Definition of MCN (mucinous cystic neoplasm of the pancreas) and a proposal for a new concept of MRN or MSN (mucinous round or spherical neoplasm)

The differential diagnosis of IPMN and MCN is very important for clinicians. MCN is reported to develop in middle-aged females (mean age 48 years) and in the body and tail of the pancreas. Some doctors insist that ovarian-like stroma is absolutely necessary for the definition of MCN. Prompt resection of MCN after diagnosis is desirable. In contrast, about 60% of cases with branch-type IPMN do not require an operation. Therefore, one of the important goals in the differential diagnosis of MCN and branch-type IPMN is to determine the surgical indications before the operation. We believe that MCN and IPMN should be defined by imaging procedures before the operation. We suggest that a neoplasm with an appearance similar to an orange should be diagnosed as MCN, while that with an appearance similar to a bunch of grapes in MRCP should be diagnosed as branch-type IPMN. Proposal of a new concept: If the term MCN is restricted to neoplasms that exhibit ovarian-like stroma, we propose that lesions which are surrounded by a very thick capsule, and which show an orange-like appearance by imaging procedures without histological ovarian-like stroma should be called MRN (mucinous round neoplasm) or MSN (mucinous spherical neoplasm).     

Pancreatic mucinous cystic neoplasm defined by ovarian stroma: demographics, clinical features, and prevalence of cancer.

BACKGROUND & AIMS: Pancreatic mucin-producing cystic neoplasms are classified into 2 distinct entities: mucinous cystic neoplasm (MCN) and intraductal papillary mucinous neoplasm (IPMN). In previous studies, MCN often has been defined loosely and has not always been distinguished clearly from IPMN. Our aims were to determine the demographics, clinical features, and prevalence of invasive cancer in MCN defined by the presence of characteristic ovarian stroma. METHODS: By using the presence of ovarian stroma as a requisite criterion for diagnosis of MCN, a single pathologist, unaware of clinical information, identified 56 MCNs from 243 mucin-producing neoplasms resected at Mayo Clinic between 1986 and 2003. Medical records of the MCN patients were reviewed to obtain clinical and demographic data. RESULTS: Patients with MCN were almost exclusively (98%) women; we identified 1 man with a neoplasm containing ovarian stroma. The mean (+/-SD) age at resection was 48 +/- 15 years (84% < 60 y). Abdominal pain was the most common presenting symptom; 16% were asymptomatic. Most MCN (93%) were in the pancreatic body/tail region. Their median size was 5 cm (61% > or =5 cm). Histologically, 50 (89%) were adenomas, 2 (4%) had carcinoma-in-situ, and 4 (7%) had invasive cancer. None of the 22 MCNs <5 cm in size had invasive cancer. No patient with noninvasive disease had a recurrence after resection. CONCLUSIONS: MCN defined by ovarian stroma has a distinct demographic and clinical profile and a low prevalence of invasive cancer. These observations suggest that ovarian stroma should be used as the defining criterion for diagnosing MCN.     

Epigenetic alterations in intraductal papillary mucinous neoplasms of the pancreas

Intraductal papillary mucinous neoplasm (IPMN), an increasingly recognized cystic neoplasm of the pancreas with a broad spectrum of malignant potential, has been considered a precursor to infiltrating ductal adenocarcinoma. Because of its unique clinical, radiological, pathological, and molecular features, IPMN has attracted considerable interest among clinicians and researchers. Although some genetic alterations have been described in IPMNs, the molecular features that characterize the evolution and progression of these neoplasms are largely unknown. Recent studies have shown that aberrant methylation of the promoter cytosine-phospho-guanine (CpG) island is a common mechanism associated with the silencing of tumor-suppressor and cancer-related genes in IPMNs. Importantly, the prevalence of such methylation increases along with the grade of neoplasia, suggesting that these epigenetic events may contribute to the progression of IPMNs. Further studies of epigenetic alterations in IPMN will shed light on the molecular pathogenesis of this unique neoplasm and lead to the identification of epigenetic markers that can be applied in the clinical setting.     

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.     

