Multifocal intraductal papillary mucinous neoplasm of the pancreas-A case report

Cystic neoplasms of the pancreas are relatively rare, comprising 10 percent of pancreatic cysts and only 1 percent of pancreatic cancers. Cystic neoplasms include mucinous cystic neoplasms, serous cystadenomas, papillary cystic tumors, cystic islet cell tumors and intraductal papillary mucinous neoplasms of the pancreas （IPMNs）. IPMN was first described in 1982. It has been most commonly described in 60 to 70 years old males, and represents a relatively ＂new＂ but increasingly recognized disease. The improvement and widespread use of modern imaging equipments and heightened awareness of physicians contribute to the increasing incidence of IPMN. The majority of IPMNs are located in the pancreatic head （75%） while the rest involves the body/tail regions. Multifocal IPMNs have been hypothesized, but the true presence of multifocality is unknown. Here we present a 72-year- old male diagnosed with IPMN （carcinoma in situ） in the pancreatic head and a branch duct type IPMN （duct atypia） in the pancreatic body and tail. The patient underwent a Whipple intervention and a distal pancreatectomy. A three-year disease-free survival has been observed so far.     

A case of intraductal papillary mucinous neoplasm of the pancreas arising from pancreas divisum without ventral pancreatic duct of Wirsung]

Most reported cases of intraductal papillary mucinous neoplasms (IPMNs) originate from Wirsung's duct or their branches. IPMNs arising from Santorini's duct and its branches have rarely been reported. Eight cases of IPMN arising from Santorini's duct have been published worldwide. However, these cases are associated with incomplete type of pancreas divisum. Recently, one report of IPMN with complete absence of Wirsung's duct has been reported. This patient was a 57-year-old woman who was admitted to the hospital due to progressive jaundice. On endoscopic retrograde cholangiopancreatography, there was a severely bulging ampulla of Vater and patulous minor papilla draining mucinous material and a cystic lesion communicating with the dilated Santorini's duct without any communication with Wirsung's duct. A pancreaticoduodenectomy was performed and the pathologic examination of resected specimen showed no evidence of Wirsung's duct, but an IPMN arising from Santorini's duct with peripancreatic lymph node metastasis. Herein, we report a case of invasive IPMN arising from pancreatic head without ventral pancreatic duct with a review of the relevant literatures.     

Clinical aspects of intraductal papillary mucinous neoplasm of the pancreas

Intraductal papillary mucinous neoplasm (IPMN) is a spectrum of neoplasia in the pancreatic duct epithelium characterized by cystic dilation of the main and/or branch pancreatic duct. According to the site of involvement IPMNs are classified into three categories, i.e., main duct type, branch duct type, and combined type. Most branch duct IPMNs are benign, whereas the other two types are often malignant. A large size of branch duct IPMN and marked dilation of the main pancreatic duct indicate the presence of adenoma at least. The additional existence of large mural nodules increases the possibility of malignancy in all types. Of recent interest is the relatively high prevalence of synchronous and/or metachronous malignancy in various organs, including the pancreas. The prognosis is favorable after complete resection of benign and noninvasive malignant IPMNs. Malignant IPMNs acquiring aggressiveness after parenchymal invasion necessitate adequate lymph node dissection. On the other hand, asymptomatic branch duct IPMNs without mural nodules can be observed without resection for a considerably long time. This review addresses available data, current understanding, controversy, and future directions.     

Management of intraductal papillary mucinous neoplasm of the pancreas

Intraductal papillary mucinous neoplasm (IPMN) of the pancreas is a distinct entity characterized by papillary proliferations of mucin-producing epithelial cells with excessive mucus production and cystic dilatation of the pancreatic ducts. IPMNs have malignant potential and exhibit a broad histologic spectrum, ranging from adenoma to invasive carcinoma. IPMNs are classified into main duct and branch duct types, based on the site of tumor involvement. IPMN patients have a favorable prognosis if appropriately treated. The postoperative 5-year survival rate is nearly 100% for benign tumors and noninvasive carcinoma, and approximately 60% for invasive carcinoma. A main duct type IPMN should be resected. Surgical treatment is indicated for a branch duct IPMN with suspected malignancy (tumor diameter ≥ 30 mm, mural nodules, dilated main pancreatic duct, or positive cytology) or positive symptoms. Malignant IPMNs necessitate lymph node dissection (D1). IPMNs are associated with a high incidence of extrapancreatic malignancies and pancreatic ductal carcinoma.     

