Pancreatic Mucinous Cystic Neoplasms Research Articles

Cytopathological Analysis of Cyst Fluid Enhances Diagnostic Accuracy of Mucinous Pancreatic Cystic Neoplasms

Widespread use of cross-sectional imaging and increasing age of the general population has increased the number of detected pancreatic cystic lesions. However, several pathological entities with a variety in malignant potential have to be discriminated to allow clinical decision making. Discrimination between mucinous pancreatic cystic neoplasms (PCNs) and nonmucinous pancreatic lesions is the primary step in the clinical work-up, as malignant transformation is mostly associated with mucinous PCN. We performed a retrospective analysis of all resected PCN in our tertiary center from 2000 to 2014, to evaluate preoperative diagnostic performance and the results of implementation of the consensus guidelines over time. This was followed by a prospective cohort study of patients with an undefined pancreatic cyst, where the added value of cytopathological mucin evaluation to carcinoembryonic antigen (CEA) in cyst fluid for the discrimination of mucinous PCN and nonmucinous cysts was investigated. Retrospective analysis showed 115 patients operated for a PCN, with a correct preoperative classification in 96.2% of the patients. High-grade dysplasia or invasive carcinoma was observed in only 32.3% of mucinous PCN. In our prospective cohort (n = 71), 57.7% of patients were classified as having a mucinous PCN. CEA ≥ 192 ng/mL had an accuracy of 63.4%, and cytopathological mucin evaluation an accuracy of 73.0%. Combining these 2 tests further improved diagnostic accuracy of a mucinous PCN to 76.8%. CEA level and mucin evaluation were not predictive of the degree of dysplasia. These findings show that adding cytopathology to cyst fluid biochemistry improves discrimination between mucinous PCN and nonmucinous cysts.

Overweight increases the risk of malignancy in patients with pancreatic mucinous cystic neoplasms.

Distinguishing between benign and malignant pancreatic cysts remains a clinical challenge. The aim of this study was to investigate the influence of body mass index (BMI) and preoperative clinical and cyst features, as described by the International Consensus Guidelines, on malignancy in patients with pancreatic mucinous cystic neoplasms (PMCNs).A retrospective cohort study was performed on patients with PMCNs who underwent surgical resection between January 1994 and June 2014. Preoperative BMI, clinical demographic data, cystic features, tumor markers, and surgical pathology results were analyzed. Predictors of malignancy were determined by univariate and multivariate analysis using logistic regression.One hundred sixty-four cases of PMCNs, including 106 intraductal papillary mucinous neoplasms (IPMNs) and 58 mucinous cystic neoplasms (MCNs), were analyzed. On univariate analysis, older age (P = 0.008), male sex (P = 0.007), high-risk stigmata (P = 0.007), diabetes mellitus (DM; P = 0.008), and BMI >25 (P < 0.001) were associated with malignancy. Multivariate analysis found that BMI >25 (odds ratio, 3.99; 95% confidence interval: 1.60–10) was an independent predictor of malignancy. In subgroup analysis, BMI >25 was an independent predictor of malignancy in IPMNs but not in MCNs.Overweight patients with IPMNs have a higher risk of malignancy and should be followed closely or undergo resection. The operative strategy for PMCNs should consider cyst-related and patient-related risk factors.

Sendai and Fukuoka Consensus Guidelines Identify Advanced Neoplasia in Patients With Suspected Mucinous Cystic Neoplasms of the Pancreas

