CD14+ Dendritic-Shaped Cells Functioning as Dendritic Cells in Rheumatoid Arthritis Synovial Tissues.

OBJECTIVE: We previously reported that CD14+ dendritic-shaped cells exhibit a dendritic morphology, engage in pseudo-emperipolesis with lymphocytes, and express CD90 in the perivascular areas of rheumatoid arthritis (RA) synovial tissues. However, it remains unclear whether these CD14highCD90intermediate(int) cells function as dendritic cells. In this study, we investigated the dendritic cell-differentiation potential of CD14highCD90int cells. METHODS: The localization and number of CD14highCD90int cells in RA synovial tissues and peripheral blood were examined. The dendritic cell-differentiation potential of CD14highCD90int cells was examined by measuring interleukin-6 and tumor necrosis factor-α levels in the supernatant and CD83 and human leukocyte antigen (HLA)-DR expression in the cells after induction of dendritic cell differentiation. Synovial cells were co-cultured with lymphocytes, and the activation of these cells was examined. RESULTS: CD14highCD90int cells were abundant in RA synovial tissues, including the sublining layer and the pannus areas. Patients with untreated and active RA had significantly higher percentages of CD14highCD90int cells in the peripheral blood and synovial tissues. In RA synovial cells, inflammatory cytokine levels increased with dendritic cell-differentiation culture, but CD83 and HLA-DR expression were significantly increased in the CD14highCD90int cell group. When co-cultured with lymphocytes, cell numbers and inflammatory cytokine levels significantly increased in both groups of synovial cells after dendritic cell induction. CONCLUSION: CD14+ cells migrate and spread from the circulating blood to RA synovial tissues while expressing CD90, and CD14highCD90int cells in contact with lymphocytes differentiate into HLA-DR+ dendritic cells, which contribute to chronic inflammation in RA.

Pancreatic ductal adenocarcinomas concomitant with intraductal papillary mucinous neoplasms of the pancreas: A investigation of those clinicopathological features by analyzing 48 patients who underwent surgery for those lesions.

BACKGROUND: Differences between pancreatic ductal adenocarcinomas (PDACs) concomitant with intraductal papillary mucinous neoplasm (IPMN) (C-PDACs), those without IPMN (NC-PDACs) and invasive cancers derived from IPMN (IC-Ds) have not been fully clarified. METHODS: Forty-eight patients with C-PDAC were included to investigate the differences in 1) clinicopathological features and 2) post-operative courses among the three invasive cancer groups. RESULTS: 1) Characteristics of C-PDACs were mostly similar to those of NC-PDACs; whereas, between C-PDACs and IC-Ds, the rate of mucinous carcinoma (2%/25%, p = 0.003) and pathological stage (IA, 15%/36%, p = 0.033; III, 31%/4%, p = 0.015) significantly differed. Most C-PDACs coexisted with small, multifocal IPMNs without mural nodules. 2) Cumulative 5-year recurrence-free survival (RFS) rate related to extra-pancreatic recurrence was significantly worse in C-PDACs than in IC-Ds (35%/69%, p = 0.008) and was not significantly different between C-PDACs and NC-PDACs (35%/18%). This related to intra-pancreatic recurrence tended to be poor in the order of IC-Ds, C-PDACs, and NC-PDACs (69%/82%/93%). CONCLUSIONS: Because characteristics of IPMNs remarkably differed between C-PDACs and IC-Ds, another algorithm specific to the early detection of C-PDACs is necessary. Appropriate post-operative managements according to the two types of recurrences may contribute to the improvement in the prognoses of C-PDACs/IC-Ds.

Pancreatic duct lavage cytology combined with a cell-block method for patients with possible pancreatic ductal adenocarcinomas, including pancreatic carcinoma in situ.

