Malignant Mucinous Cystic Neoplasms Research Articles

Invasive mucinous cystic neoplasms of the pancreas

Mucinous cystic neoplasms (MCN) and intraductal papillary mucinous neoplasms (IPMN) of the pancreas both appear to have been included and intermixed in some early reports of pancreatic cystic neoplasms. Recognition of their distinguishing features evolved during the last decade of the twentieth century. One legacy of the early period is the statement that mucinous cystic neoplasms sometimes progress to invasive colloid carcinoma. It is now recognized that colloid carcinomas characteristically arise from IPMN. We set out to see if we could find MCN that invaded as colloid carcinomas and found no examples in MCN collected in two academic medical centers. We then sought to expand the number of MCN by evaluating series from additional centers. This yielded no examples of colloid carcinomas associated with 291 MCN, however one MCN exhibited a minor component with colloid (non-cystic mucinous) growth pattern within the fibrous wall of the neoplasm. The expression of CDX2, a marker of intestinal differentiation that is found in colloid carcinomas was examined by immunostaining in the original MCN series and in the MCN with the intratumoral colloid growth pattern. Focal expression of CDX2 was found in 22 of 43 MCN including the MCN that exhibited the intratumoral colloid growth pattern. Overall, the data suggest that MCN rarely, if ever, invade as colloid carcinoma but the expression of CDX2 by some MCN and the observation of intratumoral colloid growth pattern in one MCN seems to leave open the possibility that MCN might rarely invade as colloid carcinoma.The majority of malignant MCN invade with a tubular (ductal) pattern, and rarely the invasive component was anaplastic.

Mucinous Cystic Neoplasms of the Pancreas: Definition of Preoperative Imaging Criteria for High-Risk Lesions

Background/Aim: Pancreatic mucinous cystic neoplasms (MCN) are premalignant lesions whose natural history is poorly known. Whether the dysplasia grade might be determined with precision by preoperative clinical and imaging criteria is not known. We aimed to determine if CT scan data might be useful to predict the grade of dysplasia in a series of 60 histologically proven MCN. Methods: All consecutive patients who were operated on with pathological confirmation of MCN were included. Careful CT scan evaluation was reviewed without knowledge of pathological results. Imaging and pathological results were correlated. Results: Sixty patients (59 females) were included. Low- and intermediate-grade dysplasias were identified in 47 and 3 patients (benign MCN), respectively, and high-grade dysplasia and invasive carcinoma in 7 and 3 patients (malignant MCN), respectively. Patients with benign lesions were significantly younger. None of the studied clinical data were statistically different to distinguish benign and malignant MCN, except age (42 vs. 48 years, p < 0.05). Only maximal diameter and mural nodules on CT scan were significantly more frequent in the malignant group. No malignant MCN had a maximal diameter !40 mm. At a 40-mm threshold, the sensitivity and specificity of the maximal diameter to diagnose malignant MCN were 100 and 54%, respectively. Mural nodules seen on CT scan were confirmed in all cases but one upon pathological examination of the surgical specimen. The sensitivity and specificity of the presence of a mural nodule seen on CT scan for the diagnosis of a malignant lesion were 100 and 98%, respectively. Conclusion: Preoperative CT scan detection of a mural nodule within a cystic pancreatic neoplasm suggestive of MCN strongly suggests malignancy. A diameter <40 mm is associated with no risk of malignancy.

Mucinous cystic neoplasms of the liver: a clinicopathological study and comparison with intraductal papillary neoplasms of the bile duct

