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A novel variant of chromophobe renal cell carcinoma showing an oncocytic phenotype is proposed. Two new cases of this rare entity are presented and discussed along with six previous cases from our colleagues. A 76-year-old man and a 78-year-old man had a 3.4-cm and a 3.2-cm-diameter renal mass, respectively. On histopathological examination of surgical specimens, uniform eosinophilic cuboidal cells without a perinuclear halo growing in a tubular pattern were seen, and differential diagnosis from oncocytoma was necessary. Immunohistochemical staining for cytokeratin 7 and E-cadherin showed diffusely positive patterns in both, as in the previous reports. Although monosomy of chromosomes 7, 10, 13, and 17 was commonly observed in the previous reports, gains of chromosome 19 were observed in the two present cases. Immunohistochemical and cytogenetic approaches lead to exclusion of oncocytoma and the diagnosis of an oncocytic variant of chromophobe renal cell carcinoma.

Lenvatinib is an inhibitor of tyrosine kinases, such as vascular endothelial growth factor receptor and fibroblast growth factor receptor, and was first approved for use in thyroid cancer in 2015 in Japan. Additional approval was given in March 2018 for its use as a first-line treatment for advanced or unresectable hepatocellular carcinoma. Herein, we report a case of pneumothorax during lenvatinib treatment for multiple lung metastases of hepatocellular carcinoma in a 71-year-old man. Although the development of pneumothorax during treatment with anticancer agents for lung metastases is well-known, this is the first report of pneumothorax induced by lenvatinib during treatment for lung metastases of hepatocellular carcinoma.

A 73-year-old man had multiple coronary aneurysms that resulted in acute myocardial infarction on the day before surgery for cerebral aneurysms. Emergent coronary angiography revealed that the lesion that caused the myocardial infarction was a distal left circumflex artery, and two huge coronary aneurysms were also found in the left circumflex artery. A two-stage treatment strategy was planned, including coronary aneurysm surgery, followed by cerebral aneurysm surgery. He underwent coronary artery aneurysmorrhaphy with closure of the ostia of the afferent and efferent arteries, and coronary artery bypass grafting with a saphenous vein graft applied to the left circumflex artery. The pathological findings suggested chronic thromboangiitis, as the inflammatory cells were observed to have infiltrated the coronary artery wall. The tissue remodeling of the aneurysmal wall indicated a positive response to tenascin C. We report a case of multiple coronary aneurysms, focusing on the pathological findings.

This study reports on a 67-year-old woman with partial Brown-Séquard syndrome due to a recurrent cervical neurenteric cyst at C3 to C4. The myelopathic symptoms reappeared 22 years after a previous shunting operation performed posteriorly with a silicone tube connecting the intradural cervical cyst cavity to the subarachnoid space. We have now succeeded in removing the cyst nearly completely with the anterior approach. The surgical procedure consisted of right vertebral artery exposure at C3 and C4 and a subtotal corpectomy of C3 followed by microdissection of the cyst, duraplasty, and iliac strut graft fusion. Spinal cord monitoring with motor-evoked potential studies helped us safely dissect the cyst wall tightly adhering to the spinal cord. Duraplasty with Gore-Tex patch-grafting in conjunction with postoperative lumbar subarachnoid drainage worked well in preventing a spinal fluid fistula. At two years after surgery, the patient showed a nearly complete return of function without any recurrence of the cyst.

Memory includes the processes of acquisition, consolidation and retrieval. In the study of aversive olfactory memory in Drosophila melanogaster, flies are first exposed to an odor (conditioned stimulus, CS+) that is associated with an electric shock (unconditioned stimulus, US), then to another odor (CS-) without the US, before allowing the flies to choose to avoid one of the two odors. The center for memory formation is the mushroom body which consists of Kenyon cells (KCs), dopaminergic neurons (DANs) and mushroom body output neurons (MBONs). However, the roles of individual neurons are not fully understood. We focused on the role of a single pair of GABAergic neurons (MBON-γ1pedc) and found that it could inhibit the effects of DANs, resulting in the suppression of aversive memory acquisition during the CS- odor presentation, but not during the CS+ odor presentation. We propose that MBON-γ1pedc suppresses the DAN-dependent effect that can convey the aversive US during the CS- odor presentation, and thereby prevents an insignificant stimulus from becoming an aversive US.