Current understanding of precursors to pancreatic cancer

Precursors to pancreatic cancer have been investigated for a century. Previous studies have revealed three distinct precursors,i.e. mucinous cystic neoplasm (MCN), intraductal papillary mucinous neoplasm (IPMN), and pancreatic intraepithelial neoplasia (PanIN), harboring identical or similar genetic alterations as does invasive pancreatic carcinoma. The current understanding of precursors to pancreatic cancer can be illustrated by progressive pathways from noninvasive MCN, IPMN, and PanIN toward invasive carcinoma. MCNs consist of ovarian‐type stroma and epithelial lining with varying grades of atypia, and are occasionally associated with invasive adenocarcinoma. The epithelium of noninvasive IPMNs shows a variety of different directions of differentiation, including gastric, intestinal, pancreatobiliary (PB), and oncocytic types. IPMNs can also harbor varying grades of architectural and cytologic atypia. IPMNs confined to branch ducts are mostly the gastric type, and IPMNs involving the main ducts are often intestinal type, while PB and oncocytic types are rare. Small (<1 cm) IPMNs of the gastric type are not always morphologically distinguishable from low‐grade PanINs. Mucin expression profiles suggest intestinal‐type IPMNs progress to mucinous noncystic (colloid) carcinoma, while PB‐type IPMNs progress toward ductal adenocarcinoma. It is a well‐described paradigm that PanIN lesions progress toward ductal adenocarcinoma through step‐wise genetic alterations. The activation of Hedgehog and Notch signaling pathways in PanIN lesions as well as in pancreatic adenocarcinoma suggest that developmental pathways may be disregulated during carcinogenesis of the pancreas. Further study is needed to elucidate the pathways from precursors toward invasive carcinoma of the pancreas.     

Intraductal papillary mucinous neoplasm of the pancreas: diagnosis and treatment

Intraductal papillary mucinous neoplasm (IPMN) is characterized by cystic dilatation of the main and/or branch pancreatic duct. Only one-third of all patients are symptomatic, and others are diagnosed by chance. IPMNs are classified into 3 types: main duct, branch duct, and mixed IPMN. Most branch-type IPMNs are benign, while the other 2 types are frequently malignant. The presence of large mural nodules increases the possibility of malignancy in all types. Presence of a large branch-type IPMN and marked dilatation of the main duct indicate, at the very least, the existence of adenoma. Ultrasonography, endosonography, and intraductal ultrasonography clearly demonstrate ductal dilatation and mural nodules, and magnetic resonance pancreatography best visualizes the entire outline of IPMN. Not infrequently, synchronous or metachronous malignancy develops in various organs, including the pancreas. Prognosis is excellent after complete resection of benign and noninvasive malignant IPMNs. Asymptomatic branch-type IPMNs without mural nodules may be followed up without resection. Malignant IPMNs displaying acquired aggressiveness after parenchymal invasion require adequate lymph node dissection. Total pancreatectomy is needed for some IPMNs; its benefits, however, must be balanced against operative and postoperative risks because most IPMNs are slow growing and affect elderly people, and prognosis is favorable for IPMN patients with even malignant neoplasms.     

Coexisting Type 1 Autoimmune Pancreatitis and Mixed-type Intraductal Papillary Mucinous Neoplasm

An 84-year-old man was referred to our hospital for a cystic lesion of the pancreatic head, swelling of the pancreatic tail and hilar biliary stricture, resulting in elevated liver enzyme levels. We suspected branch duct-type intraductal papillary mucinous neoplasm (IPMN) and type I autoimmune pancreatitis (AIP) associated with sclerosing cholangitis because of the high serum IgG4 levels. The main pancreatic duct on the tail side of the AIP lesion was moderately dilated. Although the biliary stricture and pancreatic swelling improved after prednisolone treatment, the pancreatic enzyme levels increased rapidly. The entire main pancreatic duct exhibited remarkable dilatation, which led to the diagnosis of mixed-type IPMN. The clinical characteristics of IPMN in the main pancreatic duct appear to have been initially masked by AIP.     

