Background: Pancreatic cancer has a high mortality rate because it is usually diagnosed when metastasis have already occurred (microscopic and gross disease). Ezrin plays important roles in cell motility, invasion and tumor progression, and it is especially crucial for metastasis. However, its function in pancreatic cancer remains elusive. Methods and Results: We found that ezrin overexpression promoted cell protrusion, microvillus formation, anchorage-independent growth, motility and invasion in a pancreatic cancer cell line, MiaPaCa-2, whereas ezrin silencing resulted in the opposite effects. Ezrin overexpression also increased the number of metastatic foci (6/8 vs. 1/8) in a spontaneous metastasis nude mouse model. Furthermore, ezrin overexpression activated Erk1/2 in MiaPaCa-2 cells, which might be partially related to the alteration of cell morphology and invasion. Immunohistochemical analysis showed that ezrin was overexpressed in pancreatic ductal adenocarcinoma (PDAC) (91.4%) and precancerous lesions, i.e. the tubular complexes in chronic pancreatitis (CP) and pancreatic intraepithelial neoplasm (PanIN) (85.7% and 97.1%, respectively), compared to normal pancreatic tissues (0%). Ezrin was also expressed in intercalated ducts adjacent to the adenocarcinoma, which has been considered to be the origin of ducts and acini, as well as the starting point of pancreatic ductal carcinoma development. Conclusions: We propose that ezrin might play functional roles in modulating morphology, growth, motility and invasion of pancreatic cancer cells, and that the Erk1/2 pathway may be involved in these roles. Moreover, ezrin may participate in the early events of PDAC development and may promote its progression to the advanced stage.

Interactions of inflammatory cells with pancreatic cancer cells play crucial roles in pancreatic cancer, however the dynamic changes of inflammatory cell populations in pancreatic cancerogensis and after chemotherapy have not been well eclucidated. The combinational use of aspirin and atrovastatin (Lipitor) have been widely prescribled for cardio-cerebral vascular diseases mainly by regulation of inflammations, and they have been also reported to have plausible anti-tumor effects, however their potential roles in pancreatic cancerogenesis and chemotherapeutic effects have been seldom investigated. We scanned the dynamic changes of pan-inflammatory cell populations in pancreatic cancerogensis and after chemotherapy and found the potential target cell populations. Then we tested the roles of aspirin and Lipitor to regulate these inflammatory cell populations and their effects on pancreatic cancerogenesis and chemotherapeutic effects. Cancerogen, dimethylbenzanthracene (DMBA), was used to induce pancreatic cancerogenesis and subcatunous implantation of syngenic murine Panc02 pancreatic cancer cells was adopted as well. Gemcitabine was used for chemotherapy. The peripheral blood, pancreatic lesions and tumor samples were harvested and analyzed to search for the potential target cell populations. The roles of aspirin and Lipitor to regulate these cell populations and their potential effects on pancreatic cancerogenesis and chemotherapeutic efficacy were investigated both in vitro and in vivo. We found progressive accumulations of myeloid-derived suppressor cells (MDSC) and M2-polarzied tumor associated macrophages(M2) in pancreatic lesions accompanied with dynamic reducations of cytotoxic T cells(CTL) and helper T cells(Th) in the progression of pancreatic cancerogenesis. After gemcitabine treatment, the MDSC significantly reduced, however M2 soared up unexpectedly. Aspirin could significantly inhibit the MDSC and M2 to prevent pancreatic cancerogenesis and improve chemotherapeutic effects of gemcitabine, however Lipitor did not significantly affect MDSC, instead it could promote M2 to attenuate the postive effects of aspirin and gemcitabine. MDSC and M2 accumulate in progression of pancreatic cancerogenesis and gemcitabine can induce M2. Aspirin could prevent pancreatic cancerogenesis and improve efficacy of gemcitabine partially by inhibiting MDSC and M2, however when used in combination, Lipitor could weaken the efficacy of aspirin and gemcitabine partially by promoting M2.

Rosai-Dorfman disease (RDD) involving the cardiovascular system is extremely rare; to our knowledge, there are only 9 cases in the literature. Here, a case of a 60-year-old male with RDD involving the right atrium is presented. A comprehensive literature review was undertaken to summarize the clinical and pathologic features of this disorder. The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/2143194139120169 .

Virtual Slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1327125766102291. Since first reported in 1986, 14 cases of extrauterine adenomyoma have been reported in the English literature, most often occurring in the ovaries. In this report, we present the first case of extrauterine adenomyoma involving the liver in a 29-year-old woman who presented with a 2-year history of low back pain with recent worsening and a history of laparoscopic myomectomy 5 years previously. Gross inspection of the specimen revealed a subcapsular mass that had a well-circumscribed margin with the adjacent liver tissue. By histopathologic examination, the multilobular mass was composed of a smooth muscle component and benign endometrioid glands and stroma. The smooth muscle component was focally cellular, and the endometrioid glands had secretory features. Both the smooth muscle component and endometrioid tissue were positive for ER and PR. The smooth muscle component was also positive for desmin and SMA, while the endometrioid stroma was positive for CD10. Other extrauterine lesions composed of a mixture of smooth muscle tissue and heterotopic endometrioid tissue, including endometriosis with a smooth muscle component, leiomyomatosis/leiomyomas associated with endometriosis and uterus-like masses, should be included in differential diagnoses. The patient was free from recurrence 5 months after liver tumor resection.