BACKGROUND/AIMS: This study aimed to clarify the efficacy and safety of pancreatic duct lavage cytology combined with a cell-block method (PLC-CB) for possible pancreatic ductal adenocarcinomas (PDACs). METHODS: This study included 41 patients with suspected PDACs who underwent PLC-CB mainly because they were unfit for undergoing endoscopic ultrasonography-guided fine needle aspiration. A 6-Fr double lumen catheter was mainly used to perform PLC-CB. Final diagnoses were obtained from the findings of resected specimens or clinical outcomes during surveillance after PLC-CB. RESULTS: Histocytological evaluations using PLC-CB were performed in 87.8% (36/41) of the patients. For 31 of the 36 patients, final diagnoses (invasive PDAC, 12; pancreatic carcinoma in situ, 5; benignancy, 14) were made, and the remaining five patients were excluded due to lack of surveillance periods after PLC-CB. For 31 patients, the sensitivity, specificity, and accuracy of PLC-CB for detecting malignancy were 94.1%, 100%, and 96.8%, respectively. In addition, they were 87.5%, 100%, and 94.1%, respectively, in 17 patients without pancreatic masses detectable using endoscopic ultrasonography. Four patients developed postprocedural pancreatitis, which improved with conservative therapy. CONCLUSION: PLC-CB has an excellent ability to detect malignancies in patients with possible PDACs, including pancreatic carcinoma in situ.

Diagnostic value of homogenous delayed enhancement in contrast-enhanced computed tomography images and endoscopic ultrasound-guided tissue acquisition for patients with focal autoimmune pancreatitis.

BACKGROUND/AIMS: We aimed to investigate (1) promising clinical findings for the recognition of focal type autoimmune pancreatitis (FAIP) and (2) the impact of endoscopic ultrasound (EUS)-guided tissue acquisition (EUS-TA) on the diagnosis of FAIP. METHODS: Twenty-three patients with FAIP were involved in this study, and 44 patients with resected pancreatic ductal adenocarcinoma (PDAC) were included in the control group. RESULTS: (1) Multivariate analysis revealed that homogeneous delayed enhancement on contrast-enhanced computed tomography was a significant factor indicative of FAIP compared to PDAC (90% vs. 7%, p=0.015). (2) For 13 of 17 FAIP patients (76.5%) who underwent EUS-TA, EUS-TA aided the diagnostic confirmation of AIPs, and only one patient (5.9%) was found to have AIP after surgery. On the other hand, of the six patients who did not undergo EUS-TA, three (50.0%) underwent surgery for pancreatic lesions. CONCLUSION: Homogeneous delayed enhancement on contrast-enhanced computed tomography was the most useful clinical factor for discriminating FAIPs from PDACs. EUS-TA is mandatory for diagnostic confirmation of FAIP lesions and can contribute to a reduction in the rate of unnecessary surgery for patients with FAIP.

Mixed neuroendocrine-non-neuroendocrine neoplasm with mucinous adenocarcinoma and amphicrine carcinoma components in the bile duct: an autopsy case.

We report the first case of bile duct mixed neuroendocrine-non-neuroendocrine neoplasm (MiNEN) that had a mucinous carcinoma component. An 88-year-old man with biliary obstruction was diagnosed as having distal bile duct cancer using imaging examinations and endoscopic biopsy. The patient received the best supportive care without surgical resection for 13 months until death. An autopsy revealed a bulky mass involving the distal bile duct and multiple metastases in intra-abdominal lymph nodes, the liver, and the lungs. The primary cancer was microscopically diagnosed as a MiNEN, which consisted of mucinous adenocarcinoma and large cell-type neuroendocrine carcinoma (NEC) components. Metastatic lesions in the liver and lungs were composed of only NEC with rich extracellular mucin without adenocarcinoma cells. Using electron microscopy and immunohistochemistry, it was proved that all NEC cells in both primary and metastatic lesions had amphicrine features. On the basis of pathological findings, we thought that the MiNEN was initially derived from a mucinous adenocarcinoma that dedifferentiated to amphicrine NEC cells with mucin production.

Tumor Microenvironment in Mixed Neuroendocrine Non-Neuroendocrine Neoplasms: Interaction between Tumors and Immune Cells, and Potential Effects of Neuroendocrine Differentiation on the Tumor Microenvironment.