Little is known about whether the 2006 Sendai guidelines or 2012 Fukuoka guidelines are being used to determine the level of risk posed by suspected pancreatic mucinous cystic neoplasms (PCNs). We evaluated whether the guidelines accurately predicted which patients with suspected PCNs, which was based on cross-sectional imaging findings, would be found to have advanced neoplasia in surgery. We performed a retrospective study of data collected from 194 patients with cystic lesions of the pancreas, which were assessed by cross-sectional imaging analyses, who underwent surgery for suspected PCNs at the Hospital at the University of Pennsylvania from 2000 through 2008. Imaging data were used to classify patients according to the Sendai guidelines as high risk or low risk and according to the Fukuoka guidelines as high risk, worrisome, or low risk. Pathology analyses of samples collected during surgery were used as the reference. A logistic regression model was created to identify factors associated with advanced neoplasia. The Sendai and Fukuoka guideline criteria were analyzed by univariate and multivariable logistic regression analyses. Advanced neoplasias were found in 36 patients (18.5%; 22 invasive cancers and 14 high-grade dysplasias). The median size of cysts was 33 mm. All patients found to have invasive cancers were accurately assigned to the Sendai guidelines high risk or Fukuoka guidelines high risk groups. However, 3 patients in the Sendai guidelines low risk and 2 patients in the Fukuoka guidelines low risk groups were found to have high-grade dysplasia. The Sendai guidelines identified patients with advanced neoplasia with 91.7% sensitivity, 21.5% specificity, 21% positive predictive value, and 91.9% negative predictive value. A designation of Fukuoka guidelines high risk identified patients with advanced neoplasia with 55.6% sensitivity, 73% specificity, 32% positive predictive value, and 87.9% negative predictive value. Overall, there was no statistically significant difference between the guidelines in predicting which patients had advanced neoplasia. On multivariate analysis, the presence of a mural nodule (odds ratio [OR], 2.88; 95% confidence interval [CI], 1.33-6.27; P = .008), dilated main pancreatic duct >10 mm (OR, 7.44; 95% CI, 2.36-23.52; P = .001), or enhancing solid component (OR, 2.92; 95% CI, 1.16-7.64; P = .02) were associated with detection of advanced neoplasia in pancreatic cysts. On the basis of a retrospective analysis, the Sendai and Fukuoka guidelines accurately determine which patients with pancreatic cysts have advanced neoplasia. The guidelines accurately recommended surgical resection for all patients found to have invasive cancer, although some patients with high-grade dysplasia were missed. The updated Fukuoka guidelines are not superior to the Sendai guidelines in identifying neoplasias. Cyst size was not associated with advanced neoplasia.

Pancreatic mucinous cystic neoplasm in a male patient.

Mucinous cystic neoplasm (MCN) of the pancreas usually affects female patients and is characterized by an ovarian-type stroma. From literature review, only 9 cases of MCNs have been reported in male patients. We describe the 10th case of a MCN in a 65-year-old male patient who underwent a distal pancreatectomy with spleen resection and standard lymphadenectomy. MCN may rarely regard male patients, probably for embryological abnormalities.

Intraductal papillary mucinous neoplasms of the pancreas (IPMNs): epidemiology, diagnosis and future aspects.

Intraductal papillary mucinous neoplasms of the pancreas (IPMNs) are potentially malignant intraductal epithelial neoplasms which consist of columnar, mucin-containing cells and arise from the epithelium of the main pancreatic duct or its branches. IPMNs as well as pancreatic intraepithelial neoplasias (PanINs) and mucinous cystic neoplasms represent noninvasive precursors of invasive ductal adenocarcinoma of the pancreas. The diagnosis of IPMNs includes radiographic (CT scanning, MRI, MRCP) and endoscopic evaluation (ERCP, EUS), PET, as well as serum tumor markers and molecular markers. The Sendai Consensus Guidelines help guide surgical resection for patients with IPMN. The follow-up of these patients, as well as of those who do not undergo surgical resection, is of great importance, since patients with IPMN appear to be at risk for other malignancies. Herein, the authors summarize the data presented at the 2013 ASCO Gastrointestinal Cancers Symposium regarding incidence and clinicopathological characteristics of IPMN (Abstracts #324, #187 and #179).

Mucinous cystic neoplasm of the pancreas activated during pregnancy.

