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Mo1437 EUS Characteristics of Pancreatic Lymphoepithelial Cysts: a Case Series From a Large Referral Center
Abstracts
retrospective chart review was performed on consecutive patients who underwent EUS with FNA of pancreatic cysts at one tertiary referral center from 2000-08 and second referral center from 2009 - 2012. Patients with personal or family history of pancreatic adenocarcinoma, known acute or chronic pancreatitis, cysts !15mm, or imaging features suspicious for malignancy on EUS (cysts with solid component, mural nodules, thick cyst wall and dilated pancreatic duct) were excluded. All patients who had either carcinoembryonic antigen (CEA) or cytological examination of the cystic fluid performed were included in the study. The cytology was considered diagnostic if it showed malignancy (defined as malignant cells, atypical cells or cells suspicious/suggestive of malignancy) or definitive diagnosis of serous or mucinous cyst. The cytology was negative if the sample was not satisfactory, acellular, paucicellular or had benign epithelial cells. Malignancy was confirmed by surgical pathology or metastases on imaging. CEA O192 ng/ml was considered mucinous, ! 5ng/ml serous and values in between indeterminate. Results: 125 patients with benign appearing pancreatic cysts were included in the study. Cyst sizes were: 42 patients (33.6%) with cyst size 15-19mm; 45 patients (36%) 20-29mm and 37 patients (29.6%) O19mm. Cyst size wasn’t available in 1 patient. Samples were sent for cytology in 111 (89%) of these patients: 3 (2.7%) patients had malignant cells, 2 (1.8%) were diagnostic of mucinous cyst and 106 (95.4%) were indeterminate. 2/3 patients with malignant cytology underwent surgery and the pathology was completely benign. The third patient did not undergo surgery. Follow-up imaging after 4 years showed stable size of cyst and no evidence of malignancy. 1/2 patients where cytology was diagnostic of mucinous cyst, CEA was O192 ng/ml, it was not sent in the other due to viscous and insufficient fluid. In cysts when CEA was measured, the diagnostic yield of CEA was 68%. Cytology did not add have incremental diagnostic value over CEA and added $150 - 250 to the total cost of the procedure. Conclusion: Cytological analysis of benign appearing cysts is unnecessary and adds cost to the procedure without any incremental benefit. It can also lead to unnecessary surgeries. Checking CEA only may be sufficient and the most costeffective approach.
Mo1437 EUS Characteristics of Pancreatic Lymphoepithelial Cysts: a Case Series From a Large Referral Center Kunal Dalal*1, John M. Dewitt1, Stuart Sherman1, Harvey Cramer2, Temel Tirkes3, Mohammad a. AL-Haddad1 1 Gastroenterology and Hepatology, Indiana University Medical Center, Indianapolis, IN; 2Pathology, Indiana University Medical Center, Indianapolis, IN; 3Radiology, Indiana University Medical Center, Indianapolis, IN Introduction: Lymphoepithelial cysts (LECs) of the pancreas are benign lesions that can mimic cystic neoplasms on imaging. EUS features are not well characterized due to the limited number of reported cases. Methods: In a retrospective, single center case series, FNA, surgical pathology, and EUS databases were searched to identify patients with pancreatic LECs who underwent EUS with confirmatory cytopathology or resection pathology. EUS characteristics of LECs, including size, location, border, components, and associated ductal dilation, were assessed. Imaging results and cyst fluid characteristics, including available CEA and amylase levels, were also recorded. Presence of nucleated and/or anucleated squamous cells admixed with a variable number of lymphocytes on FNA smear was considered diagnostic of LEC. Results: From 2004-2013, 15 patients (11 male, mean age 56 13 years) with 16 confirmed LECs underwent EUS. Presenting symptoms included: abdominal pain in 6 and weight loss in 2; 7 were asymptomatic with incidental lesions on imaging. Mean LEC diameter was 31 13.5 mm. LECs were located in the tail in 9 cases, body in 4, uncinate process in 1, and 2 were exophytic (1 from body, 1 from tail). 7 had mixed solid/cystic components (2 of which were mostly solid, 1 had calcifications), 8 were purely cystic (2 had internal debris), and 1 was solid with no cystic components. No wall nodularity or duct dilation was noted on EUS, though a mural nodule was seen on MRI in 1 lesion. 2 of 10 cases with available CT/MRI had discrepant cyst morphology as compared to EUS. When adequate fluid was aspirated, its consistency was thick/viscous in 6 or thin in 3; color was clear in 3 or turbid/opaque in 3. 10 LECs were diagnosed on cytology (1 confirmed by surgical pathology); in the 6 remaining cases, cytology was suggestive of LEC (squamous cells noted) in 3 and inconclusive in 3. In these 6, diagnosis of LEC was established by subsequent surgical pathology. Median cyst fluid CEA (nZ5) and amylase (nZ6) were 2.4 ng/ml (range 1.3-13,088), and 100 U/mL (range 5-1111), respectively. 6 patients had resection: 2 due to symptoms attributed to the cyst, and 4 due to suspected malignancy based on indeterminate clinical or imaging findings. 4 of 9 patients without resection had subsequent imaging available (median 39 months after EUS, range 19-62), and all 4 showed stable cyst size. Conclusions: LEC morphology on EUS varies from predominantly solid to purely cystic, making them difficult to distinguish from pancreatic cystic neoplasms on appearance alone. Most patients in our series were males, and LECs were commonly well-defined, and localized to the body/tail. Cyst fluid was mainly thick and turbid, but CEA and amylase levels were highly variable and may not be useful markers. Most patients avoided surgery for these benign lesions on the basis of EUS-FNA findings.
