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.     

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.     

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.     

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.     

Mass forming chronic pancreatitis mimicking pancreatic cystic neoplasm: A case report

Mass forming chronic pancreatitis is very rare. Diagnosis could be done by the pathologic findings of focal inflammatory fibrosis without evidence of tumor in pancreas. A 34-year-old man presented with right upper abdominal pain for a few weeks and slightly elevated bilirubin level on clinical findings. Radiological findings of multidetector-row computed tomography, magnetic resonance(MR) imaging with MR cholangiopancreatography and endoscopic ultrasonography revealed focal branch pancreatic duct dilatation with surrounding delayed enhancing solid component at uncinate process and head of pancreas, suggesting branch duct type intraductal papillary mucinous neoplasm. Surgery was done and pathology revealed the focal chronic inflammation, fibrosis, and branch duct dilatation. Herein, I would like to report the first case report of mass forming chronic pancreatitis mimicking pancreatic cystic neoplasm.     

Hemosuccus pancreaticus due to intraductal papillary-mucinous carcinoma of the pancreas

A 72-year-old female was referred to our hospital for evaluation of a hyperechoic mass in the pancreatic head with ultrasound sonography. She had no symptom expect slight anemia (Hb 11.3 g/dl). On endoscopy, blood was expelled from the orifice of the major duodenal papilla, but excretion of mucus was not detected. Endoscopic retrograde pancreatography revealed an irregular defect in the main pancreatic duct at the head of the pancreas. Computed tomography revealed a 2-cm mass with a low density lesion in the pancreas head. On suspicion of malignant tumor of the pancreas, pylorus-preserving pancreaticoduodenectomy was performed. Histological diagnosis was intraductal papillary-mucinous carcinoma without mucin hypersecretion. It grew within the inferior branch of the main pancreatic duct, and the top of the tumor stood out into the main pancreatic duct. As the causes of hemosuccus pancreaticus, pancreatic benign diseases, for example, chronic pancreatitis, pseudocyst, arterial aneurysm and pseudoaneurysm, are known, but pancreatic tumors are rare. In particular, this may be the first report of hemosuccus pancreaticus induced by intraductal papillary-mucinous carcinoma of the pancreas without mucin hypersecretion.     

Serous cystic neoplasms of the whole pancreas in a patient with von Hippel-Lindau disease

We describe here a case of von Hippel-Lindau (VHL) disease with a serous cystic neoplasm of the whole pancreas. The patient was a 35-year-old woman suffering from a palpable abdominal tumor. She had a history of hemangioblastomas of the cerebellum. CT revealed large solid tumors in the pancreatic head and body, and multiple cystic lesions in the whole pancreas as well as a right renal tumor. When endoscopic retrograde cholangiopancreatography (ERCP) was performed, bleeding from the duodenal papilla was detected. Since she had some distinguishing clinical features, the diagnosis of VHL disease was made. The preoperative diagnosis of the pancreatic lesion was serous cystic neoplasms with hemosuccus pancreaticus and total pancreatectomy was performed. Histological examination of the specimen revealed serous cystic neoplasms which occupied the entire pancreas. VHL cases operated on for serous cystic neoplasms of the entire pancreas are very rare.     

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 papillary mucinous tumors and mucinous cystic tumors of the pancreas: imaging

Most cystic lesions of the pancreas are nonneoplastic and inflammatory in nature. However, approximately 5%–15% of cystic pancreatic masses may be neoplastic. Among the cystic neoplasms are the mucin-producing tumors, both the intraductal papillary mucinous neoplasms and the mucinous cystic neoplasms. Their imaging features on contrast-enhanced computed tomography (CT) and magnetic resonance imaging (MRI) can assist in the differentiation of these lesions. The imaging findings of both intraductal papillary mucinous neoplasm and mucinous cystic neoplasm are reviewed with attention to CT and MRI.     

A rare ring-shaped anomaly of the main pancreatic duct accompanying a branch duct IPMN

The patient was a 74-year-old female. Screening computed tomography for examination of the abdomen showed a cystic mass in the pancreatic body. Close investigation using endoscopic retrograde cholangiopancreatography and magnetic resonance cholangiopancreatography revealed a very rare finding: the main pancreatic duct bifurcated at the pancreatic body, and these two ducts converged at the caudal side. A multilocular cystic mass in the pancreatic body and mucus discharge from the orifice of major papilla were observed. There was no protruded lesion in the main pancreatic duct. No findings suggested apparent malignancy. The patient was diagnosed as having hyperplastic intraductal papillary mucinous neoplasm of branch type showing a ring-shaped pancreatic duct, and was placed under follow-up.     

The pathology of ductal-type pancreatic carcinomas and pancreatic intraepithelial neoplasia: Insights for clinicians

The phenotypic classification of pancreatic neoplasms is based on their cellular lineage. Thus, tumors with a ductal, acinar, and endocrine phenotype can be distinguished. Most pancreatic neoplasms show a ductal phenotype and can be classified as ductal adenocarcinomas. Less common tumors with a ductal phenotype are the variants of ductal adenocarcinoma, intraductal papillary mucinous neoplasm (including colloid carcinoma), mucinous cystic neoplasm, medullary carcinoma, and other rare tumors. Ductal adenocarcinomas most likely develop from ductal proliferative lesions arising in the pancreatic duct system. A recently adopted classification system for these lesions distinguishes between three grades of pancreatic intraepithelial neoplasia (PanIN). Molecular studies have revealed that PanIN-2 and PanIN-3 lesions represent a distinct step toward invasive carcinoma.     

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.     

