2024/03/25 更新

写真a

サトウ ヤスハル
佐藤 康晴
SATO Yasuharu
所属
保健学域 教授
職名
教授

学位

  • 医学博士 ( 岡山大学 )

研究キーワード

  • 病理学

  • Pathology

  • Castleman disease

  • IgG4-related disease

  • Lymphoproliferative disorders

研究分野

  • ライフサイエンス / 膠原病、アレルギー内科学

  • ライフサイエンス / 人体病理学

経歴

  • 岡山大学学術研究院保健学域   教授

    2021年4月 - 現在

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  • 岡山大学   Graduate School of Health Sciences

    2016年 - 現在

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  • 岡山大学   Graduate School of Health Sciences

    2014年 - 2016年

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  • 岡山大学   Graduate School of Medicine , Dentistry and Pharmaceutical Sciences

    2011年 - 2014年

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  • 岡山大学   Graduate School of Medicine , Dentistry and Pharmaceutical Sciences

    2010年 - 2011年

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  • 岡山大学病院病理部 医員

    2009年4月 - 2009年12月

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所属学協会

  • International Academy of Cytology(専門医)

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  • 日本リンパ網内系学会(常任理事)

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  • 日本臨床細胞学会(評議員、専門医)

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  • 日本病理学会(評議員、専門医)

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  • 日本IgG4関連疾患学会(理事)

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委員歴

  • 血液病理認定医(日本リンパ網内系学会)  

    2024年1月 - 現在   

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  • WHO Classification 5th ed. (Heamatolymphoid tumours, Skin tumours)   Author  

    2023年 - 現在   

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  • 日本リンパ網内系学会   常任理事  

    2022年 - 現在   

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  • 分子病理専門医(日本病理学会)  

    2022年 - 現在   

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  • 日本リンパ網内系学会   理事  

    2020年 - 現在   

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  • 日本IgG4関連疾患学会   理事  

    2019年 - 現在   

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  • 日本病理学会   評議員, 専門医  

    2015年 - 現在   

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    団体区分:学協会

    日本病理学会

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  • 国際細胞学会   フェロー, 認定細胞病理医  

    2015年 - 現在   

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    団体区分:学協会

    国際細胞学会

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  • 日本臨床細胞学会   評議員, 専門医  

    2013年 - 現在   

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    団体区分:学協会

    日本臨床細胞学会

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  • 日本リンパ網内系学会   評議員  

    2010年 - 現在   

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    団体区分:学協会

    日本リンパ網内系学会

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論文

  • Analysis of Notch1 protein expression in methotrexate-associated lymphoproliferative disorders.

    Takeshi Okatani, Midori Filiz Nishimura, Yuria Egusa, Sayako Yoshida, Yoshito Nishimura, Asami Nishikori, Tadashi Yoshino, Hidetaka Yamamoto, Yasuharu Sato

    Journal of clinical and experimental hematopathology : JCEH   2024年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Methotrexate (MTX)-associated lymphoproliferative disorder (MTX-LPD) is a lymphoproliferative disorder in patients treated with MTX. The mechanism of pathogenesis is still elusive, but it is thought to be a complex interplay of factors, such as underlying autoimmune disease activity, MTX use, Epstein-Barr virus infection, and aging. The NOTCH genes encode receptors for a signaling pathway that regulates various fundamental cellular processes, such as proliferation and differentiation during embryonic development. Mutations of NOTCH1 have been reported in B-cell tumors, including chronic lymphocytic leukemia/lymphoma, mantle cell lymphoma, and diffuse large B-cell lymphoma (DLBCL). Recently, it has also been reported that NOTCH1 mutations are found in post-transplant lymphoproliferative disorders, and in CD20-positive cells in angioimmunoblastic T-cell lymphoma, which might be associated with lymphomagenesis in immunodeficiency. In this study, to investigate the association of NOTCH1 in the pathogenesis of MTX-LPD, we evaluated protein expression of Notch1 in nuclei immunohistochemically in MTX-LPD cases [histologically DLBCL-type (n = 24) and classical Hodgkin lymphoma (CHL)-type (n = 24)] and de novo lymphoma cases [DLBCL (n = 19) and CHL (n = 15)]. The results showed that among MTX-LPD cases, the expression of Notch1 protein was significantly higher in the DLBCL type than in the CHL type (P < 0.001). In addition, among DLBCL morphology cases, expression of Notch1 tended to be higher in MTX-LPD than in the de novo group; however this difference was not significant (P = 0.0605). The results showed that NOTCH1 may be involved in the proliferation and tumorigenesis of B cells under the use of MTX. Further research, including genetic studies, is necessary.

    DOI: 10.3960/jslrt.23038

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  • Primary Thyroid Lymphoma: Clinical Factors Predicting the Possibility of Diffuse Large B-Cell Lymphoma. 国際誌

    Akifumi Kariya, Tomoyasu Tachibana, Yasushi Hiramatsu, Yoji Wani, Jun-Ya Matsumoto, Chieko Furukawa, Asuka Sato, Yuto Naoi, Yorihisa Orita, Yasuharu Sato, Mizuo Ando

    Ear, nose, & throat journal   1455613231218130 - 1455613231218130   2023年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Aims: Among primary thyroid lymphomas (PTLs), diffuse large B-cell lymphoma (DLBCL) has a poorer prognosis than other indolent lymphomas such as mucosa-associated lymphoid tissue (MALT) or follicular lymphoma (FL). However, the clinical differences between DLBCL and indolent lymphoma remain unclear. Therefore, this retrospective study on PTL was aimed at investigating the clinical differences between DLBCL and indolent lymphomas and identifying the factors differentiating DLBCL from indolent lymphomas. Materials and Methods: Medical records of 28 patients diagnosed with PTL and treated at our institution between 2005 and 2022 were retrospectively analyzed. Data on the following clinical variables were extracted: sex, age, symptoms (pain and dysphagia), ultrasonographic appearance patterns, the presence of airway stenosis on computed tomography and laryngeal endoscopy, blood test results, disease stage, and pathological diagnosis. Results: In all, 13 patients were histologically diagnosed with DLBCL, 12 with MALT lymphoma, and 3 with FL. Significant differences in disease-specific survival rates were evident between the DLBCL and indolent lymphoma groups (68.2 vs 100%, P = .043). High lactate dehydrogenase levels (>230 U/mL) and airway stenosis were observed only in patients with DLBCL. Multivariate analysis identified that the presence of a linear echoic strand pattern and the absence of an echoic nodular pattern on ultrasound were independently associated with DLBCL (P = .0497 and .012, respectively). Conclusion: DLBCL can cause airway stenosis. The linear echogenic strand pattern and the absence of a nodular pattern should be recognized as predictive factors of DLBCL.

    DOI: 10.1177/01455613231218130

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  • 遺伝子解析に有用な細胞固定液と保存方法の検討

    原武 朋加, 西脇 万結, 湯浅 凌雅, 錦織 亜沙美, 西村 碧フィリーズ, 佐藤 康晴

    岡山県臨床細胞学会誌   41   44 - 44   2023年12月

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    記述言語:日本語   出版者・発行元:岡山県臨床細胞学会  

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  • 唾液腺分泌癌の細胞病理学的所見とギムザ染色の診断的有用性

    植田 向夏花, 錦織 歩, 江草 侑厘安, 錦織 亜沙美, 西村 碧フィリーズ, 柳井 広之, 佐藤 康晴

    岡山県臨床細胞学会誌   41   43 - 43   2023年12月

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    記述言語:日本語   出版者・発行元:岡山県臨床細胞学会  

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  • Pediatric IgG4-related disease: a descriptive review. 国際誌

    Satoshi Hara, Misaki Yoshida, Hajime Sanada, Yasunori Suzuki, Yasuharu Sato, Ichiro Mizushima, Mitsuhiro Kawano

    Expert review of clinical immunology   1 - 23   2023年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    INTRODUCTION: IgG4-related disease (IgG4-RD) is an immune-mediated systemic fibroinflammatory condition characterized by serum IgG4 elevation and IgG4-positive plasma cell infiltration into various organs. It generally occurs in elderly males. Pediatric cases have been reported, albeit rarely, accordingly lack of recognition of such cases could delay therapeutic intervention leading to poorer outcomes. AREAS COVERED: The present review is a descriptive review of all published case reports, cohort studies, and reviews of pediatric IgG4-RD listed in PubMed. Characteristics of pediatric IgG4-RD were clarified, including sex, organ involvement, serological and histological findings, and treatment. We assessed how many published cases met current classification and comprehensive diagnostic criteria. EXPERT OPINION: The characteristics of pediatricIgG4-RD differed from adult IgG4-RD in terms of sex and involved organs. There was no clear male dominance in numbers of cases, and surface organ involvement such as ophthalmic diseases were more common in the pediatric IgG4-RD. Organ involvement tended to be indolent and unilateral, causing difficulty in definitively diagnosing pediatric IgG4-RD. Only about 20% of published cases met IgG4-RD classification or comprehensive diagnostic criteria. Physicians should be careful in diagnosing pediatric IgG4-RD after excluding mimickers. International collaboration toward high-quality evidence to support diagnosis and treatment of pediatric IgG4-RD is advised.

    DOI: 10.1080/1744666X.2023.2274358

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  • Near-infrared photoimmunotherapy for salivary duct carcinoma. 国際誌

    Takuma Makino, Yasuharu Sato, Kensuke Uraguchi, Yuto Naoi, Yujiro Fukuda, Mizuo Ando

    Auris, nasus, larynx   2023年9月

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    記述言語:英語  

    In Japan, near-infrared photoimmunotherapy (NIR-PIT) was introduced in 2021 as a treatment option for unresectable recurrent head and neck cancer. The treatment targets the epidermal growth factor receptor (EGFR), which is overexpressed in 80-90 % of head and neck squamous cell carcinoma (HNSCC). NIR-PIT should theoretically show therapeutic efficacy if EGFR is expressed, even in nonsquamous cell carcinomas (non-SCC). To the best of our knowledge, there are no case reports of NIR-PIT for non-SCC. We performed NIR-PIT in a patient with non-SCC of the head and neck region. After performing two NIR-PIT treatments, small free clusters of residual tumor cells were observed. Immunostaining in this specimen revealed EGFR expression in residual tumor cells. The residual tumor cells had been irradiated sufficiently to achieve necrosis. It is suggested that not only laser irradiation and expression of EGFR but also other factors are involved in the efficacy of this treatment. Further investigation for these other factors is warranted.

    DOI: 10.1016/j.anl.2023.09.006

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  • Distribution and clinical impact of molecular subtypes with Dark Zone signature of DLBCL in a Japanese real-world study. 国際誌

    Tomohiro Urata, Yusuke Naoi, Aixiang Jiang, Merrill Boyle, Kazutaka Sunami, Toshi Imai, Yuichiro Nawa, Yasushi Hiramatsu, Kazuhiko Yamamoto, Soichiro Fujii, Isao Yoshida, Tomofumi Yano, Ryota Chijimatsu, Hiroyuki Murakami, Kazuhiro Ikeuchi, Hiroki Kobayashi, Katsuma Tani, Hideki Ujiie, Hirofumi Inoue, Shuta Tomida, Akira Yamamoto, Takumi Kondo, Hideaki Fujiwara, Noboru Asada, Hisakazu Nishimori, Keiko Fujii, Nobuharu Fujii, Ken-Ichi Matsuoka, Keisuke Sawada, Shuji Momose, Jun-Ichi Tamaru, Asami Nishikori, Yasuharu Sato, Tadashi Yoshino, Yoshinobu Maeda, David W Scott, Daisuke Ennishi

    Blood advances   2023年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    The distribution and clinical impact of cell-of-origin (COO) subtypes of diffuse large B-cell lymphoma (DLBCL) outside Western countries remain unknown. Recent literature also suggests that there is an additional COO subtype associated with the germinal center dark zone, that warrants wider validation to generalize clinical relevance. Here, we assembled a cohort of Japanese patients with untreated DLBCL and determined the refined COO subtypes, that include the dark zone signature (DZsig), using the NanoString DLBCL90 assay. To compare the distribution and clinical characteristics of the molecular subtypes, we used a dataset from the cohort of BC Cancer (BCC) (n = 804). Of the 1050 patients where DLBCL90 assay was successfully performed in our cohort, 35%, 45%, and 6% of patients were identified to be germinal center B-cell-like (GCB)-DLBCL, activated B-cell-like (ABC)-DLBCL, and DZsigpos-DLBCL, respectively, with the highest prevalence of ABC-DLBCL differing significantly from that of BCC (P < 0.001). GCB-DLBCL, ABC-DLBCL, and DZsigpos-DLBCL were associated with two-year overall survival rates of 88%, 75%, and 66%, respectively (P < 0.0001), with patients of the DZsigpos-DLBCL having the poorest prognosis. In contrast, GCB-DLBCL without DZsig showed excellent outcomes following rituximab-containing immunochemotherapy. DZsigpos-DLBCL was associated with the significant enrichment of tumors with CD10 expression, concurrent MYC/BCL2 expression, and depletion of microenvironmental components (all P < 0.05). These results provide evidence of the distinct distribution of clinically relevant molecular subtypes in Japanese DLBCL and that refined COO, as measured by the DLBCL90 assay, is a robust prognostic biomarker that is consistent across geographical areas.

    DOI: 10.1182/bloodadvances.2023010402

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  • Comparison of serum sIL-2R and LDH levels in patients with intravascular large B-cell lymphoma and patients with advanced stage diffuse large B-cell lymphoma 査読

    Yuki Hirami, Midori Filiz Nishimura, Tomohiro Urata, Michiko Morimoto, Yukina Maekawa, Tadashi Yoshino, Yoshito Nishimura, Yasuharu Sato

    Journal of Clinical and Experimental Hematopathology   63 ( 1 )   25 - 31   2023年1月

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    担当区分:最終著者, 責任著者   掲載種別:研究論文(学術雑誌)   出版者・発行元:Japanese Society for Lymphoreticular Tissue Research  

    DOI: 10.3960/jslrt.22043

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  • A Case of Adolescent-onset TAFRO Syndrome with Malignant Nephrosclerosis-like Lesions. 査読

    Yuki Nakayama, Hiroki Mizuno, Naoki Sawa, Tatsuya Suwabe, Masayuki Yamanouchi, Daisuke Ikuma, Eiko Hasegawa, Junichi Hoshino, Akinari Sekine, Yuki Oba, Kei Kono, Keiichi Kinowaki, Kenichi Ohashi, Kodai Suzuki, Yasuharu Sato, Akira Shimizu, Yutaka Yamaguchi, Yoshifumi Ubara

    Internal medicine (Tokyo, Japan)   62 ( 15 )   2223 - 2229   2022年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    A 16-year-old Japanese girl developed a fever, thrombocytopenia, and renal dysfunction. Treatment was started with steroids, but cervical lymphadenopathy and ascites developed. A lymph node biopsy indicated TAFRO syndrome. The patient's renal function deteriorated, and dialysis was started. Refractory hypertension and subsequent encephalopathy developed. Treatment was started with an anti-IL-6 receptor antibody and an anti-CD20 monoclonal antibody. A kidney biopsy showed malignant nephrosclerosis-like microangiopathy and glomerular collapse due to narrowing of the small arteries. The majority of TAFRO syndrome cases are adult-onset, with glomerular microangiopathy. To our knowledge, this is the first report of adolescent-onset TAFRO syndrome presenting with malignant nephrosclerosis-like lesions associated with hypertension.

    DOI: 10.2169/internalmedicine.0529-22

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  • Utility of renal biopsy in differentiating idiopathic multicentric Castleman disease from IgG4-related disease. 査読

    Miharu Kawanishi, Fumika Kamei, Hirotaka Sonoda, Masafumi Oba, Shohei Fukunaga, Masahiro Egawa, Takashi Koyama, Yasuharu Sato, Kazuaki Tanabe, Takafumi Ito

    CEN case reports   12 ( 2 )   242 - 248   2022年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Idiopathic multicentric Castleman disease (iMCD) is a subtype of human herpesvirus type 8 (HHV-8)-related Castleman disease that causes multi-organ damage, including kidney damage due to polyclonal lymphoproliferation and interleukin (IL)-6-induced cytokine storm. However, its renal pathological findings are unclear. We report the case of a woman in her 80 s who was diagnosed with iMCD based on renal pathological findings. Five years ago, hypergammaglobulinemia was detected, and her renal function declined. Renal biopsy revealed plasma cells infiltrating the stroma. Immunostaining revealed numerous IgG4-positive plasma cells. The serum IgG4 level was high, and she was initially diagnosed with IgG4-related disease (IgG4-RD) and treated with steroids. However, the therapeutic effect was poor. On re-examination, computed tomography revealed lymphadenopathy around the aorta and spleen. Renal histopathology showed numerous IL-6-positive plasma cells. Anemia and C-reactive protein (CRP) positivity persisted despite steroid administration. HHV-8 was negative, and polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes syndrome was not suspected. Thus, iMCD was diagnosed. Based on previous reports, there is no significant difference in IgG4 levels between iMCD and IgG4-RD, and IgG4-positive plasma cell infiltrates were observed in iMCD-affected organs. Therefore, it may be difficult to distinguish iMCD from IgG4-RD. In this case, high-serum IL-6 and CRP were observed, which are usually not seen in IgG4-RD but are common findings in iMCD, leading to the diagnosis. Patients with deep lymphadenopathy may be diagnosed with iMCD based on renal pathological findings. Renal biopsy is recommended for patients with suspected iMCD and decreased renal function.

    DOI: 10.1007/s13730-022-00751-w

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  • Clinical characteristics and outcomes of Castleman disease: a multicenter Consortium study of 428 patients with 15-year follow-up. 査読 国際誌

    Wanying Liu, Qingqing Cai, Tiantian Yu, Paolo Strati, Frederick B Hagemeister, Qiongli Zhai, Mingzhi Zhang, Ling Li, Xiaosheng Fang, Jianyong Li, Ruifang Sun, Shanxiang Zhang, Hanjin Yang, Zhaoming Wang, Wenbian Qian, Noriko Iwaki, Yasuharu Sato, Eric Oksenhendler, Zijun Y Xu-Monette, Ken H Young, Li Yu

    American Journal of Cancer Research   12 ( 9 )   4227 - 4240   2022年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Castleman disease (CD) has been reported as a group of poorly understood lymphoproliferative disorders, including unicentric CD (UCD) and idiopathic multicentric CD (iMCD) which are human immunodeficiency virus (HIV) negative and human herpes virus 8 (HHV-8) negative. The clinical and independent prognostic factors of CD remain poorly elucidated. We retrospectively collected the clinical information of 428 patients with HIV and HHV-8 negative CD from 12 large medical centers with 15-year follow-up. We analyzed the clinicopathologic features of 428 patients (248 with UCD and 180 with iMCD) with a median age of 41 years. The histology subtypes were hyaline-vascular (HV) histopathology for 215 patients (56.58%) and plasmacytic (PC) histopathology for 165 patients (43.42%). Most patients with UCD underwent surgical excision, whereas the treatment strategies of patients with iMCD were heterogeneous. The outcome for patients with UCD was better than that for patients with iMCD, 5-year overall survival (OS) rates were 95% and 74%, respectively. In further analysis, a multivariate analysis using a Cox regression model revealed that PC subtype, hepatomegaly and/or splenomegaly, hemoglobin ≤ 80 g/L, and albumin ≤ 30 g/L were independent prognostic factors of CD for OS. The model of iMCD revealed that age > 60 years, hepatomegaly and/or splenomegaly, and hemoglobin ≤ 80 g/L were independent risk factors. In UCD, single-factor analysis identified two significant risk factors: hemoglobin ≤ 100 g/L and albumin ≤ 30 g/L. Our study emphasizes the distinction of clinical characteristics between UCD and iMCD. The importance of poor risk factors of different clinical classifications may direct more precise and appropriate treatment strategies.

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  • Neuropeptide Y Antagonizes Development of Pulmonary Fibrosis Through IL-1β Inhibition. 国際誌

    Junko Itano, Akihiko Taniguchi, Satoru Senoo, Noboru Asada, Yuka Gion, Yuria Egusa, Lili Guo, Naohiro Oda, Kota Araki, Yasuharu Sato, Shinichi Toyooka, Katsuyuki Kiura, Yoshinobu Maeda, Nobuaki Miyahara

    American journal of respiratory cell and molecular biology   67 ( 6 )   654 - 665   2022年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Neuropeptide Y, a 36-amino acid residue polypeptide, distributed throughout the nervous system, acts on various immune cells in many organs, including the respiratory system. However, little is known about its role in the pathogenesis of pulmonary fibrosis. This study was performed to determine the effects of neuropeptide Y on pulmonary fibrosis. Neuropeptide Y-deficient and wild-type mice were intratracheally administered bleomycin. Inflammatory cells, cytokine levels, and morphological morphometry of the lungs were analyzed. Serum neuropeptide Y levels were also measured in idiopathic pulmonary fibrosis patients and healthy controls. Neuropeptide Y-deficient mice exhibited significantly enhanced pulmonary fibrosis and higher IL-1β levels in the lungs compared to wild-type mice. Exogenous neuropeptide Y treatment suppressed the development of bleomycin-induced lung fibrosis and decreased IL-1β levels in the lungs. Moreover, IL-1β neutralization in neuropeptide Y-deficient mice attenuated the fibrotic changes. Neuropeptide Y decreased IL-1β release, and Y1 receptor antagonists inhibited IL-1β release and induced epithelial mesenchymal transition in human alveolar epithelial cells. Patients with idiopathic pulmonary fibrosis had lower neuropeptide Y and greater IL-1β levels in the serums compared to healthy controls. Neuropeptide Y expression was mainly observed around bronchial epithelial cells in human idiopathic pulmonary fibrosis lungs. These data suggest that neuropeptide Y plays a protective role against pulmonary fibrosis by suppressing IL-1β release and manipulating the neuropeptide Y-Y1 receptor axis could be a potential therapeutic strategy for delaying disease progression.

    DOI: 10.1165/rcmb.2021-0542OC

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  • Idiopathic Plasmacytic Lymphadenopathy Forms an Independent Subtype of Idiopathic Multicentric Castleman Disease 査読

    Asami Nishikori, Midori Nishimura, Yoshito Nishimura, Fumio Otsuka, Kanna Maehama, Kumiko Ohsawa, Shuji Momose, Naoya Nakamura, Yasuharu Sato

    International Journal of Molecular Sciences   23 ( 18 )   10301 - 10301   2022年9月

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    担当区分:最終著者, 責任著者   掲載種別:研究論文(学術雑誌)   出版者・発行元:MDPI AG  

    Idiopathic multicentric Castleman disease (iMCD) is a type of Castleman disease that is not related to KSHV/HHV8 infection. Currently, iMCD is classified into iMCD-TAFRO (thrombocytopenia, anasarca, fever, reticulin fibrosis, and organomegaly) and iMCD-NOS (not otherwise specified). The former has been established as a relatively homogeneous disease unit that has been recently re-defined, while the latter is considered to be a heterogeneous disease that could be further divided into several subtypes. In 1980, Mori et al. proposed the concept of idiopathic plasmacytic lymphadenopathy (IPL), a disease presenting with polyclonal hypergammaglobulinemia and a sheet-like proliferation of mature plasma cells in the lymph nodes. Some researchers consider IPL to be a part of iMCD-NOS, although it has not been clearly defined to date. This is the first paper to analyze iMCD-NOS clinicopathologically, to examine whether IPL forms a uniform disease unit in iMCD. Histologically, the IPL group showed prominent plasmacytosis and the hyperplasia of germinal centers, while the non-IPL group showed prominent vascularity. Clinically, the IPL group showed significant thrombocytosis and elevated serum IgG levels compared to the non-IPL group (p = 0.007, p &lt; 0.001, respectively). Pleural effusion and ascites were less common in the IPL group (p &lt; 0.001). The IPL group was more likely to have an indolent clinical course and a good response to the anti-IL-6 receptor antibody, while the non-IPL counterpart frequently required more aggressive medical interventions. Thus, the IPL group is a clinicopathologically uniform entity that forms an independent subtype of iMCD.

    DOI: 10.3390/ijms231810301

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  • Clinicopathological characteristics of gastric IgG4-related disease: Systematic scoping review. 査読 国際誌

    Haruki Sawada, Torrey Czech, Krixie Silangcruz, Landon Kozai, Adham Obeidat, Eric Andrew Wien, Midori Filiz Nishimura, Asami Nishikori, Yasuharu Sato, Yoshito Nishimura

    Journal of gastroenterology and hepatology   2022年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: Gastric IgG4-related disease (IgG4-RD) can mimic malignancy, submucosal tumors (SMT), and ulcers, leading to over-triage and unnecessary medical interventions such as gastrectomy. The variability in the clinicopathological presentation of IgG4-related disease is not yet well defined, posing a diagnostic challenge. METHODS: Following the PRISMA Extension for Scoping Reviews, we searched MEDLINE and EMBASE for all peer-reviewed articles using keywords including"gastritis," "stomach," "gastrointestinal stromal tumor," and "IgG4-RD" from their inception to December 28, 2021. RESULTS: 39 articles, including two observational studies and 42 cases, were included in the systematic review. While bottom-heavy lymphoplasmacytic mucosal infiltration is a characteristic finding of gastric IgG4-RD, it was only present in less than half of the patients in the observational studies. Patients with Gastric IgG4-RD were more likely to be diagnosed with gastrointestinal stromal tumor (GIST), gastric cancer, or peptic ulcer disease and their clinical course involved resection (51.3%) or even gastrectomy. Diagnosis of gastric IgG4-RD was most frequently made by post-operative pathological analysis. CONCLUSION: This systematic review summarizes the current understanding of the characteristics of gastric IgG4-RD. Increased awareness of gastric IgG4-RD as a differential diagnosis of gastric SMT or ulcers among clinicians is crucial in order to reduce unnecessary high-risk, invasive interventions.

    DOI: 10.1111/jgh.15980

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  • 9p24.1 Genetic Alteration and PD-L1 Expression Are Characteristic of De Novo and Methotrexate-associated Epstein-Barr Virus-positive Hodgkin Lymphoma, But Not Methotrexate-associated Hodgkin-like Lesions. 査読 国際誌

    Sawako Shiraiwa, Yara Yukie Kikuti, Joaquim Carreras, Yusuke Kondo, Ken Ohmachi, Yoshiaki Ogawa, Hiroshi Kawada, Shinji Sato, Yuka Gion, Yasuharu Sato, Naoya Nakamura, Kiyoshi Ando

    The American journal of surgical pathology   46 ( 8 )   1017 - 1024   2022年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Although the alteration of the 9p24.1 chromosome locus and PD-L1 overexpression is found in nodular sclerosis classic Hodgkin lymphoma, whether these aberrations occur in CHL and Hodgkin-like lesion (HLL) of methotrexate-associated lymphoproliferative disorder (MTX-CHL and MTX-HLL) is unknown. We compared the clinicopathologic features, the genomic status of the 9p24.1 locus and PD-L1 expression in a series of 34 patients including 17 with Epstein-Barr virus-positive de novo CHL, 7 with MTX-CHL, 10 with MTX-HLL using an immunofluorescence in situ hybridization method and immunohistochemistry. The proportions of cells with 9p24.1 genetic alteration in CD30-positive Hodgkin/Reed-Sternberg cells of de novo CHL, MTX-CHL and MTX-HLL were 55%, 68%, and 24%, respectively. The positive rates of PD-L1 measured by immunohistochemical H-scores of de novo CHL, MTX-CHL and MTX-HLL were 142±38, 157±75, and 70±42, respectively. Alteration of the 9p24.1 gene and expression of PD-L1 protein were correlated with all 3 diseases (correlation coefficient, 0.731). Both alteration of the 9p24.1 gene and overexpression of PD-L1 protein were observed in Epstein-Barr virus-positive de novo CHL and MTX-CHL but not in MTX-HLL. In conclusion, MTX-CHL has similar pathogenesis-like de novo CHL, but MTX-HLL seems to be a different disease from de novo CHL and MTX-CHL.

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  • Global public awareness of Castleman disease and TAFRO syndrome between 2015 and 2021: A Google Trends analysis. 査読 国際誌

    Yoshito Nishimura, Midori Filiz Nishimura, David C Fajgenbaum, Frits van Rhee, Yasuharu Sato, Fumio Otsuka

    EJHaem   3 ( 3 )   748 - 753   2022年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Wiley  

    Castleman disease (CD) is a rare lymphoproliferative disorder with multiple subtypes. Thrombocytopenia, anasarca, fever, reticulin fibrosis or renal insufficiency, and organomegaly (TAFRO) syndrome can occur in the context of CD. The study evaluated worldwide public awareness of CD and TAFRO syndrome using Google Trends data between 2015 and 2021. Our results showed that global public interest steadily grew until late 2019, at a small but significant rate of 1.1% per month from the 1st to 57th month (1/2015-9/2019). The increase coincided with a peak in the United States and Japan, but the search volume decreased at a rate of 1.3% per month after that time. No clear trend changes were noted throughout the study period with the search term "TAFRO." However, the search volume significantly increased during the time period at a rate of 4.8% (confidence interval [CI]: 2.8, 6.8) and 4.7% (CI: 2.7, 6.8) per month in Japan and worldwide, respectively. There was an insufficient search volume for "TAFRO" in the United States to perform the analysis. Most searches on "TAFRO" stemmed from Japan, suggesting considerable geographical disparity in the awareness of TAFRO syndrome. Further efforts are crucial to raise the awareness of CD and TAFRO syndrome among physicians and the general public, primarily in non-USA and Japanese countries.

    DOI: 10.1002/jha2.459

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    その他リンク: https://onlinelibrary.wiley.com/doi/full-xml/10.1002/jha2.459

  • キャッスルマン病の歴史と病理 招待 査読

    佐藤康晴, 錦織亜沙美, 前濱かんな, 西村 碧フィリーズ

    診断病理   39 ( 3 )   167 - 172   2022年7月

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    担当区分:筆頭著者, 責任著者   記述言語:日本語   出版者・発行元:(一社)日本病理学会  

    キャッスルマン病は、リンパ節の病理像で特徴づけられており、いくつかの亜型が存在するヘテロな疾患単位である。原型は限局性で全身症状の乏しい単心性キャッスルマン病(UCD)であったが、その後、病変が多発し全身症状を呈する多中心性キャッスルマン病(MCD)が報告された。MCDはさらにKSHV/HHV8の感染状態によって分類され、陰性例は特発性MCD(iMCD)と定義されている。本項では、キャッスルマン病の歴史を振り返り、各亜型の臨床および病理学的特徴について述べる。(著者抄録)

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  • Clinical characteristics and outcomes of IgG4-positive marginal zone lymphoma: Systematic scoping review. 査読 国際誌

    Yoshito Nishimura, Eric Andrew Wien, Midori Filiz Nishimura, Asami Nishikori, Yasuharu Sato, Fumio Otsuka

    Pathology international   2022年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Immunoglobulin G4 (IgG4)-positive marginal zone lymphoma (MZL) is rare and undefined. It is unclear whether IgG4-positive MZLs have as favorable an outcome as MZLs in general. Also, correlation with IgG4-related disease (IgG4-RD) and IgG4-positive MZLs is unknown. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews, we searched MEDLINE and EMBASE for all peer-reviewed articles using keywords including"IgG4" and "marginal zone lymphoma" from their inception to February 20, 2022. Twenty-two articles, including six observational studies and 24 cases from 16 case reports and case series, were included. Only one study had a comparative group, and the other five were exploratory observational studies. IgG4-positive MZLs commonly occurred in males (83.3%). It primarily involved ocular adnexa (41.7%) and skin (29.2%). Only 29.2% had concurrent IgG4-RD, and no expiration was noted. While most cases were treated with excision, resection, or clinical observation, 21.7% received rituximab-cyclophosphamide, doxorubicin, vincristine, and prednisone as a first-line treatment. This systematic review summarizes the current understanding of the characteristics of IgG4-positive MZLs. While there seems to be IgG4-RD-related and de novo IgG4-positive MZLs, future research needs to clearly define MZL with polyclonal IgG4-positive cells and IgG4-producing lymphoma. Further studies are critical to clarifying long-term prognosis and optimal surveillance planning.

