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A 52‐year‐old man underwent pneumonectomy of the left lung for previously diagnosed primary spindle cell carcinoma (pT4aN1M0, stage III B) with programmed death‐ligand 1 expression (tumor proportion score ≥95%) and without epidermal growth factor receptor gene mutation and anaplastic lymphoma kinase fusion gene. However, brain metastasis and chest wall tumor relapse occurred. Considering insufficient improvement with gamma knife treatment for brain metastasis and combination chemotherapy (paclitaxel, carboplatin, and bevacizumab), pembrolizumab monotherapy and palliative irradiation therapy for chest metastases were started after brain tumor volume reduction using craniotomy. Brain edema and chest wall metastases markedly improved following a pseudoprogression of the brain edema accompanied by a performance status decline; this effect continued until 11 cycles of pembrolizumab administration., Lung spindle cell carcinoma has a poor prognosis and is usually resistant to cytotoxic chemotherapy. Our findings suggest that immune checkpoint inhibitors (ICIs) are a novel therapeutic strategy for lung spindle cell carcinoma.

We encountered a patient with multiple myeloma treated with autologous hematopoietic stem cell transplantation (HSCT) who developed repeated episodes of enteritis but regressed spontaneously. An endoscopic examination revealed no abnormalities, but biopsy specimens showed massive infiltration of CD4+ and Epstein-Barr encoding region (EBER+) abnormal lymphocytes in which a high copy number of Epstein Barr virus (EBV) genomes was detected by quantitative polymerase chain reaction (qPCR). EBV infection was exclusively detected in CD4+ T-cells, leading to a diagnosis of EBV-positive CD4+ T-cell lymphoproliferative disorder (LPD). This case suggests that an immediate biopsy and examinations, including qPCR for EBV DNA, should be considered for patients with recurrent enteritis after autologous HSCT, regardless of endoscopic findings.

Background Nonalcoholic steatohepatitis (NASH) is diagnosed with histopathologic testing, but noninvasive surrogate markers are desirable for screening patients who are at high risk of NASH. Purpose To investigate the diagnostic performance of dispersion slope, attenuation coefficient, and shear-wave speed measurements obtained using two-dimensional (2D) shear-wave elastography (SWE) in assessing inflammation, steatosis, and fibrosis and in the noninvasive diagnosis of NASH in patients suspected of having nonalcoholic fatty liver disease (NAFLD). Materials and Methods This prospective study collected data from 120 consecutive adults who underwent liver biopsy for suspected NAFLD and were enrolled between April 2017 and March 2019. Three US parameters (dispersion slope [(m/sec)/kHz], attenuation coefficient [dB/cm/MHz], and shear-wave speed [in meters per second]) were measured using a 2D SWE system immediately before biopsy. The biopsy specimens were scored by one expert pathologist according to the Nonalcoholic Steatohepatitis Clinical Research Network criteria (119 participants underwent a histologic examination). Diagnostic performance was assessed using the area under the receiver operating characteristic curve (AUC) for the categories of inflammation, steatosis, and fibrosis. Results One hundred eleven adults (mean age, 53 years ± 18 [standard deviation]; 57 men) underwent a US examination. Dispersion slope enabled the identification of lobular inflammation, with an AUC of 0.95 (95% confidence interval [CI]: 0.91, 0.10) for an inflammation grade greater than or equal to A1 (mild), 0.81 (95% CI: 0.72, 0.89) for an inflammation grade greater than or equal to A2 (moderate), and 0.85 (95% CI: 0.74, 0.97) for an inflammation grade equal to A3 (marked). Attenuation coefficient enabled the identification of steatosis, with an AUC of 0.88 (95% CI: 0.80, 0.97) for steatosis grade greater than or equal to S1 (mild), 0.86 (95% CI: 0.79, 0.93) for steatosis grade greater than or equal to S2 (moderate), and 0.79 (95% CI: 0.68, 0.89) for steatosis grade equal to S3 (severe). Shear-wave speed enabled the identification of fibrosis, with an AUC of 0.79 (95% CI: 0.69, 0.88) for fibrosis stage greater than or equal to F1 (portal fibrosis), 0.88 (95% CI: 0.82, 0.94) for fibrosis stage greater than or equal to F2 (periportal fibrosis), 0.90 (95% CI: 0.84, 0.96) for fibrosis stage greater than or equal to F3 (septal fibrosis), and 0.95 (95% CI: 0.91, 0.99) for fibrosis stage equal to F4 (cirrhosis). The combination of dispersion slope, attenuation coefficient, and shear-wave speed showed an AUC of 0.81 (95% CI: 0.71, 0.91) for the diagnosis of NASH. Conclusion Dispersion slope, attenuation coefficient, and shear-wave speed were found to be useful for assessing lobular inflammation, steatosis, and fibrosis, respectively, in participants with biopsy-proven nonalcoholic fatty liver disease. © RSNA, 2020

