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Background: Making a specific diagnosis of pancreatic cysts preoperatively is difficult. The new disposable Moray micro forceps biopsy (MFB) device allows tissue sampling from the pancreatic cyst wall/septum and aims to improve diagnosis. This study compares the diagnostic performance of the MFB with the current conventional analysis of pancreatic cyst fluid (PCF)., Methods: A total of 48 patients sampled with MFB were identified. Cysts were classified as mucinous on PCF based on extracellular mucin/mucinous epithelium, carcinoembryonic antigen (CEA) levels ≥192 ng/mL, or KRAS/GNAS mutation. A diagnosis of intraductal papillary mucinous neoplasm was supported by GNAS mutation; a diagnosis of serous cystadenoma was supported by Von Hippel-Lindau tumor suppressor (VHL) mutation. A diagnosis of mucinous cystic neoplasm required the presence of subepithelial ovarian-type stroma. A high-risk cyst was defined as a mucinous cyst with high-grade dysplasia or an adenocarcinoma. Comparisons in diagnostic performance between PCF and MFB were made., Results: The mean age of the patients was 69.6 years (range, 27-90 years); 25 of 48 patients (52.1%) were female. Cysts were in the pancreatic head (13 patients), neck (2 patients), body (20 patients), and tail (13 patients), averaging 3.1 cm (range, 1.2-6.0 cm). There was concordance with mucinous versus nonmucinous classification (60.4% for PCF vs 58.3% for MFB; P = .949). Three high-risk cysts were detected by PCF and 2 were detected by MFB (P = .670). However, MFB diagnosed significantly more specific cysts compared with PCF (50.0% for MFB vs 18.8% for PCF; P<.001)., Conclusions: PCF analysis and MFB have comparable performance in distinguishing between mucinous and nonmucinous cysts and for detecting high-risk cysts. However, MFB was found to be superior for diagnosing specific cyst subtypes, thus adding significant value to preoperative patient management. Cancer Cytopathol 2018;126:414-20. © 2018 American Cancer Society., (© 2018 American Cancer Society.)

Background: Mucinous cystic neoplasms (MCNs) of the pancreas present a management conundrum. The majority are benign but all are resected due to their malignant potential. Recent studies have recommended nonsurgical management. In the current study, the authors analyzed the preoperative imaging, cytology, and cyst fluid characteristics of 136 histologically confirmed MCNs to assess predictors of a high-risk (HR) cyst for surgical triage., Methods: MCNs resected at the Massachusetts General Hospital between 1990 and 2014 formed the study cohort. Patient demographics, cyst size, and mural nodules (MNs) by endoscopic ultrasound, cytology, and cyst fluid carcinoembryonic antigen and amylase levels were correlated with histological grade. A HR cyst was defined as high-grade dysplasia or invasive carcinoma on histology. Performance characteristics were assessed for each parameter, with a cyst size ≥3 cm or a MN on imaging and malignant cytology considered to be "true-positive" results for predicting malignancy., Results: Only 15 of the 136 cysts had HR histology (11%). On average, patients with HR cysts were older than those with low-risk cysts (55 years vs 49 years, respectively). High-grade cytology was the most accurate predictor of malignancy (95%) followed by MN and cyst size together (88%) and MN alone (83%). The average carcinoembryonic antigen level (in ng/mL) increased with the grade of dysplasia but the ranges overlapped between low risk and HR cysts., Conclusions: To the authors' knowledge, the current study is the largest series to date analyzing the cytological features of histologically confirmed MCN. Cytology is insensitive but very specific for detecting a HR MCN and outperformed imaging for the detection of HR MCN. Endoscopic ultrasound-guided fine-needle aspiration and cytology should be performed on any clinically suspected MCN that is being considered for conservative management. Cancer Cytopathol 2017;125:169-177. © 2016 American Cancer Society., (© 2016 American Cancer Society.)

