Intraductal papillary mucinous neoplasm (IPMN) was first reported by Ohhashi, a Japanese endoscopist, in 1982 and described as “varying degrees of dilatation of the main pancreatic duct, enlargement of large papillae and excessive mucus secretion” [1]. The nomenclature was once confusing, such as mucinous tumors of the pancreas, intraductal mucus-secreting tumors, ductal dilated mucinous cystic tumors, and mucinous villous adenomatosis and intraductal papillary tumors from a clinical and imaging point of view [2], and in 1997 the WHO defined tumors with a tendency to gastrointestinal epithelial differentiation and formed by mucus-producing epithelial papillary proliferation as IPMN [3]. as IPMN [3].
IPMN is characterized by papillary proliferation of pancreatic ductal epithelium accompanied by varying degrees of mucus secretion and pancreatic duct dilatation. IPMN has been reported to account for 5% of pancreatic tumors and is considered by some to be the most common cystic tumor of the pancreas [4]. Compared with classical pancreatic cancer, IPMN is characterized by low-grade malignancy, slow growth, rare invasion of surrounding tissues, low lymph node metastasis rate and recurrence rate.
1. Clinical presentation
The age of patients with IPMN ranges from 30 to 94 years old, with an average of 65.5 years old, and is more common in the age group of 60-70 years old, with a male to female ratio of 2.2:1. Most patients have prolonged recurrent acute pancreatitis or chronic pancreatitis symptoms, including abdominal pain, malaise, fever, weight loss, and some patients have nausea as well as the appearance of jaundice. Chronic obstruction can cause exocrine and endocrine deficiencies, leading to steatorrhea and diabetes mellitus. Some patients have a family history of tumors or a history of alcohol consumption. 18-22% of patients with IPMN are found incidentally without any symptoms. Laboratory tests are not significantly helpful in the diagnosis of tumors and elevated CA19C9 and CEA may be seen in 20% and 15% of patients, respectively, but there is no difference between benign and malignant cases [2].Ueda et al [5] reported that overexpression of the tissue mucin MUC1 is the most reliable marker of IPMN aggressiveness.
2, Typing
Furukawa et al [6] classified IPMN according to the features of main and branch pancreatic duct dilatation on images: type 1, diffuse dilatation of main pancreatic duct; type 2, segmental dilatation of main pancreatic duct; type 3, cystic dilatation of branch pancreatic duct; and type 4, irregular dilatation of branch pancreatic duct.Ridolfini et al [7] classified IPMN according to the different sites of pancreatic duct involvement as main pancreatic duct type, branch type and mixed type. The main pancreatic duct type refers to the tumor located in the main pancreatic duct, the branch type refers to the tumor located in the branch pancreatic duct often accompanied by moderate dilatation of the main pancreatic duct, and the mixed type refers to the involvement of both the main and branch pancreatic ducts. The Japanese Pancreatic Cancer Association classifies IPMN into main pancreatic duct type, branch type, and mixed type according to the location of the predominant tumor tissue. As the disease progresses, the main pancreatic duct type and branch type can transform into each other and eventually develop into a mixed type.
3.Pathological characteristics
Fifty-five to 60% of IPMN tumors are located in the pancreatic head and leptomeninges, with the caudal part of the body accounting for only 11% to 25%, and 33% of lesions are in diffuse or multifocal form [8]. Dilation of the main pancreatic duct can take various forms, segmental or diffuse, and severe dilatation is often accompanied by atrophy of the pancreatic parenchyma. Dilated branch ducts look like cystic tumors, 3-5 cm in diameter and up to 10 cm in size, and a large amount of mucus and prominent nodules can be seen in the dilated ducts. Histologically, IPMN can be classified into four subtypes according to the epithelial configuration and degree of cellular heterotypy: 1. simple adenoma; 2. atypical hyperplasia; 3. carcinoma in situ; 4. invasive carcinoma. Chadwick et al [9] reported the existence of intersecting molecular pathways of tumor proliferation progression between the subtypes.