Immunoglobulin G4 (IgG4)‐related disease is established as a new clinical entity, characterized by high levels of plasma IgG4 and IgG4‐positive plasma cell infiltration. However, the elevation of plasma IgG4 and infiltration of IgG4‐positive cells have been observed in other diseases, including malignancy. We experienced a case of prominent IgG4‐positive lymphadenopathy, which was diagnosed as a reactive lesion in response to lung cancer. The cancerous lesion was so small in size that it was difficult to reveal the coexisting lung cancer. Surgical lymph node biopsy and endobronchial ultrasound‐guided transbronchial needle aspiration did not reveal lymph node metastasis of cancer. Mediastinal lymph node dissection finally revealed it. After the right upper lobectomy, the patient underwent postoperative chemotherapy and remains cancer‐free after 1 year. Our case suggests that close examination and careful follow‐up are necessary when IgG4‐positive lymphadenopathy is observed., This article discussed a case in which prominent lymphadenopathy with immunoglobulin G4‐positive cell infiltration was caused in response to microscopic lung cancer. Surgical lymph node biopsy, as well as endobronchial ultrasound‐guided transbronchial needle aspiration, could not reveal coexisting malignant cells in the mediastinal lymph node.

Background Nonalcoholic fatty liver disease (NAFLD) is common in the general population but identifying patients with high-risk nonalcoholic steatohepatitis (NASH) who are candidates for pharmacologic therapy remains a challenge. Purpose To develop a score to identify patients with high-risk NASH, defined as NASH with an NAFLD activity score (NAS) of 4 or greater and clinically significant fibrosis (stage 2 [F2] or higher). Materials and Methods This was a cross-sectional secondary analysis of data prospectively collected between April 2017 and March 2019 for a group of patients with NAFLD in Japan (Japan NAFLD, the derivation data set) with contemporaneous two-dimensional shear-wave elastography and biopsy-proven NAFLD (age range, 20-89 years). Three US markers (liver stiffness [LS, measured in kilopascals], attenuation coefficient [AC, measured in decibels per centimeter per megahertz], and dispersion slope [DS, measured in meters per second per kilohertz]) were determined, together with aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels and the AST-to-ALT ratio. The best-fit multivariate logistic regression model for identifying patients with high-risk NASH was determined. Diagnostic performance was assessed by using the area under the receiver operating characteristic curve (AUC). The findings were validated in an independent data set (Korea NAFLD; age range, 20-78 years). Results The Japan NAFLD data set included 111 patients (mean age, 53 years ± 18 [standard deviation]; 57 men), 84 (76%) with NASH. The Korea NAFLD data set included 102 patients (mean age, 48 years ± 18; 43 men), 55 (36%) with NASH. The most predictive model (LAD NASH score) combined LS, AC, and DS. Performance was satisfactory in both the derivation sample (AUC, 0.86; 95% CI: 0.79, 0.93) and the validation sample (AUC, 0.88; 95% CI: 0.80, 0.95). The LAD NASH score showed a positive predictive value of 86.5% and a negative predictive value of 87.5% for high-risk NASH in the derivation sample. Conclusion A score combining three US markers may be useful for noninvasive identification of patients with high-risk nonalcoholic steatohepatitis for inclusion in clinical trials and pharmacologic therapy. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Lockhart in this issue.

Cytological detection of chordoma cells in the serosal cavity is challenging because of its rare presentation. Herein, we report a case of chordoma showing malignant pleural effusion accompanied by pleuropulmonary metastases in a 68-year-old woman. Cytological analysis was performed using pleural fluid obtained following thoracentesis. Conventional cytological staining demonstrated few clusters of large, atypical cells characterized by epithelial cell-like connectivity and rich cytoplasm with foamy and/or multivacuolar changes. The nuclei of these atypical cells were large and either round or oval with no conspicuous irregularities in the nuclear membrane. Periodic acid-Schiff staining of these atypical cells revealed fine granules in the cytoplasm. Giemsa staining showed foamy and/or multivacuolar cytoplasm in these cells, with metachromatic mucoid stroma in the surroundings. Immunocytochemistry analysis using cellblock showed these cells to be positive for broad cytokeratins, epithelial membrane antigen, S100 protein, vimentin, and Brachyury. To the best of our knowledge, this is the first case report in which chordoma cells were cytologically detected in pleural effusions. Our findings also suggest that conventional cytology combined with cellblock immunocytochemistry can increase the accuracy of chordoma cell detection in the serosal cavity.

Measurement of spleen stiffness (SS) using ultrasound (US) elastography is useful for predicting portal hypertension. However, the mechanism leading to increased SS remains unclear. We jointly developed a new US elastography system (Aplio i-series, Canon Medical Systems) that can easily measure organ viscosity (dispersion slope: DS). We analyzed the cause of increased SS by calculating the shear wave speed (SWs, which reflects fibrosis) and DS of the spleen in carbon tetrachloride (CCL4) rat liver cirrhosis models. A total of 13 Sprague–Dawley rats were randomly divided into four groups (C group: 3 rats as control, 2D group: 3 rats injected with CCL4 twice in 1 week, 4D group: 4 rats injected 4 times in 1 week, 6W group: 3 rats injected twice a week for 6 weeks). The SWs and the DS of each group were calculated, and histopathological analysis was performed. The spleen SWs of the 6W group was significantly higher than that of the C group (p = 0.044). The spleen DS did not change after CCL4. The liver SWs of the 4D and 6W groups was significantly higher than that of the C group (p = 0.012 and 0.007, respectively) with fibrosis change on histopathology, and the DS of the 4D group was significantly higher than that of the C group (p = 0.033). Splenic fibrosis was confirmed in the 6W group, but inflammation and necrosis were not seen. SS increased due to fibrosis and can be predicted based on SWs and DS values.

