Eggplant-like pancreas: transformation in a year

Intraductal tubulopapillary neoplasm (ITPN) was isolated from intraductal papillary mucinous neoplasm (IPMN) in 2009 (1). ITPN, a pancreatic intraductal neoplasm in the 2019 WHO tumor classification, are considered to lack mucin, composed of uniformly high-grade epithelial cells and have a better prognosis (2-4). ITPN shares overlapping imaging features with pancreatic ductal adenocarcinoma (PDAC) and IPMN, including intraductal solid masses and pancreatic duct dilatation. Previous studies have shown that although ITPN often appears as a solid intraductal mass with main pancreatic duct dilatation on abdominal computed tomography (CT), it typically demonstrates better-defined margins than PDAC, higher attenuation values in the portal venous phase on contrast-enhanced CT, and more pronounced contrast washout. In contrast to IPMN, the distal segment of the main pancreatic duct in ITPN is often not dilated. In addition, ITPN may exhibit the “two-tone duct sign” on magnetic resonance imaging (MRI) and contrast-enhanced CT. Some cases of ITPN have also been reported to show a “cork-of-wine-bottle sign” on magnetic resonance cholangiopancreatography (MRCP) and endoscopic retrograde cholangiopancreatography (ERCP) images, and endoscopic ultrasound (EUS) may provide superior contrast resolution compared with CT or MRCP. However, these imaging features are largely derived from small case series and remain investigational, with limited evidence to support their routine clinical application; therefore, they should be interpreted with caution (3,5,6). At present, no reliable imaging-based diagnostic strategy for ITPN has been established in clinical practice. The diagnosis of ITPN relies primarily on histopathological examination and immunohistochemistry. Grossly, ITPN are typically nodular and occasionally exhibit papillary architecture, with a soft consistency. Microscopically, tumor cells are arranged in an orderly fashion, characterized by back-to-back tubular glands and resulting cribriform structures. The lesions usually display relatively uniform morphology with high-grade dysplasia throughout, without progression from low-grade atypia, and without transition to IPMN or pancreatic intraepithelial neoplasia (PanIN). Although invasive carcinoma is frequently present, the invasive component is often limited. Immunohistochemically, ITPN displays a heterogeneous profile, with a hallmark low expression of MUC2 and MUC5AC. The majority of ITPN cases demonstrate positive staining for MUC1, MUC6, and CA19-9, and are also labeled with CAM5.2, CK7, and CK19 (4,7-9). The absence of KRAS and TP53 mutations, along with the presence of MCL amplification, FGFR2 fusion, and PIK3CA mutations, constitutes the genetic profile of ITPN (9). ITPN, a relatively rare epithelial tumor of the pancreas, has historically been regarded as an indolent neoplasm characterized by slow progression, favorable prognosis, and low recurrence rates. However, Due to the limited number of reported cases and significant pathological heterogeneity, the formulation of standardized diagnosis and treatment guidelines in clinical practice has been hindered. As a result, treatment decisions largely depend on the professional experience of various institutions and the specific circumstances of each case, and clinical diagnosis and treatment still face challenges. For example, in an unusual case we identified, the tumor showed diffuse enlargement and progressed rapidly within one year (Figure 1).

Figure 1 Timeline of the patient’s disease progression. CT, computed tomography; MRI, magnetic resonance imaging.

A 72-year-old man had experienced 5 episodes of chills and fever for 1 year and jaundice for 1 month, with a slight increase in the CA19-9 level (45.1–53.5 U/mL). He had a history of bladder stones, pulmonary tuberculosis and 2 hypoglycemic syncope events. At the initial visit to a local hospital in February 2022, a CT scan showed a mixed uneven density shadow in the whole pancreas, with a size of 46.4 mm × 143.8 mm (Figure S1). After 10 months of conservative treatment, obstructive jaundice (total bilirubin 191.5 µmol/L) accompanied by a significant increase in the CA19-9 level (1,881.8 U/mL) was observed, and percutaneous cholecystostomy was performed in a local hospital. Due to coronavirus disease 2019 (COVID-19) infection and severe malnutrition, the patient recuperated at home for two months. The patient showed no other positive signs except for emaciation when visiting our hospital in February 2023. Reexamination contrast-enhanced CT and MRI revealed diffuse pancreatic lesions with partial necrosis and bleeding, approximately 62.2 mm × 159.7 mm in size, accompanied by stenosis at the end of the common bile duct (Figure S2). Both T1WI and T2WI showed mixed high- and low-intensity signals without significant enhancement (Figure S2D-S2F).

Confirmed by pathological, the patient’s diagnosis is ITPN of the pancreas with invasive carcinoma (Figure S3).

