廣島 健三

BACKGROUND In malignant pleural mesothelioma (MPM), most patients first present with pleural effusion; thus, cytologic analysis is the primary diagnostic approach. However, the cytologic distinction between MPM and reactive mesothelial cells (RMCs) in effusions can be extremely difficult due to the lack of both well-established immunocytochemical markers and definite cytological criteria for MPM. Moreover, the existence of both MPM cells and RMCs in effusions from the same patient makes the differentiation even more challenging. Homozygous deletion of the 9p21 locus, the site of the cyclin-dependent kinase inhibitor 2A/p16 (CDKN2A/p16) gene, frequently occurs in MPM but has never been reported in RMCs. The aim of this study was to define the cytomorphological characteristics of MPM cells, identified by the presence of 9p21 homozygous deletion by fluorescence in situ hybridization (FISH). METHODS For this purpose, cells on smear preparations were recorded using a virtual microscope system and were subjected to FISH analysis. Thereafter, 9p21 homozygous deletion-positive cells were identified in the recorded virtual slides, followed by analysis of their morphological characteristics. RESULTS Mesothelioma cells positive for the 9p21 homozygous deletion exhibited significantly more frequent cell-in-cell engulfment, multinucleation (more than 2 nuclei), and larger multicellular clusters composed of more than 10 cells than did 9p21 deletion-negative RMCs. Possible cutoff values are also proposed for these morphological markers to differentiate MPM cells from RMCs. CONCLUSIONS These morphological differences and cutoff values are useful for cytological differentiation of mesothelioma cells from RMCs. In addition, the novel technique of a combination of virtual microscopy and FISH is introduced for tumor morphological analysis. Cancer (Cancer Cytopathol) 2013;121:415-22. (c) 2013 American Cancer Society. Morphological analysis of 9p21 deletion-positive malignant pleural mesothelioma cells reveals cytological characteristics useful for differentiation from reactive mesothelial cells. In addition, the novel technique of a combination of virtual microscopy and fluorescent in situ hybridization is introduced for tumor morphological analysis.

Extraskeletal osteosarcoma is a rare malignant tumor occurring very rarely in the pleura. We herein report the case of 67-year-old man with asbestos exposure, who underwent biopsies of the large tumor from the chest wall, and diagnosed as a suspicious of fibrosarcoma. Surgical resection was done, and the pathological diagnosis was extraskeletal osteosarcoma arising from the pleura. The differential diagnosis is malignant pleural mesothelioma with osseous and cartilaginous which is also very rare and one of the histopathological subtypes with heterologous elements. Identification of epithelial components, labeling for cytokeratins in spindle cells and its' anatomical distribution may help to distinguish them. In the neoplasm arising from the parietal pleura, primary extraskeletal osteosarcoma of the pleura is very rare, but should be considered.

Adamantinoma-like Ewing family tumor (EFT) is a rare subset of EFTs showing mixed features of Ewing sarcoma and adamantinoma of the long bones. All currently reported cases of the adamantinoma-like type have been associated with bone. Recently, a unique type of EFT was reported showing complex epithelial differentiation associated with the vagus nerve. Here we describe another unique type of EFT arising in the soft tissue of the neck associated with the vagus nerve. An 11-year-old girl presented to our hospital with a neck tumor on her right side. Surgical resection was performed, and histopathologic examination demonstrated a high-grade malignant neoplasm. The tumor was composed of sheets of small round proliferating cells, basaloid tumor nests with marked squamous differentiation, biphasic growth pattern with epithelioid tumor nests, and spindle cell proliferation. Immunohistochemically, the tumor cells showed diffuse expression of CD99 and FLI-1. In addition, small round cells and basaloid/squamoid components were immunoreactive for AE1/AE3, CAM5.2, cytokeratin 5/6, high-molecular weight keratin, p63, and p40 (ΔNp63). Reverse transcription polymerase chain reaction and direct sequencing analysis revealed that the tumor harbored a t(11 22) translocation, involving EWSR1 and FLI-1, which are characteristic of EFTs. According to these findings, our case has characteristics of both a subset of adamantinoma-like EFT and EFT with complex epithelial differentiation. We suggest that EFT with complex epithelial differentiation is in a common spectrum with the adamantinoma-like type and that adamantinoma-like EFTs can arise in soft tissue, leading to difficulty in differential diagnosis with malignant epithelial tumors. Copyright © 2013 by Lippincott Williams &amp Wilkins.