The tumor microenvironment is considered to play a pivotal role in various human malignancies. Neuroendocrine and non-neuroendocrine neoplasms are considered to have different tumor microenvironments. However, owing to differences in the systemic and/or local immune statuses, tumor microenvironments in different patients may be difficult to compare. Mixed neuroendocrine non-neuroendocrine neoplasms (MiNENs), although rare, could be useful for exploring the effects of neuroendocrine differentiation on the tumor microenvironment, because both neuroendocrine and non-neuroendocrine components are present in the same tumor. Here, we examined 33 cases of histologically confirmed MiNENs and evaluated the influence of neuroendocrine differentiation on the tumor microenvironment by comparing tumor-infiltrating lymphocytes, tumor-associated macrophages, and other relevant factors in the two components the same tumor. The immunoreactivity of those examined above was evaluated quantitatively. The values of vasohibin-1-positive density (p < 0.0001) and immunoreactivity (p < 0.0001) (representing the neoangiogenesis status) were significantly higher in neuroendocrine as compared to non-neuroendocrine areas of the same tumors. In addition, the Foxp3/CD8 (p = 0.0717) and the PD-1/CD8 ratios (p = 0.0176) (representing tumor immunity suppression) tend to increase in neuroendocrine carcinomas. Immunoreactivity of CD163, a marker of M2-like macrophages, was also higher in the neuroendocrine areas. Our findings indicate that neuroendocrine and non-neuroendocrine tumors differ from each other with respect to the characteristics of both tumor cells and the tumor microenvironment.

Association of CD90 Expression by CD14+ Dendritic-Shaped Cells in Rheumatoid Arthritis Synovial Tissue With Chronic Inflammation.

OBJECTIVE: CD14+ dendritic-shaped cells show a dendritic morphology under the electron microscopy and engage in a pseudoemperipolesis phenomenon with lymphocytes. CD90 has been used as a marker of a major subset of fibroblast-like synoviocytes in rheumatoid arthritis (RA). In this study, we investigated the significance of CD90 expression in CD14+ dendritic-shaped cells and its correlation with RA chronic inflammation. METHODS: Double immunofluorescence staining for CD14 and CD90 was performed in the collected tissues, including 12 active RA synovial tissues. The localization of CD14+ CD90+ cells, the percentages of CD14+ CD90+ cells and vascular areas, the degree of synovitis, and clinical data were investigated. Furthermore, CD14+ CD90+ cells analyzed by flow cytometry (CD14high CD90intermediate (int) cells) were sorted from RA synovial cells, and we examined their potential to differentiate into dendritic cells. RESULTS: Double immunofluorescence staining showed that CD14+ CD90+ cells were abundant in RA synovial tissues. The percentages of CD14+ CD90+ cells and vascular areas correlated with some of the Krenn synovitis scores, but neither showed a strong correlation with RA disease activity parameters. Flow cytometry analysis indicated that CD14high CD90int cells were more abundant in both peripheral blood samples and synovial tissues in patients with active RA. CD14high CD90int cells were more likely to differentiate into dendritic cells in vitro. CONCLUSION: CD14+ dendritic-shaped cells expressed CD90 in the perivascular areas of RA synovial tissues. These findings suggest that CD14+ CD90+ dendritic-shaped cells migrate from the peripheral blood to the synovial tissue, the site of inflammation, and may contribute to the chronic inflammation of RA as dendritic progenitor cells.

[Endoscopic mucosal resection of localized plasmablastic lymphoma with early rectal cancer:a rare case report and literature review].

A 79-year-old male with a positive fecal occult blood test result underwent total colonoscopy, which revealed a 15-mm-semipedunculated polyp in the rectum. The polyp appeared to be an adenoma using narrow-band imaging observation in magnifying endoscopy, although a 3mm reddish segment with a different surface structure was identified adjacent to the base of the polyp. En-bloc endoscopic mucosal resection (EMR) was performed. From the pathological evaluation using the specimen, the polyp was mainly a tubular adenoma with an adenocarcinoma component within the lesion. Additionally, a tiny plasmablastic lymphoma (PBL) component, which was positive for CD45, CD79a, CD30, CD38, MUM1, and lambda light chain;negative for CD3, CD5, CD20, CD56, CD138, cyclin D1, PAX5, IgG, IgA, IgM, IgE, HHV8, and kappa light chain, coexisted near the stalk. The proliferation index using Ki-67 immunohistochemistry was approximately 80%. Furthermore, Epstein-Barr virus-encoded RNAs were identified in in-situ hybridization, although the human immunodeficiency virus was not detected. The patient received contrast-enhanced computed tomography (CT) and positron emission tomography-CT (PET-CT) follow-ups after treatment without recurrence for two years. This is the first report of gastrointestinal PBL that could be treated using EMR.