The characteristic histological feature of pancreatic mucinous cystic neoplasm (MCN) is ovarian-like stroma (OS) underlying the epithelium and existence of estrogen receptors and progesterone receptors in the nucleus of OS. We experienced a case of pancreatic MCN which was activated during pregnancy and confirmed the existence of estrogen receptors and progesterone receptors. In cases with potential factors for malignancy, surgical resection of MCN may be needed during pregnancy. On the other hand, in cases without these, as female sex hormones may have an influence on the behavior of pancreatic MCN during pregnancy, the timing of surgery should be decided on a case-by-case basis, taking into consideration the status of the malignancy, the stage of the pregnancy, and the condition of the mother and fetus.

Clinicopathologic characteristics of 29 invasive carcinomas arising in 178 pancreatic mucinous cystic neoplasms with ovarian-type stroma: implications for management and prognosis.

Information on the clinicopathologic characteristics of invasive carcinomas arising from mucinous cystic neoplasms (MCNs) is limited, because in many early studies they were lumped and analyzed together with noninvasive MCNs. Even more importantly, many of the largest prior studies did not require ovarian-type stroma (OTS) for diagnosis. We analyzed 178 MCNs, all strictly defined by the presence of OTS, 98% of which occurred in perimenopausal women (mean age, 47 y) and arose in the distal pancreas. Twenty-nine (16%) patients had associated invasive carcinoma, and all were female with a mean age of 53. Invasion was far more common in tumors with grossly visible intracystic papillary nodule formation ≥1.0 cm (79.3% vs. 8.7%, P=0.000) as well as in larger tumors (mean cyst size: 9.4 vs. 5.4 cm, P=0.006); only 4/29 (14%) invasive carcinomas occurred in tumors that were <5 cm; however, none were <3 cm. Increased serum CA19-9 level (>37 U/L) was also more common in the invasive tumors (64% vs. 23%, P=0.011). Most invasive carcinomas (79%) were of tubular type, and the remainder (5 cases) were mostly undifferentiated carcinoma (2, with osteoclast-like giant cells), except for 1 with papillary features. Interestingly, there were no colloid carcinomas; 2 patients had nodal metastasis at the time of diagnosis, and both died of disease at 10 and 35 months, respectively. While noninvasive MCNs had an excellent prognosis (100% at 5 y), tumors with invasion often had an aggressive clinical course with 3- and 5-year survival rates of 44% and 26%, respectively (P=0.000). The pT2 (>2 cm) invasive tumors had a worse prognosis than pT1 (≤2 cm) tumors (P=0.000), albeit 3 patients with T1a (<0.5 cm) disease also died of disease. In conclusion, invasive carcinomas are seen in 16% of MCNs and are mostly of tubular (pancreatobiliary) type; colloid carcinoma is not seen in MCNs. Serum CA19-9 is often higher in invasive carcinomas, and invasion is typically seen in OTS-depleted areas with lower progesterone receptor expression. Invasion is not seen in small tumors (<3 cm) and those lacking intracystic papillary (mural) nodules of ≥1 cm, thus making the current branch-duct intraductal papillary mucinous neoplasm management protocols also applicable to MCNs.

A case of Peliosis and epithelial cyst of intrapancreatic heterotopic spleen: a differential diagnosis of pancreatic mucinous cystic neoplasm

A case of Peliosis and epithelial cyst of intrapancreatic heterotopic spleen: a differential diagnosis of pancreatic mucinous cystic neoplasm

LEF-1 is frequently expressed in colorectal carcinoma and not in other gastrointestinal tract adenocarcinomas: an immunohistochemical survey of 602 gastrointestinal tract neoplasms.