AB330 GASTROINTESTINAL ENDOSCOPY Volume 79, No. 5S : 2014
Mo1438 Fluid Genetic Analyses Predict Biological Behavior of Pancreatic Cysts: 3-Year Experience Jonathan Kung*1, Oscar a. Lopez2, Erin M. Mccoy2, Sofiya Reicher2, Viktor E. Eysselein2 1 Internal Medicine, Harbor UCLA Medical Center, Redondo Beach, CA; 2 Gastroenterology, Harbor UCLA Medical Center, Torrance, CA Background/Aims: The widespread use of cross-sectional imaging has led to the increased detection of pancreatic cysts. Endoscopic ultrasound (EUS) with fineneedle aspiration and cyst fluid analysis is routinely used to evaluate pancreatic cysts. However, clinical course of these lesions is often not well defined. Our study evaluated whether EUS imaging, cyst fluid CEA, and cytology combined with cyst fluid genetic analyses for allelic imbalance and genetic mutations can be used to better predict malignant potential of pancreatic cysts. Methods: In a retrospective analysis, we collected data from 72 patients (43 Women and 29 Men, Mean age 66 (30-84)) with pancreatic cysts who underwent EUS with fine-needle aspiration from 2010 to 2013. Follow-up data was obtained over a mean of 2.4 years. Cyst fluid was analyzed for CEA, KRAS, GNAS mutations, and allelic imbalance using RedPath Integrated Pathology, Inc., and sent for cytology. Cysts were categorized as serous (CEA!5 ng/ ml, no cyst nodules or cyst wall thickening on EUS, clear aspirate), mucinous (CEA O192 ng/ml, viscous aspirate), and branch duct intraductal papillary mucinous neoplasm (IPMN) (CEA O192 ng/ml, EUS characteristics consistent with IPMN, viscous aspirate). Based on KRAS/GNAS point mutations, allelic imbalance, and DNA quantity, cyst fluid genetic analyses were reported as benign, statistically indolent, or aggressive. Results: 72 patients underwent endoscopic ultrasound with fine-needle aspiration revealing 39 IPMN’s, 17 MCN’s, and 16 SCN’s. Of the 39 patients with IPMN’s, 8 (20 %) patients contained cysts with atypical or malignant cytology. 7 out of those 8 (88 %) patients had cyst fluid genetic analyses including either KRAS/ GNAS mutation or allelic imbalance or both. Out of the 56 patients with either IPMNs or MCNs, 18 (32 %) patients had pancreatic cysts with abnormal genetic fluid analysis. Of those 18 patients, 9 contained atypical or malignant cytology indicating a sensitivity of 90 %, specificity of 86 %, and a positive predictive value of 50 %. There was also a significant correlation between negative cystic fluid genetic analysis and exclusion of pancreatic cyst atypia or malignancy with a negative predictive value of 98 %. Ultimately, 11 patients were referred for surgery with 2 patients with final pathology showing adenocarcinoma. Conclusion: Genetic mutations (KRAS and GNAS) and allelic imbalance detected in pancreatic mucinous cysts are associated with progression to malignancy and could be helpful as predictors of biological behavior of pancreatic cysts. In our experience, genetic analyses when used in combination with endosonographic imaging, cytology, and fluid CEA could serve as a guide to clinical decisions regarding cyst surgical resection and follow up.