We performed a total pancreatectomy for the patient. Normal pancreatic tissue was not found in the specimen (Figure S3A,S3B). Solid, papillary, nodular masses with partial necrosis and bleeding protruding into the distal common bile duct and enlarged duodenal papilla were seen (Figure S3A-S3C). Microscopically, the tumor cells were papillary and glandular-arranged, accompanied by invasive carcinoma, which had invaded the duodenal papilla and common bile duct (Figure S3C-S3F). The immunohistochemical analysis showed EMA (+), Mucin5AC (−), CK19 (+), CK-7 (−), cell membrane β-catenin (+), CD10 (−), CgA (−), Syn (−), CA19-9 (+), p53 (2+), and Ki67 (50%+) (Figure S3G-S3I). Based on the patient’s significantly dilated pancreatic duct filled with a solid mass without mucus, a tumor exhibiting a papillary architecture with soft consistency, and invasion into the duodenum and common bile duct, as well as a back-to-back glandular arrangement with high-grade intraepithelial neoplasia observed microscopically, combined with immunohistochemical results showing positive EMA expression and negative Mucin5AC expression, we diagnosed ITPN with invasive carcinoma, while excluding PDAC, IPMN, acinar cell carcinoma, and solid pseudopapillary tumor (4,8,10). Insulin was given to regulate blood sugar, trypsin tablets were taken orally to aid digestion, and the patient was discharged on the 12th day after surgery. At the outpatient visit one month after surgery, the patient complained of oily stools 2–5 times a day. After adjusting the dose of the trypsin tablets, the patient’s stool gradually returned to normal, and his body weight increased by 5.2 kg. Gemcitabine systemic chemotherapy was given after a multidisciplinary discussion. There was no recurrence after 2 years after surgery (Figure S4), subcutaneous insulin control blood sugar was good, oral pancreatic enzyme tablets were taken orally, and digestive function was normal and the patient is currently being followed-up. All procedures performed in this study were in accordance with the Declaration of Helsinki and its subsequent amendments. The study protocol was approved by the Ethics Committee of Hunan Provincial People’s Hospital (The First Affiliated Hospital of Hunan Normal University) (No. 2024-133). Written informed consent was obtained from the patient for publication of this article and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

ITPN is a rare pancreatic intraductal tumor that and accounts for approximately 3% of all pancreatic intraductal tumors (1,2). It usually occurs in the head of the pancreas, and 23% of cases show diffuse involvement (4). ITPN is characterized by intraductal tubule formation, high cellular atypia, no obvious mucin secretion and necrotic focus formation. This patient showed a special diffuse lesion of the whole pancreas, which developed slowly and progressively within 1 year, leading to invasive canceration and obstructive jaundice. Therefore, the possibility of ITPN should be considered when there are diffuse mass-type lesions of the pancreas. Since 71% of ITPNs are associated with invasive carcinoma (4). It has been previously reported that a patient died nine months after being diagnosed with ITPN after refusing pancreatic resection (11). In clinical practice, it has also been found that atypical IPMN and PDAC have pathological features and immunostaining patterns similar to those of ITPN (8,9). In our view, genetic sequencing can be additionally performed to assist in diagnosis and treatment when it is difficult to distinguish the two via immunohistochemistry. Early surgical resection is preferred after diagnosis, although its progress is slow.

Acknowledgments

We would like to express our sincere gratitude to Professor Meiliang Li from Department of Pathology, Hunan Provincial People’s Hospital (The First Affiliated Hospital of Hunan Normal University) for providing invaluable support.

Footnote

Provenance and Peer Review: This article was a standard submission to the journal. The article has undergone external peer review.

Peer Review File: Available at https://hbsn.amegroups.com/article/view/10.21037/hbsn-2025-aw-882/prf

Funding: This study was supported by the Hunan Provincial Department of Science and Technology Health Industry Joint Fund (grant number: 2024JJ9479), the Health Research Project of Hunan Provincial Health Commission (grant number: W20242019), the Health Research Project of Hunan Provincial Health Commission (grant number: W20243204), the Excellent Youth Project of Hunan Provincial Department of Education (grant number: 23B0111), the National Clinical Key Specialty Construction Project (grant number: 20191127-1001), the Hunan Clinical Medical Technology Innovation Guidance Project (grant number: 2020SK50912), and the Hunan Natural Science Foundation Project (grant number: 2025JJ80749).

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://hbsn.amegroups.com/article/view/10.21037/hbsn-2025-aw-882/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All procedures performed in this study were in accordance with the Declaration of Helsinki and its subsequent amendments. The study protocol was approved by the Ethics Committee of Hunan Provincial People’s Hospital (The First Affiliated Hospital of Hunan Normal University) (No. 2024-133). Written informed consent was obtained from the patient for publication of this article and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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