Search

Thyroid sclerosing mucoepidermoid carcinoma with eosinophilia (SMECE) is a rare tumor that typically affects women with Hashimoto’s thyroiditis. The present case was a man in his late 50s who was diagnosed with Graves’ disease at the age of 10 and was given antithyroid hormone for five years. The computed tomography scan revealed a nodular lesion in the right lobe, and the lesion was cytologically suspected as papillary carcinoma. No lymph node metastases or distant metastases were found. Before total thyroidectomy, high serum anti-thyroid peroxidase (TPO) and antithyroglobulin (TG) antibody titers, with no eosinophilia were detected. In a few small areas of the tumor center, small tumor cell foci with mild to moderate atypia, displaying mucous glandular cell and squamous cell differentiation, were found. The tumor was completely replaced by prominent sclerosing fibrosis, which was accompanied by tumor cell infiltration. The tumor had invaded the adjacent parenchyma and perithyroidal fatty tissue. In addition to lymphocytes and plasma cells, a large number of eosinophils were observed within the tumor. Immunohistochemically, tumor cells were strongly positive for p63, 34βE12, and TTF-1, but weakly for PAX8. Using fluorescence in situ hybridization (FISH), no MAML2 translocation was detected. Taken together with these findings, the present tumor was diagnosed as primary thyroid sclerosing mucoepidermoid carcinoma with eosinophilia (SMECE). This case is the first to report thyroid SMECE associated with Graves’ disease. IL-5 immunostaining was performed to identify eosinophilia within the present tumor. As a result, the tumor cells were found to be positive for IL-5. The present tumor is also the first to indicate IL-5 production of SMECE.

PDF file - 17K

PDF file - 57K, Significant decrease of p-(Tyr416)-SRC levels upon siRNA-mediated knockdown of IGF-1R in CME-1 synovial sarcoma cells.

PDF file - 70K, As an indirect proof of specific SRC-related action of dasatinib in synovial sarcoma cells, CME-1 did not display any significant effects upon dasatinib treatement after siRNA-mediated SRC-knockdown.

PDF file - 57K, Densitometric analysis of the top five phosphorylated kinases as found in phospho kinase arrays in 1273/99 and HS-SY-II synovial sarcoma cells. Flow cytometric analysis of three synovial sarcoma cell lines treated with different doses of dasatinib for 48 hours.

Background This study explored the assessment of intrathoracic lymph node metastasis by 18F-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography computed tomography (PET/CT) in patients with asbestos-related lung cancer (ARLC). Methods We retrospectively reviewed the data on 35 patients with ARLC who underwent preoperative FDG-PET/CT and surgical resection between January 2012 and December 2018. We collected medical information from medical records and imaging systems and examined the FDG uptake in each lymph nodal region resected by surgery and the presence or absence of pathological lymph node metastasis. Results Pathological lymph node metastases were detected in 14 (8.70%) of 161 nodal stations. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of FDG-PET/CT were 71.4% (10/14), 87.8% (129/147), 35.7% (10/28), 97.0% (129/133), and 86.3% (139/161), respectively. Six of the eight false-positive patients had bilateral accumulations, whereas all six true-positive patients had unilateral accumulation (P=0.006). On histopathological examination, the false-positive nodes showed disruption of lymphoid follicles in the cortex, infiltration of histiocyte-like cells in the medulla, fibrous micronodules, and severe anthracosis. Conclusions PET/CT scans of patients with ARLC showed comparable sensitivity and specificity to those of PET/CT scans of patients with conventional lung cancer reported in the literature. Many false-positive cases also showed bilateral symmetric accumulation. This method can be used to evaluate lymph node involvement in lung cancer.

The first case is a 62-year-old female who complained of painful left axillary lymph node swelling. Six months later, a CT scan revealed multiple lung nodules. Biopsies of the axillary lymph node and lung showed metastatic carcinoma from breast cancer. However, no breast tumor was found. She was diagnosed with occult breast cancer with metastasis to the axillary lymph node and lung. ER(+), PgR(±), HER2(1+). Letrozole was administered, and effective control was achieved for 20 months. The second case is a 62-year-old female who presented with back pain. A CT scan revealed left axillary lymph node swelling and multiple osteolytic changes in the thoracolumbar spine and rib. Biopsies of the axillary lymph node and thoracic spine showed metastatic carcinoma from breast cancer. However, no breast tumor was found. She was diagnosed with occult breast cancer with metastasis to the axillary lymph nodule and bone. ER(+), PgR(+), HER2(1+). Fulvestrant and denosumab were administered. However, after 6 months, she discontinued the treatment. Our results suggested that effective control could be achieved through systemic therapy and local therapy was not necessary for Stage Ⅳ occult breast cancer.

