Intraductal papillary mucinous neoplasms and other pancreatic cystic lesions

Pancreatic cystic neoplasms are being increasingly recognized, even in the absence of symptoms, in large part, due to markedly improved imaging modalities such as magnetic resonance imaging （MRI）/magnetic resonance cholangio pancreatography （MRCP） and computer tomography （CT） scanning. During the past 2 decades, better imaging of these cystic lesions has resulted in definition of different types, including pancreatic intraductal papillary mucinous neoplasms （IPMN）. While IPMN represent only a distinct minority of all pancreatic cancers, they appear to be a relatively frequent neoplastic form of pancreatic cystic neoplasm. Moreover, IPMN have a much better outcome and prognosis compared to pancreatic ductal adenocarcinomas. Therefore, recognition of this entity is exceedingly important for the clinician involved in diagnosis and further evaluation of a potentially curable form of pancreatic cancer.     

Intraductal papillary mucinous neoplasms and other pancreatic cystic lesions

Pancreatic cystic neoplasms are being increasingly recognized, even in the absence of symptoms, in large part, due to markedly improved imaging modalities such as magnetic resonance imaging (MRI)/magnetic resonance cholangio pancreatography (MRCP) and computer tomography (CT) scanning. During the past 2 decades, better imaging of these cystic lesions has resulted in definition of different types, including pancreatic intraductal papillary mucinous neoplasms (IPMN). While IPMN represent only a distinct minority of all pancreatic cancers, they appear to be a relatively frequent neoplastic form of pancreatic cystic neoplasm. Moreover, IPMN have a much better outcome and prognosis compared to pancreatic ductal adenocarcinomas. Therefore, recognition of this entity is exceedingly important for the clinician involved in diagnosis and further evaluation of a potentially curable form of pancreatic cancer.     

International consensus guidelines for management of intraductal papillary mucinous neoplasms and mucinous cystic neoplasms of the pancreas.

Non-inflammatory cystic lesions of the pancreas are increasingly recognized. Two distinct entities have been defined, i.e., intraductal papillary mucinous neoplasm (IPMN) and mucinous cystic neoplasm (MCN). Ovarian-type stroma has been proposed as a requisite to distinguish MCN from IPMN. Some other distinct features to characterize IPMN and MCN have been identified, but there remain ambiguities between the two diseases. In view of the increasing frequency with which these neoplasms are being diagnosed worldwide, it would be helpful for physicians managing patients with cystic neoplasms of the pancreas to have guidelines for the diagnosis and treatment of IPMN and MCN. The proposed guidelines represent a consensus of the working group of the International Association of Pancreatology.     

European experts consensus statement on cystic tumours of the pancreas

Cystic lesions of the pancreas are increasingly recognized. While some lesions show benign behaviour (serous cystic neoplasm), others have an unequivocal malignant potential (mucinous cystic neoplasm, branch- and main duct intraductal papillary mucinous neoplasm and solid pseudo-papillary neoplasm). European expert pancreatologists provide updated recommendations: diagnostic computerized tomography and/or magnetic resonance imaging are indicated in all patients with cystic lesion of the pancreas. Endoscopic ultrasound with cyst fluid analysis may be used but there is no evidence to suggest this as a routine diagnostic method. The role of pancreatoscopy remains to be established. Resection should be considered in all symptomatic lesions, in mucinous cystic neoplasm, main duct intraductal papillary mucinous neoplasm and solid pseudo-papillary neoplasm as well as in branch duct intraductal papillary mucinous neoplasm with mural nodules, dilated main pancreatic duct >6 mm and possibly if rapidly increasing in size. An oncological partial resection should be performed in main duct intraductal papillary mucinous neoplasm and in lesions with a suspicion of malignancy, otherwise organ preserving procedures may be considered. Frozen section of the transection margin in intraductal papillary mucinous neoplasm is suggested. Follow up after resection is recommended for intraductal papillary mucinous neoplasm, solid pseudo-papillary neoplasm and invasive cancer.     