LEF-1 is a DNA-binding protein that interacts with β-catenin and activates Wnt-responsive target genes. We analyzed the immunohistochemical expression of LEF-1 in 602 gastrointestinal and pancreatobiliary neoplasms in an attempt to (1) investigate the utility of LEF-1 immunohistochemistry as an ancillary marker in gastrointestinal/pancreatobiliary neoplasia, and (2) to perform a clinicopathologic and survival analysis of colorectal carcinoma stratified by LEF-1 expression. LEF-1 nuclear positivity was frequently identified in colorectal carcinoma (89/241, 37%) and only infrequently identified in other neoplasms: 11% esophagus/esophagogastric adenocarcinomas, 7% gastric adenocarcinomas, 1% pancreatic ductal adenocarcinomas, 4% pancreatic intraductal papillary mucinous neoplasms, and in no cases of appendiceal mucinous neoplasms or pancreatic mucinous cystic neoplasms. LEF-1 expression was identified in 35% of colorectal carcinomas that lacked CK20 and CDX2 expression. In colorectal carcinomas, LEF-1-positive tumors more frequently harbored KRAS mutations compared with LEF-1-negative tumors (39% vs. 16%, P=0.005). Patients with moderate/strong LEF-1-positive colorectal carcinoma had a trend of worse overall survival compared with patients with colorectal carcinomas with weak/negative LEF-1 expression (5 y overall survival, 31% vs. 47%, P=0.15). In conclusion, LEF-1 is most commonly expressed in colorectal carcinoma and infrequently observed in the upper gastrointestinal tract and pancreatic adenocarcinoma. LEF-1 Immunohistochemistry may be especially useful as an ancillary diagnostic marker in colorectal carcinomas, which lack the expression of both CK20 and CDX2. LEF-1 expression is associated with the presence of KRAS mutations and may have prognostic value as a trend of worse overall survival is seen in patients with LEF-1-positive colorectal carcinoma.

Preoperative GNAS and KRAS testing in the diagnosis of pancreatic mucinous cysts.

Management guidelines for pancreatic intraductal papillary mucinous neoplasms (IPMN) and mucinous cystic neoplasms (MCN) are based on the assumption that mucinous cysts can be accurately distinguished from other pancreatic cystic lesions. Previous studies using surgical material have identified recurrent mutations in GNAS and KRAS in pancreatic mucinous neoplasms. Yet, the diagnostic utility of testing for both genes in pancreatic cyst fluid obtained by endoscopic ultrasound-fine-needle aspiration (EUS-FNA) remains unclear. GNAS and KRAS testing was performed on EUS-FNA pancreatic cyst fluid from 91 pancreatic cysts: 41 IPMNs, 9 IPMNs with adenocarcinoma, 16 MCNs, 10 cystic pancreatic neuroendocrine tumors (PanNET), 9 serous cystadenomas (SCA), 3 retention cysts, 2 pseudocysts, and 1 lymphoepithelial cyst. Mutations in GNAS were detected in 16 (39%) IPMNs and 2 (22%) IPMNs with adenocarcinoma. KRAS mutations were identified in 28 (68%) IPMNs, 7 (78%) IPMNs with adenocarcinoma, and 1 (6%) MCN. Mutations in either gene were present in 34 (83%) IPMNs, 8 (89%) IPMNs with adenocarcinoma, and 1 (6%) MCN. No mutations were found in cystic PanNETs, SCAs, retention cysts, pseudocysts, and a lymphoepithelial cyst. GNAS and KRAS mutations had 100% specificity [95% confidence interval (CI), 0.83-1.00] but 65% sensitivity (95% CI, 0.52-0.76) for mucinous differentiation. Among IPMNs, mutations in either gene had 98% specificity (95% CI, 0.86-1.00) and 84% sensitivity (95% CI, 0.70-0.92). The combination of GNAS and KRAS testing was highly specific and sensitive for IPMNs; however, the lack of sensitivity for MCNs highlights the need for additional markers to improve the detection of pancreatic mucinous neoplasms.

