Cyst Fluid Carcinoembryonic Antigen Level Research Articles

Improving diagnostic yield of pancreatic serous cystadenoma with cyst fluid ancillary testing, adjunct immunohistochemistry, and additional fine-needle biopsy sampling.

Fine-needle aspiration (FNA) diagnosis of pancreatic serous cystadenoma (SCA) remains challenging. This retrospective study aimed to evaluate the roles of cyst fluid ancillary testing and combined fine-needle biopsy (FNB) in improving the diagnostic yield. The authors retrospectively reviewed cytology cases that were histologically confirmed SCAs. Clinical features and FNA cyst fluid biochemical and molecular analysis results along FNB findings were reviewed. The study cohort included 31 cases from 13 male and 18 female patients with a mean age of 65. The original cytologic diagnoses were nondiagnostic (n=6, 19%), negative for malignant cells/cyst contents (n=7, 23%), atypical cells (n=3, 10%), nonmucinous cyst (n=11, 35%), and serous cystadenoma (n=4, 13%). Cyst fluid carcinoembryonic antigen (CEA) analysis was performed in 17 cases, all of which showed a low CEA level (<192 ng/mL). All 14 cases with molecular testing showed a wild-type KRAS. Inhibin immunohistochemistry was retrospectively performed on the FNA cell blocks, inhibin was positive in six of seven cases tested. In 15 cases with concurrent FNA and FNB biopsies, the diagnosis of SCA was seen in only one FNA case (7%) but 13 FNB cases (87%). This study suggests that FNA diagnosis of SCA remains challenging even with ancillary testing including cyst fluid CEA level and KRAS mutation analysis. Adjunct inhibin immunostaining may help improve the cytologic diagnosis of selective SCA cases. FNB appears superior to FNA for a definite diagnosis of SCA.

Optimal carcinoembryonic antigen (CEA) cutoff values in the diagnosis of neoplastic mucinous pancreatic cysts differ among assays

AimPancreatic cyst fluid carcinoembryonic antigen (CEA) is a pivotal test in the diagnosis and management of neoplastic mucinous cysts (NMC) of the pancreas. Cyst fluid CEA levels of 192 ng/mL...

Role of endoscopic ultrasound and cyst fluid tumor markers in diagnosis of pancreatic cystic lesions.

BACKGROUNDPancreatic cystic lesions (PCLs) are common in clinical practice. The accurate classification and diagnosis of these lesions are crucial to avoid unnecessary treatment of benign lesions and missed opportunities for early treatment of potentially malignant lesions. AIMTo evaluate the role of cyst fluid analysis of different tumor markers such as cancer antigens [e.g., cancer antigen (CA)19-9, CA72-4], carcinoembryonic antigen (CEA), serine protease inhibitor Kazal-type 1 (SPINK1), interleukin 1 beta (IL1-β), vascular endothelial growth factor A (VEGF-A), and prostaglandin E2 (PGE2)], amylase, and mucin stain in diagnosing pancreatic cysts and differentiating malignant from benign lesions. METHODSThis study included 76 patients diagnosed with PCLs using different imaging modalities. All patients underwent endoscopic ultrasound (EUS) and EUS-fine needle aspiration (EUS-FNA) for characterization and sampling of different PCLs. RESULTSThe mean age of studied patients was 47.4 ± 11.4 years, with a slight female predominance (59.2%). Mucin stain showed high statistical significance in predicting malignancy with a sensitivity of 87.1% and specificity of 95.56%. It also showed a positive predictive value and negative predictive value of 93.1% and 91.49%, respectively (P < 0.001). We found that positive mucin stain, cyst fluid glucose, SPINK1, amylase, and CEA levels had high statistical significance (P < 0.0001). In contrast, IL-1β, CA 72-4, VEGF-A, VEGFR2, and PGE2 did not show any statistical significance. Univariate regression analysis for prediction of malignancy in PCLs showed a statistically significant positive correlation with mural nodules, lymph nodes, cyst diameter, mucin stain, and cyst fluid CEA. Meanwhile, logistic multivariable regression analysis proved that mural nodules, mucin stain, and SPINK1 were independent predictors of malignancy in cystic pancreatic lesions. CONCLUSIONEUS examination of cyst morphology with cytopathological analysis and cyst fluid analysis could improve the differentiation between malignant and benign pancreatic cysts. Also, CEA, glucose, and SPINK1 could be used as promising markers to predict malignant pancreatic cysts.

