Pancreatic ductal adenocarcinomas arising from intraductal papillary mucinous neoplasms are aggressive despite being low stage: implications on Screening and “early diagnosis”

Abstract

The literature is highly conflicting regarding the nature and behavior of pancreatic ductal adenocarcinomas (PDAC) arising from intraductal papillary mucinous neoplasm (IPMN). We investigated and contrasted the clinicopathological features of PDACs associated with IPMN (I-PDAC, n&#x2009;=&#x2009;52 - only bona-fide and &#x2265;&#x2009;1&#xa0;cm IPMNs along with ordinary pancreatobiliary type invasive adenocarcinomas were included in this group-), versus without (NI-PDAC, n&#x2009;=&#x2009;390) versus those associated with other IPMN mimicker cysts (pseudo-IPMN-associated, ps-PDAC, n&#x2009;=&#x2009;39) including retention cysts. In I-PDAC, the average size of the IPMN was 4.05&#xa0;cm, and 36.5% were >&#x2009;3&#xa0;cm, and the PDAC components were captured at an earlier stage (49% pT1) as compared to NI-PDACs (21% pT1), and ps-PDACs (18% pT1). I-PDAC also had a lesser frequency of lymphovascular invasion and lymph node metastasis. However, despite being less advanced PDACs, the overall survival of patients with I-PDACs was only modestly superior to NI-PDACs and ps-PDACs without statistical significance (median survival 44.2 vs. 26.7 vs. 28.4 months, and 5-year survival 41.4% vs. 24% and 0%), and this gap further closed when PDAC size was matched. This data underscores: (1) In >&#x2009;60% of I-PDACs, the IPMN component is <&#x2009;3&#xa0;cm. (2) Contradictory to the prevailing impression in the literature, conventional PDACs arising from frank IPMNs do not behave that much better than ordinary PDACs despite being less advanced. (3) Even small PDACs may warrant adjuvant treatment. (4) Additional studies are needed to preoperatively distinguish "trivial cysts" from progression-prone IPMNs. 4) Following surgical resection of PDAC, it is still important to distinguish the nature of a cyst&#x2009;&#x2265;&#x2009;1&#xa0;cm as IPMN vs. pseudo-IPMN as ps-PDACs are significantly more aggressive which may be related to their ability to cause secondary cystic changes which requires further scrutiny. (5) Screening and removing IPMNs before they become invasive is crucial. 5) Even "early" may be too late: Even I-PDACs that are early stage are lethal which may necessitate re-focusing research efforts on biology, and etiopathogenesis such as anatomy associated chemical carcinogenetic factors.