Diagnosis Of Mucinous Pancreatic Cysts Research Articles

Revisiting the performance of cyst fluid carcinoembryonic antigen as a diagnostic marker for pancreatic mucinous cysts: a comprehensive 20-year institutional review

ObjectiveElevated pancreatic cyst fluid carcinoembryonic antigen (CEA) has been routinely used to classify mucinous cysts. This study incorporates original data that established the CEA ≥192 ng/mL threshold with over 20...

Pancreatic cyst fluid glucose: rapid, inexpensive, and accurate diagnosis of mucinous pancreatic cysts

BackgroundThe most widely accepted biochemical test for preoperative differentiation of mucinous from benign, nonmucinous pancreatic cysts is cyst fluid carcinoembryonic antigen. However, the diagnostic accuracy of carcinoembryonic antigen ranges from 70% to 86%. Based on previous work, we hypothesize that pancreatic cyst fluid glucose may be an attractive alternative to carcinoembryonic antigen. MethodsPancreatic cyst fluid was collected during endoscopic or operative intervention. Diagnoses were pathologically confirmed. Glucose and carcinoembryonic antigen were measured using a patient glucometer and automated analyzer/enzyme-linked immunosorbent assay. Sensitivity, specificity, accuracy, and receiver operator characteristic analyses were performed. ResultsCyst fluid samples from 153 patients were evaluated (mucinous: 25 mucinous cystic neoplasms, 77 intraductal papillary mucinous neoplasms, 4 ductal adenocarcinomas; nonmucinous: 21 serous cystic neoplasms, 9 cystic neuroendocrine tumors, 14 pseudocysts, 3 solid pseudopapillary neoplasms). Median cyst fluid glucose was lower in mucinous versus nonmucinous cysts (19 vs 96 mg/dL; P < .0001). With a threshold of ≤ 50 mg/dL, cyst fluid glucose was 92% sensitive, 87% specific, and 90% accurate in diagnosing mucinous pancreatic cysts. In comparison, cyst fluid carcinoembryonic antigen with a threshold of >192 ng/mL was 58% sensitive, 96% specific, and 69% accurate. Area under the curve for glucose and CEA were similar at 0.91 and 0.92. ConclusionCyst fluid glucose has significant advantages over carcinoembryonic antigen and should be considered for use as a routine diagnostic test for pancreatic mucinous cysts.

EUS and EUS-FNA diagnosis of suspected pancreatic cystic neoplasms: Is the sum of the parts greater than the CEA?

Carcinoembryonic antigen (CEA) is suggested as the single most useful EUS/EUS-FNA derived test for the diagnosis of mucinous pancreatic cysts. To investigate the yield and diagnostic performance of EUS/EUS-FNA on an intention to diagnose basis and to determine the utility of the recommended CEA and amylase cut-off values. A retrospective study of a prospectively maintained database of 433 procedures performed in a 10 year period. Diagnostic performance of EUS-FNA was determined in 133 procedures with a definite diagnosis. CEA value was determined in significantly fewer procedures (58.6%) than EUS diagnosis was stated (83.4%; p<0.0001), cyst fluid appearance recorded (89.4%) or adequate sample for cytology obtained (76.7%; p<0.005). Median CEA was significantly higher in mucinous cysts than non-mucinous (175ng/ml vs 3ng/ml, p<0.0001) and in malignant cysts compared to benign (8945ng/ml vs 93ng/ml, p<0.001). On an intention-to-diagnose analysis, a CEA cut-off of 110ng/ml was significantly less accurate (42.8%) than EUS diagnosis (67.7%), cytology (58.6%) or aspirate appearance (66.9%; p<0.05 for all comparisons). However, the combination of EUS diagnosis, cytology and CEA provided higher sensitivity (91%), specificity (75%) and accuracy (85.7%) than each component test alone (p<0.05 for all comparisons). Median amylase was significantly higher in benign compared to high-risk mucinous cysts ((11,429IU/L vs. 113IU/L; p<0.05. The combination of EUS, cytology and CEA performed well. Malignant cysts had a higher CEA value than benign cysts. On an intention to diagnose basis a CEA cut-off of 110ng/ml performed poorly.