BACKGROUND: The utility of rapid on-site evaluation (ROSE) during endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) for lymph node staging in lung cancer is still controversial. The aim of this study was to assess the role of ROSE during EBUS-TBNA and the interpretation of its results. METHODS: We performed a retrospective chart review of patients with suspected or diagnosed lung cancer who underwent EBUS-TBNA for lymph node staging. The slides were air-dried and Diff-Quik (American Scientific Products, McGaw Park, IL) staining was used for ROSE. Additional smears were prepared for Papanicolaou staining and any remaining sample was placed in 10% formalin for histologic evaluation. The results of ROSE were compared with the results of the final pathologic diagnosis. RESULTS: EBUS-TBNA was performed in 438 patients on 965 lymph nodes. Eighty-four lymph nodes (8.7%) were determined insufficient for definitive diagnosis by final cytologic evaluation. However 45 of the 84 lymph nodes were able to be diagnosed by histologic examination. The non-diagnostic sampling rate was 4.0%. There were no false-positive results on ROSE; however 25 cases (5.7%) were falsely evaluated as negative on ROSE. The concordance rate for staging between ROSE and final pathologic diagnosis was 94.3%. The sensitivity, specificity, negative predictive value, and diagnostic accuracy rate of EBUS-TBNA for correct lymph node staging was 96.5%, 100%, 89.8%, and 98.2%, respectively. CONCLUSIONS: ROSE during EBUS-TBNA for material adequacy showed a low rate of non-diagnostic sampling. There was a high agreement between the on-site and final pathologic evaluation during EBUS-TBNA; however immediate diagnosis should be approached with caution.

背景．良性転移性平滑筋腫は，病理組織学的に良性であるにもかかわらず子宮筋腫が肺に転移するまれな疾患である．症例．50歳女性．36歳時に2度にわたり核出術を行った子宮筋腫に対し子宮全摘術を施行した．42歳時に検診にて発見された右肺結節に対し手術を施行し，過誤腫と診断された．その後再度検診にて発見された左右肺結節に対し，胸腔鏡下左S⁶区域切除術およびS¹⁰部分切除術を施行した．肺腫瘍の病理診断はいずれも良性転移性平滑筋腫であった．過去の子宮腫瘍の病理所見を再検討したが，すべて子宮腺筋腫であった．両者の病理組織像を比較したが，子宮腺筋腫が肺に転移したとは診断できなかった．結論．今回我々は先行する子宮腺筋腫術後に出現した多発肺結節に対し，手術を施行した1例を経験したので報告する．<br>

滑膜肉腫は大腿・膝関節など下肢に多く発生するが，頚部・肺・体幹など滑膜組織のない部分にも発生する．今回われわれは非常に稀な心膜原発滑膜肉腫の1例を経験したので，報告する．<br>

Ciliated muconodular papillary tumor（線毛性粘液結節性乳頭状腫瘍）は肺末梢部に発生し，線毛細胞と杯細胞が乳頭状増殖を示す稀な腫瘍である．今回我々は，本疾患の1切除例を経験したので報告する．<br>

Elevated midkine transcription in human tumors but not in normal tissues suggests a possible use of the transcriptional unit to activate an exogenous gene preferentially in tumors. The restricted expression in tumors, mediated by the midkine promoter region, enabled us to examine a potential gene therapy for cancer. Advantages of the midkine regulatory sequences that can activate foreign gene expressions have been evidenced in a number of preclinical investigations. A promoter region of the midkine gene linked with a reporter gene showed that the 5′-side control region efficiently drove the reporter transcript in many kinds of human tumors and that the transcriptional activity was stronger than that of the SV40 T antigen promoter. Transduction of human tumors with the midkine regulatory region linked with a suicide gene increased susceptibility of the tumors to a responding prodrug. Replication-competent adenoviruses genetically modified with the midkine regulatory sequences showed preferential viral replication in tumors and subsequently cell death of the targeted tumors. The midkine promoter is thus a valuable tool to activate a therapeutic gene or viral replication in tumors and is perhaps an indispensable unit for gene medicine, which is hopefully available as novel therapeutics for intractable cancer in future.

rohibitin is localized to mitochondria where it might have a role in the maintenance of mitochondrial function and protection against senescence. In this study, we show that prohibitin is up-regulated in lung squamous cell carcinoma tissues compared with adjacent normal tissues using agarose 2-dimensional differential gel electrophoresis and immunoblotting. Prohibitin expression was further evaluated by immunohistochemistry. We statistically analyzed the association of prohibitin expression with clinicopathologic indicators in 78 patients with lung squamous cell carcinoma. Our data suggested that prohibitin expression was positively correlated with the International Union Against Cancer (UICC) classification of tumor grade (P &lt .001), pathologic stage (P &lt .001), tumor size (P =.01), and lymph node metastasis (P =.004). Furthermore, we found that prohibitin expression was an independent prognostic indicator (P =.037) for overall survival of patients with lung squamous cell carcinoma by multivariate analysis using the Cox regression method. These findings may encourage further studies investigating prohibitin function in lung squamous cell carcinoma. © 2012 Elsevier Inc. All rights reserved.