Attenuation imaging (ATI) is a new noninvasive ultrasound technique for assessing steatosis grade (S). However, validated region-of-interest (ROI) sampling strategies are not currently available. We investigated the diagnostic performance of various ATI-ROI positions for determining histopathologic S in patients with nonalcoholic fatty liver disease (NAFLD). This retrospective study included 105 patients with biopsy-proven NAFLD. All attenuation coefficient (AC, dB/cm/MHz) measurements were obtained by the same hepatologist using a commercially available ultrasound system on the same day as liver biopsy. Mean (± standard deviation) age and body mass index of the patients were 53 (± 18) years and 27.1 (± 4.1) kg/m2, respectively. The numbers of patients with steatosis affecting 66% of hepatocytes were 8, 50, 29, and 18, respectively. The ATI-ROI was placed at three different positions for AC measurement using a dedicated workstation: the upper edge of the area ROI, twice the depth of the liver capsule, and the lower edge of the area ROI. Diagnostic performance was evaluated using the area under the receiver-operating characteristic curve (AUC). The AUCs of AC at the three ATI-ROI positions were 0.734 (95% confidence interval [CI]: 0.470–0.998), 0.750 (0.639–0.861), and 0.878 (0.788–0.968) for S ≥ 1; 0.503 (0.392–0.615), 0.824 (0.741–0.907), and 0.809 (0.724–0.895) for S ≥ 2; and 0.606 (0.486–0.726), 0.849 (0.767–0.932), and 0.737 (0.626–0.848) for S = 3, respectively. For accurate steatosis grade assessment, the ATI-ROI should not be placed at the upper edge of the area ROI.

We encountered a patient with multiple myeloma treated with autologous hematopoietic stem cell transplantation (HSCT) who developed repeated episodes of enteritis but regressed spontaneously. An endoscopic examination revealed no abnormalities, but biopsy specimens showed massive infiltration of CD4+ and Epstein-Barr encoding region (EBER+) abnormal lymphocytes in which a high copy number of Epstein Barr virus (EBV) genomes was detected by quantitative polymerase chain reaction (qPCR). EBV infection was exclusively detected in CD4+ T-cells, leading to a diagnosis of EBV-positive CD4+ T-cell lymphoproliferative disorder (LPD). This case suggests that an immediate biopsy and examinations, including qPCR for EBV DNA, should be considered for patients with recurrent enteritis after autologous HSCT, regardless of endoscopic findings.

AIMS Proliferative activity, evaluated from the Ki-67 index, is a strong prognostic factor in lung adenocarcinoma (LADC). Here, we optimised a procedure to measure the Ki-67 index and establish the best cut-off value. METHODS AND RESULTS We examined 342 stage I LADCs for the immunohistochemical expression of Ki-67 using different antibodies, MIB1 and SP6. The results revealed the superior specificity of SP6; therefore, SP6 was used in subsequent analyses. Slides were scanned with a virtual slide system. Using software, tumour cells were counted in a whole tumour. Thereafter, the tumour was evenly subdivided into 0.25-mm2 tiles. The frequency of positive cells was counted in each tile of an invasive area or the whole tumour. We calculated the number of tumour cells required to produce a 95% confidence interval (CI) 70% and CI of

To investigate the usefulness of shear-wave speed and dispersion slope measurements obtained, using an ultrasound elastography system in rat livers with various degrees of necroinflammation and fibrosis. A total of 25 male Sprague Dawley rats were randomly divided into 5 groups of 5 rats each: G0 (control), G1 (CCl4 injected twice a week for 1 wk), G2 (CCl4 injected four times a wk for 1 wk), G3 (CCl4 injected twice a wk for 6 wk) and G4 (CCl4 injected twice a wk for 10 wk). The shear-wave speed (m/s) and the dispersion slope ([m/s]/kHz) were measured. Histologic features (inflammation, necrosis and fibrosis) were used as reference standards. In multivariable analysis with histologic features as independent variables, the fibrosis grade was significantly related to shear-wave speed (p < 0.05) and the necrosis grade was significantly related to dispersion slope (p < 0.05). Dispersion slope is more useful than shear-wave speed for predicting the degree of necroinflammation.

Unilateral multiple adrenocortical micronodules (UMNs) constitute a rare subset of primary aldosteronism (PA) characterized by the hypersecretion of aldosterone derived from multiple small nodules in the zona glomerulosa of the unilateral adrenal grand. This case study describes a 49-year-old man with PA and UMNs who presented with muscle cramps at rest due to hypokalemia. The patient had a 6-year history of hypertension treated with antihypertensive drugs. Imaging studies revealed bilateral adrenal nodules as large as 5 mm. Adrenal venous sampling confirmed unilateral PA; therefore, the patient underwent the removal of the affected adrenal gland. Macroscopically, the removed adrenal gland exhibited irregular adrenocortical thickening accompanied by ill-defined, adrenocortical macronodules as large as 6 mm. The zona glomerulosa was histologically hyperplastic. However, an immunohistochemistry test of the steroidogenic enzymes revealed that these macronodules and the hyperplastic glomerular layer tested negative for CYB11B2. Moreover, we observed adrenocortical micronodules as large as 0.5 mm that tested immunohistochemically positive for CYP11B2 and HSD3B2 but negative for CYP17A1 and CYP11B1. Thus, UMNs were diagnosed. This case instructively indicates that a grossly or histologically detectable nodular lesion is not necessarily a culprit lesion for PA. Therefore, functional histopathology is indispensable for the correct subclassification of PA.