    DOI: 10.1111/pin.13251

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  • Distinct disease-specific Tfh cell populations in two different fibrotic diseases: IgG4-related disease and Kimura's disease. 査読 国際誌

    Ryusuke Munemura, Takashi Maehara, Yuka Murakami, Risako Koga, Ryuichi Aoyagi, Naoki Kaneko, Atsushi Doi, Cory A Perugino, Emanuel Della-Torre, Takako Saeki, Yasuharu Sato, Hidetaka Yamamoto, Tamotsu Kiyoshima, John H Stone, Shiv Pillai, Seiji Nakamura

    The Journal of allergy and clinical immunology   2022年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: How T follicular (Tfh) cells contribute to many different B-cell class-switching events during T cell-dependent immune responses has been unclear. Diseases with polarized isotype switching offer a unique opportunity for the exploration of Tfh subsets. Secondary and tertiary lymphoid organs (SLOs and TLOs) in patients with elevated tissue expression levels of IgE (Kimura's disease, KD) and those of IgG4 (IgG4-related disease, IgG4-RD) can provide important insights regarding cytokine expression by Tfh cells. OBJECTIVE: To identify disease-specific Tfh cell subsets in SLOs and TLOs expressing IL-10 or IL-13 and thus identify different cellular drivers of class switching in two distinct types of fibrotic disorders: allergic fibrosis (driven by type 2 immune cells) and inflammatory fibrosis (driven by cytotoxic T lymphocytes). METHODS: Single-cell RNA-sequencing, in situ sequencing, and multi-color immunofluorescence analysis was used to investigate B cells, Tfh cells and infiltrating type 2 cells in lesion tissues from patients with KD or IgG4-RD. RESULTS: Infiltrating Tfh cells in TLOs from IgG4-RD were divided into six main clusters. We encountered abundant infiltrating IL-10-expressing LAG3+ Tfh cells in patients with IgG4-RD. Furthermore, we found that infiltrating AID+CD19+B cells expressing IL-4, IL-10, and IL-21 receptors correlated with IgG4 expression. In contrast, we found that infiltrating IL-13-expressing Tfh cells were abundant in affected tissues from patients with KD. Moreover, we observed few infiltrating IL-13-expressing Tfh cells in tissues from patients with IgG4-RD, despite high serum levels of IgE (but low IgE in the disease lesions). Cytotoxic T cells were abundant in IgG4-RD, and in contrast Type 2 immune cells were abundant in KD. CONCLUSIONS: This single-cell dataset revealed a novel subset of IL10+LAG3+Tfh cells infiltrating the affected organs of IgG4-RD patients. In contrast, IL13+Tfh cells and type 2 immune cells infiltrated those of KD patients.

    DOI: 10.1016/j.jaci.2022.03.034

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  • Historical and pathological overview of Castleman disease. 招待 査読

    Midori Filiz Nishimura, Yoshito Nishimura, Asami Nishikori, Tadashi Yoshino, Yasuharu Sato

    Journal of clinical and experimental hematopathology : JCEH   2022年4月

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    担当区分:最終著者, 責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Castleman disease consists of several lymphoproliferative subtypes that share some histological features in the lymph nodes. On the other hand, numerous clinical findings and etiologies make the disease challenging to understand. The origin of the disease is the hyaline vascular-type unicentric Castleman disease (UCD), first reported by Benjamin Castleman et al. in 1954. Although UCD is characterized by localized lesions and lack of symptoms, multicentric Castleman disease (MCD) with multiple lesions and systemic symptoms was reported by Frizzera in 1983. MCD is further divided according to KSHV/HHV8 infection status. In KSHV/HHV8-related MCD, viral infection signals lead to excessive cytokine production, and cause clinical and pathologic abnormalities. Some cases of plasma cell-type KSHV/HHV8-negative MCD can be found in association with POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, M-proteins, and skin changes), which is a paraneoplastic syndrome. The others are idiopathic MCD, which are currently considered a heterogeneous group of diseases with overlapping pathological and clinical features. In this article, we summarize the historical evolution of Castleman disease to help understand the disease concept. We also review the latest ideas and definitions of the subtypes within the MCD spectrum and summarize the histopathological findings.

    DOI: 10.3960/jslrt.21036

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  • International definition of iMCD-TAFRO: future perspectives. 招待 査読

    Yoshito Nishimura, Midori Filiz Nishimura, Yasuharu Sato

    Journal of clinical and experimental hematopathology : JCEH   2022年4月

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    担当区分:最終著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Since thrombocytopenia, anasarca, fever, reticulin fibrosis, renal insufficiency, and organomegaly (TAFRO) syndrome was first proposed in 2010, there has been considerable progress in this area, particularly regarding its association with idiopathic multicentric Castleman disease (iMCD). TAFRO syndrome is a heterogeneous category with a constellation of symptoms that can develop in the setting of infection, rheumatologic disorder, malignancy, and iMCD. Now, iMCD with TAFRO symptoms is subtyped as iMCD-TAFRO. However, confusion between TAFRO syndrome and iMCD-TAFRO remains. In this article, we discuss the current understanding and future research agenda of TAFRO syndrome and iMCD-TAFRO from the perspective of its new validated international definition.

    DOI: 10.3960/jslrt.21037

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  • Idiopathic multicentric Castleman disease with positive antiphospholipid antibody: atypical and undiagnosed autoimmune disease? 査読

    Yoshito Nishimura, Asami Nishikori, Haruki Sawada, Torrey Czech, Yuki Otsuka, Midori Filiz Nishimura, Hiroki Mizuno, Naoki Sawa, Shuji Momose, Kumiko Ohsawa, Fumio Otsuka, Yasuharu Sato

    Journal of clinical and experimental hematopathology : JCEH   2022年3月

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    担当区分:最終著者, 責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Idiopathic multicentric Castleman disease (iMCD) is a systemic disorder characterized by systemic inflammation and organ dysfunction associated with an increase in pro-inflammatory cytokines. Some patients with iMCD are positive for autoantibodies, although their significance and relationship with specific associated autoimmune diseases are unclear. This study retrospectively analyzed the clinicopathological features of iMCD patients focusing on autoantibodies. Among 63 iMCD patients in our database, 19 were positive for at least one autoantibody. Among the 19, we identified five with plasma cell type (PC)-iMCD lymph node histopathology and positive anti-phospholipid antibodies. These patients were likely to have thrombocytopenia, anasarca, fever, reticulin fibrosis or renal insufficiency, organomegaly (TAFRO) symptoms, and thrombotic events. The present study suggests that patients with undiagnosed or atypical autoimmune diseases, including anti-phospholipid syndrome (APS), were treated for iMCD. APS may present with thrombocytopenia or even multi-organ failure, which overlap with clinical presentations of iMCD. Due to differences in the treatment regimen and follow-up, recognition of the undiagnosed autoimmune disease process in those suspected of iMCD is essential. Our study highlights the importance of complete exclusion of differential diagnoses in patients with iMCD in their diagnostic workup.

    DOI: 10.3960/jslrt.21038

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  • The fine-needle aspiration cytology and clinical findings of Kikuchi-Fujimoto disease in pediatric patients: a retrospective clinical study. 査読 国際誌

    Yuto Naoi, Tomoyasu Tachibana, Yoji Wani, Machiko Hotta, Katsuya Haruna, Yasutoshi Komatsubara, Kazunori Kuroda, Soichiro Fushimi, Tami Nagatani, Yuko Kataoka, Kazunori Nishizaki, Yasuharu Sato, Mizuo Ando

    Acta oto-laryngologica   142 ( 3-4 )   1 - 5   2022年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: Histological evaluation of lymph node is crucial for the definitive diagnosis of Kikuchi-Fujimoto disease (KFD). However, lymph node biopsy under local anesthesia is often difficult in pediatric patients. OBJECTIVES: We evaluated cytological findings for pediatric patients with prolonged cervical lymphadenitis clinically suggestive of KFD and investigated the clinical characteristics of patients diagnosed with KFD by fine-needle aspiration cytology (FNAC). METHODS: This retrospective clinical study included 58 Japanese pediatric patients with cervical lymphadenitis who underwent FNAC. RESULTS: Cytological diagnosis was KFD for 22 and suspicion of KFD for 11 patients. The remaining 25 patients were diagnosed with non-specific lymphadenitis (NSL). Tenderness was independently associated with a higher frequency of both KFD in narrow and broad senses, compared with NSL (p = .009; p = .038). The percentage of patients who underwent FNAC within 28 days from symptom onset tended to be higher among patients with KFD in a narrow sense than those with NSL (p = .052). CONCLUSION: This study indicated that the period from symptom onset to FNAC (<28 days) and the symptom of tenderness were associated with the cytological diagnosis of KFD.

    DOI: 10.1080/00016489.2022.2040744

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  • CD30-targeted therapy induces apoptosis of inflammatory cytokine-stimulated synovial fibroblasts and ameliorates collagen antibody-induced arthritis in mice. 査読 国際誌

    Minami Matsuhashi, Keiichiro Nishida, Misa Sakamoto, Yuka Gion, Aki Yoshida, Takayuki Katsuyama, Ryuichi Nakahara, Yoshihisa Nasu, Yoshinori Matsumoto, Yasuharu Sato, Toshifumi Ozaki

    Inflammation research : official journal of the European Histamine Research Society ... [et al.]   71 ( 2 )   215 - 226   2022年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    OBJECTIVE: It has been reported that levels of soluble CD30 in serum and joint fluid are significantly elevated in patients with rheumatoid arthritis (RA). This study aimed to investigate whether CD30 could be a therapeutic target for RA. METHODS: The expression and localization of CD30 were examined by immunohistochemical and double immunofluorescence staining on synovial tissue samples obtained from patients with RA or osteoarthritis (OA) during surgery. Changes in CD30 expression of fibroblast-like synoviocytes (FLS) from RA patients with or without TNFα and IL-1β stimulation were examined by the polymerase chain reaction (PCR) and flow cytometry. Collagen antibody-induced arthritis (CAIA) was created in DBA/1 mice, and the therapeutic effect of brentuximab vedotin (BV) was examined by clinical score, histological findings and measurement of serum levels of SAA, IL-6, and TNFα. RESULTS: CD30 expression was significantly higher in samples from patients with RA than from those with OA. Double immunofluorescence showed a low rate of co-localization of CD30 with CD20 or CD90, but a high rate of co-localization of CD30 and CD138. CD30 mRNA expression was upregulated 11.7-fold in FLS following stimulation by inflammatory cytokines. The clinical scores of CAIA mice were significantly lower following both BV treatments, however, the histological scores of CAIA mice were significantly lower only following treatment with high dose BV (70 mg/kg). CONCLUSIONS: CD30 was expressed on immunocompetent cells in synovial tissue from RA patients and in cytokine-stimulated FLS in vitro. High dose BV (70 mg/kg) showed significant therapeutic effects in ameliorating inflammation and joint destruction in CAIA mice, but low dose BV (30 mg/kg) was insufficient.

    DOI: 10.1007/s00011-021-01537-z

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  • Clinicopathologic Analysis of Sinonasal Inverted Papilloma, with Focus on Human Papillomavirus Infection Status 査読

    Munechika Tsumura, Seiichiro Makihara, Asami Nishikori, Yuka Gion, Toshiaki Morito, Shotaro Miyamoto, Tomoyuki Naito, Kensuke Uraguchi, Aiko Oka, Tomoyasu Tachibana, Yorihisa Orita, Shin Kariya, Mitsuhiro Okano, Mizuo Ando, Yasuharu Sato

    Diagnostics   12 ( 2 )   454 - 454   2022年2月

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    担当区分:最終著者   掲載種別:研究論文(学術雑誌)   出版者・発行元:MDPI AG  

    Sinonasal inverted papilloma (SNIP) can recur; however, the factors related to tumor recurrence remain unclear. This study aimed to analyze risk factors, including human papillomavirus (HPV) infection, as well as other factors associated with SNIP recurrence. Thirty-two patients who were diagnosed with SNIP and underwent surgery between 2010 and 2019 were enrolled: 24 men and 8 women, with a mean age of 59.2 years. The mean follow-up was 57.3 months. Demographics and information about history of smoking, diabetes mellitus (DM), hypertension, allergic rhinitis, alcohol consumption, tumor stage, surgical approach, and recurrence were reviewed retrospectively. Specimens were investigated using polymerase chain reaction to detect HPV DNA (high-risk subtypes: 16, 18, 31, 33, 35, 52b, and 58; low-risk subtypes: 6 and 11). Seven patients (21.9%) experienced recurrence. HPV DNA was detected in five (15.6%) patients (high-risk subtypes, n = 2; low-risk subtypes, n = 3). Patients with recurrence of SNIP had a higher proportion of young adults and displayed higher rates of HPV infection, DM, and advanced tumor stage than those without recurrence. HPV infection, young adulthood, DM, and advanced tumor stage could be associated with a high recurrence rate, which suggests that patients with these risk factors could require close follow-up after surgery.

    DOI: 10.3390/diagnostics12020454

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  • Investigation of IgG4-positive cells in idiopathic multicentric Castleman disease and validation of the 2020 exclusion criteria for IgG4-related disease. 査読 国際誌

    Asami Nishikori, Midori Filiz Nishimura, Yoshito Nishimura, Kenji Notohara, Akira Satou, Masafumi Moriyama, Seiji Nakamura, Yasuharu Sato

    Pathology international   72 ( 1 )   43 - 52   2022年1月

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    担当区分:最終著者, 責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Wiley  

    Patients with plasma cell type idiopathic multicentric Castleman disease (PC-iMCD) often show elevated serum IgG4 levels and IgG4-positive cell infiltration in tissues due to overproduction of interleukin-6, and may meet the diagnostic criteria for IgG4-related disease (IgG4-RD). Although PC-iMCD has been listed as a major exclusion disease for IgG4-RD, distinguishing between these diseases is challenging due to a lack of highly specific diagnostic biomarkers. In 2020, we proposed exclusion criteria of IgG4-RD mimickers. In this paper, we validated the accuracy of the criteria in excluding one of the mimickers, PC-iMCD, from IgG4-RD. Validation was performed on 57 PC-iMCD patients (39 presenting lymph node lesions and 19 with lung lesions) and 29 IgG4-RD patients (22 presenting lymph node lesions and seven with lung lesions). According to our results, 20.5% of the PC-iMCD patients with lymph node lesions and 42.1% of those with lung lesions met the diagnostic criteria for IgG4-RD. All these patients with PC-iMCD were excluded from a diagnosis of IgG4-RD by the proposed criteria. Additionally, 6.9% of IgG4-RD patients met the exclusion criteria. Thus, if the exclusion criteria are met, diagnosis should be made based on a combination of findings including organ distribution of disease, response to steroid therapy, and other pathological findings.

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  • PD-L1 expression is associated with the spontaneous regression of patients with methotrexate-associated lymphoproliferative disorders. 査読 国際誌

    Yuka Gion, Misato Doi, Yoshito Nishimura, Tomoka Ikeda, Midori Filiz Nishimura, Misa Sakamoto, Yuria Egusa, Asami Nishikori, Azusa Fujita, Noriko Iwaki, Naoya Nakamura, Tadashi Yoshino, Yasuharu Sato

    Cancer medicine   11 ( 2 )   417 - 432   2022年1月

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    担当区分:最終著者, 責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Wiley  

    BACKGROUND: Most patients with methotrexate-associated lymphoproliferative disorder (MTX-LPD) show diffuse large B-cell lymphoma (DLBCL) or classic Hodgkin lymphoma (CHL) types. Patients with MTX-LPD often have spontaneous remission after MTX discontinuation, but chemotherapeutic intervention is frequently required in patients with CHL-type MTX-LPD. In this study, we examined whether programmed cell death-ligand 1 (PD-L1) expression levels were associated with the prognosis of MTX-LPD after MTX discontinuation. METHODS: A total of 72 Japanese patients diagnosed with MTX-LPD were clinicopathologically analyzed, and immunohistochemical staining of PD-L1 was performed in 20 DLBCL-type and 24 CHL-type MTX-LPD cases to compare with the clinical course. RESULTS: PD-L1 was expressed in 5.0% (1/20) of patients with DLBCL-type MTX-LPD, whereas it was expressed in 66.7% (16/24) of the patients with CHL-type MTX-LPD in more than 51% of tumor cells. Most CHL-type MTX-LPD patients with high PD-L1 expression required chemotherapy owing to exacerbations or relapses after MTX discontinuation. However, no significant differences in clinicopathologic findings at diagnosis were observed between PD-L1 high- and low-expression CHL-type MTX-LPD. CONCLUSION: PD-L1 expression was significantly higher in patients with CHL-type than DLBCL-type MTX-LPD, suggesting the need for chemotherapy in addition to MTX discontinuation in CHL-type MTX-LPD patients to achieve complete remission. No association was observed between PD-L1 expression levels and clinical findings at diagnosis, suggesting that PD-L1 expression in tumor cells influences the pathogenesis of CHL-type MTX-LPD after MTX discontinuation.

    DOI: 10.1002/cam4.4462

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  • Cytopathological Findings of Secretory Carcinoma of the Salivary Gland and the Diagnostic Utility of Giemsa Staining 査読

    Yuria Egusa, Midori Filiz Nishimura, Satoko Baba, Kengo Takeuchi, Takuma Makino, Tomoyasu Tachibana, Asami Nishikori, Azusa Fujita, Hiroyuki Yanai, Yasuharu Sato

    Diagnostics   11 ( 12 )   2284 - 2284   2021年12月

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    担当区分:最終著者, 責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:MDPI AG  

    Secretory carcinoma is a salivary gland neoplasm first described as a mammary analogue secretory carcinoma by Skalova et al. in 2010 and redesignated as a secretory carcinoma in the 2017 World Health Organization Classification of Head and Neck Tumors. Secretory carcinoma diagnosis is reliant on specific cytological and histological findings and the detection of an ETV6-NTRK3 fusion gene. Here, we examined the clinical and cytopathological features of four cases of secretory carcinoma occurring in three males and a female, aged between 39 and 74 years. All four tumors involved the parotid gland, and were found to have the ETV6-NTRK3 fusion gene. Fine-needle aspiration-based cytology smears of all tumors displayed papillary and/or dendritic pattern clusters, some of which were associated with blood vessels. The neoplastic cells displayed enlarged nuclei with fine chromatin and small, distinct, single nucleoli. Furthermore, several neoplastic cells with a characteristic vacuolated cytoplasm were identified in each specimen. Giemsa staining revealed cytoplasmic vacuolation, intracytoplasmic metachromatic secretions and/or various sized metachromatic granules, and a background of metachromatic mucin in all four specimens. Given this, we conclude that these cytological findings, especially those of the Giemsa staining, might be helpful in the diagnosis of secretory carcinoma.

    DOI: 10.3390/diagnostics11122284

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  • Primary Gastrointestinal T-Cell Lymphoma and Indolent Lymphoproliferative Disorders: Practical Diagnostic and Treatment Approaches. 査読 国際誌

    Midori Filiz Nishimura, Yoshito Nishimura, Asami Nishikori, Tadashi Yoshino, Yasuharu Sato

    Cancers   13 ( 22 )   2021年11月

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    担当区分:最終著者, 責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Primary gastrointestinal (GI) T-cell neoplasms are extremely rare heterogeneous disease entities with distinct clinicopathologic features. Given the different prognoses of various disease subtypes, clinicians and pathologists must be aware of the key characteristics of these neoplasms, despite their rarity. The two most common aggressive primary GI T-cell lymphomas are enteropathy-associated T-cell lymphoma and monomorphic epitheliotropic intestinal T-cell lymphoma. In addition, extranodal natural killer (NK)/T-cell lymphoma of the nasal type and anaplastic large cell lymphoma may also occur in the GI tract or involve it secondarily. In the revised 4th World Health Organization classification, indolent T-cell lymphoproliferative disorder of the GI tract has been incorporated as a provisional entity. In this review, we summarize up-to-date clinicopathological features of these disease entities, including the molecular characteristics of primary GI T-cell lymphomas and indolent lymphoproliferative disorders. We focus on the latest treatment approaches, which have not been summarized in existing reviews. Further, we provide a comprehensive review of available literature to address the following questions: How can pathologists discriminate subtypes with different clinical prognoses? How can primary GI neoplasms be distinguished from secondary involvement? How can these neoplasms be distinguished from non-specific inflammatory changes at an early stage?

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  • Epstein-Barr virus-positive mucocutaneous ulcer is characterized by relatively low serum soluble IL-2 receptor levels regardless of methotrexate use; Reply to Ramia de Cap and Michaels. 査読 国際誌

    Tomoka Ikeda, Yuka Gion, Yoshito Nishimura, Asami Nishikori, Midori Filiz Nishimura, Tadashi Yoshino, Yasuharu Sato

    Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc   34 ( 11 )   2085 - 2086   2021年11月

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    担当区分:最終著者, 責任著者   記述言語:英語  

    DOI: 10.1038/s41379-021-00892-w

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  • Clinical and Pathological Characteristics of Hyaline-Vascular Type Unicentric Castleman Disease: A 20-Year Retrospective Analysis. 査読 国際誌

    Midori Filiz Nishimura, Yoshito Nishimura, Asami Nishikori, Yukina Maekawa, Kanna Maehama, Tadashi Yoshino, Yasuharu Sato

    Diagnostics (Basel, Switzerland)   11 ( 11 )   2008 - 2008   2021年10月

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    担当区分:最終著者, 責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:MDPI AG  

    The first case of hyaline vascular type of unicentric Castleman disease (HV-UCD) was reported more than six decades ago. Since patients with HV-UCD are often asymptomatic and this condition is generally discovered incidentally on imaging tests, most of the previous reports were of mediastinal origin detected by chest radiography. In recent years, improved access to imaging modalities has provided new insights in the diagnosis of this condition. In this study, we reviewed the detailed clinical and pathological findings of 38 HV-UCD cases (20 males and 18 females, mean age: 42.8 years). The most common site involved was the abdominal cavity (34.2%), followed by mediastinum (23.7%) and retroperitoneum (15.8%). In the abdominal cavity, mesenteric origin was the most common. The mean size of masses was 4.8 cm. Pathologically, thick hyalinized collagen fibers surrounding large blood vessels and calcification were observed (81.6% and 23.7%, respectively). Multinucleated giant cells resembling Warthin–Finkeldey cell were also observed in occasional cases (23.7%). This is a unique paper that summarizes detailed clinical and pathological findings of a large series of a rare disease. The clinical information presented in this paper is more plausible than previous views and is useful for accurate diagnosis and understanding of the disease.

    DOI: 10.3390/diagnostics11112008

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  • Validated international definition of the thrombocytopenia, anasarca, fever, reticulin fibrosis, renal insufficiency, and organomegaly clinical subtype (TAFRO) of idiopathic multicentric Castleman disease. 査読 国際誌

    Yoshito Nishimura, David C Fajgenbaum, Sheila K Pierson, Noriko Iwaki, Asami Nishikori, Mitsuhiro Kawano, Naoya Nakamura, Koji Izutsu, Kengo Takeuchi, Midori Filiz Nishimura, Yoshinobu Maeda, Fumio Otsuka, Kazuyuki Yoshizaki, Eric Oksenhendler, Frits van Rhee, Yasuharu Sato

    American journal of hematology   96 ( 10 )   1241 - 1252   2021年10月

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    担当区分:最終著者, 責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Thrombocytopenia, anasarca, fever, reticulin fibrosis, renal insufficiency, and organomegaly (TAFRO) syndrome is a heterogeneous entity manifesting with a constellation of symptoms described above that can occur in the context of idiopathic multicentric Castleman disease (iMCD) as well as infectious diseases, malignancies, and rheumatologic disorders. So, iMCD-TAFRO is an aggressive subtype of iMCD with TAFRO syndrome and often hyper-vascularized lymph nodes. Since we proposed diagnostic criteria of iMCD-TAFRO in 2016, we have accumulated new insights on the disorder and additional cases have been reported worldwide. In this systematic review and cohort analysis, we established and validated a definition for iMCD-TAFRO. First, we searched PubMed and Japan Medical Abstracts Society databases using the keyword "TAFRO" to extract cases. Patients with possible systemic autoimmune diseases and hematologic malignancies were excluded. Our search identified 54 cases from 50 articles. We classified cases into three categories: (1) iMCD-TAFRO (TAFRO syndrome with lymph node histopathology consistent with iMCD), (2) possible iMCD-TAFRO (TAFRO syndrome with no lymph node biopsy performed and no other co-morbidities), and (3) TAFRO without iMCD or other co-morbidities (TAFRO syndrome with lymph node histopathology not consistent with iMCD or other comorbidities). Based on the findings, we propose an international definition requiring four clinical criteria (thrombocytopenia, anasarca, fever/hyperinflammatory status, organomegaly), renal dysfunction or characteristic bone marrow findings, and lymph node features consistent with iMCD. The definition was validated with an external cohort (the ACCELERATE Natural History Registry). The present international definition will facilitate a more precise and comprehensive approach to the diagnosis of iMCD-TAFRO.

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  • Transformation to diffuse large B-cell lymphoma with germinal center B-cell like subtype and discordant light chain expression in a patient with Waldenström macroglobulinemia/lymphoplasmacytic lymphoma. 査読

    Hiroki Kobayashi, Noboru Asada, Yuria Egusa, Tomoka Ikeda, Misa Sakamoto, Masaya Abe, Daisuke Ennishi, Masahiro Sakata, Akinobu Takaki, Soichiro Kawahara, Yusuke Meguri, Hisakazu Nishimori, Nobuharu Fujii, Ken-Ichi Matsuoka, Yasuharu Sato, Tadashi Yoshino, Yoshinobu Maeda

    International journal of hematology   114 ( 3 )   401 - 407   2021年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Waldenström macroglobulinemia (WM)/lymphoplasmacytic lymphoma (LPL) is a rare indolent B-cell neoplasm, and a gain-of-function mutation in the myeloid differentiation primary response 88 (MYD88), L265P, is a commonly recurring mutation in patients with WM/LPL. Histological transformation of WM/LPL to an aggressive lymphoma such as diffuse large B-cell lymphoma (DLBCL) is rare, and transformed DLBCL has a worse prognosis than de novo DLBCL, partly because transformed DLBCL is mostly classified as non-germinal center B-cell-like (non-GCB) subtype. We herein describe a 75-year-old man with DLBCL with a history of WM/LPL. DLBCL in this patient showed the GCB subtype, and the light chain restriction of DLBCL was different from that of the antecedent WM/LPL, indicating that the two types of lymphoma cells had distinctive origins. However, DLBCL in this patient harbored the MYD88 L265P mutation, and polymerase chain reaction and Sanger sequencing of the DLBCL and WM/LPL for immunoglobulin heavy chain gene rearrangement suggested a clonal relationship between the two lymphomas. Since the outcome of transformed DLBCL is worse than for de novo DLBCL, it is important to evaluate the clonal relationship between primary WM/LPL and the corresponding transformed DLBCL, even if the DLBCL expresses a GCB subtype or discordant light chain restriction.

    DOI: 10.1007/s12185-021-03157-z

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  • Exacerbation of pulmonary cryptococcosis associated with enhancement of Th2 response in the postpartum period. 査読 国際誌

    Shota Miyoshi, Naohiro Oda, Yuka Gion, Takahiro Taki, Reo Mitani, Ichiro Takata, Akihiko Taniguchi, Yasuharu Sato, Nobuaki Miyahara

    Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy   27 ( 8 )   1248 - 1250   2021年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Cryptococcosis is an invasive mycosis that has become increasingly prevalent in immunocompromised patients. Pregnant women are also one of the risk populations for cryptococcosis. Reversal of Th2 to Th1 response following resolution of immunosuppression during the postpartum period can lead to overt clinical manifestations of a previously silent infection, resembling an immune reconstitution inflammatory syndrome. Here, we report a case of a 30-year-old woman who had an exacerbation of pulmonary cryptococcosis in the postpartum period mimicking an immune reconstitution inflammatory syndrome. In the present case, chest computed tomography showed multiple small nodules on the day of the delivery; however, pulmonary cryptococcosis, which was subclinical during pregnancy, rapidly worsened to mass-like consolidation at one month after the delivery. Pathohistological examination of the lung specimen showed lung parenchyma infiltration with histiocytes and numerous lymphocytes without granulomatous formations, and a small number of yeast-like organisms consistent with Cryptococcus without capillary involvement. Immunohistochemical staining showed predominance of CD3+ cells and CD4+ cells over CD8+ cells. In addition, GATA3+ cells dominated over T-bet + cells. These data suggested exacerbation of pulmonary cryptococcosis associated with enhancement of Th2 response in the postpartum period.

    DOI: 10.1016/j.jiac.2021.03.025

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  • The 2020 revised comprehensive diagnostic (RCD) criteria for IgG4-RD. 査読 国際誌

    Hisanori Umehara, Kazuichi Okazaki, Shigeyuki Kawa, Hiroki Takahashi, Hiroshi Goto, Shoko Matsui, Nobukazu Ishizaka, Takashi Akamizu, Yasuharu Sato, Mitsuhiro Kawano

    Modern rheumatology   31 ( 3 )   529 - 533   2021年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    IgG4-related disease (IgG4-RD) is a fascinating clinical entity first reported in this century in Japan, and includes a wide variety of diseases, such as formerly named Mikulicz's disease (MD), autoimmune pancreatitis (AIP), interstitial nephritis, prostatitis and retroperitoneal fibrosis. The Japanese IgG4 team organized by the Ministry of Health, Labor and Welfare (MHLW) of Japan has published the first criteria, comprehensive diagnostic (CD) criteria for IgG-RD 2011. Thereafter, IgG4-RD has been accepted widely and many cases have been reported from all over the world. Several problems have arisen in clinical practice, however, including the difficulty obtaining biopsy samples, and the sensitivity and specificity in cut off level of serum IgG4 and impaired immunostaining of IgG4. Given these situations, the Japanese IgG4 team has updated the 2011 comprehensive diagnostic criteria for IgG4-RD and propose the 2020 revised comprehensive diagnostic (RCD) criteria for IgG4-RD, which consists of 3 domains; 1) Clinical and radiological features, 2) Serological diagnosis and 3) Pathological diagnosis. In addition, the new pathological diagnosis is composed by three sub-items including storiform fibrosis and obliterative phlebitis.

    DOI: 10.1080/14397595.2020.1859710

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  • Nodal EBV-positive polymorphic B cell lymphoproliferative disorder with plasma cell differentiation: clinicopathological analysis of five cases. 査読 国際誌

    Akira Satou, Tetsuya Tabata, Yuka Suzuki, Yasuharu Sato, Ippei Tahara, Kunio Mochizuki, Naoki Oishi, Taishi Takahara, Tadashi Yoshino, Toyonori Tsuzuki, Shigeo Nakamura

    Virchows Archiv : an international journal of pathology   478 ( 5 )   969 - 976   2021年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Plasma cell differentiation (PCD) is frequently observed in some entities of non-Hodgkin B cell lymphoma, including both low-grade and high-grade lymphomas. However, except for plasmablastic lymphoma and primary effusion lymphoma, EBV+ B cell lymphoproliferative disorder (LPD) with PCD has not been well addressed due to its rarity. We clinicopathologically examined five cases of nodal EBV+ polymorphic B cell LPD with PCD (PBLPD-PCD) initially diagnosed as polymorphic EBV+ diffuse large B cell lymphoma, not otherwise specified (DLBCL-NOS) with PCD (n = 3) and methotrexate-associated B cell LPD (MTX-associated B-LPD) (n = 2). One case had a concomitant brain lesion which was clinically diagnosed as EBV-related encephalitis. This patient received therapy with vidarabine, and both the brain lesion and the nodal EBV+ PBLPD-PCD lesions disappeared. Another case was characterized by Mott cell differentiation. This case was the first reported case of EBV+ B cell lymphoma or LPD with Mott cell differentiation. The two cases of MTX-associated B cell LPD which arose in patients with rheumatoid arthritis spontaneously regressed after MTX cessation. TCRγ and IGH PCR analysis was performed in four cases. Two cases had TCRγ rearrangements, but no IGH rearrangements. The other two cases had no rearrangements in these genes. We concluded that nodal EBV+ PBLPD-PCD is rare, with heterogeneous characteristics. PCR analysis revealed that nodal EBV+ PBLPD-PCD may have only TCR clonality and no IGH clonality. Considering the partial or complete loss of CD20 expression on the tumor cells, this result may be confusing for accurate diagnosis of EBV+ PBLPD-PCD, and pathologists need to be aware of this phenomenon to avoid misdiagnosis.