Cyst fluid metabolites distinguish malignant from benign pancreatic cysts.

OBJECTIVESCurrent standard of care imaging, cytology, or cystic fluid analysis cannot reliably differentiate malignant from benign pancreatic cystic neoplasms. This study sought to determine if the metabolic profile of cystic fluid could distinguish benign and malignant lesions, as well as mucinous and non-mucinous lesions.MethodsMetabolic profiling by untargeted mass spectrometry and quantitative nuclear magnetic resonance was performed in 24 pancreatic cyst fluid from surgically resected samples with pathological diagnoses and clinicopathological correlation.Results(Iso)-butyrylcarnitine distinguished malignant from benign pancreatic cysts, with a diagnostic accuracy of 89%. (Iso)-butyrylcarnitine was 28-fold more abundant in malignant cyst fluid compared with benign cyst fluid (P=.048). Furthermore, 5-oxoproline (P=.01) differentiated mucinous from non-mucinous cysts with a diagnostic accuracy of 90%, better than glucose (82% accuracy), a previously described metabolite that distinguishes mucinous from non-mucinous cysts. Combined analysis of glucose and 5-oxoproline did not improve the diagnostic accuracy. In comparison, standard of care cyst fluid carcinoembryonic antigen (CEA) and cytology had a diagnostic accuracy of 40% and 60% respectively for mucinous cysts. (Iso)-butyrylcarnitine and 5-oxoproline correlated with cyst fluid CEA levels (P<.0001 and P<.05 respectively). For diagnosing malignant pancreatic cysts, the diagnostic accuracies of cyst size > 3 cm, ≥ 1 high-risk features, cyst fluid CEA, and cytology are 38%, 75%, 80%, and 75%, respectively.Conclusions(Iso)-butyrylcarnitine has potential clinical application for accurately distinguishing malignant from benign pancreatic cysts, and 5-oxoproline for distinguishing mucinous from non-mucinous cysts.

Cyst Fluid Carcinoembryonic Antigen Level Difference between Mucinous Cystic Neoplasms and Intraductal Papillary Mucinous Neoplasms.

Background/AimsThe role of cyst fluid carcinoembryonic antigen (CEA) level in differentiating mucinous pancreatic cystic lesions (PCLs) is controversial. We investigated the role of cyst fluid CEA in differentiating low-risk (LR)-intraductal papillary mucinous neoplasms (IPMNs) from high-risk (HR)-IPMNs and LR-mucinous cystic neoplasms (MCNs). MethodsThis was a retrospective study of 466 patients with PCLs who underwent endoscopic ultrasound-guided fine-needleaspiration over a 7-year period. On histology, low-grade dysplasia and intermediate-grade dysplasia were considered LR, whereas high-grade dysplasia and invasive carcinoma were considered HR. ResultsData on cyst fluid CEA levels were available for 50/102 mucinous PCLs with definitive diagnoses. The median CEA (range) levels were significantly higher in HR cysts than in LR cysts (2,624 [0.5–266,510] ng/mL vs. 100 [16.8–53,445]ng/mL, p=0.0012). The area under the receiver operating characteristic curve (AUROC) was 0.930 (95% confidence interval [CI], 0.5–0.8; p<0.001) for differentiating LR-IPMNs from LR-MCNs. The AUROC was 0.921 (95% CI, 0.823–1.000; p<0.001) for differentiating LR-IPMNs from HR-IPMNs. Both had a CEA cutoff level of >100ng/mL, with a negative predictive value (NPV) of 100%. ConclusionsCyst fluid CEA levels significantly vary between LR-IPMNs, LR-MCNs, and HR-IPMNs. A CEA cutoff level of >100ng/mL had a 100% NPV in differentiating LR-IPMNs from LR-MCNs and HR-IPMNs.