Excessive apoptosis and prolonged inflammation of alveolar cells are associated with the pathogenesis of pulmonary emphysema. We aimed to deter- mine whether CD40 affects alveolar epithelial cells and endothelial cells, with regard to evoking apoptosis and inflammation. Mice were repeatedly treated with agonistic-anti CD40 antibody (Ab), with or without agonisticanti Fas Ab, and evaluated for apoptosis and in- flammation in lungs. Human pulmonary microvascular endothelial cells and alveolar epithelial cells were treated with agonistic anti- CD40 Ab and/or anti-Fas Ab to see their direct effect on apoptosis and secretion of proinflammatory molecules in vitro. Furthermore, plasma soluble CD40 ligand (sCD40L) level was evaluated in patients with chronic obstructive pulmonary disease (COPD). In mice, inhaling ago- nistic anti-CD40 Ab induced moderate alveolar enlargement. CD40 stimulation, in combination with anti-Fas Ab, induced significant emphysematous changes and increased alveolar cell apoptosis. CD40 stimulation also enhanced IFN-γ-mediated emphysematous changes, not via apoptosis induction, but via inflammation with lymphocyte accumulation. In vitro, Fas-mediated apoptosis was enhanced by CD40 stimulation and IFN- in endothelial cells and by CD40 stimulation in epithelial cells. CD40 stimulation induced secretion of CCR5 ligands in endothelial cells, enhanced with IFN-γ. Plasma sCD40L levels were significantly increased in patients with COPD, inversely correlating to the percentage of forced expiratory volume in 1 s and positively correlating to low attenuation area score by CT scan, regardless of smoking history. Collectively CD40 plays a contributing role in the development of pulmonary emphysema by sensitizing Fas-mediated apoptosis in alveolar cells and increasing the secretion of proinflammatory chemokines. © 2012 the American Physiological Society.

Background. The aims of the study were to identify the significance of interleukin (IL)-6 production and to determine whether IL-6 production influences long-term survival in patients with non-small-cell lung cancer (NSCLC). Method. A series of 90 patients with NSCLC who underwent surgery between 2005 and 2007 was analyzed. Preoperative serum IL-6 was measured, and tumor samples were immunohistochemically stained for IL-6. Results. Serum IL-6 levels were elevated in 43 of 90 cases (47.7%), and 23 (25.5%) of 90 cases stained positively for IL-6 (P =.00265). The prognosis of patients with NSCLC who had positive immunohistochemical staining was significantly worse than that for those who had negative staining, by univariate analysis (P =.0027). Multivariate analysis indicated that tumor size, postoperative stage, and overexpression of IL-6 were independent prognostic factors. Conclusions. The expression of IL-6 in tumor correlated with the concentration of serum IL-6, tumor progression, and overall survival in patients with NSCLC. © The Author(s) 2012.

Background: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) has a high diagnostic value in sarcoidosis if the obtained histological specimen is indicative of a non-caseating epithelioid-cell granuloma. However, EBUS-TBNA in sacoidosis sometimes affords solely cytological specimens. Objective: To investigate the relevance of EBUS-TBNA cytology specimens in diagnosing sarcoidosis. Design: The study population comprised 72 patients with sarcoidosis and 116 patients who had thoracic malignancies and intrathoracic lymphadenopathy but were eventually proven to be metastasis-free (controls). The EBUS-TBNA samples obtained for these subjects were blindly evaluated for the presence of epithelioid cell clusters by 2 independent cytoscreeners and a pathologist. Results: Interobserver variability in the specimen grading was minimal. The sensitivity and specificity were 65.3% and 94.0%, respectively. The sensitivity was high, at 87.5%, for the combined cytological and histological examinations. Of 7 controls whose cytological specimens showed epithelioid cell clusters, 3 were also deemed positive for sarcoidosis on histological examination, which indicated that they had sarcoid reaction to cancer. Conclusions: Cytological evaluation of the EBUS-TBNA specimens had higher sensitivity than histological evaluation alone for intrathoracic lymphadenopathy due to sarcoidosis. It should be recognized, however, that up to 6% of patients with thoracic malignancy may have sarcoid reaction in non-metastatic lymph nodes.

Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are effective in prolonging progression-free survival time of patients with non-small cell lung carcinoma, typically adenocarcinoma, bearing some active EGFR mutations in their tumors. However, the close relationship between the EGFR mutations and pleomorphic carcinoma of the lung, which is a very rare type of primary lung cancer, has never been elucidated. We present a 60-year-old Japanese woman with pleomorphic carcinoma of the lung that became resistant to cytotoxic chemotherapies including platinum-based chemotherapy, and her general condition seriously deteriorated. Thereafter, treatment with gefitinib was started and resulted in significant tumor shrinkage and a dramatic improvement in her general condition for up to 8.5 months. Analyses of the EGFR mutation in separately microdissected specimens from adenocarcinoma and spindle cell components revealed that both components possessed the L858R point mutation. These findings gave us some insight into the carcinogenesis of pleomorphic carcinoma of the lung in relation to EGFR gene alteration. Testing for EGFR mutation may be important in patients with advanced pleomorphic carcinoma including adenocarcinoma component that is usually chemoresistant.

Introduction/Background: Pyrimidine antimetabolites' target molecules thymidylate synthase (TS) and flopropyrimidine-metabolising enzymes such as dihydropyrimidine dehydrogenase (DPD), thymidine phosphorylase (TP) and orotate phosphoribosyltransferase (OPRT) are known as biomarkers of 5-fluorouracil (5-FU) treatment. The purpose of this study was to evaluate the feasibility of mRNA expression analysis for TS, DPD, TP, and OPRT using metastatic lymph node samples obtained by endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) in patients with Non-small-cell lung cancer (NSCLC). Materials and Methods: Metastatic lymph nodes from 20 patients with NSCLC diagnosed by EBUS-TBNA were analyzed. After pathological diagnosis, additional sections were made and confirmed the existence of tumor cells by hematoxylin and eosin staining. Tumor cells were extracted using laser-captured microdissection and the mRNA levels were measured by quantitative reverse-transcriptase polymerase chain reaction (RT-PCR) for each marker. Results: There were 17 mediastinal and 3 hilar lymph nodes. The histology included 13 cases of adenocarcinoma and 7 cases of squamous cell carcinoma. DPD and TP could be successfully analyzed in all samples and TS and OPRT could be measured in 18 samples. The median values of the relative TS, DPD, TP, and OPRT mRNA expression levels were 10.68, 6.23, 18.32, and 1.77, respectively. Conclusion: TS, DPD, TP, and OPRT mRNA expression levels could be analyzed using metastatic lymph node samples obtained by EBUS-TBNA. The result of this pilot study may be applicable for further translational research for the treatment of locally advanced NSCLC. © 2011 Elsevier Inc. All rights reserved.

We report the case of a dumbbell-shaped vertebral hemangioma mimicking a neurogenic tumor. A 73-year-old male was found on chest X-ray to have an abnormal shadow at the apex of the right upper lung field. Chest computed tomography revealed a 4.0-cm mass in the posterior right paravertebral region, adjacent to the T1 and T2 vertebral bodies. Given the location and shape of the tumor, it was suspected to be a neurogenic tumor. Magnetic resonance imaging revealed that the tumor extended into the spinal canal via the second intervertebral foramen. The tumor was resected successfully via hemilaminectomy with costotranversectomy. On pathological examination, the tumor was found to be a benign hemangioma. The patient is free of recurrence at 10 months post-resection. Vertebral hemangioma should be considered in the differential diagnosis of dumbbell-shaped tumors of the upper or posterior mediastinum.

Intraosseous benign notochordal cell tumor (BNCT) is a lesion postulated to be of notochordal cell origin. BNCT has recently been recognized as a potential precursor of classic chordoma, a rare malignant neoplasm usually presenting in the sacrococcygeal region, skull base, or mobile spine. Extra-axial chordoma is extremely rare, and only 2 cases of pulmonary chordoma have been reported previously. We describe herein 2 cases of hitherto-unreported lung tumors that were diagnosed as BNCT. The patients were a middle-aged asymptomatic man and woman who were each incidentally found to have a 15-mm pulmonary nodule on computed tomography. They underwent surgical resection of the tumors under a diagnosis of probable benign tumor of uncertain nature. Histopathologically, both tumors showed solid sheets of peculiar adipocyte-like univacuolated cells, multivacuolated cells, and less vacuolated cells with small, round nuclei and mildly eosinophilic cytoplasm. Mitosis was absent. These features were typical of BNCT. Immunohistochemically, the tumor cells in both cases were positive for brachyury, a transcription factor essential for notochordal cell differentiation and for other markers of notochordal cells including cytokeratins, vimentin, and S-100 protein. Postoperatively, extensive radiographic examination of the whole body revealed no evidence of a primary tumor elsewhere, and both patients are alive and well, with no evidence of disease 1 year after surgery. These 2 cases raise the possibility of a new explanation for the histogenesis of extra-axial chordomas: BNCT may be a precursor lesion of not only conventional axial chordoma but also of extra-axial chordoma. Copyright © 2011 by Lippincott Williams &amp Wilkins.