Mucinous cystic neoplasm of the liver has been a controversial entity, in particular, regarding differentiation from intraductal papillary neoplasm of the bile duct. In this study, we compared the characteristics of hepatic mucinous cystic neoplasms with ovarian-like stroma (n=29) to those of cyst-forming intraductal papillary neoplasms of the bile duct (n=12). Radiological or macroscopic appearance, histological grade of malignancy, and postoperative clinical course were recorded. Immunohistochemistry for biliary or gastrointestinal markers was performed to characterize cell phenotypes. The patients with hepatic mucinous cystic neoplasm were all female and ranged in age from 21 to 67 years, which was significantly younger than that in the patients with biliary intraductal papillary neoplasm. Eighteen mucinous cystic neoplasms (76%) were located in the left lobe, with 13 (54%) in segment IV. Mucinous cystic neoplasms were significantly larger than intraductal papillary neoplasms (median diameter: 110 vs 50 mm, P=0.008). In contrast to intraductal papillary neoplasms that were all histologically malignant, 26 mucinous cystic neoplasms (90%) were adenomas, 2 (7%) were borderline malignant, and 1 (3%) was a carcinoma in situ. Benign mucinous cystadenomas had the pure biliary immunophenotype, whereas gastrointestinal markers including cytokeratin 20 and mucin core proteins 2, 5AC, and 6 were more frequently expressed in borderline or malignant mucinous cystic neoplasms and biliary intraductal papillary neoplasms. There was no mortality in the patients with mucinous cystic neoplasm, whereas one patient with intraductal papillary neoplasm died of cancer. In conclusion, hepatic mucinous cystic neoplasms and biliary intraductal papillary neoplasms have different clinicopathological characteristics as evidenced by differences in the age and gender of patients, macroscopic appearance, immunophenotypes, and grades of malignancy.

Clinicopathological Features and Prognosis of Mucinous Cystic Neoplasm With Ovarian-Type Stroma

The aim of this study was to elucidate the clinicopathological features and prognosis of mucinous cystic neoplasms (MCNs). We performed a multi-institutional, retrospective study on a collected series of patients with MCN pathologically defined by ovarian-type stroma. Clinicopathological features and prognosis were investigated. Mucinous cystic neoplasm was confirmed in 156 cases, including 129 adenomas (82.7%) and 21 noninvasive (13.4%) and 6 invasive carcinomas (3.9%). Patients with MCN were exclusively women (98.1%) with the mean age of 48.1 years. All but 1 MCN were in the pancreatic body/tail region with a mean size of 65.3 mm. Communication between the cyst and the pancreatic duct was found in 18.1%. The 3-, 5-, and 10-year survival rates were 97.6%, 96.6%, and 96.6%, respectively. A significant difference in the survival rates was observed between adenomas and carcinomas and between minimally invasive carcinomas and invasive carcinomas. Cyst diameter and presence of mural nodule were predictive of malignant MCN. Mucinous cystic neoplasm is a rare but distinctive pancreatic cystic neoplasm with a favorable overall prognosis. All MCNs should be resected to prevent malignant changes but can be observed for an appropriate time when the lesion is small without the presence of mural nodules.

Mucinous Cystic Neoplasms of the Pancreas: How Much Preoperative Evaluation is Needed?

Cystic lesions of the pancreas are identified with increasing frequency by modern imaging. The mucinous cystic neoplasm (MCN) is treated with resection for its malignant potential. How much preoperative evaluation is needed before undertaking operation is frequently a diagnostic dilemma. A retrospective review of 32 patients who underwent resection of a MCN between 1994 and 2007 was performed to define the preoperative evaluation and operative treatment of MCN patients. Thirty-two patients (30 women; mean age 49) had histology-proven MCN. Twenty-seven patients had symptomatic cysts (84%). Five had a history of gallstones and/or acute pancreatitis. All patients were worked up with CT and/or MRI. Endoscopic ultrasound was performed in 14 (44%) and endoscopic retrograde cholangiopancreatography in six (18%). Cytology was obtained in 13 (40%). Pathology revealed 22 benign MCNs (68%), five malignant MCNs (16%), and five MCNs with borderline pathology. Preoperative workup including CT or MRI imaging and cytology suggested MCN as the lesion in 15 patients (46%). CT features by itself predicted MCN in three patients (9%). Cytology revealed another six patients (19%) with possible MCN. In this series, preoperative workup did not identify three of five patients with MCN malignancy. A preoperative diagnosis cannot be made in most patients with MCN. Operative treatment can be based on clinical presentation and CT imaging because endoscopic ultrasound and fine needle aspiration for evaluation may be misleading. Middle-aged women with cystic lesions in the tail of the pancreas without prior gallstone or pancreatitis history most typically fit the profile of the MCN patient.