This case was observed in a man in his 70s. Although symptomatic treatment was performed for epigastralgia, endoscopic examination revealed a type 3 tumor on the fornix of the stomach to the lesser curvature of the body just above the esophagogastric junction, and the patient was diagnosed with moderately differentiated tubular adenocarcinoma(cT4bN3aM0, cStage ⅣA). As esophageal and diaphragmatic invasion was suspected based on CT findings, S-1 plus CDDP was started as preoperative chemotherapy. Although the primary lesion and lymph node metastasis decreased in size, chemotherapy was discontinued after one course due to stenosis symptoms, and total gastrectomy and D2 dissection were performed. Postoperative adjuvant chemotherapy with S-1 was started. However, 6 months after starting the treatment, para-aortic lymph node recurrence was observed, and the treatment strategy was changed to weekly PTX. After 5 courses of weekly PTX, the lymph nodes continued to increase in size, and chemotherapy was discontinued per the patient's request. The patient was followed up with CT and PET-CT; however, no new recurrent lesions were found in other sites for approximately 1 year. Therefore, para-aortic lymph node dissection was performed as the salvage surgery. Pathological findings showed that gastric cancer metastasis was present in 1 swollen lymph node only, as confirmed by PET. At present, 6 years have passed since the first operation, and there has been no recurrence. In general, para-aortic lymph node metastasis is considered to result in poor prognosis in gastric cancer. However, in the absence of other noncurative factors, a good prognosis may be obtained with combined therapeutic modalities.

The oxidation rates of Ni–Al alloys in an atmosphere of Ar–12 vol.% H2O were evaluated by a hydrogen sensor and oxygen pump–sensor installed in the latter stage of an oxidizing furnace. Steam oxidation behavior was also investigated. The oxygen pump–sensor was evaluated using Ar–1000 ppm H2 gas. It was found that the H2 gas concentration could be accurately measured as an oxidation current, such that the hydrogen concentration could be measured by the oxygen pump–sensor, and the oxidation rate could be calculated using this hydrogen concentration. From an isothermal oxidation experiment at 1523 K for 14.4 ks, the oxidation rates measured by the hydrogen sensor and the oxygen pump–sensor were almost the same values in each sample. In addition, the mass gain curve was obtained for each sample based on the result of the time change in the oxidation rate. Furthermore, from a cycle oxidation experiment in which the temperature was varied between 1173 and 1523 K it was found that for the Ni–11 at.% Cr–10 at.%Al and Ni–50 at.%Al alloys, during the temperature increase process of the first cycle, a sharp decrease in the oxidation rate was observed around 1373 K. This was considered to be due to the transformation from θ- to α-Al2O3 since the scales formed on both alloys consisted of Al2O3. However, during the temperature increase process of the second cycle, this decrease was not observed in both alloys. Both the hydrogen sensor and the oxygen pump–sensor method could measure small changes in the oxidation rate during the steam oxidation process, so it became clear that the change in the oxidation rate accompanying the phase transformation of the oxide scale could be determined.

The oxidation behaviors of the Fe, Fe–15mass%Cr and Fe–30mass%Cr alloys were investigated at 1173 K in Ar–H2O and Ar–O2–H2O atmospheres using an oxygen sensor and a hydrogen sensor installed at the outlet of an experimental reactor. In Ar–H2O, the changes in the hydrogen partial pressure were continuously measured using the hydrogen sensor, and the amounts of generated hydrogen and resultant consumed oxygen were calculated. The calculated gross mass gain was in close agreement with that gravimetrically obtained after the experiment. In Ar–O2–H2O, the amount of oxygen consumed from the ambient oxygen gas in the atmosphere was calculated from the change in the oxygen partial pressure measured using the oxygen sensor. In this case, the gross mass gain was analyzed as the sum of the amount of oxygen consumed from the ambient oxygen and that supplied from the steam dissolution. The oxidation patterns were classified into three types: (1) water vapor oxidation (in Ar–H2O), (2) water vapor oxidation and oxygen oxidation (in Ar–500 ppmO2–H2O except for Fe–30Cr), and (3) oxygen oxidation (in Ar–1%O2–H2O). It was demonstrated that a gas monitoring method using a combination of hydrogen and oxygen sensors is useful for investigating the water vapor oxidation in an atmosphere containing water vapor and oxygen.

