Intraductal papillary mucinous neoplasm (IPMN) of the pancreas that recurred as a ductal adenocarcinoma likely via intraductal spread: A case report and review of the literature

It is hypothesized that cells of intraductal papillary mucinous neoplasms (IPMNs) of the pancreas can move through the pancreatic duct and seed to form a new tumor (intraductal spread). Although this hypothesis typically refers to recurrent IPMNs in the remnant pancreas of patients who underwent operation for IPMN, studies providing sufficient evidence to prove this hypothesis are limited. Furthermore, if pancreatic ductal adenocarcinoma (PDAC) occurs in the remnant pancreas of patients who underwent complete resection for IPMN, any recurrence of PDAC with no associated IPMN is generally considered independent of prior IPMN. Here, we present a case of a minimally invasive IPMN occurring in the head of the pancreas that recurred as a PDAC in the tail of the pancreas ten years after the first operation for IPMN, likely via intraductal spread. Although the IPMN was surgically resected with negative margins and the recurrent adenocarcinoma did not accompany an IPMN, we found that both lesions shared an exceedingly rare KRAS mutation (p.A11delinsGGGV). Furthermore, we identified a microscopic, low-grade intraepithelial lesion in the main pancreatic duct adjacent to the adenocarcinoma that also harbored the same KRAS mutation. Immunohistochemically, the intraepithelial lesion retained SMAD4 expression, whereas the recurrent adenocarcinoma showed loss of SMAD4 expression, indicating that the intraepithelial lesion was a pancreatic intraepithelial neoplasia (PanIN) rather than adenocarcinoma (cancerization of the duct). These findings suggested that the initial IPMN, recurrent adenocarcinoma, and PanIN were clonally related, and intraductal spread of precursor neoplastic cells may have played a role in developing the adenocarcinoma. This case provides new insight into the process of how metachronous PDAC occurs in patients who undergo complete resection for IPMN.