Clinicopathologic review of 41 cases of pancreatic mucinous cystic neoplasms]

BACKGROUND/AIMS: Intraductal papillary mucinous neoplasms (IPMN) and mucinous cystic neoplasms are included in mucin-producing pancreatic tumors. The reports about IPMN are not uncommon but those about the mucinous cystic neoplasms are relatively few. The aims of this study were to define the natural history of resected mucinous cystic neoplasms of the pancreas and to identify the findings which suggest malignancy. METHODS: The authors retrospectively evaluated the clinical outcomes of 41 patients with mucinous cystic neoplasms who were surgically resected at Asan Medical Center between 1995 and 2004. RESULTS: Women (n=33) were more frequently affected than men (n=8). Thirty three patients (80.6%) had adenoma, 1 (2.4%) borderline malignancy, 1 (2.4%) carcinoma in situ, and 6 (14.6%) invasive mucinous cystadenocarcinoma. The most frequent symptom was abdominal pain (39%). About half of the enrolled patients were asymptomatic. Unilocular type (79%) was more frequent than the multilocular type (21%) on gross morphology. The tumor size of invasive mucinous cystic neopolasms was larger than that of non-invasive mucinous cystic neoplalsms (p=0.01). Abdominal pain was more frequent in invasive mucinous cystic neoplasms (p=0.026). On gross morphology, mural nodules were detected in 4 of 6 patients with invasive mucinous cystic neoplasms. However, they were not detected in any patients with non-invasive mucinous cystic neoplasms. Recurrence developed in none of the 35 patients with non-invasive mucinous cystic neoplasms, however 2 of the 6 patients with invasive mucinous cystic neoplasms died within 5 years. CONCLUSIONS: Clinical predictors of invasive mucinous cystic neoplasms are suggested to be tumor size and abdominal pain. The prognosis of the non-invasive mucinous cystic neoplasms is excellent when curative resection is performed.     

Zystische Pankreasl?sionen

Cystic changes of the pancreas comprise a large spectrum of neoplastic and non-neoplastic lesions. Among these are five entities, i.e. pseudocysts, intraductal papillary mucinous neoplasms (IPMN), mucinous cystic neoplasms (MCN), serous cystic neoplasms (SCN) and solid pseudopapillary neoplasms (SPN), which represent 95% of all cystic pancreatic lesions. While SCN and SPN have a good prognosis, IPMN and MCN have a high risk of malignancy as they are potential precursors of pancreatic ductal adenocarcinoma. The differential diagnosis between these five entities is based on epidemiology, pathology and clinical criteria. Consideration of these criteria allows in many cases a preoperative stratification that is the basis for an adequate therapy.     

Mucinous cystic neoplasms of the pancreas: pathology and molecular genetics

Mucinous cystic neoplasm (MCN) of the pancreas is a distinct clinicopathological entity characterized by mucin-producing epithelial and cyst-forming neoplasm with “ovarian-type” stroma beneath the epithelial component. It is clearly distinguished from ductal adenocarcinoma and intraductal papillary mucinous neoplasm (IPMN). However, MCN can progress to infiltrating carcinoma, and frequently shows a similar histological pattern to ductal adenocarcinoma. Several genetic alterations such as K-ras oncogene mutation, and epigenetic alterations such as hypermethylation of p16 in the invasive component of MCN are also common with ductal adenocarcinoma. Furthermore, recent technologies, including a laser-assisted microdissection system for histological slides and global gene expression profilings using DNA microarrays, made possible to identify more information about molecular abnormalities of MCNs. It is important to diagnose the lesions before they progress to an invasive carcinoma. MCN is one of the precursors of invasive pancreatic carcinoma.     

Management of mucinous cystic neoplasms of the pancreas

The purpose of this study was to investigate the actual management of mucinous cystic neoplasm (MCN) of the pancreas. A systematic review was performed in December 2009 by consulting PubMed MEDLINE for publications and matching the "pancreatic mucinous cystic neoplasm", "pancreatic mucinous cystic tumour", "pancreatic mucinous cystic mass", "pancreatic cyst", and "pancreatic cystic neoplasm" to identify English language articles describing the diagnosis and treatment of the mucinous cystic neoplasm of the pancreas. In total, 16 322 references ranging from January 1969 to December 2009 were analysed and 77 articles were identified. No articles published before 1996 were selected because MCNs were not previously considered to be a completely autonomous disease. Definition, epidemiology, anatomopathological findings, clinical presentation, preoperative evaluation, treatment and prognosis were reviewed. MCNs are pancreatic mucinproducing cysts with a distinctive ovarian-type stroma localized in the body-tail of the gland and occurring in middle-aged females. The majority of MCNs are slow growing and asymptomatic. The prevalence of invasive carcinoma varies between 6% and 55%. Preoperative diagnosis depends on a combination of clinical features, tumor markers, computed tomography (CT), magnetic resonance imaging, endoscopic ultrasound with cyst fluid analysis, and positron emission tomography-CT. Surgery is indicated for all MCNs.     