Evaluation of Cyst Fluid CEA Analysis in the Diagnosis of Mucinous Cysts of the Pancreas

BackgroundAlthough cyst fluid carcinoembryonic antigen (CEA; >192 ng/ml) is the preferred test for identifying mucinous pancreatic cysts, the data are more robust for mucinous cystic neoplasms (MCN) than for intraductal papillary mucinous neoplasms (IPMN). The role of cyst fluid CEA as a marker for either malignancy or malignant progression is uncertain. MethodsAll patients with pancreatic cysts who had undergone endoscopic ultrasound with cyst fluid CEA measurement between 2001 and 2009 were identified. Patient outcomes and pathology from operative resections were recorded. ResultsTwo hundred sixty-seven patients were identified; pathological diagnosis was obtained in 97. Mucinous cysts were identified in 66 of 97 (68%): benign IPMN, n = 42; malignant IPMN, n = 10; benign MCN, n = 12; malignant MCN, n = 2. CEA > 192 ng/mL had a sensitivity and specificity of 73% and 65% for identifying mucinous cysts; cyst fluid CEA was not associated with malignancy (p = 0.85). One hundred seventy-eight patients were managed with an initial non-operative strategy. Eight (4%) developed radiographic changes necessitating surgery; pathology demonstrated seven benign mucinous cysts and one retention cyst. CEA was not associated with radiographic progression (p = 0.37). ConclusionsCyst fluid CEA is a useful test for identifying mucinous cysts, including MCN and IPMN. In mucinous cysts, cyst fluid CEA is not associated with malignancy or radiographic progression.

Malignant Mucinous Cystic Neoplasms of the Pancreas(MCNs). Surgical Management and Outcome.

Malignant Mucinous Cystic Neoplasms of the Pancreas(MCNs). Surgical Management and Outcome.

A malignant mucinous cystic neoplasm arising within a mycrocystic adenoma of the pancreas

A malignant mucinous cystic neoplasm arising within a mycrocystic adenoma of the pancreas

Optimal Management of Pancreatic Cysts - A Cost-Effectiveness Analysis

The management of asymptomatic pancreatic cysts, increasingly identified as incidental findings on abdominal imaging tests is a dilemma. A small proportion of mucinous cysts may progress to invasive cancer and an aggressive strategy of surgical resection of all cysts is often pursued with the attendant risk of surgery. Objective: We performed a decision analysis comparing the cost-effectiveness of different strategies for managing solitary, asymptomatic pancreatic cysts. Methods: Incremental cost-effectiveness ratio (ICER) of three primary strategies were examined in a Markov model with a societal perspective. Strategy I was a wait and watch approach with follow-up MRI every 3 years. Development of specific alarm symptoms or imaging features suggesting malignant transformation during surveillance would trigger further evaluation with EUS-FNA and appropriate management, including resection. In Strategy II, an initial EUS-FNA was performed and patients with increased cyst fluid CEA or positive cytology underwent resection. A. Strategy III was surgical resection of all cysts without prior EUS evaluation. Results: In a 60 year old person Strategy I yielded highest quality adjusted life years (QALY) with an acceptable ICER (Table) in both the baseline and a second order Monte Carlo analysis. Strategy II dominated strategy III, and was both cheaper and yielded more QALYs. Test characteristics of EUS-FNA, surgical risk score and the annual mortality rate of malignant mucinous cystic neoplasm were the three important threshold variables that influenced the optimal strategy. Conclusion: A conservative strategy is generally more cost-effective than surgical resection in managing incidental asymptomatic pancreatic cysts. An initial EUS-FNA based strategy is favored in selecting patients who may benefit from resection.

Significance of Cellular Distribution of Ezrin in Pancreatic Cystic Neoplasms and Ductal Adenocarcinoma