Endoscopic Ultrasonography-guided Fine-needle Aspiration Cytology Combined with a Cell-block Method for Gastrointestinal Subepithelial Lesions.

Objective The diagnostic accuracy of an endoscopic ultrasound-guided fine-needle aspiration cytology/biopsy combined with a cell-block method (FNA-CB) for gastrointestinal subepithelial lesions (GI-SELs) has not been fully studied. Methods A total of 109 patients (with 110 GI-SELs) were evaluated to clarify the rate of obtaining evaluable histology specimens using FNA-CB. In addition, we investigated the following: 1) the accuracy for determining the histology, 2) effects of the number of cell clusters obtained via FNA-CB, 3) correlation of the Ki67 labelling index (Ki67LI) of the gastrointestinal stromal tumor (GIST) lesions between FNA-CB and resected specimens, and 4) clinical courses for patients followed up after FNA-CB. Results Of the 110 GI-SELs for which FNA-CB was performed, 95 (86%) were able to be histologically evaluated using the first FNA-CB. For the 70 resected GI-SELs, the accuracy of FNA-CB to determine histology was 96%, remaining at 90% even when only a few cell clusters were obtained. The concordance rate of the risk-grouping of GIST (high-risk, Ki67LI ≥8; low-risk, <8) between FNA-CB and resected specimens was 84%. Of the 29 patients followed up after the first FNA-CB, 12 with benign GI-SELs determined using the first FNA-CB showed no obvious increases in their GI-SEL sizes. Conclusion Since FNA-CB can be used to determine the histology and reproductive activity of GI-SELs accurately, not only preoperative histological confirmation but also reliable information to determine clinical plans, such as follow-up without surgery or neoadjuvant chemotherapy, can be obtained.

Pancreatic Ductal Adenocarcinoma Concomitant with Main Duct Type Intraductal Papillary Mucinous Neoplasm of the Pancreas: A Case Report.

BACKGROUND Intraductal papillary mucinous neoplasm of the pancreas (IPMN) and pancreatic ductal adenocarcinoma (PDAC) often coexist in the same pancreas. Almost all IPMNs involving PDACs concomitant with IPMN have been shown to be branch duct type IPMNs (BD-IPMNs), and their histological subtypes are gastric type. Therefore, PDACs concomitant with main duct type IPMNs (MD-IPMNs) are considered to be rare. We herein report a rare case preoperatively diagnosed as being a PDAC concomitant with MD-IPMN on the basis of imaging findings and histological findings of pancreatic specimens endoscopically obtained from 2 lesions. CASE REPORT A 67-year-old man was referred to our hospital due to an enlarged pancreas. Using imaging studies, a solid mass was found in the pancreatic head and intraductal papillary masses in the dilated main pancreatic duct of the body and tail with a fistula in the duodenum. On the basis of histological results using specimens endoscopically obtained from each of the 2 lesions, total pancreatectomy was planned due to suspected PDAC concomitant with an MD-IPMN. Finally, resected specimens were used to confirm the presence of a rare case of PDAC concomitant with MD-IPMN. CONCLUSIONS We encountered a rare case of a PDAC concomitant with an MD-IPMN which could be preoperatively diagnosed by using imaging studies and histological specimens endoscopically obtained. In addition to invasive cancers derived from IPMNs, PDACs concomitant with IPMNs can rarely develop in the pancreas involving MD-IPMNs.

Value of repeated cytology for intraductal papillary mucinous neoplasms of the pancreas with high risk potential of malignancy: Is it a promising method for monitoring a malignant transformation?