Differential diagnosis of pancreatic serous oligocystic adenoma and mucinous cystic neoplasm with spectral CT imaging: Initial results

To investigate the imaging characteristics of pancreatic serous oligocystic adenoma (SOA) and mucinous cystic neoplasms (MCNs) using spectral computed tomography (CT) and to evaluate whether quantitative information derived from spectral imaging can improve the differential diagnosis of these diseases. From February 2010 to June 2013, 44 patients (24 SOAs and 20 MCNs) who underwent spectral CT imaging were included in the study. Conventional characteristics and quantitative parameters were compared between the two disease groups. Logistic regression was used for multiparametric analysis. The receiver-operating characteristic curve was used to evaluate the diagnostic performance of single parameter and multiparametric analysis. Two radiologists diagnosed the diseases blinded and independently, without and with the information of the statistical analysis. Tumour location, contour, size, and monochromatic CT values at 40 keV to 70 keV, iodine concentration, and effective atomic number (effective-Z) in the late arterial phase were the independent factors correlated with category. Multiparametric analysis with logistic regression showed that tumour size, location, and contour were the most effective variations, and obtained an area under the ROC curve (AUC) of 0.934. With the knowledge of statistical analysis, the accuracy of the first reader increased from 70.5% to 86.4%, and the accuracy of the second reader increased from 81.8% to 90.9%. Although CT spectral imaging provided additional information and multiparametric analysis obtained better performance than single-parameter analysis in differentiating MCNs from SOAs, multiparametric analysis with the combination of quantitative parameters derived from CT spectral imaging did not improve the diagnostic performance. Tumour size, location, and contour played an important role in differentiating MCNs from SOAs.

Clinicopathological and CT features of mucinous cystic neoplasms of the pancreas

To evaluate the clinicopathological and CT features of mucinous cystic neoplasms (MCNs) of the pancreas and analyze the correlative risk factors for malignant pancreatic mucinous cystic neoplasms. Ninety-eight patients who underwent curative resection for mucinous cystic neoplasms of the pancreas at PLA General Hospital from April 1994 to January 2013 were included in this study. All clinicopathological data available were retrospectively analyzed. All patients were divided into benign tumors + premalignant lesion group (70 patients) and malignant tumor group (28 patients). Clinicopathological and CT features of the mucinous cystic neoplasms of the pancreas and risk factors of malignant pancreatic mucinous cystic neoplasms were analyzed. Mucinous cystic neoplasms were seen mostly in perimenopausal women (71.4%, 70/98 cases,), and 51.0% (50/98 cases) of the patients had obvious clinical signs, mostly non-specific abdominal pain, but jaundice was present only in cases of malignant mucinous cystic neoplasms. Benign mucinous cystic neoplasms were mostly located in the distal pancreas (74.3%) and characterized with septa and thin cystic wall, while more malignant mucinous cystic neoplasms were located at the proximal pancreas (57.1%) and characterized with thick cystic wall and solid components. Univariate analysis showed that findings associated with malignancy gender, age ≥ 60, presence of symptoms, jaundice, weight loss, tumor location, margin, wall thickness, solid components and dilation of the main pancreatic duct were significantly correlated with malignant tumor development (P < 0.05 for all). The results of multiple logistic regression analysis showed that thick wall and solid components were independent prognostic factors for malignancy (OR = 31.417 and 34.976, P < 0.05 for both). Gender, age ≥ 60, presence of symptoms, jaundice, weight loss, tumor location, margin, wall thickness, solid components and dilation of the main pancreatic duct are important diagnostic indices of malignant mucinous cystic tumors of the pancreas, while thick wall and solid components are independent risk factors of malignant pancreatic mucinous cystic neoplasms.

