We encountered a case of surgically resected ITPN that had caused MPD rupture. Macroscopically and microscopically, the tumor showed tubulopapillary growth within the MPD, and at the distal side of the tumor, a fistula connected the MPD to the extrapancreatic scar tissue.
The main characteristics of ITPN are a solid nodular tumor macroscopically obstructing dilated ducts, no visible secreted mucin; tubulopapillary growth; uniform high-grade atypia throughout the neoplasm; easily recognizable necrotic foci; ductal differentiation as indicated by MUC1 and CK7 expression; absence of acinar differentiation as indicated by the absence of trypsin; absence of MUC2, MUC5AC, and fascine; and absence of KRAS and BRAF mutations [7]. Most of these important histopathological characteristics of ITPN were present in our case. The characteristic imaging findings of ITPN are a two-tone duct sign and cork-of-wine-bottle sign on MRI or endoscopic retrograde cholangiopancreatography [8]. In the present case, although these findings were not obvious on MRI, MDCT showed similar findings (Fig. 1b). In addition, upon retrospective examination, findings that seemed to indicate MPD rupture and the formation of a fistula extending outside of the pancreas were present on MDCT (Fig. 1b).
Regarding treatment, several authors have recommended radical surgery for resectable ITPN, just as for PDAC [9, 10]. The prognosis of ITPN is considered to be better than that of intraductal papillary mucinous carcinoma or PDAC [9, 11]; however, there have been no comprehensive reports on the efficacy of chemotherapy for ITPN. In the present case, the final diagnosis was ITPN with associated invasive carcinoma. The MPD had ruptured and cancer cells were scattered toward the extrapancreatic tissues. However, intraoperative lavage cytology was negative for cancer, and curative resection was achieved. We considered that additional treatment was needed because of the risk of peritoneal dissemination recurrence due to MPD rupture and potential leakage of tumor cells despite the fact that the intraoperative lavage cytology was negative. Although its efficacy was unclear, S-1 was administered as adjuvant chemotherapy because this is the standard treatment for PDAC in Japan [6].
A literature review of 73 cases of ITPN showed that approximately 90% of the cases were associated with MPD dilatation [12]. However, the rupture of the MPD was extremely rare. A PubMed search using the key words “ITPN” and “rupture” revealed only one case, in which an ITPN with the formation of gigantic pancreatic cysts ruptured and caused acute peritonitis [4]. The authors considered that solid ITPN formation in the MPD had obstructed the flow of pancreatic juice and increased the internal pressure of the distal pancreatic duct, leading to the development of gigantic pancreatic cysts and MPD rupture [4].
Regarding the mechanisms underlying MPD rupture, differences in the tumor nature between ITPN and PDAC may be important. PDAC is morphologically characterized by an intense fibrotic process called a desmoplastic reaction. Therefore, PDAC is often associated with chronic obstructive pancreatitis with extensive fibrosis and atrophy of acinar cells in the pancreatic parenchyma on the tail side of the tumor [13, 14]. In PDAC, pancreatic duct stenosis develops slowly, and the internal pressure within the pancreatic duct rises gradually. At the same time, the pancreatic parenchyma becomes fibrotic and hardens. Therefore, the pancreatic duct may not easily rupture outside the pancreas. In contrast, in the present case, atrophy of acinar cells and fibrosis were localized at the tail side of the tumor, and the acinar cells were relatively retained (Fig. 5). Based on these findings, we speculated that the MPD rupture was caused by the following three mechanisms: the tumor gradually grew within the MPD and suddenly obstructed its lumen, causing a rapid rise in the internal pressure of the pancreatic duct and acute inflammation; the remaining pancreatic exocrine function distal to the tumor caused pancreatic juice to be retained, contributing to the rapid increase in the MPD pressure; and the pancreatic parenchyma distal to the tumor was softer and less pressure-resistant than that of PDAC because the fibrosis was localized.
However, considering that perforations are extremely rare, patient-specific factors such as anatomical features and tissue strength are likely involved in such cases. Unfortunately, no pre-perforation images were available in our patient, and elaborate discussion was difficult. Further case reports are desired.
In conclusion, we encountered an extremely rare case of ITPN with the rupture of the MPD. A sudden increase in pancreatic duct internal pressure or acute inflammation likely caused the MPD rupture.