Human malignant pleural mesothelioma (HMPM) is highly resistant to conventional therapy, and therefore novel therapies are required. We previously reported that overexpression of the FUSE-binding protein-interacting repressor (FIR), a c-myc transcriptional repressor, induces apoptosis via c-Myc suppression, and is thus a suitable cancer therapy. In the current preclinical trial, a fusion gene deleted non-transmissible Sendai virus vector encoding FIR (SeV/Delta F/FIR) was prepared and its cytotoxic activity against an orthotopic xenograft model of HMPM, in combination with cisplatin, was assessed. SeV/Delta F/FIR and a fusion gene deleted non-transmissible Sendai virus vector encoding green fluorescent protein (SeV/Delta F/GFP) were prepared. The transduction efficiency of these agents in terms of dose-dependent cytotoxicity and/or apoptosis induction was then assessed in a few HMPM cells. Combination therapy with SeV/Delta F/FIR plus cisplatin was evaluated in vitro and in a mouse model. SeV/Delta F/FIR significantly reduced cell viability in three HMPM cell lines but was less effective in non-tumor immortalized mesothelial cells. SeV/Delta F/FIR cytotoxicity was partly due to apoptosis induction via c-Myc suppression. In addition, SeV/Delta F/FIR showed synergistic antitumor effects in combination with cisplatin, as was revealed by isobologram analysis in MSTO-211H. Moreover, combination therapy with SeV/Delta F/FIR plus cisplatin demonstrated significant tumor reduction and improvement in survival rate in an animal model. Combination therapy with SeV/Delta F/FIR plus cisplatin has therapeutic potential against HMPM. SeV/Delta F/FIR plus cisplatin will be an attractive modality against HMPM in the future. (Cancer Sci 2011; 102: 1366-1373)

Objectives: To assess risk of lung cancer (LC) in patients with preinvasive bronchial lesions and to identify factors associated with higher risk. Methods: 124 patients with one or more preinvasive bronchial lesions and normal chest computed tomography (CT) (mean age 66.7 years, 121 males and 3 females), followed-up by white light and autofluorescence bronchoscopy (AFB) every 4-6 mo and chest CT every 6-12 mo, end points were development of carcinoma in situ (CIS) or LC. Results: Among 124 patients with 240 preinvasive bronchial lesions, 20 CIS or LC lesions were detected during follow-up in 20 (16%) patients, 7 were detected as new endobronchial lesions, 10 as new peripheral lesions and 3 as local progression from severe dysplasia to CIS. Median time to progression from the same site or development of CIS/LC elsewhere was 24 months (range: 6-54 mo). The Cumulative risk of development of CIS/LC was 7% at one year, 20% at three years and 44% at 5 years. Among detected lung cancers, 80% were stage 0 or stage I and underwent treatment with curative intent. Diagnosis of new SD during follow-up (p = 0.0001), chronic obstructive pulmonary disease (COPD) (p = 0.001) or smoking index &gt;52 pack-year (p = 0.042) was associated with higher risk. Even after controlling for other risk factors, COPD was associated with risk for lung cancer. Baseline lesion grade was not predictive of patient outcome (p = 0.146). Conclusion: Patients with preinvasive bronchial lesions, especially those with new SD during follow-up, COPD or smoking &gt;52 pack-year are at high risk of LC, AFB and CT follow-up facilitated early detection and treatment with curative intent. (C) 2010 Elsevier Ireland Ltd. All rights reserved.