OBJECTIVES: The efficacy of and indications for cytological reexamination to detect malignant changes in branch duct type intraductal papillary mucinous neoplasms (BD-IPMNs) have not been studied in detail. We conducted a retrospective study to evaluate the efficacy and indications of cytological reexamination by using pancreatic juice (repeated cytology) for BD-IPMNs. METHODS: Forty-five patients who underwent repeated cytology after a diagnosis of benignancy by using initial cytology were recruited for this study. RESULTS: Thirty-eight patients, excluding 7 patients with lack of surveillance period after the final cytology, were classified into Malignancy (n = 13) and Benignancy groups (n = 25) on the bases of the findings from resected specimens or changes in BD-IPMNs after repeated cytology. The sensitivity and specificity to detect malignant changes in BD-IPMNs by using repeated cytology were 62% and 100%, respectively. For the 12 patients with mural nodules (MNs) ≥ 5 mm (67% of them were malignant), the sensitivity was 50%, whereas, for the 26 patients without MNs ≥ 5 mm (19% of them were malignant), it was 80%. In addition, malignant changes in BD-IPMNs after initial cytology occurred in 62% of the patients with changes in the MNs and 27% of the patients with an increase in the cyst size. CONCLUSION: Repeated cytology can play a role in the determination for surgery even after a diagnosis of benignancy by using initial cytology, especially for BD-IPMNs without MNs ≥5 mm. In addition, changes in the MNs or cyst size may be appropriate indications for repeated cytology.

Immune microenvironment in Barrett's esophagus adjacent to esophageal adenocarcinoma: possible influence of adjacent mucosa on cancer development and progression.

The immune microenvironment plays a pivotal role in cancer development and progression. Therefore, we studied the status of immune cells in esophageal adenocarcinoma (EAC) and adjacent Barrett's esophagus (BE) and their association with the clinical course of patients. We included 87 patients with EAC who underwent surgical resection or endoscopic submucosal dissection. CD3, CD8, Foxp3, p53, and Ki-67 were immunolocalized in EAC and adjacent BE (N = 87) and BE without EAC (N = 13). BE adjacent to EAC exhibited higher CD3+ lamina propria lymphocyte (LPL) numbers than BE without EAC. Abundant Foxp3+ LPLs in BE were associated with dysplasia and increased Ki-67 labeling index (LI) in BE glandular cells and tended to link to aberrant p53 expression. Abundant CD8+ LPLs in adjacent BE were associated with worse prognosis of EAC patients (P = 0.019). Results of our present study firstly revealed the potential influence of the tissue immune microenvironment of BE adjacent to EAC on cancer development and eventual clinical outcome of EAC patients. T cell infiltration could play pivotal roles in facilitating the dysplasia-adenocarcinoma sequence in BE. The number of Foxp3+ T cells is increased at the early stage of carcinogenesis and could help identify patients harboring dysplastic and highly proliferating cells. CD8+ T cells could reflect unfavorable inflammatory response in adjacent tissue microenvironment and help predict worse prognosis of EAC patients.

[Helicobacter pylori-negative gastric mucosa-associated lymphoid tissue (MALT) lymphoma with MALT translocation gene 1 diagnosed using an endoscopic submucosal dissection specimen].

A 15-mm whitish, depressed lesion was observed in the stomach of a 39-year-old using screening esophagogastroduodenoscopy. The lesion had grown to a size of 40mm and had a cobblestone-like appearance at an 11-year endoscopic follow-up. Using endoscopic submucosal dissection (ESD) as a diagnostic therapy, gastric mucosa-associated lymphoid tissue (MALT) lymphoma with MALT translocation gene 1 without Helicobacter pylori infection was detected. Although the patient did not undergo additional treatments, he remained alive without for recurrence 5 years after ESD.

Glucocorticoid receptor and serum- and glucocorticoid-induced kinase-1 in esophageal adenocarcinoma and adjacent Barrett's esophagus.