Rationale: Primary carcinosarcoma of the upper urinary tract is rare. Ureteral duplication is one of the most common urinary tract malformations. Additionally, the association between ureteral duplication and malignancy is unknown. To the best of our knowledge, no cases of malignant tumors diagnosed as carcinosarcoma with ureteral duplication have been reported. We herein report the case of a patient with carcinosarcoma of the ureteropelvic junction associated with incomplete ureteral duplication. Patient concerns: A 60-year-old Japanese woman presented with painless gross hematuria. She had a history of total hysterectomy and chemotherapy for endometrioid carcinoma 5 years before. She had no history of occupational chemical exposure. Diagnoses: Radiographic imaging revealed right incomplete ureteral duplication, hydronephrosis, and a polypoid tumor in the ureteropelvic junction of the lower moiety of the right kidney. Urine cytology showed a small amount of degenerated atypical epithelial and nonepithelial cells. The transureteral biopsy specimen showed dysplastic urothelial cells and atypical myoid spindle cells. These findings were indefinite for malignancy. Interventions: The patient underwent right nephroureterectomy. Pathological examination of the resected tumor showed a biphasic neoplasm composed of carcinomatous and sarcomatous components. The sarcomatous component was immunohistochemically positive for vimentin, desmin, h-caldesmon, and α-SMA and negative for pancytokeratin (AE1/AE3), low molecular weight cytokeratin (CAM 5.2), EMA, E-cadherin, GATA3, uroplakin 2, and p63. Based on these findings, we diagnosed the tumor as carcinosarcoma. Outcomes: The postoperative course was uneventful. No additional therapy was administered. The patient has remained alive without recurrence for 21 months since surgery. Lessons: Carcinosarcoma can arise from ureteral duplication. Although the majority of carcinosarcomas of the upper urinary tract are diagnosed at an advanced stage and have a poor prognosis, some can have a less aggressive course. Further studies are needed to determine the association between ureteral duplication and malignancy.

Shear wave (SW) dispersion imaging is a newly developed imaging technology for assessing the dispersion slope of SWs, which is related to tissue viscosity in diffuse liver disease. Our preclinical and preliminary clinical studies have shown that SW speed is more useful than dispersion slope for predicting the degree of fibrosis and that dispersion slope is more useful than SW speed for predicting the degree of necroinflammation. Thus, dispersion slope, which reflects viscosity, may provide additional pathophysiological insight into diffuse liver disease.

Bile duct cancer is known to contain numerous fibroblasts, and reported to recruit cancer- associated fibroblasts by secreting platelet-derived growth factor-D (PDGF-D) which needs serine proteases, such as matriptase, to behave as a ligand. However, their expression pattern, and prognostic value have not been clarified. In this study, we investigated the clinicopathological significance of PDGF-D and matriptase expression in patients with extrahepatic bile duct cancer. The samples were obtained from 256 patients who underwent the surgical resection between 1991 and 2015, and the expression levels of PDGF-D and matriptase were evaluated immunohistochemically. Staining intensities and distribution were scored, and finally classified into low and high expression groups in cancer cells and stroma respectively. High expression of matriptase in the cancer stroma was detected in 91 tumors (40%). The high stromal matriptase expression was significantly associated with shorter recurrence-free survival (RFS) and overall survival (OS) (P = 0.0027 and 0.0023, respectively). Multivariate analyses also demonstrated that the stromal matriptase expression level was an independent influential factor in RFS (P = 0.0050) and OS (P = 0.0093). Our findings suggest that the high stromal matriptase expression was strongly associated with tumor progression, recurrence and poor outcomes in patients with extrahepatic bile duct cancer.

The aim of the present study was to investigate two methods of determining liver stiffness in rats with various degrees of non-alcoholic steatohepatitis induced by a methionine- and choline-deficient (MCD) diet by comparing each finding with reference to histopathological liver findings. Twenty male Wister rats were fed an MCD diet for up to 32 weeks, and four were fed a normal diet. Ultrasound-based shear wave elastography (SWE) and mechanical compression testing using an Instron Universal Testing machine were performed on each rat at designated time points. After each examination, liver histopathology was analyzed to evaluate the degrees of steatosis, inflammation, and fibrosis based on non-alcoholic fatty liver disease (NAFLD) activity score, and each finding was compared with reference to liver histopathologic findings. Median liver stiffness values measured using SWE showed a stepwise increase with increasing histological inflammation score (P = 0.002), hepatic fibrosis stage (P = 0.029), ballooning score (P = 0.012), and steatosis grade (P = 0.030). Median liver stiffness measured using an Instron machine showed a stepwise increase only with increasing histological fibrosis stage (P = 0.033). Degree of liver stiffness measured by SWE and the Instron machine differed. SWE reflected mainly inflammation, whereas Instron machine-derived values primarily reflected fibrosis. This is the main source of discrepancies between measurements made with these two modalities.