Objectives: We investigated the capabilities of an endo-cytoscopy system (ECS) that enables microscopic imaging of the tracheobronchial tree during bronchoscopy, including normal bronchial epithelium, dysplastic mucosa and squamous cell carcinoma. Methods: The newly developed ECS has a 3.2. mm diameter that can be passed through the 4.2. mm working channel of a mother endoscope for insertion of the ECS. It has a high magnification of 570× on a 17. in. video monitor. Twenty-two patients (7 squamous cell carcinoma, 11 squamous dysplasia and 4 after PDT therapies) were underwent white light, NBI light and AFI bronchoscopy. Both abnormal areas of interest and normal bronchial mucosa were stained with 0.5% methylene blue and examined with ECS at high magnification (570×). Histological examinations using haematoxylin and eosin staining were made of biopsied specimens. Analyzed ECS images were compared with the corresponding histological examinations. Results: In normal bronchial mucosa, ciliated columnar epithelial cells were visible. In bronchial squamous dysplasia, superficial cells with abundant cytoplasm were arranged regularly. In squamous cell carcinoma, large, polymorphic tumor cells showed increased cellular densities with irregular stratified patterns. These ECS images corresponded well with the light-microscopic examination of conventional histology. Conclusion: ECS was useful for the discrimination between normal bronchial epithelial cells and dysplastic cells or malignant cells during bronchoscopy in real time. This novel technology has an excellent potential to provide in vivo diagnosis during bronchoscopic examinations. © 2010 Elsevier Ireland Ltd.

Although the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) and Lambert-Eaton myasthenic syndrome (LEMS) are often individually accompanied by small-cell lung carcinoma, simultaneous occurrence of the 2 syndromes is rare. A 61-year-old man was admitted to our hospital because of fatigue and myasthenia in the extremities, and small-cell lung carcinoma with pulmonary metastasis was diagnosed, together with SIADH and LEMS. These syndromes markedly ameliorated following tumor shrinkage, with 4 cycles of chemotherapy consisting of carboplatin and etoposide. On progression of the tumor thereafter, neither syndrome recurred. A literature review disclosed that these syndromes frequently resolve with tumor shrinkage.

Pulmonary sclerosing hemangioma is relatively rare and is usually considered a benign tumor. There have been no reports of pulmonary sclerosing hemangioma with pleural dissemination. This report presents an extremely rare case of pulmonary sclerosing hemangioma with pulmonary dissemination. A 57-year-old woman was found to have an abnormal shadow in the right lower lung field on chest X-ray. Chest computed tomography (CT) indicated a 2.5-cm mass in the right lower lobe. A bronchoscopic biopsy failed to identify malignant cells, which led to the patient undergoing an excisional lung biopsy. Intraoperative findings showed a tumor in the right lower lobe with multiple small nodules in the pleura. The pathological findings revealed that the tumor was sclerosing hemangioma with pleural dissemination. Annual follow-up CT showed irregular pleural thickness, which suggested progressive dissemination 3 years after the operation. Although pulmonary sclerosing hemangioma is regarded as a benign tumor, the potential for malignancy may be a consideration in this setting.

Objective: To establish cytological features of pulmonary pleomorphic carcinoma (PC) or giant cell carcinoma (GC), we evaluated the cytological characteristics of these tumors using a multidisciplinary approach. Study Design: Samples from 13 surgically resected and histologically confirmed PC or GC patients were collected from our institutes. Eight cases without prior chemotherapy before surgery were selected, and cytological features were analyzed. Results: The background contained numerous lymphocytes and neutrophils. The tumor cells were arranged in flat loose clusters, but some were in fascicles. The shape of the tumor cell was spindle or pleomorphic, and the sizes of the tumor cells varied by more than 5-fold. The tumor cells had an abundant, thick and well-demarcated cytoplasm. The location of the nucleus was centrifugal, and the nucleus was oval or irregularly shaped. Multinucleated giant cells were frequently observed. The size of the nucleus was more than 5 times that of normal lymphocytes, and its size also varied by more than 5-fold. The nuclear membrane was thin, and nuclear chromatin was coarsely granular, while the nucleolus was single and round. Conclusion: PC or GC has characteristic cytological features, however, spindle cells tended to be hardly observed in cytological specimens in some cases. Copyright © 2011 S. Karger AG, Basel.