Barrett's esophagus (BE) is a consequence of gastroesophageal reflux disease and is predisposed to esophageal adenocarcinoma (EAC). EAC is an exemplar model of inflammation-associated cancer. Glucocorticoids suppress inflammation through glucocorticoid receptor (GR) and serum- and glucocorticoid-induced kinase-1 (Sgk1) expressions. Therefore, we immunolocalized GR and Sgk1 in EAC and the adjacent BE tissues and studied their association with clinical disease course in 87 patients with EAC who underwent surgical resection (N = 58) or endoscopic submucosal dissection (N = 29). Low GR and Sgk1 expressions in adjacent BE tissues were associated with adverse clinical outcomes (P = 0.0008 and 0.034, respectively). Patients with low Sgk1 expression in EAC cells exhibited worse overall survival (P = 0.0018). In multivariate Cox regression analysis, low GR expression in the adjacent nonmalignant BE tissues was significantly associated with worse overall survival (P = 0.023). The present study indicated that evaluation of GR and Sgk1 expressions in both the EAC cells and adjacent nonmalignant BE tissues could help to predict clinical outcomes following endoscopic and surgical treatments. In particular, the GR status in BE tissues adjacent to EAC was an independent prognostic factor.

[Synchronous double primary cancers of a mixed adenoneuroendocrine carcinoma of the distal bile duct and a carcinoma in situ in the perihilar bile duct].

We report the rare case of a 69-year-old man who underwent resection of a mixed adenoneuroendocrine carcinoma (MANEC) of the distal bile duct and a carcinoma in situ in the perihilar bile duct. The patient was admitted to our hospital for obstructive jaundice. Imaging studies revealed a mass in the distal bile duct, and an abnormal epithelium was detected in the perihilar bile duct using peroral cholangioscopy. Bile cytology and transpapillary biopsy of the tumor revealed adenocarcinoma. We diagnosed this patient with distal cholangiocarcinoma with extensive intraepithelial progression toward the perihilar bile duct and performed a subtotal stomach-preserving pancreaticoduodenectomy and left hepatectomy. According to the histological examination of the resected specimens, we found a MANEC in the distal bile duct and a carcinoma in situ in the perihilar bile duct. Together, they were diagnosed as synchronous double primary cancers due to the lack of pathological transition between them.

Should we regard all main duct type intraductal papillary mucinous neoplasms of the pancreas (MD-IPMN) as an indication of surgery? -A retrospective study in 29 patients with MD-IPMN showing mural nodules.

PURPOSE: To elucidate predictive factors for malignant main duct type IPMN (MD-IPMN). METHODS: All 29 subjects had mural nodules (MNs) in the main pancreatic duct (MPD) on preoperative endoscopic ultrasonography and underwent surgery (19, malignant; 10, benign). Possible predictive factors for malignancy such as background, imaging, and histological factors including histological subtype (HS), were evaluated. RESULTS: Multivariate analysis revealed an MPD diameter of ≥12 mm (p = 0.042) and non-gastric type (p = 0.001) to be the statistically significant predictive factors for malignancy. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy to detect malignancy by using "an MPD diameter of ≥12 mm and/or non-gastric type" were 95%, 70%, 86%, 88%, and 86%, respectively. In 7 subjects in whom HS was preoperatively evaluated using pancreatic specimens obtained before surgery, the agreement rate of the preoperative HS with definitive HS evaluated using resected specimens was 86%. CONCLUSIONS: For MD-IPMNs with MNs, "an MPD diameter of ≥12 mm and/or non-gastric type" are indicated for surgery. On the other hand, careful surveillance without immediate pancreatic surgery may be an option for MD-IPMNs showing both an MPD diameter of <12 mm and gastric type.

[Detection of small pancreatic cancer during surveillance of the main pancreatic duct stenosis].

An 83-year-old man with main pancreatic duct (MPD) stenosis in the pancreatic body had undergone surveillance with semiannual imaging studies for 3 years. During surveillance, magnetic resonance cholangiopancreatography revealed gradual enlargement of a small cyst near the MPD stenosis and contrast-enhanced computed tomography revealed locally progressive atrophic parenchyma in the pancreatic body. On endoscopic retrograde pancreatography, the MPD stenosis was more severe than it had been at diagnosis 3 years earlier. Endoscopic ultrasonography (EUS) showed a 10-mm hypoechoic mass adjacent to the MPD stenosis. The mass was pathologically diagnosed as an adenocarcinoma using EUS-guided fine needle aspiration, and distal pancreatectomy was performed. On histopathological examination, the resected specimen was found to be a moderately differentiated 9-mm invasive ductal carcinoma. Additionally, multiple high-grade pancreatic intraepithelial neoplasms (i.e., carcinoma in situ) were detected in the MPD and branch ducts near the invasive carcinoma.

