Pancreatic cystic lesions (PCLs) are becoming more readily identified with advances in imaging technology; however, distinguishing which cysts harbor the potential for malignancy continues to remain a clinical challenge. Identifying premalignant mucinous PCLs including mucinous cystic neoplasms (MCNs) may guide early surgical intervention versus endoscopic surveillance. Novel diagnostic modalities such as EUS-guided needle based confocal laser endomicroscopy (EUS-nCLE) provide real-time in vivo imaging of PCL epithelium and may aide in diagnosing mucinous PCLs. While MCNs are particularly frequent (90%-98%) in women, we present an unusual case of pancreatic MCN in a young man who was diagnosed by EUS-nCLE when current standard of care failed to reveal the diagnosis. A 38-year-old man with well-controlled ulcerative colitis presented with persistent right lower quadrant pain. Imaging with MRI enterography to evaluate for possible small bowel disease incidentally revealed a 5.9 cm pancreatic tail cyst. Patient denied prior history of smoking, alcohol use, gallstone disease or acute pancreatitis. He underwent an EUS which revealed a 5x6 cm anechoic cystic tail lesion with a thick wall. Fine needle aspiration indicated fluid CEA of 9.9ng/ml, amylase of 65,800 U/L and no malignant cells or mucin on cytology. Furthermore, molecular analysis of the cyst fluid by next generation sequencing did not reveal any known mutations. EUS-nCLE was performed and real-time image acquisition revealed multiple solitary epithelial bands in a horizon configuration with variable thickness, consistent with MCN features (Figure 1). The patient underwent a distal pancreatectomy and splenectomy with final pathology revealing MCN with low grade dysplasia (Figure 2). The postoperative course was uncomplicated and in follow up visits patient reported resolution of abdominal pain. Here we show a case where current standard of care (CEA and cytology) failed to identify a MCN lesion. The differentiation of PCLs continues to remain challenging and novel technology including nCLE may improve diagnostic accuracy of mucinous PCLs. Of note, the nCLE description of epithelial bands in horizon configuration have been reproduced in both in vivo and ex vivo CLE imaging with histopathological correlation. Moreover, this case is further unique in that MCNs are only present in 2-10% of men. This report further adds to the current literature on CLE supplementation in the management of PCLs.Figure: MCN with Gross HE 40x. The corresponding histologic section shows that the cyst is lined by columnar cells overlying ovarian type-stroma. The atypia seen in the columnar cells is classified as low-grade dysplasia.Figure: EUS-nCLE demonstrated epithelial bands (black arrows) which are characteristic of mucinous cystic neoplasms. These can be either solitary or appear in layers. (Resolution 20 microns).