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  • Diagnostic Utility of SOX4 Expression in Adult T-Cell Leukemia/Lymphoma. 査読 国際誌

    Atsuko Nasu, Yuka Gion, Yoshito Nishimura, Asami Nishikori, Misa Sakamoto, Yuria Egusa, Azusa Fujita, Tadashi Yoshino, Yasuharu Sato

    Diagnostics (Basel, Switzerland)   11 ( 5 )   2021年4月

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    担当区分:最終著者, 責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Differentiation between adult T-cell leukemia/lymphoma (ATLL) and peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS), is often challenging based on pathological findings alone. Although serum anti-HTLV-1 antibody positivity is required for ATLL diagnosis, this information is often not available at the time of pathological diagnosis. Therefore, we examined whether the expression of SOX4 and p16 would be helpful for differentiating the two disease entities. We immunohistochemically examined SOX4 and p16 expression (which have been implicated in ATLL carcinogenesis) in 11 ATLL patients and 20 PTCL-NOS patients and classified them into four stages according to the percentage of positive cells. Among the ATLL cases, 8/11 (73%) were SOX4-positive, while only 2/20 (10%) PTCL-NOS cases expressed SOX4. The mean total score was 4.2 (standard deviation (SD): 0.61) in the ATLL group and 0.50 (SD: 0.46) in the PTCL-NOS group (p < 0.001). Positive expression of p16 was noted in 4/11 (36%) patients with ATLL and 3/20 (15%) patients with PTCL-NOS, with mean total scores of 1.9 (SD: 0.64) and 0.70 (SD: 0.48) in the ATLL and PTCL-NOS groups, respectively (p = 0.141). These results suggest that SOX4 may be strongly expressed in ATLL compared to PTCL-NOS cases. Therefore, it may be helpful to perform immunohistochemical staining of SOX4 when pathologists face challenges discriminating between ATLL and PTCL-NOS.

    DOI: 10.3390/diagnostics11050766

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  • Upregulated Expression of Activation-Induced Cytidine Deaminase in Ocular Adnexal Marginal Zone Lymphoma with IgG4-Positive Cells. 査読 国際誌

    Asami Nishikori, Yoshito Nishimura, Rei Shibata, Koh-Ichi Ohshima, Yuka Gion, Tomoka Ikeda, Midori Filiz Nishimura, Tadashi Yoshino, Yasuharu Sato

    International journal of molecular sciences   22 ( 8 )   2021年4月

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    担当区分:最終著者, 責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Immunoglobulin G4-related disease (IgG4-RD) is a systemic disorder characterized by tissue fibrosis and intense lymphoplasmacytic infiltration, causing progressive organ dysfunction. Activation-induced cytidine deaminase (AID), a deaminase normally expressed in activated B-cells in germinal centers, edits ribonucleotides to induce somatic hypermutation and class switching of immunoglobulin. While AID expression is strictly controlled under physiological conditions, chronic inflammation has been noted to induce its upregulation to propel oncogenesis. We examined AID expression in IgG4-related ophthalmic disease (IgG4-ROD; n = 16), marginal zone lymphoma with IgG4-positive cells (IgG4+ MZL; n = 11), and marginal zone lymphoma without IgG4-positive cells (IgG4- MZL; n = 12) of ocular adnexa using immunohistochemical staining. Immunohistochemistry revealed significantly higher AID-intensity index in IgG4-ROD and IgG4+ MZL than IgG4- MZL (p < 0.001 and = 0.001, respectively). The present results suggest that IgG4-RD has several specific causes of AID up-regulation in addition to inflammation, and AID may be a driver of oncogenesis in IgG4-ROD to IgG4+ MZL.

    DOI: 10.3390/ijms22084083

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  • PD-L1 expression in tongue squamous cell carcinoma

    Naoki Akisada, Kohei Nishimoto, Soshi Takao, Yuka Gion, Hidenori Marunaka, Tomoyasu Tachibana, Takuma Makino, Kentaro Miki, Yusuke Akagi, Munechika Tsumura, Tomohiro Toji, Tadashi Yoshino, Kazunori Nishizaki, Yorihisa Orita, Yasuharu Sato

    Medical Molecular Morphology   54 ( 1 )   52 - 59   2021年3月

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    掲載種別:研究論文(学術雑誌)  

    Purpose: Immune checkpoint proteins programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) are important therapeutic targets for head and neck cancer. This large-scale case study aimed to analyze tongue squamous cell carcinomas (SCCs) and evaluate the correlation between PD-L1 expression and clinical prognosis. So far, this study is the largest case study on PD-L1 expression in tongue SCCs. Methods: This is a case–control study that analyzed 121 tongue SCCs. Paraffin-embedded sections and clinical data were obtained retrospectively and immunohistochemistry with PD-L1 was performed. Results: 11.6% contained ≥ 50% of PD-L1-positive cells, 57.1% of these cases had a poor prognosis with nodal metastasis. Among cases of T1/2 primary lesions with nodal metastasis, cases of high PD-L1 expression had a significantly shorter disease-free survival than cases of no PD-L1 expression (p = 0.018). The hazard ratio for high PD-L1 expression was 3.21 (95 per cent CI, 1.26–8.72) compared with no PD-L1 expression after adjusting for other factors. Conclusions: These data indicate that PD-L1 upregulation in tongue SCCs is associated with a more advanced stage and shorter disease-free survival. PD-1/PD-L1 inhibitors might hence constitute potential adjuvant therapy for tongue SCCs with PD-L1 upregulation.

    DOI: 10.1007/s00795-020-00261-7

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  • Comment on: HHV-8-negative multicentric Castleman disease patients with serological, histopathological and imaging features of IgG4-related disease: reply. 査読 国際誌

    Mitsuhiro Kawano, Yasuharu Sato, David C Fajgenbaum

    Rheumatology (Oxford, England)   60 ( 2 )   e76-e77   2021年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1093/rheumatology/keaa754

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  • Epstein-Barr Virus-Positive Mucocutaneous Ulcer: A Unique and Curious Disease Entity. 査読 国際誌

    Tomoka Ikeda, Yuka Gion, Yoshito Nishimura, Midori Filiz Nishimura, Tadashi Yoshino, Yasuharu Sato

    International journal of molecular sciences   22 ( 3 )   2021年1月

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    担当区分:最終著者, 責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Epstein-Barr virus (EBV)-positive mucocutaneous ulcer (EBVMCU) was first described as a lymphoproliferative disorder in 2010. EBVMCU is a unifocal mucosal or cutaneous ulcer that often occurs after local trauma in patients with immunosuppression; the patients generally have a good prognosis. It is histologically characterized by proliferating EBV-positive atypical B cells accompanied by ulcers. On the basis of conventional pathologic criteria, EBVMCU may be misdiagnosed as EBV-positive diffuse large B-cell lymphoma or other lymphomas. However, its prognosis differs from that of EBV-associated lymphomas, in that patients with EBVMCU frequently show spontaneous regression or complete remission without chemotherapy. Therefore, EBVMCU is now recognized as a low-grade malignancy or a pseudo-malignant lesion. Avoiding unnecessary chemotherapy by distinguishing EBVMCU from other EBV-associated lymphomas will reduce the burden and unnecessary harm on patients. On the basis of these facts, EBVMCU was first described as a new clinicopathological entity by the World Health Organization in 2017. In this review, we discuss the clinicopathological characteristics of previously reported EBVMCU cases, while focusing on up-to-date clinical, pathological, and genetic aspects.

    DOI: 10.3390/ijms22031053

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  • HHV-8-negative multicentric Castleman disease patients with serological, histopathological and imaging features of IgG4-related disease. 査読 国際誌

    Mitsuhiro Kawano, Satoshi Hara, Akihiro Yachie, Dai Inoue, Yasuharu Sato, David C Fajgenbaum

    Rheumatology (Oxford, England)   60 ( 1 )   e3-e4   2021年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1093/rheumatology/keaa362

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  • Follow-up with serum IgG4-monitoring in 8 patients with IgG4-related disease diagnosed by a lacrimal gland mass. 査読

    Toshihiko Matsuo, Takehiro Tanaka, Yasuharu Sato, Hitomi Kataoka, Mayu Uka, Daisuke Ennishi, Tomofumi Yano

    Journal of clinical and experimental hematopathology : JCEH   61 ( 1 )   10 - 21   2021年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    The diagnostic criteria for IgG4-related disease were previously published and serum IgG4 measurement has been reimbursed by national health insurance in Japan since 2012. Eight patients diagnosed with IgG4-related disease based on lacrimal gland masses were retrospectively reviewed. The 8 patients were 3 men and 5 women ranging in age from 52 to 77 (median, 63) years at the initial visit and their follow-up period ranged from 0.25 to 11 (median, 7) years. Bilateral and unilateral involvement were noted in 4 patients each; 2 on the right side and 2 on the left side in those with unilateral involvement. Serum IgG4 was high in 5 of 8 patients at the initial visit. Five patients with no systemic signs were followed without treatment, whereas oral steroids were administered and tapered in the other 3 patients who exhibited systemic signs. One patient with a history of radiation for MALT lymphoma in bilateral lacrimal glands developed IgG4-related disease in the left lacrimal gland 10 years later and was followed without treatment. Nine years later, her serum IgG4 level increased to 1500 mg/dL and paracardiac lesions, found on positron emission tomography, were confirmed to be MALT lymphoma by needle biopsy, leading to systemic chemotherapy. The other 7 patients had neither local recurrence nor additional systemic signs. Serum IgG4 monitoring may be useful to detect systemic complications in IgG4-related ophthalmic disease and markedly high serum IgG4 levels may indicate new lymphoma at other sites.

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  • IgG4 Expression in Patients with Eosinophilic Otitis Media 査読

    Masahiro Takahashi, Aiko Oka, Shin Kariya, Yuka Gion, Yasuharu Sato, Satoshi Iwasaki, Shogo Oyamada, Atsushi Matsubara, Mitsuhiro Okano

    ORL   83 ( 3 )   167 - 171   2021年

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:S. Karger AG  

    &lt;b&gt;&lt;i&gt;Objective:&lt;/i&gt;&lt;/b&gt; Eosinophilic otitis media (EOM) is an intractable middle ear disease recognized by an eosinophil enriched middle ear effusion and mucosa. Although precise pathogenesis of EOM remains unclear, it is characterized by type 2 inflammation. Since IgG4 is an IgG subclass induced by type 2 cytokines such as IL-4 and IL-13, we sought to characterize and compare local IgG4 expression in patients with and without EOM. &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; Twelve patients with bilateral profound hearing loss, 9 of which underwent a cochlear implant surgery, were enrolled in this study (6 with EOM and 6 without EOM). The surgical specimens were harvested during surgery and were subjected to IgG4 immunostaining. &lt;b&gt;&lt;i&gt;Result:&lt;/i&gt;&lt;/b&gt; The middle ear mucosa showed the presence of a large number of IgG4-positive cells in patients with EOM, which was significantly higher than that in patients without EOM. &lt;b&gt;&lt;i&gt;Conclusion:&lt;/i&gt;&lt;/b&gt; Local IgG4 expression was observed in patients with EOM in comparison to those without EOM, suggesting that IgG4 contributes to EOM pathogenesis.

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  • Differential diagnosis of chronic lymphocytic leukemia/small lymphocytic lymphoma and other indolent lymphomas, including mantle cell lymphoma. 査読

    Tadashi Yoshino, Takehiro Tanaka, Yasuharu Sato

    Journal of clinical and experimental hematopathology : JCEH   60 ( 4 )   124 - 129   2020年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) accounts for approximately 1% of all lymphomas in our department. In this article, we describe the differential diagnosis of CLL/SLL from other indolent lymphomas, with special reference to follicular lymphoma, marginal zone B-cell lymphoma, lymphoplasmacytic lymphoma, and mantle cell lymphoma, although the latter is considered to be aggressive. CLL/SLL often exhibits proliferation centers, similar to follicular lymphoma. Immunohistological examination can easily distinguish these two lymphomas. The most important characteristic of CLL/SLL is CD5 and CD23 positivity. Mantle cell lymphoma is also CD5-positive and there are some CD23-positive cases. Such cases should be carefully distinguished from CLL/SLL. Some marginal zone lymphomas are also positive for CD5 and such cases are often disseminated. Lymphoplasmacytic lymphoma should also be a differential diagnosis for CLL/SLL. It frequently demonstrates MYD88 L265P, which is a key differential finding. By immunohistological examination, the expression of lymphoid enhancer-binding factor 1 is specific for CLL/SLL and can be a good marker in the differential diagnosis.

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  • Pulmonary Manifestations of Plasma Cell Type Idiopathic Multicentric Castleman Disease: A Clinicopathological Study in Comparison with IgG4-Related Disease. 査読 国際誌

    Midori Filiz Nishimura, Takuro Igawa, Yuka Gion, Sakura Tomita, Dai Inoue, Akira Izumozaki, Yoshifumi Ubara, Yoshito Nishimura, Tadashi Yoshino, Yasuharu Sato

    Journal of personalized medicine   10 ( 4 )   2020年12月

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    担当区分:最終著者, 責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Plasma cell type idiopathic multicentric Castleman disease (PC-iMCD) occasionally manifests as parenchymal lung disease. This study aimed to elucidate the detailed clinicopathological features of lung lesions in PC-iMCD and compare the findings with those in immunoglobulin (Ig) G4-related disease (IgG4-RD), the most difficult differential diagnosis of PC-iMCD. We analyzed the clinicopathological findings and immunohistochemical expression patterns of interleukin-6 (IL-6) and Igs in lung specimens from 16 patients with PC-iMCD and 7 patients with IgG4-RD. Histologically, pulmonary PC-iMCD could not be differentiated from IgG4-RD based on lesion distribution patterns, the number of lymphoid follicles and obliterative vasculitis, or fibrosis types. The eosinophil count was higher in the IgG4-RD group than in the PC-iMCD group (p = 0.004). The IgG4/IgG-positive cell ratio was significantly higher in the IgG4-RD group (p < 0.001). The IgA-positive cell count and IL-6 expression intensity were higher in the PC-iMCD group than in the IgG4-RD group (p < 0.001). Based on these findings, we proposed a new diagnostic approach to differentiate lung lesions of PC-iMCD and IgG4-RD. Our approach can be utilized to stratify patients with suspected lung-dominant PC-iMCD to identify candidates for strong immunosuppressive treatment, including IL-6 blockade, at an early stage.

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  • Treatment outcomes of IgG4-producing marginal zone B-cell lymphoma: a retrospective case series. 査読

    Yuichi Sumii, Noboru Asada, Yasuharu Sato, Koh-Ichi Ohshima, Masanori Makita, Yusuke Yoshimoto, Yuka Sogabe, Kenji Imajo, Yusuke Meguri, Daisuke Ennishi, Hisakazu Nishimori, Nobuharu Fujii, Ken-Ichi Matsuoka, Tadashi Yoshino, Yoshinobu Maeda

    International journal of hematology   112 ( 6 )   780 - 786   2020年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    IgG4-producing marginal zone B-cell lymphomas (MZLs) have been recently proposed as a subtype of MZLs. Despite the abundant literature on pathophysiological features of this type of lymphoma, only a few retrospective studies pertaining to the treatment outcomes have been reported, and its prognosis remains unclear. We retrospectively analyzed seven patients with IgG4-producing MZLs diagnosed at our institute, with specific reference to treatment and outcomes. The median age was 69.0 years (55-79), and all were males. The median follow-up period was 66.6 months (8-121). All patients had localized disease; four patients had tumors of the ocular adnexa, whereas two had retroperitoneal tumors. Five patients were treated with irradiation (30 Gy/15 fr) (n = 4) or surgery (n = 1), resulting in tumor reduction. Two patients were treated by chemotherapy or irradiation. Among them, one commenced rituximab monotherapy, which led to an inadequate reduction of the tumor. Subsequent irradiation induced complete response (CR). The other patient experienced repeated relapses during follow-up and finally achieved CR by combination chemotherapy. Treatment was well tolerated in all cases, and none of the patients showed disease progression at the last follow-up visit. Our results indicate that the standard treatments for MZLs are generally appropriate for IgG4-producing MZL.

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  • Insufficient evidence exists to use histopathologic subtype to guide treatment of idiopathic multicentric Castleman disease. 査読 国際誌

    David C Fajgenbaum, David Wu, Aaron Goodman, Raymond Wong, Amy Chadburn, Sunita Nasta, Gordan Srkalovic, Sudipto Mukherjee, Heather Leitch, Raj Jayanthan, Simone Ferrero, Yasuharu Sato, Steve Schey, Angela Dispenzieri, Eric Oksenhendler, Pier Luigi Zinzani, Mary Jo Lechowicz, Christian Hoffmann, Naveen Pemmaraju, Adam Bagg, Alexander Fossa, Megan S Lim, Frits van Rhee

    American journal of hematology   95 ( 12 )   1553 - 1561   2020年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Idiopathic multicentric Castleman disease (iMCD) is a rare immunologic disorder characterized by systemic inflammation, multicentric lymphadenopathy, and organ dysfunction. Enlarged lymph nodes demonstrate a spectrum of characteristic but variable histopathologic features historically categorized into hyaline vascular (HV) (or hypervascular [HyperV] more recently), plasmacytic, or "mixed." Though the etiology is unknown, a pro-inflammatory cytokine storm, often involving interleukin-6 (IL-6), contributes to pathogenesis. Anti-IL-6 therapy with siltuximab is the only FDA- or EMA-approved treatment based on efficacy and safety in multiple studies. Importantly, no patients considered to have HV histopathology achieved the primary endpoint in the Phase II study. NCCN currently recommends siltuximab first-line for iMCD, except for patients considered to have HV histopathology. We investigated whether histopathologic subtype should guide siltuximab treatment decisions. Secondary analyses of clinical trial and real-world data revealed similar clinical benefit across histopathologic subtypes. Notably, only 18 of 79 patients in the Phase II study were consistently classified into histopathologic subtype by three independent review panels, demonstrating limited reliability to guide treatment decisions. Real-world data further demonstrate siltuximab's effectiveness in patients considered to have HV (or HyperV). Though histopathology is a critical component for diagnosis, there is insufficient evidence to guide treatment based solely on lymph node histopathologic subtype.

    DOI: 10.1002/ajh.25992

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  • Deletion of BART miRNA-encoding cluster in Epstein-Barr virus DNA in classic Hodgkin lymphoma. 査読 国際誌

    Akihiro Kawatsuki, Takuro Igawa, Tomohiro Urata, Takehiro Tanaka, Yasuharu Sato, Tadashi Yoshino

    Pathology international   70 ( 12 )   1032 - 1033   2020年12月

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    記述言語:英語  

    DOI: 10.1111/pin.13022

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  • Clinicopathological analysis of 34 Japanese patients with EBV-positive mucocutaneous ulcer. 査読 国際誌

    Tomoka Ikeda, Yuka Gion, Misa Sakamoto, Tomoyasu Tachibana, Asami Nishikori, Midori Filiz Nishimura, Tadashi Yoshino, Yasuharu Sato

    Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc   33 ( 12 )   2437 - 2448   2020年12月

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    担当区分:最終著者, 責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Epstein-Barr virus (EBV)-positive mucocutaneous ulcer (EBVMCU) is a unifocal mucosal or cutaneous ulcer that is histologically characterized by proliferating EBV-positive atypical B cells. While EBVMCU demonstrates a histology similar to that of EBV-positive diffuse large B-cell lymphoma (DLBCL), their clinical behavior differs. Thus, characterizing distinguishing features of EBVMCU and EBV-positive DLBCL is critical. To identify unique characteristics between EBVMCU and lymphoma, we analyzed the clinicopathological and genetic features of 34 Japanese patients with EBVMCU and compared them to those of 24 EBV-positive DLBCL patients and 25 EBV-negative DLBCL patients. All patients with EBVMCU had localized ulcerative lesions, and 31 patients (91%) were using immunosuppressants, such as methotrexate (MTX) or hydroxycarbamide. All patients that were followed up with exhibited good prognosis following immunosuppressant reduction or chemotherapy. In addition, 17 EBV-positive DLBCL patients, and 15 EBV-negative DLBCL patients, received chemotherapy (P < 0.001, P < 0.001, respectively). Our data showed that EBVMCU did not increase indicators associated with lymphoma prognosis, such as soluble interleukin 2 receptor (sIL-2R) and lactate dehydrogenase (LDH) compared to those in the EBV-positive DLBCL or EBV-negative DLBCL groups (sIL-2R, P < 0.001, P = 0.025; LDH, P = 0.018, P = 0.038, respectively). However, histologically, EBVMCU exhibited EBV-positive, variable-sized, atypical B-cell proliferation. Thus, EBVMCU was histologically classified as: (1) polymorphous; (2) large cell-rich; (3) classic Hodgkin lymphoma-like; and (4) mucosa-associated lymphoid tissue lymphoma-like. Moreover, genetic analysis showed that immunoglobin heavy chain (IGH) gene rearrangement did not differ significantly between EBVMCU and EBV-positive DLBCL (44% vs. 32%; P = 0.377), or between EBVMCU and EBV-negative DLBCL (44% vs. 58%; P = 0.280). Therefore, it is difficult to distinguish EBVMCU from EBV-positive DLBCL using only pathological and genetic findings, suggesting that clinical information is important in accurately distinguishing between EBVMCU and EBV-positive DLBCL.

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  • Methotrexate-Associated Lymphoproliferative Disorders Mimicking Granulomatosis With Polyangiitis: A Radiological Diagnostic Challenge. 査読 国際誌

    Tomoyasu Tachibana, Tomoaki Sasaki, Yoji Wani, Yasutoshi Komatsubara, Kazunori Kuroda, Yuto Naoi, Yuka Gion, Yorihisa Orita, Kazunori Nishizaki, Yasuharu Sato

    Ear, nose, & throat journal   101 ( 8 )   145561320970685 - 145561320970685   2020年11月

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    担当区分:最終著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Methotrexate-associated lymphoproliferative disorders (MTX-LPD) frequently involve the extranodal organs throughout the body. Among the extranodal occurrences of MTX-LPD, pulmonary involvement is most frequent. In contrast, there are only a few reports of MTX-LPD in the nasal cavity or paranasal sinuses. Moreover, there are no previous reports of MTX-LPD mimicking granulomatosis with polyangiitis (GPA) in imaging examinations. We describe a case of a 53-year-old woman with MTX-LPD mimicking GPA in the nasal cavity and lungs. She complained of left nasal obstruction and discharge, general fatigue, and continual fever for 2 months. The patient had been diagnosed with rheumatoid arthritis and received methotrexate (MTX) for over 10 years. Contrast-enhanced computed tomography revealed unenhanced masses in the nasal cavity and multiple masses with cavitary changes in the bilateral lungs, suggesting GPA. However, histological examination of the nasal lesion and a history of MTX treatment indicated a diffuse large B-cell lymphoma type MTX-LPD. Two weeks after MTX withdrawal, prominent improvements in both lesions were observed. Complete regression of the nasal lesion was observed 3 months after discontinuation of MTX. Thus, MTX-LPD may mimic GPA in imaging examinations.

    DOI: 10.1177/0145561320970685

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  • Application of Lip Biopsy for the Histological Diagnosis of Immunoglobulin G4-Related Disease. 査読 国際誌

    Tomoyasu Tachibana, Yorihisa Orita, Yoji Wani, Yasutoshi Komatsubara, Kazunori Kuroda, Yuto Naoi, Yuka Gion, Takuma Makino, Kazunori Nishizaki, Yasuharu Sato

    Ear, nose, & throat journal   101 ( 8 )   145561320971932 - 145561320971932   2020年11月

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    担当区分:最終著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

    We describe the case of a 51-year-old woman with immunoglobulin G4-related disease (IgG4-RD) diagnosed using lip biopsy. She reported having bilateral submandibular nodules for a month. Magnetic resonance imaging showed diffuse swelling in the bilateral submandibular glands (SMGs), suggesting inflammatory changes. Laboratory data revealed an elevated level of serum IgG4. Fine needle aspiration cytology of the SMG showed a considerable number of lymphocytes with degeneration but did not demonstrate specific findings for a definitive diagnosis of IgG4-RD. Lip biopsy was performed, and a biopsy specimen from the labial salivary gland showed abundant lymphoplasmacytic infiltration with a large number of IgG4-positive cells. The patient was diagnosed with IgG4-RD based on histological and laboratory findings. Findings of further examinations revealed that the patient had autoimmune pancreatitis, confirming our diagnosis. Four months after prednisolone administration, improvement of the submandibular and pancreatic lesions was observed. One year after the initial presentation, the serum IgG4 level was normalized. In cases of IgG4-RD with salivary gland involvement, lip biopsy might be one of the options for the histological diagnosis of IgG4-RD.

    DOI: 10.1177/0145561320971932

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  • A Novel Predictive Model for Idiopathic Multicentric Castleman Disease: The International Castleman Disease Consortium Study. 査読 国際誌

    Li Yu, Menghan Shi, Qingqing Cai, Paolo Strati, Fredrick Hagemeister, Qiongli Zhai, Ling Li, Xiaosheng Fang, Jianyong Li, Ruifang Sun, Shanxiang Zhang, Hanjin Yang, Zhaoming Wang, Wenbin Qian, Noriko Iwaki, Yasuharu Sato, Lu Zhang, Jian Li, Eric Oksenhendler, Zijun Y Xu-Monette, Ken H Young

    The oncologist   25 ( 11 )   963 - 973   2020年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: Patients with multicentric Castleman disease (MCD) who are negative for human immunodeficiency virus and human herpesvirus 8 are considered to have idiopathic MCD (iMCD). The clinical presentation of iMCD varies from mild constitutional symptoms to life-threatening symptoms or death. The treatment strategy varies from "watchful waiting" to high-dose chemotherapy. This diverse clinical presentation calls for a classification stratification system that takes into account the severity of the disease. SUBJECTS, MATERIALS, AND METHODS: We analyzed the clinical, laboratory, and pathologic abnormalities and treatment outcomes of 176 patients with iMCD (median follow-up duration 12 years) from the U.S. and China to better understand the characteristics and prognostic factors of this disease. This discovery set of iMCD results was confirmed from the validation set composed of additional 197 patients with iMCD organized from The International Castleman Disease Consortium. RESULTS: Using these data, we proposed and validated the iMCD international prognostic index (iMCD-IPI), which includes parameters related to patient characteristics (age > 40 years), histopathologic features (plasma cell variant), and inflammatory consequences of iMCD (hepatomegaly and/or splenomegaly, hemoglobin <80 g/L, and pleural effusion). These five factors stratified patients according to their performance status and extent of organ dysfunction into three broad categories: low risk, intermediate risk, and high risk. The iMCD-IPI score accurately predicted outcomes in the discovery study cohort, and the results were confirmed on the validation study cohort. CONCLUSION: This study represents the largest series of studies on patients with iMCD in the field and proposed a novel risk-stratification model for iMCD-IPI that could be used to guide risk-stratified treatment strategies in patients with iMCD. IMPLICATIONS FOR PRACTICE: Patients with idiopathic multicentric Castleman disease (iMCD) can benefit from care based on clinical symptoms and disease severity. This study in 176 patients with iMCD constructed an iMCD-IPI score based on five clinical factors, including age >40 years, plasmacytic variant subtype, hepatomegaly and/or splenomegaly, hemoglobin <80 g/L, and pleural effusion, and stratified patients into three risk categories: low risk, intermediate risk, and high risk. The predictive value was validated in an independent set of 197 patients with iMCD from The International Castleman Disease Consortium. The proposed novel model is valuable for predicting clinical outcome and selecting optimal therapies using clinical parameters.

    DOI: 10.1634/theoncologist.2019-0986

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  • Pathological evaluation of radiotherapy and concomitant intraarterial cisplatin for maxillary sinus cancer. 査読 国際誌

    Takuma Makino, Tomoyasu Tachibana, Shin Kariya, Yusuke Matsui, Hidenobu Matsuzaki, Shohei Fujimoto, Yorihisa Orita, Kuniaki Katsui, Takao Hiraki, Yasuharu Sato, Susumu Kanazawa, Kazunori Nishizaki

    Auris, nasus, larynx   47 ( 5 )   881 - 886   2020年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    OBJECTIVE: Since 2010, we have mainly performed surgical treatment following radiotherapy and concomitant intraarterial cisplatin (RADPLAT) for locally advanced maxillary sinus cancer (MSC). The present study investigated treatment results and pathological evaluations following RADPLAT for MSC. METHODS: Pathological response to RADPLAT was evaluated using surgical specimens. Pathological response was graded in accordance with the classification method that Shimosato reported in 1964, as grade V (no tumor cells remain in any of section), grade IV, III, II, I, and 0. Five-year overall and disease-specific survival rates were estimated using Kaplan-Meier methods. Univariate analyses of correlations between recurrence of MSC and other clinicopathological parameters were evaluated using the chi-square or Fisher's exact tests. RESULT: 19 patients were enrolled in this study, 5 patients showed T3 disease and 14 had T4 disease. One patient demonstrated local recurrence and 3 patients experienced distant metastasis. The 5-year overall survival rate was 67.1% (T3, 50.0%; T4, 69.6%), and the 5-year disease-specific survival rate was 81.9% (T3, 100%; T4, 76.0%). Histological response was categorized as grade V in 9 cases. No significant risk factors for residual cancer were identified. CONCLUSION: Our study suggested that RADPLAT not only has a low risk of side effects, but also could represent an effective procedure for locally advanced MSC by pathological evaluation. Increasing the therapeutic intensity of RADPLAT might provide an effective modality to avoid highly invasive surgery.

    DOI: 10.1016/j.anl.2020.04.004

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  • Clinicopathological significance of CD79a expression in classic Hodgkin lymphoma. 査読

    Akio Sakatani, Takuro Igawa, Takeshi Okatani, Megumu Fujihara, Hideki Asaoku, Yasuharu Sato, Tadashi Yoshino

    Journal of clinical and experimental hematopathology : JCEH   60 ( 3 )   78 - 86   2020年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Classic Hodgkin lymphoma (CHL) is a lymphoid neoplasia characterized by the presence of large tumor cells, referred to as Hodgkin and Reed-Sternberg (HRS) cells, originating from B-cells in an inflammatory background. As the clinical significance of B-cell markers has yet to be fully elucidated, this study aimed to clarify the clinicopathological significance of CD79a in 55 patients with CHL. They were immunohistochemically divided into two groups, comprising of 20 CD79a-positive and 35 CD79a-negative patients. There was no significant correlation between CD79a and CD20 expression (rs = 0.125, P = 0.362). CD79a-positive patients were significantly older at onset (P = 0.011). There was no significant correlation between CD79a-positivity and clinical stage (P = 0.203), mediastinal involvement (P = 0.399), extranodal involvement (P = 0.749), or laboratory findings, including serum levels of lactate dehydrogenase (P = 1) and soluble interleukin-2 receptor (P = 0.251). There were significant differences in overall survival (OS) (P = 0.005) and progression-free survival (PFS) (P = 0.007) between CD79a-positive and CD79a-negative patients (5-year OS: 64.6% and 90.5%; 5-year PFS: 44.0% and 76.6%, respectively). Five patients in whom the majority (> 80%) of HRS cells expressed CD79a consisted of 4 males and 1 female aged between 52 and 81 years; 4 of them were in a limited clinical stage. We concluded that CD79a-positive CHL may have unique clinicopathological features.

    DOI: 10.3960/jslrt.20010

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  • Primary human herpesvirus 8-negative effusion-based lymphoma: a large B-cell lymphoma with favorable prognosis. 査読 国際誌

    Daisuke Kaji, Yasunori Ota, Yasuharu Sato, Koji Nagafuji, Yasunori Ueda, Masataka Okamoto, Yasushi Terasaki, Naoko Tsuyama, Kosei Matsue, Tomohiro Kinoshita, Go Yamamoto, Shuichi Taniguchi, Shigeru Chiba, Koichi Ohshima, Koji Izutsu

    Blood advances   4 ( 18 )   4442 - 4450   2020年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Primary effusion-based lymphoma (EBL) presents as a malignant effusion in a body cavity. The clinicopathologic features and prognosis of primary human herpesvirus 8 (HHV8)-negative EBL remain unclear. We therefore conducted a retrospective study of 95 patients with EBL, regardless of HHV8 status, in Japan. Of 69 patients with EBL tested for HHV8, a total of 64 were negative. The median age of patients with primary HHV8-negative EBL at diagnosis was 77 years (range, 57-98 years); all 58 tested patients were negative for HIV. Primary HHV8-negative EBL was most commonly diagnosed in pleural effusion (77%). Expression of at least 1 pan B-cell antigen (CD19, CD20, or CD79a) was observed in all cases. According to the Hans algorithm, 30 of the 38 evaluated patients had nongerminal center B-cell (non-GCB) tumors. Epstein-Barr virus-encoded small RNA was positive in 6 of 45 patients. In 56 of 64 HHV8-negative patients, systemic therapy was initiated within 3 months after diagnosis. Cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) or CHOP-like regimens with or without rituximab (n = 48) were the most common primary treatments. The overall response and complete response rates were 95% and 73%, respectively. Three patients did not progress without systemic treatment for a median of 24 months. With a median 25-month follow-up, the 2-year overall survival and progression-free survival rates were 84.7% and 73.8%. Sixteen patients died; 12 were lymphoma-related deaths. Thus, most EBL cases in Japan are HHV8-negative and affect elderly patients. The non-GCB subtype is predominant. Overall, primary HHV8-negative EBL exhibits a favorable prognosis after anthracycline-based chemotherapy.

