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The transcription factor capicua (CIC) regulates mammalian development and homeostasis. Growing evidence shows that CIC suppresses various human cancers by directly repressing the downstream cancer-related target genes. This study investigated the clinical and biologic significance of CIC expression in pancreatic cancer (PC). The study reviewed 132 patients with PC who underwent curative resection. The patients were divided into two groups according to CIC immunoreactivity score by immunohistochemistry, and the associations between CIC expression, clinicopathologic characteristics, and postoperative prognosis were investigated. Moreover, the influence of CIC expression on the malignant potential of PC cells was assessed with cell proliferation, motility assays, and use of quantitative real time-polymerase chain reaction and Western blot on the downstream target genes of CIC in knockdown experiments. The low-CIC expression group showed a higher proportion of lymphatic invasion (72.9% vs. 53.1%; p = 0.024), intrapancreatic neural invasion (94.1% vs. 81.3%; p = 0.021), and extrapancreatic plexus invasion (30.9% vs. 7.8%; p = 0.0006) than the high-CIC expression group as well as significantly worse overall survival (p = 0.0002) and recurrence-free survival (p = 0.0041) rates. Low CIC expression was an independent risk factor for poor prognosis (p = 0.038). Pancreatic cancer cells with knockdown CIC significantly enhanced cell motilities and cell cycle progression, promoted expression levels of ETV4 and MMP-9, and induced EMT. The study elucidated the association of low CIC expression with a poor prognosis for patients with PC and suggested that the CIC–ETV4–MMP-9 axis might control PC progression.

Background/Objectives: 8-Hydroxydeoxyguanosine (8-OHdG) is an indicator of oxidative stress and causes transversion mutations and carcinogenesis. 8-OHdG is excision repaired by 8-OHdG DNA glycosylase 1 (OGG1), which is classified as nuclear and mitochondrial subtypes. We aimed to clarify the role of OGG1 in pancreatic ductal adenocarcinoma (PDAC). Methods Ninety-two patients with PDAC who had undergone surgical resection at multiple institutions were immunohistochemically analyzed. The OGG1 and 8-OHdG expression levels were scored using the Germann Immunoreactive Score. The cutoff values of OGG1, as well as that of 8-OHdG, were determined. Results The low nuclear OGG1 expression group (n = 41) showed significantly higher carbohydrate antigen (CA)19–9 (p = 0.026), and higher s-pancreas antigen (SPAN)-1 (p = 0.017) than the high expression group (n = 51). Nuclear OGG1 expression has no effect on the prognosis. The low mitochondrial OGG1 expression group (n = 40) showed higher CA19-9 (p = 0.041), higher SPAN-1 (p = 0.032), and more histological perineural invasion (p = 0.037) than the high expression group (n = 52). The low mitochondrial OGG1 expression group had a significantly shorter recurrence-free survival (p = 0.0080) and overall survival (p = 0.0073) rates. The Cox proportional hazards model revealed that low mitochondrial OGG1 expression is an independent risk factor of the PDAC prognosis. OGG1 expression was negatively correlated with 8-OHdG expression (p = 0.0004), and high 8-OHdG expression shortened the recurrence-free survival of patients with PDAC. Conclusions Low mitochondrial OGG1 expression might aggravate the PDAC prognosis.

Papillary renal neoplasm with reverse polarity (PRNRP) is a recently proposed entity of renal tumor. It shows a far better prognosis than papillary renal cell carcinoma (PRCC) and frequently has KRAS missense mutation. In this study, we compared 14 cases of PRNRP and 10 cases of PRCC type 1 (PRCC1) and type 2 (PRCC2) from clinical, morphological, immunohistochemical, and molecular biological perspectives. We subjected all PRNRP and PRCC cases to immunohistochemical analysis. Whole-exome sequencing using next-generation sequencing (NGS) was performed for six cases of PRNRP, three cases of PRCC1, and four cases of PRCC2. A search for KRAS gene mutation in the remaining eight cases of PRNRP was performed by polymerase chain reaction (PCR) sequencing. The results showed that all cases of PRNRP were pT1N0M0, none of which followed a course of recurrence or tumor-related death. Immunohistochemical analysis revealed diffuse staining of CK7, EMA, PAX8, and GATA3 but weak or negative staining of CD10, CD15, and AMACR in PRNRP. By NGS and PCR, KRAS missense mutation was detected in 11 of 14 PRNRP cases, although pathogenic KRAS mutation was not observed in PRCC1 and PRCC2. NGS analysis revealed less tumor mutation burden in PRNRP than in PRCC. PRNRP also showed no specific chromosomal copy number abnormalities, including gains of 7 and 17. In conclusion, we propose that PRNRP is a distinct condition from PRCC.