Intraductal papillary mucinous tumor: diagnostic and therapeutic approach

Primary cystic pancreatic neoplasms are rare tumors, with an approximate prevalence of 10% of cystic pancreatic lesions. Most of these lesions correspond to mucinous cystic neoplasm, serous cystoadenoma and intraductal papillary mucinous tumor (IPMT). IPMT is characterized by diffuse dilatation of the main pancreatic duct and/or side branches with inner defects related to mucin or tumor, or mucin extrusion from a patent ampulla. IPMT has a low potential for malignancy, with a low growth rate, a low rate of metastatic spread and postsurgical recurrence. Over the last few years, major advances have been made in the diagnostic and therapeutic management of this tumor.     

Intraductal mucinous tumors occurring simultaneously in the liver and pancreas

A case of simultaneous intraductal mucinous tumors of the liver and pancreas in a 67-year-old man is described. Abdominal ultrasonography and computed tomography (CT) revealed the presence of cystic lesions with intraluminal septae both in the caudate lobe of the liver and in the uncinate process of the pancreas; these cystic lesions communicated with the hepatic duct and pancreatic duct, respectively. Mucin retention was observed in the cysts, and cholestasis was induced by mucin secretion into the common bile duct. The lesions were resected by left hepatic lobectomy with caudate lobectomy, and segmental pancreatectomy. Both lesions were multilocular cystic tumors with no papillary projections or focal mass effect in their walls. Histologically, both cystic lesions were a mixture of hyperplasia and adenoma lined by low papillary columnar epithelium. There were no cellular or histological features to suggest malignant change. The fibrous intratumor interstitium lacked any mesenchymal or ovarian-like stroma. The hepatic lesion was considered to be of a similar nature to intraductal papillary mucinous tumor (IPMT) of the pancreas. However, the two lesions occurred simultaneously in the liver and pancreas. This case is of interest in regard to the diagnosis and management of mucinous hepatopancreatobiliary lesions. Received: March 16, 2001 / Accepted: September 14, 2001     

Intraductal papillary mucinous tumors of the pancreas

Cystic neoplasms of the exocrine pancreas are a small fraction of pancreatic tumors. Within that group of cystic neoplasms, intraductal papillary mucinous tumors (IPMTs) can be distinguished from mucinous cystic neoplasms, serous cystic neoplasms, and pseudopapillary cystic tumors. Awareness of IPMTs has increased since the World Health Organization classified these tumors as its own group in 1996. Because of their favorable prognosis, an extensive diagnostic workup for IPMTs should be performed in patients presenting with cystic lesions of the pancreas. This workup often leads to the diagnosis and the predominant tumor location and size, although the extent of the ductal changes can only be established by histopathology. Surgical resection is the therapy of choice for IPMTs. The type of resection depends upon the extent of the quantitative and qualitative ductal involvement. Total pancreatectomy is currently the treatment for an IPMT that comprises the entire main duct.     

Gd-EOB-DTPA-enhanced magnetic resonance imaging for bile duct intraductal papillary mucinous neoplasms