Mo1439 Management Strategy of Pancreatic Cyst Patients Based on Integrated Molecular Pathology in 492 Patients: the Final Results of a Multicenter Study Mohammad a. AL-Haddad*1, Thomas E. Kowalski2, Ali Siddiqui2, Howard Mertz3, Damien Mallat4, Nadim Haddad5, Nidhi Malhotra5, Brett Sadowski5, Mark J. Lybik6, Sandeep Patel7, Emuejevoke Okoh7, Laura Rosenkranz7, Michael Karasik8, Michael Golioto8, Jeffrey D. Linder9, Marc F. Catalano10 1 Indiana University, Indianapolis, IN; 2Thomas Jefferson University, Philadelphia, PA; 3Nashville GI Associates, Nashville, TN; 4Premier Gastroenterology of Texas, Dallas, TX; 5Georgetown University, Washington, DC; 6Northside Gastroenterology, Indianapolis, IN; 7 University of Texas San Antonio, San Antonio, TX; 8Connecticut GI, PC, Hartford, CT; 9Digestive Health Associates of Texas, Dallas, TX; 10St. Luke’s Medical Center, Milwaukee, WI Introduction: Guideline-recommended first-line tests cannot effectively stratify pancreatic cysts according to malignant potential, resulting in many avoidable surgeries in patients with benign disease and jeopardizing earliest possible interventions in patients with malignancy. We evaluated how integrated molecular pathology (IMP) diagnoses might be used in patient management when cytology is non-malignant given the ability of IMP to risk stratify patients. Methods: The cohort consisted of 492 patients who had non-malignant cytology results at the time of IMP diagnosis (RedPath). Patient outcomes were classified as benign or malignant based on subsequent surgical pathology (nZ209) or subsequent clinical course (nZ283) including malignant cytology results on follow up, clinical cancer management, or 23+ months (23-92 months; median 35 months) imaging follow-up. IMP diagnoses were classified as: Benign (Ben), Statistically Indolent (SI), Statistically Higher Risk (SHR), or Aggressive (Agg) based on integration of clinical, imaging, and molecular characteristics associated with malignancy. Ben signified lack of molecular characteristics. SI signified presence of a single molecular characteristic but absence of concerning clinical features. SHR signified presence of a single molecular characteristic accompanied by concerning clinical features. Agg signified presence of at least two molecular characteristics. Results: After 23 months from initial IMP, no patient (0/397) with Ben or SI diagnosis had malignancy (Figure 1); prior to 23
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retrospective chart review was performed on consecutive patients who underwent EUS with FNA of pancreatic cysts at one tertiary referral center from 2000-08 and second referral center from 2009 - 2012. Patients with personal or family history of pancreatic adenocarcinoma, known acute or chronic pancreatitis, cysts !15mm, or imaging features suspicious for malignancy on EUS (cysts with solid component, mural nodules, thick cyst wall and dilated pancreatic duct) were excluded. All patients who had either carcinoembryonic antigen (CEA) or cytological examination of the cystic fluid performed were included in the study. The cytology was considered diagnostic if it showed malignancy (defined as malignant cells, atypical cells or cells suspicious/suggestive of malignancy) or definitive diagnosis of serous or mucinous cyst. The cytology was negative if the sample was not satisfactory, acellular, paucicellular or had benign epithelial cells. Malignancy was confirmed by surgical pathology or metastases on imaging. CEA O192 ng/ml was considered mucinous, ! 5ng/ml serous and values in between indeterminate. Results: 125 patients with benign appearing pancreatic cysts were included in the study. Cyst sizes were: 42 patients (33.6%) with cyst size 15-19mm; 45 patients (36%) 20-29mm and 37 patients (29.6%) O19mm. Cyst size wasn’t available in 1 patient. Samples were sent for cytology in 111 (89%) of these patients: 3 (2.7%) patients had malignant cells, 2 (1.8%) were diagnostic of mucinous cyst and 106 (95.4%) were indeterminate. 2/3 patients with malignant cytology underwent surgery and the pathology was completely benign. The third patient did not undergo surgery. Follow-up imaging after 4 years showed stable size of cyst and no evidence of malignancy. 1/2 patients where cytology was diagnostic of mucinous cyst, CEA was O192 ng/ml, it was not sent in the other due to viscous and insufficient fluid. In cysts when CEA was measured, the diagnostic yield of CEA was 68%. Cytology did not add have incremental diagnostic value over CEA and added $150 - 250 to the total cost of the procedure. Conclusion: Cytological analysis of benign appearing cysts is unnecessary and adds cost to the procedure without any incremental benefit. It can also lead to unnecessary surgeries. Checking CEA only may be sufficient and the most costeffective approach.