Background Colorectal T/natural killer (NK)-cell lymphomas (TNKCL) are very rare. Endoscopic and clinicopathological characteristics of colorectal TNKCL have not been clearly demonstrated. In this study, we demonstrated the clinical characteristics of colorectal TNKCL. Methods Endoscopic and clinicopathological characteristics were investigated in 27 patients with colorectal monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL), adult T-cell leukemia/lymphoma (ATLL), and other types of TNKCL. Results Nine TNKCL patients (33%) were classified as MEITL, 11 (41%) as ATLL, and seven (26%) as other. Four patients with Epstein-Barr Virus-positive (EBV+) TNKCL, two indolent T-cell lymphoproliferative disorder and one anaplastic large cell lymphoma were included in the other group. Endoscopically, six MEITL (67%) and five ATLL (46%) showed diffuse-infiltrating type, in which the main endoscopic lesion was edematous mucosa in MEITL, while aphthoid erosion and edematous mucosa were typical in ATLL. Ulcerative type was identified in four other group patients (57%), including two EBV+ TNKCL. An increase in atypical T-intraepithelial lymphocytes (T-IELs) was noted in seven MEITL (88%) and six ATLL (60%) patients, but not in the other group (0%) patients. Five MEITL patients (56%) showed features of lymphocytic proctocolitis with increased CD8+ T-IELs. Conclusions MEITL and ATLL occasionally invaded the colorectum, and primary involving MEITL was observed. Diffuse infiltrating type was the characteristic endoscopic finding in colorectal MEITL and ATLL, while ulcerative type was observed in the other group. Features of lymphocytic proctocolitis may be prodromal findings of MEITL.

Small cell carcinoma in the ureter is extremely rare, with few cases reported in the literature. The current report describes the case of a 63-year-old man who presented with right-side back pain. A mass was identified in the right ureter. A nephroureterectomy was performed. Subsequent microscopic examination revealed that the mass comprised a monotonous population of small cells and that the carcinoma cells were positive for cluster of AE1/AE3 and synaptophysin. The tumor was diagnosed as a ureteral small cell carcinoma. Adjuvant chemotherapy was administered with 80 mg/m2 intravenous cisplatin on day 1 and 100 mg/m2 etoposide on days 1–3, every 21 days for 2 cycles. The patient has remained disease-free 6 months after surgery. Keywords: Small cell carcinoma, Ureteral cancer

Background and study aims The presence of white opaque substance (WOS) is an endoscopic marker of intestinal metaplasia. Considering that the nature of WOS is absorbed lipid droplets, lipase plays an important role in the lipid absorption process and is inactivated at strong acidity. WOS may only be present in a hypochlorhydria state following Helicobacter pylori infection, and, thus, may not be highly sensitive marker, especially in H. pylori-eradicated patients. We investigated the relationship between WOS and gastric acid conditions. Patients and methods A total of 501 patients were retrospectively evaluated for the presence of WOS at 2 regions of interest using magnifying narrow-band imaging. The pH level of collected gastric juice was also measured. Study end points were (1) prevalence of WOS and its relationship with gastric juice pH in 3 groups: H. pylori-uninfected, H. pylori-infected, and H. pylori-eradicated; (2) the relationship between prevalence of WOS and gastric juice pH before and after proton pump inhibitor (PPI) administration in 29 H. pylori-eradicated cases. Results Prevalence of WOS was 0 % (0 /206), 28.4 % (31/109), and 3.2 % (6/186) in the H. pylori-uninfected, H. pylori-infected, and H. pylori-eradicated groups, respectively. Mean gastric juice pH was significantly higher in WOS-positive cases than in WOS-negative cases in the H. pylori-infected and H. pylori-eradicated groups (P Conclusion The prevalence of WOS is closely associated with the neutralization of intragastric pH.

To reveal the prevalence of small (≤ 20 mm) pancreatic ductal carcinomas with enhanced rims on triple-phase contrast-enhanced CT and correlate the CT images with the pathologic findings. Between April 2005 and April 2016, 45 patients underwent preoperative triple-phase contrast-enhanced CT and were pathologically diagnosed with small pancreatic ductal carcinoma. CT images were independently reviewed by two radiologists. The attenuation values of the enhanced rims, internal areas of the tumors, and surrounding pancreatic parenchyma were compared using Mann–Whitney U test. These areas were also correlated with the pathologic findings. Tumor invasiveness was compared between the tumors with and without enhanced rims using Fisher’s exact test. Enhanced rims were identified in 18 tumors (40%) by consensus between the two reviewers. The enhanced rims showed significantly higher mean attenuation values compared with the internal areas of the tumors (p

The pathophysiology of bladder leiomyosarcoma, a rare disease with aggressive mesenchymal tumor, is not certain, but its main symptoms are hematuria, dysuria and abdominal pain. Cases described in the literature are few. This report describes a case of a leiomyosarcoma of the urinary bladder in a 49-year-old woman. After CT scanning revealed a heterogeneously enhanced 4-cm mass involving the bladder neck and anterior wall, further examinations detected no metastatic lesion. Cystoscopy and transurethral resection of bladder tumor (TURBT) were performed. The histopathological diagnosis was leiomyosarcoma. Postoperative period was uneventful. The patient experienced complete resolution of urologic symptoms. Repeat-TURBT was performed 70 days after first surgery. The patient has remained disease-free 18 months after surgery. Keywords: Leiomyosarcoma, Nonurothelial bladder tumor, TURBT

Background and study aims White opaque substance (WOS) in gastric epithelial neoplasia is helpful for qualitative diagnosis of neoplasia. We hypothesized that WOS of neoplasia is strongly influenced by acid recovery after Helicobacter pylori eradication, similar to that of gastric intestinal metaplasia. The aim of this study was to investigate whether antacids increase the appearance of the WOS in H. pylori-eradicated neoplasia. Patients and methods A total of 38 gastric epithelial neoplasias (12 adenomas and 26 adenocarcinomas) detected after H. pylori eradication were retrospectively evaluated. Presence or absence of WOS was evaluated by magnifying endoscopy with narrow band imaging before and after antacid administration. The pH of collected gastric juice was also measured. Study endpoints were (1) prevalence of WOS in the neoplasia before and after antacid administration, and the histological difference (adenoma and adenocarcinoma); and (2) relationship between the prevalence of WOS and gastric juice pH. Results WOS prevalence increased from 0 % (0/38) to 44.8% (17/38) after antacid administration. WOS prevalence in adenomas was more significantly increased compared to that in adenocarcinomas (83.3 % vs 26.9 %, P = 0.0077). Prevalence of WOS in gastric neoplasias was only observed at neutral levels of gastric juice pH, and WOS was not observed at strong acidic levels. Conclusions Antacid administration may increase the appearance of WOS in gastric epithelial neoplasia (especially adenomas) detected after H. pylori eradication with acid recovery.