AIM: To investigate gadolinium-ethoxybenzyl-diethylenetriamine-pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) of intraductal papillary mucinous neoplasms of the bile duct (IPMN-B).METHODS: The imaging findings of five cases of IPMN-B which were pathologically confirmed at our hospital between March 2012 and May 2013 were retrospectively analyzed. Three of these cases were diagnosed by duodenal endoscopy and biopsy pathology, and two cases were diagnosed by surgical pathology. All five patients underwent enhanced and non-enhanced computed tomography (CT), magnetic resonance cholangiopancreatography, and Gd-EOB-DTPA-enhanced MRI; one case underwent both Gd-EOB-DTPA-enhanced MRI and positron emission tomography-CT. The clinical data and imaging results for these cases were compared and are presented.RESULTS: Conventional imaging showed diffuse dilatation of bile ducts and multiple intraductal polypoid and papillary neoplasms or serrated changes along the bile ducts. In two cases, Gd-EOB-DTPA-enhanced MRI revealed dilated biliary ducts and intraductal tumors, as well as filling defects caused by mucin in the dilated bile ducts in the hepatobiliary phase. Gd-EOB-DTPA-enhanced MRI in one case clearly showed a low-signal tumor in the hepatobiliary phase, similar to what was seen by positron emission tomography-CT. In two patients, routine inspection was unable to discern whether the lesions were inflammation or tumors. However, Gd-EOB-DTPA-enhanced MRI revealed a pattern of gradual enhancement during the hepatobiliary phase, and the signal intensity of the lesions was lower than the surrounding liver parenchyma, suggesting tissue inflammation in both cases, which were confirmed by surgical pathology.CONCLUSION: Gd-EOB-DTPA-enhanced MRI reveals the intraductal mucin component of IPMN-B in some cases and the extent of tumor infiltration beyond the bile ducts in invasive cases.     

Hemosuccus pancreaticus caused by a mucinous cystic neoplasm of the pancreas

Hemosuccus pancreaticus is a gastrointestinal hemorrhage through the main pancreatic duct. Here, we report a rare case of hemosuccus pancreaticus due to a mucinous cystic neoplasm of the pancreas. A 62-year-old woman who had been followed for a branch duct intraductal papillary mucinous neoplasm visited our emergency room due to severe abdominal pain and bloody discharge. Computed tomography revealed that the pancreatic cyst increased the tension of the wall and a high-density area indicative of bleeding into the cyst was observed. Endoscopy showed opening of and hemorrhaging from the papilla of Vater. The patient was diagnosed with hemosuccus pancreaticus caused by hemorrhaging into the cyst from the branch duct intraductal papillary mucinous neoplasm. Based on this diagnosis, elective distal pancreatectomy was performed. The histopathological diagnosis was a mucinous cystic neoplasm with intermediate-grade dysplasia based upon the pathological findings that fibrous ovarian-type stroma existed abundantly and the stroma cells were positive for progesterone receptor and inhibin. Hemosuccus pancreaticus caused by a mucinous cystic neoplasm is extremely rare and there has been only one case reported to date. In conclusion, it should be recognized that pancreatic cystic neoplasms including mucinous cystic neoplasms may cause hemosuccus pancreaticus.     

Precursor lesions of pancreatic cancer: molecular pathology and clinical implications.

BACKGROUND: Pancreatic cancer is a lethal disease, with near uniform 5-year mortality rates. The key to improving survival of pancreatic cancer rests upon early detection of this neoplasm at a resectable, and hence potentially curable, stage. METHODS: We review the current state of the literature vis-à-vis the three common precursor lesions of pancreatic adenocarcinoma: pancreatic intraepithelial neoplasia, intraductal papillary mucinous neoplasm, and mucinous cystic neoplasm. We also discuss two clinical scenarios of emerging importance, namely asymptomatic pancreatic cysts ('pancreatic incidentalomas') and the significance of precursor lesions in familial pancreatic cancer kindreds. RESULTS: Pancreatic intraepithelial neoplasias are the microscopic precursor lesions of pancreatic adenocarcinomas, while intraductal papillary mucinous neoplasms and mucinous cystic neoplasms are macroscopic, cystic precursor lesions. All three noninvasive entities demonstrate a multistep morphologic and genetic progression that culminates in frank invasive adenocarcinoma. Despite these commonalities, each precursor lesion harbors a unique repertoire of clinicopathologic and genetic characteristics that has an impact on natural history and prognosis of these lesions. Due to improvements in radiological techniques, asymptomatic pancreatic cysts are being increasingly discovered in the general population; intraductal papillary mucinous neoplasms and mucinous cystic neoplasms are the most common underlying histology in resected incidentalomas of the pancreas. Pancreatic asymptomatic cysts present an enormous challenge in terms of accurate diagnosis and management stratification. Incorporating molecular signatures of cystic precursor lesions into the diagnostic algorithm will likely become a standard of care for asymptomatic pancreatic cysts. High-risk individuals from familial pancreatic cancer kindreds are another group of individuals where knowledge of precursor lesions has had a therapeutic impact; sensitive imaging technologies have enabled the identification and subsequent resection of pancreatic cancer precursors in these high-risk individuals, preventing the progression to invasive cancer. CONCLUSIONS: Precursor lesions of pancreatic adenocarcinomas represent a unique opportunity for diagnosis and intervention for a malignancy with near uniform lethality. Further studies on these precursors will enable the development of rational early detection and therapeutic strategies in order to ameliorate pancreatic cancer survival.     