Mo1437 EUS Characteristics of Pancreatic Lymphoepithelial Cysts: a Case Series From a Large Referral Center Kunal Dalal*1, John M. Dewitt1, Stuart Sherman1, Harvey Cramer2, Temel Tirkes3, Mohammad a. AL-Haddad1 1 Gastroenterology and Hepatology, Indiana University Medical Center, Indianapolis, IN; 2Pathology, Indiana University Medical Center, Indianapolis, IN; 3Radiology, Indiana University Medical Center, Indianapolis, IN Introduction: Lymphoepithelial cysts (LECs) of the pancreas are benign lesions that can mimic cystic neoplasms on imaging. EUS features are not well characterized due to the limited number of reported cases. Methods: In a retrospective, single center case series, FNA, surgical pathology, and EUS databases were searched to identify patients with pancreatic LECs who underwent EUS with confirmatory cytopathology or resection pathology. EUS characteristics of LECs, including size, location, border, components, and associated ductal dilation, were assessed. Imaging results and cyst fluid characteristics, including available CEA and amylase levels, were also recorded. Presence of nucleated and/or anucleated squamous cells admixed with a variable number of lymphocytes on FNA smear was considered diagnostic of LEC. Results: From 2004-2013, 15 patients (11 male, mean age 56 13 years) with 16 confirmed LECs underwent EUS. Presenting symptoms included: abdominal pain in 6 and weight loss in 2; 7 were asymptomatic with incidental lesions on imaging. Mean LEC diameter was 31 13.5 mm. LECs were located in the tail in 9 cases, body in 4, uncinate process in 1, and 2 were exophytic (1 from body, 1 from tail). 7 had mixed solid/cystic components (2 of which were mostly solid, 1 had calcifications), 8 were purely cystic (2 had internal debris), and 1 was solid with no cystic components. No wall nodularity or duct dilation was noted on EUS, though a mural nodule was seen on MRI in 1 lesion. 2 of 10 cases with available CT/MRI had discrepant cyst morphology as compared to EUS. When adequate fluid was aspirated, its consistency was thick/viscous in 6 or thin in 3; color was clear in 3 or turbid/opaque in 3. 10 LECs were diagnosed on cytology (1 confirmed by surgical pathology); in the 6 remaining cases, cytology was suggestive of LEC (squamous cells noted) in 3 and inconclusive in 3. In these 6, diagnosis of LEC was established by subsequent surgical pathology. Median cyst fluid CEA (nZ5) and amylase (nZ6) were 2.4 ng/ml (range 1.3-13,088), and 100 U/mL (range 5-1111), respectively. 6 patients had resection: 2 due to symptoms attributed to the cyst, and 4 due to suspected malignancy based on indeterminate clinical or imaging findings. 4 of 9 patients without resection had subsequent imaging available (median 39 months after EUS, range 19-62), and all 4 showed stable cyst size. Conclusions: LEC morphology on EUS varies from predominantly solid to purely cystic, making them difficult to distinguish from pancreatic cystic neoplasms on appearance alone. Most patients in our series were males, and LECs were commonly well-defined, and localized to the body/tail. Cyst fluid was mainly thick and turbid, but CEA and amylase levels were highly variable and may not be useful markers. Most patients avoided surgery for these benign lesions on the basis of EUS-FNA findings.