Periportal low attenuation (PPLA) associated with metastatic liver cancer is occasionally seen on multi-detector-row CT (MDCT). The purpose of this study was to investigate the MDCT patterns of the PPLA and to correlate it with pathological findings. We retrospectively reviewed the MDCT images of 63 patients with metastatic liver cancers from colorectal adenocarcinoma. On MDCT scans, PPLA associated with liver metastasis was visualized in six patients with colorectal cancer. In these six patients who had undergone surgical resection, the radiologic-pathologic correlation was analyzed. All patients underwent a single contrast-enhanced MDCT within 1 month before surgical resection. The six liver cancers were pathologically proven to be moderately differentiated adenocarcinoma. We assessed the PPLA on MDCT concerning the distribution patterns and contrast enhancement with pathological correlation. In five of the patients, the PPLA extended to the hilar side from metastatic liver cancer. Pathologically, there was no cancer invasion into the intra-hepatic periportal area; however, massive lymphedema and fibrosis occurred in all six cases. PPLA on the hilar and peripheral sides of hepatic metastasis from colorectal cancer may be present suggesting lymphedema and fibrosis of portal tracts not always indicating cancer infiltration.

A 62-year-old man with epigastralgia was referred to our hospital for the evaluation of an intractable duodenal ulcer, which did not improve following proton pump inhibitor treatment. An upper gastrointestinal endoscopy revealed that the base of the ulcer was gray-white in color with conspicuous fibrosis tissue, unlike the appearance of common ulcers. A contrast-enhanced abdominal CT scan and angiography revealed tortuous and dilated vascular structures in the pancreatic head. This was diagnosed as a pancreatic arteriovenous malformation. We suggest that the intractable duodenal ulcer was caused by the pancreatic arteriovenous malformation. Therefore, we performed a pancreaticoduodenectomy. Pancreatic arteriovenous malformations should be considered as one of the causes of treatment-resistant duodenal ulcers.

An odontogenic myxoma occurring in the mandible of a 54-year-old Japanese male is described; this contained unusual osteocement-like spherules, which are rarely reported. The radiological examination revealed a multilocular lesion with mixed radiolucent–radiopaque content. We performed a segmental mandibulectomy, and reconstructed the mandible using a titanium plate and iliac bone. Histopathologically, the tumor was composed mainly of myxomatous stroma in which a few stellate and spindle-shaped cells were suspended. A few odontogenic epithelial nests were also observed. In addition, there were osteocement-like spherules, showing concentric lamination. The presence of these osteocement-like structures has only been reported in three previous cases.

Background and Aim White opaque substance (WOS) in gastric neoplasias is a unique finding visualized in magnifying endoscopy (ME) with narrow band imaging (NBI) and it represents intramucosal accumulation of lipid droplets using oil red O staining. Methods Subjects were 26 WOS-positive (13 adenomas and 13 well-differentiated adenocarcinomas) and 27 WOS-negative gastric epithelial neoplasias. We carried out immunohistochemical staining using a monoclonal antibody specific for adipophilin as a marker of lipids. Immunoelectron microscopy was used to evaluate morphology of the lipid droplets. Results Adipophilin was detected in 24 of 25 (96.0%) WOS-positive neoplasias, but it was detected in only two of 27 (7.4%) WOS-negative neoplasias. Lipid droplets were only seen in the surface epithelium in 10 of 11 (91.1%) adenomas, whereas the lipid droplets also existed in the cryptal epithelium in seven of 13 (53.8%) adenocarcinomas. Immunoelectron microscopy revealed numerous lipid droplets mainly existing in the subnuclear cytoplasm of the epithelium. The shape of the lipid droplets in adenomas was round and uniform, whereas that in adenocarcinomas was irregular. Conclusions The present study confirmed that the presence of WOS in gastric neoplasias was dependent upon intramucosal accumulation of lipid droplets using anti-adipophilin staining. Intraepithelial distribution and morphology of the lipid droplets differed between adenoma and adenocarcinoma.

Background and study aims: The authors previously reported that the white opaque substance (WOS) in gastric epithelial neoplasia was caused by accumulation of lipid droplets by immunohistochemical and immunoelectron microscopic studies of adipophilin, which was recently identified and validated as a marker of lipid droplets. The aim of the current study was to investigate the characteristics of the histologic differentiation and mucin phenotype in WOS-positive gastric epithelial neoplasias. Patients and methods: A total of 130 gastric epithelial neoplasias (45 adenomas and 85 early adenocarcinomas) from 120 patients were retrospectively evaluated. The presence or absence of WOS was evaluated by M-NBI. Lipids were examined by immunohistochemical staining for adipophilin. Tissue phenotypes were immunohistochemically classified as intestinal (I), gastrointestinal (GI), and gastric (G) using antibodies against CD10, MUC2, MUC5AC and MUC6. The histologic differentiation and mucin phenotype of WOS-positive neoplasias were characterized and examined according to adipophilin expression. Results: The presence of WOS by M-NBI was correlated with histologic differences between adenoma or differentiated type adenocarcinoma and mixed type or undifferentiated type adenocarcinoma (P = 0.0153). Adipophilin was only expressed in primary adenoma and well to moderately differentiated adenocarcinoma components but not in undifferentiated components. WOS and adipophilin expression were only observed in neoplasias with I or GI phenotypes, but not in those with the G phenotype (P