    DOI: 10.1182/bloodadvances.2020002293

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  • Clinical characteristics of subglottic cancer: emphasis on therapeutic management strategies for stage II subglottic cancer. 査読 国際誌

    Yasutoshi Komatsubara, Tomoyasu Tachibana, Yorihisa Orita, Takuma Makino, Kazunori Kuroda, Yuto Naoi, Yuko Kataoka, Yasuharu Sato, Shin Kariya, Kazunori Nishizaki

    Acta oto-laryngologica   140 ( 9 )   773 - 778   2020年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Background: Subglottic cancer (SGC) is extremely rare, as most laryngeal cancers are localized to the glottic region. Accordingly, the clinical characteristics of SGC have not been well characterized.Objectives: In the current study, SGCs were clinically evaluated, and the outcomes of radiotherapy (RT) in patients with stage II SGC were assessed.Materials and Methods: Medical data derived from 11 patients with SGC, who were treated at our hospital between 1995 and 2019, were retrospectively reviewed.Results: In our department SGC accounted for 3.9% of the 280 laryngeal cancer patients treated during the study period. At the time of SGC diagnosis, 9 (81.8%) had stage II cancer, 1 had stage III cancer, and 1 had stage IV cancer. Stage II SGC patients treated with concurrent chemoradiotherapy (CCRT) showed a significantly higher local control rate (p = .026) and laryngeal dysfunction free rate (p = .026) than those treated with RT alone. Salvage surgery, performed in 4 patients whose disease was not locally controlled with CCRT/RT, was successful in 3 patients.Conclusion: As a treatment strategy for stage II SGC, CCRT is an acceptable initial treatment for laryngeal function and preservation while salvage surgery is effective for recurrence after CCRT/RT treatment.

    DOI: 10.1080/00016489.2020.1767303

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  • Clinicopathologic analysis of gastric mucosa-associated lymphoid tissue lymphoma with or without c-Met expression. 査読

    Rika Omote, Yuka Gion, Shizuma Omote, Akira Tari, Takehiro Tanaka, Asami Nishikori, Tadashi Yoshino, Yasuharu Sato

    Medical molecular morphology   53 ( 3 )   149 - 155   2020年9月

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    担当区分:最終著者, 責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT) lymphoma of the stomach is mainly associated with Helicobacter pylori infection, and H. pylori eradication therapy is often effective. However, 20-30% of the cases of MALT lymphoma are resistant to the eradication therapy, and translocation of the API2-MALT1 gene is often found in these cases. Most cases without translocation of API2-MALT1 are localized to the stomach, whereas some cases with this translocation are a more advanced stage of MALT lymphoma that spreads to other organs. The c-Met receptor is a prognostic factor involved in infiltration and metastasis in many malignant tumors, including gastric, pancreatic, lung, and kidney cancer. In the present study, the expression of c-Met in 43 cases of gastric MALT lymphomas was immunohistochemically examined and compared with clinicopathological factors. To elucidate the significance of c-Met in MALT lymphoma, the expression intensity of c-Met in 22 API2-MALT1 translocation-positive and 21 API2-MALT1 translocation-negative cases was scored, compared, and examined. The immunohistochemistry analysis revealed strong staining for c-Met in 21 API2-MALT1 translocation-positive cases and in 1 translocation-negative case (P = 0.00). This result indicates the relationship between strong expression of c-Met and the progression of MALT lymphoma with API2-MALT1 gene translocation.

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  • Comparison of the Hybrid Capture II Method with a PCR-Based Screening Method Using a Carboxyfluorescein-Labeled Primer for Detecting Human Papillomavirus in Cervicovaginal Liquid-Based Cytology 査読

    Yusuke Saiki, Yuka Gion, Asami Nishikori, Yoshiaki Norimatsu, Yasuharu Sato

    Journal of Molecular Pathology   1 ( 1 )   9 - 18   2020年9月

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    担当区分:最終著者   掲載種別:研究論文(学術雑誌)   出版者・発行元:MDPI AG  

    Objective: Human papillomaviruses (HPVs) are DNA viruses, of which over 120 types have been identified. The main screening methods for HPV-DNA include the hybrid capture II (HC-II) and polymerase chain reaction (PCR) assays. Liquid-based cytology (LBC) is a high-quality technique developed to improve the diagnostic reliability of traditional Papanicolaou tests (Pap tests). However, relatively few studies have compared the efficacy of PCR and HC-II assays using cervicovaginal LBC specimens. In this study, we conducted a comparative analysis with results derived from the HC-II assay to assess whether a PCR-based assay using a novel carboxyfluorescein (FAM)-labeled primer could be applied to cervicovaginal LBC specimens. Methods and Results: We analyzed 59 specimens diagnosed as atypical squamous cells of undetermined significance (ASCUS) by Pap tests. After extracting DNA from cervicovaginal LBC specimens, we performed PCR using a FAM-labeled consensus primer, and then conducted fragment analysis to confirm the results. The value of the kappa statistic measuring the agreement between the PCR and HC-II results was 0.8557, or “almost perfect agreement.” Conclusion: Our novel HPV-PCR assay can be successfully applied to cervicovaginal LBC specimens for the detection of HPV subtypes.

    DOI: 10.3390/jmp1010003

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  • PD-L1 expression in tongue squamous cell carcinoma 査読

    Naoki Akisada, Kohei Nishimoto, Soshi Takao, Yuka Gion, Hidenori Marunaka, Tomoyasu Tachibana, Takuma Makino, Kentaro Miki, Yusuke Akagi, Munechika Tsumura, Tomohiro Toji, Tadashi Yoshino, Kazunori Nishizaki, Yorihisa Orita, Yasuharu Sato

    Medical Molecular Morphology   54 ( 1 )   68 - 68   2020年7月

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    担当区分:最終著者   記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Springer Science and Business Media LLC  

    PURPOSE: Immune checkpoint proteins programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) are important therapeutic targets for head and neck cancer. This large-scale case study aimed to analyze tongue squamous cell carcinomas (SCCs) and evaluate the correlation between PD-L1 expression and clinical prognosis. So far, this study is the largest case study on PD-L1 expression in tongue SCCs. METHODS: This is a case-control study that analyzed 121 tongue SCCs. Paraffin-embedded sections and clinical data were obtained retrospectively and immunohistochemistry with PD-L1 was performed. RESULTS: 11.6% contained ≥ 50% of PD-L1-positive cells, 57.1% of these cases had a poor prognosis with nodal metastasis. Among cases of T1/2 primary lesions with nodal metastasis, cases of high PD-L1 expression had a significantly shorter disease-free survival than cases of no PD-L1 expression (p = 0.018). The hazard ratio for high PD-L1 expression was 3.21 (95 per cent CI, 1.26-8.72) compared with no PD-L1 expression after adjusting for other factors. CONCLUSIONS: These data indicate that PD-L1 upregulation in tongue SCCs is associated with a more advanced stage and shorter disease-free survival. PD-1/PD-L1 inhibitors might hence constitute potential adjuvant therapy for tongue SCCs with PD-L1 upregulation.

    DOI: 10.1007/s00795-020-00261-7

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    その他リンク: http://link.springer.com/article/10.1007/s00795-020-00261-7/fulltext.html

  • Clinicopathological differential diagnosis of IgG4-related disease: A historical overview and a proposal of the criteria for excluding mimickers of IgG4-related disease. 査読 国際誌

    Akira Satou, Kenji Notohara, Yoh Zen, Shigeo Nakamura, Tadashi Yoshino, Kazuichi Okazaki, Yasuharu Sato

    Pathology international   70 ( 7 )   391 - 402   2020年7月

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    担当区分:最終著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

    IgG4-related disease (RD) is a relatively new entity, which was first proposed in 2001. Since then, clinical and pathological characteristics of the disease have been investigated. As IgG4-RD has been studied extensively, the diagnostic criteria for IgG4-RD of each organ and the comprehensive diagnostic criteria for IgG4-RD have also been developed. However, one of the biggest challenges in the field is distinguishing between IgG4-RD and mimickers, which show overlapping features with IgG4-RD. It is now known that some non-IgG4-RDs may meet the diagnostic criteria of IgG4-RD and can be misdiagnosed as IgG4-RD. However, accurate diagnosis is crucial, as the treatments for IgG4-RD and those for other diseases that may be misdiagnosed as IgG4-RD are different. This prompted us to create and propose comprehensive exclusion criteria for IgG4-RD. In this review, we have described the comprehensive exclusion criteria for IgG4-RD, with a historical overview of the disease. These exclusion criteria were recently created by the Research Program for Intractable Disease of the Ministry of Health, Labor, and Welfare of Japan, All Japan IgG4 team, to support correct and accurate diagnosis of IgG4-RD.

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  • MACC1 expression is an indicator of recurrence in early-stage glottic cancer. 査読 国際誌

    Takuma Makino, Yorihisa Orita, Yuka Gion, Tomoyasu Tachibana, Soshi Takao, Hidenori Marunaka, Kentaro Miki, Naoki Akisada, Yusuke Akagi, Tadashi Yoshino, Kazunori Nishizaki, Yasuharu Sato

    Japanese journal of clinical oncology   50 ( 4 )   392 - 398   2020年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: Metastasis-associated in colon cancer 1 (MACC1) has been reported to be an independent indicator of poor prognoses in some kinds of cancer due to disease metastasis or recurrence. We investigated the correlation between MACC1 expression and the prognosis of glottic cancer. METHODS: Paraffin-embedded, early-stage (I or II) glottic cancer specimens (n = 52) were immunohistochemically analyzed to explore MACC1 expression. The clinical records associated with each case were also examined. Recurrence-free survival (RFS) was estimated using the Kaplan-Meier method, and between-group RFS differences were assessed using the log-rank test. The multivariate analyses were evaluated using the Cox's proportional-hazard model. RESULTS: Patients were treated with only radiotherapy (RT) (n = 37, including 18 with T1 disease and 19 with T2 disease), or with chemoradiotherapy (CRT) (n = 15, including 1 with T1 disease and 14 with T2 disease). Eleven patients demonstrated local recurrence and two patients experienced cervical lymph node recurrence. Tumor specimens were MACC1-positive in 9 of the 13 (69.2%) patients with local or neck recurrence, and 7 of the 11 (63.6%) patients with local recurrence. The RFS rate of patients who were treated with only RT was significantly lower than that of patients who were treated with CRT (P = 0.0243). The RFS rate was significantly lower in cases with MACC1 expression than in those without MACC1 expression (P = 0.0003). Multivariate analysis revealed that MACC1 expression was an independent risk factor of local recurrence (P = 0.0016). CONCLUSION: MACC1 is an independent indicator of recurrence related to RFS in early-stage glottic cancer.

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  • Hemosiderin deposition in lymph nodes of patients with plasma cell-type Castleman disease. 査読

    Yanyan Han, Takuro Igawa, Kyohei Ogino, Asami Nishikori, Yuka Gion, Tadashi Yoshino, Yasuharu Sato

    Journal of clinical and experimental hematopathology : JCEH   60 ( 1 )   1 - 6   2020年3月

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    担当区分:最終著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Plasma cell-type Castleman disease (PCD) is a rare idiopathic atypical lymphoproliferative disorder. It is difficult to differentiate between PCD and IgG4-related disease (IgG4-RD) based on histology alone. As PCD often presents with abundant hemosiderin deposition, lymph node lesions obtained from 22 PCD patients and 12 IgG4-RD patients were analyzed using Prussian blue staining to clarify whether hemosiderin deposition is effective in distinguishing between these two diseases. The analysis disclosed that hemosiderin was more densely deposited in PCD than in IgG4-RD. The median number of Prussian blue-positive cells ± standard deviation (SD) in PCD and IgG4-RD cases was 13 ± 36 cells/3HPFs and 4 ± 8 cells/3HPFs (P = 0.034), respectively. In addition, we analyzed the relationship between hemosiderin deposition and levels of serum interleukin (IL)-6, serum C-reactive protein (CRP), and anemia-related biomarkers. We found that hemosiderin deposition was significantly correlated with the level of serum CRP (P = 0.045); however, no significant correlation was observed between hemosiderin deposition and serum IL-6 levels (P = 0.204). A non-significant positive correlation was observed between hemosiderin deposition and serum hemoglobin levels (P=0.09). Furthermore, no significant correlation was observed between hemosiderin deposition and serum iron levels (P = 0.799). In conclusion, hemosiderin deposition characteristically observed in PCD may be related to the inflammatory aggressiveness of the disease and could be used for its differential diagnosis.

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  • Serum IgG4 as a biomarker reflecting pathophysiology and post-operative recurrence in chronic rhinosinusitis. 査読 国際誌

    Oka A, Ninomiya T, Fujiwara T, Takao S, Sato Y, Gion Y, Minoura A, Haruna SI, Yoshida N, Sakuma Y, Izuhara K, Ono J, Taniguchi M, Haruna T, Higaki T, Kariya S, Koyama T, Takabayashi T, Imoto Y, Sakashita M, Kidoguchi M, Nishizaki K, Fujieda S, Okano M

    Allergology international : official journal of the Japanese Society of Allergology   69 ( 3 )   417 - 423   2020年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1016/j.alit.2019.12.004

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  • Clinical significance of cytoplasmic IgE-positive mast cells in eosinophilic chronic rhinosinusitis 査読 国際誌

    Gion Y, Okano M, Koyama Y, Oura T, Nishikori A, Orita Y, Tachibana T, Marunaka H, Makino T, Nishizaki K, Sato Y

    Int J Mol Sci   7 ( 21 )   2020年

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    担当区分:最終著者, 責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Cross-linking of antigen-specific IgE bound to the high-affinity IgE receptor (FcεRI) on the surface of mast cells with multivalent antigens results in the release of mediators and development of type 2 inflammation. FcεRI expression and IgE synthesis are, therefore, critical for type 2 inflammatory disease development. In an attempt to clarify the relationship between eosinophilic chronic rhinosinusitis (ECRS) and mast cell infiltration, we analyzed mast cell infiltration at lesion sites and determined its clinical significance. Mast cells are positive for c-kit, and IgE in uncinated tissues (UT) and nasal polyps (NP) were examined by immunohistochemistry. The number of positive cells and clinicopathological factors were analyzed. Patients with ECRS exhibited high levels of total IgE serum levels and elevated peripheral blood eosinophil ratios. As a result, the number of mast cells with membranes positive for c-kit and IgE increased significantly in lesions forming NP. Therefore, we classified IgE-positive mast cells into two groups: membrane IgE-positive cells and cytoplasmic IgE-positive cells. The amount of membrane IgE-positive mast cells was significantly increased in moderate ECRS. A positive correlation was found between the membrane IgE-positive cells and the radiological severity score, the ratio of eosinophils, and the total serum IgE level. The number of cytoplasmic IgE-positive mast cells was significantly increased in moderate and severe ECRS. A positive correlation was observed between the cytoplasmic IgE-positive cells and the radiological severity score, the ratio of eosinophils in the blood, and the total IgE level. These results suggest that the process of mast cell internalization of antigens via the IgE receptor is involved in ECRS pathogenesis.

    DOI: 10.3390/ijms21051843

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  • Clinical and Pathological Characteristics of IgG4-Related Periaortitis/Periarteritis and Retroperitoneal Fibrosis Diagnosed Based on Experts' Diagnosis. 査読

    Ichiro Mizushima, Satomi Kasashima, Yasunari Fujinaga, Kenji Notohara, Takako Saeki, Yoh Zen, Dai Inoue, Motohisa Yamamoto, Fuminari Kasashima, Yasushi Matsumoto, Eisuke Amiya, Yasuharu Sato, Kazunori Yamada, Yukako Domoto, Shigeyuki Kawa, Mitsuhiro Kawano, Nobukazu Ishizaka

    Annals of vascular diseases   12 ( 4 )   460 - 472   2019年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    IgG4-related disease is a systemic disease, characterized by elevation of serum IgG4 and, histopathologically, massive infiltration of IgG4+ lymphocyte and plasma cell infiltration, storiform fibrosis, causing enlargement, nodules or thickening. It may affect various organs simultaneously or metachronously. Here we analyzed the clinical and pathological characteristics of 99 patients diagnosed with IgG4-related periaortitis/periarteritis and retroperitoneal fibrosis. Of 99 patients (women/men, 15/84; mean age 67.3±9.5 years), 33 were diagnosed based on the histopathological findings of perivascular/retroperitoneal lesions, 50 were diagnosed based on the characteristic imaging findings of perivascular/retroperitoneal lesions and the presence of definitive IgG4-related disease in other organ(s), and the remaining 16 patients were diagnosed by experts based on the characteristic imaging findings of perivascular/retroperitoneal legions, serological findings, response to glucocorticoid treatment, and/or the presence of suspected IgG4-related disease in other organ(s). According to the new organ-specific criteria proposed by experts, 73 (73.7%) diagnoses were categorized to be definitive, and 6 (6.1%) and 17 (17.2%) diagnoses were categorized to be probable and possible, respectively. Further analyses are needed to clarify the optimal diagnostic and therapeutic strategy of IgG4-related periaortitis/periarteritis and retroperitoneal fibrosis. (This is a translation of J Jpn Coll Angiol 2018; 58: 117-129.).

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  • Molecular heterogeneity in peripheral T-cell lymphoma, not otherwise specified revealed by comprehensive genetic profiling. 査読 国際誌

    Yosaku Watatani, Yasuharu Sato, Hiroaki Miyoshi, Kana Sakamoto, Kenji Nishida, Yuka Gion, Yasunobu Nagata, Yuichi Shiraishi, Kenichi Chiba, Hiroko Tanaka, Lanying Zhao, Yotaro Ochi, Yasuhide Takeuchi, June Takeda, Hiroo Ueno, Yasunori Kogure, Yusuke Shiozawa, Nobuyuki Kakiuchi, Tetsuichi Yoshizato, Masahiro M Nakagawa, Yasuhito Nanya, Kenichi Yoshida, Hideki Makishima, Masashi Sanada, Mamiko Sakata-Yanagimoto, Shigeru Chiba, Ryota Matsuoka, Masayuki Noguchi, Nobuhiro Hiramoto, Takayuki Ishikawa, Junichi Kitagawa, Nobuhiko Nakamura, Hisashi Tsurumi, Tatsuhiko Miyazaki, Yusuke Kito, Satoru Miyano, Kazuya Shimoda, Kengo Takeuchi, Koichi Ohshima, Tadashi Yoshino, Seishi Ogawa, Keisuke Kataoka

    Leukemia   33 ( 12 )   2867 - 2883   2019年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Peripheral T-cell lymphoma, not otherwise specified (PTCL, NOS) is a diagnosis of exclusion, being the most common entity in mature T-cell neoplasms, and its molecular pathogenesis remains significantly understudied. Here, combining whole-exome and targeted-capture sequencing, gene-expression profiling, and immunohistochemical analysis of tumor samples from 133 cases, we have delineated the entire landscape of somatic alterations, and discovered frequently affected driver pathways in PTCL, NOS, with and without a T-follicular helper (TFH) cell phenotype. In addition to previously reported mutational targets, we identified a number of novel recurrently altered genes, such as KMT2C, SETD1B, YTHDF2, and PDCD1. We integrated these genetic drivers using hierarchical clustering and identified a previously undescribed molecular subtype characterized by TP53 and/or CDKN2A mutations and deletions in non-TFH PTCL, NOS. This subtype exhibited different prognosis and unique genetic features associated with extensive chromosomal instability, which preferentially affected molecules involved in immune escape and transcriptional regulation, such as HLA-A/B and IKZF2. Taken together, our findings provide novel insights into the molecular pathogenesis of PTCL, NOS by highlighting their genetic heterogeneity. These results should help to devise a novel molecular classification of PTCLs and to exploit a new therapeutic strategy for this group of aggressive malignancies.

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  • Hepatic Campylobacter jejuni infection in patients with Castleman-Kojima disease (idiopathic multicentric Castleman disease with thrombocytopenia, anasarca, fever, reticulin fibrosis, and organomegaly (TAFRO) syndrome). 査読 国際誌

    Chihiro Kageyama, Takuro Igawa, Yuka Gion, Noriko Iwaki, Tetsuya Tabata, Takehiro Tanaka, Eisei Kondo, Hajime Sakai, Koichi Tsuneyama, Kazuhiro Nomoto, Hiroko Noguchi, Tadashi Yoshino, Kenji Yokota, Yasuharu Sato

    Pathology international   69 ( 10 )   572 - 579   2019年10月

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    担当区分:最終著者, 責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Castleman-Kojima disease, also known as idiopathic multicentric Castleman disease with TAFRO syndrome (iMCD-TAFRO), is a recently recognized systemic inflammatory disorder with a characteristic series of clinical symptoms, including thrombocytopenia (T), anasarca (A), fever (F), reticulin fibrosis (R), and organomegaly (O). Patients with iMCD-TAFRO often develop severe abdominal pain, elevated alkaline phosphatase levels, and systemic inflammation, but the etiological factors are unknown. To investigate the potential role of bacterial infection in the pathogenesis of iMCD-TAFRO, we performed polymerase chain reaction (PCR) for the bacterial 16S rRNA gene with DNA extracted from liver specimens of three patients with iMCD-TAFRO, four patients with amyotrophic lateral sclerosis, and seven patients with inflammatory conditions. Sequencing of the PCR product showed 99% DNA sequence identity with Campylobacter jejuni in all three patients with iMCD-TAFRO and in two patients with inflammatory conditions. Immunohistochemical and electron microscopy analyses could not identify C. jejuni in patients with iMCD-TAFRO. The findings indicated that C. jejuni infection is not the pathological cause of iMCD-TAFRO; however, this ubiquitous bacterium may play a role in uncontrolled systemic hypercytokinemia, possibly through the development of cross-reactive autoantibodies.

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  • The efficacy of OK-432 sclerotherapy on thyroglossal duct cyst and the influence on a subsequent surgical procedure. 査読 国際誌

    Tachibana T, Kariya S, Orita Y, Makino T, Haruna T, Matsuyama Y, Komatsubara Y, Naoi Y, Nakada M, Wani Y, Fushimi S, Hotta M, Haruna K, Nagatani T, Sato Y, Nishizaki K

    Acta Otolaryngol.   139 ( 9 )   788 - 792   2019年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1080/00016489.2019.1633019

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  • Focus on immunodeficiency-associated lymphoproliferative disorders. 招待 査読

    Sato Y

    J Clin Exp Hematop.   59 ( 2 )   64 - 71   2019年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

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  • Clinical and biochemical characteristics of patients having general symptoms with increased serum IgG4. 査読 国際誌

    Hasegawa K, Hanayama Y, Obika M, Miyoshi T, Ogawa H, Kondo E, Kataoka H, Sato Y, Otsuka F

    Mod Rheumatol.   30 ( 4 )   721 - 728   2019年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1080/14397595.2019.1642291

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  • A review of EBV-positive mucocutaneous ulcers focusing on clinical and pathological aspects. 招待 査読

    Ikeda T, Gion Y, Yoshino T, Sato Y

    Journal of clinical and experimental hematopathology   59 ( 2 )   64 - 71   2019年8月

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    担当区分:最終著者, 責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

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  • Methotrexate-associated lymphoproliferative disorders of T-cell phenotype: clinicopathological analysis of 28 cases. 査読 国際誌

    Akira Satou, Tetsuya Tabata, Hiroaki Miyoshi, Kei Kohno, Yuka Suzuki, Daisuke Yamashita, Kazuyuki Shimada, Tomonori Kawasaki, Yasuharu Sato, Tadashi Yoshino, Koichi Ohshima, Taishi Takahara, Toyonori Tsuzuki, Shigeo Nakamura

    Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc   32 ( 8 )   1135 - 1146   2019年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Methotrexate-associated lymphoproliferative disorders are categorized as "other immunodeficiency-associated lymphoproliferative disorders in the WHO classification. Methotrexate-associated lymphoproliferative disorder is mainly a B-cell lymphoproliferative disorders or Hodgkin lymphoma type, whereas T-cell lymphoproliferative disorders are relatively rare (4-8%). Only a small number of methotrexate-associated T-cell lymphoproliferative disorders have been detailed thus far. Because of the rarity, methotrexate-associated T-cell lymphoproliferative disorder has not been well studied and its clinicopathological characteristics are unknown. A total of 28 cases of methotrexate-associated T-cell lymphoproliferative disorders were retrospectively analyzed. Histologically and immunohistochemically, they were divided into three main types: angioimmunoblastic T-cell lymphoma (n = 19), peripheral T-cell lymphoma, NOS (n = 6), and CD8+ cytotoxic T-cell lymphoma (n = 3). Among the 28 cases, only one CD8+ cytotoxic T-cell lymphoma case was Epstein-Barr virus-positive. The other 27 cases were negative for Epstein-Barr virus on tumor cells, but scattered Epstein-Barr virus-infected B-cells were detected in 24 cases (89%), implying the reactivation of Epstein-Barr virus caused by immunodeficient status of the patients. After the diagnosis of methotrexate-associated T-cell lymphoproliferative disorder, methotrexate was immediately withdrawn in 26 cases. Twenty (77%) cases presented with spontaneous regression. Compared to methotrexate-associated B-cell lymphoproliferative disorder, patients with methotrexate-associated T-cell lymphoproliferative disorder had a significantly higher proportion of males (p = 0.035) and presence of B-symptoms (p = 0.036), and lower proportion of Epstein-Barr virus+ tumor cells (p < 0.001). Although the difference was not significant, the methotrexate-associated T-cell lymphoproliferative disorder also had more frequent spontaneous regression (p = 0.061). In conclusion, methotrexate-associated T-cell lymphoproliferative disorder was divided into three main types: angioimmunoblastic T-cell lymphoma, peripheral T-cell lymphoma, NOS, and CD8+ cytotoxic T-cell lymphoma. Angioimmunoblastic T-cell lymphoma was the most common type. Methotrexate-associated T-cell lymphoproliferative disorder was characterized by a high rate of spontaneous regression after methotrexate cessation. Epstein-Barr virus positivity was relatively rare in methotrexate-associated T-cell lymphoproliferative disorder, significantly less frequent than methotrexate-associated B-cell lymphoproliferative disorder, suggesting different pathogenesis.

    DOI: 10.1038/s41379-019-0264-2

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  • Activated M2 macrophage contributes to the pathogenesis of IgG4-related disease via TLR7/IL-33 signaling. 査読 国際誌

    Ishiguro N, Moriyama M, Furusho K, Furukawa S, Shibata T, Murakami Y, Chinju A, Rafiul Haque ASM, Gion Y, Ohta M, Maehara T, Tanaka A, Yamauchi M, Sakamoto M, Mochizuki K, Ono Y, Hayashida JN, Sato Y, Kiyoshima T, Yamamoto H, Miyake K, Nakamura S

    Arthritis Rheumatol.   72 ( 1 )   166 - 178   2019年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1002/art.41052

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  • KRAS mutations in tongue squamous cell carcinoma. 査読

    Akagi Y, Tachibana T, Orita Y, Gion Y, Marunaka H, Makino T, Miki K, Akisada N, Yoshino T, Nishizaki K, Sato Y

    Acta Oto-Laryngologica   139 ( 7 )   647 - 651   2019年7月

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    担当区分:最終著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1080/00016489.2019.1610574

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  • Spontaneous closure of traumatic tympanic membrane perforation following long-term observation. 査読

    Tachibana T, Kariya S, Orita Y, Makino T, Haruna T, Matsuyama Y, Komatsubara Y, Naoi Y, Nakada M, Noda Y, Sato Y, Nishizaki K

    Acta Otolaryngol.   139 ( 6 )   487 - 491   2019年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1080/00016489.2019.1592225

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  • Virome capture sequencing does not identify active viral infection in unicentric and idiopathic multicentric Castleman disease. 査読 国際誌

    Nabel CS, Sameroff S, Shilling D, Alapat D, Ruth JR, Kawano M, Sato Y, Stone K, Spetalen S, Valdivieso F, Feldman MD, Chadburn A, Fosså A, van Rhee F, Lipkin WI, Fajgenbaum DC

    PLoS One.   14 ( 6 )   e0218660   2019年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1371/journal.pone.0218660

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  • Molecular heterogeneity in peripheral T-cell lymphoma, not otherwise specified revealed by comprehensive genetic profiling. 査読

    Watatani Y, Sato Y, Miyoshi H, Sakamoto K, Nishida K, Gion Y, Nagata Y, Shiraishi Y, Chiba K, Tanaka H, Zhao L, Ochi Y, Takeuchi Y, Takeda J, Ueno H, Kogure Y, Shiozawa Y, Kakiuchi N, Yoshizato T, Nakagawa MM, Nanya Y, Yoshida K, Makishima H, Sanada M, Sakata-Yanagimoto M, Chiba S, Matsuoka R, Noguchi M, Hiramoto N, Ishikawa T, Kitagawa J, Nakamura N, Tsurumi H, Miyazaki T, Kito Y, Miyano S, Shimoda K, Takeuchi K, Ohshima K, Yoshino T, Ogawa S, Kataoka K

    Leukemia.   59   113 - 113   2019年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

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  • Significance of IgG4-positive cells in severe eosinophilic chronic rhinosinusitis. 査読

    Koyama T, Kariya S, Sato Y, Gion Y, Higaki T, Haruna T, Fujiwara T, Minoura A, Takao S, Orita Y, Kanai K, Taniguchi M, Nishizaki K, Okano M

    Allergol Int.   68 ( 2 )   216 - 224   2019年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1016/j.alit.2018.09.002

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  • Up-regulation of activation-induced cytidine deaminase and its strong expression in extra-germinal centres in IgG4-related disease. 査読

    Gion Y, Takeuchi M, Shibata R, Takata K, Miyata-Takata T, Orita Y, Tachibana T, Yoshino T, Sato Y

    SCIENTIFIC REPORTS   9 ( 1 )   761   2019年1月

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    担当区分:最終著者, 責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1038/s41598-018-37404-x

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  • Young adult patients with squamous cell carcinoma of the tongue strongly express p16 without human papillomavirus infection. 査読

    Tachibana T, Orita Y, Gion Y, Miki K, Ikegami K, Marunaka H, Makino T, Akagi Y, Akisada N, Tsumura M, Ito T, Yoshino T, Nishizaki K, Sato Y

    Acta Otolaryngol.   139 ( 1 )   80 - 84   2019年1月

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    担当区分:最終著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1080/00016489.2018.1541506

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  • Factors that prolong the duration of recovery in acute rhinosinusitis with orbital complications. 査読 国際誌

    Tachibana T, Kariya S, Orita Y, Nakada M, Makino T, Haruna T, Matsuyama Y, Komatsubara Y, Naoi Y, Sato Y, Nishizaki K

    Acta Otolaryngol.   139 ( 1 )   52 - 56   2019年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1080/00016489.2018.1539516

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  • Frequent structural variations involving programmed death ligands in Epstein-Barr virus-associated lymphomas. 査読 国際誌

    Kataoka K, Miyoshi H, Sakata S, Dobashi A, Couronne L, Kogure Y, Sato Y, Nishida K, Gion Y, Shiraishi Y, Tanaka H, Chiba K, Watatani Y, Kakiuchi N, Shiozawa Y, Yoshizato T, Yoshida K, Makishima H, Sanada M, Onozawa M, Teshima T, Yoshiki Y, Ishida T, Suzuki K, Shimada K, Tomita A, Kato M, Ota Y, Izutsu K, Demachi-Okamura A, Akatsuka Y, Miyano S, Yoshino T, Gaulard P, Hermine O, Takeuchi K, Ohshima K, Ogawa S

    Leukemia.   33 ( 7 )   1687 - 1699   2019年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1038/s41375-019-0380-5

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  • A Long-term Survival after Surgical Treatment for Atypical Aortic Coarctation Complicating Takayasu Arteritis with Inactive Disease at the Diagnosis: An Appropriately Treated Autopsy Case. 査読

    Yoshida M, Zoshima T, Hara S, Mizushima I, Fujii H, Yamada K, Sato Y, Harada K, Kawano M

    Intern Med.   58 ( 15 )   2241 - 2246   2019年

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  • Computed Tomography Findings for Diagnosing Follicular Thyroid Neoplasms. 査読

    Takuma Makino, Yorihisa Orita, Tomoyasu Tachibana, Hidenori Marunaka, Kentaro Miki, Naoki Akisada, Yusuke Akagi, Yoshiyuki Usui, Yasuharu Sato, Tadashi Yoshino, Kazunori Nishizaki

    Acta medica Okayama   72 ( 6 )   577 - 581   2018年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Since no diagnostic method has been established to distinguish follicular thyroid carcinoma (FTC) from follicular thyroid adenoma (FTA), surgery has been the only way to reach a diagnosis of follicular neoplasm. Here we investigated the computed tomography (CT) features of follicular neoplasms, toward the goal of being able to identify specific CT features allowing the preoperative differentiation of FTC from FTA. We retrospectively analyzed the cases of 205 patients who underwent preoperative CT of the neck and were histopathologically diagnosed with FTC (n=31) or FTA (n=174) after surgery between January 2002 and June 2016 at several hospitals in Japan. In each of these 205 cases, non-enhanced and contrast-enhanced CT images were obtained, and we analyzed the CT features. On univariate analysis, inhomogeneous features of tumor lesions on contrast-enhanced CT were more frequently observed in FTC than in FTA (p=0.0032). A multivariate analysis identified inhomogeneous features of tumor lesions on contrast-enhanced CT images as an independent variable indicative of FTC (p=0.0023). CT thus offers diagnostic assistance in distinguishing FTC from FTA.