Cystic micropapillary neoplasm of peribiliary glands with concomitant perihilar cholangiocarcinoma

We report a case of a 75-year-old man with cystic micropapillary neoplasm of peribiliary glands detected preoperatively by radiologic examination. Enhanced computed tomography showed a low-density mass 2.2 cm in diameter in the right hepatic hilum and a cystic lesion around the common hepatic duct. cholangiocarcinoma, right hepatectomy with caudate lobectomy and bile duct resection were performed. Pathological examination revealed perihilar cholangiocarcinoma mainly involving the right hepatic duct. The cystic lesion was multilocular and covered by columnar lining epithelia exhibiting increased proliferative activity and p53 nuclear expression; it also contained foci of micropapillary and glandular proliferation. Therefore, the lesion was diagnosed as a cystic micropapillary neoplasm of peribiliary glands and resembled flat branch-type intraductal papillary mucinous neoplasm of the pancreas. Histological examination showed the lesion was discontinuous with the perihilar cholangiocarcinoma. Immunohistochemistry showed the cystic neoplasm was strongly positive for MUC6 and that the cholangiocarcinoma was strongly positive for MUC5 AC and S100 P. These results suggest these two lesions have different origins. This case warrants further study on whether this type of neoplasm is associated with concomitant cholangiocarcinoma as observed in pancreatic intraductal papillary mucinous neoplasm with concomitant pancreatic duct adenocarcinoma.     

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.     

Laparoscopic resection of synchronous intraductal papillary mucinous neoplasms: A case report

We describe herein a 68-year-old woman who was diagnosed with a quite rare entity of intraductal papillary mucinous neoplasms (IPMNs) occurring simultaneously in the left lateral lobe of liver and the tail of pancreas. Abdominal computed tomography and magnetic resonance cholangiopancreatography showed a cystic dilatation of the pancreatic duct in the pancreatic tail, which suggested an IPMN, and multiple intrahepatic duct stones in the left lateral lobe. The patient underwent a laparoscopic left lateral hepatolobectomy and spleen-preserving distal pancreatectomy. Intra-operative finding of massive mucin in the dilated bile duct implied an intraductal mucinous tumor in the liver. The diagnosis of synchronous IPMNs in the liver and pancreas was confirmed by pathological examination. The patient was followed up for 6 mo without signs of recurrence. Although several cases of IPMN of liver without any pancreatic association have been reported, the simultaneous occurrence of IPMNs in the liver and pancreas is very rare. To the best of our knowledge, it is the first reported case treated by laparoscopic resection.     

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.     

Air in the main pancreatic duct associated with a pancreatic intraductal papillary mucinous neoplasm

A 62-year-old man was referred to our hospital after ultrasonographic mass screening detected a pancreatic cyst that proved to be an intraductal papillary mucinous neoplasm. Computed tomography additionally demonstrated air in the main pancreatic duct. Magnetic resonance cholangiopancreatography and endoscopic retrograde cholangiopancreatography delineated a filling defect in the main pancreatic duct in the body of the pancreas. The sphincter of Oddi was open. The main pancreatic duct was dilated by viscous mucin; air in the duct was attributed to consequent dysfunction of the sphincter. Laboratory findings included no significant abnormality. The patient has remained asymptomatic during follow-up. Of 25 previously reported cases with air in the duct, only 1 involved an intraductal papillary mucinous neoplasm.     

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.     

ENDOSCOPIC DIAGNOSIS OF INTRADUCTAL PAPILLARY MUCINOUS NEOPLASM USING PERORAL PANCREATOSCOPY WITH NARROW BAND IMAGING

A 77‐year‐old man was diagnosed with a pancreas cyst at another hospital. Abdominal ultrasonography revealed a cyst in the head of the pancreas and a small protrusion. These findings suggested intraductal papillary mucinous neoplasm. Cytologic finding of the pancreatic juice revealed a Class III lesion, and intraductal ultrasonography and peroral pancreatoscopy (PPS) were performed. An abnormal course of main pancreatic duct (MPD) prevented the insertion of an ultrasonography probe into the MPD, and PPS was performed. The mucosal surface of the MPD near the papillary area was normal, and narrow band imaging (NBI) clearly showed the vascular structure. When the PPS was inserted more deeply, many small protrusions were observed and NBI delineated the protrusions more clearly. Papillary protrusions were observed in the cyst, but NBI did not reveal any tumor vessels. These findings led to a diagnosis of benign intraductal papillary mucinous neoplasm lesion. Since then, follow‐up examinations have been made. Changes in the cyst and protrusion have not been observed.     

Updates in diagnosis and management of pancreatic cysts

Incidental pancreatic cysts are commonly encountered with some cysts having malignant potential. The most common pancreatic cystic neoplasms include serous cystadenoma, mucinous cystic neoplasm and intraductal papillary mucinous neoplasm. Risk stratifying pancreatic cysts is important in deciding whether patients may benefit from endoscopic ultrasound (EUS) or surgical resection. Surgery should be reserved for patients with malignant cysts or cysts at high risk for developing malignancy as suggested by various risk features including solid mass, nodule and dilated main pancreatic duct. EUS may supplement magnetic resonance imaging findings for cysts that remain indeterminate or have concerning features on imaging. Various cyst fluid markers including carcinoembryonic antigen, glucose, amylase, cytology, and DNA markers help distinguish mucinous from nonmucinous cysts. This review will guide the practicing gastroenterologist in how to evaluate incidental pancreatic cysts and when to consider referral for EUS or surgery. For presumed low risk cysts, surveillance strategies will be discussed. Managing pancreatic cysts requires an individualized approach that is directed by the various guidelines.