The patient was a 67-year-old man with a 39-mm unilocular pancreatic tumor detected by computed tomography (CT). Further examinations with contrast-enhanced CT, magnetic resonance imaging, endoscopic ultrasonography, and endoscopic retrograde cholangiopancreatography revealed an internal heterogeneous structure attributed to bleeding or necrosis. Consequently, we expected either a pancreatic neuroendocrine tumor or a solid pseudopapillary neoplasm and performed pancreaticoduodenectomy. Pathological examination showed that the tumor had a denatured structure with evidence of internal bleeding and cubic epithelial cysts of various sizes. The final diagnosis was a macrocystic-type serous cystic neoplasm.

A 78-year-old Japanese man with undifferentiated carcinoma of the common bile duct is presented. Upon gross examination, the common bile duct was found to be obstructed by a nodule measuring 10 x 10 mm. Microscopically, the nodule was ill-defined and composed of atypical spindle-shaped and pleomorphic tumor cells. The spindle-shaped cells proliferated in a whirled or interlacing pattern simulating a sarcoma, and the pleomorphic tumor cells had abundant eosinophilic cytoplasm and bizarre nuclei. Histochemically, a few tumor cells contained mucosubstances stained with the alcian blue (AB) method in their cytoplasm. Immunohistochemically, the tumor cells were diffusely positive for CAM5.2 and AE1/AE3. The histological diagnosis was undifferentiated carcinoma (spindle cell carcinoma) of the common bile duct. Other than our patient, only four other cases of undifferentiated carcinoma in the extrahepatic bile duct have been reported in the literature.

We describe here a rare case of hepatoid adenocarcinoma (HAC) of the gallbladder without the production of alpha-fetoprotein (AFP). A 77-year-old man was referred to our division with complaints of general fatigue, loss of appetite, and loss of body weight. A preoperative diagnosis of advanced gallbladder cancer was made, and cholecystectomy with combined resection of two liver subsegments (S4a + S5) and lymph node dissection were performed. Microscopically, the tumor was mainly composed of characteristic cells featuring eosinophilic cytoplasm, enlarged nuclei, and prominent nucleoi, arranged in nests or proliferated in a trabecular pattern. These features were highly suggestive of HAC of the gallbladder, and the tumor cells were negative for AFP immunohistochemical staining. The patient is doing well and has survived for 15 months postoperatively without any recurrence.

A 63-year-old man with a combination of early pancreatic carcinoma and an intraductal papillary adenoma was reported. A pancreatic cyst was detected by chance at the head of the pancreas by computed tomography for a follow-up study of early rectal carcinoma previously operated. Detailed studies by endoscopic retrograde pancreatography (ERP) showed irregular narrowing of the main pancreatic duct at the pancreatic body and magnetic resonance cholangiopancreatography (MRCP) revealed dilatation of ductal branches draining there. Brushing cytology of the pancreatic duct demonstrated cancer cells and total pancreatectomy was performed. Stepwise histo-pathological examinations of the specimen showed two foci of invasive carcinoma in the neck and body and multiple foci of severe dysplasia, some of which contained carcinoma in situ, in the body of the pancreas. The cystic tumor in the head of the pancreas was an intraductal papillary adenoma. In this case, the scrutiny of a pancreatic cyst including MRCP and ERP led to an early diagnosis of pancreatic cancer. Dilatation of ductal branches depicted by MRCP might be a new hint for early diagnosis of pancreatic carcinoma.

To assess of the grade of malignancy of intraductal papillary neoplasm of the pancreas (IPNP).Retrospective analysis.University hospital, Japan.8 men and 9 women, mean age 67 years, with IPNP.12 lesions were in the head of the pancreas, two in the body and three in the tail. There were no differences in the age and sex of the patients, the presence of diabetes mellitus or history of pancreatitis, serum concentrations of carcinoembryonic antigen, and CA 19-9, pancreatic function test, and the site of origin of benign and malignant IPNP. The mean diameter of the main pancreatic duct was 16 mm in the four malignant tumours, but 6 mm in the 13 benign IPNP (p0.05). 10 of the 13 benign IPNP were located in the branch duct, two in the main pancreatic duct, and another in both the main and branch ducts, while all four malignant IPNP were situated in the main duct (p0.01). Mural nodules were detectable preoperatively in all four malignant IPNP but in only 5 of the 13 benign tumours (39%). The mean diameter of the mural nodules in the five benign IPNPs was 3 mm, whereas that in the four malignant ones was 24 mm (p0.01). All but one patient (who had a malignant IPNP) were alive for one to 36 months (mean 16 months) after resection.IPNP is a unique variant of pancreatic exocrine neoplasm with a good prognosis after resection. The diameter of the main pancreatic duct, size of the mural nodule, and site of the tumour (main pancreatic duct or branch duct) differ significantly between benign and malignant tumours.