Sa1443 CYST FLUID CARCINOEMBRYONIC ANTIGEN DIFFERENCE AMONG MUCINOUS CYSTIC NEOPLASMS AND INTRADUCTAL PAPILLARY MUCINOUS NEOPLASMS

Cyst fluid carcinoembryonic antigen (CEA) is a useful marker for differentiating between mucinous from nonmucinous pancreatic cystic lesions (PCLs). However, the role of cyst fluid CEA levels in differentiation between mucinous cystic neoplasms (MCNs) and intraductal papillary mucinous neoplasms (IPMNs) as well as between the low risk (LR) and high risk (HR) mucinous lesions are scanty. We aimed to analyse this subject. This was a retrospective study of 52 patients with mucinous PCls diagnosed by cyto/histo-pathology out of 466 patients who underwent endoscopic-ultrasonography-guided fine-needle aspiration for PCLs over a seven-year period. On histology, low- and intermediate-grade dysplasia were considered as LR, and high-grade dysplasia and invasive carcinoma were considered as HR. Cyst fluid CEA was available for 52/102 mucinous and 44/121 nonmucinous PCLs with definitive diagnoses. The median cyst fluid CEA [Range] values were significantly higher in mucinous compared with nonmucinous cysts (1079 ng/mL [0.5-266510 ] versus 6 ng/mL [0.2-309]), and LR-MCNs compared with LR-IPMNs (7954.7 ng/mL, [299.6-53445] versus 51.3 ng/mL [16.8-132.2]), and HR-IPMNs compared with LR-IPMNs (2624 ng/mL [0.5-266510] versus 100 ng/mL [16.8-53445]). The AUROC was 0.930 (95% confidence interval [CI]: 0.5-0.8) to differentiate between LR-IPMNs and LR-MCNs and 0.921 (95% CI: 0.823-1.000) to differentiate between LR-IPMNs and HR-IPMNs using cyst fluid CEA. Both showed cutoff values of >100 ng/mL and demonstrated a sensitivity of 100/100, specificity of 75/75, and positive and negative predictive values of 66.7/78.9 and 100/100, respectively. Cyst fluid CEA is useful in differentiation between LR-MCNs from LR-IPMNs and LR-IPMNs from HR-IPMNs. Diagnosis using a cyst fluid CEA cutoff value of 100 ng/mL showed a 100% negative predive value in differentiating LR-IPMNs from LR-MCNs and HR-IPMNs.

Cell block processing is optimal for assessing endoscopic ultrasound fine needle aspiration specimens of pancreatic mucinous cysts

AimsThe cell block technique for assessing endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) specimens from pancreatic mucinous cystic lesions (MCLs) was systematically evaluated for the first time, including comparisons with three...

Technical feasibility, diagnostic yield, and safety of microforceps biopsies during EUS evaluation of pancreatic cystic lesions (with video)

Through-the-needle microforceps are a recent addition to the EUS armamentarium for evaluation of pancreatic cystic lesions (PCLs). The main aim of this study was to assess the technical feasibility, diagnostic yield, and safety of EUS-guided microforceps biopsy for PCLs. Our electronic endoscopy database was queried to identify patients who underwent EUS-guided FNA(EUS-FNA) of PCLs and microforceps biopsies during the same procedure. A biopsy was done on the wall of the cyst with the microforceps through the 19-gauge needle, and cyst fluid was collected for cytology and carcinoembryonic antigen (CEA) levels. Adverse events were recorded per published American Society for Gastrointestinal Endoscopy criteria. Twenty-seven patients underwent EUS-FNA and microforceps biopsy of PCLs from February 2016 to July 2017. Fourteen cysts were located in the pancreatic head and/or uncinate, and 13 were located in the body and/or tail region. Microforceps biopsies were technically successful in all cases and provided a pathology diagnosis in 24 of 27 cases (yield 88.9%). Microforceps biopsies diagnosed mucinous cyst in 9 patients (33.3%), serous cystadenoma in 4 (14.8%), neuroendocrine tumor in 1 (3.7%), and benign and/or inflammatory cyst in 10 (37.1%). In 7 patients (26%), microforceps biopsy results drastically changed the diagnosis, providing diagnoses otherwise not suggested by cytology or cyst fluid CEA levels. However, cytology provided a diagnosis of mucinous cyst in 4 cases (14.8%) not detected by microforceps biopsies. No adverse events were noted. Microforceps biopsies were associated with high technical success, and an excellent safety profile and may be a useful adjunctive tool, complementing existing EUS-FNA sampling protocols for PCLs.