A 66-year-old woman underwent distal gastrectomy because of gastric cancer(stage ⅠB)and received no adjuvant chemotherapy. Eight years after the operation, computed tomography showed a small nodule in the right breast. Mammography did not reveal any abnormalities. Ultrasound sonography showed a diffuse and gradual non-mass-like low echoic lesion. Core needle biopsy indicated a malignancy. Partial resection of the right breast was performed to obtain a diagnosis. On postoperative histopathological examination, signet-ring cells were found in the tumor, and immunohistochemical analysis showed that both the breast tumor and the gastric carcinoma were MUC5AC-positive and MUC1-negative. We diagnosed this breast tumor as metastasis from gastric cancer. The patient has received chemotherapy with no subsequent metastatic tumors, and good control has been achieved for 21 months after the detection of the breast metastasis.

We report a unique case of a B-cell lymphoma patient in whom IgM monoclonal gammopathy resulted in a prolonged activated partial thromboplastin time (APTT) and false-positive results for fibrinogen and fibrin degradation products (FDPs). An 86-year-old man was referred to our hospital for further examination of abnormal cells in his peripheral blood. Laboratory data upon admission revealed an elevation of monoclonal IgM, presence of FDPs and marked prolongation of APTT (180 s). Bone marrow examination revealed a predominant involvement of B lymphoma cells.

Aims Peritoneal malignant mesothelioma (PMM) is an uncommon tumour, accounting for only 7–9% of all mesotheliomas in Japan. Differential diagnosis between PMM and primary peritoneal serous carcinoma (PPSC), a high-grade serous carcinoma, may be difficult, and separating reactive mesothelial hyperplasia (RMH) from PMM can be even more challenging. Methods To help differentiate PMM from PPSC and RMH, we used immunohistochemistry to examine mesothelial-associated markers (calretinin, AE1/AE3, CK5/6, CAM5.2, D2-40, WT-1, HBME1, thrombomodulin), adenocarcinoma-associated markers (CEA, BerEP4, MOC31, ER (estrogen receptor), PgR, TTF-1, Claudin-4, Pax8), and malignant-related and benign-related markers (epithelial membrane antigen (EMA), desmin, GLUT-1, CD146 and IMP3), and FISH to examine for homozygous deletion of 9p21. We used formalin-fixed, paraffin-embedded blocks from 22 PMMs (M:F=18:4; subtypes: 16 epithelioid, 6 biphasic), 11 PPSCs and 23 RMHs. Results Seventeen of the mesotheliomas (four PMM from women) were classified as diffuse, while five were localised. Calretinin was 91% positive in PMM, but negative in PPSC (specificity, 100%). BerEP4, Claudin-4 and PAX8 were all 100% positive in PPSC (specificities, 100%, 95% and 95%, respectively, for excluding PMM). For distinguishing PMM and RMH, sensitivity for EMA in mesothelioma was 68%, while for IMP3 and GLUT-1 it was 64% and 50%, respectively, all with high specificities. FISH analysis revealed homozygous deletion of the 9p21 locus in 11/13 PMMs, but in 0/11 RMHs. Conclusions Calretinin and BerEP4 may be the best positive markers for differentiating PMM from PPSC. EMA, in combination with IMP3 and desmin, is useful, and homozygous deletion of 9p21 may be helpful, for differentiating PMM from RMH.

Capsule endoscope aspiration into the respiratory tract is a rare complication of capsule endoscopy. Despite the potential seriousness of this complication, no accepted methods exist to accurately predict and therefore prevent it. We describe the case of an 85-year-old male who presented for evaluation of iron deficiency anemia. He complained of dysphagia while ingesting a patency capsule, with several attempts over a period of 5 min before he was successful. Five days later, he underwent capsule endoscopy, where he experienced similar symptoms in swallowing the capsule. The rest of the examination proceeded uneventfully. On reviewing the captured images, the capsule endoscope was revealed to be aspirated, remaining in the respiratory tract for approximately 220 s before images of the esophagus and stomach appeared. To our knowledge, this is the first documented case of a patient who experienced capsule endoscope aspiration after ingestion of a patency capsule. This case suggests that repeated attempts required for ingesting the patency capsule can predict capsule endoscope aspiration. We presume that paying sufficient attention to the symptoms of a patient who ingests a patency capsule could help us prevent serious complications such as aspiration of the capsule endoscope. In addition, this experience implies the potential risk for ingesting the patency capsule. We must be aware that the patency capsule could also be aspirated and there may be more unrecognized aspiration cases.

