Undifferentiated carcinoma with osteoclast-like giant cells arising in a mucinous cystic neoplasm of the pancreas

A 26-year-old woman presented with pain in the left hypochondrium, for which pancreatectomy and splenectomy was performed, with total gross excision of a mass. A tumor measuring 11 × 9 cm was found in the pancreas. On cut surface there were two cysts filled with a necrotic substance and hemorrhagic content. Spindle or ovoid-shaped cells, in the sarcomatous component, had diffusely infiltrated along the inner side of the walls of one cyst. Osteoclast-like giant cells (OGC) were also contained in the sarcomatous component. Adenoma components of mucinous epithelium with foci of borderline and adenocarcinomatous components were seen on the inner side of the other cyst. An ovarian-type stroma beneath the epithelial component was seen in the cyst wall. A diagnosis of undifferentiated carcinoma with OGC arising in a mucinous cystic neoplasm (MCN) of the pancreas, was made. Seven months after the initial operation the patient had a local recurrence, and the tumor was removed. One month after the second operation, the patient was free of symptoms. Only four cases of undifferentiated carcinoma with OGC arising in MCN, involving an ovarian-type stroma of the pancreas, have been reported.     

K-Ras and microsatellite marker analysis of fine-needle aspirates from intraductal papillary mucinous neoplasms of the pancreas

Preoperative diagnosis of pancreatic cystic lesions is difficult despite the combination of cytomorphology, radiographic imaging characteristics, and fluid tumor markers such as carcinoembryonic antigen. Intraductal papillary mucinous neoplasms (IPMNs) represent a subset of preinvasive pancreatic cystic neoplasms and are associated with accumulated genetic mutations, especially K-ras and tumor suppressor genes such as p53. Application of molecular techniques to cyst fluid obtained by endoscopic ultrasound guided fine-needle aspiration (EUSFNA) may contribute to preoperative assessment.Sixteen patients with pancreatic cystic lesions had cyst fluid obtained by preoperative pancreatic EUSFNA or intraoperative aspiration. All patients subsequently underwent surgical resection of the pancreas and IPMN was documented in all (6 adenomas, 6 borderline tumors, and 4 carcinomas). DNA was extracted from the cyst fluids and mutational analysis for K-ras point mutations and loss of heterozygosity (LOH) analysis using a preselected panel of genomic loci were performed. LOH was observed in 3 of 4 carcinomas as compared to 4 of 11 adenomas and borderline lesions (1 was QNS). LOH and K-ras mutations were both acquired in 2 of 4 carcinomas and in 1 of 12 adenoma/borderline lesions.Although the study is small, molecular analysis for LOH and K-ras mutations is useful in the preoperative evaluation of cystic pancreatic lesions. Increasing degree of neoplasia appears to correlate with increased genetic abnormality using a panel of selected genomic markers.     

Bone morphogenetic protein‐2 expression in an intraductal papillary mucinous neoplasm with marked ossification: A case report

Intratumoral ossification has been reported in a number of epithelial tumors, but its presence in intraductal papillary mucinous neoplasms (IPMNs) is very rare. Herein, we present a rare case of IPMN with marked ossification. A 56‐year‐old Japanese man was under follow‐up for a previously diagnosed IPMN. Seven years later, he was found to have dilatation of the main pancreatic duct and an enlarged solid mass, for which pancreaticoduodenectomy was performed. Macroscopically, multiple and cystically dilated pancreatic branch ducts, as well as a dilated main pancreatic duct, were identified. There was a solid, polypoid hard mass measuring 15 × 12 mm in the cystically dilated branch of the duct in the pancreatic head. Histological examination revealed papillary proliferation of atypical cuboidal or columnar epithelial cells in the dilated main and branch pancreatic ducts. The solid mass included an invasive adenocarcinoma component with a tubular or trabecular structure that showed pronounced ossification. We diagnosed the patient with invasive IPMN accompanied by marked ossification. Immunohistochemically, tumor cells in both the non‐invasive and invasive lesions expressed bone morphogenetic protein‐2 (BMP‐2). While the mechanism of intratumoral ossification is unclear, it may have involved BMP‐2 in the present case.     

Expression of Wnt-signaling pathway proteins in intraductal papillary mucinous neoplasms of the pancreas: a tissue microarray analysis

Abrogation of the Wnt-signaling pathway is implicated in the carcinogenesis of several malignancies, especially colorectal cancer where up to 90% of cases are thought to have impaired Wnt signaling. It is less frequently involved in conventional ductal pancreatic adenocarcinoma. This pathway has not been explored in intraductal papillary mucinous neoplasms (IPMNs) of the pancreas previously and formed the basis of this study. A tissue microarray of 18 cases of IPMN was stained for proteins involved in the Wnt pathway: adenomatous polyposis coli (APC), pan-beta-catenin, axin 2, glycogen synthase 3alphabeta and 3beta, c-myc, E-cadherin, and cyclin D1. The IPMNs were classified as 8 adenomas, 3 borderline, and 7 cases with carcinoma in situ and/or invasive carcinoma, occurring in 13 females, and the overall age range was 45 to 73 years. Immunohistochemical analysis showed nuclear beta-catenin staining in 7 (39%) of the 18 cases. The cases with nuclear beta-catenin localization included 1 adenoma, 2 borderline IPMN, and 4 carcinomas in situ and/or invasive carcinomas. Seven cases showed absence of APC immunostaining and these included 4 cases with nuclear beta-catenin localization. Fourteen cases displayed marked diffuse up-regulation of c-myc protein, and 12 cases also showed diffuse cyclin D1 protein overexpression. E-cadherin expression was intense and membrane in location (comparable to normal tissue) in 6 of 8 adenomas (no tissue was available in 1 case). Decreased E-cadherin staining was noted in 8 cases where tissue was available for assessment. There was progressive decrease in membrane staining of E-cadherin in 2 of 3 borderline lesions, 1 of 2 carcinomas in situ, and 4 of 5 invasive carcinomas. All other immunostains were either normal in distribution or did not show any correlation with beta-catenin or clinicopathologic parameters. In conclusion, 7 (39%) of 18 cases of IPMN in this study demonstrated abnormal localization of beta-catenin, 4 of which also lacked APC expression. Of 5 carcinomas arising in IPMN, 4 displayed a decrease in E-cadherin expression. There was also a trend for the higher grades of IPMN to show nuclear localization of beta-catenin. These findings suggest that a proportion of cases of IPMN may show abnormalities in the Wnt-signaling pathway with consequent altered expression of downstream related proteins.     