同時性に多発した大腸原発のT細胞性悪性リンパ腫を経験した. 症例は89歳の男性, 主訴は下痢. 注腸造影検査, 大腸内視鏡検査にて, S状結腸, 直腸に潰瘍性病変を認め, 同部よりの生検にて上記と診断された. 手術待機中にS状結腸腫瘍部が穿孔をきたし, 緊急手術を施行した. 切除標本では大小の病変が多発し小腸にも病変を認めた. 本症例は術後も血性水様便が持続し, 貧血, 低蛋白血症が進行して71日目に死亡したが, 残存腸管にもT細胞性悪性リンパ腫が多発していることが推察された. 本疾患はまれで, 本邦では16例の報告がみられたが, B細胞性悪性リンパ腫と比べ予後は極端に悪く, 注意すべき疾患であると考えられた.

A case of mucin hypersecreting invasive carcinoma of the pancreas penetrating into the stomach and duodenum in a 56-year-old Japanese man is reported. The patient survive for more than five years after a complete resection. It has been reported that the clinical course of patients with non-invasive mucin hypersecreting carcinoma of the pancreas is favorable, whereas that with invasive mucin hypersecreting carcinoma of the pancreas is as dismal as usual pancreatic carcinomas. In this case report, we recommend a complete resection even for invasive mucin hypersecreting carcinoma of the pancreas that can provide a long survival.

Twenty-six Japanese cases of type II enteropathy-associated T-cell lymphoma (EATL) were examined. Multiple tumors throughout the small intestine were found in 15 patients (58%) and duodenal and colonic mucosal lesions in 8 and 6 cases, respectively. Histologically, intramucosal tumor spread and a zone of neoplastic intraepithelial lymphocytes (IELs) neighboring the main transmural tumors were detected in 20 (91%) and 17 (77%) of the 22 cases examined, respectively. Inside and outside the IEL zone, some degree of enteropathy with many reactive small IELs and villous atrophy was detected in 11 cases (50%). Immunohistologically, many CD56/CD8-positive small IELs were found in the enteropathic lesions of 4 (36%) and 7 (64%) of these 11 cases. Lymphoma cells expressed tyrosine kinase receptor c-Met, serial phosphorylated (p)-mitogen-activated protein kinase/extracellular signal-regulated kinase, c-Myc, and Bcl2 in 18 (78%), 21 (91%), 11 (42%), and 19 (73%) of the total cases, respectively. By fluorescence in situ hybridization, chromosomal loci 7q31 (c-Met) and 8q24 (c-Myc) were amplified in 11 (65%) and 12 (71%) of the 17 cases analyzed. Gain of 7q31 and c-Met expression were significantly (P.01) higher than in peripheral CD8-positive T-cell or CD56-positive natural killer-cell lymphomas. Enteropathy was seen near the IEL zone in type II EATL, and activation of the c-Met, mitogen-activated protein kinase/extracellular signal-regulated kinase-mitogen-activated protein kinase pathway, and c-Myc-Bcl2-mediated cell survival may play important roles in lymphomagenesis, converting enteropathy to type II EATL. Seven cases in the early clinical stages I and II-1 showed significantly (P.01) better prognoses than did those in the advanced stages. Early detection of the mucosal lesions and tumors may improve patient prognosis.

Gastric fundic gland polyps (FGPs) are common non-adenomatous gastric polyps arising from normal fundic mucosa without Helicobacter pylori (H. pylori) infection. Although systemic FGPs associated with familial adenomatous polyposis (FAP) often have dysplasia, there are few reports of dysplasia occurring in sporadic FGPs, especially when detected by magnifying endoscopy with narrow band imaging (ME-NBI). We experienced two cases of adenocarcinoma occurring in sporadic FGPs, and their ME-NBI findings were very useful for differentiating FGP with cancer from non-dysplastic FGP. A 68-year-old man and a 63-year-old woman were referred to our institution for medical checkup. H. pylori was negative in both patients. Endoscopic examination revealed a small reddish polypoid lesion on the anterior wall of the upper gastric body and several FGPs. ME-NBI showed an irregular microvascular architecture composed of closed loop- or open loop-type vascular components, plus an irregular microsurface structure composed of oval-type surface components which was different from that of FGPs. FAP was denied because of the absence of colon polyps and no familial history of FAP. Pathological diagnosis was adenocarcinoma occurring in sporadic FGP.

White opaque substance (WOS) in gastric neoplasias is a unique finding visualized in magnifying endoscopy (ME) with narrow band imaging (NBI) and it represents intramucosal accumulation of lipid droplets using oil red O staining.Subjects were 26 WOS-positive (13 adenomas and 13 well-differentiated adenocarcinomas) and 27 WOS-negative gastric epithelial neoplasias. We carried out immunohistochemical staining using a monoclonal antibody specific for adipophilin as a marker of lipids. Immunoelectron microscopy was used to evaluate morphology of the lipid droplets.Adipophilin was detected in 24 of 25 (96.0%) WOS-positive neoplasias, but it was detected in only two of 27 (7.4%) WOS-negative neoplasias. Lipid droplets were only seen in the surface epithelium in 10 of 11 (91.1%) adenomas, whereas the lipid droplets also existed in the cryptal epithelium in seven of 13 (53.8%) adenocarcinomas. Immunoelectron microscopy revealed numerous lipid droplets mainly existing in the subnuclear cytoplasm of the epithelium. The shape of the lipid droplets in adenomas was round and uniform, whereas that in adenocarcinomas was irregular.The present study confirmed that the presence of WOS in gastric neoplasias was dependent upon intramucosal accumulation of lipid droplets using anti-adipophilin staining. Intraepithelial distribution and morphology of the lipid droplets differed between adenoma and adenocarcinoma.