Examination of >12 lymph nodes (LNs) is important for the diagnostic accuracy of nodal status following resection of colorectal cancer. In the present study, the efficacy of a fat dissolution technique for LN retrieval was evaluated using resected colon and rectum mesentery. First, the resected mesentery was searched for LNs by inspection and palpation immediately after surgery. Subsequently, fat dissolution liquid was applied to the remnant fat and the LN search was repeated. The primary endpoint was whether the second assessment would increase the number of evaluated LNs. Recruitment of 20 patients was planned. The study was conducted after institutional review board approval and written informed consent was obtained. Among 20 participants, 1 patient was excluded because LN dissection was not performed. The median number of LNs identified at the first and second assessments was 13 and 6, respectively, producing a significant increase in total LNs evaluated (13 vs. 20, respectively; P12 in 4 patients, and although staging was not changed, the treatment was potentially altered in 2 stage II patients. The maximum diameter of the additionally obtained LNs was significantly smaller compared with those from the first assessment (4 vs. 7.7 mm, respectively; P

Summary: During olfactory associative learning in Drosophila, odors activate specific subsets of intrinsic mushroom body (MB) neurons. Coincident exposure to either rewards or punishments is thought to activate extrinsic dopaminergic neurons, which modulate synaptic connections between odor-encoding MB neurons and MB output neurons to alter behaviors. However, here we identify two classes of intrinsic MB γ neurons based on cAMP response element (CRE)-dependent expression, γCRE-p and γCRE-n, which encode aversive and appetitive valences. γCRE-p and γCRE-n neurons act antagonistically to maintain neutral valences for neutral odors. Activation or inhibition of either cell type upsets this balance, toggling odor preferences to either positive or negative values. The mushroom body output neurons, MBON-γ5β′2a/β′2mp and MBON-γ2α′1, mediate the actions of γCRE-p and γCRE-n neurons. Our data indicate that MB neurons encode valence information, as well as odor information, and this information is integrated through a process involving MBONs to regulate learning and memory. : Aversive and appetitive olfactory memories in fruit flies are formed in third order olfactory neurons, the mushroom body Kenyon cells (KCs). Yamazaki et al. identify parallel pathways consisting of two subpopulations of KCs and their output neurons that encode aversive and appetitive valences. Keywords: Drosophila, olfactory memory, γCRE-p neurons, γCRE-n neurons, valences, mutual inhibition, MBON-γ5β′2a/β′2mp, MBON-γ2α′1

External aortic wrapping may overcompress the aortic wall. An 18-year-old man underwent valve-sparing aortic root replacement for annuloaortic ectasia caused by Loeys-Dietz syndrome. External Dacron graft wrapping was performed to protect the ascending aorta. A year later, he underwent mitral valve repair. Intraoperatively, after unwrapping the external graft, the wrapped ascending aortic wall appeared necrotic. Histopathology showed damaged smooth muscle cells in the adventitia and outer media with unaffected inner layers and an intact intimal surface. Ischaemic necrosis of the aortic wall was associated with arterial insufficiency secondary to overcompression of the aortic wall that was already weakened by Loeys-Dietz syndrome. We describe a patient with Loeys-Dietz syndrome in whom pathognomonic necrosis in the wrapped aortic wall was observed histopathologically.

Preoperative diagnosis of aortic sarcomas is often difficult. Herein, we describe a case of a 68-year-old man who had an aortic intimal sarcoma with aortic wall hypertrophy that masqueraded as a thrombosed aortic dissection or mural thrombus on computed tomography. Because of the sudden appearance and rapid growth of the tumour surrounding the left subclavian artery with precordial pain and haemosputum, left subclavian arterial rupture caused by aortic dissection was suspected, requiring emergent total arch replacement. Surgery revealed an intimal sarcoma, not an aortic dissection, with the thickening of the fragile intima spreading into the aorta. Thus, an intramurally spreading aortic intimal sarcoma should be suspected when computed tomography reveals an irregular thickening of the aortic intima.

The Rac-Cofilin pathway is essential for cytoskeletal remodeling to control axonal development. Rac signals through the canonical Rac-Pak-LIMK pathway to suppress Cofilin-dependent axonal growth and through a Pak-independent non-canonical pathway to promote outgrowth. Whether this non-canonical pathway converges to promote Cofilin-dependent F-actin reorganization in axonal growth remains elusive. We demonstrate that Sickie, a homolog of the human microtubule-associated protein neuron navigator 2, cell-autonomously regulates axonal growth of Drosophila mushroom body (MB) neurons via the non-canonical pathway. Sickie was prominently expressed in the newborn F-actin-rich axons of MB neurons. A sickie mutant exhibited axonal growth defects, and its phenotypes were rescued by exogenous expression of Sickie. We observed phenotypic similarities and genetic interactions among sickie and Rac-Cofilin signaling components. Using the MARCM technique, distinct F-actin and phospho-Cofilin patterns were detected in developing axons mutant for sickie and Rac-Cofilin signaling regulators. The upregulation of Cofilin function alleviated the axonal defect of the sickie mutant. Epistasis analyses revealed that Sickie suppresses the LIMK overexpression phenotype and is required for Pak-independent Rac1 and Slingshot phosphatase to counteract LIMK. We propose that Sickie regulates F-actin-mediated axonal growth via the non-canonical Rac-Cofilin pathway in a Slingshot-dependent manner.