CLINICAL SIGNIFICANCE OF INTRADUCTAL ULTRASONOGRAPHY FOR DIAGNOSIS OF INTRADUCTAL PAPILLARY MUCINOUS NEOPLASM OF THE PANCREAS

Intraductal ultrasonography (IDUS) is useful for evaluating the horizontal spread along the main pancreatic duct in cases of intraductal papillary mucinous neoplasm (IPMN) of the pancreas, thus providing valuable information for the determination of the resection line at surgery. Differentiation between benign and malignant IPMN is also indispensable for management decisions. Measurement of the height of mural nodules by IDUS is expected to be useful for differential diagnosis of IPMN. Because IDUS cannot always demonstrate whole lesions, especially in branch duct IPMN, endoscopic ultrasonography plays a complementary role in such cases.     

Pseudomyxoma peritonei arising from intraductal papillary neoplasm after surgical pancreatectomy: report of 2 cases and review of the literature

We report 2 cases of pseudomyxoma peritonei (PMP) combined with an intraductal papillary mucinous neoplasm (IPMN) and a review of the literature. In both cases, PMP emerged after surgical resection of the IPMN. In one case, neoplastic foci were present in the surgical margin and PMP was found 1 year after the initial resection, while PMP emerged 5 years after surgical resection in the other case. Including these 2 cases, 8 cases of PMP arising from IPMN have been reported. This condition occurs more frequently in males (7 males, 1 female), while the age at diagnosis ranges from 49 to 82 years, with a mean of 63.3 years. IPMNs occur more commonly in the tail of the pancreas (62.5%). Two different patterns regarding the mechanism of PMP arising from IPMN have been indicated; a rupture of the pancreatic duct, after which the neoplasm spreads through the fistula into the peritoneal cavity, and post-surgical development of PMP after insufficient surgical treatment for an IPMN. Our findings indicate that attention must be given to avoid mucous leakage and obtain a negative surgical margin during surgical treatment of an IPMN.     

A case of intraductal papillary mucinous neoplasms after recurrent acute pancreatitis

We report a case of main pancreatic duct (MPD)-type intraductal papillary mucinous neoplasms of the pancreas (IPMNs), in whom diagnostic imaging modalities showed abnormal findings after 4 episodes of acute pancreatitis. The patient was 51 years old at his first admission for acute pancreatitis. He experienced two more episodes of acute pancreatitis, though repeated computed tomography (CT) and endoscopic retrograde cholangiopancreatography (ERCP) showed no abnormality to explain the cause of the pancreatitis. After 3? years from his first episode of pancreatitis, CT and endoscopic ultrasonography revealed pancreatic duct dilation of the pancreas head. Seven years after the first admission, a second ERCP and intraductal ultrasonography revealed a partially dilated MPD with papillary tumors. He underwent pancreaticoduodenectomy, and the pathological diagnosis was intraductal papillary mucinous adenoma with moderate atypia. This case suggests that acute pancreatitis can precede visualized IPMNs. Therefore, acute recurrent pancreatitis with unknown etiology should be followed up for the possibility of IPMNs, in order to detect neoplastic changes in the early stage to provide a better prognosis for the patient.     