Pancreatic cystic neoplasms and ductal adenocarcinoma manifest diverse clinical features and prognoses, which might be related to cellular distribution of ezrin modulated through various trophic molecules. Laboratory investigation and retrospective analysis. Medical school-affiliated university hospital. Patients with solid pseudopapillary tumor (SPT) (n = 12), mucinous cystic neoplasm (MCN) (n = 18), intraductal papillary mucinous tumor (IPMT) (n = 18), and ductal adenocarcinoma (PA) (n = 73) of the pancreas were studied. Expression of epidermal growth factor (EGF) and its receptor (EGFR) and ezrin were determined using immunohistochemistry. Epidermal growth factor receptor and ezrin expression in sodium butyrate (SB)-treated PA cell line PANC-1 was determined using immunocytochemistry. Messenger RNA expression of ezrin in the PANC-1 cell line treated with SB was determined using reverse transcriptase-polymerase chain reaction. Multivariate analysis of survival of patients with PA was performed. None of 12 SPTs displayed synchronous expression of EGF and EGFR, while all 3 malignant SPTs displayed membranous ezrin expression. One of 18 MCNs displayed synchronous expression of EGF and EGFR, while 4 of 6 borderline malignant and 8 of 8 malignant MCNs displayed membranous ezrin expression. Two of 4 borderline malignant and 11 of 11 malignant IPMTs displayed synchronous expression of EGF and EGFR, and all borderline malignant and malignant IPMTs displayed membranous ezrin expression. Less differentiated PA displayed EGF, EGFR, and membranous ezrin expression more frequently compared with more differentiated PA. Epidermal growth factor receptor expression of PANC-1 cells decreased in an SB dose dependent manner, in which PANC-1 cells became more differentiated and membranous ezrin expression of PANC-1 cells decreased correspondingly. Messenger RNA expression of ezrin in PANC-1 cells also decreased in an SB dose dependent manner. Patients with PA with membranous ezrin expression had a poorer prognosis compared with those without (P = .02). Membranous translocation of ezrin might play a role during malignant transformation of SPT, MCN, IPMT, and PA, which are either dependent on (IPMT and PA) or independent of (SPT and MCN) the EGF-EGFR pathway. Membranous ezrin expression represents a prognostic factor for PA.

Cyst Fluid Cea Concentration, Age and a Diagnosis of Malignancy Are Associated with Increased Mortality: An Update From the Cooperative Pancreatic Cyst (CPS) Study

The natural history of mucinous cystic lesions is unknown. Mucinous cystic neoplasms (MCN) and intraductal papillary mucinous neoplasms (IPMN) are pre-malignant or malignant lesions that may be associated with a greater mortality rate compared to non-mucinous lesions. We have monitored the outcome of patients in the CPC study to identify risk factors for mortality. Methods: Clinical testing results and patient outcome were prospectively collected in the CPC Study from May 1, 1999 to November 19, 2004. We hypothesized that mortality rate would be determined by type of cystic lesion, presence of malignancy, and cyst fluid CEA concentration (conc). Results: There were 699 EUS-guided aspirations in 625 consecutive patients with a cystic lesion on cross sectional imaging. 209 patients had a diagnosis established by surgical pathology or cytology. The median follow-up period was 1124d (37.5 mo). 125 mucinous lesions (71 IPMN and 54 MCN), 11 serous cystadenomas, 45 inflammatory cysts, 6 neuroendocrine tumors and 20 other cystic lesions were analyzed. Among the mucinous lesions, 46 were benign, 21 had borderline histology and 59 were malignant (carcinoma-in-situ or invasive). During the study period, there were 45 deaths. 30/45 (67%) of these patients had malignant mucinous lesions (8 malignant MCN, 22 malignant IPMN). The mortality rate for patients with malignant mucinous lesions was 51% (30/59) vs. 3% (2/67) for those with benign mucinous lesions (p < 0.001), and 0% for those with serous cystadenomas (p < 0.01). The mortality rate for malignant MCN was 53% (8/15) and 50% (22/44) for malignant IPMN. The mortality rate of patients with a mucinous lesion and who were >70 y old was 38% compared to 15% for <70y old (p < 0.01). The relative risk (RR) of mortality in patients with a malignant mucinous lesion was 34 (95% confidence interval [CI] 4.8-242.2). Age > 70y had a RR of mortality of 2.45 (95% CI 1.29-4.66). Cyst fluid CEA conc. > 500ng/ml was found in 80% of deaths v. 49% in surviving patients (p < 0.01) and had a RR of mortality of 2.95 (95% CI 1.31-6.66). Conclusions: Patients with a malignant mucinous cystic lesion have a significantly higher mortality rate (51%) than those with a benign mucinous cystic lesion (3%). Risk factors for death include increased age and cyst fluid CEA conc >500 ng/ml. The results of cyst fluid aspiration offer prognostic information in the management of patients with a cystic lesion.

Sequential accumulation of K-ras mutations and p53 overexpression in the progression of pancreatic mucinous cystic neoplasms to malignancy.