Introduction Breast adenomyoepithelioma (AME) is a rare tumor composed of myoepithelial cells and ductal or luminal cells. Most cases of AME are benign, but rare cases in which either or both cell types exhibited malignant features have been reported. Due to its rarity, no diagnostic criteria for malignancy have been established for AME. Patient concerns A 64-year-old woman presented with a mass in her right breast. Fine-needle aspiration cytology and biopsy examinations revealed lesions composed of spindle-shaped cells and round epithelial cells. AME was suspected, and partial mastectomy was performed. Diagnosis The tumor specimen showed AME, which mainly consisted of spindle-shaped myoepithelial cells with slight atypia, admixed with tubular luminal cells and small areas of atypical intraductal proliferative lesions. No apparent features of malignancy, such as necrosis or invasion, were seen in the myoepithelial cells or the luminal or intraductal component. However, the atypical intraductal component exhibited focal nuclear atypia, a cribriform pattern, and moderate to strong membranous human epidermal growth factor receptor 2 (HER2) immunoreactivity. HER2 amplification was detected in focal regions of the atypical intraductal component by fluorescence in situ hybridization (FISH), which resulted in a diagnosis of AME with ductal carcinoma in situ. Outcomes The patient did not receive further therapy and was free from tumor recurrence at 23 months after the operation. Conclusion HER2 FISH might be useful for evaluating suspected AME tumors for malignancy when an atypical ductal lesion that lacks definitive features of malignancy is encountered.

TAFRO syndrome, a rare systemic inflammatory disease, can lead to multiorgan failure without appropriate treatment. Although thrombocytopenia is frequently seen in patients with TAFRO syndrome, little is known about its pathogenesis. Moreover, while recent studies have reported the presence of an anterior mediastinal mass in some patients, the pathological status of this remains unclear. Here, we report a case of fatal bleeding in a patient with TAFRO syndrome accompanied by an anterior mediastinal mass. A 55-year-old female was transferred to our hospital with a 2-week history of fever, epistaxis, and dyspnea. Laboratory tests revealed severe thrombocytopenia, computed tomography (CT) showed pleural effusions, and bone marrow biopsy revealed reticulin myelofibrosis. We suspected TAFRO syndrome, but the CT scan showed an anterior mediastinal mass that required a biopsy to exclude malignancy. She soon developed severe hemorrhagic diathesis and died of intracranial hemorrhage despite intensive treatment. She had multiple autoantibodies against platelets, which caused platelet destruction. An autopsy of the mediastinal mass revealed fibrous thymus tissues with infiltration by plasma cells. Our case suggests that thrombocytopenia could be attributed to antibody-mediated destruction and could be lethal. Hence, immediate treatment is imperative in cases of severe thrombocytopenia, even when accompanied by an anterior mediastinal mass.

Lymphatic stomata are small lymphatic openings in the serosal membrane that communicate with the serosal cavity. Although these stomata have primarily been studied in experimental mammals, little is known concerning the presence and properties of lymphatic stomata in the adult human pleura. Thus, adult human pleurae were examined for the presence or absence of lymphatic stomata.A total of 26 pulmonary ligaments (13 left and 13 right) were obtained from 15 adult human autopsy cases and examined using electron and light microscopy. The microscopic studies revealed the presence of apertures fringed with D2-40-positive, CD31-positive, and cytokeratin-negative endothelial cells directly communicating with submesothelial lymphatics in all of the pulmonary ligaments. The apertures' sizes and densities varied from case to case according to the serial tissue section. The medians of these aperture sizes ranged from 2.25 to 8.75 μm in the left pulmonary ligaments and from 2.50 to 12.50 μm in the right pulmonary ligaments. The densities of the apertures ranged from 2 to 9 per mm(2) in the left pulmonary ligaments and from 2 to 18 per mm(2) in the right pulmonary ligaments. However, no significant differences were found regarding the aperture size (p=0.359) and density (p=0.438) between the left and the right pulmonary ligaments.Our study revealed that apertures exhibit structural adequacy as lymphatic stomata on the surface of the pulmonary ligament, thereby providing evidence that lymphatic stomata are present in the adult human pleura.

Shear wave elastography (SWE) has been validated in chronic hepatitis C and B; however, limited data are available in non-alcoholic fatty liver disease (NAFLD). This study aimed to evaluate the accuracy of SWE and FIB4 index for the diagnosis of fibrosis in a cohort of consecutive patients with biopsy-proven NAFLD, and to evaluate the effects of other histologic parameters on SWE measurement. Written informed consent was obtained from all patients, and this study was approved by our internal review board and ethics committee. Seventy-one patients with histologically proven NAFLD (mean age 50.8 years ± 15.7) were examined. All patients underwent SWE (Aixplorer™; SuperSonic Imagine) and FIB4 index (based on age, aspartate aminotransferase and alanine aminotransferase levels, and platelet counts) measurements. SWE measurements were compared with the histologic features based on the NAFLD activity score and FIB4 index. The area under the ROC curve for the diagnosis of hepatic fibrosis stage 3 or higher was 0.821 (optimal cut-off value 13.1 kPa, sensitivity 62.5%, specificity 57.4%) for SWE and 0.822 (optimal cut-off value 1.41, sensitivity 71.9%, specificity 53.9%) for FIB4 index. The median liver stiffness values measured using SWE showed a stepwise increase with increasing hepatic fibrosis stage (P