Olfactory information in Drosophila is conveyed by projection neurons from olfactory sensory neurons to Kenyon cells (KCs) in the mushroom body (MB). A subset of KCs responds to a given odor molecule, and the combination of these KCs represents a part of the neuronal olfactory code. KCs are also thought to function as coincidence detectors for memory formation, associating odor information with a coincident punishment or reward stimulus. Associative conditioning has been shown to modify KC output. This plasticity occurs in the vertical lobes of MBs containing α/α' branches of KCs, which is shown by measuring the average Ca(2+) levels in the branch of each lobe. We devised a method to quantitatively describe the population activity patterns recorded from axons of >1000 KCs at the α/α' branches using two-photon Ca(2+) imaging. Principal component analysis of the population activity patterns clearly differentiated the responses to distinct odors.

Axonal branching is one of the key processes within the enormous complexity of the nervous system to enable a single neuron to send information to multiple targets. However, the molecular mechanisms that control branch formation are poorly understood. In particular, previous studies have rarely addressed the mechanisms underlying axonal bifurcation, in which axons form new branches via splitting of the growth cone. We demonstrate that DISCO Interacting Protein 2 (DIP2) is required for precise axonal bifurcation in Drosophila mushroom body (MB) neurons by suppressing ectopic bifurcation and regulating the guidance of sister axons. We also found that DIP2 localize to the plasma membrane. Domain function analysis revealed that the AMP-synthetase domains of DIP2 are essential for its function, which may involve exerting a catalytic activity that modifies fatty acids. Genetic analysis and subsequent biochemical analysis suggested that DIP2 is involved in the fatty acid metabolization of acyl-CoA. Taken together, our results reveal a function of DIP2 in the developing nervous system and provide a potential functional relationship between fatty acid metabolism and axon morphogenesis.

Translocation-type renal carcinoma has been recently discovered, and it is possible that this tumor may have been previously diagnosed as other types of renal tumor. We have subjected 41 renal tumors, including VHL gene mutation-negative clear cell renal cell carcinoma (RCC), papillary RCC, and chromophobe RCC, to immunohistochemistry of transcription factor E3 (TFE3) and TFEB. All tumors were histologically evaluated by additional immunohistochemical study. As a result, 5 tumors showed a positive reaction for TFE3 with a range from 1+ to 2+ in intensity. No tumors were positive for TFEB. In 5 tumors immunohistochemically positive for TFE3, chimeric transcripts including ASPL-TFE3, PRCC-TFE3, CLTCTFE3, PSF-TFE3, or Nono-TFE3 were not detected. The diagnosis of 6 tumors was changed by reevaluation through retrospective histological and immunohistochemical study. In 4 of 6 tumors, the diagnosis of clear cell RCC was changed to chromophobe RCC. In 1 tumor, oncocytoma was detectable, and RCC with rhabdoid features and sarcomatoid changes was detected in 1 tumor. Finally, the cutoff value of TFE3 immunohistochemistry should be more than 2+ with a wide range. The translocation-type renal carcinoma seems to be quite rare.

Primary undifferentiated carcinoma of the small intestine is an extremely rare neoplasm. Here, we report a case of primary undifferentiated carcinoma that arose from the ileum in a 65-year-old woman. Laboratory data revealed anemia and slightly elevated inflammatory parameters. Computed tomography showed a heterogeneous mass in the pelvic cavity, and magnetic resonance imaging revealed that the margin of the tumor mass was clear. Positron emission tomography using (18)F-fluoro-2-deoxy-D: -glucose (FDG) showed accumulation of FDG on the tumor mass with a standardized uptake value of 8.3. Partial resection of the ileum to remove the tumor was performed under a clinical diagnosis of small intestinal carcinoma. The tumor was nodulated and had a circumscribed margin 6.5 x 5.5 x 4 cm in diameter. Microscopically, the tumor was composed of giant polygonal cells with cellular atypia. Immunohistochemical examination revealed that the tumor cells expressed epithelial markers including AE1/AE3, CAM5.2, and EMA; however, lymphocytic, mesenchymal, and gastrointestinal stromal tumor markers were not expressed. We made a final diagnosis of primary undifferentiated carcinoma of the small intestine. The prognosis of patients with undifferentiated carcinoma of the small intestine is very poor. To improve the outcome of treatment, early and accurate diagnosis is essential, and additional therapy, including multimodality adjuvant therapy or the administration of novel molecular targeted drugs, should be considered.