4. Imaging manifestations
4.1 Ultrasound endoscopy (EUS) EUS can clearly show different degrees and ranges of dilated main pancreatic duct, cystic dilated branch pancreatic ducts, intracapsular structures (such as prominent nodules), ductal tumors and ductal wall strong echogenicity exhibited by pancreatic atrophy, traffic between tumor and main pancreatic duct, which can accurately evaluate the dilatation of main pancreatic duct as well as the progression of malignancy.The following signs seen on EUS are highly suggestive of IPMN Maire et al [10] used ultrasound endoscopy-guided fine-needle aspiration (EUS-FNA) to obtain mucus specimens from 41 cases of IPMN and measured their biochemical indices, and found that the levels of CEA and CA724 were higher than those of benign ones when compared with surgical findings. CA724 levels showed statistically significant differences between benign and malignant IPMN, with a negative predictive value of 96% for both preoperative identification of benign and malignant properties.Michaels et al [11] reported that ultrasound endoscopy-guided fine-needle aspiration biopsy (EUS-FNAB) could be used to analyze the mucus in the ducts of IPMN, tightly attached clusters of mucosal epithelial cells in the ducts, stromal inflammatory infiltration of the lesioned tissue, the presence of necrosis, etc., and is relevant for the assessment of the degree of heterogeneous type of IPMN.
Pancreatic ductoscopy (POPS) is currently the only method that can directly visualize lesions in the pancreatic duct in vitro and the most effective method to identify benign and malignant IPMN. The sensitivity, specificity, and accuracy of POPS in identifying benign and malignant IPMN are 68%, 87%, and 75%, respectively.Itoi et al [12] For the first time, narrow-band imaging (NBI) combined with POPS was used to diagnose three cases of IPMN, which could observe mucosal structures and capillary lesions more sensitively than conventional POPS and detected tumor lesions in the tail of the pancreas that were missed by conventional POPS.
4.2 ERCP Mucus spillage from the enlarged duodenal papilla visible before intubation is a typical ERCP presentation of IPMN. The former is mostly an image of mucus plug, which is indefinite and located in the lumen, while the latter suggests a papillary tumor, which is a well-defined nodule with attached wall. Branched pancreatic duct type IPMN shows contrast-filled branching pancreatic ducts that are cystically dilated and set off by intracapsular striated compartments and papillary protrusions on the cyst wall, but is seen in only 55% of patients with IPMN. The disadvantage of ERCP for the diagnosis of IPMN is that it requires retrograde injection of contrast agent, but on the one hand, the thick mucus secreted by IPMN can block the lumen and prevent the contrast agent from entering the distal main pancreatic duct or small branch pancreatic ducts, and on the other hand, the thick mucus accumulated in the lumen of the proximal main pancreatic duct increases the intraluminal pressure and the contrast agent tends to spill out with the On the other hand, the thick mucus accumulated in the proximal lumen of the main pancreatic duct increases the pressure in the lumen, and the contrast agent easily spills into the duodenal cavity with the high-pressure mucus, resulting in poorly displayed lesions or not. The contrast agent can be injected after the mucus is attracted, or a catheter with a balloon can be used to temporarily seal the opening of the pancreatic duct by inflating the balloon so that the contrast agent is not easily spilled, which can improve the display rate.
4.3CT The typical CT imaging features of main pancreatic duct type IPMN are diffuse or segmental dilatation of main pancreatic duct >2 mm, atrophy of pancreatic parenchyma, inhomogeneous increase of mucus density in the pancreatic duct, and enhancement of papillary tumor. The branched type is characterized by lobulated or grape-like lesions, consisting of multiple small cysts of 1 to 2 cm in diameter, with a few fused into a single larger cystic lesion, which is often separated by cords; the mixed type shows dilated main pancreatic duct and cystic tumor-like changes, and dilated branch pancreatic ducts communicating with dilated or normal diameter main pancreatic ducts are its important imaging features. CT is also valuable in the diagnosis of malignant IPMN peripheral infiltrates, such as peripancreatic infiltrates, peripancreatic and retroperitoneal lymph node metastases, vascular infiltrates, liver The CT presentation of IPMN is divided into three types: simple main pancreatic duct dilatation; main pancreatic duct dilatation with pancreatic cystic foci; and simple pancreatic cystic foci.Zhang et al [13] study suggests that CT staging correlates well with pathologic staging.