To assess the utility of axial and coronal reformatted multidetector computed tomographic (CT) images in the evaluation of the invasion of posterior hepatic plexuses by extrahepatic bile duct cancer.This retrospective study was approved by the institutional review board, and informed consent was waived. Forty-three patients (22 men, 21 women; age range, 40-80 years; mean age, 65 years) with surgically resected cancer involving the extrahepatic bile duct between December 2004 and September 2010 were included. Posterior hepatic plexus 1 runs from the superior and middle bile duct to the right celiac ganglion, and posterior hepatic plexus 2 runs between the lower bile duct and right celiac ganglion behind the portal vein. Invasion of the posterior hepatic plexuses was elucidated by using pathologic and postoperative multidetector CT findings. Three radiologists independently evaluated the preoperative axial and coronal reformatted images with a separate viewing session for the invasion of posterior hepatic plexuses that was detected on the basis of the presence of increased attenuation of fat tissue along the nerve routes. Receiver operating characteristic analysis was performed to compare the diagnostic performance of the two image interpretations.Invasion of posterior hepatic plexus 1 and of posterior hepatic plexus 2 was recognized in 10 (23%) and nine (21%) of 43 patients, respectively. The diagnostic performance of coronal reformatted image interpretation was significantly greater than that for axial image interpretation (mean area under the curve, 0.99 vs 0.89, P = .04; mean accuracy, 95% vs 82%, P = .003). In all reviewers, one false-positive diagnosis of the invasion of posterior hepatic plexus occurred on axial and/or coronal image display types because of fibrosis and inflammatory cell infiltration along these plexus routes.Coronal reformatted images can be useful for accurate diagnosis of the invasion of posterior hepatic plexuses and may facilitate surgical decision making in regard to the resection of celiac ganglion.

In pancreatic body and tail carcinoma, “peripancreatic strands appearance” is frequently seen on multidetector CT (MDCT). The purpose of this study was to clarify the pathological and clinical implications of peripancreatic strands appearance. We retrospectively evaluated MDCT images in 17 patients with pancreatic body and tail carcinoma who underwent surgical resection. Peripancreatic strands appearance was defined as the strands structure deriving from the primary lesion and associated with increased CT attenuation of surrounding adipose tissues. All CT examinations were performed by contrast-enhanced MDCT with a multiplanar reformation technique. Peripancreatic strands appearance was detected on MDCT in 13 (76%) patients. The maximum width of the peripancreatic strands seen on MDCT was 1.55 ± 0.36 mm (range, 1.0–2.5 mm). This CT finding was well correlated with extrapancreatic carcinoma invasion with marked fibrotic thickening of adipose tissue septa, including microvessels. This pathological finding was confirmed in all 13 patients with positive CT finding whereas it was not confirmed in the 4 patients with negative CT finding. Peripancreatic strands appearance on MDCT in pancreatic body and tail carcinoma reflects extrapancreatic carcinoma invasion with marked fibrotic thickening of adipose tissue septa. This CT finding would indicate the property of carcinoma aggressiveness.

A 46-year-old man was admitted to our hospital for further evaluation of a hypoechogenic mass in the pancreatic body. He had no history of hypertension, pancreatitis, abdominal trauma, or portal hypertension. He had no abdominal symptoms. A contrast-enhanced CT scan demonstrated a hypodense, round shaped mass. EUS and MRI also showed it to be a pancreatic mass. Because of the tumor size of more than 30mm and the possibility of malignancy, distal pancreatectomy was performed. Microscopic findings showed the mass was the dissection of the proximal splenic artery. The true lumen of the dissecting aneurysm was occluded and the false lumen developed fusiform dilatation. Moreover, microscopic findings revealed the rupture of the false lumen complicated by pseudoaneurysm. We finally diagnosed the lesion simulating a pancreatic tumor as the pseudoaneurysm of the splenic artery.

Takeshita M, Nakamura S, Kikuma K, Nakayama Y, Nimura S, Yao T, Urabe S, Ogawara S, Yonemasu H, Matsushita Y, Karube K & Iwashita A (2011) Histopathology58, 395–407 Pathological and immunohistological findings and genetic aberrations of intestinal enteropathy-associated T cell lymphoma in Japan Aims: To elucidate the clinicopathological findings of primary intestinal enteropathy-associated T cell lymphoma (EATL) in Japan, a non-endemic area for coeliac disease. Methods and results: Of the 24 cases, four (17%) had large-cell lymphoma (type I), and the remaining 20 (83%) had medium-sized lymphoma (type II). Lymphoma cells of the three type I cases were CD56-positive. Only one (4%) case showed typical CD56- and CD8-negative and CD30-positive type I EATL. In type II EATL, lymphoma cells of the 16 (80%) and 11 (55%) cases were positive for CD56 and CD8, respectively. Intramucosal tumour spreading and adjacent enteropathy-like lesions were detected in 15 (71%) and 16 (76%) of 21 cases, with a severe increase of intraepithelial lymphocytes (IELs) in 12 (57%). IELs of enteropathy-like lesions in five (24%) cases expressed T-bet, with no cases of CD30-positive IELs. Characteristic findings from comparative genomic hybridization of 15 cases indicated gains of 8q2 (47%), Xp (53%) and Xq (73%), but no gain of 9q3. Regarding, human leucocyte antigen (HLA) status, six cases examined did not express the DQB1*02 allele. Conclusions: Japanese EATL exhibited different histology, cytogenetic findings and HLA status from those of typical type I EATL. The rare incidence of coeliac disease may influence the tumour cell characteristics of EATL and IELs.