The detection of water and the regulation of water intake are essential for animals to maintain proper osmotic homeostasis. Drosophila and other insects have gustatory sensory neurons that mediate the recognition of external water sources, but little is known about the underlying molecular mechanism for water taste detection. Here we identify a member of the degenerin/epithelial sodium channel family, PPK28, as an osmosensitive ion channel that mediates the cellular and behavioural response to water. We use molecular, cellular, calcium imaging and electrophysiological approaches to show that ppk28 is expressed in water-sensing neurons, and that loss of ppk28 abolishes water sensitivity. Moreover, ectopic expression of ppk28 confers water sensitivity to bitter-sensing gustatory neurons in the fly and sensitivity to hypo-osmotic solutions when expressed in heterologous cells. These studies link an osmosensitive ion channel to water taste detection and drinking behaviour, providing the framework for examining the molecular basis for water detection in other animals.

We describe a 43-year-old woman who underwent laparoscopic distal pancreatectomy preserving the spleen and splenic vessels for the treatment of insulinoma in the pancreatic body. The patient experienced cold sweats on fasting, received diagnosis of insulinoma, and was referred to our hospital for laparoscopic surgery. Blood biochemistry studies showed low fasting blood glucose of 42 mg/dL, serial immunoreactive insulin of 15.2 microU/mL, and a Fajans index (immunoreactive insulin/blood glucose) of 0.36 (normal

Having noted a discrepancy between endoscopic and histopathological diagnoses in cases of minute adenomas of the colon, a prospective study was designed to clarify which is appropriate, magnifying chromoendoscopy or histopathology of a specimen obtained by biopsy forceps. A total of 208 patients comprised the study population. The endoscopic diagnoses were performed with magnifying colonoscopies. We separated the detected lesions with type III(L) pit pattern following Kudo's classification into two groups at random: in group A (n = 104) resected specimens were fixed with 20% buffered formalin without being flattened, whereas in group B (n = 104) the resected specimens were flattened using forceps before fixation and the specimens were cut under observation of their surface structure with stereomicroscopy. Comparison of the initial diagnoses between groups A and B showed that a total of 84.6% (88/104) of the lesions were diagnosed to be tubular adenomas histopathologically in group A, compared with 100% (104/104) in group B (P < 0.0001). Results for comparison of the secondary diagnoses between group A and group B showed that 14 of the 16 lesions were diagnosed as tubular adenomas histopathologically. Thereafter, 98.1% (102/104) of the lesions were diagnosed to be tubular adenomas histopathologically in group A (P = 0.4976). In conclusion, high-resolution magnifying chromoendoscopy is an appropriate procedure for the diagnosis of minute adenomas in comparison with histopathology of specimens obtained by biopsy forceps in this prospective study.

A 70-year-old man was admitted to our hospital for evaluation of multiple pancreatic tumors. Twelve years earlier he had undergone left radical nephrectomy for renal cell carcinoma (RCC). Computed tomography revealed two well-defined mass lesions in the head and tail of the pancreas, with strong contrast enhancement in the arterial phase. Fluorine-18 fluorodeoxyglucose positron emission tomography detected an elevated uptake within the lesions but no extrapancreatic uptake. The preoperative diagnosis was isolated multifocal metastatic pancreatic tumors from RCC. The patient underwent total pancreatectomy with splenectomy. Both of the tumors were well-demarcated, gray-white, and firm on gross observation. Microscopic examination, meanwhile, revealed solid tumors consisting of clear oval cells with severe nuclear atypia. These pathologic findings were consistent with the preoperative diagnosis of pancreatic metastasis from RCC. Radical resection improves the long-term survival of patients, and total pancreatectomy may be an appropriate procedure.

We developed short-term pancreatic cancer models in hamsters using PGHAM-1 cells and examined the utility of the models for research on metastasis and for therapeutic trials. With 3 PGHAM-1 models, including 1) primary pancreatic cancer and simultaneous liver metastasis by intrapancreatic transplantation, 2) liver metastasis alone by intrasplenic transplantation, 3) peritoneal dissemination by intraperitoneal transplantation, within 21 days after inoculation, we studied the specific characteristics of metastases and the effects of several antiangiogenic substances on primary and metastatic pancreatic tumors. Several experiments showed that vascular endotherial growth factor and anatomical characteristics were important factors for metastasis. In therapeutic experiments, the incidence, size, diameter, microvessel density, and apoptotic index of the tumors were preferably influenced by the antiangiogenic substances. In addition, PGHAM-1-Luc, which is luciferase-positive PGHAM-1 cell line, was newly developed and is expected to be a useful new animal model. These models would be suitable for the study of pathogenesis of pancreatic cancer and its metastasis and for preclinical trials of chemotherapeutic agents, such as antiangiogenic substances.