Synchronous pancreatic solid pseudopapillary neoplasm and intraductal papillary mucinous neoplasm

Solid pseudopapillary neoplasm (SPN) is a rare and low-grade malignant pancreatic neoplasm composed of poorly cohesive monomorphic neoplastic cells forming solid and pseudopapillary structures with frequent hemorrhagic-cystic degeneration. Intraductal papillary mucinous neoplasm (IPMN) is a pancreatic exocrine tumor composed of intraductal papillary growth of mucin containing neoplastic cells in the main pancreatic duct or its major branches. In the case presented here, a 53-year-old, Japanese man was found to have multiple cystic lesions and dilatation of the main pancreatic duct in the neck of the pancreas. Histological examination revealed a main-duct and branch-duct type IPMN, of the gastric-type, involving the neck of the pancreas, associated with a 0.5 cm SPN in the caudal side of the IPMN. We diagnosed this case as synchronous SPN and IPMN. As far as we know, only one other case of synchronous SPN and IPMN has been reported. Both the present case and the previously reported case showed abnormal nuclear expression of β-catenin in SPN, whereas IPMN showed no abnormal nuclear expression. These results suggest that β-catenin abnormality is not a common pathogenetic factor of synchronous SPN and IPMN.     

胰腺导管内乳头状黏液瘤

胰腺导管内乳头状黏液瘤（IPMN）是由胰腺导管内产生黏液的上皮细胞呈乳头状增殖形成的肿瘤。与经典的胰腺癌相比,IPMN具有低度恶性、生长缓慢、少有侵犯周围组织、淋巴结转移率和再发率低的特点。IPMN根据肿瘤累及的部位可分为主胰管型、分支胰管型和混合型,病理组织特征涵盖从单纯腺瘤到浸润癌等多个亚型,临床表现多样,多种影像学检查手段可显示弥漫性或节段性扩张的主胰管和囊状扩张的分支胰管,ERCP经扩大的乳头获取黏液和胰液,取胰腺导管内皮组织和壁结节供活检均有助于诊断。IPMN确诊后应积极手术,手术切除率高,术后5年生存率高于一般的胰腺癌。本文就其临床表现、分类、病理特征、影像学诊断和治疗等方面做一综述。     

Intraductal papillary mucinous neoplasm and acute pancreatitis

Intraductal papillary mucinous neoplasms (IPMNs) are cystic pancreatic tumors that arise from the pancreatic ducts and are increasingly reported worldwide. Both benign and malignant tumors of the pancreas are thought to contribute to recurrent pancreatitis possibly by pancreatic duct obstruction, and IPMNs contribute to a major share of this burden. The rate of acute pancreatitis (AP) in IPMN patients in the largest published surgical series has varied from 12% to 67%. IPMN may be categorized into 3 forms on the basis of the areas of involvement: main pancreatic duct (MD-IPMN), side branch (SB-IPMN), or combined. Both MD-IPMN and SB-IPMN may be the cause of pancreatitis. The risk of AP seems to be similar with both main duct IPMN and SB-IPMN, although data are controversial. AP in IPMN patients is not severe and often recurs without treatment. The rate of AP does not seem to differ among benign and malignant IPMNs, and the correlation between the malignant potential and the occurrence of AP is ill defined. AP seems to occur more often in patients with IPMN that in those with usual pancreatic adenocarcinoma possibly because of obstruction of the main duct by thick, abundant mucus secretion. Although the Sendai guidelines recommend surgical resection in patients with SB-IPMN with AP, data are controversial. Moreover, in patients with an episode of pancreatitis, the finding of pancreatic cysts is often attributed to pseudocysts or fluid collections that make the diagnosis of IPMN less suspicious. Future longitudinal and prospective studies to understand the natural history of AP in patients with IPMN are required to better manage patients with recurrent AP in the setting of IPMN.     

LATERAL SPREAD ALONG THE MAIN PANCREATIC DUCT IN BRANCH‐DUCT INTRADUCTAL PAPILLARY‐MUCINOUS NEOPLASMS OF THE PANCREAS: USEFULNESS OF INTRADUCTAL ULTRASONOGRAPHY FOR ITS EVALUATION