Lymphomatoid gastropathy, which was first reported in 2010, is a rare NK-cell proliferation of cyCD3, CD4, CD5, CD8, CD56 phenotypes with unknown etiology. The diagnosis is challenging, as there is histopathologic similarity to malignant lymphoma. In the 2010 report on 10 cases, all lesions were located in the stomach, and all regressed without any therapy. In the present study, we analyzed 6 cases of lymphomatoid gastropathy by investigating the clinicopathologic, immunohistochemical, and molecular findings. Endoscopic and morphologic appearances of all cases were consistent with previous reports, but 2 cases showed previously unreported unique immunophenotypes of CD4CD8. Three of 6 patients underwent lower gastrointestinal examination (1 case underwent double-balloon endoscopic examination), but no patient had lesions in the lower gastrointestinal tract. No obvious difference of histology was found between the cases of CD4-CD8-typical phenotype and ones of CD4CD8 phenotype. Both cases had similar clinical behavior as the other 4 cases, implying that the spectrum of the disease is broader than initially thought. Careful clinical and endoscopic follow-up is required for the diagnosis of lymphomatoid gastropathy, and additional case studies and molecular studies are warranted to further investigate the pathophysiology of this peculiar benign mimic of lymphoma.

A 74-year-old man with a history of occupational asbestos exposure in a shipyard was diagnosed with lymphohistiocytoid mesothelioma (LHM). Systemic chemotherapy consisted of cisplatin, and pemetrexed was administered. After six courses of chemotherapy, multiple tumours had regressed. Six months after chemotherapy, the tumours on the pleura exhibited regrowth and partly invaded the liver. Salvage chemotherapies, including irinotecan and vinorelbine, were administered and his disease was stable for several months. Then he suddenly vomited and complained of abdominal pain. Contrast CT showed small intestine intussusception. Partial resection of the small intestine was performed. We found a tumour in the resected small intestine. Review the …

Cases of low-grade B-cell lymphoma presenting primarily in the bone marrow are rare, and its clinicopathology remains unclear. We retrospectively examined patients with low-grade B-cell lymphoma presenting primarily in the bone marrow. Fourteen patients met the inclusion criteria, including 5 with lymphoplasmacytic lymphoma (LPL), 3 with chronic lymphocytic leukemia/small lymphocytic lymphoma, 2 with follicular lymphoma (FL), and 4 with low-grade B-cell lymphoma not otherwise specified (LGBCL-NOS). The median age was 69.5 years (range, 42-89 years), and a slight male predominance was noted (9 men and 5 women, 1.8: 1). Immunohistochemically, all cases were positive for CD20. One case was positive for CD138. Both cases of FL were positive for CD10 and B-cell lymphoma 2 (BCL-2), and immunoglobulin heavy locus (IgH)/B-cell lymphoma 2 rearrangement was observed by fluorescence in situ hybridization. The myeloid differentiation primary response gene (88) leucine to proline mutation was observed in 3 of 5 LPL, 1 of 2 FL, and 2 of 4 LGBCL-NOS patients. Paraproteinemia was observed in 10 patients; IgM and IgG paraproteinemia were observed in 6 and 3 patients, respectively. In this patient series, 3 patients had died at a median follow-up of 36.5 months; the cause of death of 1 LPL patient was malignant lymphoma itself. Thus, low-grade B-cell lymphoma presenting primarily in the bone marrow has various subtypes, and approximately one-third of the patients had LGBCL-NOS. The immunophenotypic features and myeloid differentiation primary response gene (88) leucine to proline mutation data of LGBCL-NOS suggested that some cases present with characteristics similar to those of LPL or marginal zone lymphoma.

Synovial sarcoma is a high-grade soft tissue malignancy characterized by a specific reciprocal translocation t(X;18), which leads to the fusion of the SS18 (SYT) gene to one of three SSX genes (SSX1, SSX2 or SSX4). The resulting chimeric SS18-SSX protein is suggested to act as an oncogenic transcriptional regulator. Despite multimodal therapeutic approaches, metastatic disease is often lethal and the development of novel targeted therapeutic strategies is required. Several expression-profiling studies identified distinct gene expression signatures, implying a consistent role of Wnt/β-catenin signaling in synovial sarcoma tumorigenesis. Here we investigate the functional and therapeutic relevance of Wnt/β-catenin pathway activation in vitro and in vivo. Immunohistochemical analyses of nuclear β-catenin and Wnt downstream targets revealed activation of canonical Wnt signaling in a significant subset of 30 primary synovial sarcoma specimens. Functional aspects of Wnt signaling including dependence of Tcf/β-catenin complex activity on the SS18-SSX fusion proteins were analyzed. Efficient SS18-SSX-dependent activation of the Tcf/β-catenin transcriptional complex was confirmed by TOPflash reporter luciferase assays and immunoblotting. In five human synovial sarcoma cell lines, inhibition of the Tcf/β-catenin protein-protein interaction significantly blocked the canonical Wnt/β-catenin signaling cascade, accompanied by the effective downregulation of Wnt targets (AXIN2, CDC25A, c-MYC, DKK1, CyclinD1 and Survivin) and the specific suppression of cell viability associated with the induction of apoptosis. In SYO-1 synovial sarcoma xenografts, administration of small molecule Tcf/β-catenin complex inhibitors significantly reduced tumor growth, associated with diminished AXIN2 protein levels. In summary, SS18-SSX-induced Wnt/β-catenin signaling appears to be of crucial biological importance in synovial sarcoma tumorigenesis and progression, representing a potential molecular target for the development of novel therapeutic strategies.