We report a case of hepatoid adenocarcinoma of the uterus in an 86-year-old woman. Serum AFP was elevated (7824 ng/ml) on admission. The surgical specimen obtained by simple hysterectomy and bilateral salpingo-oophorectomy showed an exophytic tumor, 10.5 cm x 6.0 cm x 3.7 cm in size, in the uterine corpus. Microscopically, tumor cells proliferated in trabecular or cord-like arrangement, which was considered as "hepatoid appearance". An adenocarcinomatous component was intermingled. The expressions of liver-enriched transcription factors, hepatocyte nuclear factor (HNF)-1 beta, HNF-3, HNF-4 alpha, and CCAAT/enhancer binding protein (C/EBP)-beta, were investigated in the present case and in 19 cases of endometrioid adenocarcinoma (11 cases of Grade 2 and 8 cases of Grade 3), because these nuclear factors are involved in embryonal hepatogenesis. HNF-4 alpha was diffusely positive in the present case, but negative in all cases of endometrioid adenocarcinoma. HNF-3 and C/EBP-beta were positive for the present case and control adenocarcinoma cases (HNF-3, 36.8% and C/EBP-beta, 84.2%). HNF-1 beta was negative for both the present case and endometrioid adenocarcinomas. This is the first report to demonstrate HNF-4 alpha expression in this rare uterine tumor. (c) 2011 Elsevier GmbH. All rights reserved.

We examined possible combinatory antitumor effects of replication-competent type 5 adenoviruses (Ad) lacking E1B-55kDa molecules (Ad-delE1B55) and chemotherapeutic agents in nine human esophageal carcinoma cells. Ad-delE1B55 produced cytotoxic effects on all the carcinoma cells and the cytotoxicity is not directly linked with the p53 status of the tumors or with the infectivity to respective tumors. A combinatory treatment with Ad-delE1B55 and an anticancer agent, 5-fluorouracil (5-FU), mitomycin C or etoposide, produced greater cytotoxic effects than that with either the Ad or the agent. Administration of 5-FU could minimally inhibit the viral replication and a simultaneous treatment with the Ad and 5-FU achieved better cytotoxicity than sequential treatments. We also confirmed the antitumor effects by the combination of Ad-delE1B55 with 5-FU in vivo. Cisplatin, however, did not achieve the combinatory effects in most of the cells tested. These data indicate that the Ad-delE1B55 produce combinatory antitumor effects with a chemotherapeutic agent irrespective of the administration schedule, but the effects depend on an agent in esophageal carcinoma. © 2010 Nature America, Inc. All rights reserved.

Information regarding prognosis of thymoma patients stratified by both World Health Organization classification and Masaoka staging system is very limited. Analyze 5-year survival data from a large number of thymoma patients stratified by both World Health Organization histologic type and Masaoka stage using meta-analysis. Perform power analysis to estimate the number of cases that would be needed to test the null hypothesis to a power of 80%. Five-year survival data from 905 thymoma patients treated with thymectomy at seven hospitals in America, Japan, Korea, India, Italy, and Germany. Survival data was reported as "dead" or "alive" to facilitate meta-analysis. Significant differences were detected only when comparing survival rates of thymoma patients in stages I to III with those of stage IV disease. Analysis by World Health Organization histologic type and stage yielded significant differences only in patients with thymomas A vs. B2 and A vs. B3 in stage III disease. No significant data heterogeneity was detected with funnel plots and Egger's regression test. Power analysis estimated that a study with 7077 patients is needed to evaluate the prognostic significance of all thymomas stratified by both World Health Organization histologic type and stage to a power of 80%. Selected World Health Organization histologic types are significantly associated with prognosis in stage III thymoma patients and may help select individuals benefiting from neoadjuvant therapy. Power analysis shows that studies with much larger number of patients are needed to exclude the possibility that histologic type may provide significant prognostic information in other stages of the disease. © 2010 Elsevier Inc. All rights reserved.

Background: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a minimally invasive procedure with a high yield for lymph node staging of lung cancer. The aim of this study was to assess the utility of sonographic features of lymph nodes during EBUS-TBNA for the prediction of metastasis in patients with lung cancer and to establish a standard endobronchial ultrasound (EBUS) image classification system. Methods: Digital images of lymph nodes obtained during EBUS-TBNA in patients with lung cancer were categorized according to the following characteristics: (1) size (short axis) less or more than 1 cm, (2) shape (oval or round), (3) margin (indistinct or distinct), (4) echogenicity (homogeneous or heterogeneous), (5) presence or absence of central hilar structure, and (6) presence or absence of coagulation necrosis sign. The sonographic findings were compared with the final pathologic results. Results: A total of 1,061 lymph nodes were retrospectively evaluated in 487 patients. The accuracy of predicting metastatic property for each category was as high as 63.8% to 86.0%. A multivariate analysis revealed that round shape, distinct margin, heterogeneous echogenicity, and presence of coagulation necrosis sign were independent predictive factors for metastasis. Two hundred eighty-five of the 664 lymph nodes (42.9%) having at least one metastatic feature of the four categories were pathologically proven metastatic, and 96.0% of lymph nodes (381/397) were proven not metastatic when all four categories were determined as benign. Conclusions: Sonographic features of lymph nodes based on the new EBUS imaging classification may be helpful in the prediction of metastatic lymph nodes during EBUS-TBNA. © 2010 American College of Chest Physicians.