"Simple Mucinous Cyst" of the Pancreas: A Clinicopathologic Analysis of 39 Examples of a Diagnostically Challenging Entity Distinct From Intraductal Papillary Mucinous Neoplasms and Mucinous Cystic Neoplasms.

Pancreatic cysts >1 cm lined by nonpapillary mucinous epithelium without ovarian-type stroma pose diagnostic challenges. The term "simple mucinous cyst" was recently proposed for this entity. Our goal was to determine the clinicopathologic characteristics of these cysts, as they have not been previously described. Of the 39 patients with pancreatic resections included in this study, the mean age was 65 years and the female-to-male ratio was 4:1. The characteristics of the cysts are as follows: 82% had elevated cyst fluid carcinoembryonic antigen levels, 67% were unilocular, 69% occurred in the body/tail, 92% did not communicate with pancreatic ducts, the mean size was 2.4 cm (range, 1.0 to 5.5 cm), the cyst contents tended to be serous (48%) or viscous (28%), all had a smooth lining (only 1 had focal excrescences) composed of bland columnar mucinous epithelium (low-grade dysplasia) in 92% with focal high-grade dysplasia in 8%, and 65% had degenerative changes (granulation-like tissue, hemorrhage, and myxoid stroma). The cyst lining was CK7+ and 97% had a MUC5AC+ and/or MUC6+ gastric phenotype; overt intestinal features were absent. In total, 55% of cysts tested (fluid and/or resections) harbored KRAS mutations. The term "simple mucinous cyst" is useful to apply to >1 cm mucinous cysts that do not have characteristic features of intraductal papillary mucinous neoplasms or mucinous cystic neoplasms. KRAS mutations can be detected in these typically bland cysts, and in rare instances, focal high-grade dysplasia may be present. Hence, these cysts should be viewed as neoplastic and treated similarly to other mucinous pancreatic cysts.

Suboptimal accuracy of carcinoembryonic antigen in differentiation of mucinous and nonmucinous pancreatic cysts: results of a large multicenter study

The exact cutoff value at which pancreatic cyst fluid carcinoembryonic antigen (CEA) level distinguishes pancreatic mucinous cystic neoplasms (MCNs) from pancreatic nonmucinous cystic neoplasms (NMCNs) is unclear. The aim of this multicenter retrospective study was to evaluate the diagnostic accuracy of cyst fluid CEA levels in differentiating between MCNs and NMCNs. Consecutive patients who underwent EUS with FNA at 3 tertiary care centers were identified. Patients with histologic confirmation of cyst type based on surgical specimens served as the criterion standard for this analysis. Demographic characteristics, EUS morphology, FNA fluid, and cytology results were recorded. Multivariate logistic regression analysis to identify predictors of MCNs was performed. Receiver-operating characteristic (ROC) curves were generated for CEA levels. A total of 226 patients underwent surgery (mean age, 61 years, 96% white patients, 39% female patients) of whom 88% underwent Whipple's procedure or distal pancreatectomy. Based on surgical histopathology, there were 150 MCNs and 76 NMCNs cases. The median CEA level was 165 ng/mL. The area under the ROC curve for CEA levels in differentiating between MCNs and NMCNs was 0.77 (95% confidence interval, 0.71-0.84, P < .01) with a cutoff of 105 ng/mL, demonstrating a sensitivity and specificity of 70% and 63%, respectively. The cutoff value of 192 ng/mL yielded a sensitivity of 61% and a specificity of 77% and would misdiagnose 39% of MCN cases. Cyst fluid CEA levels have a clinically suboptimal accuracy level in differentiating MCNs from NMCNs. Future studies should focus on novel cyst fluid markers to improve risk stratification of pancreatic cystic neoplasms.