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  • Recent progress in follicular lymphoma in Japan and characteristics of the duodenal type

    Tadashi Yoshino, Katsuyoshi Takata, Takehiro Tanaka, Yasuharu Sato, Akira Tari, Hiroyuki Okada

    PATHOLOGY INTERNATIONAL   68 ( 12 )   665 - 676   2018年12月

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    記述言語:英語   出版者・発行元:WILEY  

    The incidence of lymphoma has rapidly increased over the last 40 years in Japan, following a trend that is very similar to that of breast cancer. In particular, the relative frequency of follicular lymphoma (FL) has reached that in Western countries. Given its indolence, a "watch-and-wait" approach is often applied to FL patients. We have shown that FL is often detected in the second portion of the duodenum and has a distinct follicular dendritic cell distribution and heavy chain variable usage similar to mucosa-associated lymphoid tissue (MALT) lymphoma. Although the t(14;18)(q32;q21) frequency is the same as in the nodal subtype of FL, there are also ongoing mutations, immunopositivity for cluster of differentiation 10 and B-cell lymphoma (BCL)6, and overexpression of BCL2. Gene expression profiling has shown that it is more similar to gastric MALT lymphoma than to nodal FL. Duodenal-type FL lacks the activation-induced cytidine deaminase (AID) expression observed in nodal ones, although this may be compensated for by BTB domain and CNC homolog 2. Based on these findings, duodenal-type FL has been included in the Revised 4th edition of the World Health Organization classification published in late 2017.

    DOI: 10.1111/pin.12733

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  • The efficacy and safety of anti-interleukin-6 receptor monoclonal blockade in a renal transplant patient with Castleman disease: early post-transplant outcome. 査読 国際誌

    Masatoshi Matsunami, Yoshifumi Ubara, Keiichi Sumida, Yoichi Oshima, Masahiko Oguro, Kazuya Kinoshita, Kiho Tanaka, Yuki Nakamura, Keiichi Kinowaki, Kenichi Ohashi, Takeshi Fujii, Takuro Igawa, Yasuharu Sato, Yasuo Ishii

    BMC nephrology   19 ( 1 )   263 - 263   2018年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: Multicentric Castleman disease (MCD) is an uncommon lymphoproliferative disease characterized by systemic inflammatory reactions associated with the dysregulated production of interleukin-6 (IL-6). In patients with MCD, renal involvement is uncommon, with only one report published regarding kidney transplantation (KTx) to treat end-stage renal disease (ESRD) secondary to MCD. Recent clinical observations have shown that IL-6 production is implicated in allograft rejection, while IL-6 receptor blockade (with tocilizumab [TCZ]) reduces alloantibody generation and thereby improves graft survival; however, the efficacy and safety of TCZ in MCD patients undergoing KTx is still unknown. CASE PRESENTATION: Herein, we describe the case of a 50-year-old man with MCD who received living-donor KTx for ESRD. Post-operative immunosuppression consisted of a triple-drug regimen (tacrolimus, mycophenolate mofetil and methylprednisolone) with TCZ that was administered intravenously every 2 weeks. At 17 months post-transplantation, the patient remains asymptomatic, and the allograft pathology has shown no evidence of rejection and no development of de novo donor-specific antibody (DSA). CONCLUSIONS: To our knowledge, this is the second reported case of an MCD patient with ESRD who underwent successful KTx. TCZ safely supported the patient during the perioperative period, and this drug may be useful for blocking the generation of donor-specific antibodies and reducing the risk of rejection episodes. KTx in combination with TCZ is thus considered a viable treatment option for ESRD due to MCD.

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  • Serum soluble interleukin-2 receptor as a biomarker in immunoglobulin G4-related disease 査読

    Tomohiro Handa, Shoko Matsui, Hajime Yoshifuji, Yuzo Kodama, Hiroshi Yamamoto, Seijiro Minamoto, Yuko Waseda, Yasuharu Sato, Keishi Kubo, Tsuneyo Mimori, Tsutomu Chiba, Toyohiro Hirai, Michiaki Mishima

    Modern Rheumatology   28 ( 5 )   838 - 844   2018年9月

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    掲載種別:研究論文(学術雑誌)  

    © 2017, © 2017 Japan College of Rheumatology. Objectives: Serum soluble interleukin-2 (IL-2) receptor (sIL-2R) might reflect disease activity in immunoglobulin G4-related disease (IgG4-RD). We aimed to elucidate the clinical significance of blood markers, including sIL-2R, in patients with IgG4-RD. Methods: We enrolled 59 patients with IgG4-RD and investigated the association between blood markers (white blood cells, C-reactive protein, sIL-2R, IgG, IgG4, IgE, total hemolytic complement), and clinical indices. Results: At baseline, serum sIL-2R (Rs = 0.532, p <.001) and IgG4 (Rs = 0.545, p <.001) levels showed significant correlation to the number of organs involved. During follow-up period (median, 70 months; range, 7–195 months), 40 patients were treated with corticosteroids. Receiver operating characteristic (ROC) analysis showed that baseline sIL-2R levels most accurately predicted patients requiring glucocorticoid treatment (area under the ROC curve, 0.807). Among the 46 patients who improved, sIL-2R and IgG4 levels decreased in 42 and 41 patients, respectively. Among them, serum sIL-2R levels decreased to a normal range in 42 patients (91%), whereas IgG4 levels normalized in 19 (41%). Conclusion: The serum sIL-2R level is a potential biomarker for IgG4-RD that may reflect the number of involved organs and may predict patients requiring glucocorticoid treatment.

    DOI: 10.1080/14397595.2017.1416739

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  • Gastrointestinal manifestation of immunoglobulin G4-related disease: clarification through a multicenter survey 査読

    Kenji Notohara, Terumi Kamisawa, Kazushige Uchida, Yoh Zen, Mitsuhiro Kawano, Satomi Kasashima, Yasuharu Sato, Masahiro Shiokawa, Takeshi Uehara, Hajime Yoshifuji, Hiroko Hayashi, Koichi Inoue, Keisuke Iwasaki, Hiroo Kawano, Hiroyuki Matsubayashi, Yukitoshi Moritani, Katsuhiko Murakawa, Yoshio Oka, Masatoshi Tateno, Kazuichi Okazaki, Tsutomu Chiba

    Journal of Gastroenterology   53 ( 7 )   845 - 853   2018年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Springer Tokyo  

    Background: Several reports on immunoglobulin (Ig)G4-related disease (IgG4-RD) with gastrointestinal involvement (IgG4-related gastrointestinal disease
    IgG4-GID) have been published, although this entity has not been fully established clinicopathologically. Thus, we carried out a multicenter survey. Methods: Patients with possible IgG4-GID who underwent resection were collected. Histologic slides were reevaluated, and eight cases with diffuse lymphoplasmacytic infiltration but without numerous neutrophils, granulations or epithelioid granulomas were further analyzed. Results: Overall, the IgG4 counts (87–345/high-power field) and IgG4/IgG-positive ratio were high (44–115%). The demographic findings included advanced age among the patients (55–80 years) and male preponderance (six cases). Six lesions (five gastric, one esophageal), consisting of lymphoplasmacytic infiltration with neural involvement in the muscularis propria and/or bottom-heavy plasmacytosis in the gastric mucosa, were histologically regarded as highly suggestive of IgG4-RD. Storiform fibrosis and obliterative phlebitis were found in two cases, and the former gave rise to a 7-cm-sized inflammatory pseudotumor (IPT) in one case. Ulceration and carcinoma co-existed in three and two lesions, respectively. All the patients had other organ involvement (OOI), and serum IgG4 levels were markedly elevated (four of five patients). The remaining two cases with gastric IPTs featuring reactive nodular fibrous pseudotumor or nodular lymphoid hyperplasia were regarded as possible cases of IgG4-RD because of the histologic findings and lack of OOI. Conclusions: IgG4-GID is found in the setting of IgG4-RD, often with ulceration or cancer. Characteristic histologic findings are observed in the muscularis propria and gastric mucosa. Cases with IPT may be heterogeneous, and there may be mimickers of IgG4-GID.

    DOI: 10.1007/s00535-017-1420-4

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  • Overexpression of folate receptor alpha is an independent prognostic factor for outcomes of pancreatic cancer patients 査読

    Shizuma Omote, Katsuyoshi Takata, Takehiro Tanaka, Tomoko Miyata-Takata, Yoshiyuki Ayada, Mai Noujima-Harada, Rika Omote, Tetsuya Tabata, Yasuharu Sato, Tatsuya Toyokawa, Hironari Kato, Takahito Yagi, Hiroyuki Okada, Tadashi Yoshino

    Medical Molecular Morphology   51 ( 4 )   1 - 7   2018年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Springer Tokyo  

    Pancreatic cancer has a poor prognosis
    hence, novel prognostic markers and effective therapeutic targets should be identified. We aimed to evaluate folate receptor alpha (FR-α) expression in pancreatic cancer and examine its association with clinicopathological features. We utilized tissue samples from 100 primary pancreatic cancer patients who underwent surgery. FR-α was expressed in 37 of 100 cases (37%). The FR-α-positive group (median, 18.8 months) had a significantly poorer prognosis than the FR-α-negative group [median 21.3 months
    HR 1.89 (1.12–3.12)
    P = 0.017]. These groups were not significantly different regarding progression-free survival (P = 0.196). Furthermore, other serum tumor markers including CA19-9 (mean, 186 vs. 822 U/ml
    P = 0.001), Dupan-2 (286 vs. 1133 U/ml
    P = 0.000), and Span-1 (69.7 vs. 171.9 U/ml
    P = 0.006) were significantly downregulated in the FR-α-positive group. CA19-9 was another prognostic factor, in addition to FR-α, and patient prognosis showed clear stratification curves with the expression of these two molecules. Along with CA19-9, FR-α expression was an independent prognostic factor for the overall survival. FR-α and CA19-9 helped predict patient prognosis based on stratification curves.

    DOI: 10.1007/s00795-018-0197-8

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  • Prognostic factors and importance of recognition of adult croup 査読

    Tomoyasu Tachibana, Yorihisa Orita, Takuma Makino, Yasutoshi Komatsubara, Yuko Matsuyama, Yuto Naoi, Michihiro Nakada, Yasuharu Sato, Kazunori Nishizaki

    Acta Oto-Laryngologica   138 ( 6 )   579 - 583   2018年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Taylor and Francis Ltd  

    Objectives: Croup, or laryngotracheobronchitis, is a common disease in childhood. On the other hand, to our knowledge, there are only 14 cases in six English literatures describing adult croup (AC). The clinical features of AC have not been well known. Methods: We conducted a retrospective analysis of medical records of 18 patients with AC during the period from 2008 to 2016. Results: None of the 18 patients required an urgent airway intervention. Univariate analysis indicated that the duration of symptoms was significantly longer in patients with cough (p &lt
    .01) and younger patients (age &lt
    60, p =.037). The duration of subglottic edema was significantly longer in female (p =.035), patients with high levels of CRP (≥1 mg/dL, p =.049), and patients with cough symptom (p =.035). Conclusions: Female, young age (&lt
    60 years), the symptom of cough, and high levels of CRP should be recognized as signs of prolonged AC. It is important to confirm the diagnosis of AC by laryngoscopic examination, which also help to avoid airway intervention.

    DOI: 10.1080/00016489.2017.1422140

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  • Neck metastasis in patients with T1-2 supraglottic cancer 査読

    Tomoyasu Tachibana, Yorihisa Orita, Hidenori Marunaka, Sei-ichiro Makihara, Misato Hirai, Yuka Gion, Kana Ikegami, Kentaro Miki, Takuma Makino, Yasuyuki Noyama, Yasutoshi Komatsubara, Miyuki Kimura, Tadashi Yoshino, Kazunori Nishizaki, Yasuharu Sato

    Auris Nasus Larynx   45 ( 3 )   540 - 545   2018年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Elsevier Ireland Ltd  

    Objectives: Unlike glottic cancer, supraglottic cancer often presents with neck metastases. This different might be attributable to the location of the primary lesion. This study aimed to clarify the relationships between the sublocation of T1-2 supraglottic cancer, human papillomavirus (HPV) infection, neck metastasis, and prognosis of supraglottic cancer. Methods: This retrospective clinical study investigated 55 Japanese patients with T1-2 supraglottic cancer treated between 1994 and 2015. Results: Of 55 patients with T1-2 supraglottic cancer, neck metastasis was present at initial diagnosis in 14 patients (25.5%). Presence of neck metastasis was the only factor associated with worse prognosis of T1-2 supraglottic cancer (p = 0.004). In multivariate analysis, age &lt
    70 years (p = 0.033) and sublocation of the primary lesion in the superior epilaryngeal portion (p = 0.017) were significantly associated with presence of neck metastasis in multivariate analysis. Twelve (27.9%) of 43 patients showed positive results for human papillomavirus infection. However, human papillomavirus infection was not associated with prognosis, presence of neck metastasis, or primary lesion sublocation in T1-2 supraglottic cancer. Conclusion: Relatively young patients with supraglottic cancer at the superior epilaryngeal portion are more likely to show neck metastasis. Human papillomavirus infection was not associated with frequency of neck metastasis.

    DOI: 10.1016/j.anl.2017.06.002

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  • Diffuse large B-cell lymphoma of the lacrimal sac arising from a patient with IgG4-related disease 査読

    Hidenori Marunaka, Yorihisa Orita, Tomoyasu Tachibana, Kentaro Miki, Takuma Makino, Tadashi Yoshino, Kazunori Nishizaki, Yasuharu Sato

    Modern Rheumatology   28 ( 3 )   559 - 563   2018年5月

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    担当区分:最終著者   記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Taylor and Francis Ltd  

    A rare case of diffuse large B-cell lymphoma (DLBCL) possibly induced by IgG4-related disease is described. A 78-year-old woman was presented with a mass of the right lacrimal sac that extended to the inferior nasal meatus through the nasolacrimal duct. Pathological diagnosis was DLBCL with diffuse distribution of IgG4 + cells in the background of this lesion. The chronic inflammatory state of IgG4-related disease could have caused the development of DLBCL.

    DOI: 10.3109/14397595.2015.1131353

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  • Gastrointestinal follicular lymphoma: Current knowledge and future challenges 招待 査読

    Katsuyoshi Takata, Tomoko Miyata-Takata, Yasuharu Sato, Masaya Iwamuro, Hiroyuki Okada, Akira Tari, Tadashi Yoshino

    Pathology International   68 ( 1 )   1 - 6   2018年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Blackwell Publishing  

    The gastrointestinal (GI) tract is the most commonly involved site of extranodal follicular lymphoma (FL). GI-FL shows very indolent clinical behavior and localized at GI tract without any progression or transformation compared to nodal FL. The most frequently involved site of the GI tract was the duodenum followed by the jejunum and ileum, and only 15% of FL arising in the second part of the duodenum were localized there without scattered very small daughter lesions in other GI tract examined by double-balloon endoscopy. The typical macroscopic appearance of GI-FL was multiple white nodules. Microscopically, neoplastic cells were small- to medium-sized lymphoid cells and formed neoplastic follicles. Most of the cases (&gt
    95%) were histologically Grade 1 to 2 (low grade). Several pathological and molecular characteristics were seen in GI-FL (especially duodenal FL) compared with nodal FL: immunoglobulin heavy chain deviation to VH4 and VH5
    memory B-cell immunophenotype
    and molecular features shared by mucosa-associated lymphoid tissue lymphoma. Considering the pathological and molecular uniqueness of this disease, GI-FL should be separately managed from nodal FL.

    DOI: 10.1111/pin.12621

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  • Expression of T-cell receptor signalling pathway components in extranodal NK/T-cell lymphoma. 査読

    Miyata-Takata T, Chuang SS, Takata K, Toji T, Maeda Y, Sato Y, Yoshino T

    Histopathology   98   559 - 559   2018年

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  • Factors in glucocorticoid regimens associated with treatment response and relapses of IgG4-related disease: a multicentre study. 査読 国際誌

    Shirakashi M, Yoshifuji H, Kodama Y, Chiba T, Yamamoto M, Takahashi H, Uchida K, Okazaki K, Ito T, Kawa S, Yamada K, Kawano M, Hirata S, Tanaka Y, Moriyama M, Nakamura S, Kamisawa T, Matsui S, Tsuboi H, Sumida T, Shibata M, Goto H, Sato Y, Yoshino T, Mimori T

    Scientific Reports   8 ( 1 )   10262 - 10262   2018年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1038/s41598-018-28405-x.

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  • Mast cells exhibiting storong cytoplasmic staining for IgE and high affinity IgE receptor are increased in IgG4-related disease. 査読 国際誌

    Nishida K, Gion Y, Takeuchi M, Tanaka T, Kataoka RT, Yoshino T, Sato Y

    Scientific Reports   8 ( 1 )   4656 - 4656   2018年

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    担当区分:最終著者, 責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1038/s41598-018-23043-9.

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  • Laryngeal squamous cell papilloma is highly associated with human papillomavirus. 査読

    Orita Y, Gion Y, Tachibana T, Ikegami K, Marunaka H, Makihara S, Yamashita Y, Miki K, Makino T, Akisada N, Akagai Y, Kimura M, Yoshino T, Nishizaki K, Sato Y

    Japanese Journal of Clinical Oncology   48 ( 4 )   350 - 355   2018年

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    掲載種別:研究論文(学術雑誌)  

    DOI: 10.1093/jjco/hyy009.

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  • A20 (TNFAIP3) alterations in primary intestinal diffuse large B-cell lymphoma. 査読

    Fujii M, Takata K, Chuang SS, Miyata-Takata T, Ando M, Sato Y, Yoshino T

    Acta Medica Okayama   72 ( 1 )   23 - 30   2018年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

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  • Characteristic Distribution Pattern of CD30-positive Cytotoxic T Cells Aids Diagnosis of Kikuchi-Fujimoto Disease 査読

    Tetsuya Tabata, Katsuyoshi Takata, Tomoko Miyata-Takata, Yasuharu Sato, Shin Ishizawa, Tomoyoshi Kunitomo, Keina Nagakita, Nobuhiko Ohnishi, Kohei Taniguchi, Mai Noujima-Harada, Yoshinobu Maeda, Mitsune Tanimoto, Tadashi Yoshino

    Applied Immunohistochemistry and Molecular Morphology   26 ( 4 )   274 - 282   2018年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Lippincott Williams and Wilkins  

    Introduction: Histiocytic necrotizing lymphadenitis (or Kikuchi-Fujimoto disease) frequently occurs in Asian young adult females and typically presents as cervical lymphadenopathy with unknown etiology. Although large immunoblasts frequently appear in Kikuchi-Fujimoto disease, the diffuse infiltration of these cells can cause difficulty in establishing a differential diagnosis from lymphoma. In such cases, CD30 immunostaining may be used
    however, the extent or distribution pattern of CD30-positive cells in Kikuchi-Fujimoto disease remains largely unknown. Here we investigated the expression of CD30 and its clinicopathologic significance. Materials and Methods: We investigated 30 Kikuchi-Fujimoto disease and 16 control [6, systemic lupus erythematosus (SLE)
    10, reactive lymphoid hyperplasia (RLH)] cases. Results: The number of CD30-positive cells in Kikuchi-Fujimoto disease was significantly more than that in SLE and RLH, and majority of these cells were located around necrotic areas. Moreover, double immunohistochemical staining showed these CD30-positive cells to be CD8-positive cytotoxic T cells, suggesting that activated cytotoxic T cells around necrotic areas are a characteristic feature of this disease. Clinicopathologic analysis showed that cases with abundant CD30-positive cells were predominantly female with only mild symptoms and normal laboratory data. Conclusions: In Kikuchi-Fujimoto disease cases, CD30-positive cytotoxic T cells were abundant around necrotic areas
    this histologic feature may be helpful to differentiate this disease from SLE and RLH.

    DOI: 10.1097/PAI.0000000000000411

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  • TAFRO syndrome 招待 査読

    Igawa T, Sato Y

    Hematol Oncol Clin N Am   107 - 118   2018年

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    担当区分:最終著者, 責任著者   記述言語:英語  

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  • International, evidence-based consensus treatment guidelines for idiopathic multicentric Castleman disease. 査読

    van Rhee F, Voorhees P, Dispenzieri A, Fosså A, Srkalovic G, Ide M, Munshi N, Schey S, Streetly M, Pierson SK, Partridge HL, Mukherjee S, Shilling D, Stone K, Greenway A, Ruth J, Lechowicz MJ, Chandrakasan S, Jayanthan R, Jaffe ES, Leitch H, Pemmaraju N, Chadburn A, Lim MS, Elenitoba-Johnson KS, Krymskaya V, Goodman A, Hoffmann C, Zinzani PL, Ferrero S, Terriou L, Sato Y, Simpson D, Wong R, Rossi JF, Nasta S, Yoshizaki K, Kurzrock R, Uldrick TS, Casper C, Oksenhendler E, Fajgenbaum DC

    Blood   132 ( 20 )   2115 - 2124   2018年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1182/blood-2018-07-862334.

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  • IgG4陽性形質細胞の集簇を認めた鼻腔底Reactive lymphoid hyperplasia症例

    金井 健吾, 岡野 光博, 折田 頼尚, 野山 和廉, 檜垣 貴哉, 春名 威範, 假谷 伸, 小山 貴久, 大道 亮太郎, 佐藤 康晴, 安藤 翠, 平田 裕二, 西崎 和則

    日本鼻科学会会誌   56 ( 4 )   619 - 624   2017年12月

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    記述言語:日本語   出版者・発行元:(一社)日本鼻科学会  

    Reactive lymphoid hyperplasia(RLH)は、組織学的に胚中心を伴うリンパ濾胞の反応性過形成を示し、個々のリンパ球の異型が少なくpolyclonalな増殖を認めるものと定義される。今回我々は、IgG4陽性形質細胞の集簇を認めた鼻腔底RLHの一例を経験した。症例は69歳女性。主訴は左鼻腔腫瘤、右難聴。右難聴で近医受診した際に、左鼻腔底前方に隆起性病変を認めた。唾液腺腫脹や鼻症状は認めなかった。IgG4値は45.5mg/dlと正常範囲内であった。2度の生検を施行し悪性リンパ腫の可能性も否定できず、摘出術を施行した。病理組織所見は、HE染色では、粘膜上皮下に著明なリンパ球・形質細胞の浸潤を認め、リンパ濾胞の過形成を伴っていた。免疫染色では、濾胞間に多数のIgG4陽性形質細胞を認め、400倍1視野あたり100個を超え、IgG4/IgG陽性細胞比は40%を超えていた。しかし、線維化の所見や高IgG4血症を認めず、包括診断基準に照らしIgG4関連疾患には合致しなかった。摘出後、約1年を経過するが、再発所見を認めていない。今後、病変の再発や悪性転化する可能性も考えられることから、治療後も厳重な経過観察を行う必要があると考えられる。(著者抄録)

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    その他リンク: https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2017&ichushi_jid=J01675&link_issn=&doc_id=20180122310011&doc_link_id=10.7248%2Fjjrhi.56.619&url=https%3A%2F%2Fdoi.org%2F10.7248%2Fjjrhi.56.619&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

  • A Multi-Organ Inflammatory Condition with Features of Idiopathic Multicentric Castleman's Disease and IgG4-Related Disease: An Unrecognized Mimicker of IgG4-RD

    Zachary S. Wallace, Yasuharu Sato, Kazuichi Okazaki, Judith Ferry, Hisanori Umehara, Aliyah Sohani, Mitsuhiro Kawano, Nancy Harris, Yoshiya Tanaka, Cory A. Perugino, Satoshi Kubo, James Stone, Robert Colvin, Tsutomu Chiba, John H. Stone, Yoh Zen

    ARTHRITIS & RHEUMATOLOGY   69   2017年10月

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    記述言語:英語   出版者・発行元:WILEY  

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  • Clinicopathological analysis of primary central nervous system NK/T cell lymphoma: rare and localized aggressive tumour among extranasal NK/T cell tumours 査読

    Tomoko Miyata-Takata, Katsuyoshi Takata, Seiichi Kato, Lei-Ming Hu, Mai Noujima-Harada, Shih-Sung Chuang, Yasuharu Sato, Yoshinobu Maeda, Tadashi Yoshino

    HISTOPATHOLOGY   71 ( 2 )   287 - 295   2017年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY  

    AimsThe central nervous system (CNS) is a rare primary site of non-Hodgkin lymphoma. Although direct invasion of nasal natural killer (NK)/T cell tumours into CNS is reported occasionally, primary CNS NK/T cell lymphoma is extremely rare, and the clinicopathological features of primary CNS NK/T cell lymphoma remain largely unknown.
    Methods and resultsWe identified four cases from our consultation files and analysed the clinicopathological features. Three were immunocompetent and one was immunosuppressed. There were three males and one female and their ages ranged from 21 to 77 years (median: 46 years). Radiotherapy was rendered for all patients, and methotrexate was administered to two patients. The overall survival was 4-29 months (median, 19 months) for the three immunocompetent patients. Neoplastic cells exhibited medium to large atypical nuclei. Angiocentric growth and necrosis were observed. The immunophenotype was typical of NK cell tumours: CD3 epsilon, 100%; CD56, 67%; CD5, 50%; cytotoxic molecules, 100%; Epstein-Barr virus encoded small RNA (EBER), 100% and T cell receptor (TCR)- or , 0%. No TCR-gene rearrangements were detected. Reviewing 10 additional cases from the literature and comparing with extranasal NK/T cell lymphoma of the more frequent origins (skin or gastrointestinal tract), primary CNS NK/T cell lymphoma was diagnosed at an earlier stage without B symptoms but exhibited aggressive clinical behaviours.
    ConclusionsAlthough extremely rare, primary CNS NK/T cell lymphoma does occur and should always be included in the differential diagnosis and we should apply relevant markers routinely in conjunction with exploring the patient background. The accumulation of cases is indispensable to establish an effective treatment strategy for this rare and aggressive malignancy.

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  • Extranodal Marginal Zone B-Cell Lymphoma of Mucosa-Associated Lymphoid Tissue with Plasma Cell Differentiation: Periodic Acid-Schiff Reaction-Positive Dutcher Body is a Diagnostic Clue to Distinguish it from Plasmacytoma 査読

    Atsuko Nasu, Takuro Igawa, Hiaki Sato, Hiroyuki Yanai, Tadashi Yoshino, Yasuharu Sato

    DIAGNOSTIC CYTOPATHOLOGY   45 ( 6 )   547 - 551   2017年6月

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    担当区分:最終著者, 責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY  

    We herein report a case of primary parotid extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) with Dutcher bodies. An 82-year-old man presented with a 4 cm x 2.5 cm mass in the left parotid region. Positron emission tomography/computed tomography (PET/CT) showed localized abnormal fluorodeoxyglucose (FDG) uptake in the left parotid gland and lymph nodes of the left cervical region. Fine needle aspiration (FNA) cytology of the left parotid gland showed lymphoplasmacytoid cells with periodic acid-Schiff (PAS)-positive Dutcher bodies. A subsequent excisional biopsy showed sheets of small- to medium-sized neoplastic B cells with abundant IgM in the cytoplasm as detected by immunohistochemistry. A diagnosis of stage II MALT lymphoma was made, but the patient did not receive therapeutic intervention. As previously reported, Dutcher bodies are mainly observed in B-cell neoplasms with IgM production. Because these characteristic intranuclear inclusions can be easily observed by PAS staining, the presence of PAS reaction-positive Dutcher bodies in FNA cytology can serve as a clue to differentially diagnose MALT lymphoma from plasmacytoma. (C). 2017 Wiley Periodicals, Inc.

    DOI: 10.1002/dc.23691

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  • Clinicopathological analysis of methotrexate-associated lymphoproliferative disorders: Comparison of diffuse large B-cell lymphoma and classical Hodgkin lymphoma types 査読

    Yuka Gion, Noriko Iwaki, Katsuyoshi Takata, Mai Takeuchi, Keiichiro Nishida, Yorihisa Orita, Tomoyasu Tachibana, Tadashi Yoshino, Yasuharu Sato

    CANCER SCIENCE   108 ( 6 )   1271 - 1280   2017年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY  

    Patients with rheumatoid arthritis often develop methotrexate-associated lymphoproliferative disorders (MTX-LPD) during MTX treatment. MTX-LPD occasionally regresses spontaneously after simply discontinuing MTX treatment. In patients without spontaneous regression, additional chemotherapy is required to avoid disease progression. However, the differences between spontaneous and non-spontaneous regression have yet to be elucidated. To clarify the factors important for spontaneous regression, we analyzed the clinicopathological features of 51 patients with rheumatoid arthritis who developed MTX-LPD (diffuse large B-cell lymphoma [DLBCL]-type [n = 34] and classical Hodgkin lymphoma [CHL]-type [n = 17]). We examined the interval from MTX discontinuation to the administration of additional chemotherapy. The majority of DLBCL-type MTX-LPD patients (81%) exhibited remission with MTX discontinuation alone. In contrast, the majority of CHL-type MTX-LPD patients (76%) required additional chemotherapy. This difference was statistically significant (P = 0.001). However, overall survival was not significantly different between DLBCL-type and CHL-type (91% vs 94%, respectively; P &gt; 0.05). Thus, the morphological differences in the pathological findings of MTX-LPD may be a factor for spontaneous or non-spontaneous regression after discontinuation of MTX.