Objectives: We investigated the ability of a high-resolution bronchovideoscopy system with narrow band imaging (NB!) to detect blood vessel structures in squamous cell carcinoma (SCC) of bronchi, as well as squamous dysplasia. Methods: Seventy-nine patients with either abnormal sputum cytology or lung cancer were entered into the study. First, high-resolution bronchovideoscopy with white light was performed. Observations were repeated using NBI light to examine microvascular structures in the bronchial mucosa. Spectral features of the RGB (red/green/blue) sequential videoscope system were changed from a conventional RGB filter to the new NBI filter. The wavelength ranges of the NBI filter were: 400-430 nm (blue), 400-430 nm (green) and 520-560 nm (red). Results: The following were clearly observed with NBI with high-resolution bronchovideoscopy: increased vessel growth and complex networks of tortuous vessels of various sizes, in squamous dysplasia; some dotted vessels, in addition to increased vessel growth and complex networks of tortuous vessels, in ASD; several dotted vessels and spiral or screw type tumor vessels of various sizes and grades, in SCC. Capillary blood vessel and/or tumor vessel mean diameters of ASD, CIS, microinvasive and invasive carcinoma were 41.4 +/- 9.8 mu m, 63.7 +/- 8.2 mu m, 136.5 +/- 29.9 mu m and 259.4 +/- 29.6 mu m, respectively. These results indicated a statistically significant increase of mean vessel diameters in the four groups (P &lt;0.0001). Conclusion: NW with high-resolution bronchovideoscopy was useful for detecting the increased vessel growth and complex networks of tortuous vessels, dotted vessels and spiral or screw type tumor vessels of bronchial mucosa. This may enable detecting the onset of angiogenesis during multi-step carcinogenesis of the lung. (C) 2010 Elsevier Ireland Ltd. All rights reserved.

近年，高分解能CT（high resolution computed tomography；HRCT）の普及に伴い末梢小型肺結節が多く検出されるようになった．高分化腺癌である細気管支肺胞上皮癌（bronchioloalveolar carcinoma；BAC）は，肺胞上皮置換性に増殖しHRCTですりガラス陰影（ground glass opacity；GGO）を呈する．一方，末梢型肺扁平上皮癌はCT及び病理組織学的に充実性結節として認められることが多く，BACのように肺胞壁に沿って進展することは極めて稀である．今回我々は，CT上GGOを呈し病理組織所見で肺胞壁に沿って伸展する末梢の扁平上皮癌を経験したので，文献的考察を加えて報告する．<br>

Background. Surgical treatment of small cell lung cancer (SCLC) is limited to stage I disease. Therefore, accurate lymph node staging is mandatory in SCLC patients. The purpose of this study was to evaluate the utility of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) for the evaluation of mediastinal and hilar lymph node metastasis in patients with SCLC. Methods. Forty patients with untreated SCLC who underwent EBUS-TBNA for lymph node staging between November 2002 and September 2008 were retrospectively analyzed. The convex probe endobronchial ultrasonography was used for EBUS-TBNA. Lymph nodes assessed by the convex probe endobronchial ultrasonography were aspirated until EBUS-TBNA revealed malignant cells by rapid on-site cytology. Results. Endobronchial ultrasound-guided transbronchial needle aspiration was successfully performed in all patients, and revealed lymph node status as follows: N0, 13 cases; N1, 5 cases; and N2, 22 cases. Among the 13 N0 cases, 9 patients underwent surgery, whereas 4 patients did not undergo surgical intervention because of enlargement of subaortic or paraaortic lymph nodes (stations 5 and 6) that precluded EBUS-TBNA assessment (n = 3) or poor performance status (n = 1). Pathologic examination of dissected nodes confirmed an N0 diagnosis in 8 patients, whereas 1 patient had hilar lymph node metastasis (N1). The sensitivity, specificity, and diagnostic accuracy rate of EBUS-TBNA were 96.4%, 100%, and 97.2%, respectively. The overall 5-year survival rate for the 9 patients who underwent surgery was 77.8%. Conclusions. Endobronchial ultrasound-guided transbronchial needle aspiration has a high diagnostic yield for the evaluation of mediastinal and hilar lymph node metastasis in SCLC and has a high impact on patient management.