1037 Serum Human Telomerase Reverse Transcriptase Messenger RNA As a Novel Marker for Pancreatic Ductal Adenocarcinoma

1037 Serum Human Telomerase Reverse Transcriptase Messenger RNA As a Novel Marker for Pancreatic Ductal Adenocarcinoma

Cyst fluid carcinoembryonic antigen concentration and cytology by endosonography‐guided fine needle aspiration in predicting malignant pancreatic mucinous cystic neoplasms

To assess the value of carcinoembryonic antigen (CEA) level and cytology examination obtained by endosonography-guided fine needle aspiration (EUS-FNA) in predicting the malignancy of pancreatic mucinous cystic neoplasm (MCN). The data of patients with pancreatic MCN who underwent EUS-FNA in Changhai Hospital, Second Military Medical University (Shanghai, China) from November 2005 to April 2010 were collected and analyzed. The area under receiver operating characteristic (ROC) curve of cyst fluid CEA, sensitivity, specificity, positive (PPV) and negative predictive value (NPV) of the cytology as well as cyst fluid CEA were determined. Of the 20 MCNs confirmed by surgical pathology, 10 were malignant and the remainder were premalignant. Cytology had some value in differentiating malignant from premalignant MCN with a sensitivity of 60.0%, specificity of 100.0%, PPV of 100.0% and NPV of 71.4%. CEA of > 692.8 ng/mL was able to predict malignancy (P = 0.007) with sensitivity of 80.0%, specificity of 90.0%, PPV of 88.9% and NPV of 81.8%, and its area under ROC curve was 0.855. Cyst fluid CEA level and cytology obtained by EUS-FNA are useful for predicting the malignancy of pancreatic MCN.

Cystic pancreatic neuroendocrine tumors: endoscopic ultrasound and fine-needle aspiration characteristics

Limited data are available on the endoscopic ultrasound (EUS) and fine-needle aspiration (FNA) characteristics of cystic pancreatic neuroendocrine tumors (CPanNets). The aims of this study were to describe the EUS and FNA characteristics of pathologically confirmed CPanNets and to compare these characteristics with mucinous cysts from matched patients. From an EUS - FNA database (between 1999 and 2011), 19 patients with a pathologically confirmed CPanNet were identified. Patient characteristics, cyst fluid carcinoembryonic antigen (CEA) levels, pathology, and EUS findings were analyzed. For comparison, age- and sex-matched patients with mucinous cysts were randomly chosen from the same database. Of the 19 patients, two had multiple endocrine neoplasia type 1 and two had metastases. The median diameter of the lesions was 24 mm. EUS revealed unilocular lesions in 7 patients, thinly septated lesions with thin walls in 1, and mixed solid-cystic lesions in 11. EUS - FNA cytology confirmed neoplasm in 12 of the 19 patients (63.2 %). The median cyst fluid CEA level (n = 15) was 1.1 ng/mL (range 0.3 - 500 ng/mL). Compared with matched patients with mucinous cysts, the median cyst fluid CEA was lower (1.1 ng/mL vs. 400 ng/mL), thick walls were more common (66.7 % vs. 13.3 %), and diagnostic cytology was more likely (73.3 % vs. 20.0 %). Analysis of EUS and FNA results showed that the cyst fluid from CPanNets had a lower CEA concentration, a higher frequency of thick walls on EUS, and higher diagnostic cytology compared with mucinous cysts. These findings may aid in the diagnosis of CPanNets.

Endoscopic Ultrasound (EUS) Guided Pancreatic Fluid Aspiration for DNA Analysis of KRAS and GNAS Mutations for the Evaluation of Pancreatic Cystic Neoplasia