Aim: In the present study, we aimed to clarify the parameters that can be used for clinically relevant treatment decisions. Patients and methods: During the period from July 1985 to April 2005, 283 pT1 cancers were selected for this study. Risk factors for lymph node (LN) metastasis were evaluated as follows: endoscopic appearance, tumor size, location, lymphatic permeation, venous invasion, patterns of cancer invasion into the submucosal layer, and depth of vertical invasion in the submucosal layer. Results: Results of the logistic regression analysis from these significant parameters were as follows: infiltrating growth pattern (odds ratio: 12.63); lymphatic permeation positive (odds ratio: 5.726); sigmoid colon (odds ratio: 4.585); tumor size (odds ratio: 1.718). However, the leading edge of only one cancer with LN metastasis in the expanding growth group was also cribriform pattern. Conclusion: The invasive growth patterns of infiltrating growth, lymphatic permeation, tumor location of the sigmoid colon, and maximum tumor size were independent and significant risk factors for LN metastasis in our logistic regression analysis. In particular, the former three factors (infiltrating growth, lymphatic permeation and sigmoid colon) revealed high odds ratio and covered all cases of LN metastasis. From the results of our study, the indication for operative intervention after EMR in pT1 cancer is those lesions which possess at least one factor among the three (infiltrating growth, lymphatic permeation and sigmoid colon). Also, assessment of the leading edge with a cribriform pattern should be dealt with carefully.

Recently, autoimmune pancreatitis (AIP) has been reported with a variety of extra-pancreatic manifestations and infiltration of IgG4-positive cells into the affected organs. We report herein two cases with prostatitis. One was seen in a patient with typical AIP, and the other was observed without any clinical manifestation of AIP. Serum IgG4 levels were elevated in both cases. Histological examination of the prostates showed that parenchymal cells were partially or totally replaced with fibrosis and abundant infiltration of IgG4-positive cells. Significant uptake of [18F] fluorodeoxyglucose by the prostate was seen in both cases. In the case with AIP, the uptake completely disappeared after steroid therapy. The findings observed in these cases suggest that the pathological mechanism for prostatitis is similar to the mechanism previously implicated in AIP, namely IgG4-related autoimmune prostatitis.

We report the case of an 80-year-old man who presented with pathologically diagnosed chromophobe renal cell carcinoma composed of eosinophilic cells with partial papillary growth. The patient had a 2.5 cm diameter renal mass incidentally detected by abdominal ultrasound examination. Laparoscopic left partial nephrectomy was performed under a diagnosis of left renal tumor. Histopathology demonstrated uniform eosinophilic cuboidal cells growing with a partially papillary pattern: differential diagnosis of oncocytoma, papillary renal cell carcinoma, or oncocytic papillary renal cell carcinoma was necessary. Immunohistochemical staining with anti-monoclonal antibody 31 and -CD82 antibody, and choroid iron staining, were positive. Cytogenetic analysis by comparative genomic hybridization showed gains of chromosomes 1p, 9q, 19q, 20, and 21q, and losses of chromosomes 1p and q, 2q, 6q and 7q, leading to diagnosis of chromophobe RCC. We describe differential diagnosis for chromophobe renal cell carcinoma, eosinophilic variant, growing in a papillary fashion in the kidney.

A 20-year-old woman had a fever, pancytopenia, and liver failure, and was suspected to be suffering from chronic active Epstein-Barr virus (EBV) infection, based on the detection of high EBV-DNA and EBV antibody titers at another hospital. At our institution one month later, clinical manifestations had diminished, and antibody titers had decreased but remained elevated relative to normal levels. Four days later, the patient required hospitalization due to fever, liver damage, and cervical lymphadenopathy. Bone marrow examination and lymph node biopsy results showed EBV-positive cytotoxic T-cells that were predominantly CD4-positive. The disease followed a fulminant course and the patient died of multiple organ failure on hospitalization day 11. Because complicated chromosomal aberrations and T-cell receptor gene rearrangements were identified, we diagnosed her as having systemic EBV-positive T-cell lymphoproliferative disorder of childhood. This disease type includes a lymphoproliferative disorder that is associated with chronic active EBV infection. However, it is clinically different from the type following acute EBV infection. We consider distinguishing between these two types to be important for selecting an early diagnostic procedure and the optimal therapy.

Sir, A 74-year-old man presented with anorexia, general fatigue, weight loss and purpura on the lower legs. Auscultation revealed trivial fine crackle. The white blood cell count was 5600/mm3, with 6.0% eosinophils. Haemoglobin was 8.5 g/dl. The C-reactive protein was 5.2 mg/dl. BUN, creatinine and uric acid were 11, 0.86 and 5.9 mg/dl, respectively. Liver enzymes were within normal limits. IgG, IgA and IgM were 6170 mg/dl, 129 mg/dl and 38 mg/ dl, respectively. IgG1, IgG2, IgG3 and IgG4 were 3470, 1460, 552 and 807 mg/dl. IgE was 1070 IU/ml. Proteinuria was 100 mg/dl (0.7 g/day), and trivial microhaematuria was observed. NAG was 23.1 U/g·Crn. CH50, C3 and C4 were

A 64-year-old woman was accidentally detected to have multiple cystic tumors measuring 30 mm in diameter in the pancreatic head in 2009. The probable diagnosis was a serous cystic neoplasm of the pancreas. However, the tumor had grown to 52 mm in diameter in 4 years, and endoscopic retrograde pancreatography (ERCP) showed stenosis of the main pancreatic duct. We performed subtotal stomach-preserving pancreaticoduodenectomy, and histopathological diagnosis was serous cystadenoma.