    DOI: 10.1111/cas.13249

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  • Frequent downregulation of BTB and CNC homology 2 expression in Epstein-Barr virus-positive diffuse large B-cell lymphoma 査読

    Mai Noujima-Harada, Katsuyoshi Takata, Tomoko Miyata-Takata, Hiroaki Sakurai, Kazuhiko Igarashi, Etsuro Ito, Keina Nagakita, Kohei Taniguchi, Nobuhiko Ohnishi, Shizuma Omote, Tetsuya Tabata, Yasuharu Sato, Tadashi Yoshino

    CANCER SCIENCE   108 ( 5 )   1071 - 1079   2017年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY  

    Diffuse large B-cell lymphoma (DLBCL) is the most common B-cell lymphoma subtype, and the Epstein-Barr virus (EBV)-positive subtype of DLBCL is known to show a more aggressive clinical behavior than the EBV-negative one. BTB and CNC homology 2 (BACH2) has been highlighted as a tumor suppressor in hematopoietic malignancies; however, the role of BACH2 in EBV-positive DLBCL is unclear. In the present study, BACH2 expression and its significance were studied in 23 EBV-positive and 43 EBV-negative patient samples. Immunohistochemistry revealed BACH2 downregulation in EBV-positive cases (P &lt; 0.0001), although biallelic deletion of BACH2 was not detected by FISH. Next, we analyzed the contribution of BACH2 negativity to aggressiveness in EBV-positive B-cell lymphomas using FL-18 (EBV-negative) and FL-18-EB cells (FL-18 sister cell line, EBV-positive). In BACH2-transfected FL-18-EB cells, downregulation of phosphorylated transforming growth factor--activated kinase 1 (pTAK1) and suppression in p65 nuclear fractions were observed by Western blot analysis contrary to non-transfected FL-18-EB cells. In patient samples, pTAK1 expression and significant nuclear p65, p50, and p52 localization were detected immunohistochemically in BACH2-negative DLBCL (P &lt; 0.0001, P = 0.006, and P = 0.001, respectively), suggesting that BACH2 downregulation contributes to constitutive activation of the nuclear factor-B pathway through TAK1 phosphorylation in BACH2-negative DLBCL (most EBV-positive cases). Although further molecular and pathological studies are warranted to clarify the detailed mechanisms, downregulation of BACH2 may contribute to constitutive activation of the nuclear factor-B pathway through TAK1 activation.

    DOI: 10.1111/cas.13213

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  • 様々な悪性リンパ腫におけるPD-L1/PD-L2ゲノム異常

    片岡 圭亮, 三好 寛明, 坂田 征士, 土橋 映仁, 木暮 泰寛, 佐藤 康晴, 加藤 元博, 伊豆津 宏二, 吉野 正, 竹内 賢吾, 大島 孝一, 小川 誠司

    日本臨床分子医学会学術総会プログラム・抄録集   54回   63 - 63   2017年4月

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    記述言語:日本語   出版者・発行元:日本臨床分子医学会  

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  • Immunohistochemical analysis of IgA expression differentiates IgG4-related disease from plasma cell-type Castleman disease 査読

    50 ( 1 )   34 - 41   2017年3月

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    担当区分:最終著者, 責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1007/s00795-016-0145-4

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  • Elevated serum interferon gamma-induced protein 10 kDa is associated with TAFRO syndrome 査読

    7   164 - 173   2017年2月

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    担当区分:最終著者, 責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1038/srep42316

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  • 多発肝腫瘤を呈し肝悪性腫瘍との鑑別に苦慮した多中心性キャッスルマン病 査読

    植木俊充, 那須野将, 貝梅紘子, 廣島由紀, 住昌彦, 渡辺正秀, 井上大, 正木康史, 佐藤康晴, 小島勝, 小林光

    臨床血液   58 ( 6 )   630 - 636   2017年

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    記述言語:日本語   出版者・発行元:一般社団法人 日本血液学会  

    <p>26歳女性。検診で貧血,低アルブミン血症,高γグロブリン血症を指摘され受診した。自覚症状はなく,血液検査では上記の他,高CRP血症,高IL-6血症,高VEGF血症を認めた。CTにて,肝右葉中心部に石灰化を伴う最大径10 cmの多発肝腫瘤と,肝門部および心横隔膜角リンパ節腫脹を認めた。肝悪性腫瘍を疑い超音波ガイド下肝生検を行ったが診断には至らず,心横隔膜角のリンパ節生検を追加したところポリクローナルな形質細胞の浸潤を認め,他疾患を除外した上で多中心性キャッスルマン病(plasma cell type)と診断した。Prednisolone 1 mg/kgを開始したところ画像上腫瘤およびリンパ節の縮小がみられ,貧血,低アルブミン血症,高CRP血症も改善し効果を認めた。肝実質に腫瘤を形成するキャッスルマン病の報告は一報告があるのみで,plasma cell typeの組織像を呈する症例報告はない。</p>

    DOI: 10.11406/rinketsu.58.630

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    その他リンク: http://search.jamas.or.jp/link/ui/2017370560

  • A multicenter phase II prospective clinical trial of glucocorticoid for patients with untreated IgG4-related disease 査読

    Yasufumi Masaki, Shoko Matsui, Takako Saeki, Hiroto Tsuboi, Shintaro Hirata, Yasumori Izumi, Taiichiro Miyashita, Keita Fujikawa, Hiroaki Dobashi, Kentaro Susaki, Hisanori Morimoto, Kazutaka Takagi, Mitsuhiro Kawano, Tomoki Origuchi, Yoko Wada, Naoki Takahashi, Masanobu Horikoshi, Hiroshi Ogishima, Yasunori Suzuki, Takafumi Kawanami, Haruka Kawanami Iwao, Tomoyuki Sakai, Yoshimasa Fujita, Toshihiro Fukushima, Masatoshi Saito, Ritsuro Suzuki, Yuko Morikawa, Tadashi Yoshino, Shigeo Nakamura, Masaru Kojima, Nozomu Kurose, Yasuharu Sato, Yoshiya Tanaka, Susumu Sugai, Takayuki Sumida

    MODERN RHEUMATOLOGY   27 ( 5 )   849 - 854   2017年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:TAYLOR & FRANCIS LTD  

    Objective: Although glucocorticoids are effective for patients with IgG4-related disease, the treatment has not yet been standardized. Therefore, the treatment strategy should be established.
    Patients and methods: Patients who fulfilled the comprehensive diagnostic criteria for definite IgG4-related disease were started on prednisolone (0.6mg/ kg body weight) with the dose reduced every two weeks. The subsequent maintenance dose and need for prednisolone were determined for individual patients. The primary endpoint was the complete remission (CR) rate at one year. Secondary end-points included overall response rate (ORR), the maintenance dose, the relapse rate, and adverse events.
    Results: This study enrolled 61 patients. After clinicopathological review, three patients were excluded, and one, 13, and 44 patients were diagnosed with probable, possible, and definite IgG4-related disease, respectively. Of the 44 patients with definite IgG4-RD, 29 (65.9%) achieved CR, and the ORR was 93.2%. No patient was refractory to primary treatment. The most frequent adverse events were glucose intolerance. Six patients relapsed.
    Conclusions: Glucocorticoid treatment is usually effective for patients with IgG4-RD, and we should examine the possibility of other disorders when a patient is glucocorticoid refractory. Some patients are misdiagnosed, making central clinicopathological review of diagnosis very important in conducting clinical studies.

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  • A possible new morphological variant of mantle cell lymphoma with plasma-cell type Castleman disease-like features 査読

    Takuro Igawa, Rika Omote, Hiaki Sato, Kohei Taniguchi, Katsuya Miyatani, Tadashi Yoshino, Yasuharu Sato

    PATHOLOGY RESEARCH AND PRACTICE   213 ( 11 )   1378 - 1383   2017年

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    担当区分:最終著者, 責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER GMBH, URBAN & FISCHER VERLAG  

    Mantle cell lymphoma (MCL) is an aggressive B-cell lymphoma characterized by overexpression of cyclin Dl resulting from t(11;14)(q13;q32) translocation. Herein, we report 3 cases of MCL with features of plasma cell type Castleman disease (CD). The 3 patients were all men, ranging from 51 to 74 years in age, and they all presented with systemic lymphadenopathy with anemia, hypoalbuminemia, elevated serum levels of C-reactive protein, and polyclonal hypergammaglobulinemia. Lymph node biopsy specimens of the 3 cases showed histological features of plasma cell-type CD, including atrophic germinal centers and interfollicular plasmacytosis, with no light chain restriction. However, flow cytometric analysis demonstrated an abnormal B-cell population with CD5 expression, and further analysis using cyclin Dl immunostaining highlighted a neoplastic component that was restricted to the mantle zone. These neoplastic cells were immunohistochemically positive for CD20, CD5, and SOX11, and negative for CD3, CD10, and HHV8. The Ki67 index was low. All patients were finally diagnosed with MCL. This rare type of MCL can be misdiagnosed clinically and histologically as CD. Therefore, it is important to recognize this rare type of MCL, and careful examination is required using both histological and flow cytometric analyses.

    DOI: 10.1016/j.prp.2017.09.015

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  • Tumor-Associated Macrophages in the Development of 4-Nitroquinoline-1-Oxide-Induced Tongue Squamous Cell Carcinoma in a Mouse Model 査読

    93 ( 3 )   204 - 212   2017年

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    担当区分:最終著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1159/000477301

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  • Clinicopathological analysis of primary central nervous system NK/T-cell lymphoma: rare and localised aggressive tumour among extranasal NK/T-cell tumours.

    Miyata-Takata T, Takata K, Kato S, Hu LM, Noujima-Harada M, Chuang SS, Sato Y, Maeda Y, Yoshino T

    0 ( 0 )   0-0   2017年

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  • The role of bacteriological studies in the management of peritonsillar abscess

    Tomoyasu Tachibana, Yorihisa Orita, Soshi Takao, Yuya Ogawara, Yuko Matsuyama, Aiko Shimizu, Iku Fujisawa, Michihiro Nakada, Yasuharu Sato, Kazunori Nishizaki

    Journal of Otolaryngology of Japan   120 ( 5 )   772 - 773   2017年

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    記述言語:日本語   出版者・発行元:Oto-Rhino-Laryngological Society of Japan Inc.  

    DOI: 10.3950/jibiinkoka.120.772

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  • The role of bacteriological studies in the management of peritonsillar abscess 査読

    Tomoyasu Tachibana, Yorihisa Orita, Soshi Takao, Yuya Ogawara, Yuko Matsuyama, Aiko Shimizu, Iku Abe-Fujisawa, Michihiro Nakada, Yasuharu Sato, Kazunori Nishizaki

    AURIS NASUS LARYNX   43 ( 6 )   648 - 653   2016年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER SCI LTD  

    Objective: Since most patients with peritonsillar abscess (PTA) can be successfully treated with surgical drainage and empirical antibiotic therapy, routine bacteriologic studies for all patients with PTA may be unnecessary. This study tried to evaluate which patients with PTA should certainly undergo bacteriologic studies.
    Methods: Hundred consecutive patients with PTA were treated and underwent culture tests of purulent contents obtained by surgical drainage between April 2008 and December 2013.
    Results: In 62 of the 100 patients, 71 pathogenic bacteria were identified; 61 (86%) were Gram-positive cocci (GPC), 8 (11%) were Gram-negative rods (GNR), and 6 (8%) were anaerobes. Normal flora were isolated in 27 patients, and culture results were negative in 11 patients. Although not significant, primary (without prior antibiotic therapy) case (odds ratio (OR) = 2.19; 95% CI, 0.95-5.05) and laryngeal edema (OR = 2.04; 95% CI, 0.82-5.03) showed a tendency of associations with detection of pathogenic bacteria. After taking into account interactions between smoking habit and laryngeal edema, the covariate-adjusted OR for non-smokers with laryngeal edema was significant and showed a strong relationship (OR = 7.43; 95% confidence interval, 1.05-52.73) compared to non-smokers without laryngeal edema.
    Conclusion: Although empirical antibiotic therapy was effective for most of the PTA patients, bacteriologic studies might be indispensable for the patients with laryngeal edema considering the failure of the first treatments. Particularly, the culture tests may be useful for non-smokers with laryngeal edema. (C) 2016 Elsevier Ireland Ltd. All rights reserved.

    DOI: 10.1016/j.anl.2016.01.009

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  • IgG4-producing lymphoma arising in a patient with IgG4-related disease 査読

    Takuro Igawa, Toshiaki Hayashi, Kazuya Ishiguro, Yumiko Maruyama, Mai Takeuchi, Katsuyoshi Takata, Tadashi Yoshino, Yasuharu Sato

    MEDICAL MOLECULAR MORPHOLOGY   49 ( 4 )   243 - 249   2016年12月

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    担当区分:最終著者, 責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPRINGER JAPAN KK  

    We herein report a case in which an IgG4-producing lymphoma arose in a patient with a previous diagnosis consistent with an IgG4-related disease. A 43-year-old man presented with enlarged cervical lymph nodes and was treated with steroids and radiation for what was initially assumed to be Kimura's disease, although the lesions were later histologically re-diagnosed as IgG4-related lymphadenopathy. Fourteen years later, when the patient was 58-years-old, he presented with retroperitoneal fibrosis and swollen lymph nodes. The suspicious lesions were not histologically examined as the patient did not give consent. However, the serum IgG4 concentration was high (1400 mg/dL) and he was clinically diagnosed with systemic IgG4-related disease. Although steroid administration reduced the size of the lesions, tapering the dose finally resulted in systemic, prominently enlarged lymph nodes. Analysis of the biopsy specimen revealed that these multiple lymph node lesions were marginal zone B cell lymphomas that themselves expressed IgG4. Complete remission was achieved after a total of six courses of chemotherapy including rituximab. This case suggests that the infiltrating IgG4-expressing cells observed in IgG4-related disease can clonally expand to malignant lymphomas.

    DOI: 10.1007/s00795-016-0139-2

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  • Structural Variations Involving Programmed Death Ligands in B-Cell and T-Cell Lymphomas

    Keisuke Kataoka, Hiroaki Miyoshi, Yasunori Kogure, Yasuharu Sato, Kenji Nishida, Yuichi Shiraishi, Hiroko Tanaka, Kenichi Chiba, Yosaku Watatani, Yusuke Shiozawa, Kenichi Yoshida, Masashi Sanada, Motohiro Kato, Satoru Miyano, Koji Izutsu, Kengo Takeuchi, Tadashi Yoshino, Koichi Ohshima, Seishi Ogawa

    BLOOD   128 ( 22 )   2016年12月

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    記述言語:英語   出版者・発行元:AMER SOC HEMATOLOGY  

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  • Molecular Heterogeneity in Peripheral T-Cell Lymphoma Not Otherwise Specified Revealed By Comprehensive Mutational Profiling

    Yosaku Watatani, Yasuharu Sato, Kenji Nishida, Hiroaki Miyoshi, Yuichi Shiraishi, Kenichi Chiba, Tanaka Hiroko, Hiroo Ueno, Nobuyuki Kakiuchi, Yusuke Shiozawa, Tetsuichi Yoshizato, Kenichi Yoshida, Masashi Sanada, Satoru Miyano, Koichi Ohshima, Tadashi Yoshino, Seishi Ogawa, Keisuke Kataoka

    BLOOD   128 ( 22 )   2016年12月

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    記述言語:英語   出版者・発行元:AMER SOC HEMATOLOGY  

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  • CD10 down expression in follicular lymphoma correlates with gastrointestinal lesion involving the stomach and large intestine 査読

    Nobuhiko Ohnishi, Katsuyoshi Takata, Tomoko Miyata-Takata, Yasuharu Sato, Akira Tari, Yuka Gion, Mai Noujima-Harada, Kohei Taniguchi, Tetsuya Tabata, Keina Nagakita, Shizuma Omote, Hiroyuki Takahata, Masaya Iwamuro, Hiroyuki Okada, Yoshinobu Maeda, Hiroyuki Yanai, Tadashi Yoshino

    CANCER SCIENCE   107 ( 11 )   1687 - 1695   2016年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-BLACKWELL  

    Follicular lymphoma (FL) shows co-expression of B-cell lymphoma 2 (BCL2) and CD10, whereas downexpression of CD10 is occasionally experienced in gastrointestinal (GI) FL with unknown significance. Gastrointestinal FL is a rare variant of FL, and its similarity with mucosa-associated lymphoid tissue lymphoma was reported. We investigated the clinicopathological and genetic features of CD10 downexpressed (CD10(down)) GI-FL. The diagnosis of CD10(down) FL was carried out with a combination of pathological and molecular analyses. The incidence of CD10(down) GI-FL was shown in 35/172 (20.3%) cases, which was more frequent than nodal FL (3.5%, P &lt; 0.001). The difference was additionally significant between GI-FL and nodal FL when the analysis was confined to primary GI-FL (55.2% vs 3.5%, P &lt; 0.001). Compared to CD10(+) GI-FL, CD10(down) GI-FL significantly involved the stomach or large intestine (P = 0.015), and additionally showed the downexpression of BCL6 (P &lt; 0.001). The follicular dendritic cell meshwork often showed a duodenal pattern in the CD10(down) group (P = 0.12). Furthermore, a lymphoepithelial lesion was observed in 5/12 (40%) gastric FL cases, which indicated caution in the differentiation of mucosa-associated lymphoid tissue lymphoma. Molecular analyses were undertaken in seven cases of CD10(down) GI-FL, and an identical clone was found between CD10(down) follicles and CD10(+)BCL2(+) neoplastic follicles. In the diagnosis of cases with CD10(down) BCL2(+) follicles, careful examination with molecular studies should be carried out.

    DOI: 10.1111/cas.13031

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  • Regulatory T cells function at the early stage of tumor progression in a mouse model of tongue squamous cell carcinoma 査読

    Kentaro Miki, Yorihisa Orita, Yuka Gion, Soshi Takao, Kyotaro Ohno, Mai Takeuchi, Toshihiro Ito, Hiroyuki Hanakawa, Tomoyasu Tachibana, Hidenori Marunaka, Takuma Makino, Akira Minoura, Akihiro Matsukawa, Kazunori Nishizaki, Tadashi Yoshino, Yasuharu Sato

    CANCER IMMUNOLOGY IMMUNOTHERAPY   65 ( 11 )   1401 - 1410   2016年11月

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    担当区分:最終著者   記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPRINGER  

    The objective of this study was to observe the distribution of regulatory T cells (Tregs) in the development of tongue squamous cell carcinoma (SCC) and to determine the role of Tregs in the progression of tongue SCC. A mouse model of 4-nitroquinoline-1-oxide (4NQO)-induced-tongue SCC was established. The expression of Forkhead box P3 (Foxp3), interleukin 10, transforming growth factor-beta, chemokine CC motif ligands 17, 20, and CC chemokine receptor 4 was determined using real-time quantitative polymerase chain reaction. Foxp3 expression was also analyzed using immunohistochemistry. The results were compared with those of control mice and of 4NQO-treated mice treated with a cyclooxygenase-2 (COX-2) inhibitor. Well to moderately differentiated tongue SCC was induced in all of the experimental mice. The amount of Tregs of the experimental mice was over 10 times as much as control mice at the early stage of tumor progression. COX-2 inhibitor did not prevent the progression of tongue SCC and did not reduce the total amount of Tregs. Tregs function at the early stage of the development of tongue SCC, and it may be effective to suppress Tregs at the early stage of tumor progression for the treatment and/or prevention of tongue SCC.

    DOI: 10.1007/s00262-016-1902-x

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  • Protocadherin gamma A3 is expressed in follicular lymphoma irrespective of BCL2 status and is associated with tumor cell growth 査読

    Xueyan Zhang, Katsuyoshi Takata, Wei Cui, Tomoko Miyata-Takata, Yasuharu Sato, Mai Noujima-Harada, Tadashi Yoshino

    MOLECULAR MEDICINE REPORTS   14 ( 5 )   4622 - 4628   2016年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPANDIDOS PUBL LTD  

    Protocadherin genes (PCDHs) have been suggested to act as tumor suppressor genes in various tumor types. Previous studies have demonstrated the upregulation of certain PCDH-gamma subfamily genes in nodal and duodenal follicular lymphoma (FL) using gene expression analyses. However, the mechanisms and associated molecular function of PCDH-gamma subfamily gene upregulation in FL remain to be elucidated. The present study examined the expression of PCDHGA3, an upregulated PCDH-gamma gene subfamily member, in B-cell lymphoma 2 (BCL2)-positive and-negative FL, and evaluated its association with tumor cell proliferation in an FL-derived cell line. Immunohistochemical analysis demonstrated that the majority of FL grade 1-2 samples (19/20; 95%) and over half of grade 3A FL samples (5/9; 56%) were PCDHGA3-positive, whereas only 1/17 reactive lymphoid hyperplasia samples was positive. Notably, this positivity was widely observed in samples of BCL2-negative FL (13/15; 87%) and FL with diffuse area (10/10; 100%). The FL-derived cell line FL18 exhibited strong PCDHGA3 expression, similar to the patient samples, and its proliferation was suppressed by PCDHGA3 gene knockdown. Genes expressed concomitantly with PCDHGA3 were selected from gene expression data, and TNFRSF6B, a member of the tumor necrosis factor receptor superfamily, was among the top five most strongly correlated genes. Coexpression of TNFRSF6B and PCDHGA3 was observed immunohistochemically in FL18 cells, suggesting potential cooperation in tumor cell maintenance. In conclusion, the results of the present study indicated that PCDHGA3 was expressed in FL irrespective of BCL2 status and grading and was associated with cell proliferation. Further studies involving molecular genetic analyses are required to elucidate the mechanisms underlying the activity of PCDHGA3 in FL.

    DOI: 10.3892/mmr.2016.5808

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  • A case of IgG4-related lymphadenopathy, pericarditis, coronary artery periarteritis and luminal stenosis 査読

    Ryoto Hourai, Masatoshi Miyamura, Ryunosuke Tasaki, Akiko Iwata, Yoshihiro Takeda, Hideaki Morita, Nobuharu Hanaoka, Jun Tanigawa, Kensaku Shibata, Atsushi Takeshita, Mitsuhiro Kawano, Yasuharu Sato, Yoshinobu Hirose, Nobukazu Ishizaka

    HEART AND VESSELS   31 ( 10 )   1709 - 1713   2016年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPRINGER  

    Immunoglobulin G4 (IgG4)-related disease is an emerging new clinicopathological disorder that is characterized by elevation of serum IgG4 levels and histological findings of IgG4-positive plasmacytic infiltration. IgG4-related disease may appear synchronously or metachronously in a wide variety of organs. The current patient was found to have pericardial effusion and retroperitoneal fibrosis. He was subsequently diagnosed with coronary artery stenosis. F-18-FDG positron emission tomography showed enhanced FDG uptake in lymph nodes as well as pericardial and peri-aortic tissue. Histopathology of the mediastinal lymph node showed the infiltration of numerous IgG4-positive cells, leading to the diagnosis of IgG4-related lymphadenopathy with pericardial and periarterial involvement.

    DOI: 10.1007/s00380-016-0794-1

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  • Clinical and Laboratory Features of IgG4-Related Retroperitoneal Fibrosis/Periarteritis in Japan: Retrospective Multicenter Study of 99 Cases

    Ichiro Mizushima, Satomi Kasashima, Motohisa Yamamoto, Takako Saeki, Kazunori Yamada, Dai Inoue, Fuminori Kasashima, Yasushi Matsumoto, Eisuke Amiya, Kenji Notohara, Yasuharu Sato, Yoh Zen, Shigeyuki Kawa, Mitsuhiro Kawano, Nobukazu Ishizaka

    ARTHRITIS & RHEUMATOLOGY   68   2016年10月

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    記述言語:英語   出版者・発行元:WILEY  

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  • Kikuchi-Fujimoto disease: evaluation of prognostic factors and analysis of pathologic findings 査読

    Hidenori Marunaka, Yorihisa Orita, Tomoyasu Tachibana, Kentaro Miki, Takuma Makino, Yuka Gion, Kazunori Nishizaki, Tadashi Yoshino, Yasuharu Sato

    ACTA OTO-LARYNGOLOGICA   136 ( 9 )   944 - 947   2016年9月

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    担当区分:最終著者   記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:TAYLOR & FRANCIS LTD  

    Conclusion: In Kikuchi-Fujimoto disease (KFD), a low ratio of blastic cells (&lt;70%) in lymph node specimens and absence of atypical lymphocytes in peripheral blood are predictive of a protracted clinical course. Objectives: Since KFD is a self-limiting disorder that does not require any specific management, prognostic factors have received little attention. The present study identified clinical and pathological factors that may affect the period from onset to cure of KFD. Methods: This retrospective study investigated 43 KFD patients who underwent lymph node biopsy diagnosed by immunohistochemical staining at Okayama University Hospital and Okayama Medical Center from January 2001 to December 2013. Results: Mean total period from onset to cure was 6 months (median =9.4 months; range =1-37 months). Low ratios of blastic cell proliferation area (&lt;70%) in lymph node specimens (p=0.011) and absence of atypical lymphocytes in peripheral blood (p=0.026) were associated with a relatively long duration of KFD.

    DOI: 10.3109/00016489.2016.1164895

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  • Distribution and components of interstitial inflammation and fibrosis in IgG4-related kidney disease: analysis of autopsy specimens 査読

    Satoshi Hara, Mitsuhiro Kawano, Ichiro Mizushima, Kenichi Harada, Takuma Takata, Takako Saeki, Yoshifumi Ubara, Yasuharu Sato, Michio Nagata

    HUMAN PATHOLOGY   55   164 - 173   2016年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:W B SAUNDERS CO-ELSEVIER INC  

    IgG4-related kidney disease (IgG4-RKD) occasionally progresses to chronic renal failure and is pathologically characterized by IgG4-positive lymphoplasmacyte-rich tubulointerstitial nephritis with storiform fibrosis (bird's-eye pattern fibrosis). Although radiology reveals a heterogeneous distribution of affected areas in this disease, their true distribution within the whole kidney is still unknown because of difficulty in estimating this from needle biopsy samples. Using 5 autopsy specimens, the present study histologically characterized the distribution and components of interstitial inflammation and fibrosis in IgG4-RKD. Interstitial lymphoplasmacytic infiltration or fibrosis was observed in a variety of anatomical locations such as intracapsular, subcapsular, cortical, perivascular, and perineural regions heterogeneously in a patchy distribution. They tended to be more markedly accumulated around medium- and small-sized vessels. Storiform fibrosis was limited to the cortex. Immunostaining revealed nonfibrillar collagens (collagen IV and VI) and fibronectin predominance in the cortical lesion, including storiform fibrosis. In contrast, fibril-forming collagens (collagen I and 111), collagen VI, and fibronectin were the main components in the perivascular lesion. In addition, a-smooth muscle actin positive myofibroblasts were prominently accumulated in the early lesion and decreased with progression, suggesting that myofibroblasts produce extracellular matrices forming a peculiar fibrosis. In conclusion, perivascular inflammation or fibrosis of medium- and small-sized vessels is a newly identified pathologic feature of IgG4-RKD. Because storiform fibrosis contains mainly nonfibrillar collagens, "interstitial fibrosclerosis" would be a suitable term to reflect this. The relation between the location and components of fibrosis determined in whole kidney samples provides new clues to the pathophysiology underlying IgG4-RKD. (C) 2016 The Authors. Published by Elsevier Inc.

    DOI: 10.1016/j.humpath.2016.05.010

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  • Clinicopathological features of 49 primary gastrointestinal diffuse large B-cell lymphoma cases; comparison with location, cell-of-origin, and frequency of MYD88 L265P 査読

    Keina Nagakita, Katsuyoshi Takata, Kohei Taniguchi, Tomoko Miyata-Takata, Yasuharu Sato, Akira Tari, Nobuhiko Ohnishi, Mai Noujima-Harada, Shizuma Omote, Naoya Nakamura, Masaya Iwamuro, Yoshinobu Maeda, Hiroyuki Okada, Mitsune Tanimoto, Tadashi Yoshino

    PATHOLOGY INTERNATIONAL   66 ( 8 )   444 - 452   2016年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-BLACKWELL  

    The gastrointestinal (GI) tract is the most common primary site of extranodal diffuse large B-cell lymphoma (DLBCL), with approximately one-third of extranodal DLBCL occurring in the GI tract. We investigated the clinicopathological features and immunohistochemically-assessed cell-of-origin of 49 GI DLBCL cases (stomach, 24; small intestine, 10; colon, 15) and also examined the presence of MYD88 L265P as recently this mutation has been frequently identified in ABC-like DLBCL, particularly in extranodal sites. Small intestinal DLBCL was characterized by the preponderance of women (P = 0.041) and elevated LDH (P = 0.002) and soluble interleukin-2 receptor (P = 0.033). Small intestinal DLBCL more frequently showed anemia (P = 0.031) and elevated CRP (P = 0.029) than gastric DLBCL. ABC-like phenotype was seen in 71.4 % cases (stomach, 79 %; small intestine, 70 %; colon, 60 %). MYD88 L265P was detected in 6.1 % cases; all were primary gastric DLBCL with ABC-like phenotype but had no distinct clinicopathological features. In conclusion, GI DLBCL had different clinicopathological features according to the primary site especially in the small intestine. Also, MYD88 L265P had little involvement in GI DLBCL compared with other extranodal DLBCLs, suggesting that its pathogenesis might be different from that of organs with a high frequency of MYD88 L265P.

    DOI: 10.1111/pin.12439

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  • Multicentric Castleman Disease With Tubulointerstitial Nephritis Mimicking IgG4-related Disease Two Case Reports 査読

    Takeshi Zoshima, Kazunori Yamada, Satoshi Hara, Ichiro Mizushima, Masakazu Yamagishi, Kenichi Harada, Yasuharu Sato, Mitsuhiro Kawano

    AMERICAN JOURNAL OF SURGICAL PATHOLOGY   40 ( 4 )   495 - 501   2016年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:LIPPINCOTT WILLIAMS & WILKINS  

    Multicentric Castleman disease is a benign lymphoproliferative disorder with heterogenous clinical symptoms and involves systemic organs in addition to lymph nodes. Elevated serum IgG4 levels and IgG4-positive plasma cell (IgG4+PC) infiltrates have been reported in lymph nodes, lung and skin in some multicentric Castleman disease cases, resembling IgG4-related disease (IgG4-RD) histologically. However, no report has been available regarding IgG4+PC infiltration in the kidneys of multicentric Castleman disease. Here, we report 2 cases of multicentric Castleman disease complicated by IgG4-related disease (IgG4-RD) histologically. However, there has been no report published on PC-rich tubulointerstitial nephritis, lymphadenopathy, with numerous IgG4+PC infiltration, and elevated serum IgG4 levels, mimicking IgG4-RD. The blood examinations revealed systemic inflammation and elevated C-reactive protein and interleukin-6 levels. Corticosteroid therapy was partially effective in both cases, and combination therapy of corticosteroid and tocilizumab was needed in both cases. Moreover, after triple therapy with corticosteroid, rituximab and cyclophosphamide were used in 1 case to tame the severe inflammation. The present cases suggest that if continuously elevated serum C-reactive protein levels and partial corticosteroid responsiveness are encountered, multicentric Castleman disease should be considered rather than IgG4-RD as a differential diagnosis even if serum IgG4 is elevated and IgG4+PCs infiltrate systemic organs.

    DOI: 10.1097/PAS.0000000000000575

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  • Glottic cancer in patients without complaints of hoarseness 査読

    Tomoyasu Tachibana, Yorihisa Orita, Hidenori Marunaka, Seiichiro Makihara, Misato Hirai, Kentaro Miki, Yuya Ogawara, Hisashi Ishihara, Yuko Matsuyama, Iku Abe-Fujisawa, Aiko Shimizu, Yasuharu Sato, Kazunori Nishizaki

    HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK   38   E316 - E320   2016年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-BLACKWELL  

    Background. Few studies have investigated the clinical characteristics of patients with glottic cancer without hoarseness.
    Methods. This retrospective clinical study investigated 371 patients with glottic cancer.
    Results. Thirty-two of the 371 patients (8.6%) with glottic cancer first presented to hospitals with complaints other than hoarseness. Although proportions of stage I and T1 disease were significantly higher among patients without hoarseness than among those with hoarseness (p = .0036 and p = .0004, respectively), survival curves showed no significant differences between groups (p = .1334).
    Conclusion. Patients with glottic cancer without complaints of hoarseness were diagnosed at an earlier stage than those with hoarseness. Accumulation of more cases may lead to better survival of patients with glottic cancer without hoarseness compared to those with hoarseness. Checking the larynx of patients without hoarseness or encouraging internists to check the larynx when performing gastroscopic or respiratory examinations may lead to improvement of glottic cancer prognosis. (C) 2015 Wiley Periodicals, Inc.