AB330 GASTROINTESTINAL ENDOSCOPY Volume 79, No. 5S : 2014
Mo1438 Fluid Genetic Analyses Predict Biological Behavior of Pancreatic Cysts: 3-Year Experience Jonathan Kung*1, Oscar a. Lopez2, Erin M. Mccoy2, Sofiya Reicher2, Viktor E. Eysselein2 1 Internal Medicine, Harbor UCLA Medical Center, Redondo Beach, CA; 2 Gastroenterology, Harbor UCLA Medical Center, Torrance, CA Background/Aims: The widespread use of cross-sectional imaging has led to the increased detection of pancreatic cysts. Endoscopic ultrasound (EUS) with fineneedle aspiration and cyst fluid analysis is routinely used to evaluate pancreatic cysts. However, clinical course of these lesions is often not well defined. Our study evaluated whether EUS imaging, cyst fluid CEA, and cytology combined with cyst fluid genetic analyses for allelic imbalance and genetic mutations can be used to better predict malignant potential of pancreatic cysts. Methods: In a retrospective analysis, we collected data from 72 patients (43 Women and 29 Men, Mean age 66 (30-84)) with pancreatic cysts who underwent EUS with fine-needle aspiration from 2010 to 2013. Follow-up data was obtained over a mean of 2.4 years. Cyst fluid was analyzed for CEA, KRAS, GNAS mutations, and allelic imbalance using RedPath Integrated Pathology, Inc., and sent for cytology. Cysts were categorized as serous (CEA!5 ng/ ml, no cyst nodules or cyst wall thickening on EUS, clear aspirate), mucinous (CEA O192 ng/ml, viscous aspirate), and branch duct intraductal papillary mucinous neoplasm (IPMN) (CEA O192 ng/ml, EUS characteristics consistent with IPMN, viscous aspirate). Based on KRAS/GNAS point mutations, allelic imbalance, and DNA quantity, cyst fluid genetic analyses were reported as benign, statistically indolent, or aggressive. Results: 72 patients underwent endoscopic ultrasound with fine-needle aspiration revealing 39 IPMN’s, 17 MCN’s, and 16 SCN’s. Of the 39 patients with IPMN’s, 8 (20 %) patients contained cysts with atypical or malignant cytology. 7 out of those 8 (88 %) patients had cyst fluid genetic analyses including either KRAS/ GNAS mutation or allelic imbalance or both. Out of the 56 patients with either IPMNs or MCNs, 18 (32 %) patients had pancreatic cysts with abnormal genetic fluid analysis. Of those 18 patients, 9 contained atypical or malignant cytology indicating a sensitivity of 90 %, specificity of 86 %, and a positive predictive value of 50 %. There was also a significant correlation between negative cystic fluid genetic analysis and exclusion of pancreatic cyst atypia or malignancy with a negative predictive value of 98 %. Ultimately, 11 patients were referred for surgery with 2 patients with final pathology showing adenocarcinoma. Conclusion: Genetic mutations (KRAS and GNAS) and allelic imbalance detected in pancreatic mucinous cysts are associated with progression to malignancy and could be helpful as predictors of biological behavior of pancreatic cysts. In our experience, genetic analyses when used in combination with endosonographic imaging, cytology, and fluid CEA could serve as a guide to clinical decisions regarding cyst surgical resection and follow up.
Mo1439 Management Strategy of Pancreatic Cyst Patients Based on Integrated Molecular Pathology in 492 Patients: the Final Results of a Multicenter Study Mohammad a. AL-Haddad*1, Thomas E. Kowalski2, Ali Siddiqui2, Howard Mertz3, Damien Mallat4, Nadim Haddad5, Nidhi Malhotra5, Brett Sadowski5, Mark J. Lybik6, Sandeep Patel7, Emuejevoke Okoh7, Laura Rosenkranz7, Michael Karasik8, Michael Golioto8, Jeffrey D. Linder9, Marc F. Catalano10 1 Indiana University, Indianapolis, IN; 2Thomas Jefferson University, Philadelphia, PA; 3Nashville GI Associates, Nashville, TN; 4Premier Gastroenterology of Texas, Dallas, TX; 5Georgetown University, Washington, DC; 6Northside Gastroenterology, Indianapolis, IN; 7 University of Texas San Antonio, San Antonio, TX; 8Connecticut GI, PC, Hartford, CT; 9Digestive Health Associates of Texas, Dallas, TX; 10St. Luke’s Medical Center, Milwaukee, WI Introduction: Guideline-recommended first-line tests cannot effectively stratify pancreatic cysts according to malignant potential, resulting in many avoidable surgeries in patients with benign disease and jeopardizing earliest possible interventions in patients with malignancy. We evaluated how integrated molecular pathology (IMP) diagnoses might be used in patient management when cytology is non-malignant given the ability of IMP to risk stratify patients. Methods: The cohort consisted of 492 patients who had non-malignant cytology results at the time of IMP diagnosis (RedPath). Patient outcomes were classified as benign or malignant based on subsequent surgical pathology (nZ209) or subsequent clinical course (nZ283) including malignant cytology results on follow up, clinical cancer management, or 23+ months (23-92 months; median 35 months) imaging follow-up. IMP diagnoses were classified as: Benign (Ben), Statistically Indolent (SI), Statistically Higher Risk (SHR), or Aggressive (Agg) based on integration of clinical, imaging, and molecular characteristics associated with malignancy. Ben signified lack of molecular characteristics. SI signified presence of a single molecular characteristic but absence of concerning clinical features. SHR signified presence of a single molecular characteristic accompanied by concerning clinical features. Agg signified presence of at least two molecular characteristics. Results: After 23 months from initial IMP, no patient (0/397) with Ben or SI diagnosis had malignancy (Figure 1); prior to 23
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