Background: Cystic pancreatic neuroendocrine tumors (cPanNETs) account for 13% to 17% of PanNETs. Although the value of endoscopic ultrasound (EUS) imaging and cyst fluid analysis (CFA) in their preoperative diagnosis has been well described, limited information is available about the diagnostic role of cytology samples obtained from fine-needle aspiration (FNA)., Methods: Cytopathology records between 1992 and 2013 were searched for all reports of cysts interpreted as PanNET. Patient demographics, clinical and radiologic information, CFA, histopathology, and cytopathology findings were recorded. Performance characteristics of cytology and EUS for the accurate diagnosis of cPanNET were calculated., Results: In total, 35 FNAs from 33 patients with cPanNETs were identified, and 34 EUS were performed. Cytology made a specific diagnosis of a cPanNET in 71% of the biopsies compared with a specific diagnosis by EUS in 38% of cases. An interpretation of suspicious for cPanNET was given in 77% of cases by cytology and in 47% by EUS. Cytology identified 86% of the lesions as high-risk pancreatic cysts compared with 56% by EUS. Diagnostic morphology was present on both cytology and cell block preparations in 60% of aspirates, on cytology only in 20%, and on cell block only in 20%. CFA was performed on 51% cyst fluids. All cysts but 1 revealed low carcinoembryonic antigen levels (range, 0.2 to >500 ng/mL; mean, 29.5 ng/mL), and amylase levels were <500 U/L in all but 2 cases (range, 16-1493 U/L; mean, 205 U/L)., Conclusions: Cytology is the most accurate test for preoperative diagnosis of cPanNETs. EUS is insufficiently accurate for independent diagnosis, and carcinoembryonic antigen and amylase analyses are noncontributory., (© 2014 American Cancer Society.)

Background: Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) of pancreatic cysts obtains cyst fluid for cytologic and biochemical analysis, which may determine whether the cyst is mucinous and malignant, contributing to patient management. Despite this added value, EUS-FNA remains controversial in the preoperative assessment of pancreatic cysts. The objective of this study was to assess the utility of EUS-FNA in a cohort of small pancreatic cysts that were benign on imaging studies., Methods: All pancreatic cysts that underwent initial EUS-FNA in 2006 and 2007 were retrospectively analyzed. Ninety-two patients with pancreatic cysts met the inclusion criteria. Patients who had high-risk or worrisome features on imaging studies were excluded. Cytology, histology, and cyst fluid analysis data were collected. The main outcome measurements were radiologic and clinical follow-up as well as cytopathologic and histologic results., Results: EUS-FNA supported a diagnosis of a mucinous cyst in 38 of 92 patients (41%) by carcinoembryonic antigen (CEA) measurement and/or cytology. Cytology demonstrated an absence of high-grade atypia (HGA) in 89 of 92 patients (97%). The mean follow-up was 4.4 years (range, 0-7.7 years), during which 6 cysts were surgically resected and 16 cysts were resampled by at least 1 subsequent EUS-FNA. The overall negative predictive value of cytologic examination for HGA was 99%., Conclusions: EUS-FNA is a screening test that contributes to a triple-negative test for pancreatic cysts--no high-risk stigmata, no worrisome features, and no HGA on cytology--providing a negative predictive value of 99% for conservative management., (© 2013 American Cancer Society.)

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.)

Background: Pancreatic cysts are aspirated to assess whether a cyst is mucinous on one hand and malignant on the other. The authors' retrospective data have indicated that high-grade atypical epithelial cells (AECs) identified on cytology are a high-risk feature and a better threshold than "positive" for detecting malignancy. The objective of the current study was to assess the accuracy of AECs in predicting malignancy in pancreatic cysts., Methods: Cysts aspirated by endoscopic ultrasound (EUS)-guided fine-needle aspiration (EUS-FNAs) obtained between January 2006 and June 2011 were evaluated. Cytologic, histologic, imaging, and cyst fluid analysis data were recorded. AECs were defined as cells that had an increased nuclear-to-cytoplasmic ratio and nuclear hyperchromasia with or without membrane abnormalities and with or without cytoplasmic vacuoles, but of insufficient quality and quantity for a "positive" interpretation. Malignancy included mucinous cysts with high-grade dysplasia and invasive carcinoma. Performance characteristics of cytology with AECs or worse (high-grade atypia [HGA]) for predicting malignancy were assessed., Results: There were 70 FNAs that had histologic confirmation from 404 EUS-FNAs in 352 patients. Excluding 4 nondiagnostic FNAs, the study cohort consisted of 66 FNAs for analysis. There were 24 malignant cysts with 20 true-positive, 4 false-negative, 36 true-negative, and 6 false-positive results. For the detection of malignancy, HGA had 83% sensitivity, 86% specificity, a positive predictive value of 77%, a negative predictive value of 90%, and 85% overall accuracy. The lower threshold for malignancy with AECs resulted in a 12% increase in the detection of malignancy., Conclusions: A finding of AECs on cytology is a high-risk feature for malignancy and is an accurate triage threshold for resection. Cancer (Cancer Cytopathol) 2013;121:29-36 © 2012 American Cancer Society., (Copyright © 2012 American Cancer Society.)

Background: 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., Methods: 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)., Results: 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., Conclusions: 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., (Copyright © 2010 American Cancer Society.)