In this study, we examined the distribution and origin of myofibroblasts around the perforations of appendicitis. Stromal cells of 45 cases were studied by immunohistochemistry. In the normal appendix, myofibroblasts were restricted to the mucosa, and CD34-positive stromal cells were distributed in the submucosal and subserosal layers. Some mesothelial cells were positive for cytokeratin CAM5.2, cytokeratin 5, or mesothelial cells (HBME-1). In perforation of appendicitis with both abscess and granulation tissue, a small to moderate or a moderate to large number of myofibroblasts appeared in the subserosal area around the perforation, respectively, but CD34-positive stromal cells were completely absent there. In the subserosal area of the perforation of appendicitis with abscess, cytokeratin 5-positive stromal cells were absent. However, a small to moderate number of cytokeratin CAM5.2-positive stromal cells were observed there. Double immunostaining showed the coexpression of alpha-smooth muscle actin (ASMA) and cytokeratin CAM5.2 and the coexpression of cytokeratin 5 and cytokeratin CAM5.2 in many or some stellate-shaped or spindle-shaped stromal cells existing in the subserosal area with granulation tissue around the perforation of appendicitis, respectively. Finally, many myofibroblasts appearing in the subserosal area of the perforation of appendicitis may be derived from submesothelial cells or mesothelial cells.

We observed postnecrotic tissue remodeling to examine vascularization in adult rat livers. Livers, bone marrow, and peripheral blood from rats at 24 h to 14 days after an injection of dimethylnitrosamine (DMN) were examined by light microscopic, immunohistochemical, and ultrastructural methods. Numerous ED-1 (a marker for rat monocytes/macrophages)-positive round mononuclear cells infiltrated in the necrotic areas at 36 h after DMN treatment. On day 5, when necrotic tissues were removed, some of the cells were transformed from round to spindle in shape. On day 7, these cells were contacted with residual reticulin fibers and became positive for SE-1, a marker of hepatic sinusoidal endothelial cells and Tie-1, an endothelial cell-specific surface receptor, associated with frequent occurrence of ED-1/SE-1 and ED-1/Tie-1 double-positive spindle cells. Ultrastructurally, the spindle cells simultaneously showed phagocytosis and endothelial cell-like morphology. With time necrotic areas diminished, and on day 14, the necrotic tissues were almost replaced by regenerated liver tissues and thin bundles of central-to-central bridging fibrosis. Bone marrow from 12 h to day 2 showed an increase of BrdU-positive mononuclear cells. Some of them were positive for ED-1. The BrdU-labeled and ED-1-positive cells appeared as early as 12 h after DMN injection and reached a peak in number at 36 h. They were similar in structure to ED-1-positive cells in necrotic liver tissues. These findings suggest that round mononuclear ED-1-positive cells proliferate first in bone marrow after DMN treatment, reach necrotic areas of the liver through the circulation, and differentiate to sinusoidal endothelial cells. Namely, hepatic sinusoids in DMN-induced necrotic areas may partly be reorganized possibly by vasculogenesis.

The patient was a 65-year-old woman who complained of lower abdominal pain. Salpingo-oophorectomy and hysterectomy were performed due to suspicion of ovarian cancer. At surgery a polypoid mass was observed in the fimbria of the left fallopian tube. Histologically, proliferation of undifferentiated neoplastic cells with marked cytological atypia predominated in the tumor. Proliferation of rhabdomyoblastic cells or spindle cells, as well as adenocarcinoma arising from the mucosa of the fallopian tube, was observed. A diagnosis of malignant müllerian mixed tumor (MMMT) was made. CD10 was expressed in adenocarcinoma, undifferentiated, spindle and rhabdomyoblastic cells. Furthermore, rhabdomyoblastic cells were positive for desmin and myoglobin. Undifferentiated and spindle neoplastic cells were focally positive for ASMA and negative for h-caldesmon. Finally, our preliminary report suggests that MMMT of the fallopian tube may contain immature smooth muscle cells or cells with the myofibroblast-like immunohistochemical phenotype in the undifferentiated component.