Surgically resected pancreatic metastasis from nasal malignant melanoma: case report and literature review.

A 13-mm mass was observed in the pancreatic head of a 70-year-old woman who had undergone melanoma resection in the nasal cavity 10 years earlier. Endoscopic ultrasonography (EUS) showed that the mass consisted of multiple hypoechoic nodules. EUS-guided fine needle aspiration and pancreatic juice cytologies revealed neoplastic cells positive for HMB45 and melan-A staining with a few melanin granules, indicating the presence of a metastatic malignant melanoma. These additional stainings were evaluated after surgery. In the surgically resected specimen, the mass had multiple nodule-like structures, some of which were brown colored. Immunocytochemistry and electronic microscopy findings confirmed the diagnosis of malignant melanoma. Microscopic findings were similar to the nasal specimen; therefore, the pancreatic lesion was considered to be a metastasis from the nasal cavity.

Nurse-like cells in rheumatoid arthritis: Formation of survival niches cooperating between the cell types.

Nurse-like cells (NLCs) established from bone marrow and synovial tissue of rheumatoid arthritis (RA) patients were found to promote maturation and differentiation of B lineage cells as well as T cells. In co-culture of RA-NLCs and B cells, tight physical interactions (pseudoemperipolesis) developed, which resulted in activation of both cell types. RA-NLCs also supported myeloid cell maturation, promoting their differentiation into tartrate-resistant acid phosphatase-positive mononuclear cells, which are precursor cells of osteoclasts. In RA synovial tissue, the characteristic dendritic-shaped cells (the DCs) were electron microscopically found to form direct physical interactions with adjacent plasma cells (PCs) suspecting to be pseudoemperipolesis. The numbers of PCs accumulating in various areas tended to correlate with the numbers of the DCs, which appeared to have RA-NLC functions forming survival niches for PCs. Immunohistochemical staining analysis indicated that CD14+ cells including the DCs formed survival niches for CD138+ PCs by RA-NLC functions. Quantitative dual immunofluorescence staining studies of these areas indicated that the majority of CD14+ cells were of myeloid lineage. These survival niches promoted by RA-NLCs appear to play important roles in supporting immunological functions in RA bone marrow and synovial tissues.

Expression of Epithelial-Mesenchymal Transition Proteins in Pancreatic Anaplastic (Undifferentiated) Carcinoma.

OBJECTIVES: The aim of this study was to identify an association of pancreatic anaplastic carcinoma (APC) with the epithelial-mesenchymal transition (EMT). METHODS: Resected APCs (n = 24) were examined to assess components of APCs, including carcinomatous, transitional, and sarcomatous regions. Analysis was performed based on the immunoreactivity of E-cadherin and 3 EMT-related proteins: Slug (zinc finger protein SNAI2), Twist (Twist-related protein 1), and Zeb1 (zinc finger E-box-binding homeobox 1). Expression score was determined based on staining intensity and stained area of the target cells. Finally, we performed a hierarchical clustering based on the expression pattern of E-cadherin and EMT-related proteins of the sarcomatous component. RESULTS: The expression score of E-cadherin decreased in the order of sarcomatous > transitional > carcinomatous components (P < 0.01). Although there were significant differences in the immunohistochemical scores of Slug, Twist, and Zeb1 between carcinomatous and transitional components (P < 0.01), the significant difference in immunohistochemical score of Zeb1 between transitional and sarcomatous components was found (P < 0.05). Furthermore, APCs were divided into 2 subgroups based on the expression patterns of E-cadherin and EMT-related proteins (hierarchical clustering analysis). Consequently, these subgroups were distinguished by Twist expression. CONCLUSIONS: Epithelial-mesenchymal transition plays an essential role in the pathogenesis of APC.