Precursors to pancreatic cancer

Infiltrating ductal adenocarcinoma of the pancreas is believed to arise from morphologically distinct noninvasive precursor lesions. These precursors include the intraductal papillary mucinous neoplasm, the mucinous cystic neoplasm, and pancreatic intraepithelial neoplasia. Intraductal papillary mucinous neoplasms are grossly visible mucin-producing epithelial neoplasms that arise in the main pancreatic duct or one of its branches. The cysts of mucinous cystic neoplasms do not communicate with the major pancreatic ducts, and these neoplasms are characterized by a distinct ovarian-type stroma. Pancreatic intraepithelial neoplasia is a microscopic lesion. This article focuses on the clinical significance of these three important precursor lesions, with emphasis on their clinical manifestations, detection, and treatment.     

Pancreatic incidentalomas: Investigation and management

The incidence of pancreatic incidentalomas (PIs) detected in otherwise asymptomatic patients is growing with the increasing quality and use of advanced imaging techniques. PI can present as isolated main pancreatic duct dilation or as a solid or cystic lesion. Although historically thought to be relatively rare, PIs are rather common, particularly cystic lesions of the pancreas, which can be detected in up to 49% of the general population. With the poor prognosis of pancreatic cancer, PIs are an opportunity for prevention and early diagnosis, but when managed poorly, they can also lead to overtreatment and unnecessary morbidity. The management of PI should begin with a dedicated pancreas protocol computed tomography (CT) scan or magnetic resonance imaging (MRI) to accurately characterize duct size, lesion characteristics and establish an accurate baseline for subsequent follow up. Diagnosis and subsequent management depends on the extent of main duct dilation and solid versus cystic appearance. Solid lesions are highly concerning for malignancy. Cystic lesions can be further categorized as intraductal papillary mucinous neoplasms of the pancreas (IPMNs) or mucinous cystic neoplasms (MCNs), both of which harbour malignant potential, or as serous cystic neoplasms (SCNs) that are benign. In this paper, we summarize the major challenges related to PI and present pragmatic suggestions for management.     

Study of recurrence after surgical resection of intraductal papillary mucinous neoplasm of the pancreas

BACKGROUND & AIMS: The aim of this study was to determine recurrence and long-term survival after resection of pancreatic intraductal papillary mucinous neoplasm and to correlate recurrence and survival with histology, extent of resection, and duration of follow-up. METHODS: A single pathologist, without knowledge of previous interpretations of histology or clinical data, retrospectively reviewed and classified 113 resected intraductal papillary mucinous neoplasms as invasive carcinoma (n = 40) or as noninvasive neoplasms (adenoma, borderline, or carcinoma in situ; n = 73). Data on recurrence (locoregional or metastatic), follow-up, and cause of death were obtained from patient records and/or by contacting patients and their physicians. RESULTS: In invasive intraductal papillary mucinous neoplasm, recurrence was similar after partial pancreatectomy (18/27; 67%) and total pancreatectomy (8/13; 62%) and occurred within 3 years of resection in 91%. Among noninvasive neoplasms, 5 of 60 (8%) recurred after partial pancreatectomy (median follow-up, 37 months); none recurred after total pancreatectomy (n = 13; median follow-up, 32 months). Recurrence after resection in noninvasive neoplasms was diagnosed after a median of 40 months (range, 23-75 months); recurrence was noninvasive in 3 and invasive cancer in 2. Five-year survival was better for noninvasive compared with invasive intraductal papillary mucinous neoplasm (84.5% vs. 36%; P < 0.001). CONCLUSIONS: Invasive intraductal papillary mucinous neoplasm recurs frequently even after a complete "curative" resection and portends poor survival. In contrast, noninvasive intraductal papillary mucinous neoplasm recurs infrequently after resection, and survival is excellent regardless of the degree of epithelial dysplasia in the tumor.     

