Intraductal tubulopapillary neoplasm (ITPN) of the pancreas: a distinct entity among pancreatic tumors

Abstract

Aims: intraductal tubulopapillary neoplasm (ITPN)of the pancreas is a recently recognized pancreatictumor entity. Here we aimed to determine the mostimportant features with a systematic review coupledwith an integrated statistical approach.Methods and results: PubMed, SCOPUS, and Embasewere searched for studies reporting data on pancreaticITPN. The clinicopathological, immunohistochemical,and molecular data were summarized. Then a compre-hensive survival analysis and a comparative analysis ofthe molecular alterations of ITPN with those of pancre-atic ductal adenocarcinoma (PDAC) and intraductalpapillary mucinous neoplasm (IPMN) from referencecohorts (including the International Cancer GenomeConsortium- ICGC dataset and The Cancer GenomeAtlas, TCGA program) were conducted. The core find-ings of 128 patients were as follows: (i) Clinicopathologi-cal parameters: pancreatic head is the most commonsite; presence of an associated adenocarcinoma wasreported in 60% of cases, but with rare nodal metastasis.(ii) Immunohistochemistry: MUC1 (>90%) and MUC6(70%) were the most frequently expressed mucins. ITPNlacked the intestinal marker MUC2; unlike IPMN, it didnot express MUC5AC. (iii) Molecular landscape: Com-pared with PDAC/IPMN, the classic pancreatic driversKRAS,TP53,CDKN2A,SMAD4,GNAS,andRNF43were less altered in ITPN (P<0.001), whereasMCLamplifications,FGFR2fusions, andPI3KCAmutationswere commonly altered (P<0.001). (iv) Survival anal-ysis: ITPN with a “pure” branch duct involvementshowed the lowest risk of recurrence.Conclusion: ITPN is a distinct pancreatic neoplasmwith specific clinicopathological and molecular char-acteristics. Its recognition is fundamental for its clini-cal/prognostic implications and for the enrichment ofpotential targets for precision oncology.