Pancreatic ductal adenocarcinoma with a predominant large duct pattern has better recurrence-free survival than conventional pancreatic ductal adenocarcinoma: a comprehensive histopathological, immunohistochemical, and mutational study.

Large duct pattern of pancreatic ductal adenocarcinomas (PDACs) comprises occasional large cancer glands (>0.5 mm in size), along with conventional smaller cancer glands. They histologically mimic intraductal papillary mucinous neoplasms. However, the clinicopathologic significance of PDACs with predominant large duct pattern (PLDP) has not been systematically evaluated. A total of 41 cases of PDACs with PLDP, which were defined as irregularly-shaped cancer glands >0.5 mm in size occupied >50% of tumor volume, were enrolled and their clinicopathological, immunohistochemical, and targeted exome-wise mutational characteristics were compared with 298 conventional PDACs. PDACs with PLDP had cancers with larger tumor sizes (P = 0.025), which were more frequently well to moderately differentiation (P < 0.001), with less lymphovascular invasion (P = 0.013) and had a higher T category (P = 0.023) than conventional PDACs. Immunohistochemically, PDACs with PLDP showed similar abnormal p53 (61%) and SMAD4 (59%) expression patterns as conventional PDACs. In addition, PDACs with PLDP showed diffuse MUC1 (88%), MUC5AC (100%), MUC6 (66%), and focal MUC2 (20%) expressions. More frequent ROS1 mutations were observed in PDACs with PLDP. PDAC patients with PLDP had a better overall and recurrence-free survival (OS and RFS; median, 42 and 34 months) than that of patients with conventional PDACs (34 and 16 months) as per univariate (P = 0.037 and P = 0.001) and multivariate (P = 0.031 and P = 0.034) analyses. PDACs with PLDP showed mutational patterns similar to those of conventional PDACs. They had unique histologic features and longer OS and RFS compared to those of conventional PDACs. Therefore, PDACs with PLDP could be considered a histologic subtype of PDACs.