A 61-year-old male patient without a previous medical history was diagnosed with pancreatic cancer in August 2015 and underwent PD. However, a postoperative pathologic examination yielded a diagnosis of ITPN with associated invasive carcinoma. The patient underwent routine examinations after receiving postoperative chemotherapy with S-1 for 6 months (60 mg, orally administered twice a day for 28 days followed by a 14-day rest period). During hospitalization due to acute pancreatitis in December 2016, ITPN recurrence was diagnosed by detailed examinations.
Although he used to smoke 20 cigarettes and drink 700 ml of beer a day, the patient quit smoking and drinking after the first surgery. There was no remarkable past history.
First surgery for primary ITPN
Laboratory data were normal, except for amylase (298 UI/I; normal, 10-20 UI/l) and lipase (352 UI/I; normal, 10-20 UI/I). Regarding tumor markers, carbohydrate antigen 19-9 (CA19-9) was slightly increased at 37.3 U/ml, but carcinoembryonic antigen (CEA) and DUPAN-2 were within normal limits.
Preoperative computed tomography (CT) showed a tumor with a low-contrast effect approximately 1 cm in the head of the pancreas and dilatation of the upstream main pancreatic duct (Fig. 1a, b). At the stenosis of the pancreatic duct, there was a tumor that showed a low signal by fat suppression T1WI and a high signal by T2WI and diffusion-weighted imaging (DWI) (Fig. 1c).
Endoscopic retrograde cholangiopancreatography (ERCP) was performed before the operation. ERCP showed an irregular defect in the main pancreatic duct at the head of the pancreas (Fig. 1d). No image suggested mucus in the pancreatic duct. Brush cytology of the stenosis revealed only pancreatic duct epithelial cells with low atypia.
Given that pancreatic cancer was diagnosed based on these examinations, subtotal stomach-preserving pancreatoduodenectomy (SSPPD) was performed in August 2015.
The macroscopic findings of the resected specimen showed that the tumor filled the pancreatic duct (Fig. 2a). A tumor was growing with tubular or cribriform features in the vascular stroma at the main pancreatic duct. The tumor was accompanied by necrosis in some locations and invaded the stroma around the main pancreatic duct (Fig. 2b, c). Mucus production from the tumor was not observed. The results of immunohistochemical staining were as follows: cytokeratin7 (+), cytokeratin19 (+), MUC5AC (−), MUC2 (−), MUC6 (+), chromogranin A (−), synaptophysin (−), and P53 (+). The Ki-67 labeling index was 35.3%, resulting in a final diagnosis of ITPN with associated invasive carcinoma. A histopathological examination revealed no ITPN at the resection stump of the pancreas.
Second surgery for recurrence
When recurrence was diagnosed, amylase and lipase levels were as high as 269 UI/I and 784 UI/I, respectively, but the other data were within normal limits. Each tumor marker, such as CEA, CA 19-9, and DUPAN-2, was within normal limits.
The CT showed a low concentration region of 2 cm in size near the pancreato-jejunal anastomosis, which was similar to the primary ITPN (Fig. 3a). Dilatation of the upstream main pancreatic duct was observed (Fig. 3b). MRI revealed a tumor showing a high signal by DWI at the stenosis of the pancreatic duct (Fig. 3c). Positron emission tomography/computed tomography (PET-CT) revealed an accumulation of SUV max 4.0 at the tumor, while any findings suggestive of other metastases were not observed (Fig. 3d).
As ITPN was not observed at the resection stump of the pancreas by pathological examination of the first surgery, the tumor was diagnosed as recurrence after complete resection rather than residual ITPN in the first operation. A total remnant pancreatectomy was performed in January 2017.
In the histopathological investigation, ITPN polypoid recurrence in the pancreatic duct was observed at a distance of 2.5 cm from the pancreatic stump. Moreover, three tumor masses were observed in the main pancreatic duct at sites distant from the main tumor (Fig. 4). The main tumor did not show invasion but infiltrated into the main duct and the branches of the pancreatic duct (Fig. 5a, b).
Immunohistochemical staining results revealed cytokeratin7 (+), cytokeratin19 (+), MUC5AC (+/−), MUC2 (−), MUC6 (−), chromogranin A (+/−), synaptophysin (+/−), and p53 (+), which were similar to the primary ITPN. The expression of trypsin, which is indicative of acinar cell carcinoma, was negative. The Ki-67 labeling index was 45.1%, which was very similar to the 35.3% of the primary lesion. Three tumor masses were observed floating in the main pancreatic duct at sites distant from the tumor, while there were no obvious malignant findings in the pancreatic duct epithelium at each region (Fig. 5c–e).
Recurrence was not observed for 23 months after the second surgery.