Endoscopic ultrasound-guided fine-needle aspiration for the differential diagnosis of intraductal papillary mucinous neoplasms and size stratification for surveillance

We read with great interest the paper by Kamata et al. published in the January issue of Endoscopy [1]. The authors examined (1) the incidence of pancreatic ductal adenocarcinomas (PDACs) concomitant to or derived from branch duct intraductal papillary mucinous neoplasm (IPMN), and (2) the usefulness of endoscopic ultrasound (EUS) relative to other imaging methods for detecting these tumors. They found that IPMN-concomitant PDACs were quite often detected at diagnosis and during follow-up, and that EUS plays an important role in management as it allows detection of small carcinomas at an early stage. We think the results make an important contribution to the current knowledge on the topic. However, there are some points that need to be clarified and discussed further.

First, the authors defined branch duct IPMN as a dilated branch duct that was connected to the pancreatic duct without main duct dilation, according to international consensus guidelines [2]. Although this is an important criterion for the definition of branch duct IPMN, the sensitivity and specificity of radiological tests and EUS are not satisfactory to exclude nonmucinous cysts and mucinous cystic neoplasms of the pancreas [3] [4]. The same guideline also stresses that such a connection is not always observed and chemical analysis of the fluid for carcinoembryonic antigen (CEA) and amylase levels as well as cytology by EUS-guided fine-needle aspiration (FNA) are often useful for the differential diagnosis of branch duct IPMN. In particular, the guideline recommends cyst fluid analysis for evaluation of small branch duct IPMNs without “worrisome features” in centers with expertise in EUS-FNA. We agree with the consensus report that distinction of branch duct IPMNs, especially from small oligocystic serous cystic neoplasms, is challenging when only imaging tests are used and that EUS-FNA with cyst fluid CEA determination may also be required. Recently, molecular analysis of fluid to detect a GNAS mutation was shown to be highly specific to distinguish branch duct IPMN from serous and mucinous cystic neoplasms [5]. As a new technology, needle-based confocal laser endomicroscopy has demonstrated potential utility for the detection of IPMN, with 100 % specificity and 59 % sensitivity [6]. In addition, the presence of high grade epithelial atypia in the cyst fluid analysis has a high accuracy of 80 % to predict malignancy and detects 30 % more cancers in small branch duct IPMN than the presence of “worrisome features” [2] [7] [8]. Based on these results, new high risk factors proposed include a rapidly increasing cyst size and high grade atypia [2]. This may prevent unnecessary surgery, which may occur when the decision is based on an increase in cyst size alone. The issue of whether a rapid growth rate is correlated with an increased risk of malignancy remains unclear, and close follow-up of such patients rather than immediate resection is recommended [2]. We think EUS-FNA is an important method for the differential diagnosis of pancreatic cysts, and without it, the diagnosis and management of branch duct IPMN would be controversial in some cases. EUS-FNA is also helpful for risk stratification and surgery decisions in selected cases.

Our second point is that the last two consensus reports suggested surveillance of branch duct IPMN cases according to size stratification of cysts [2] [4]. The authors have not mentioned the cyst size in their study. In their conclusion, they suggest performing EUS at regular follow-up visits and we wonder whether cyst size is used to determine follow-up interval.

• References

• 1 Kamata K, Kitano M, Kudo M et al. Value of EUS in early detection of pancreatic ductal adenocarcinomas in patients with intraductal papillary mucinous neoplasms. Endoscopy 2014; 46: 22-29
• 2 Tanaka M, Fernandez-del Castillo C, Adsay V et al. International consensus guidelines 2012 for the management of IPMN and MCN of the pancreas. Pancreatology 2012; 12: 183-197
• 3 Brugge WR, Lewandrowski K, Lee-Lewandrowski E et al. Diagnosis of pancreatic cystic neoplasms: a report of the cooperative pancreatic cyst study. Gastroenterology 2004; 126: 1330-1336
• 4 Tanaka M, Chari S, Adsay V et al. International consensus guidelines for management of intraductal papillary mucinous neoplasms and mucinous cystic neoplasms of the pancreas. Pancreatology 2006; 6: 17-32
• 5 Dal Molin M, Matthaei H, Wu J et al. Clinicopathological correlates of activating GNAS mutations in intraductal papillary mucinous neoplasm (IPMN) of the pancreas. Ann Surg Oncol 2013; 20: 3802-3808
• 6 Konda VJ, Meining A, Jamil LH et al. A pilot study of in vivo identification of pancreatic cystic neoplasms with needle-based confocal laser endomicroscopy under endosonographic guidance. Endoscopy 2013; 45: 1006-1013
• 7 Pitman MB, Genevay M, Yaeger K et al. High-grade atypical epithelial cells in pancreatic mucinous cysts are a more accurate predictor of malignancy than “positive” cytology. Cancer Cytopathol 2010; 118: 434-440
• 8 Genevay M, Mino-Kenudson M, Yaeger K et al. Cytology adds value to imaging studies for risk assessment of malignancy in pancreatic mucinous cysts. Ann Surg 2011; 254: 977-983