Purpose: Discriminating benign from premalignant cysts of the pancreas is limited by the performance of cyst fluid aspirate and cytology. The presence of KRAS mutations in cyst fluid has been reported to increase the yield of cyst fluid aspirate for the presence of neoplastic cysts. Recently, mutations in GNAS have been found to have an oncogenic role in intraductal papillary mucinous neoplasms (IPMN) through promotion of adenyl cyclase activity and cAMP levels. Our aim was to evaluate whether analysis of cyst fluid DNA obtained by EUS for GNAS mutations can enhance the preoperative diagnosis of neoplastic pancreatic cysts. Methods: Endoscopic ultrasound-guided pancreatic cyst aspirates were collected during a 24-month period and investigated for cytology, carcinoembryonic antigen (CEA) level, and molecular analysis. KRAS and GNAS point mutations were detected by dideoxy chain termination sequencing (Applied Biosystems) of extracted DNA (qiagen) from cyst fluid. The cyst fluid analysis was compared to the final surgical pathology or cytology. Results: We identified 23 patients (11 male, mean age = 68.2 ± 13.8 [SD] years) with pancreatic cysts who underwent EUS-guided cyst aspiration. The mean cyst diameter was 2.3 cm (range 1-8 cm). Cysts were located in the head (n=10), body (n=8), and tail (n=5) of the pancreas. The cohort consisted of four serous cystadenomas (SCA), three mucinous cyst neoplasms (MCN), one pseudocyst, five solid-cystic adenocarcinoma (PDA), two solid-cystic endocrine neoplasms, one lymphoepithelial cyst, and seven IPMNs. The mean cyst fluid CEA levels in IPMNs was 3,895 ng/mL (range 22-24,747); 3/7 patients with IPMN had CEA levels <192 ng/mL. Mutations in KRAS were present in 5/7 (71%) IPMNs; LOH was demonstrated in three of these. Three of seven (43%) IPMNs carried a mutation in GNAS, all of which harbored degrees of dysplasia. The mutations in GNAS occurred at codon 201. All IPMNs carried a mutation in at least one of the two oncogenes. No mutations were identified in the SCA, in contrast to the IPMNs (p<0.01). GNAS mutations were not identified in any of the MCNs or PDA (p<0.005 when compared to IPMNs), although KRAS mutations were found in 1/3 (33%) of MCNs and 3/5 (60%) of PDAs. Cyst fluid CEA >192 ng/mL had a sensitivity of 57% to predict the presence of an IPMN. The sensitivity of KRAS mutation in cyst fluid was 71% for the diagnosis of IPMN, but with the addition of GNAS mutations, all IPMNs were identified (sensitivity = 100%, p<0.05). Conclusion: The presence of GNAS in combination with KRAS in pancreatic cystic fluid improves the sensitivity for diagnosis of IPMN when compared to CEA or KRAS alone. This demonstrates the feasibility of GNAS analysis from pancreatic cyst fluid obtained by EUS guided aspiration.

Cyst fluid carcinoembryonic antigen level is not predictive of invasive cancer in patients with intraductal papillary mucinous neoplasm of the pancreas.

Cyst fluid CEA concentration>192 ng/mL has proven accurate to differentiate mucinous from non-mucinous pancreatic cystic neoplasms. It is unclear whether the degree of cyst fluid CEA elevation is predictive of malignant behavior in IPMNs.To determine whether elevated cyst fluid CEA concentrations were predictive of invasive cancer.Cross sectional study.Single National Cancer Institute comprehensive cancer care center experience.47 patients underwent preoperative EUS-FNA with cyst fluid analysis and surgical resection of an IPMN over a 9 year period.Cyst fluid CEA concentrations among the four grades associated with IPMN (low grade dysplasia, moderate dysplasia, high grade dysplasia, and invasive cancer).The mean±standard deviation cyst fluid CEA concentration increased as the pathology progressed from low grade dysplasia (1,261±1,679 ng/mL) to moderate dysplasia (7,171±22,210 ng/mL) to high grade dysplasia (10,807±36,203 ng/mL). However, the mean CEA level decreased (462±631 ng/mL) once invasive cancer developed (P=0.869). The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of a cyst fluid CEA concentration greater than 200 ng/mL for the diagnosis of malignant IPMN (cases of high grade dysplasia and invasive IPMN) was 52.4%, 42.3%, 42.3%, 52.4% and 46.8%, respectively.Single center experience, small patient numbers, retrospective data collection.The degree of cyst fluid CEA elevation is a poor predictor of malignant degeneration within IPMNs. Clinical management decisions regarding surgical resection should not be based upon degree of cyst fluid CEA elevation.

Diagnosis of congenital cervical cysts using carcinoembryonic antigen levels in cyst fluid

To investigate whether carcinoembryonic antigen (CEA) levels in the fluid of median or lateral cervical cysts can improve diagnosis. Cyst fluid CEA levels in 10 cases of median cervical or lateral cervical cysts based on pathological diagnoses (congenital cervical cyst group) were measured. These results were compared with the CEA levels of the control group comprising 10 cases of other head and neck cyst disorders. The CEA levels in nine out of ten cases in the congenital cervical cyst group were ≥10,000ng/mL. The CEA level in the remaining case was 8290ng/mL. In contrast, the CEA levels were low in the control group (>1000ng/mL). The optimal cut-off level between these groups was 8290ng/mL in the receiver operating characteristic curve (p<0.01). Cyst fluid CEA levels may assist in the diagnosis of median and lateral cervical cysts.

