Intraductal tubulopapillary neoplasm (ITPN) is a rare disease accounting for approximately 3% of all intraductal pancreatic tumors, with intraductal papillary mucinous neoplasm (IPMN) being one of the most common differential diagnoses. Both ITPN and IPMN display slow growth. A branched pancreatic duct type is commonly observed in IPMN, whereas ITPN derived from the branched pancreatic duct has been reported in a limited number of cases; hence, its pathogenesis remains unclear.

Here, we present the case of a patient with ITPN localized in a branched pancreatic duct, with poorly controlled irritable bowel syndrome. A contrast-enhanced computed tomography scan of the abdomen incidentally revealed a 5-mm oligemic nodule-like change in the body of the pancreas. Endoscopic ultrasound (EUS) indicated a 10-mm hypoechoic mass without any cystic structures that had grown within 2 mo. EUS-guided fine needle aspiration was performed for definitive diagnosis, and the findings suggested ductal papillary carcinoma. Distal pancreatectomy was performed, and the tumor was pathologically diagnosed as ITPN with an invasive cancerous component, pT3N1aM0, pStage IIB (International Cancer Control, 8^th edition). The patient underwent treatment with postoperative adjuvant chemotherapy (S-1 monotherapy); however, relapse was observed 1 year and 10 mo after surgical resection, and subsequent treatment involving a combination of chemotherapy and radiotherapy was administered. Maintenance therapy has since facilitated a stable disease state.

Regardless of the microscopic size of the neoplasm, early diagnosis of ITPN with EUS-guided fine needle aspiration and surgical resection are crucial.

Intraductal tubulopapillary neoplasm (ITPN) is a recently reported type of intraductal pancreatic tumor[1,2]. ITPN is extremely rare, accounting for approximately 3% of all intraductal tumors; its pathogenesis remains unclear[1]. Most ITPNs have a primary pancreatic ductal origin, while those growing exclusively in the branching duct are rare[3]. Despite ITPN being considered a precursor to invasive ductal adenocarcinoma, with 70% of cases associated with adenocarcinoma at diagnosis[4,5], ITPN progresses more slowly than conventional pancreatic ductal carcinoma. Further, even with invasive lesions, the prognosis is generally better than that for ductal carcinoma.

Herein, we present the case of a 59-year-old male with ITPN localized in a branched pancreatic duct.

The pathological diagnosis was ITPN (pT3N1aM0, pStageIIB, according to the eighth edition of the Union for International Cancer Control) with an invasive cancer component. The patient had no postoperative complications and was discharged from the hospital on postoperative day 13.

The patient underwent treatment with postoperative adjuvant chemotherapy [S-1 monotherapy (80 mg/day)] for 6 mo following the treatment protocol for pancreatic cancer in Japan, and recurrence-free survival was maintained for 10 mo.

Magnetic resonance imaging performed at 1 year and 10 mo postoperatively revealed recurrence in the retroperitoneal lymph nodes at the surgical site (Figure 5). This postoperative recurrence was treated with oral S-1 in combination with radiation therapy (S-1: 120 mg for 4 wk, 100 mg for 2 wk, and 80 mg for 2 wk), and a reduction in the tumor size at the site of recurrence was observed. Following completion of radiotherapy (total 50 Gy), gemcitabine plus nab-paclitaxel (1000 mg/m², 125 mg/m²) therapy was continued. To date, 2 years and 6 mo postoperatively, the patient’s condition has remained in a stable state of disease[6].

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Figure 5 Magnetic resonance imaging 1 year and 10 mo postoperatively. A: T2-weighted magnetic resonance imaging showed a small nodule in the postoperative area; B: Diffusion-weighted imaging showed a high signal in the same area, indicating recurrence in the retroperitoneal lymph nodes, arrow.

ITPN was described for the first time in 2009 by Yamaguchi et al[1] and is characterized by papillary growth in the pancreatic duct without mucous production, unlike intraductal papillary mucinous neoplasm (IPMN), which typically involves excessive mucin production. ITPN is a highly rare disease, with a frequency of 0.9% among pancreatic exocrine tumors and 3% among intraductal tumors[1]. The average patient age is 58 (25–82) years, and there are no sex differences[1,7]. The 5-year survival rate of ITPN is 81.5%, which is higher than that of pancreatic ductal carcinoma[3]. This type of tumor tends to grow slowly, and the average tumor diameter at the time of detection is 4.5 (0.5–15.0) cm[4].

ITPN is frequently compared to IPMN. Both are intraductal pancreatic tumors with a common intraductal growth pattern and the potential for malignant transformation; however, ITPN and IPMN differ in their immunohistological features. In the gross view, ITPN is a tumor that fills, expands, and proliferates in the pancreatic duct[1,2]. Although the caudal pancreatic duct may dilate due to its obstruction, the tumor does not have a cystic appearance or mucus deposits as in IPMN[1,2]. The Vaters papilla is not enlarged, and mucus outflow is not as observed in IPMN[1,2].

In IPMN, branched pancreatic duct types are common (88%), whereas in ITPN, this is a relatively rare feature (14%)[8]. Additionally, IPMN is positive for MUC5AC in all subtypes, including the oncocytic subtype. Conversely, ITPN is positive for MUC1 and MUC6 and negative for MUC2 and MUC5AC[9], which is consistent with our findings.

Surgical resection is the recommended treatment for ITPN[1,4,7,10]. Date et al[10] reported that among 37 patients with ITPN, the 1-year, 3-year, and 5-year overall survival (OS) rates after surgery were 97.3%, 80.7%, and 80.7%, respectively. Patients with ITPN-associated carcinoma had a favorable 5-year OS of 81.5% compared with the OS of those with ductal adenocarcinoma of the pancreas or IPMN-associated pancreatic cancer. Regarding ITPN prognosis, the recurrence-free survival rate tends to differ according to tumor size (< 4.0 cm vs > 4.0 cm) and Ki-67 labeling index (< 20% vs > 20%); however, these differences are not statistically significant[11]. Currently, there are no comprehensive reports on the efficacy of chemotherapy for ITPN. In the present case, when ITPN with invasive cancer was finally diagnosed, S-1 was administered as postoperative adjuvant chemotherapy following the standard treatment for conventional pancreatic ductal carcinoma in Japan[12]. It should be noted that the efficacy of S-1 for ITPN treatment is unknown.

Our report described a rare case of ITPN originating from a branched pancreatic duct that was incidentally observed in imaging studies and diagnosed using EUS-FNA. In this case, the tumor was small (3 cm in diameter), and the Ki-67 labeling index was approximately 50%, although it varied depending on the site. Despite being microscopic, the tumor rapidly increased in size, and the resected specimen demonstrated an invasive cancerous component. Thus, despite the general tendency of ITPN to grow slowly, in this case, the tumor rapidly progressed to invasive cancer and recurred 1 year and 10 mo postoperatively. As the occurrence of ITPN in the branched pancreatic duct is extremely rare, the nature of the tumor remains unclear.

Based on this case, we suggest that ITPN of the branched pancreatic duct type may have a worse prognosis than that of the main pancreatic duct. Further investigation of such cases is warranted. Moreover, early diagnosis of ITPN through EUS-FNA and subsequent surgical resection of the tumor are crucial. Further studies, especially multicenter studies, are required to validate our findings.

We would like to express our appreciation to Dr. Yutaka Takada for his thoughtful guidance.