Background: Intraductal papillary mucinous neoplasms (IPMN) of the pancreas tend to spread intraepithelially along the pancreatic duct wall. We evaluated histopathological intraductal lateral spread (LS) along the main pancreatic duct (MPD) from branch‐duct IPMN and investigated the usefulness of intraductal ultrasonography (IDUS) for its preoperative diagnosis. Patients and Methods: Twenty‐four patients with branch‐duct IPMN who had undergone preoperative IDUS and surgery were reviewed clinicopathologically. The prevalence and histological length of LS along the MPD from branch‐duct IPMN, characteristics of the patients with LS, and efficacy of LS assessment by IDUS were examined. Results: LS along the MPD was observed in 54% of the subjects. In the group of patients with LS, its mean length was 25.2 ± 16.8 mm (5–50 mm) and the diameter of the MPD was 6 mm or greater. Of the patients with LS, those in whom the length of LS along the MPD was longer than the diameter of the cystically dilated branch accounted for 30%. The diameter of the MPD in the group with LS was significantly greater than that in the group without LS (P = 0.03). The sensitivity, specificity, and overall accuracy of IDUS in the detection of LS were 92%, 91%, and 92%, respectively. Conclusion: LS along the MPD was detected in about half of the resected cases of branch‐duct IPMN. Preoperative transpapillary IDUS may be beneficial for the determination of the resection line, especially in those branch‐duct IPMN patients in whom the MPD is 6 mm or greater in diameter.     

A case of minimal invasive carcinoma from intraductal papillary mucinous neoplasm with invasive ductal carcinoma of the pancreas]

A 69-year-old man was referred to our hospital for epigastralgia. He was found to have elevation of serum amylase and CA19-9. Ultrasonography, abdominal CT, MRCP, ERCP and EUS showed the cystic lesion and a possibility of an other tumor. There was a stenosis of the main pancreatic duct (MPD) at the pancreas head and dilatation of the MPD from the body to the tail. Intraductal papillary mucinous neoplasm (IPMN) of the branch pancreatic duct was diagnosed, and there was a likelihood of ductal carcinoma of the pancreas. We therefore performed pancreatoduodenectomy. Pathological finding showed invasive carcinoma from an intraductal papillary mucinous neoplasm with invasive ductal carcinoma of the pancreas.     

Mucin expression profile in pancreatic cancer and the precursor lesions

In this review article, we demonstrate the mucin expression profile in normal tissue, invasive ductal carcinoma (IDC), two subtypes of intraductal papillary–mucinous neoplasm (IPMN dark cell type and IPMN clear cell type), pancreatic intraepithelial neoplasia (PanIN), and mucinous cystic neoplasm (MCN) of the pancreas. In MUC1, there are various glycoforms, such as poorly glycosylated MUC1, sialylated MUC1, and fully glycosylated MUC1. IDCs showed high expression of all the glycoforms of MUC1. IPMNs dark cell type showed no expression or low expression of all the glycoforms of MUC1. IPMNs clear cell type showed low expression of poorly glycosylated MUC1, but expression of sialylated MUC1 and fully glycosylated MUC1. Expression of MUC2 was negative in IDCs, high in IPMNs dark cell type and low in IPMNs clear cell type. MUC5AC was highly expressed in IDCs, IPMNs dark cell type, and IPMNs clear cell type. MUC6 expression was higher in IPMNs clear cell type than in IDCs and IPMNs dark cell type. Our recent study demonstrated that high expression of MUC4 in IDCs is correlated with a poor outcome for patients. In PanINs, expression of both MUC5AC and MUC6 are an early event, whereas up-regulation of MUC1 is a late event. MCNs do not look as if they will show a specific mucin expression profile according to the literature review.     

A case of mixed adenoneuroendocrine carcinoma of the pancreas mimicking intraductal papillary mucinous carcinoma

A previously healthy 52-year-old man was referred to our hospital for further evaluation of main pancreatic duct dilatation. The preoperative work-up was consistent with intraductal papillary mucinous carcinoma (IPMC) derived from a mixed type intraductal papillary mucinous neoplasm (IPMN), because multilocular cysts with enhancing thickened pancreatic head walls and dilated pancreatic ducts lined with dysplastic mucinous epithelium, with papillary proliferation from the pancreatic body to the tail, were observed; in addition, the pancreatic juice cytology was class V, which is suggestive of adenocarcinoma. Total pancreatectomy was performed because a definite mass was not found before surgical resection and the tumors could have spread to the tail. The pathological diagnosis was mixed adenoneuroendocrine carcinoma of the pancreatic head. IPMN with high- or low-grade dysplasia was not observed anywhere in the pancreatic duct. The pancreatic ductal adenocarcinoma consisted of large caliber malignant glands with intraluminal flat or papillary structures; therefore, we were unable to recognize a definite pancreatic mass before surgical resection, and suspected an IPMC derived from a mixed type IPMN.     