Intraductal papillary neoplasms and mucinous cystic neoplasms of the hepatobiliary system: demographic differences between Asian and Western populations, and comparison with pancreatic counterparts

To improve the characterization of intraductal papillary neoplasm of the bile duct (IPNB) and mucinous cystic neoplasm of the liver (MCN-L). A retrospective review of pathology archives (1999-2011) in our three institutions identified cases of IPNB (n=138) and MCN-L (n=54). The IPNB/MCN-L ratio was 5.7:1 at Samsung Medical Centre in Seoul, which was significantly higher than those at the University of Washington Medical Center in Seattle (1:3.0) and King's College Hospital in London (1:6.3). This difference was mainly attributable to the considerably larger number of patients with IPNB in Seoul (n=131) than in Seattle and London (n=7). Western patients with IPNB were all non-Asian in ancestry. IPNB differed from pancreatic intraductal papillary neoplasm in its higher histological grade, more advanced stage of an associated invasive cancer, and worse prognosis. In contrast, MCN-L showed significantly lower histological grade than its pancreatic counterpart (P=0.022). Unlike in pancreatic mucinous cystic neoplasm, malignant transformation was very rare in MCN-L (10% versus 2%). This study demonstrated demographic differences in IPNB and MCN-L among regions. IPNB and MCN-L differ from their pancreatic counterparts in the risk of malignant transformation and patients' prognosis.

Multidisciplinary diagnostic and therapeutic approaches to pancreatic cystic lesions

Pancreatic cystic lesions are commonly encountered today with the routine use of cross-sectional imaging modalities such as computed tomography (CT) and magnetic resonance imaging (MRI). The majority of patients discovered to have a pancreatic cyst are completely asymptomatic; yet the presence of such a finding instills fear in the minds of both patient and physician, as the concern for malignant transformation to pancreatic cancer is great despite the relatively low overall likelihood of cyst progression. Not all cysts in the pancreas represent pancreatic cystic neoplasms (PCNs), and not all PCNs have significant malignant potential. Mucinous PCNs are the most concerning, as these lesions have the greatest potential for cancerous transformation to adenocarcinoma. Within the group of mucinous PCNs, intraductal papillary mucinous neoplasms (IPMNs) involving the main pancreatic duct are the most worrisome, and surgical resection should be pursued if the patient has appropriate operative risks. IPMN lesions involving the branch ducts, and mucinous cystadenomas, have a lower likelihood for malignancy, and they may be closely followed for the development of any worrisome or high-risk features. Surveillance of known PCNs is performed with a combination of CT, MRI and endoscopic ultrasound (EUS). EUS-guided fine-needle aspiration (EUS-FNA) may be used to assess cyst fluid cytology, and also to detect cyst fluid amylase level, carcinoembryonic antigen level, and DNA molecular analysis in certain cases. The presence or absence of specific cyst morphological features, as well as the cyst fluid analysis, is what enables the physician to guide the patient towards continued surveillance, versus the pursuit of surgical resection.

The expression of FOXL2 in pancreatic, hepatobiliary, and renal tumors with ovarian-type stroma.

FOXL2, a gene encoding a member of the fork-head-winged-helix family of transcription factors, is one of the earliest expressed genes during female gonadal development. It is expressed in normal ovarian stroma and ovarian neoplasms with granulosa cell lineage. Nonovarian tumors such as pancreatic mucinous cystic neoplasms (PMCs), hepatobiliary cystadenomas (HBCs), and mixed epithelial and stromal tumor of the kidney (MEST) have ovarian-type stroma. Immunohistochemical staining with FOXL2, estrogen receptor, and progesterone receptor was performed on 21 PMCs, 13 HBCs, and 10 MESTs and assessed for nuclear immunohistochemical positivity in the tumor stroma. All cases of PMC and HBC demonstrated nuclear reactivity for FOXL2 in the subepithelial stromal cells. Ninety percent of MEST demonstrated nuclear FOXL2 positivity. Estrogen receptor nuclear positivity was demonstrated in 57% of PMC, 77% of HBC, and 80% of MEST. Progesterone receptor nuclear positivity was present in 67% of PMC, 100% of HBC, and 90% of MEST. Clinical information was available for 37 patients. Seventy-eight percent of the patients had a history of obesity, heavy alcohol use, or hormone-related therapy. The 2 male patients had histories significant for morbid obesity and chronic alcoholism. FOXL2 is expressed from the early stages of ovarian development and has been shown to be mandatory for normal ovarian function. We have shown that it is also expressed in the aberrant ovarian-type stroma characteristic of PMC, HBC, and MEST. Most of such patients, including the rare male patients, have risk factors for hormonal abnormalities such as obesity and hormonal replacement therapy.