Analysis of c-kit protein expression in pancreatic neoplasms and its implication for prognosis

BACKGROUND/AIMS: To evaluate the expression and role of c-kit protein in the neoplasia of pancreatic neoplasms and its relationship to prognosis in invasive ductal carcinoma (IDC) of the pancreas. METHODOLOGY: The immunohistochemical expression of c-kit protein was studied in normal pancreatic tissues, intraductal papillary-mucinous neoplasms of the pancreas (IPMN), mucinous cystic neoplasm of the pancreas (MCN), and IDC of the pancreas. The immunoreactive score (IRS) of c-kit protein expression was examined in normal pancreatic ductal cells, neoplastic cells, and pancreatic endocrine cells. RESULTS: The IRS values of c-kit protein expression in various neoplastic cells were significantly higher than those in normal ductal cells. No significant difference was seen between IRS values of c-kit protein expression in various pancreatic neoplastic cells of IDC of the pancreas, IPMN and MCN. No significant difference was seen between IRS values of c-kit expression in endocrine cells among various pancreatic tissues. Furthermore, a survival analysis in patients with IDC of the pancreas showed an obvious trend toward decreased survival in patients with c-kit-positive cancer, and c-kit protein expression did not correlate with any clinicopathological factors in IDC of the pancreas. CONCLUSIONS: c-kit protein expression may play an important role in neoplasia of pancreatic neoplasms. In view of the result that c-kit protein expression was found in 8% of IDC of the pancreas, a clinical trial for STI-571 (Glivec) against pancreatic cancer may be warranted for selected pancreatic cancer patients with c-kit protein expression.     

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.     

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.     

International guidelines for the management of pancreatic intraductal papillary mucinous neoplasms

The management of intraductal papillary mucinous neoplasms(IPMN) is presently evolving as a result of the improved understanding of the natural history and biological behavior of the different pancreatic cystic neoplasms; and better preoperative diagnosis of these neoplasms due to advancement in preoperative diagnostic tools. International consensus guidelines for the management of IPMN were first formulated in 2006 and subsequently revised in 2012. Both these guidelines were constructed based on expert opinion and not on robust clinical data. The main limitation of the original Sendai guidelines was that it had a low positive predictive value resulting in many benign neoplasms being resected. Hence,these guidelines were revised in 2012. However,although the updated guidelines resulted in an improvement in the positive predictive value over the Sendai Guidelines,the results of several studies validating these guidelines demonstrated that its positive predictive value remained low. Furthermore,although both guidelines were associated with high negative predictive values,several investigators have demonstrated that some malignant IPMNs may be missed. Finally,it is imperative to emphasize that major considerations when managing a patient with IPMN including the patient's surgical risk,life-expectancy and even cost of investigations are not taken into account in current guidelines. The management of a patient with IPMN should be individualized and tailored according to a patient's risk benefit profile for resection vs surveillance.     

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.     

Epidemiology,clinical features and diagnostic work-up of cystic neoplasms of the pancreas: Interim analysis of the prospective PANCY survey

IntroductionA prospective survey to evaluate the diagnostic workup of cystic pancreatic neoplasms (CPNs) according to the Italian guidelines.MethodsAn online data sheet was built.ResultsFifteen of the 1385 patients (1.1%) had non cystic neoplastic lesions. Forty percent (518/1295) had at least one 1st degree relative affected by a solid tumor of the digestive and extra-digestive organs. Symptoms/signs associated with the cystic lesion were present in 24.5% of the patients. The cysts were localized in the head of the pancreas in 38.5% of patients. Of the 2370 examinations (1.7 examinations per patient) which were carried out for the diagnosis, magnetic resonance imaging was performed as a single test in 48.4% of patients and in combination with endoscopic ultrasound in 27% of the cases. Of the 1370 patients having CPNs, 89.9% had an intraductal papillary mucinous neoplasm (IPMN) (70.1% a branch duct IPMN, 6.2% a mixed type IPMN and 4.6% a main duct IPMN), 12.7% had a serous cystadenoma, 2.8% a mucinous cystadenoma, 1.5% a non-functioning cystic neuroendocrine neoplasm, 0.7% a solid-pseudopapillary cystic neoplasm, 0.3% a cystic adenocarcinoma, and 1.2% an undetermined cystic neoplasm. Seventy-eight (5.7%) patients were operated upon after the initial work-up.ConclusionsThis prospective study offers a reliable real-life picture of the diagnostic work-up CPN.     

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.     

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.     

Precancerous lesions of the pancreas

Pancreatic cancer has a very poor prognosis, with a five year survival of only 5%. New studies have shown that it takes over 11 years for cells to develop invasive capability. This provides an opportunity to intervene if precursor lesions can be detected. This paper reviews the molecular, pathological, clinical findings and management of pancreatic intraepithelial neoplasia (PanIN), intraductal pancreatic mucinous neoplasm (IPMN) and mucinous cystic neoplasm (MCN), three precursor lesions which can give rise to invasive carcinoma of the pancreas.