内镜诊治胰腺导管内乳头状粘液性肿瘤的应用

目的探讨胰腺导管内乳头状粘液性肿瘤(IPMN)的诊断、内镜下治疗,以提高对该疾病的认识及内镜对其诊断及治疗的意义。方法回顾性分析经内镜诊治的IPMN患者12例,总结并分析他们的一般情况、临床症状、影像学检查、实验室检查、内镜下治疗等方面资料。结果 12例IPMN患者以老年男性为主,无特异性临床表现,主要发生部位为胰头或钩突部,CT主要表现为囊实性低密度影,其内可有壁结节,胰管扩张伴或不伴胆管扩张,2例侵及胰腺实质。磁共振胰胆管造影(MRCP)主要表现为胰管扩张,胰腺萎缩,胰头部圆形高信号影。内镜下逆行胰胆管造影(ERCP)显示十二指肠乳头膨大,开口扩张,可见胶冻样粘液流出,胰管造影显示胰管全程扩张或胰头部囊状扩张,3例伴胆总管、肝内胆管扩张。9例行ERCP治疗,清除粘液栓并置入胰管支架,3例同时置入胆管支架。结论 IPMN是一种特殊类型的胰腺囊性疾病,影像学检查有其独特的表现,ERCP对其诊断及治疗有重要意义。     

Imaging features of intraductal papillary mucinous neoplasms of the pancreas in multi-detector row computed tomography

AIM： To retrospectively evaluate the imaging features of pancreatic intraductal papillary mucinous neoplasms （IPMNs） in multi-detector row computed tomography （MDCT）.
METHODS： A total of 20 patients with pathologicallyconfirmed intraductal papillary mucinous neoplasms （IPMNs） were included in this study. Axial MDCT images combined with CT angiography （CTA） and multiplanar volume reformations （MPVR） or curved reformations （CR） were preoperatively acquired. Two radiologists （Tan L and Wang DB） reviewed all the images in consensus using an interactive picture archiving and communication system. The disputes in readings were resolved through consultation with a third experienced radiologist （Chen KM）. Finally, the findings and diagnoses were compared with the pathologic results.
RESULTS： The pathological study revealed 12 malignant IPMNs and eight benign IPMNs. The diameters of the cystic lesions and main pancreatic ducts （MPDs） were significantly larger in malignant IPMNs compared with those of the benign IPMNs （P 〈 0.05）. The combinedtype IPMNs had a higher rate of malignancy than the other two types of IPMNs （P 〈 0.05）. Tumors with mural nodules and thick septa had a significantly higher incidence of malignancy than tumors without these features （P 〈 0.05）. Communication of side-branch IPMNs with the MPD was present in nine cases at pathologic examination. Seven of them were identified from CTA and MPVR or CR images. From comparison with the pathological diagnosis, the sensitivity, specificity, and accuracy of MDCT in characterizing the malignancy of IPMN of the pancreas were determined to be 100%, 87.5% and 95%, respectively.
CONCLUSION： MDCT with CTA and MPVR or CR techniques can elucidate the imaging features of IPMNs and help predict the malignancy of these tumors.     

Surgical decompression in the patients of pancreatic intraductal papillary mucinous neoplasm

Intraductal papillary mucinous neoplasm (IPMN) is characterized by cystic dilatation of the main and/or branch pancreatic duct by intraductal growth of mucin-producing columnar epithelia. The malignancy is determined by the degree of epithelial dysplasia. Because most IPMNs are slow growing and the prognosis may be favorable even when the IPMN is malignant, aggressive surgical treatment is suggested after considering operative and postoperative risks. Palliative surgery should be considered in some circumstances, such as other synchronous malignancy or systemic comorbidity. Here, we report two patients with IPMN treated successfully by surgical decompression of pancreatic duct.