Synovial sarcoma is a soft-tissue malignancy characterized by a reciprocal t(X;18) translocation encoding a chimeric transcriptional modifier. Several receptor tyrosine kinases have been found activated in synovial sarcoma; however, no convincing therapeutic concept has emerged from these findings. On the basis of the results of phosphokinase screening arrays, we here investigate the functional and therapeutic relevance of the SRC kinase in synovial sarcoma. Immunohistochemistry of phosphorylated SRC and its regulators CSK and PTP1B (PTPN1) was conducted in 30 synovial sarcomas. Functional aspects of SRC, including dependence of SRC activation on the SS18/SSX fusion proteins, were analyzed in vitro. Eventually, synovial sarcoma xenografts were treated with the SRC inhibitor dasatinib in vivo. Activated phospho (p)-(Tyr416)-SRC was detected in the majority of tumors; dysregulation of CSK or PTP1B was excluded as the reason for the activation of the kinase. Expression of the SS18/SSX fusion proteins in T-REx-293 cells was associated with increased p-(Tyr416)-SRC levels, linked with an induction of the insulin-like growth factor pathway. Treatment of synovial sarcoma cells with dasatinib led to apoptosis and inhibition of cellular proliferation, associated with reduced phosphorylation of FAK (PTK2), STAT3, IGF-IR, and AKT. Concurrent exposure of cells to dasatinib and chemotherapeutic agents resulted in additive effects. Cellular migration and invasion were dependent on signals transmitted by SRC involving regulation of the Rho GTPases Rac and RhoA. Treatment of nude mice with SYO-1 xenografts with dasatinib significantly inhibited tumor growth in vivo. In summary, SRC is of crucial biologic importance and represents a promising therapeutic target in synovial sarcoma. Cancer Res; 73(8); 2518–28. ©2013 AACR.

Diffuse large B-cell lymphoma (DLBCL) is the most common form of non-Hodgkin's lymphoma. Although many investigations have been performed on the prognostic factors of DLBCL, no reports have focused on localized nodal DLBCL. We examined the prognostic significance of 39 Japanese patients with localized nodal DLBCL with special reference to the germinal center B-cell-like (GCB) versus non-germinal center B-cell-like (NGCB) types. The median age was 65 years with 23 males and 16 females. Using Hans algorithm of immunohistochemistry, 18 patients (46%) exhibited GCB type and 21 (54%) exhibited NGCB type. Twenty-nine patients (74%) presented with disease in the neck (neck group) and 10 (26%) had disease in non-neck regions (non-neck group). Comparing Hans, Choi, and Muris algorithms, patients with GCB type showed statistically significant progression-free survival (PFS) only with Hans algorithm (P = 0.022, P = 0.100, and P = 0.130, respectively). Patient survival analyses revealed that GCB-type patients by Hans algorithm had a better PFS (P = 0.012), and neck-group patients had better PFS and overall survival (OS) (P = 0.018 and P = 0.012, respectively). Univariate analysis revealed that only neck vs. non-neck exhibited a significant difference in terms of OS (P = 0.026). Multivariate analysis revealed that GCB type by Hans algorithm and neck vs. non-neck were significantly different in terms of PFS (P = 0.025 and P = 0.033, respectively). Therefore, the subclassifications of GCB type vs. NGCB type and neck vs. non-neck are important predictive prognostic factors in localized nodal DLBCL.