    DOI: 10.1002/hed.23992

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  • Frequent MYD88 L265P and CD79B Mutations in Primary Breast Diffuse Large B-Cell Lymphoma 査読

    Kohei Taniguchi, Katsuyoshi Takata, Shih-Sung Chuang, Tomoko Miyata-Takata, Yasuharu Sato, Akira Satou, Yuko Hashimoto, Maiko Tamura, Keina Nagakita, Nobuhiko Ohnishi, Mai Noujima-Harada, Tetsuya Tabata, Yara Yukie Kikuti, Yoshinobu Maeda, Naoya Nakamura, Mitsune Tanimoto, Tadashi Yoshino

    AMERICAN JOURNAL OF SURGICAL PATHOLOGY   40 ( 3 )   324 - 334   2016年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:LIPPINCOTT WILLIAMS & WILKINS  

    Primary breast diffuse large B-cell lymphoma (PB-DLBCL) is a rare disease comprising &lt; 3% of extranodal lymphomas. It frequently reveals an activated B-cell (ABC)-like phenotype. ABC-like DLBCL was reported to have gain-of-function mutations in MYD88, CD79B, CARD11, and TNFAIP3, resulting in constitutive activation of the NF kappa B pathway. Because of the rare occurrence of PB-DLBCL, the frequency of MYD88 and CD79B mutations is still unknown. We used Sanger sequencing to study these mutations from 46 breast DLBCL cases and also investigated the associated clinicopathologic factors. MYD88 L265P was confirmed by allele-specific polymerase chain reaction and compared with the Sanger sequencing results. MYD88 L265P and CD79B mutations were detected in 27/46 (58.7%) and 11/33 (33.3%) cases, respectively. Twenty-eight of 46 cases met the criteria for PB-DLBCL, and the latter 18 cases were further classified as clinical breast DLBCL (CLB-DLBCL). The frequency of MYD88 L265P and CD79B mutations was 16/28 (57.1%) and 9/23 (39.1%), respectively, in PB-DLBCL and 11/18 (61.1%) and 2/10 (20%), respectively, in CLB-DLBCL. When the cutoff value was set at Delta Ct &lt;= 1, the result of allele-specific polymerase chain reaction for MYD88 corresponded to those of the Sanger sequence at 92.6% sensitivity and 100% specificity. According to Choi's algorithm, 16/27 (59.3%) demonstrated an ABC-like phenotype in PB-DLBCL, and 15/18 (83.3%) demonstrated an ABC-like phenotype in CLB-DLBCL. In conclusion, MYD88 L265P and CD79B mutations were frequently detected in PB-DLBCL, and they may be key molecules associated with PB-DLBCL lymphomagenesis. Further analysis will be required to clarify the mechanism of its pathogenesis.

    DOI: 10.1097/PAS.0000000000000592

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  • Clinicopathologic analysis of TAFRO syndrome demonstrates a distinct subtype of HHV-8-negative multicentric Castleman disease 査読

    Noriko Iwaki, David C. Fajgenbaum, Christopher S. Nabel, Yuka Gion, Eisei Kondo, Mitsuhiro Kawano, Taro Masunari, Isao Yoshida, Hiroshi Moro, Koji Nikkuni, Kazue Takai, Kosei Matsue, Mitsutoshi Kurosawa, Masao Hagihara, Akio Saito, Masataka Okamoto, Kenji Yokota, Shinichiro Hiraiwa, Naoya Nakamura, Shinji Nakao, Tadashi Yoshino, Yasuharu Sato

    AMERICAN JOURNAL OF HEMATOLOGY   91 ( 2 )   220 - 226   2016年2月

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    担当区分:最終著者, 責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-BLACKWELL  

    Multicentric Castleman disease (MCD) describes a heterogeneous group of disorders involving systemic inflammation, characteristic lymph node histopathology, and multi-organ dysfunction because of pathologic hypercytokinemia. Whereas Human Herpes Virus-8 (HHV-8) drives the hypercytokinemia in a cohort of immunocompromised patients, the etiology of HHV-8-negative MCD is idiopathic (iMCD). Recently, a limited series of iMCD cases in Japan sharing a constellation of clinical features, including thrombocytopenia (T), anasarca (A), fever (F), reticulin fibrosis (R), and organomegaly (O) has been described as TAFRO syndrome. Herein, we report clinicopathological findings on 25 patients (14 males and 11 females; 23 Japanese-born and two US-born), the largest TAFRO syndrome case series, including the first report of cases from the USA. The median age of onset was 50 years old (range: 23-72). The frequency of each feature was as follows: thrombocytopenia (21/25), anasarca (24/25), fever (21/25), organomegaly (25/25), and reticulin fibrosis (13/16). These patients frequently demonstrated abdominal pain, elevated serum alkaline phosphatase levels, and acute kidney failure. Surprisingly, none of the cases demonstrated marked hypergammoglobulinemia, which is frequently reported in iMCD. Lymph node biopsies revealed atrophic germinal centers with enlarged nuclei of endothelial cells and proliferation of endothelial venules in interfollicular zone. 23 of 25 cases were treated initially with corticosteroids; 12 patients responded poorly and required further therapy. Three patients died during the observation period (median: 9 months) because of disease progression or infections. TAFRO syndrome is a unique subtype of iMCD that demonstrates characteristic clinicopathological findings. Further study to clarify prognosis, pathophysiology, and appropriate treatment is needed. (C) 2015 Wiley Periodicals, Inc.

    DOI: 10.1002/ajh.24242

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  • DNA Microarray Analysis of Submandibular Glands in IgG4-Related Disease Indicates a Role for MARCO and Other Innate Immune-Related Proteins 査読

    Miho Ohta, Masafumi Moriyama, Takashi Maehara, Yuka Gion, Sachiko Furukawa, Akihiko Tanaka, Jun-Nosuke Hayashida, Masaki Yamauchi, Noriko Ishiguro, Yurie Mikami, Hiroto Tsuboi, Mana Iizuka-Koga, Shintaro Kawano, Yasuharu Sato, Tamotsu Kiyoshima, Takayuki Sumida, Seiji Nakamura

    MEDICINE   95 ( 7 )   e2853   2016年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:LIPPINCOTT WILLIAMS & WILKINS  

    IgG4-related disease (IgG4-RD) is a novel systemic disease entity characterized by elevated serum IgG4 and tissue infiltration of IgG4-positive plasma cells accompanied by severe fibrosis. Although recent studies demonstrated that innate immune cells including monocytes and macrophages might promote local fibrosis and IgG4 production, the pathological mechanism remains unclear. In this study, we sought to identify the disease-associated genes, especially innate immune molecules.
    Gene expression was analyzed by DNA microarray in submandibular glands (SMGs) from patients with IgG4-RD (n=5), chronic sialoadenitis (CS) (n=3), and controls (n=3). Differentially expressed genes (DEGs) were validated by real-time polymerase chain reaction (PCR) and immunohistochemical staining in IgG4-RD (n=18), CS (n=4), Sjogren syndrome (n=11), and controls (n=10).
    Gene expression patterns in the 3 groups were quite different from each other by the pvclust method and principal components analysis. In IgG4-RD, 1028 upregulated genes and 692 downregulated genes were identified as DEGs (P&lt;0.05). Gene Ontology (GO) term analysis indicated that the upregulated DEGs in IgG4-RD encoded proteins involved in T/B cell activation and chemotaxis. PCR validated significantly higher expression of macrophage receptor with collagenous structure (MARCO), a pattern-recognition receptor, in IgG4-RD compared with the other groups (P&lt;0.01). Immunohistochemical analysis confirmed that the expression pattern of MARCO was similar to that of the M2 macrophage marker CD163.
    MARCO was identified as a disease-associated molecule in IgG4-RD by DNA microarray. Moreover, M2 macrophages might contribute to the initiation of IgG4-RD via MARCO.

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  • Characteristic distribution of inflammatory lesions in IgG4-related kidney disease: Findings from autopsy case series 査読

    Satoshi Hara, Mitsuhiro Kawano, Ichiro Mizushima, Kenichi Harada, Takuma Takata, Takako Saeki, Yoshifumi Ubara, Yasuharu Sato, Michio Nagata

    IgG4-Related Kidney Disease   187 - 191   2016年1月

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    記述言語:英語   掲載種別:論文集(書籍)内論文   出版者・発行元:Springer Japan  

    IgG4-related tubulointerstitial nephritis (TIN) reveals specific histologies such as storiform (“bird’s-eye pattern”) fibrosis, regional lesion distribution, and extension of inflammation into and beyond the renal capsule, all of which clearly serve to distinguish IgG4-related TIN from non-IgG4-related TIN. However, the histological extent of IgG4-related TIN in the kidney remains unclear, largely because histological analyses of IgG4-related TIN to date have been based generally only on renal needle biopsy specimens. We histologically analyzed five autopsy specimens of IgG4-related TIN cases. The lymphoplasmacytic infiltration or fibrosis was mainly located in the cortex and perivasculature. Notably, inflammation or fibrosis generally appeared prominently around the interlobar, arcuate and interlobular arteries or veins. In addition, all specimens included various stages of fibrosis in the same kidneys. Storiform fibrosis (bird’s-eye pattern fibrosis) was limited to the cortex. These results indicate that inflammation or fibrosis is predominantly located in the renal cortex and perivasculature in IgG4-related TIN. Of note is that the lesions showed a predilection to develop around medium- and small-sized arteries in addition to forming nodular lesions in the renal cortex.

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  • Multicentric castleman’s disease mimicking IgG4-related disease: A case report 査読

    Eiko Hasegawa, Akinari Sekine, Jun-Ichi Inenaga, Takeshi Fujii, Kenichi Ohashi, Yasuharu Sato, Yoshifumi Ubara

    IgG4-Related Kidney Disease   293 - 301   2016年1月

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    記述言語:英語   掲載種別:論文集(書籍)内論文   出版者・発行元:Springer Japan  

    A 63-year-old Japanese man was admitted to our hospital for the evaluation of hypergammaglobulinemia, lymphadenopathy, interstitial lung disease and nephritis. His serum level of IgG and IgG4 were 8198 mg/dL and 3360 mg/dL, respectively. Renal biopsy revealed focal interstitial nephritis with IgG4 positive plasma cells, with an IgG4/IgG ratio of &gt
    0.6. Inguinal lymph node biopsy showed hyperplasia of the lymphoid follicles with prominent infiltration of mature plasma cells between normal germinal centers. Immunostaining showed that the IgG4-positive plasma cells were prominent, and the IgG4/IgG ratio within the lymph node was &gt
    0.8. Although these findings were consistent with IgG4-related disease (IgG4-RD), other laboratory findings such as high serum concentrations of C-reactive protein, interleukin-6, IgA, and IgM, as well as positive staining of the lymph node for IgA and IL-6, suggested multicentric Castleman’s disease (MCD). Following unsuccessful therapy with glucocorticoids, treatment with an anti-interleukin-6 receptor monoclonal antibody (tocilizumab) exerted disease control. Understanding the crucial differences between MCD and IgG4-RD may contribute to understanding the pathogenesis of both diseases.

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  • Anti-high mobility group box 1 monoclonal antibody improves ischemia/reperfusion injury and mode of liver regeneration after partial hepatectomy 査読

    Masahiro Sugihara, Hiroshi Sadamori, Masahiro Nishibori, Yasuharu Sato, Hiroshi Tazawa, Susumu Shinoura, Yuzo Umeda, Ryuichi Yoshida, Daisuke Nobuoka, Masashi Utsumi, Kyotaro Ohno, Takeshi Nagasaka, Tadashi Yoshino, Hideo Kohka Takahashi, Takahito Yagi, Toshiyoshi Fujiwara

    AMERICAN JOURNAL OF SURGERY   211 ( 1 )   179 - 188   2016年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC  

    BACKGROUND: The purpose of this study is to determine the effects of anti-high mobility group box 1 (HMGB1) monoclonal antibody (mAb) on ischemia/reperfusion injury (IRI) and the mode of liver regeneration.
    METHODS: Rats underwent 70% hepatectomy with IRI caused by clamping the hepatoduodenal ligament for 20 minutes, followed by the administration of anti-HMGB1 mAb immediately before declamping the hepatoduodenal ligament. Five animals were used for each time point. We then evaluated IRI, regeneration parameters and the status of HMGB1 in remnant livers.
    RESULTS: The anti-HMGB1 mAb significantly ameliorated the degree of IRI in the remnant livers in association with the downregulation of HMGB1 protein. The ratio of Ki67-positive hepatocytes at 48 hours after 70% hepatectomy was significantly improved. Mean hepatocyte size was significantly reduced and cyclin-dependent kinase inhibitor 1 expression was significantly attenuated.
    CONCLUSIONS: Anti-HMGB1 mAb ameliorated IRI and improved the mode of liver regeneration after IRI followed by 70% hepatectomy in rats. (C) 2016 Elsevier Inc. All rights reserved.

    DOI: 10.1016/j.amjsurg.2015.06.025

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  • Ocular adnexal marginal zone lymphoma arising in a patient with IgG4-related ophthalmic disease 査読 国際誌

    Kenji Nishida, Yuka Sogabe, Ayako Makihara, Akemi Senoo, Hisanori Morimoto,Mai Takeuchi, Yuka Gion, Tadashi Yoshino, Yasuharu Sato

    Modern Rheumatology   29 ( 2 )   1 - 5   2016年

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    担当区分:最終著者, 責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1080/14397595.2016.1216733

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  • Peripheral T-Cell Lymphoma, Not Otherwise Specified and Concurrent Seminoma in Testis. 査読

    Kitagawa J, Goto N, Shibata Y, Nakamura N, Nakamura H, Kanemura N, Hara T, Takata K, Sato Y, Yoshino T, Tsurumi H

    Journal of Clinical and Experimental Hematopathology   55 ( 3 )   169 - 174   2016年

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  • A condition closely mimicking IgG4-related disease despite the absence of serum IgG4 elevation and IgG4-positive plasma cell infiltration 査読

    Satoshi Hara, Mitsuhiro Kawano, Ichiro Mizushima, Kazunori Yamada, Kentaro Fujita, Kenichi Harada, Masami Matsumura, Masakazu Yamagishi, Yasuharu Sato, Yutaka Yamaguchi, Yasuni Nakanuma, Michio Nagata

    MODERN RHEUMATOLOGY   26 ( 5 )   784 - 789   2016年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPRINGER  

    We describe a 74-year-old Japanese man with systemic fibroinflammatory conditions closely resembling those of immunoglobulin G4-related disease (IgG4-RD). Radiology and histology showed characteristics of IgG4-related tubulointerstitial nephritis, despite normal serum IgG4 value and scanty IgG4-positive plasma cell infiltration in each organ. This case suggests that a condition closely mimicking IgG4-RD may develop without IgG4-positive plasma cells and those exceptional cases should also be taken into account in the differential diagnosis of IgG4-RD.

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  • Elevation of serum interleukins 8, 4, and 1 beta levels in patients with gastrointestinal low-grade B-cell lymphoma 査読

    Tomoko Miyata-Takata, Katsuyoshi Takata, Tomohiro Toji, Naoe Goto, Senji Kasahara, Takeshi Takahashi, Akira Tari, Mai Noujima-Harada, Takafumi Miyata, Yasuharu Sato, Tadashi Yoshino

    SCIENTIFIC REPORTS   5   18434   2015年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:NATURE PUBLISHING GROUP  

    Proinflammatory cytokines that are produced by helper T cells (Th) regulate immune reactions, facilitate class switching of B cells, and prolong the lifespan of B and T cells. Eradication therapy using antibiotics is sometimes effective against gastrointestinal (GI) malignant lymphoma, suggesting that the tumor development or progression is affected by the inflammatory microenvironment. In the present study, serum samples from 148 patients with various subtypes of malignant lymphoma were tested for 11 proinflammatory Th1/Th2 cytokines. In the comparison by subtype or GI lesions, serum interleukin (IL)-8 (P= 6.7E-05), IL-4 (P = 7.5E-05), and IL-10 (P = 0.0043) levels showed significant differences among subtypes, being particularly elevated in follicular lymphomas (FL) and mucosa-associated lymphoid tissue (MALT) lymphomas. Serum IL-8 levels were elevated in GI-FL and MALT lymphomas, and serum IL-4 and IL-10 levels were elevated in MALT lymphomas. These findings show that GI low-grade B-cell lymphoma could develop against the background of an inflammatory microenvironment. Thus, these cytokines may be useful as diagnostic markers and could provide new insights into tumor development.

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  • Spontaneous regression of plasmablastic lymphoma in an elderly human immunodeficiency virus (HIV)-negative patient 査読

    Takuro Igawa, Yasuharu Sato, Hotaka Kawai, Eisei Kondo, Mai Takeuchi, Tomoko Miyata-Takata, Katsuyoshi Takata, Tadashi Yoshino

    DIAGNOSTIC PATHOLOGY   10   2015年10月

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    担当区分:最終著者, 責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:BIOMED CENTRAL LTD  

    Plasmablastic lymphoma (PBL) is an aggressive lymphoma commonly associated with human immunodeficiency virus (HIV) infection. Herein we describe a rare case of PBL that spontaneously regressed. An 80-year-old man was referred to our hospital owing to an exophytic gingival tumor in the right maxillary second molar region. He had no significant past medical history, and a screening test for HIV was negative. Imaging showed that the tumor measured 26 x 23 x 16 mm and was confined in the alveolar bone. The tumor was histologically comprised of highly proliferative immunoblastic cells positive for CD138 and Epstein-Barr virus (EBV)-encoded RNA. Monoclonal IgH chain gene rearrangement was detected via polymerase chain reaction. After biopsy and diagnosis of PBL, the tumor began to decrease in size and had apparently disappeared at the time of surgery. There was no histological evidence of a residual lesion in the surgical specimen. In conclusion, a minority of immunosenescence-associated PBLs in the elderly should be recognized as a unique clinicopathological entity distinct from common aggressive PBL.

    DOI: 10.1186/s13000-015-0421-y

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  • Human immunodeficiency virus-positive secondary syphilis mimicking cutaneous T-cell lymphoma 査読

    Michiko Yamashita, Yoshiyuki Fujii, Keiji Ozaki, Yoshio Urano, Masami Iwasa, Shingen Nakamura, Shiro Fujii, Masahiro Abe, Yasuharu Sato, Tadashi Yoshino

    DIAGNOSTIC PATHOLOGY   10   2015年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:BIOMED CENTRAL LTD  

    Malignant syphilis or lues maligna is a severe form of secondary syphilis that was commonly reported in the pre-antibiotic era, and has now reemerged with the advent of the human immunodeficiency virus (HIV) epidemic. However, the characteristic histopathological findings of malignant syphilis remain controversial. The aim of this case report was to clarify the clinical and histopathological findings of HIV-positive malignant secondary syphilis. A Japanese man in his forties complained of fever, skin lesions, headache, and myalgia without lymphadenopathy during the previous 4 weeks. The skin lesions manifested as erythematous, nonhealing, ulcerated papules scattered on his trunk, extremities, palm, and face. Although the skin lesions were suspected to be cutaneous T-cell lymphomas on histological analyses, they lacked T-cell receptor J gamma rearrangement; moreover, immunohistochemical analyses confirmed the presence of spirochetes. The patient was administered antibiotics and anti-retroviral therapy, which dramatically improved the symptoms. On the basis of these observations of the skin lesions, we finally diagnosed the patient with HIV-associated secondary syphilis that mimicked cutaneous T-cell lymphoma. The patient's systemic CD4+ lymphocyte count was very low, and the infiltrate was almost exclusively composed of CD8+ atypical lymphocytes; therefore, the condition was easily misdiagnosed as cutaneous lymphoma. Although the abundance of plasma cells is a good indicator of malignant syphilis on skin histological analyses, in some cases, the plasma cell count may be very low. Therefore, a diagnosis of malignant secondary syphilis should be considered before making a diagnosis of primary cutaneous peripheral T-cell lymphoma or lymphoma associated with HIV infection.

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  • Clinicopathologic Analysis of 6 Lymphomatoid Gastropathy Cases Expanding the Disease Spectrum to CD4(-) CD8(+) Cases 査読

    Katsuyoshi Takata, Mai Noujima-Harada, Tomoko Miyata-Takata, Koichi Ichimura, Yasuharu Sato, Takafumi Miyata, Keishi Naruse, Toshiyuki Iwamoto, Akira Tari, Taro Masunari, Hiroshi Sonobe, Hiroyuki Okada, Masaya Iwamuro, Kohichi Mizobuchi, Yuka Gion, Tadashi Yoshino

    AMERICAN JOURNAL OF SURGICAL PATHOLOGY   39 ( 9 )   1259 - 1266   2015年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:LIPPINCOTT WILLIAMS & WILKINS  

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

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  • Serum level of soluble interleukin-2 receptor correlates with CD25 expression in patients with T lymphoblastic lymphoma 査読

    Tomohiro Toji, Katsuyoshi Takata, Yasuharu Sato, Tomoko Miyata-Takata, Eiko Hayashi, Toshiyuki Habara, Yoshinobu Maeda, Mitsune Tanimoto, Tadashi Yoshino

    JOURNAL OF CLINICAL PATHOLOGY   68 ( 8 )   622 - 627   2015年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:BMJ PUBLISHING GROUP  

    Acute lymphoblastic leukaemia/lymphoma (ALL/LBL) is an aggressive form of non-Hodgkin's lymphoma (NHL) affecting B-cells or T-cells, respectively. The serum level of soluble interleukin-2 receptor (sIL-2R) is known to reflect the immune activity and tumour volume in aggressive NHL; however, the release of sIL-2R in LBL has not been extensively studied. Further, the relationship between sIL-2R release and the expression level of IL-2R alpha subunit (CD25) remains unknown.
    In the present study, we examined the serum level of sIL-2R in 23 patients with T lymphoblactic lymphoma (T-LBL) and compared these with the levels in 20 patient with T acute lymphoblastic leukaemia (T-ALL), 40 patients with diffuse large B-cell lymphoma (DLBCL) and 40 patients with peripheral T-cell lymphoma (PTCL), not otherwise specified. The release of sIL-2R into the serum in patients with T-LBL was significantly lower than that for T-ALL, DLBCL and PTCL (p&lt;0.001).
    Immunohistochemistry revealed that CD25 expression was correlated with the serum level of sIL-2R in T-LBL (p=0.0069), whereas no correlation was found to exist between serum sIL-2R levels and CD25 expression in patients with DLBCL (p=0.348) and PTCL (p=0.266). Furthermore, double immunohistochemical analysis revealed that CD25-positive cells were also found to be Foxp3-positive non-neoplastic T-cells. In conclusion, CD25-positive non-neoplastic T-cells in T-LBL are presumed to be the primary source of sIL-2R, and the low number of cells present results in a lower level of sIL-2R released into the serum compared with the other aggressive and highly aggressive lymphomas.

    DOI: 10.1136/jclinpath-2015-202934

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  • A subset of ocular adnexal marginal zone lymphomas may arise in association with IgG4-related disease 査読

    Kyotaro Ohno, Yasuharu Sato, Koh-ichi Ohshima, Katsuyoshi Takata, Tomoko Miyata-Takata, Mai Takeuchi, Yuka Gion, Tomoyasu Tachibana, Yorihisa Orita, Toshihiro Ito, Steven H. Swerdlow, Tadashi Yoshino

    SCIENTIFIC REPORTS   5   13539   2015年8月

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    担当区分:責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:NATURE PUBLISHING GROUP  

    We previously suggested a relationship between ocular immunoglobulin (Ig)G4-related disease (IgG4-RD) and marginal zone lymphomas (MZLs). However, the cytokine background associated with these disorders and whether it differs between ocular adnexal MZLs with (IgG4-associated MZL) and without (IgG4-negative MZL) numerous IgG4(+) plasma cells are unknown. In this study, we identified the mRNA expression pattern of Th2 and regulatory T-cell (Treg) cytokines in IgG4-RD and in IgG4-associated MZL and IgG4-negative MZL using real-time polymerase chain reaction analysis. Ocular IgG4-RD and IgG4-associated MZL exhibited significantly higher expression ratios of interleukin (1Q-4/beta-actin, IL-10/beta-actin, IL-13/beta-actin, transforming growth factor (TGF) beta 1/beta-actin, and FOXP3/beta-actin than did IgG4-negative MZL (p &lt; 0.05). This finding further supports our prior observations that a significant subset of ocular MZLs arises in the setting of IgG4-RD. Furthermore, the presence of a different inflammatory background in IgG4-negative MZLs suggests that IgG4-associated MZLs may have a different pathogenesis. Immunoglobulin (Ig)G4-related

    DOI: 10.1038/srep13539

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  • Aggressive Garcin's syndrome by acquired cystic disease of kidney-related renal cell carcinoma in a long-term hemodialytic patient 査読

    Yuko Kawahara, Kentaro Deguchi, Kota Sato, Nozomi Hishikawa, Syoichiro Kono, Yasuyuki Ohta, Toru Yamashita, Eiko Hayashi, Yasuharu Sato, Koji Abe

    JOURNAL OF THE NEUROLOGICAL SCIENCES   355 ( 1-2 )   216 - 218   2015年8月

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    記述言語:英語   出版者・発行元:ELSEVIER SCIENCE BV  

    DOI: 10.1016/j.jns.2015.06.006

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  • Cytokeratin-positive fibroblastic reticular cell tumor with follicular dendritic cell features : A case report and review of the literature 査読

    Naoe Goto, Hisashi Tsurumi, Tsuyoshi Takami, Manabu Futamura, Kasumi Morimitsu, Katsuyoshi Takata, Yasuharu Sato, Tadashi Yoshino, Seiji Adachi, Koshiro Saito, Mitsunori Yamakawa

    American Journal of Surgical Pathology   39 ( 4 )   573 - 580   2015年3月

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    記述言語:英語   出版者・発行元:Lippincott Williams and Wilkins  

    Fibroblastic reticular cell (FRC) neoplasms, which are one of the histiocyte tumor types, are very rare. Here we report a cytokeratin (CK)-positive FRC neoplasm having features of follicular dendritic cells in a 54-year-old woman with right axillary lymph node swelling. The resected lymph node showed multiple nodular aggregations simulating and replacing normal follicles. The tumor cells had a uniform, large and oval to polygonal shape, abundant cytoplasm, and various sizes of nuclei with central eosinophilic nucleoli and coarse nuclear chromatin. They were positive for CK AE1/AE3+CAM5.2, CK7, tenascin C, l-caldesomone, and CD21, weakly positive for S100, and negative for CD1a. Ultrastructurally, the tumor cells had long interdigitating microvillus-like cell processes and oval to elongated vesicular nuclei. In addition, the intercellular spaces contained accumulations of collagen, and some tumor cells had desmosomal-like junctions. These findings suggest that the present case is a CK-positive FRC tumor with follicular dendritic cell features.

    DOI: 10.1097/PAS.0000000000000362

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  • Interleukin 13-positive mast cells are increased in immunoglobulin G4-related sialadenitis 査読

    Mai Takeuchi, Kyotaro Ohno, Katsuyoshi Takata, Yuka Gion, Tomoyasu Tachibana, Yorihisa Orita, Tadashi Yoshino, Yasuharu Sato

    SCIENTIFIC REPORTS   5   2015年1月

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    担当区分:最終著者, 責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:NATURE PUBLISHING GROUP  

    Interleukin (IL)-13 is a T helper 2 (Th2) cytokine that plays important roles in the pathogenesis of asthma. IL-13 induces hypersensitivity of the airways, increased mucous production, elevated serum immunoglobulin (Ig) E levels, and increased numbers of eosinophils. Many patients with IgG4-related disease have allergic backgrounds and show elevated serum IgE levels and an increase in the number of eosinophils. Upregulation of Th2/regulatory T (Treg) cytokines, including IL-13, has been detected in affected tissues of patients with IgG4-related disease. We previously reported that mast cells might be responsible for the production of the Th2/Treg cytokines IL-4, IL-10, and transforming growth factor (TGF)-beta 1 in IgG4-related disease. In this study, immunohistochemical analysis showed increased numbers of IL-13-positive mast cells in IgG4-related disease, which suggests that mast cells also produce IL-13 and contribute to elevation of serum IgE levels and eosinophil infiltration in IgG4-related disease.

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  • How long should we continue S-1 as adjuvant chemotherapy for squamous cell carcinoma of the head and neck? 査読

    Misato Hirai, Yorihisa Orita, Soshi Takao, Tomoyasu Tachibana, Hidenori Marunaka, Seiichiro Makihara, Kentaro Miki, Yasuyuki Noyama, Sayaka Fuji, Akiko Torigoe, Yasuharu Sato, Kazunori Nishizaki

    ACTA OTO-LARYNGOLOGICA   135 ( 10 )   1079 - 1085   2015年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:TAYLOR & FRANCIS LTD  

    Conclusion: It appears that patients with SCCHN should be recommended to take S-1 for more than 1 year and, if possible, more than 2 years, as adjuvant chemotherapy for SCCHN. Objectives: There is no established consensus on the duration of administration of S-1 as adjuvant chemotherapy for squamous cell carcinoma of the head and neck (SCCHN). Since it might be difficult to undergo prospective randomized study to identify the optimal duration of the administration period of S-1 without a standard, the authors have undergone a retrospective clinical study to decide the tentative standard of therapeutic duration of S-1 as adjuvant chemotherapy for SCCHN. Methods: The clinical records of 89 patients with SCCHN who underwent adjuvant chemotherapy with S-1 were investigated. Results: The median duration of S-1 administration as adjuvant chemotherapy for SCCHN was 7 months (range = 0.1-58 months). Disease-free survivals (DFSs) were generally longer when S-1 administration periods were longer. After adjusting for prognostic factors, S-1 administration periods of 24 months or longer showed significantly lower hazard ratios (HRs) than 0-12 months.

    DOI: 10.3109/00016489.2015.1049664

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  • Diffuse large B-cell lymphoma of the lacrimal sac arising from a patient with IgG4-related disease. 査読 国際誌

    Marunaka H, Orita Y, Tachibana T, Miki K, Makino T, Yoshino T, Nishizaki K, Sato Y

    Modern Rheumatology   28 ( 3 )   559 - 563   2015年

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    担当区分:最終著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.3109/14397595.2015.1131353

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  • HHV8-Negative Body Cavity-Based Lymphoma Is Mature Large B-Cell Lymphoma That Affects Elderly and Displays Favorable Prognosis: A Multi-Center Retrospective Study of 50 Patients in Japan

    Daisuke Kaji, Yasunori Ota, Yasuharu Sato, Koji Nagafuji, Masataka Okamoto, Yasushi Terasaki, Naoko Tsuyama, Tomohiro Kinoshita, Shuichi Taniguchi, Koichi Ohshima, Koji Izutsu

    BLOOD   124 ( 21 )   2014年12月

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    記述言語:英語   出版者・発行元:AMER SOC HEMATOLOGY  

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  • Prognostic factors and effects of early surgical drainage in patients with peritonsillar abscess 査読

    Tomoyasu Tachibana, Yorihisa Orita, Iku Abe-Fujisawa, Yuya Ogawara, Yuko Matsuyama, Aiko Shimizu, Michihiro Nakada, Yasuharu Sato, Kazunori Nishizaki

    JOURNAL OF INFECTION AND CHEMOTHERAPY   20 ( 11 )   722 - 725   2014年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPRINGER JAPAN KK  

    Peritonsillar abscess is a frequently encountered otorhinolaryngological emergency, but the characteristics of patients with this disease have not been described in detail. The objective of this study was to delineate prognostic factors associated with peritonsillar abscess and the effects of early surgical drainage for the treatment of peritonsillar abscess. We conducted a retrospective analysis of the medical records of 240 consecutive patients with PTA during the period from 2007 to 2013. Univariate analysis indicated that the period between symptom onset and relief was significantly longer in patients with high levels of C-reactive protein (CRP) (&gt;8.53 mg/dL, p = 0.0073) and without early surgical drainage of pus (p &lt; 0.0001). Multivariate analysis identified both of these values as independently associated with longer duration of symptoms (high CRP, P &lt; 0.0001; no early drainage, P &lt; 0.0001). Univariate analysis indicated that the duration between symptom onset and complete recovery from the disease was significantly longer with age &gt;= 40 years (P = 0.0004), no history of recurrent tonsillitis (P = 0.022), high CRP level (P = 0.0017), and no early surgical drainage of the abscess (P = 0.0014). Multivariate analysis identified older age (P = 0.0004), high CRP level (P = 0.0001), and no early drainage (P &lt; 0.0001) as independently associated with longer duration between symptom onset and complete recovery. Early surgical drainage of the abscess is important for the treatment of peritonsillar abscess. Patients &gt;40 years old with peritonsillar abscess and high CRP levels should be recognized as a high-risk group. (C) 2014, Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

    DOI: 10.1016/j.jiac.2014.07.018

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  • A case of diffuse large B-cell lymphoma transformed from primary duodenal follicular lymphoma 査読

    Tomoko Miyata-Takata, Katsuyoshi Takata, Yasuharu Sato, Kohei Taniguchi, Yuka Takahashi, Nobuya Ohara, Tadashi Yoshino

    PATHOLOGY INTERNATIONAL   64 ( 10 )   527 - 532   2014年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-BLACKWELL  

    Primary intestinal follicular lymphoma (FL) is a variant of FL characterized by frequent duodenal involvement and a very indolent clinical behavior without therapy. Unlike nodal FL, there have been no reports of histologic transformation (HT) or death attributable to primary intestinal FL. Here, we report the first case of primary duodenal FL showing HT. A Grade 1 FL in the duodenum was incidentally detected in a 73-year-old man. A watch-and-wait strategy was adopted because the disease was stage IE. Six months later, bone marrow involvement was suspected. The intestinal lesions had not changed during the first year since the initial diagnosis. Sixty-two months after the initial diagnosis, a biopsy specimen showed diffuse large B-cell lymphoma (DLBCL). A perforation of the intestine occurred before chemotherapy was started. Partial resection was performed and subsequent chemotherapy was administered. The clone of the initial FL and DLBCL were identical according to PCR analysis, indicating that the primary intestinal FL had transformed into DLBCL. Although HT is rare, it could occur in some patients with primary intestinal FL. Based on this case, it may be necessary to re-evaluate the clinical watch-and-wait strategy for primary intestinal FL in some patients.