The “String Sign” for Diagnosis of Mucinous Pancreatic Cysts

Purpose: To assess the performance characteristics of the “string sign” in pancreatic cyst fluid for the diagnosis of mucinous cysts, and the utility of a novel sequential interpretation model for cyst fluid tests. Methods: Medical records of all patients undergoing EUS FNA (fine needle aspiration) of pancreatic cystic lesions at one institution from 2003 to 2012 were reviewed. String sign was performed prospectively, and results were obtained from EUS reports. The string sign was performed at the time of EUS FNA by placing a drop of fluid between two gloved fingers, or watching the fluid drip from the FNA needle. A positive sign was defined as formation of a string at least 1 cm in length and lasting for at least 1 second. Diagnosis for each cystic lesion was independently determined using standardized criteria including histology results. A sequential cyst fluid test interpretation model was created, in which the string sign was interpreted first, followed by additional tests interpreted sequentially. Results: String sign results were available for 318 cystic lesions, of which 232 had an independent basis for diagnosis, including 118 mucinous lesions. For 98 histologically proven cases the sensitivity, specificity, PPV, NPV, +LR, and -LR of the string sign for diagnosis of mucinous cysts was 58%, 95%, 94%, 60%, 11.3, and 0.45 respectively. Results were similar for all 232 lesions. String sign performance was comparable to cyst fluid CEA at a diagnostic threshold of 800 ng/ml. The string sign had a superior sensitivity to mucin staining (p=0.029) and cytology (p=0.002). In 10 cases the string sign was positive and cyst fluid CEA was < 200 ng/ml; 6 of these were IPMN. The remaining 4, which were not mucinous, all had cyst fluid CEA < 5 ng/ml. The sequential testing model is shown in the table. When the string sign was positive, specificity was high without further cyst fluid test interpretation. When the string sign was negative, additional stepwise test interpretation improved the sensitivity for diagnosis of a mucinous lesion from 58% to 96%.Table: Table. Performance of a sequential test interpretation modelConclusion: The string sign is highly specific for mucinous pancreatic cysts, and improves overall diagnostic accuracy of pancreatic cyst fluid analysis. A sequential test interpretation model incorporating the string sign yields high diagnostic specificity and sensitivity for mucinous pancreatic lesions.

Performance characteristics of molecular (DNA) analysis for the diagnosis of mucinous pancreatic cysts

Diagnosis of mucinous pancreatic cysts (MPCs) is challenging due to the poor sensitivity of cytology provided by EUS-guided-FNA (EUS-FNA). To quantify the test characteristics of molecular (DNA) analysis in suspected low-risk MPCs. A prospective cohort study performed in between 2008 and 2011. Academic referral center. Consecutive patients who underwent EUS-FNA of suspected MPCs. EUS-FNA and molecular (DNA) analysis of cyst fluid. The sensitivity and specificity of molecular analysis in the diagnosis of MPCs using the criterion standard of surgical pathology in resected cysts. Patients with suspected MPCs underwent EUS-FNA and cyst fluid DNA analysis. Surgical resection was performed in 48 patients (17%), confirming a mucinous pathology in 38 (79%). In this group, molecular analysis had a sensitivity of 50% and a specificity of 80% in identifying MPCs (accuracy of 56.3%). The combination of molecular analysis with cyst fluid carcinoembryonic antigen (CEA) and cytology resulted in higher MPC diagnostic performance than either one of its individual components, with a sensitivity, specificity, and accuracy of 73.7%, 70%, and 72.9%, respectively. There was no significant difference in accuracy between molecular analysis and CEA/cytology in this group. Single-center experience. Molecular analysis aids in the diagnosis of MPCs when cytology is nondiagnostic or cyst fluid is insufficient for CEA or its level is indeterminate. Our results do not support the routine use of molecular analysis, which should be used selectively after review of imaging findings and cyst fluid studies. Further studies are needed to assess DNA's performance in malignant cysts.

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.

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