目的 : 本研究の目的は, 循環障害, 肝硬変, 癌性腹膜炎, 腹膜透析の各疾患群において, 腹腔内に出現する反応性中皮の細胞学的および形態計測上の特徴を明らかにすることにある.方法 : 腹水 67 例 (循環障害 7 例, 肝硬変 25 例, 癌性腹膜炎 35 例) と腹膜透析液 9 例を用い, 各疾患群における反応性中皮の出現様式と形態計測結果について比較検討した.成績 : 反応性中皮の出現様式では, いずれの疾患群でも単個と細胞相接や窓形成を示す 2∼4 個までの小集塊が主体 (94.6∼98.6%) を占めた. 平均細胞面積は, 腹膜透析液中にみられる反応性中皮が 165.2μm2と最も大きく, 続いて癌性腹膜炎 145.8μm2, 肝硬変 123.9μm2, 循環障害 119.2μm2の順であった. 平均核面積は, いずれの疾患群でも 50μm2前後に集中しており, 標準偏差は細胞面積が核面積よりも有意に大きかった.結論 : 腹腔に出現する反応性中皮の基本的な細胞所見は, 細胞の大小不同にかかわらず, 核の大小不同が乏しく, 孤立性から小集塊状に出現する点が特徴と考えられる. このような反応性中皮の特徴を理解することは, 体腔液細胞診の診断精度の向上に寄与するものと考えられる.

We experienced 20 patients with distal bile duct carcinoma from May, 1997 to December, 2007. The male/female ratio was 11/9 and the average age was 69.6 years. The operative procedures were as follows : pancreaticoduodenectomy (PD), 9 ; pyrolus preserving pancreaticoduodenectomy (PPPD), 8 ; subtotal stomach preserving pancreaticoduodenectomy (SSPPD), 2 and hepatico-jejunostomy without resection, 1. We performed a clinicopathological study on 16 patients with distal bile duct carcinoma, excluding 3 operation-related deaths and 1 unresectable case. The cumulative survival rate was 70% at 3 years and 11% at 5 years. The 3-year survival rates at fStageII, fStageIVa and fStageIVb were 100%, 80% and 0%, respectively. Log-rank analysis revealed that pathological pancreatic and duodenal invasion and curative resectability may be prognostic factors, while lymph node metastasis and perineural and stump invasion did not affect prognosis. Six recurrences in the 11 curative resection cases (54.5%) were observed ; therefore, postoperative systemic chemotherapy is warranted to curtail recurrence in advanced distal bile duct carcinoma.

Periosteal osteosarcoma is an exceedingly rare type of chondroblastic osteosarcoma, showing rather better prognosis, and secondary bone marrow involvement is unusual. A case of a 22 year old male with periosteal osteosarcoma of the right femur with an associated bone marrow lesion is presented. The juxtacortical tumor, 16 x 11 x 9 cm, was located on the bone cortex of the upper diaphysis and extended into the surrounding soft tissues. A minimal bone marrow lesion was present, although the bone cortex was quite intact. Microscopically, the tumor consisted exclusively of atypical chondroblastic cells with a small osteoblastic area. The bone marrow lesion, interestingly, contained both multiple nodules of well-differentiated chondrosarcomatous components and a few demarcated foci of atypical spindle cells producing a fine osteoid matrix. It was reasonable to conclude, therefore, that this tumor was a periosteal osteosarcoma with an unusual secondary bone marrow lesion rather than a conventional (central) chondroblastic osteosarcoma with soft tissue invasion. The patient's good prognosis with no tumor recurrence or metastasis during more than 7 years follow-up after surgery supports this conclusion.

Synovial sarcoma is a relatively common soft tissue sarcoma with an aggressive clinical course. Although surgery is currently the first treatment modality, improvement of adjuvant chemotherapy is deemed essential to improve the clinical outcome. Nuclear factor-kappaB (NF-kappaB) is constitutively activated in various cancer cells and has emerged as a potential therapeutic molecular target; however, the possible involvement of NF-kappaB in the pathology of sarcomas remains to be clarified. Herein we examined the effects of a novel NF-kappaB inhibitor, dehydroxymethylepoxyquinomicin (DHMEQ) on two synovial sarcoma-derived cell lines, HS-SY-II and SYO-1. The growth of both cell lines was completely inhibited by DHMEQ and apoptosis was induced at 10 microg/ml. Additionally, we found that DHMEQ showed additive effects when used in combination with other cytotoxic agents. These observations indicate that inhibition of NF-kappaB activity may serve as a potential therapeutic target for synovial sarcoma.