Surgical treatment for mucin-producing tumors of the pancreas

BACKGROUND/AIMS: Our objectives in this study were to evaluate the surgical treatment for mucin-producing tumor of the pancreas from the clinicopathological and imaging features. METHODOLOGY: Thirty-one patients with mucin-producing tumor of the pancreas were examined based on clinicopathological analyses to determine the appropriate surgical treatment. RESULTS: The clinical and imaging features easily distinguished the main duct type of intraductal papillary lesions (type Ia), branch type of intraductal papillary lesions (type Ib) and mucinous cystic neoplasms (type II). From pathological examinations, a dilated main pancreatic duct had the malignant potentiality and multicentric development. CONCLUSIONS: Pancreatic segments containing a dilated main pancreatic duct should be resected in type Ia. Type Ib is sufficient for partial resection without lymphadenectomy. Type II also requires partial resection of the cystic neoplasm. A standard lymphadenectomy may be an option when type Ia and II show invasive features.     

Update on the pathology and genetics of exocrine pancreatic tumors with ductal phenotype: precursor lesions and new tumor entities

The majority of pancreatic neoplasms show a ductal phenotype and can be classified as ductal adenocarcinomas. Pancreatic duct lesions have been discussed as tumor precursors. This review presents a recently adopted standard system for these lesions which distinguishes among three grades of pancreatic intraepithelial neoplasia (PanIN). Molecular studies revealed that PanIN-2 and PanIN-3 lesions represent a distinct step towards invasive carcinoma. Another focus of the review is the advances that have been made in the further immunohistochemical and molecular characterization of special pancreatic neoplasms showing a ductal phenotype, such as undifferentiated carcinoma, mucinous noncystic (colloid) carcinoma, intraductal papillary mucinous neoplasm, mucinous cystic neoplasm, medullary carcinoma, and other rare tumors.     

Tumeurs intracanalaires papillaires et mucineuses du pancréas découvertes fortuitement : à propos d’un cas

Intraductal papillary mucinous neoplasms of pancreas (IPMN) are cystic lesions of the pancreas than can be associated with extra-pancreatics malignancies. We report a case of intraductal papillary mucinous neoplasm discovered incidentally during the staging of rectal adenocarcinoma. This observation illustrates the high frequency of IPMN incidentally discovered, for instance during the work-up of an extrapancreatic tumor.     

Endoscopic ultrasound characteristics of mucinous cystic neoplasms of the pancreas

OBJECTIVE: Mucinous cystic neoplasms of the pancreas have a more favorable prognosis than ductal adenocarcinoma. Management of a subgroup, intraductal papillary-mucinous neoplasms, is controversial. Endoscopic ultrasound (EUS) with fine-needle aspiration biopsy may emerge as the imaging modality of choice. There are few studies describing the EUS features of these tumors. METHODS: A total of 35 consecutive cases of cystic tumors of the pancreas with an established pathological diagnosis were analyzed for characteristic EUS features. RESULTS: Mucinous cystadenocarcinomas (n = 14) were more likely to be characterized by hypoechoic cystic/solid mass or complex cyst and were frequently associated with a dilated main pancreatic duct. Benign mucinous duct ectasia (n = 6) were characterized by a dilated main pancreatic duct in conjunction with hyperechoic thickening of the duct wall. The two cases of intraductal mucinous hyperplasia additionally showed a hypoechoic mass. Intraductal papillary carcinoma (n = 11) had features in common with mucinous cystadenocarcinoma but also had echogenic foci in the mass and intraductal hyperechoic lesions. The two cases of microcystic cystadenoma showed either a mixed hypoechoic solid/cystic mass or a complex cyst without the additional features seen in mucinous cystadenocarcinoma. CONCLUSIONS: EUS features seem to exist that may help to differentiate cystic neoplasms from adenocarcinoma of the pancreas and, thus, to establish the preoperative diagnosis of cystic tumors of the pancreas.     

