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

Abstract

Intraductal tubulopapillary neoplasm (ITPN) of the pancreas: a distinct entity among pancreatic tumorsAims: Intraductal tubulopapillary neoplasm (ITPN) of the pancreas is a recently recognized pancreatic tumor entity. Here we aimed to determine the most important features with a systematic review coupled with an integrated statistical approach. Methods and results: PubMed, SCOPUS, and Embase were searched for studies reporting data on pancreatic ITPN. The clinicopathological, immunohistochemical, and molecular data were summarized. Then a comprehensive survival analysis and a comparative analysis of the molecular alterations of ITPN with those of pancreatic ductal adenocarcinoma (PDAC) and intraductal papillary mucinous neoplasm (IPMN) from reference cohorts (including the International Cancer Genome Consortium-ICGC dataset and The Cancer Genome Atlas, TCGA program) were conducted. The core findings of 128 patients were as follows: (i) Clinicopathological parameters: pancreatic head is the most common site; presence of an associated adenocarcinoma was reported in 60% of cases, but with rare nodal metastasis. (ii) Immunohistochemistry: MUC1 (>90%) and MUC6 (70%) were the most frequently expressed mucins. ITPN lacked the intestinal marker MUC2; unlike IPMN, it did not express MUC5AC. (iii) Molecular landscape: Compared with PDAC/IPMN, the classic pancreatic drivers KRAS, TP53, CDKN2A, SMAD4, GNAS, and RNF43 were less altered in ITPN (P < 0.001), whereas MCL amplifications, FGFR2 fusions, and PI3KCA mutations were commonly altered (P < 0.001). (iv) Survival analysis: ITPN with a "pure" branch duct involvement showed the lowest risk of recurrence. Conclusion: ITPN is a distinct pancreatic neoplasm with specific clinicopathological and molecular characteristics. Its recognition is fundamental for its clinical/prognostic implications and for the enrichment of potential targets for precision oncology.

Integrative characterization of intraductal tubulopapillary neoplasm (ITPN) of the pancreas and associated invasive adenocarcinoma

“…The present study confirmed the genomic distinctiveness of ITPN by showing that typical PDAC drivers, including KRAS, TP53, SMAD4, and CDKN2A, are less frequently altered in this lesion in comparison with conventional PDAC. Alterations in PDAC drivers, at similar or lower frequency, have already been reported in previous studies of pancreatic ITPNs 38 . The relative paucity of PDAC alterations in this case series highlights the molecular differences with conventional PDAC, but it should be acknowledged that KRAS alterations are still present in a not-negligible subset of cases (4/16 cases in this series, 25%).…”

Adenocarcinoma in Intraductal Tubulopapillary Neoplasm of the Pancreas: A Case Report and Literature Review

“…ITPN is positive for the pancreatic duct differentiation markers CK7, CK19, MUC1, and MUC6 [ 7 , 8 , 15 ] but negative for CDX2, MUC2, and MUC5AC [ 7 ]. These negative IHC results demonstrated no gastroenteric differentiation [ 8 ].…”

“…Basturk et al and Paolino et al discovered that approximately 70% and 60% of ITPN cases were associated with invasive carcinoma, respectively [ 7 , 15 ]. Invasive foci have features comparable to PDAC; biopsy of the tumor cells, including invasive cells, may lead to a false diagnosis of PDAC.…”

“…ITPN is distinguished from IPMN and ductal adenocarcinoma primarily by the absence of KRAS and BRAF mutations [ 2 , 7 , 8 , 18 , 19 ]. In addition, the usual pancreatic regulators (CDKN2, TP53, GNAS, SMAD4, and RNF43) were less changed in ITPN compared to PDAC [ 15 ]. Unfortunately, in our case, mutation detection was performed for only the breast cancer gene BRCA1, which was negative.…”

Modern aspects of the management of pancreatic intraductal papillary mucinous neoplasms: a narrative review

“…The newest edition (the 5th in 2019) of the World Health Organization (WHO) Guidelines classified the intraductal precursors of adenocarcinoma as IPMNs and included the previously considered variants of IPMNs, i.e., intraductal oncocytic papillary neoplasms (IOPNs) and ITPNs, as distinct neoplasms [ 10 , 29 ]. The dysplasia of these lesions may be either of low grade or high grade, and they eventually progress to invasive carcinoma.…”