Herein is presented a case of carcinosarcoma of the pancreas in an 82-year-old woman, analyzed on immunohistochemistry and K-ras sequence. The tumor, which arose in the pancreas head, was removed on pancreaticoduodenectomy. The patient died, however, of disseminated intravascular coagulation syndrome from postoperative sepsis 13 days later. Microscopically, the tumor consisted of malignant epithelial (well-differentiated adenocarcinoma cells) and mesenchymal (spindle-shaped tumor cells) components. The adenocarcinoma cells had positive immunostaining for cytokeratin AE1/AE3, cytokeratin 7, epithelial membrane antigen (EMA), CEA and carbohydrate antigen 19-9 (CA 19-9), while focal staining of these proteins was observed in the sarcomatous cells. In contrast, the sarcomatous cells had diffuse immunostaining for vimentin, CD10 and p53, while these proteins were not expressed in the ductal adenocarcinoma cells. These findings support the dual characteristics of a carcinosarcoma. DNA sequencing of the present case indicated point mutations of K-ras in both codons 12 and 34 on exon 2. The latter mutation is likely to correlate with the sarcomatous characteristics of this tumor. The tumor cells had specific and diffuse positive staining for CD10 and p53, with features characteristic of rapid growth.

Trastuzumab, a humanized monoclonal antibody against human epidermal growth factor receptor 2 (HER2), has been proven to result in a survival benefit for the treatment of patients with HER2-positive advanced gastric cancer (AGC). However, data are lacking for the treatment of those with disseminated intravascular coagulation (DIC) and diffuse bone marrow carcinomatosis. A 77-year-old woman presented with back pain and fatigue since 2 months. Esophagogastroduodenoscopy showed a scirrhous lesion in the gastric corpus, which was biopsied and identified as signet-ring cell carcinoma with HER2 overexpression on immunohistochemistry. Laboratory testing, bone scintigraphy, and bone marrow biopsy were conducted, and she was diagnosed with HER2-positive AGC with DIC and diffuse bone marrow carcinomatosis. She underwent chemotherapy with the following regimen: oral administration of 80 mg/m2 S-1 for 2 weeks and 6 mg/kg trastuzumab infusion on day 6 every 3 weeks, which significantly improved the DIC. She was discharged from the hospital 73 days after admission and survived for 438 days after diagnosis. To the best of our knowledge, this is the first case report in which HER2-positive AGC complicated by DIC with diffuse bone marrow carcinomatosis was successfully treated with combined chemotherapy consisting of S-1 plus trastuzumab.

The authors report a case of interhemispheric ependymal cyst accompanied with agenesis of the corpus callosum in a fetus. Routine ultrasound and subsequent magnetic resonance imaging of a 20-year-old woman at 33 weeks and 1 day of gestation detected a large interhemispheric cystic lesion in the fetal cranial cavity. Caesarian section was carried out at 36 weeks because of the progressive enlargement of the fetal head. The cyst was multiloculated and a cyst peritoneal shunt placement resulted in collapse of the drained cyst components followed by enlargement of others. After wrack-a-mole-like shunt revisions, open surgery was performed at the age of 2 years. Cyst walls were fenestrated and the cavities were communicated with each other and eventually with the lateral ventricle. Pathological diagnosis of the cyst wall was ependymal cyst. The boy is now 3 years old, and growing without apparent developmental delay or recurrence. Current concept and management policy of the interhemispheric cyst accompanied with agenesis of the corpus callosum is reviewed.

Histone deacetylases (HDAC) are key players in epigenetic regulation of gene expression and HDAC inhibitor (HDACi) treatment seems to be a promising anticancer therapy in many human tumours, including soft tissue sarcomas. HR23b has been shown to be a potential biomarker for sensitivity to HDACi therapy in cutaneous T-cell lymphoma and hepatocellular carcinoma. We aimed to evaluate HR23b as a candidate biomarker for HDACi response in sarcomas and gastrointestinal stromal tumours (GIST). Therefore, HR23b expression was analysed comprehensively by western blot in sarcoma and GIST cell lines covering all major clinically relevant subtypes. MTT assay and ApoTox-Glo(TM) Triplex assay were performed after treatment with vorinostat, belinostat, mocetinostat and entinostat. HR23b protein expression was measured under HDACi treatment. Furthermore, HR23b expression levels were immunohistochemically determined in a large set of 523 clinical samples from sarcoma and GIST patients. Western blot analyses showed that sarcomas differ significantly in their expression of HR23b protein. All HDACi were able to regulate proliferation and apoptosis in vitro. Sensitivity to vorinostat correlated significantly with HR23b protein expression. Immunohistochemical prevalence screening in clinical samples of relevant adult-type tumours revealed that 12.5% of sarcomas (among them malignant peripheral nerve sheath tumours, pleomorphic liposarcomas, leiomyosarcomas, dedifferentiated liposarcomas, synovial sarcomas and angiosarcomas) and 23.2% of GIST show high HR23b expression. Therefore, HDACi have antiproliferative and proapoptotic effects in sarcomas depending on the expression level of HR23b. These findings suggest that HR23b represents a candidate biomarker for HDACi sensitivity in certain sarcoma types and in GIST. CA extern