Pancreatic lymphoepithelial cysts express CEA and can contain mucous cells: potential pitfalls in the preoperative diagnosis

Pancreatic lymphoepithelial cysts are rare benign cysts that cannot be reliably differentiated from neoplastic mucinous cysts preoperatively. Although elevated cyst fluid carcinoembryonic antigen (CEA) levels support a diagnosis of a mucinous cyst, the finding of increased CEA levels in lymphoepithelial cysts prompted this study. Nine resected lymphoepithelial cysts were examined for expression of CEA, carbohydrate antigen (CA) 19-9, CK7, p63, PAS-D and a panel of mucins. The pathology data were correlated with clinical information, including serum, cyst fluid and imaging studies. By computed tomography scan, although most lymphoepithelial cysts appeared cystic, 23% were described as masses. The endoscopic ultrasound findings were variable, but the lymphoepithelial cysts tended to be hypoechoic cystic lesions or masses. On cytology, 44% of the cysts had squamous cells, 67% had glandular cells and 56% had atypical cells. The cysts were resected because of size ≥3 cm (89%), symptoms (44%) and/or elevated cyst fluid CEA levels (33%). The cyst fluid CEA levels in the three cysts tested were >450 ng/ml. Histopathologically, all cysts were lined by mature, stratified squamous-type cells and produced keratin. Mucous cells were present in 78% of the cysts. The immunohistochemical profile of the squamous lining was CK7+, p63+, MUC1+, MUC4+, MUC2−, MUC5AC− and MUC6−. Even though lymphoepithelial cysts are lined by squamous-type epithelium, all our resected lymphoepithelial cysts expressed CEA and/or CA19-9, many contained mucous cells, and three exhibited markedly elevated cyst fluid CEA levels. Although cyst fluid CEA levels >200 ng/ml support the diagnosis of mucinous neoplasms, this study emphasizes the need for clinicians and pathologists to recognize that lymphoepithelial cysts can mimic neoplastic mucinous cysts clinically, radiographically and on cyst fluid CEA analysis.

T1370 Elevated Cyst Fluid Carcinoembryonic Antigen (CEA) Level is Not a Accurate Predictive Marker of Invasive Cancer in Patients With Intraductal Papillary Mucinous Neoplasm (IPMN) of the Pancreas

Background: In the preoperative management of cystic lesions of the pancreas, an elevated CEA level >192ng/ml has been proven to be the most accurate marker to differentiate between a mucinous or nonmucinous neoplasm. One factor in the decision to operate on these cystic lesions is determined on the degree of CEA elevation. Whether CEA level results can be applied to IPMN’s has not been well studied, but given the mucinous nature of these neoplasms, management decisions are partially based on the degree of cyst fluid CEA level elevation. Aim: The aim of this study was to determine whether a markedly elevated CEA level was predictive of invasive cancer in patients with surgically resected IPMNs. Methods: For this study we identified all patients from our IRB approved Pancreatic IPMN Surgical Database who have undergone an Endoscopic Ultrasound(EUS) procedure at H. Lee Moffitt Cancer Center. 87 patients were included in the analysis with surgical resections from 2000-2009. From this population we included all patients who had preoperative cyst fluid CEA levels obtained by EUS-Guided FNA recorded. One-way ANOVA was performed to examine the differences of CEA levels among pathologic stages. Results: 47 patients (32 men) underwent preoperative EUS-FNA and surgical resection of an IPMN. The mean level of CEA increased as the pathology worsened from no dysplasia (adenoma) to high-grade dysplasia (Carcinoma in situ). Surprisingly, once invasive cancer developed the CEA level markedly decreased to levels comparable to the most benign surgical pathology. Furthermore, there was no difference in CEA levels with statistical significance between pathologic stages (p = 0.35). The Fluid CEA levels and corresponding surgical pathologic diagnoses are summarized in the table below. Conclusion: Based on this retrospective study, a markedly elevated cyst fluid CEA level was not an accurate predictor of invasive cancer in surgically resected IPMNs. In contrast, the appearance of invasive cancer in an IPMN lesion is associated with a decline in mean CEA level and there was no statistical significant difference in the CEA levels between the pathologic groups. Therefore the decision not to resect a cystic lesion should not be based solely on the observation that the CEA is low. Larger studies are needed to better define the role of cyst fluid CEA level in the management of pancreatic IPMNs.