Mantle cell lymphoma (MCL) comprises 2.5%-7% of all non-Hodgkin's lymphomas, and the gastrointestinal tract is involved in about 20% of cases. Multiple lymphomatous polyposis (MLP) is an uncommon disease that is regarded as the intestinal form of MCL. We present a rare case of gastrointestinal MCL without MLP, and demonstrate that rituximab was effective for the treatment of this patient. A 61-year-old man presented with continuous diarrhea and hematochezia for a period of 5 months. Superficial lymph nodes were not palpable, but both tonsilla were enlarged. The level of soluble interleukin (IL)2-receptor was 3480 U/ml (normal

Sertoli cell tumor of the testis (not otherwise specified) in a 43-year-old man is reported. Macroscopically, the testicular mass measured 3.0 x 2.3 x 1.5 cm and was well circumscribed. The cut surface was white to tan-gray in color. Neoplastic cells with eosinophilic cytoplasm proliferated with solid and tubular structures. Neoplastic cells focally contained vacuoles of various sizes in the cytoplasm. Cystic formation and cord formation in the hyalinized stroma was also observed. Immunohistochemically, neoplastic cells were positive for cytokeratin 8, chromogranin A and synaptophysin, but neoplastic cells were negative for placental alkaline phosphatase, inhibin-alpha and pancytokeratin. The stroma in the tumor center and capsule contained a significant number of myofibroblasts that were positive for alpha-smooth muscle actin and negative for h-caldesmon, but no CD34-positive stromal cells were detected in the stroma of the tumor center. Ultrastructurally, neoplastic cells had cytoplasmic processes and abundant rough endoplasmic reticulum and lipid droplets in the cytoplasm. However, dense core granules were absent. It is important to differentiate between Sertoli cell tumor and carcinoid tumor because of the positive reaction for neuroendocrine markers in both tumors. Myofibroblasts are a major stromal component of Sertoli cell tumor of the testis.

The purpose of this study is to report and describe the clinical and histopathologic findings in a patient with juvenile xanthogranuloma presenting as a relatively large, solitary, pedunculated mass on the left upper eyelid.A 31-month-old Japanese girl presented with a pedunculated nodular lesion that had been developing since 4 months earlier. Otherwise, no abnormal findings were identified in either eye. In addition, no other abnormalities, including skin eruptions or nodules, were detected anywhere. The lesion was completely excised and examined histopathologically.Microscopic study revealed a histiocytic proliferation accompanied by lymphocytes and occasional plasma cells and eosinophils within the dermis. A moderate number of giant cells of the foreign-body and Touton types were present. In the immunohistochemical analysis, the proliferative histiocytes and giant cells showed positive immunoreactivity for vimentin and macrophage markers and negativity for S-100 protein. The diagnosis of juvenile xanthogranuloma was made. The findings of further detailed ophthalmologic and systemic examinations and evaluations were unremarkable. Therefore, the diagnosis was made of juvenile xanthogranuloma, solitary type, occurring on the eyelid.Although juvenile xanthogranuloma of the eyelid is uncommon and its occurrence anywhere in the eye is rare, ophthalmologists should be familiar with this entity. Juvenile xanthogranuloma should be included in the differential diagnosis of eyelid mass lesions.

Background: Obesity, hypertriglyceridemia, and diabetes have been reported as frequent complications observed in patients with nonalcoholic steatohepatitis (NASH) in Western countries. The aim of this study was to investigate the genetic predisposition on NASH pathogenesis in the Japanese population. Methods: Genotypes of two previously described functional polymorphisms—β3-adrenergic receptor 190 T/A polymorphism, which results in Trp64Arg (W64R) amino acid replacement, and interleukin-1β-511 T/C polymorphism in the promoter sequence—were determined in 63 Japanese NASH patients and 100 healthy volunteers using polymerase chain reaction and restriction fragment length polymorphism. Results: β3-adrenergic receptor R allele frequency and the R/− (W/R and R/R) genotype frequency were significantly higher in NASH patients than those in control subjects. Interleukin-1β-511 T allele frequency and the T/T genotype frequency were significantly higher in NASH patients than those in control subjects. Obesity, hypertriglyceridemia, and hyperinsulinemia were associated with NASH patients with the R/− genotype, whereas an increase in fasting plasma glucose level and a decrease in insulinogenic index were associated with NASH patients with the W/W genotype. Conclusion: This study confirmed the contribution of obesity, glucose intolerance, and hypertriglyceridemia to NASH development in the Japanese population. In addition to these factors, genetic predispositions to obesity and inflammation in the Japanese population were shown to contribute much to the development of NASH.