Carbonic anhydrase-related protein VIII (CA-RP VIII) is believed to be an oncofetal antigen and is overexpressed in colorectal and non-small cell lung cancer. However, the pathobiological properties of CA-RP VIII in lung cancer remain unclear. In the present study, we examined ultrastructural changes caused by exogenous CA-RP VIII expression in a well-differentiated lung adenocarcinoma cell line, PC-9. Many vacuoles lined by cilia, sometimes large vacuoles pushing the nuclei to one side, were found in the cytoplasm of CA-RP VIII-expressing PC-9 cells, but not in control PC-9 cells. Moreover, signet-ring cells containing abundant intracytoplasmic mucin were often found among CA-RP VIII-expressing PC-9 cells, but rarely among control PC-9 cells. We subsequently examined CA-RP VIII expression in atypical adenomatous hyperplasia and early-stage lung adenocarcinoma (Stage Ia). Significant expression of CA-RP VIII was observed in invasive lung adenocarcinoma but not in noninvasive adenocarcinoma. Interestingly, CA-RP VIII was strongly expressed in signet-ring cell cancer and invasive mucinous adenocarcinoma components. CA-RP VIII also appeared to enhance the invasiveness of PC-9 cells in Matrigel invasion assay. The present findings suggest that CA-RP VIII expression in lung adenocarcinoma is related to cancer cell invasion.

Imatinib is a specific inhibitor of c-KIT that has recently been approved for the treatment of chronic myeloid leukemia and gastrointestinal stromal tumor (GIST). Thapsigargin is an inhibitor of calcium transport to the endoplasmic reticulum (ER) and can inhibit protein maturation. In this study, we evaluated the synergistic cytotoxic effect of thapsigargin and imatinib on the GIST cell line, GIST-T1. Cell viability and cell death were determined by 3,-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay and flow cytometry, respectively. In addition, the amount and activation of c-KIT on the cell surface were measured by flow cytometry and western blot analysis, respectively. Thapsigargin alone (for 5 hr incubation) was shown to decrease the amount of c-KIT on the GIST-T1 cell surface and to slightly inhibit the associated tyrosine kinase activity. Interestingly, thapsigargin significantly enhanced the cell death induced by imatinib compared with the effect of imatinib alone. The results further suggested that thapsigargin induced the increased cell death in GIST-T1 cells co-treated with imatinib, at least in part, via disrupting the translocation of c-KIT to the cell surface, and decreasing the activated c-KIT molecules.

Dysadherin is a cancer-associated cell membrane glycoprotein, which downregulates E-cadherin and promotes metastasis. We studied the clinicopathological features in 72 cases of epithelioid sarcoma and in six cases of malignant rhabdoid tumor, and also assessed the immunohistochemical expression of dysadherin, E-cadherin and MIB-1 in epithelioid sarcoma and malignant rhabdoid tumor cases. In addition, we compared dysadherin mRNA expression between epithelioid sarcoma and malignant rhabdoid tumor cell lines, using RT-PCR and real-time quantitative RT-PCR analysis. Immunohistochemical dysadherin expression was more frequently observed in proximal-type epithelioid sarcoma (71%) in comparison with distal-type epithelioid sarcoma (36%) (P = 0.037). Furthermore, seven proximal-type epithelioid sarcoma cases mimicking malignant rhabdoid tumor (histologically classified as the large cell type, accompanied by frequent rhabdoid cells and located in deep soft tissue) were all positive for dysadherin (100%), whereas dysadherin expression was not detected at all in any of the true six malignant rhabdoid tumors (0%). Cell lines established from proximal-type epithelioid sarcoma revealed significantly higher levels of dysadherin mRNA expression, compared with the levels seen in malignant rhabdoid tumor cell lines by real-time quantitative RT-PCR (P = 0.0433). Epithelioid sarcoma patients with dysadherin expression survived for a significantly shorter time than those without dysadherin expression (P = 0.001). In multivariate analysis, dysadherin immunopositivity (P = 0.0004) was one of the two independent adverse prognostic factors. We conclude that dysadherin expression in epithelioid sarcoma is a significant poor prognostic factor and that it is a powerful diagnostic marker for distinguishing epithelioid sarcoma, including the proximal-type epithelioid sarcoma, from malignant rhabdoid tumor. In epithelioid sarcoma, especially in proximal-type epithelioid sarcoma, increased cell disadhesion and motility by dysadherin plays an important role to acquire aggressive biological behavior. However, in malignant rhabdoid tumor, cell growth cycle that is regulated by hSNF5/INI1 gene seems to be critical to lethal biological behavior rather than dysadherin.