4.4 Magnetic resonance biliopancreatic duct hydrography (MRCP) After reconstructed MRCP three-dimensional images, the whole main pancreatic duct, the number of tortuous dilated branch pancreatic ducts, and the connecting ducts between the above two can be observed from different angles.MRCP can simultaneously show the high-signal dilated main pancreatic duct and branch ducts, and distinguish the low-signal wall nodules that are significantly different from mucus. It is effective in staging the lesion and determining the size and progression of the tumor. Cross-sectional MRCP images can show well the internal structures of pancreatic cystic tumors such as compartments and wall nodules. Compared to ERCP, MRCP is not affected by thick mucus, shows significantly more cystic dilated branching pancreatic ducts than ERCP, and measures their size more realistically and reliably.MRCP does not show mucus plugs as filling defects, does not require contrast, and is noninvasive and reproducible. However, MRCP is not as sensitive as ERCP in showing normal-sized branches of the pancreatic ducts, cannot distinguish between mucus and pancreatic fluid, and does not provide information about the pathological aspects of the tumor. There is no significant difference between the two in terms of showing internal details of the tumor, such as separation and wall nodules.
5.Differential diagnosis
IPMN can be associated with chronic inflammation and should be differentiated from chronic pancreatitis, which is characterized by a diffuse moderately dilated main pancreatic duct, rarely accompanied by dilatation of branch pancreatic ducts, and may be accompanied by calcification and pseudocysts communicating with the main pancreatic duct. The presence of wall nodules is an important clue for the diagnosis of IPMN, and the presence of enlarged large papillae protruding from the duodenal lumen is a qualitative diagnosis of IPMN. IPMN and other cystic pancreatic tumors, such as mucinous cystadenoma, both originate from mucus-secreting pancreatic duct endothelial cells, and both have wall nodules and segregation on imaging, and both can appear as clusters of multiple small cystic structures, which can be difficult to differentiate. However, IPMN is mostly seen in elderly men, and is located in the hooked part of the pancreas, mostly in the large branches adjacent to the main pancreatic duct, and the lesion is connected with the dilated main pancreatic duct, while mucinous cystadenoma of the pancreas is more common in middle-aged women, and is usually found in the caudal part of the pancreatic body, and the tumor originates from the terminal branches of the pancreatic duct, often protrudes from the surface of the pancreas and does not connect with the main pancreatic duct, which is not dilated.
6.Treatment
After the diagnosis of IPMN, surgery should be actively performed, and the surgical resection rate is high, reaching 87%, and the overall 5-year survival rate after surgery is 82%, which is higher than that of general pancreatic cancer [14]. ] study indicated that diffuse main pancreatic duct type should undergo total pancreatectomy, while the assessment of surgical approach and extent for pure branching pancreatic duct type involves various factors such as malignant tendency, clinical symptoms, imaging features, and tumor size, and no definite study has been concluded. Non-surgical treatment methods include endoscopic mucin plug removal and endoscopic pancreatic duct stenting, which have only been reported sporadically both at home and abroad and may increase the risk of developing malignancy.Seynaeve et al [17] reported a case of IPMN with jaundice caused by mucus obstruction of the bile duct, in which plastic-coated biliary stents were placed several times to drain the duct but failed due to displacement of the stents by mucus flow, and later Later, multiple metal stents without membrane were implanted to avoid displacement and relieve the obstruction.
7. Outlook
IPMN differs significantly from other pancreatic-related tumors in terms of pathogenetic characteristics, clinical course, pathological pattern and prognosis. The current and future research hotspots are the molecular pathological changes of IPMN, clinical features and the connection between imaging features and histopathological changes, how to effectively use multiple imaging examinations to make correct diagnosis at an early stage, and the timing and mode of surgical intervention.