Pancreatic mucinous cystic neoplasms (MCNs) provide a spectrum of neoplastic changes ranging from benign to malignant. The authors have correlated K-ras mutations and p53 overexpression with the evolution of these tumors. Areas of mild, moderate, or severe dysplasia were microdissected from paraffin-embedded tissue sections of 28 different MCNs (10 benign, 9 borderline, 9 malignant). Nonneoplastic pancreatic ducts were also microdissected from tissues adjacent to the tumors. Ten serous cystadenomas served as negative controls. K-ras codon 12 mutations were identified by a mutant-enriched nested polymerase chain reaction-restriction fragment length polymorphism assay and confirmed by sequencing. p53 overexpression was demonstrated by immunohistochemistry. K-ras mutations were detected in 20% of benign, 33% of borderline, and 89% of malignant MCNs. Histologically, mutations were found in 26% (7/27) of MCN epithelia with mild dysplasia, 38% (5/13) of MCN epithelia with moderate dysplasia, and 89% (8/9) of MCN epithelia with severe dysplasia or carcinoma. Ten percent (4/39) of nonneoplastic pancreatic ducts at the margins of MCN harbored mutations, all associated with borderline or malignant tumors. Overexpression of p53 occurred in none of the benign or borderline MCNs but in 44% (4/9) of the malignant tumors (p = 0.006 benign/borderline vs. malignant). p53 immunoreactivity was concentrated in areas of severe dysplasia/carcinoma or invasion, where K-ras mutation had been detected. These findings demonstrate a sequential accumulation of genetic changes in the carcinogenesis of MCN. K-ras mutations appear early and increase in proportion with increasing dysplasia. Overexpression of p53 is a late finding observed only in carcinomas, and in combination with mutated K-ras genes. The presence of K-ras mutations in nonneoplastic ducts supports formal pancreatic resection over enucleation for treatment. Mucinous cystic neoplasms may be a useful model to study the evolution of pancreatic ductal adenocarcinomas, in which precursor lesions remain unknown.

Giant cell tumor of the pancreas arising in the ovarian-like stroma of a mucinous cystadenocarcinoma

We describe a malignant mucinous cystic neoplasm of the pancreas with ovarian-like stroma within which an osteoclast-like giant cell rich tumor arose. This rare tumor had a unique immunohistochemical profile with the giant cells staining for vimentin, leukocyte common antigen, and the monocyte/macrophage marker CD68, whereas the mucinous epithelium stained for epithelial membrane antigen and cytokeratin. The immunohistochemical findings are consistent with two lines of differentiation, one epithelial and the other suggesting mesenchymal differentiation of the giant cell tumor with an immunophenotype similar to giant cell tumor of bone. The coexistence of these two rare tumors suggests that they are histogenetically related. The findings of a giant cell tumor arising in the ovarian stroma indicates that the stroma of mucinous tumors is not always an innocuous component of the tumor.

Diagnostic dilemmas in patients with cystic neoplasms of the pancreas.

Cystic neoplasms of the pancreas (CNP) are rare lesions that can be difficult to diagnose preoperatively. Twenty patients with cystic neoplasms of the pancreas including five microcystic adenomas, six benign mucinous cystic neoplasms, three malignant mucinous cystic neoplasms, two solid and papillary epithelial neoplasms, and four cystic neuroendocrine tumors were treated at a single institution between 1962 and 1987. The average duration of symptoms prior to diagnosis was 10 months. Five patients were asymptomatic. Forty percent of patients presented with an abdominal mass. Plain abdominal x-rays and UGI barium contrast studies were never diagnostic. Ultrasonography, computerized tomography (CT) and visceral angiography aided in the correct diagnosis in 28%, 36%, and 75% of patients studied, respectively. Overall a correct diagnosis was made preoperatively in only 35% of patients. Twelve of 13 patients were correctly diagnosed at laparotomy with intraoperative biopsy. Without biopsy the mass was misdiagnosed at laparotomy in five of six cases. CNP must be suspected in any patients who present with an upper abdominal mass with or without abdominal pain and no history of pancreatitis. CT may be diagnostic in up to one third of cases and should be obtained routinely to demonstrate the proximity of the lesion to other structures. Visceral angiography should also be obtained prior to operation. A generous incisional biopsy should be obtained of all pancreatic cysts that are not to be resected.