Intraductal papillary mucinous neoplasm (IPMN) of the pancreas is one of the most well-established precursors of pancreatic cancer. Its progression to acquire invasiveness is a complex process, based on the accumulation of morphological and genetic alterations. Recent advances in DNA sequencing also showed that co-occurring IPMNs and pancreatic cancers could be totally independent, further complicating our understanding of this complex scenario. The distinction between IPMN and related pancreatic cancer vs IPMN and co-occurring—but not related—pancreatic cancer is a challenging task in routine diagnostic activity, but may have important implications for precision oncology. Of note, recent multiregional sequencing-based studies focused not only on IPMN multi-step tumourigenesis, but also on the divergent intratumoural heterogeneity of this neoplasm. Globally considered, there are three different situations in which co-occurring IPMNs and invasive carcinomas can be found in the same pancreata, indicated with different terminologies: (1) IPMN-associated carcinoma: this definition indicates a carcinoma arising from an IPMN and can be also defined as IPMN-derived carcinoma, sequential or likely related; (2) independent IPMN and invasive carcinoma: the two lesions are not related, and this situation is defined as concomitant, de novo or likely independent; (3) branch-off pathway, where an invasive carcinoma and an adjacent IPMN develop divergently in a forked fashion from a common ancestral clone. In this review, we aim at clarifying the most important nomenclature/definitions of these different situations, also providing an overview of the molecular state-of-the-art and of the clinical implications of this complex landscape.
- Pancreatic Neoplasms
- Pathology, Molecular
- Pathology, Surgical
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Handling editor Yoh Zen.
Contributors YO and CL contributed to researching data for the article, made a substantial contribution to discussion of content and wrote and reviewed/edited the manuscript before submission. TF and AS wrote and reviewed/edited the manuscript before submission. All authors approved the current version of the manuscript to be submitted.
Funding This work was supported by JSPS KAKENHI to YO (Grant Numbers JP22KK0282 and JP22K15401). This study was also supported by the Associazione Italiana Ricerca sul Cancro (AIRC IG no. 26343); Fondazione Cariverona: Oncology Biobank Project 'Antonio Schiavi' (prot. 203885/2017); Fondazione Italiana Malattie Pancreas (FIMP-Ministero Salute J38D19000690001); Italian Ministry of Health (RF CO-2019-12369662: CUP: B39C21000370001).
Competing interests None declared.
Provenance and peer review Not commissioned; externally peer reviewed.