Mammary analogue secretory carcinoma (MASC) is a recently described salivary gland neoplasm that is defined by ETV6-NTRK3 gene fusion. There have been few case reports on the cytopathologic features of MASC to date. We examined the clinicopathological and cytological features of seven cases of MASC defined by RT-PCR analysis of the ETV6-NTRK3 fusion gene. The cases occurred in three men and four women aged between 39 and 68 years, with a mean of 51.6 years. In five of these seven cases, the tumor involved the parotid gland. Histologically, all cases displayed predominantly microcystic patterns, often a mixture of follicular and papillary-cystic structures. All tumors were immunoreactive for mammaglobin, S-100 protein, and vimentin. Available fine-needle aspiration cytology smears were cellular and exhibited many loosely cohesive syncytial clusters or isolated cells. Many histiocytes, some of which contained hemosiderin pigments, and variously shaped mucinous material were evident in the background or within the epithelial clusters. The majority of cases showed small to medium-sized follicular structures with secreted materials. Papillary clusters were occasionally found. Tumor cells exhibited small to medium-sized round to oval nuclei, with a smooth contour and indistinct or small nucleoli, and vacuolated cytoplasm. No tumor cells had obvious intracytoplasmic zymogen granules. It appeared that clusters of small to medium-sized follicular and papillary configurations consisting of bland tumor cells with vacuolated cytoplasm, but lack of intracytoplasmic zymogen granules, in a mucinous or hemosiderin-laden histiocyte-rich background, were a characteristic cytological feature highly suggestive of MASC.

Great progress has been made in the diagnosis of focal nodular hyperplasia (FNH) and hepatocellular adenoma (HCA) in the last few years due to the use of molecular criteria. This has allowed us to identify a new type of hepatic nodule. In this case report, we present a male patient with a hepatic nodule associated with idiopathic portal hypertension (IPH) pathologically exhibiting not only the morphological features of FNH, such as ductular reactions, dilated sinusoids, major vascular abnormalities and an immunohistochemical "map-like" pattern of glutamine synthetase (GS), but also the immunohistological features of focal HCA, such as strong expression of serum amyloid A and C-reactive protein and weak expression of GS. As the final diagnosis, the nodule was identified as an FNH-like lesion with focal inflammatory hepatocellular adenoma.

Objectives Shear wave elastography is a novel noninvasive method for assessing liver fibrosis by measuring liver stiffness. This study was conducted to evaluate how pathologic changes could have an impact on measured elasticity values in both resected hepatocellular carcinomas and adjacent liver tissue. Methods Intraoperative shear wave elastography was performed in 7 patients who underwent liver resection at our institution; 7 hepatocellular carcinomas and adjacent liver tissue were subjected to elastographic measurements. A total of 48 circular regions of interest (ROIs; 3-8 mm in diameter) were located in the hepatocellular carcinomas (n = 37) and adjacent liver tissue (n = 11), and mean stiffness values were obtained from each ROI. All of the histologic images corresponding to the 48 ROIs after surgery were transformed into digital microscopic images by a scanning system, and histologic parameters, such as the proportions of nuclear areas, fatty areas, fibrous areas, and vessel areas, were quantitatively assessed. Relationships between the mean stiffness and the histologic parameters were investigated by the mixed effects model. Results By univariate analysis, the proportions of collagen fiber areas (P = .039), fibrous areas (P = .045), hepatocellular nuclear areas (P = .045), and nuclear areas other than hepatocellular and lymphoplasmacytic areas (P = .039) showed statistically positive associations with mean stiffness values. Multivariate analysis indicated that the proportion of collagen fiber areas was the strongest pathologic determinant of mean stiffness (P = .008), with hepatocellular nuclear areas also having a significant effect (P = .010). Conclusions Fibrosis predictably affects elastographic estimation, but hepatocellular density (ie, hepatocellular nuclear areas) also alters elastographic assessment.

Objective: This study aimed to evaluate the usability of peritoneal swabbing cytology (PSC) with cotton swabs as an effective method for the detection of peritoneal metastasis during the staging laparotomy of epithelial ovarian carcinomas and borderline tumours (EOC/BT). Study Design: One hundred and ninety-two patients with EOC/BT who underwent laparotomy at the Yokohama City University Hospital from 2004 to 2010 were analysed retrospectively. The positive rates of the PSC and ascites/peritoneal-wash cytology (A/PWC) were compared. Results and Conclusion: Both A/PWC and PSC were performed during laparotomy (n = 140). The rate of metastasis detection with A/PWC was significantly higher than with PSC (50.0 vs. 20.7%, p < 0.001 by χ2 test). The superior detection ability of A/PWC was observed regardless of the presence of macroscopic peritoneal metastasis in 56 cases with macroscopic peritoneal metastasis, with A/PWC detecting 80.3% of cases versus PSC detecting 37.5% (p = 0.013). In 84 cases without macroscopic peritoneal metastasis, A/PWC detected 29.8% of cases versus 9.5% with PSC (p = 0.003). Our results suggest that PSC is insufficient to evaluate the peritoneal metastasis for the surgical staging of EOC/BT. Other procedures such as subdiaphragmatic A/PWC should be included when possible to maximize the accuracy of diagnosis.