A case of pancreatic mucinous cystic neoplasm that enlarged during pregnancy and was resected after childbirth

A case of pancreatic mucinous cystic neoplasm that enlarged during pregnancy and was resected after childbirth

Abstract A11: Common links suggest a shared embryologic origin for pancreatic and ovarian mucinous tumors

Abstract Background: Mucinous ovarian tumors (MOT) have been linked to mucinous colorectal and appendiceal adenocarcinomas. However, recent molecular studies suggest MOT may share more in common with pancreatic mucinous cystic neoplasms (MCN). Commonalities between these seemingly disparate tumors are explored. Methods: Epidemiologic features of MOT and mucinous gastrointestinal tumors were compared using the SEER database. Regional cases of 287 mucinous ovarian tumors were examined against 2,339 age-matched controls to delineate MOT risk factors. A case series of MCN was identified by chart review. Protein expression patterns among tumors were examined using seven immunohistochemical markers. Results: SEER revealed that among GI neoplasms the epidemiology of MCN was most similar to MOT by age, race, and stage. MCN occurred almost exclusively in women, with a sex ratio of 19:1, compared to 1•1:1 and 1•2:1 for mucinous colorectal and appendiceal adenocarcinomas. In the case-control study, appendectomy and cervical conization did not reduce the risk of MOT, while smoking (OR 2•68, 95% CI 1•85-3•89, p&amp;lt;0•001), was associated with an increased risk of MOT. Smoking was similarly common among MCN patients. Histologically, MOT and MCN were CK7+, CK20-, MUC2-, and CDX2-, whereas mucinous colorectal and appendiceal adenocarcinomas were CK7-, CK20+, MUC2+, and CDX2+. Interpretation: Clinical and morphologic similarities between MOT and MCN suggest a common pathogenesis, potentially a shared precursor such as embryologic rests that stopped in the pancreatic buds during migration of the primordial follicles to the gonads during development. This implies mucinous ovarian tumors may originate from primordial follicles, not the ovarian surface epithelium, offering a novel explanation for their pathogenesis. Citation Format: Intidhar Labidi-Galy, Kevin M. Elias, Allison F. Vitonis, Jason L. Hornick, Leona A. Doyle, Michelle S. Hirsch, Daniel W. Cramer, Ronny Drapkin. Common links suggest a shared embryologic origin for pancreatic and ovarian mucinous tumors. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research: From Concept to Clinic; Sep 18-21, 2013; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2013;19(19 Suppl):Abstract nr A11.

Activated Wnt Signaling in Stroma Contributes to Development of Pancreatic Mucinous Cystic Neoplasms