Patient- and Cyst-Related Factors for Improved Prediction of Malignancy within Cystic Lesions of the Pancreas

Background and Aims: Early diagnosis of cancer in pancreatic cysts is important for timely referral to surgery. The aim of this study was to develop a predictive model for pancreatic cyst malignancy to improve patient selection for surgical resection. Methods: We performed retrospective analyses of endoscopic ultrasound (EUS) and pathology databases identifying pancreatic cysts with available final pathological diagnoses. Main-duct intraductal papillary mucinous neoplasms (IPMNs) were excluded due to the clear indication for surgery. Patient demographics and symptoms, cyst morphology, and cyst fluid characteristics were studied as candidate riskfactors for malignancy. Results: 270 patients with pancreatic cysts were identified and analyzed (41% men, mean age 61.8 years). Final pathological diagnoses were branch-duct IPMN (n = 118, 50% malignant), serous cystadenoma (n = 71), pseudocyst (n = 37), mucinous cyst adenoma/adenocarcinoma (n = 36), islet cell tumor (n = 4), simple cyst (n = 3), and ductal adenocarcinoma with cystic degeneration (n = 1). Optimal cut-off points for surgical resection were cyst fluid carcinoembryonic antigen (CEA) ≥3,594 ng/ml, age >50, and cyst size >1.5 cm. Cyst malignancy was independently associated with white race (OR = 4.1, p = 0.002), weight loss (OR = 3.9, p = 0.001), cyst size >1.5 cm (OR = 2.4, p = 0.012), and high CEA >3,594 (OR = 5.3, p = 0.04). In white patients >50 years old presenting with weight loss and cyst size >1.5 cm, the likelihood of malignancy was nearly sixfold greater than in those patients who had none of these factors (OR = 5.8,95% CI = 2.1-16.1, p = 0.004). Conclusions: Riskfactors other than cyst size are important for determination of malignancy in pancreatic cysts. Exceptionally high cyst fluid CEA levels and certain patient-related factors may help to better predict cyst malignancy and the need for surgical treatment.

Preoperative evaluation of pancreatic cystic lesions: Cost-benefit analysis and proposed management algorithm

This study was performed to develop a management algorithm that accurately predicts the necessity of operative intervention and results in significant cost savings for patients with cystic pancreatic tumors. We reviewed 60 patients treated between 1992 and 2003. Accuracy rates of tests used to differentiate benign from premalignant and malignant cysts were calculated. A management algorithm was generated that incorporated clinical presentation, radiologic findings, and selective use of endoscopic procedures. This algorithm was tested for predictive accuracy, and savings between actual management and proposed management were compared. There was an average of 3 preoperative tests performed per patient. Endoscopic procedures included endoscopic retrograde cholangiopancreatography in 21 patients and endoscopic ultrasound in 25 patients. A cyst fluid carcinoembryonic antigen (CEA) level of 158 ng/mL or greater had an accuracy rate of 87.5% that was significantly higher than endoscopic retrograde cholangiopancreatography (72%), endoscopic ultrasound morphology (45%), or endoscopic ultrasound cytology (66.7%). There was no combination of tests that provided greater accuracy than cyst fluid CEA level alone (P < .05). The management algorithm had a positive predictive value of 81%. The average actual cost of radiographic and endoscopic procedures was dollar 8,080 per patient. The proposed cost based on the algorithm was dollar 6,677 with a savings of dollar 1,403 per patient (P = .009). In patients with clinical symptoms or radiographic findings of mucinous or malignant tumors, further testing is excessive. Of endoscopic tests available, the cystic fluid CEA level most accurately predicts the presence of a mucinous neoplasm. A management algorithm based on presenting symptoms, radiographic findings, and cyst fluid CEA level provides a guideline for the evaluation of cystic lesions in the most cost-efficient manner while ensuring proper care.