Rationale Liver heterotopia associated with congenital diaphragmatic hernia (CDH) is a rare condition; to the best of our knowledge, only 17 cases have been reported to date. The histogenesis and clinicopathological features are largely unknown. We herein report 2 cases of liver heterotopia associated with CDH along with 17 cases described in the literature to shed light on their clinicopathological characteristics. Patient concerns Case 1 was a vaginally delivered male newborn who presented with respiratory distress immediately after birth. Case 2 was a female fetus who was found to have left-sided CDH during gestation. Diagnosis In case 1, a chest X-ray revealed left-sided CDH. In case 2, magnetic resonance imaging performed at 33 weeks of gestation revealed left-sided CDH. Interventions Case 1 underwent diaphragmatic patch repair surgery 3 days after birth. Histopathological examination following surgery in case 1 revealed the presence of ectopic liver tissue in the hernia sac. Case 2 was delivered by Cesarean section, and diaphragmatic patch surgery was performed 3 days after birth. During surgery, an isolated nodule was identified on the peritoneal side of the border of the defective foramen of the diaphragm. Histopathological examination following surgery in case 2 confirmed the presence of an epidermal cyst in the hernia sac. In addition, the isolated nodule was histopathologically found to be ectopic liver tissue. Outcomes In Case 1, CDH recurred at 6 months after surgery, and a second patch repair surgery was performed. The surgically removed hernia sac was found to contain microscopic ectopic liver tissue on histopathology. Case 1 recovered well after surgery, and there was no critical change during the 10-month postoperative period. Case 2 recovered well after surgery, and there was no critical change during the 20-month postoperative period. Lessons There were no secondary pathological conditions associated with the presence of ectopic liver in CDH, such as torsion, infarction, rupture, intra-abdominal bleeding, or tumorization. Our observations suggest that liver heterotopia is a rare but asymptomatic condition in patients with CDH.

Little is known concerning the prognostic significance of the degree of lymphatic vessel invasion in pancreatic head cancer. To address this gap in knowledge, we retrospectively examined 60 patients with locally advanced, surgically resectable pancreatic head cancer who underwent pancreaticoduodenectomy and lymph node (LN) dissection.All cases were histopathologically diagnosed as ductal adenocarcinoma, stage II (25 pT3N0 cases, 35 pT3N1 cases). The following variables were investigated: age; sex; neoadjuvant therapy; adjuvant therapy; tumor size; tumor grade; invasion into the serosa, retropancreatic tissue, duodenum, bile duct, portal venous system and perineural area; cut margins; LN metastasis; and the number of invaded lymphatic vessels (LVI-score).Univariate analysis demonstrated that LN metastasis and an LVI-score ≥5 were significantly associated with poor disease-free survival. Multivariate Cox regression analysis confirmed that LN metastasis and an LVI-score ≥7 were significantly associated with poor disease-free survival. Additionally, LVI-scores ≥9 and ≥10 were comparable to or surpassed the significance of LN metastasis based on the hazard ratio. Univariate analysis demonstrated that tumor size >30 mm, duodenal invasion, LN metastasis and an LVI-score ≥2 were significantly associated with poor overall survival. Multivariate Cox regression analysis confirmed that LN metastasis and LVI-scores ≥9 and ≥10 were significantly associated with poor overall survival, and an LVI-score ≥10 was comparable to or surpassed the significance of LN metastasis based on the hazard ratio.Our study strongly suggests that a high degree of lymphatic vessel invasion is associated with a poor prognosis in patients with locally advanced, surgically resectable pancreatic head cancer.

We present a case of a 67-year-old man with intussusception of the right ureter associated with a fibroepithelial polyp. The concentric sign and line sign are characteristic radiological findings in intussusception, and these findings could be seen in the present case. Although this entity is rare, its radiological findings are specific. Multidetector row computed tomography and its multiplanar reconstruction make the diagnosis feasible, although the qualitative diagnosis of the tumor was difficult.

Sclerosing angiomatoid nodular transformation (SANT) is a recently recognized and rare, nonneoplastic lesion of the spleen. Some papers have reported an increased SANT diameter during the follow-up period. We present two cases of SANT whose size increased during the follow-up period. Diffusion-weighted magnetic resonance imaging (DWI) findings correlated well with the pathological findings of SANT, the multinodular high-intensity area as the angiomatoid nodules and the peripheral low-intensity area as fibrous tissues. Therefore, DWI may be a useful imaging tool.

