A case of incipient pancreatic ductal adenocarcinoma concomitant with intraductal papillary mucinous neoplasm, confirmed by multiregion sequencing analysis

Abstract

Concomitant pancreatic ductal adenocarcinoma (PDA) is observed in a subset of patients with intraductal papillary mucinous neoplasm (IPMN) of the pancreas, and early detection of those progressing lesions is difficult. We present a case with a de novo carcinoma in situ (CIS) discovered incidentally around the resection margin of IPMNs. A man in his 70s with a history of acute pancreatitis at the age of 50 years and no family history of PDA had a pancreatoduodenectomy for three isolated branch duct IPMNs that caused recurrent pancreatitis. During the 2-year follow-up period, the index lesion in the pancreatic head grew significantly, whereas the other cysts remained small and without mural nodules. The majority of the cysts are histologically composed of low-grade dysplasia and are classified as gastric-type IPMN. CIS with nuclear overexpression of p53 was located in the main pancreatic duct and adjacent brunch duct, which involved the pancreatic resection margin. The precise pathological analysis combined with multiregion sequencing revealed the CIS harbored KRAS G12V and TP53 R248W. Conversely, IPMNs contained GNAS mutant cells as well as components containing additional KRAS mutations. These findings suggested that the CIS formed independently of the multiple IPMNs and appeared to be an early manifestation of concomitant PDA with coexisting IPMNs. Despite widespread agreement on the resection of the radiographically significant IPMN lesion (s), the latent invasive cancer was not eradicated. A detailed pathological and molecular assessment of the resected materials may aid in a better management strategy for concurrent lesions.