presidential Poster

Purpose: To prospectively evaluate the individual or combined accuracy of cytopathology, cyst fluid tumor markers (CEA) and molecular analysis to differentiate mucinous from non-mucinous cysts. Methods: Consecutive patients with pancreatic cysts referred to our institution for EUS-FNA who were determined have suspected MPCs and subsequently underwent surgical resection at our institution. Cyst fluid was aspirated for cytopathology, DNA analysis (RedPath®, Pittsburgh, PA) and CEA when quantity was sufficient. DNA quantity ≥40ng/ul and/or k-rasmutation and/or ≥2 allelic imbalance mutations and/or CEA>192 ng/ml were all criteria for a MPC. Surgical pathology from pancreas resection was considered the gold standard for diagnosis. Results: 27 patients underwent surgery following EUS-FNA. Final surgical pathology revealed mucinous lesions in 22 (all were intraductal papillary mucinous neoplasms (IPMN)), and non-mucinous lesions in 5 (serous cystadenoma in 2, retention cyst in 1, and pancreatic intraepithelial neoplasia (PanIN) in non-mucinous background in 2). Only one patient had invasive malignancy and another had high grade dysplasia on final pathology. Cytopathology was highly specific in MPC but with low sensitivity of 9%. Mean CEA levels in cyst fluid were numerically higher in the mucinous compared to the non-mucinous group but the difference didn't reach statistical significance due to small sample size (11799 ng/ml vs. 59 ng/ml, p=0.49). Molecular analysis (any criterion) had a sensitivity of 46% and specificity of 100% to detect mucinous lesions. K-ras mutation alone was the single most reliable molecular criterion with a specificity of 100%. K-ras mutation identified one additional mucinous cyst not identified as such by CEA. Combining all molecular markers with CEA improved sensitivity to 74% (table 1). Conclusion: In this series, the sensitivity of pancreatic cyst fluid CEA outperforms any of the individual molecular criteria evaluated for the diagnosis of MPCs. Therefore, we advocate initial screening of cyst fluid CEA prior to obtaining molecular studies. Molecular markers combined with cyst fluid CEA marginally increase sensitivity for MPC and could add diagnostic value in suspected malignant cysts; however, the limited number of malignant cysts in this study precludes a definitive conclusion. A larger sample size with more malignant cysts is required.Table