Supplemental Digital Content is available in the text, Recent tissue microarray (TMA)-based studies have shown that cell proliferation- and apoptosis-related biomarkers are associated with clinical outcomes in patients with bladder urothelial carcinoma. However, little is known about the differences in these biomarker measurements between whole mount tissue preparations and TMAs. This study aimed to elucidate the discrepancy in the measurements of Ki-67 indices (KIs) and apoptosis indices (AIs) between whole mount tissue preparations and TMAs of bladder urothelial carcinoma samples. Whole mount tissue preparations for Ki-67 immunohistochemistry and terminal deoxynucleotidyl transferase dUTP nick end labeling were made from 30 patients who underwent transurethral resection of bladder urothelial carcinoma. Digital microscopy-assisted virtual TMAs, consisting of 3 small round areas (1 or 0.6 mm in diameter), were generated from the same whole mount tissue preparations. The measurement results in highly reactive areas of biomarkers were compared between the whole mount tissue preparation- and the TMA-based methods. Bland–Altman plot analysis, regression analysis, and Kendall τ were performed to investigate differences in the measurement results, systematic biases, and correlations between biomarkers. Although the Bland–Altman plot analysis demonstrated that almost all the plots were within the limits of agreement, fixed biases were detected in the 1- and 0.6-mm TMAs for the KI (0.181 and 0.222, respectively) and the AI (0.055 and 0.063, respectively). Proportional biases were also detected in the 1- and 0.6-mm TMAs for the AI (P

We previously investigated the utility of μ-oxo N,N′- bis(salicylidene)ethylenediamine iron (Fe(Salen)) nanoparticles as a new anti-cancer agent for magnet-guided delivery with anti-cancer activity. Fe(Salen) nanoparticles should rapidly heat up in an alternating magnetic field (AMF) and we hypothesized that these single-drug nanoparticles would be effective for combined hyperthermia-chemotherapy. Conventional hyperthermic particles are usually made of iron oxide and thus cannot exhibit anti-cancer activity in the absence of an AMF. We found that Fe(Salen) nanoparticles induced apoptosis in cultured cancer cells and that AMF exposure enhanced the apoptotic effect. Therefore, we evaluated the combined three-fold strategy, i.e., chemotherapy with Fe(Salen) nanoparticles, magnetically guided delivery of the nanoparticles to the tumor and AMF-induced heating of the nanoparticles to induce local hyperthermia, in a rabbit model of tongue cancer. Intravenous administration of Fe(Salen) nanoparticles per se inhibited tumor growth before the other two modalities were applied. This inhibition was enhanced when a magnet was used to accumulate Fe(Salen) nanoparticles at the tongue. When an AMF was further applied (magnet-guided chemotherapy plus hyperthermia), the tumor masses were dramatically reduced. These results indicate that our strategy of combined hyperthermia-chemotherapy using Fe(Salen) nanoparticles specifically delivered with magnetic guidance represents a powerful new approach for cancer treatment.

a b s t r a c t We have previously shown that when siRNA against Int6 (siRNA-Int6) was used, hypoxia-inducible fac- tor 2 (HIF2) activity was stabilized even under normoxic conditions, and the expression of several angiogenic factors was increased. In neuronal tissues, the mechanism underlying angiogenesis remains largely unknown. In the current study, we investigate the role of the tumor suppressor Int6/eIF3e in the regulation of the expression of angiogenic factors in neuronal cells. In addition, we test whether siRNA- Int6 reduces cold-induced brain damage in rats. We used human neuroblastoma SHSY5Y cells transfected with either siRNA-Int6, or a negative control siRNA. Real-time PCR and supersensitive multiplex assay were used to detect gene and protein expression of several angiogenic factors after transfection. For the animal studies, Wistar rats were subjected to brain damage by cold injury, and 50 g siRNA-Int6, 100 g siRNA-Int6, or negative control was administrated. At day 7 post-treatment, brain sections were stained and image analysis system was used to determine the damaged area. Our experiments using SHSY5Y cells revealed a significant effect of siRNA-Int6 on the expression of HIF2 but not HIF1, both at 8 and 24 h after transfection. The siRNA-Int6 led to significant up-regulation of angiogenic factors, including vascular endothelial growth factor and platelet-derived growth factor-B, both at the mRNA and protein levels. Furthermore, our animal studies revealed significantly reduced area of cold-induced damage in rats receiving siRNA-Int6, compared to negative controls. Our findings indicate that Int6 act as a hypoxia- independent master switch of angiogenesis in neuronal cells, and that inhibition of Int6 by siRNA may be an effective therapeutic strategy in treating ischemic diseases such as brain ischemia and injury. © 2012 Elsevier Ireland Ltd. All rights reserved.

Salivary gland tumors are relatively uncommon and there exists a considerable diagnostic difficulty owing to their diverse histological features in individual lesions and the presence of a number of types and variants, in addition to overlapping histological patterns similar to those observed in different tumor entities. The classification is complex, but is closely relevant to the prognostic and therapeutic aspects. Although hematoxylin-eosin staining is still the gold standard method used for the diagnosis, immunohistochemistry (IHC) can enhance the accuracy and be a helpful tool when in cases to investigate the subjects that cannot be assessed by histological examination, such as the cell nature and differentiation status, cell proliferation, and tumor protein expression. This review depicts on the practical diagnostic utility of IHC in salivary gland tumor pathology under the following issues: assessment of cell differentiation, focusing on neoplastic myoepithelial cells; discrimination of histologically mimic tumor groups; diagnosis of specific tumor types, e.g., pleomorphic adenoma, adenoid cystic carcinoma, and salivary duct carcinoma; and evaluation of malignancy and prognostic factors. IHC plays a limited, even though important, role in the diagnosis of salivary gland tumors, but is often useful to support the histological assessment. However, unfortunately few tumor type-specific markers are still currently available. For these reasons, IHC should be considered a method that can be used to assist the final diagnosis, and its results themselves do not directly indicate a definitive diagnosis.