Simultaneous liver mucinous cystic and intraductal papillary mucinous neoplasms of the bile duct:A case report

Cystic hepatic neoplasms are rare tumors,and are classified into two separate entities:mucinous cystic neoplasms(MCNs)and intraductal papillary mucinous neoplasms of the bile duct(IPMN-B).We report the case of a 56-year-old woman who presented with abdominal pain and jaundice due to the presence of a large hepatic multilocular cystic tumor associated with an intraductal tumor.Partial hepatectomy with resection of extrahepatic bile ducts demonstrated an intrahepatic MCN and an intraductal IPMN-B.This is the first report of the simultaneous occurrence of these two histologically distinct entities in the liver.     

Cyst fluid glucose: An alternative to carcinoembryonic antigen for pancreatic mucinous cysts

Pancreatic cystic lesions(PCLs) have been increasingly recognized in clinical practice. Although inflammatory cysts(pseudocysts) are the most common PCLs detected by cross-sectional imaging modalities in symptomatic patients in a setting of acute or chronic pancreatitis, incidental pancreatic cysts with no symptoms or history of pancreatitis are usually neoplastic cysts. For these lesions,it is imperative to identify mucinous cysts(intraductal papillary mucinous neoplasms and mucinous cystic neoplasms) due to the risk of their progression to malignancy. However, no single imaging modality alone is sufficient for a definitive diagnosis of all PCLs. The cyst fluid obtained by endoscopic ultrasound-guided fine needle aspiration provides additional information for the differential diagnosis of PCLs. Current recommendations suggest sending cyst fluid for cytology evaluation and measurement of carcinoembryonic antigen(CEA) levels. Unfortunately, the sensitivity of cytology is greatly limited, and cyst fluid CEA has demonstrated insufficient accuracy as a predictor of mucinous cysts. More recently, cyst fluid glucose has emerged as an alternative to CEA for distinguishing between mucinous and nonmucinous lesions. Herein, the clinical utility of cyst fluid glucose and CEA for the differential diagnosis of PCLs was evaluated.     

Familial intraductal papillary mucinous neoplasms of the pancreas

The prevalence of intraductal papillary mucinous neoplasms in patients with a high risk of pancreatic adenocarcinoma was estimated to be 15%. However, a familial form of intraductal papillary mucinous neoplasms was never described.MethodsThree families (8 patients) with intraductal papillary mucinous neoplasms familial forms were described. Diagnosis was made according to radiological criteria and was confirmed by pathological data. Genetic predisposing factors of pancreatic cancer were searched for.ResultsSymptoms related to intraductal papillary mucinous neoplasms were recurrent acute pancreatitis (n = 3) or fortuitous discovery (n = 5). Number of cystic lesions was ≤3 (n = 4) or >3 (n = 4). Intraductal papillary mucinous neoplasms involved branch ducts (n = 7) or both main pancreatic duct and branch duct (n = 1). Severe and moderate dysplasia was found on surgical specimens. No genetic alteration was found (BRCA2, p16 or CDKN2A genes).ConclusionA familial form of intraductal papillary mucinous neoplasms was found in three families. No pancreatic cancer was found in relatives but an attentive survey has to be proposed.