Pancreatic mucinous cystic neoplasm (MCN), a cystic tumor of the pancreas that develops most frequently in women, is a potential precursor to pancreatic ductal adenocarcinoma. MCNs develop primarily in the body and tail of the pancreas and are characterized by the presence of a mucinous epithelium and ovarian-like subepithelial stroma. We investigated the involvement of Wnt signaling in KRAS-mediated pancreatic tumorigenesis and development of MCN in mice, and Wnt activation in human MCN samples. LSL-Kras(G12D), Ptf1a-cre mice were crossed with elastase-tva mice to allow for introduction of genes encoded by the replication-competent avian sarcoma-leukosis virus long-terminal repeat with splice acceptor viruses to pancreatic acinar cells and acinar cell progenitors, postnatally and sporadically. Repeat with splice acceptor viruses that expressed Wnt1 were delivered to the pancreatic epithelium of these mice; pancreatic lesions were analyzed by histopathology and immunohistochemical analyses. We analyzed levels of factors in Wnt signaling pathways in 19 MCN samples from patients. Expression of Wnt1 in the pancreatic acinar cells and acinar cell progenitors of female mice led to development of unilocular or multilocular epithelial cysts in the pancreas body and tail, similar to MCN. The cystic lesions resembled the estrogen receptor- and progesterone receptor-positive ovarian-like stroma of MCN, but lacked the typical mucinous epithelium. Activated Wnt signaling, based on nuclear localization of β-catenin, was detected in the stroma but not cyst epithelium. Wnt signaling to β-catenin was found to be activated in MCN samples from patients, within the ovarian-like stroma, consistent with the findings in mice. Based on studies of mice and pancreatic MCN samples from patients, the canonical Wnt signaling pathway becomes activated and promotes development of the ovarian-like stroma to contribute to formation of MCNs.

Incidentally Discovered Pancreatic Intraepithelial Neoplasia: What Is Its Clinical Significance?

Pancreatic intraepithelial neoplasia (PanIN) is a presumed precursor of pancreatic ductal adenocarcinoma (PDAC). We assessed the relationship between incidental PanIN after resection of non-adenocarcinoma lesions and the development of metachronous PDAC in the remnant. We retrospectively reviewed the clinicopathologic data of patients who underwent pancreatectomy for non-PDAC from January 2000 to January 2010. Intraductal papillary mucinous lesions were excluded. All available postoperative imaging and clinical follow-up data were reviewed; the risk of developing PDAC was assessed in patients with a minimum follow-up time of 6months and with imaging studies available for review. A total of 584 patients were analyzed. Median age was 59years (range 10-85years), and 338 (58%) were female. The most common lesions for which resection was performed were serous cystic neoplasms (17%), pancreatic neuroendocrine tumors (38%), metastatic tumors (9%), and mucinous cystic neoplasms (7%). PanIN was identified in 153 (26%) patients. The majority of these patients had PanIN-1 or -2 (50 and 41%, respectively), whereas 13 (8%) had PanIN-3. Of the 506 (87%) patients with adequate follow-up (median 3.7years, range 0.5-12.6years), 1 patient (0.2%) with PanIN identified at the time of initial resection developed cancer in the remnant. This occurred 4.4years after a distal pancreatectomy in the setting of PanIN-1B. No patient with PanIN-3 developed cancer during follow-up. PanIN was identified in 26% of patients who underwent resection for histopathology other than PDAC. The presence of PanIN of any grade did not result in an appreciable cancer risk in the pancreatic remnant after short-term follow-up.

Pancreatic mucinous cystic neoplasm with sarcomatous stroma metastasizing to liver: a case report and review of literature

We report a case of mucinous cystic neoplasm of pancreas with sarcomatous stroma metastasizing to the liver. The tumor occurred in a male patient aged 46 years. Symptoms included persistent epigastric and right upper quadrant pain. Radiographically, the pancreas contained four large cystic masses located in the neck, body, and tail. Histologically, the cysts were lined with benign, mucinous epithelium with underlying bland, storiform, ovarian-like stroma. An undifferentiated focally hyalinized, sarcomatous stroma composed of bland spindle cells showing short fascicular growth pattern and focal nuclear palisading was associated with the epithelial component in one of the cysts. These cells showed strong immunoreactivity with vimentin and inhibin (weak), they were negative for CD34, estrogen receptor, progesterone receptor, androgen, calretinin, S-100, CD117, melan A, chromogranin, and synaptophysin. A morphologically and immunohistochemically identical metastatic sarcomatous focus was identified in the liver without any glandular component. This case is unique in its clinically malignant behaviour and metastatic nature despite its morphologically benign epithelial and stromal components.