Fine‐needle aspiration of cystic pancreatic mucinous tumor: Oncotic cell as an aiding diagnostic feature in paucicellular specimens

In juxtaposition with imaging studies, endoscopic ultrasound‐guided fine‐needle aspiration has gained popularity in the initial evaluation of pancreatic masses, especially cystic lesions of pancreas. Cystic pancreatic mucinous tumors include mucinous cystic neoplasm and intraductal papillary mucinous tumor, both of which have been known to have a low malignant potential and a high rate of association with invasive adenocarcinoma. As such, preoperative diagnosis is of great significance in guiding patient management. Although fine‐needle aspiration cytological diagnosis of pancreatic tumor in cellular specimens has been well described, as with other cystic lesions, the yield of diagnostic cells from needle aspiration of cystic pancreatic mucinous tumors is typically low. Cytological diagnosis from these paucicellular specimens remains challenging. An additional compounding problem is the high frequency of gastrointestinal mucin and epithelial contamination. The diagnostic morphology and criteria in these paucicellular specimens have not been well addressed in the literature. The cytopathologists' ongoing efforts tend to improve the diagnostic accuracy. In this current study, oncotic cells, characterized by cytoplasmic swelling and karyolysis, were analyzed from 17 cases of cystic pancreatic mucinous tumor, of which the diagnosis was either confirmed by surgical resection or supported by cell block and/or increased CEA. Oncotic cells were found in variable amounts in almost all the cystic pancreatic mucinous tumors in this series. None of the five fine‐needle aspirations intended for aspirations of hypoechoic nonlesional pancreas, which yielded either gastrointestinal tract material only or admixture of gastrointestinal and normal pancreatic components, was found to contain oncotic cells, evidencing the utility of oncotic cell as a surrogate morphologic marker in aiding the diagnosis of cystic pancreatic mucinous tumor as well as its differentiation from gastrointestinal contaminant, particularly in paucicellular specimens. Diagn. Cytopathol. 2009. © 2008 Wiley‐Liss, Inc.     

Comparison of efficacy of enucleation and pancreaticoduodenectomy for small (<3 cm) branch duct type intraductal papillary mucinous neoplasm located at the head of pancreas and the uncinate process

Purpose

Accurate indications and the extent of surgery for branch duct intraductal papillary mucinous neoplasm (IPMN) of the pancreas are still debatable. In particular, small tumor is located at the head portion of pancreas presents a dilemma. The purpose of this study is to compare the efficacy of enucleation (EN) with that of pancreaticoduodenectomy (PD) in patients with small (2 cmMaterials and MethodsAmong 155 patients who underwent pancreatic surgery due to pancreatic cystic tumors between January 2000 and December 2007 at Yonsei University Health System in Seoul, Korea, 14 patients with small (2 cmp-values less than 0.05 were considered significant.

Results

The average age was 62.21 years (±6.71 years) and consisted of 8 men and 6 women. The mean operation time and blood loss were significantly lower in EN group. There were no significant differences in other surgical morbidities.

Conclusion

The result suggests that enucleation for small branch duct IPMN located at the head of pancreas or uncinate process is feasible and as safe as PD, despite a high rate of minor complications.     

CD44‐expressing undifferentiated carcinoma with rhabdoid features of the pancreas: Molecular analysis of aggressive invasion and metastasis

Carcinoma with rhabdoid features is a rare malignant tumor with a poor prognosis whose molecular mechanism for aggressive behavior is unclear. We describe an undifferentiated pancreatic carcinoma with rhabdoid features that demonstrated extensive invasion and metastasis. Examination of a 63‐year‐old man with back pain disclosed a retroperitoneal tumor with multiple metastases. Lymph node biopsy revealed an undifferentiated carcinoma of unknown origin. Intensive chemotherapy was ineffective; the patient died 3 months after initial symptoms. Autopsy showed that the tumor displaced the retroperitoneal space: it diffusely invaded and destroyed the pancreas and duodenum. Histology demonstrated tumor cells with eccentric vesicular nuclei, large nucleoli, juxtanuclear eosinophilic inclusions, and poor cell adhesion. Immunohistochemistry showed that tumor cells expressed cytokeratin and vimentin, and electron microscopy confirmed a perinuclear mass of intermediate fibrils and lipid droplets, which indicated an undifferentiated carcinoma with rhabdoid features. Tumor tissue contained hyaluronan; tumor cells strongly expressed CD44, matrix metalloproteinase‐9, hypoxia‐inducible factor‐1α, hyaluronan synthase 2, and acyl‐CoA:cholesterol acyltransferase 1 and had a high Ki‐67⁺ ratio. Since hyaluronan is a ligand for CD44, formation of CD44‐hyaluronan complex on the cell surface activates CD44 and this activation may explain why the tumor manifested aggressive invasion and metastasis throughout the clinical course.