Basaloid squamous cell carcinoma is a rare aggressive malignancy that is a distinct variant of squamous cell carcinoma. This report presents 2 cases of basaloid squamous cell carcinoma in the gingiva. Case 1 is a 55-year-old Japanese man who presented with a painful, red, and irregular mass on the left mandibular gingiva. Case 2 is a 65-year-old Japanese man who presented with a painless mass on the right mandibular gingiva. Both tumors were diagnosed histopathologically as basaloid squamous cell carcinoma. In case 1, the patient underwent wide resection of the gingival tumor with a partial mandibulectomy and ipsilateral functional neck dissection. The mandible was reconstructed with a titanium plate and forearm flap. In case 2, the patient underwent wide resection of the gingival tumor after local irradiation (60 Gy). At the time of writing, both patients remained in good health and free of disease.

Benign cementoblastoma, first described by Dewey in 1927, 1 is an odontogenic tumor of mesenchymal origin characterized by proliferation of the cellular cementum. 2 It is a rare odontogenic tumor 3 that almost always occurs in the premolar or molar region and more commonly in the mandible than in the maxilla. 2,4-8 We present an unusual case of benign cementoblastoma in the anterior maxilla.

Gallbladder carcinoma (GC) is a relatively uncommon malignancy and is often caused by diagnostic difficulties in distinguishing the extension of carcinoma in situ (CIS) from invasive carcinoma along Rokitansky-Aschoff sinuses (RAS). The laminin-5, a heterotrimer, is composed of alpha-3, beta-3 and gamma-2 chains. The gamma-2 chain is expressed in various invasive carcinoma cells. There are numerous reports that have described that laminin-5-gamma-2 is associated with tissue invasion in many organs. However, few studies are found in gallbladder carcinoma. To clarify the relationship between laminin-5-gamma-2 chain (LN-5) expression and the development of GCs, we performed an immunohistochemical study of 93 GCs. Cases were classified into three groups: CIS with/without the extension along RAS (Group A; n=17), carcinoma invading mucosa or muscular layer (Group B; n=5) and carcinoma invading beyond perimuscular connective tissue (Group C; n=71). The immunohistochemical intracytoplasmic expression was detected in the invasive fronts of the tumor. In the invasive components of Group B and C, LN-5 was expressed in 100 and 97% of cases, respectively, whereas in the CIS lesions of GCs, expression was not observed in Group A. LN-5 expression in the GCs tended to increase as tumors developed, which may be an indicator of the potential invasiveness of the tumor. Our results indicate that, in GCs, a strong intracytoplasmic expression of LN-5 was identified in the cancer cells whether in situ they extend along RAS or invading stroma.

Gallbladder carcinoma (GC) is a relatively uncommon malignancy and is often caused by diagnostic difficulties in distinguishing the extension of carcinoma in situ (CIS) from invasive carcinoma along Rokitansky-Aschoff sinuses (RAS). The laminin-5, a heterotrimer, is composed of alpha-3, beta-3 and gamma-2 chains. The gamma-2 chain is expressed in various invasive carcinoma cells. There are numerous reports that have described that laminin-5-gamma-2 is associated with tissue invasion in many organs. However, few studies are found in gallbladder carcinoma. To clarify the relationship between laminin-5-gamma-2 chain (LN-5) expression and the development of GCs, we performed an immunohistochemical study of 93 GCs. Cases were classified into three groups: CIS with/without the extension along RAS (Group A; n=17), carcinoma invading mucosa or muscular layer (Group B; n=5) and carcinoma invading beyond perimuscular connective tissue (Group C; n=71). The immunohistochemical intracytoplasmic expression was detected in the invasive fronts of the tumor. In the invasive components of Group B and C, LN-5 was expressed in 100 and 97% of cases, respectively, whereas in the CIS lesions of GCs, expression was not observed in Group A. LN-5 expression in the GCs tended to increase as tumors developed, which may be an indicator of the potential invasiveness of the tumor. Our results indicate that, in GCs, a strong intracytoplasmic expression of LN-5 was identified in the cancer cells whether in situ they extend along RAS or invading stroma.

Background: A proper understanding of prostatic and periprostatic anatomy is essential for surgical procedures and pathological diagnosis; however, the detailed features have not been commonly investigated and completely understood. Methods: Seventy-nine non-nerve-sparing radical prostatectomy specimens were microscopically investigated for Denonvilliers’ fascia, lateral pelvic fascia, prostatic capsule, anterior fibromuscular stroma and the neurovascular bundle. Results:Atthelateralaspect,thelateralpelvicfasciaandtheprostaticcapsulewereseparatedby adipose tissue in 41 cases (52%), whereas they adhered in 38 cases (48%). In only 41 cases (52%), the neurovascular bundle existed locally at the postero-lateral region with definite‘bundle’ formations. Denonvilliers’ fascia and the prostatic capsule adhered tightly at the center of the posterior aspect in 77 cases (97%). A smooth transition from the prostatic capsule to the anterior fibromuscular stroma was observed in all cases. In 70 cases (89%), no prostatic capsule was independentlyrecognizedattheanterioraspect.Intheremaining9cases(11%),thecapsulewas recognizable as distinct from the anterior fibromuscular stroma. In 67 cases (85%), the lateral pelvic fascia connected and fused with the anterior fibromuscular stroma, and covered the outermost regions of the lateral and anterior surfaces. Conclusions: All the periprostatic structures are closely related and influence each other. The results support the rationale of anatomical radical prostatectomy, and should be taken into consideration for surgical procedures and pathological diagnosis.

