Clinical Impact of Needle-based Confocal Laser Endomicroscopy of Cystic Pancreatic Lesions

Clinical Impact of Needle-based Confocal Laser Endomicroscopy of Cystic Pancreatic Lesions (CINE-Cyst)

Background The diagnostic evaluation of cystic pancreatic lesions represents a difficult problem for clinical decision making, due to the increased incidental discovery of such lesions during cross-sectional imaging (computed tomography or magnetic resonance). Prevalence of cystic pancreatic lesions is estimated between 2 to 20% in the adult population (1-3), while autopsy studies show that the prevalence increases with age (4). The WHO classification (revised in 2010) reported several categories, with serous cystadenoma (SCA), mucinous cystic neoplasms (MCN), intraductal papillary mucinous neoplasms (IPMN) and pseudopapillary neoplasms representing more than 90% (5). Several of these lesions progress to cystadenocarcinoma (with the notable exception of SCA), hence the differential diagnosis is extremely important for the clinical decisions that currently involve either imaging follow-up (usually based on EUS and magnetic resonance imaging [MRI]) or referral to surgery with a final pathological diagnosis established after resection.

Nevertheless, there is considerable overlap in the imaging characteristics of benign, premalignant or malignant pancreatic cysts which leads to unclear clinical management algorithms. Several international guidelines addressed the diagnosis and management of cystic pancreatic lesions (6-8). The most comprehensive guideline reported a clinical decision algorithm which included clinical and imaging criteria, like pancreatitis / jaundice or cyst size > 3 cm, thickening / enhancing cyst walls, main pancreatic duct (MPD) size 5-9 mm, non-enhancing mural nodules and abrupt changes in the caliber of pancreatic duct with distal pancreatic atrophy [8]. If any of these clinical / imaging characteristics are present then EUS is considered mandatory to assess a definite mural nodule, main duct features suspicious for involvement, as well as to perform EUS-guided fine needle aspiration (FNA) with cytopathology exam in order to exclude malignancy.

Endoscopic ultrasound (EUS) represents a highly valuable tool in the management of patients with focal pancreatic masses, either solid or cystic. As a minimally invasive technique that enables high-resolution imaging of the pancreatic parenchyma and surrounding structures it is considered the method of choice for the detection of clinically suspected pancreatic lesions, with a negative predictive value close to 100% [9]. Its diagnostic sensitivity was shown by previous studies to be superior compared to other imaging techniques, especially in the case of smaller tumors [10, 11]. After detection of cystic pancreatic lesions, certain morphological features allow the discrimination of specific types [12]:

• pseudocysts - parenchymal changes , without septation or nodules
• serous cystadenomas - multiple microcysts and honeycomb appearance
• mucinous cystadenoma - thickened septations and wall, with calcifications
• intrapapillary mucinous neoplasia (IPMN) - communication with the MPD There aren't universally accepted morphological parameters to predict either the type or the risk of malignancy by EUS [8]. "Worrisome features" on imaging include cyst size (above 3 cm), thickened cyst walls, MPD size of 5-9 mm, non-enhanced mural nodules, abrupt changes in MPD caliber with distal pancreatic atrophy, and lymphadenopathy. "High risk stigmata" include obstructive jaundice in a cystic pancreatic head mass, enhanced solid component or MPD size of over 10 mm, thus warranting an indication for surgery, if clinically feasible. Generally, all cysts with "worrisome features" and cysts over 3 cm, without worrisome features, should undergo EUS, while all cysts with "high-risk stigmata" should undergo surgical resection [8].