A case of anal canal neuroendocrine carcinoma with Pagetoid intraepithelial extension is presented. An 80-year-old man was admitted to hospital with a complaint of pain in the anorectal region. Clinical examination revealed a hard and fixed mass in the anal canal, and subsequent biopsy of the lesion showed it to be a carcinoma. The surgically resected specimen showed a solid tumor measuring 3.4 x 3.2 cm within the area from the surgical anal canal to the anatomical anal canal. Tumor cells proliferated predominantly with compact nests. Many tumor cells had a high nuclear-to-cytoplasmic ratio, dispersed chromatin, and conspicuous nucleoli. Additionally, neoplastic cells focally formed a glandular structure. Some polygonal neoplastic cells were small with round nuclei. A rosette-like arrangement was also focally observed. In addition, tumor cells exhibited Pagetoid extension into the overlying epithelium of the histological anal canal. Both the underlying original neoplastic cells and the Pagetoid spreading tumor cells showed cytoplasmic granules positive for Grimelius staining and immunopositivity for carcinoembryonic antigen, synaptophysin and cytokeratins 7 and 20. These findings are highly suggestive of neuroendocrine differentiation of adenocarcinoma cells. To the best of our knowledge, this is the first case of anal canal neuroendocrine carcinoma with Pagetoid extension into the overlying epithelium of the histological anal canal.

Background/Aims The pathogenesis of non-alcoholic steatohepatitis (NASH) is poorly understood. The aim of this study was to examine genetic influences on NASH pathogenesis. Methods Blood samples from 63 patients with biopsy-proven NASH and 150 healthy controls were analyzed by the polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). Two functional polymorphisms were studied: the −493 G/T polymorphism in the promoter of microsomal triglyceride transfer protein (MTP) and the 1183 T/C polymorphism in the mitochondrial targeting sequence of manganese superoxide dismutase (MnSOD). Results NASH patients had a much higher incidence of the MTP gene G allele ( P =0.001) and of the G/G genotype ( P =0.002) compared to the controls. Fat occupied more area in liver lobules and the stage of NASH was advanced in patients with the G/G-genotype than in patients with G/T-genotype ( P =0.04). NASH patients also had a higher incidence of the MnSOD T/T genotype ( P =0.016). Conclusions The G allele in the MTP promoter leads to decreased MTP transcription, less export of triglyceride from hepatocytes, and greater intracellular triglyceride accumulation. The T allele in MnSOD mitochondrial targeting sequence leads to less transport of MnSOD to the mitochondria. Therefore, functional polymorphisms in MTP and MnSOD may be involved in determining susceptibility of NASH.

Low-grade tubular-mucinous renal neoplasm (LGTMRN) was recently established as a distinct carcinoma classification. A 70-year-old, female traffic accident victim underwent a detailed examination that disclosed a huge mass in the lower pole of the left kidney. The patient underwent a nephrectomy based on a diagnosis of renal tumor. Macroscopically, the tumor was well demarcated and a whitish color with focal hemorrhage. Histological examination showed that tumor cells proliferated through tubular, trabecular, and solid growth patterns in the mucinous background. Focally, foci of clear cells or the proliferation of spindle cells was also observed. Nuclei were generally round and uniform in size. No abnormal mitotic figures were identified. Immunohistochemically, tumor cells were diffusely positive for AE1/AE3, vimentin and chromogranin A, and focally positive for cytokeratin (CK) 18, CK19, Ulex europaeus agglutinin-1, epithelial membrane antigen, neuron-specific enolase (NSE), CD9 and CD57. Ultrastructurally, tumor cells contained a moderate number of mitochondria, rough endoplasmic reticulum and dense-core granules. No renin granules or glycogen were observed. Microvilli were focally seen. Our results render further evidence that LGTMRN is a distinct entity from the hitherto established renal neoplasms. Foci of clear cells and neuroendocrine differentiation should be added to the histological spectrum of LGTMRN.

In Drosophila, gustatory receptor neurons (GRNs) occur within hair-like structures called sensilla. Most taste sensilla house four GRNs, which have been named according to their preferred sensitivity to basic stimuli: water (W cell), sugars (S cell), salt at low concentration (L1 cell), and salt at high concentration (L2 cell). Labellar taste sensilla are classified into three types, l-, s-, and i-type, according to their length and location. Of these, l- and s-type labellar sensilla possess these four cells, but most i-type sensilla house only two GRNs. In i-type sensilla, we demonstrate here that the first GRN responds to sugar and to low concentrations of salt (10-50 mM NaCl). The second GRN detects a range of bitter compounds, among which strychnine is the most potent; and also to salt at high concentrations (over 400 mM NaCl). Neither type of GRN responds to water. The detection of feeding stimulants in i-type sensilla appears to be performed by one GRN with the combined properties of S+L1 cells, while the other GRN detects feeding inhibitors in a similar manner to bitter-sensitive L2 cells on the legs. These sensilla thus house two GRNs having an antagonistic effect on behavior, suggesting that the expression of taste receptors is segregated across them accordingly.