The new histopathological classification of exocrine pancreatic tumors by the World Health Organization, now includes "ovarian-type stroma" ("OS") in the definition of mucinous cystic tumor of the pancreas (MCT-P). This study investigated the clinicopathological findings of the MCT-P according to WHO classification and scrutinize the function of "OS" in MCT-P immunohistochemically. Thirty-four cases of MCT-P (28 adenomas, 2 borderline tumors and 4 adenocarcinomas) were examined clinicopathologically. The "OS" of 34 MCTs-P were studied immunohistochemically and compared with the stroma of 10 mucinous cystic tumors of the ovary (MCTs-O), 10 conventional pancreatic carcinomas and 6 normal ovaries. Almost all 34 MCTs-P were located in the body-tail of the pancreas of middle-aged women. Histologically the "OS" cells exhibited luteinization in 11/34 (32.4%). Immunohistochemically, both "OS" cells and the stromal cells in MCT-O showed similar positivity rates; calponin (34/34 and 9/10), h-caldesmon (28/34 and 8/10), alpha-inhibin (29/34 and 9/10), estrogen-receptor (21/34 and 6/10) and progesterone-receptor (28/34 and 9/10, respectively). Some neoplastic epithelial cells of MCT-P were positive for human chorionic gonadotropin (hCG) (21/34, 61.8%). This study indicates the predominance of MCT in the distal pancreas of middle-aged women. Furthermore, the immunohistochemical and histological results demonstrate that the "OS" of MCT-P and the stroma of MCT-O share the same characteristics. The results also suggested that the hCG produced by the neoplastic epithelium probably plays an important role in the luteinization of the stroma of MCT-P. We therefore conclude there is a possibility that MCT-P originates from the left remnant primordial gonadal cells which migrated to the pancreatic anlage during the early development of the fetus.

The alterations of the chromatin structure by histone acetylases (HATs) and histone deacetylases (HDACs) are implicated in the regulation of gene transcription and also in the process of carcinogenesis. HDAC inhibitors have been shown to be potent inducers of growth arrest, differentiation and/or apoptotic cell death of transformed cells and, as a result, they are currently receiving considerable attention as antitumor agents. In this study, we examined the status of histone H4 acetylation and the level of HDAC1 expression in surgically resected specimens of human esophageal squamous cell carcinoma by immunohistochemistry. We herein demonstrate that histone H4 of esophageal carcinoma cells was significantly hyperacetylated in the early stage of cancer invasion and thereafter changed into a hypoacetylated state according to the degree of cancer progression. The cases in which HDAC1 was less expressed in esophageal carcinoma cells than in the normal mucosa significantly increased as the carcinoma invaded into the deeper layers of the esophageal wall. Furthermore, both the hyperacetylation of histone H4 and the high expression of HDAC1 were shown to topologically colocalize in the same tumor. These results suggested that a dynamic equilibrium between the HAT and HDAC activities is disrupted in esophageal carcinoma, thus implying that a certain interaction may exist between the hyperacetylation of histone H4 and the HDAC 1 expression.

Primary carcinoma of the small intestine is rare and represent about 0.5% of all gastrointestinal malignancies. The aim of this study was to examine the biological characteristics of primary carcinoma of the small intestine by immunohistochemical and nested polymerase chain reaction methods. Thirty-five primary carcinomas (12 in the duodenum and 23 in the jejunum or ileum) from 35 patients were studied clinicopathologically and examined for overexpression of p53 protein. In 22 of these 35 cases, point mutation at codon 12 of the K-ras gene was detected by the nested polymerase chain reaction and restriction fragment length polymorphism method. All the duodenal carcinomas were well-differentiated type and the rate of these carcinomas was significantly higher than that of jejunal or ileal carcinomas (100% vs. 65%). Fourteen cases showed overexpression of p53 (40%), and p53 tended to be expressed more frequently in poorly-differentiated type (71%) compared to well-differentiated type (30%). Only 2 out of 22 carcinoma cases showed K-ras gene mutation, and both were duodenal carcinomas. These findings suggest that p53 plays a major role in the progression of carcinoma of the small intestine, whereas the role of K-ras mutation is much less significant.

We describe a rare case of a benign pseudotumorous lesion (fibroangiomyomatous hyperplasia with elastosis) in the gallbladder in a 44-year-old Japanese woman, and discuss the rarity of elastosis in the gallbladder. To our knowledge, this case may be the first report of a pseudotumorous lesion of the gallbladder with elastosis in Japan.

The characteristics of undifferentiated (anaplastic) carcinoma (UC) of the pancreas were analysed and compared with those of poorly differentiated adenocarcinoma (PA). Eight cases of UC of the pancreas were evaluated by clinicopathological and immunohistochemical methods and compared with 20 cases of PA. Large size of the tumor, local invasion and lymph node metastasis were frequently seen in UC, leading to a significantly worse prognosis compared to that of PA (p=0.022). Immunohistochemically, E-cadherin expression was completely lost in 7/8 UC cases, whereas half the PA cases revealed a strong reactivity for E-cadherin. alpha- and beta-catenin expressions tended to be impaired in UC compared with PA. The results suggest that the altered expression of adhesion molecules is correlated with dedifferentiated change and is contributory to its aggressive biological behaviour.