Pancreatic tumors that develop and grow within the pancreatic ducts include ITPN, IPMN, PDAC, neuroendocrine neoplasm (NEN), and acinar cell carcinoma (ACC) [2]. While these tumors have distinct characteristics, their similar growth patterns within the pancreatic duct can make differentiation challenging through conventional diagnostic approaches. ITPN, classified as a pancreatic intraductal neoplasm in the 2019 WHO tumor classification, is a rare solid nodular tumor obstructing dilated pancreatic ducts, lacking mucin, and composed of uniformly high-grade epithelial cells [8].

The differentiation between ITPN and PDAC is sometimes particularly challenging, as both can present as solid tumors with similar enhancement patterns in imaging studies [9]. In our case, despite comprehensive imaging studies and immunohistochemical analysis of the biopsy specimen, a definitive preoperative diagnosis remained elusive. The postoperative pathological examination revealed features characteristic of both ITPN and PDAC, necessitating additional diagnostic approaches.

The genetic profile of pancreatic tumors has emerged as a crucial differentiating factor in such challenging cases. Table 1 shows the comparison of gene alterations in PDAC and ITPN, and the results for this case. The genetic mutations observed in our case—notably KRAS and TP53 mutations—strongly aligned with the characteristic mutation pattern of PDAC. These mutations, present in approximately 95% and 75% of PDAC cases respectively, are rarely observed in ITPN. Conversely, genetic changes typically associated with ITPN, such as MCL amplifications (31.8%), FGFR2 fusions (18.2%), and PIK3CA mutations (13.6%), were absent in our case [5,6,7]. Recent comprehensive analysis has shown that these distinct genetic profiles reflect fundamentally different oncogenic pathways between PDAC and ITPN. While PDAC is characterized by KRAS-dependent signaling activation and loss of tumor suppressor function through TP53 mutations, ITPN shows enrichment of alterations affecting growth factor signaling pathways through FGFR2 fusions and PI3K pathway activation. Furthermore, molecular pathway analysis has demonstrated that PI3K-Akt signaling is the most activated pathway in ITPN, suggesting potential therapeutic implications [5]. In our case, genetic testing proved particularly valuable as conventional histopathological and immunohistochemical findings were inconclusive. The molecular profile definitively supported the diagnosis of PDAC, enabling us to implement appropriate adjuvant chemotherapy based on established evidence. This case highlights the critical role that comprehensive genetic analysis can play in resolving diagnostically challenging cases, ultimately leading to optimal treatment selection.

An intraductal growth pattern called “cancerization of ducts (COD)” is reported in approximately 60% of surgically resected PDAC cases [10]. Recent studies have shown that COD is associated with female gender, advanced T stage, lymphovascular invasion, perineural invasion, and R1 resection margin status. Notably, it does not significantly impact overall survival or recurrence-free survival [11]. These findings suggest that COD status may have implications for treatment planning, particularly in the preoperative setting.

The treatment approach for resectable PDAC has been well-established, with proven efficacy of neoadjuvant chemotherapy using gemcitabine and S-1 combination therapy [12] and adjuvant chemotherapy with either gemcitabine monotherapy [13, 14] or S-1 monotherapy [3]. In contrast, rare pancreatic tumors such as ITPN lack established evidence for pre- or post-operative chemotherapy, necessitating careful case-by-case consideration. In our patient, although the preoperative diagnosis of PDAC was not possible, precluding neoadjuvant chemotherapy, the postoperative diagnosis of PDAC through genetic testing enabled the implementation of evidence-based adjuvant chemotherapy. The patient’s recurrence-free survival of 15 months to date may be partly attributed to this accurate postoperative diagnosis and subsequent appropriate adjuvant therapy. This case highlights the critical impact that an accurate diagnosis can have on treatment decisions and potentially on patient outcomes.

This case emphasizes the importance of a multifaceted diagnostic approach for pancreatic tumors, particularly when conventional imaging and postoperative pathology yield inconclusive results. The integration of genetic testing can play a crucial role in confirming the diagnosis and guiding treatment decisions, particularly regarding chemotherapy. However, it is essential that no single diagnostic modality be relied upon exclusively. A comprehensive evaluation incorporating imaging, pathological findings, and genetic testing results is necessary for an accurate diagnosis and optimal treatment planning.

Given the rarity of intraductal PDAC and ITPN, a further case accumulation and analysis are vital to establish robust evidence for future treatment strategies and enhance our understanding of these challenging pancreatic neoplasms. Future research should focus on developing more specific imaging criteria to differentiate pancreatic intraductal tumors and identify novel biomarkers for an accurate diagnosis. In addition, long-term follow-up studies of cases such as ours could provide valuable insights into the natural history and prognosis of intraductal PDAC misdiagnosed as ITPN.

In conclusion, we experienced a case in which we initially diagnosed ITPN based on preoperative imaging tests and finally diagnosed PDAC based on a detailed pathological examination and genetic testing and were able to perform appropriate postoperative adjuvant chemotherapy.