    DOI: 10.1111/pin.12197

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  • Does HMGB1 predict occult neck lymph node metastasis in early tongue carcinoma? A case-control study of 26 patients 査読

    H. Hanakawa, Y. Orita, Y. Sato, M. Takeuchi, S. Takao, K. Ohno, T. Kohno, N. Iwaki, H. Marunaka, R. Tamamura, M. Nishibori, H. Nagatsuka, K. Nishizaki, T. Yoshino

    JOURNAL OF LARYNGOLOGY AND OTOLOGY   128 ( 10 )   926 - 931   2014年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:CAMBRIDGE UNIV PRESS  

    Objective: This study examined whether the occurrence of late neck metastasis in early tongue squamous cell carcinoma can be predicted by evaluating HMGB1 (high mobility group box 1) expression in the primary lesion.
    Methods: A case-control study was conducted. The cases comprised 10 patients with late neck metastasis. The controls consisted of 16 patients without recurrence. All were examined immunohistochemically for HMGB1 protein expression. The odds ratio for late neck metastasis in relation to HMGB1 was estimated.
    Results: Results for HMGB1 were dichotomised into positive staining scores (score, 5-7) and negative scores (0-4). Six cases (60 per cent) and four controls (25 per cent) were HMGB1-positive. Although no significant result was seen, compared with HMGB1-negative patients the odds ratio for late neck metastasis in HMGB1-positive patients was 3.8 (95 per cent confidence interval, 0.6-26.5) after adjusting for other factors.
    Conclusion: In the present study, immunohistochemical study of HMGB1 in early tongue squamous cell carcinoma did not appear to be very useful for predicting occult neck metastasis. Further study is necessary to clarify the relationship between HMGB1 expression and late neck metastasis in early tongue squamous cell carcinoma.

    DOI: 10.1017/S0022215114001819

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  • Mantle cell lymphoma with a unique pattern of CD5 expression: a case report with review of the literatures 査読

    Toshiki Yamada, Naoe Goto, Hisashi Tsurumi, Katsuyoshi Takata, Yasuharu Sato, Tadashi Yoshino, Hisataka Moriwaki, Yusuke Kito, Tamotsu Takeuchi, Hitoshi Iwata

    MEDICAL MOLECULAR MORPHOLOGY   47 ( 3 )   169 - 175   2014年9月

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    記述言語:英語   出版者・発行元:SPRINGER JAPAN KK  

    Mantle cell lymphoma (MCL) is a unique subtype of B-cell non-Hodgkin's lymphoma characterized by chromosomal translocation t(11;14)(q13;q32), positive CD5, and nuclear cyclin D1 overexpression with unfavorable prognosis. We report herein a case of MCL in a 73-year-old male diagnosed with diffuse large B-cell lymphoma (ileal tumor) at another hospital, who subsequently relapsed with CD5-negative MCL. At the 1st relapse, he developed neck lymph node swelling, of which biopsy showed proliferation of atypical large pleomorphic cells with CD5-negativity by both immunohistochemistry and flow cytometry. At the 2nd relapse, he again developed an ileal tumor, of which biopsy showed positivity for CD5, CD20, and cyclin D1. In MCL, CD5-negative expression has sometimes been reported as having pleomorphic and blastoid variants. The present case was also histologically the pleomorphic type, but the CD5 expression changed from negative at the onset and the 1st relapse to positive at the 2nd relapse. This is a rare and interesting case because of the different expression of CD5 at all stage. This phenomenon made the diagnosis of MCL difficult.

    DOI: 10.1007/s00795-013-0060-x

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  • Detection of T- cell receptor γ gene rearrangement in paraffin-embedded T or NK/T cell lymphoma samples by using the BIOMED-2 protocol. 査読

    Miyata-Takata T, Takata K, Yamanouchi S, Sato Y, Oka T, Tanaka T, Maeda Y, Tanimoto M, Yoshino T

    Leukemia and Lymphoma   55 ( 9 )   2161 - 2164   2014年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.3109/10428194.2013.871634

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  • Regulatory T-cell infiltration in tongue squamous cell carcinoma

    Hiroyuki Hanakawa, Yorihisa Orita, Yasuharu Sato, Mai Takeuchi, Kyotaro Ohno, Yuka Gion, Kiyoaki Tsukahara, Ryo Tamamura, Toshihiro Ito, Hitoshi Nagatsuka, Kazunori Nishizaki, Tadashi Yoshino

    ACTA OTO-LARYNGOLOGICA   134 ( 8 )   859 - 864   2014年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:INFORMA HEALTHCARE  

    Conclusion: In tongue squamous cell carcinoma (SCC), high levels of regulatory T-cell (Treg) infiltration in tumor nests are observed in the cases with poor prognosis. Objectives: The role of Tregs in head and neck cancers remains unclear. The aim of this study was to observe the distribution of Tregs in different stages of tongue SCC and estimate the effects on prognosis. Methods: Thirty-four cases with tongue SCC were examined immunohistochemically for CD4, CD8, and Forkhead box P3 (Foxp3). Immunoreactive cells were counted in cancer stroma and nest regions, and relationships between cell numbers and disease-free survival rates were analyzed. Results: In the 34 cases, univariate analysis for disease-free survival indicated high-level infiltration of Tregs (CD4(+)Foxp3+) into both cancer nests and stroma and presence of helper T (CD4(+)Foxp3-) cells in cancer stroma as potential predictors of significantly worse prognosis. In early-stage cases (stage I/II), high-level infiltration of Tregs in cancer nests correlated significantly with poor disease- free survival rate. Multivariate analysis for disease-free survival found no independent variables.

    DOI: 10.3109/00016489.2014.918279

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  • T helper 2 and regulatory T-cell cytokine production by mast cells: a key factor in the pathogenesis of IgG4-related disease

    Mai Takeuchi, Yasuharu Sato, Kyotaro Ohno, Satoshi Tanaka, Katsuyoshi Takata, Yuka Gion, Yorihisa Orita, Toshihiro Ito, Tomoyasu Tachibana, Tadashi Yoshino

    MODERN PATHOLOGY   27 ( 8 )   1126 - 1136   2014年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:NATURE PUBLISHING GROUP  

    IgG4-related disease is a systemic disorder with unique clinicopathological features and uncertain etiological features and is frequently related to allergic disease. T helper 2 and regulatory T-cell cytokines have been reported to be upregulated in the affected tissues; thus, the production of these cytokines by T helper 2 and regulatory T cells has been suggested as an important factor in the pathogenesis of IgG4-related disease. However, it is not yet clear which cells produce these cytokines in IgG4-related disease, and some aspects of the disorder cannot be completely explained by T-cell-related processes. To address this, we analyzed paraffin-embedded sections of tissues from nine cases of IgG4-related submandibular gland disease, five cases of submandibular sialolithiasis, and six cases of normal submandibular gland in order to identify potential key players in the pathogenesis of IgG4-related disease. Real-time polymerase chain reaction analysis confirmed the significant upregulation of interleukin (IL)4, IL10, and transforming growth factor beta 1 (TGF beta 1) in IgG4-related disease. Interestingly, immunohistochemical studies indicated the presence of mast cells expressing these cytokines in diseased tissues. In addition, dual immunofluorescence assays identified cells that were double-positive for each cytokine and for KIT, which is expressed by mast cells. In contrast, the distribution of T cells did not correlate with cytokine distribution in affected tissues. We also found that the mast cells were strongly positive for IgE. This observation supports the hypothesis that mast cells are involved in IgG4-related disease, as mast cells are known to be closely related to allergic reactions and are activated in the presence of elevated non-specific IgE levels. In conclusion, our results indicate that mast cells produce T helper 2 and regulatory T-cell cytokines in tissues affected by IgG4-related disease and possibly have an important role in disease pathogenesis.

    DOI: 10.1038/modpathol.2013.236

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  • Clinicopathological analysis of 17 primary cutaneous T-cell lymphoma of the gamma delta phenotype from Japan

    Yuka Takahashi, Katsuyoshi Takata, Seiichi Kato, Yasuharu Sato, Naoko Asano, Tetsuro Ogino, Kimio Hashimoto, Yukie Tashiro, Shogo Takeuchi, Taro Masunari, Yasushi Hiramatsu, Yoshinobu Maeda, Mitsune Tanimoto, Tadashi Yoshino

    CANCER SCIENCE   105 ( 7 )   912 - 923   2014年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-BLACKWELL  

    Primary cutaneous gamma delta T-cell lymphoma (PCGD-TCL) is an aggressive lymphoma consisting of clonal proliferation of mature activated gamma delta T-cells of a cytotoxic phenotype. Because primary cutaneous gamma delta T-cell lymphoma is a rare disease, there are few clinicopathological studies. In addition, T-cell receptor (TCR) gamma delta cells are typically immunostained in frozen sections or determined by TCR beta negativity. We retrospectively analyzed 17 primary cutaneous T-cell lymphomas of the gamma delta phenotype (CTCL-gamma delta) in a clinicopathological and molecular study using paraffin-embedded sections. Among 17 patients, 11 had CTCL-gamma delta without subcutaneous panniculitis-like T-cell lymphoma (SPTCL) features and six had CTCL-gamma delta with SPTCL features. Immunophenotypically, some significant differences were found in CD8 and CD56 positivity between our patient series of CTCL-gamma delta patients with SPTCL features and SPTCL-gamma delta patients described in the previous literature. A univariate analysis of 17 CTCL-gamma delta patients showed that being more than 60 years old, presence of visceral organ involvement, and small-to-medium cell size were poor prognostic factors. In addition, the 5-year overall survival rate was 42.4% for the CTCL-gamma delta patients without SPTCL features and 80.0% for those with SPTCL features. Consequently, there was a strikingly significant difference in overall survival among SPTCL, CTCL-gamma delta with SPTCL features and CTCL-gamma delta without SPTCL features (P = 0.0005). Our data suggests that an indolent subgroup may exist in CTCL-gamma delta. Studies on more cases, including those from other countries, are warranted to delineate the clinicopathological features and the significance in these rare lymphomas.

    DOI: 10.1111/cas.12439

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  • Epstein-Barr Virus-infected Cells in IgG4-related Lymphadenopathy With Comparison With Extranodal IgG4-related Disease

    Mai Takeuchi, Yasuharu Sato, Hiroshi Yasui, Hiroaki Ozawa, Kyotaro Ohno, Katsuyoshi Takata, Yuka Gion, Yorihisa Orita, Tomoyasu Tachibana, Tomoo Itoh, Naoko Asano, Shigeo Nakamura, Steven H. Swerdlow, Tadashi Yoshino

    AMERICAN JOURNAL OF SURGICAL PATHOLOGY   38 ( 7 )   946 - 955   2014年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:LIPPINCOTT WILLIAMS & WILKINS  

    IgG4-related lymphadenopathy with increased numbers of Epstein-Barr virus (EBV)-infected cells has been reported but not fully described. We analyzed 31 cases of IgG4-related lymphadenopathy and 24 cases of extranodal IgG4-related diseases for their possible relationship with EBV. Other types of reactive lymph nodes (22) and angioimmunoblastic T-cell lymphoma (AITL) (10) were also studied for comparison. EBV-encoded RNA (EBER) in situ hybridization revealed EBER+ cells in 18 of 31 cases (58%) of IgG4-related lymphadenopathy. Increased EBER+ cells were found in only 4 of 22 (18.1%) non-IgG4-related reactive lymphoid hyperplasia in patients of a similar age (P = 0.002) and in only 5 of 24 (21%) extranodal IgG4-related biopsies (P = 0.006). Interestingly, all patients with EBER+ progressively transformed germinal center-type IgG4-related lymphadenopathy had systemic lymphadenopathy and/or extranodal involvement. AITL also is associated with EBV, and IgG4-related lymphadenopathy sometimes mimics the morphology of AITL; however, the number of IgG4(+) cells in AITL was significantly less than that in IgG4-related lymphadenopathy (P &lt; 0.001). Increased numbers of regulatory T cells are seen in IgG4-related disease; however, there was not a significant difference between the EBER+ and EBER- cases. In conclusion, the presence of increased numbers of EBV-infected cells in IgG4-related lymphadenopathy, compared with other reactive lymphadenopathy or extranodal IgG4-related disease, suggests that there may be a relationship at least between nodal IgG4-related disease and EBV. It is important to avoid overdiagnosing these cases as malignant lymphomas or EBV-related lymphoproliferative disorders.

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  • Low-grade B-cell lymphoma presenting primarily in the bone marrow

    Kayoko Iwatani, Katsuyoshi Takata, Yasuharu Sato, Tomoko Miyata-Takata, Noriko Iwaki, Wei Cui, Seiko Sawada-Kitamura, Hiroshi Sonobe, Maiko Tamura, Katsuhiko Saito, Katsuya Miyatani, Rie Yamasaki, Ichiro Yamadori, Nobuharu Fujii, Yasushi Terasaki, Yoshinobu Maeda, Mitsune Tanimoto, Naoya Nakamura, Tadashi Yoshino

    HUMAN PATHOLOGY   45 ( 7 )   1379 - 1387   2014年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:W B SAUNDERS CO-ELSEVIER INC  

    Cases of low-grade B-cell lymphoma presenting primarily in the bone marrow are rare, and its clinicopathology remains unclear. We retrospectively examined patients with low-grade B-cell lymphoma presenting primarily in the bone marrow. Fourteen patients met the inclusion criteria, including 5 with lymphoplasmacytic lymphoma (LPL), 3 with chronic lymphocytic leukemia/small lymphocytic lymphoma, 2 with follicular lymphoma (FL), and 4 with low-grade B-cell lymphoma not otherwise specified (LGBCL-NOS). The median age was 69.5 years (range, 42-89 years), and a slight male predominance was noted (9 men and 5 women, 1.8: 1). Immunohistochemically, all cases were positive for CD20. One case was positive for CD138. Both cases of FL were positive for CD10 and B-cell lymphoma 2 (BCL-2), and immunoglobulin heavy locus (IgH)/B-cell lymphoma 2 rearrangement was observed by fluorescence in situ hybridization. The myeloid differentiation primary response gene (88) leucine to proline mutation was observed in 3 of 5 LPL, 1 of 2 FL, and 2 of 4 LGBCL-NOS patients. Paraproteinemia was observed in 10 patients; IgM and IgG paraproteinemia were observed in 6 and 3 patients, respectively. In this patient series, 3 patients had died at a median follow-up of 36.5 months; the cause of death of 1 LPL patient was malignant lymphoma itself. Thus, low-grade B-cell lymphoma presenting primarily in the bone marrow has various subtypes, and approximately one-third of the patients had LGBCL-NOS. The immunophenotypic features and myeloid differentiation primary response gene (88) leucine to proline mutation data of LGBCL-NOS suggested that some cases present with characteristics similar to those of LPL or marginal zone lymphoma. (C) 2014 Elsevier Inc. All rights reserved.

    DOI: 10.1016/j.humpath.2014.02.010

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  • Duodenal follicular lymphoma: Comprehensive gene expression analysis with insights into pathogenesis

    Katsuyoshi Takata, Motohiko Tanino, Daisuke Ennishi, Akira Tari, Yasuharu Sato, Hiroyuki Okada, Yoshinobu Maeda, Naoe Goto, Hiroshi Araki, Mai Harada, Midori Ando, Masaya Iwamuro, Mitsune Tanimoto, Kazuhide Yamamoto, Randy D. Gascoyne, Tadashi Yoshino

    CANCER SCIENCE   105 ( 5 )   608 - 615   2014年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-BLACKWELL  

    Follicular lymphoma (FL) of the gastrointestinal tract, particularly duodenal follicular lymphoma (DFL), is a rare variant of FL with indolent clinical behavior, and this disease is included in the 2008 World Health Organization classification system. In contrast to nodal follicular lymphoma (NFL), DFL occurs most frequently in the second part of the duodenum, lacks follicular dendritic cell meshworks and has memory B-cell characteristics. However, its molecular pathogenesis is still unclear. In the present study, we examined 10 DFL, 18 NFL and 10 gastric MALT lymphoma samples using gene expression analysis. Quantitative RT-PCR experiments and immunohistochemical analysis for 72 formalin-fixed, paraffin-embedded tissues from an independent series, including 32 DFL, 19 gastric MALT lymphoma and 27 NFL samples, were performed for validation of microarray data. Gene expression profiles of the three lymphoma types were compared using 2918 differentially expressed genes (DEG) and results suggested that DFL shares characteristics of MALT lymphoma. Among these DEG, CCL20 and MAdCAM-1 were upregulated in DFL and MALT but downregulated in NFL. In contrast, protocadherin gamma subfamily genes were upregulated in DFL and NFL. Quantitative RT-PCR and immunohistochemical studies demonstrated concordant results. Double immunofluorescence studies revealed that CCL20 and CCR6 were co-expressed in both DFL and MALT. We hypothesize that increased expression of CCL20 and MAdCAM-1 and co-expression of CCL20 and CCR6 may play an important role in tumorigenesis.

    DOI: 10.1111/cas.12392

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  • CHARACTERISTIC PATHOLOGY OF IgG4-RELATED KIDNEY DISEASE

    Nagata Michio, Hara Satoshi, Mizushima Ichiro, Kawano Mitsuhiro, Saeki Takako, Ubara Yoshifumi, Ohara Nobuya, Sato Yasuharu, Yamada Kazunori, Nakashima Hitoshi, Nishi Shinichi, Yamaguchi Yutaka, Hisano Satoshi, Yamanaka Nobuaki, Saito Takao

    NEPHROLOGY   19   11 - 12   2014年5月

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    記述言語:英語   出版者・発行元:WILEY-BLACKWELL  

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  • Novel and simple prognostic index for nasal natural killer/T- cell lymphoma

    Hiroyuki Hanakawa, Yorihisa Orita, Yasuharu Sato, Soshi Takao, Hidenori Marunaka, Tokiwa Morishita, Yasuhiko Yamashita, Yasutaka Hori, Shuhei Domae, Ikuo Inokuchi, Seiko Akagi, Eisei Kondo, Noriko Iwaki, Kana Motomiya, Hirokazu Okumura, Tadashi Yoshino, Kazunori Nishizaki

    HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK   36 ( 4 )   551 - 556   2014年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-BLACKWELL  

    BackgroundFew studies have investigated the prognostic factors for nasal natural killer (NK)/T-cell lymphoma.
    MethodsThis was a retrospective multicenter clinical study. The clinical records of 36 patients with nasal NK/T-cell lymphoma who had been first treated between 1996 and 2011 were collected from 12 hospitals.
    ResultsHigh serum levels of C-reactive protein (1.0 mg/dL), lactate dehydrogenase (350 IU/L), and soluble interleukin-2 receptor (sIL-2R; 600 U/mL) were associated with worse prognosis. A prognostic score was devised by totaling the number of these 3 predictors: 0 or 1 = score 0; and 2 or 3 = score 1. As for tumor invasion, local invasion beyond the nasal cavity was associated with poor prognosis, and a prognostic score was devised as: tumor restricted to nasal cavity, yes = score 0; no = score 1. A novel prognostic index (NPI) was established based on these scores from 0 to 2. Disease-specific survival rates at 5 years were: 90.0% for NPI = 0; 29.3% for NPI = 1; and 0.0% for NPI = 2.
    ConclusionOur NPI is valid for anticipating prognosis of nasal NK/T-cell lymphoma. (c) 2013 Wiley Periodicals, Inc. Head Neck36: 551-556, 2014

    DOI: 10.1002/hed.23322

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  • Leriche operation for parotid gland pathology

    Yorihisa Orita, Toshiaki Ogawara, Ryutaro Endo, Sayaka Fuji, Kentaro Miki, Misato Hirai, Yohei Noda, Hidenori Marunaka, Tomoyasu Tachibana, Yasuharu Sato, Kazunori Nishizaki

    ACTA OTO-LARYNGOLOGICA   134 ( 4 )   413 - 415   2014年4月

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    記述言語:英語   出版者・発行元:INFORMA HEALTHCARE  

    DOI: 10.3109/00016489.2013.871749

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  • Systemic IgG4-related disease with extensive peripheral nerve involvement that progressed from localized IgG4-related lymphadenopathy: an autopsy case

    Masayoshi Fujii, Yasuharu Sato, Nobuya Ohara, Kenji Hashimoto, Haruhiko Kobashi, Yoshinobu Koyama, Tadashi Yoshino

    DIAGNOSTIC PATHOLOGY   9 ( 1 )   41   2014年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:BIOMED CENTRAL LTD  

    A 77-year-old man, with a lengthy medical history of chronic dysuria, constipation, hypertension, myocardial infarction, and a submandibular lymphadenopathy that was excised 3 years ago, was hospitalized due to elevated liver enzyme levels. He demonstrated hypergammaglobulinemia, hyperproteinemia, high levels of IgG and IgG4, eosinophilia, sclerosing cholangitis, and retroperitoneal fibrosis. He was diagnosed with IgG4-related disease (IgG4-RD). While hospitalized, he had several episodes of syncope while standing and was diagnosed with autonomic nerve dysfunction. Thirty days after hospitalization, he died of nonocclusive mesenteric ischemia (NOMI). Post-mortem, his submandibular lymphadenopathy lesion was diagnosed with progressively transformed germinal center (PTGC)-type IgG4-related lymphadenopathy. At autopsy, small and large intestines showed mucosal necrosis and the wall muscles of the transverse to sigmoid colon were necrotic. The sigmoid colon was fibrotic and infiltrated with numerous IgG4(+) plasma cells and eosinophils; infiltration into Auerbach's plexus was also observed. The IgG4-RD lesions were also detected in the mesentery of the sigmoid colon, retroperitoneal soft tissue, abdominal aorta, liver, extrahepatic bile duct, bilateral lungs, bilateral kidneys, urinary bladder, prostate, epicardium, bilateral coronary arteries, and lymph nodes. Interestingly, infiltration into the lesions was most notable around the peripheral nerves in every organ. Thus, this case describes an IgG4-RD that progressed from PTGC-type IgG4-related lymphadenopathy to systemic IgG4-RD, suggesting that IgG4-RD may affect many organs through peripheral nerve involvement. Virtual slide: The virtual slides for this article can be found here: http://www.diagnosticpathology. diagnomx.eu/ vs/ 9995992971155224.

    DOI: 10.1186/1746-1596-9-41

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  • Lymph node lesions 査読

    Yasuharu Sato, Tadashi Yoshino

    Igg4-Related Disease   187 - 193   2014年1月

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    記述言語:英語   掲載種別:論文集(書籍)内論文   出版者・発行元:Springer Japan  

    Pathological examination of involved tissue occupies an extremely important place in establishing the diagnosis of IgG4-related disease (IgG4-RD). However, the histological picture in IgG4-RD can vary significantly from organ to organ in this disease even while adhering to basic tenets. Consequently, the pathological diagnosis of this condition is often challenging even in the setting of adequate tissue specimens. This is particularly true with regard to the assessment of lymph nodes in patients who may have IgG4-RD. The diagnosis of IgG4-related lymphadenopathy is complicated owing to a great histological diversity. At least five histological subtypes have already been identified. Lymph node biopsies are often performed because of suspicion that the lymphadenopathy might reflect a malignant lymphoma or other lymphoproliferative disorder. In general, if the IgG4+/IgG+ plasma cell ratio is ≥40 %, the possibility of IgG4-RD is high, but cases of patients with diagnosis other than IgG4-RD who fulfill this criterion are well described in the literature. In practice, patients with hyper-interleukin (IL)-6 syndromes such as multicentric Castleman’s disease, rheumatoid arthritis, and other immune-mediated conditions frequently show lymph node involvement and often fulfill the diagnostic criteria for IgG4-RD. For this reason, it is important that the diagnosis of IgG4-RD relies not only on the pathological findings, but be the result of a careful clinicopathologic collaboration that considers the overall clinical context and appropriate serologic (in particular, serum IL-6, C-reactive protein, IgG4 concentration) and radiologic data as well.

    DOI: 10.1007/978-4-431-54228-5_27

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  • IgG4-related disease involving the sclera

    Kyotaro Ohno, Yasuharu Sato, Koh-ichi Ohshima, Katsuyoshi Takata, Midori Ando, Lamia Abd Al-Kader, Noriko Iwaki, Mai Takeuchi, Yorihisa Orita, Tadashi Yoshino

    MODERN RHEUMATOLOGY   24 ( 1 )   195 - 198   2014年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPRINGER  

    A 49-year-old female patient previously treated for scleritis and uveitis-induced cataract in the right eye presented with a subretinal white lesion in the same eye. With a preliminary diagnosis of choroidal tumor, enucleation of the eyeball was performed in accordance with the patient's request. Histologic and immunohistologic examinations were consistent with immunoglobulin G4-related disease. The case demonstrates that it is important to consider IgG4-related disease in the differential diagnosis of an intraocular tumor.

    DOI: 10.3109/14397595.2013.852842

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  • Characteristic ultrasound features of mucosa-associated lymphoid tissue lymphoma of the salivary and thyroid gland

    Yorihisa Orita, Yasuharu Sato, Nobuhiko Kimura, Hidenori Marunaka, Tomoyasu Tachibana, Yasuhiko Yamashita, Hiroyuki Hanakawa, Tadashi Yoshino, Kazunori Nishizaki

    ACTA OTO-LARYNGOLOGICA   134 ( 1 )   93 - 99   2014年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:INFORMA HEALTHCARE  

    Conclusion: The characteristic ultrasound appearance of mucosa-associated lymphoid tissue (MALT) lymphoma of the head and neck provides diagnostic information regarding masses or swellings in the head and neck region. Objectives: There are only a few reports about ultrasound features of malignant lymphoma (ML) of the head and neck. We have noticed that the ultrasound appearances of cases with MALT lymphoma resembled each other even when the appearances of other images like computed tomography were absolutely different. The objective of this study was to delineate the reliability of this characteristic ultrasound appearance of MALT lymphoma of the head and neck. Methods: The ultrasound examinations of 30 patients with histopathologically proven primary ML of the head and neck (15 cases of MALT) were reviewed. The ultrasound results of each case were independently compared to the results of the histopathological examination. Results: Two ultrasound patterns were observed for MALT lymphoma. The first was characterized by a marked hypoechoic area with interspersed linear echogenic strands (linear echogenic strands pattern), and the second was characterized by multiple, relatively large, hypoechoic segments (segmental pattern). Histopathologically, these patterns could be explained on the basis of the expansion of lymphoma cells demarcated by narrow or wide fibrous bands.

    DOI: 10.3109/00016489.2013.831994

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  • Simultaneous immunostaining with anti-S100P and anti-SV40 antibodies revealed the origin of BK virus-infected decoy cells in voided urine samples.

    Ariyasu S, Yanai H, Sato M, Shino Y, Taniguchi K, Yamadori I, Miki Y, Sato Y, Yoshino T, Takahashi K

    Cytopathology   26 ( 4 )   250 - 255   2014年

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  • IgG4-related renal disease: clinical and pathological characteristics

    Naoto Kuroda, Tomoya Nao, Hideo Fukuhara, Takashi Karashima, Keiji Inoue, Yoshinori Taniguchi, Mai Takeuchi, Yoh Zen, Yasuharu Sato, Kenji Notohara, Tadashi Yoshino

    INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL PATHOLOGY   7 ( 9 )   6379 - 6385   2014年

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    記述言語:英語   出版者・発行元:E-CENTURY PUBLISHING CORP  

    IgG4-related disease is a recently established systemic condition. Tubulointerstitial nephritis is the most common renal manifestation. Glomerular lesions, particularly membranous glomerulonephritis, can develop simultaneously. Some patients present with serological renal dysfunction associated with elevated IgG or IgE levels and hypocomplementemia, while others are incidentally found to have abnormalities in kidneys on imaging. A majority of patients with IgG4-related kidney disease have similar lesions at other anatomical sites, which help us to suspect this condition. Serum IgG4 elevation (&gt;135 mg/dL) is the most, although not entirely, specific marker for the diagnosis. Imaging findings varies from small nodules to bilateral diffuse abnormalities. In addition to the renal parenchyma, the renal pelvis and perirenal adipose tissue can be affected. Histological features include dense lymphoplasmacytic infiltration, storiform or "bird's eye" fibrosis (highlighted by PAM stain), and IgG4-positive plasma cell infiltration (&gt;10 cells/high-power field and IgG4/IgG-positive cell ratio &gt;40%). Immune complex deposition is detectable in the tubular basement membrane by immunofluorescence and/or electron microscopy. Patients usually respond well to corticosteroids, but highly active diseases may require other immunosuppressive therapies. Further investigations will be required to fully understand pathophysiology underlying this emerging condition.

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  • Pathology of follicular lymphoma.

    Takata K, Miyata-Takata T, Sato Y, Yoshino T

    Jornal of Clinical Experimental Hematopathology   54 ( 1 )   3 - 9   2014年

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  • A condition closely mimicking IgG4-related disease despite the absence of serum IgG4 elevation and IgG4-positive plasma cell infiltration.

    Hara S, Kawano M, Mizushima I, Yamada K, Fujita K, Harada K, Matsumura M, Yamagishi M, Sato Y, Yamaguchi Y, Nakanuma Y, Nagata M

    Modern Rheumatology   2014年

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  • Time-lag between symptom onset and laboratory findings in patients with subacute thyroiditis 査読

    Tachibana T, Orita Y, Ogawara Y, Matsuyama Y, Abe I, Nakada M, Sato Y, Nishizaki K

    Auris Nasus Larynx   41 ( 4 )   369 - 372   2014年

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    掲載種別:研究論文(学術雑誌)  

    Objective: The objective of this study was to delineate the frequency of delayed diagnosis in cases of subacute thyroiditis (SAT) and intervals between onset of clinical symptoms and appearance of abnormal laboratory findings. Methods: We reviewed the medical records of 27 patients (7 men and 20 women) with SAT who visited our hospital between 2007 and 2013. Results: On presentation to the hospital, 5 of 27 SAT cases (18.5%) showed normal laboratory findings. Among these 5 cases, the mean interval between symptom onset and thyrotropin (TSH) suppression was 6.3 weeks, and the mean interval to elevation of fT4 was 6.7 weeks. The longest interval from symptom onset to appearance of an abnormal laboratory finding was 11 weeks. Conclusion: Sometimes time-lag exists between onset of clinical symptoms and the appearance of abnormal laboratory findings in patients with SAT. The possibility of this disease should not be excluded from the differential diagnoses for patients with clinical symptoms consistent with SAT but showing normal laboratory findings. © 2013 Elsevier Ireland Ltd.

    DOI: 10.1016/j.anl.2013.11.003

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  • Mucosa-associated lymphoid tissue lymphoma of the thyroid with abundant IgG4-positive plasma cells

    Kentaro Miki, Yorihisa Orita, Yasuharu Sato, Iwao Sugitani, Misato Noyama, Sayaka Fuji, Shuhei Domae, Soichiro Nose, Kazuo Hamaya, Tadashi Yoshino, Kazunori Nishizaki

    AURIS NASUS LARYNX   40 ( 6 )   587 - 590   2013年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER SCI LTD  

    A case of thyroidal mucosa-associated lymphoid tissue (MALT) lymphoma mimicking IgG4-related disease is described. A 54-year-old male presented with acute swelling of the anterior neck. Anaplastic thyroid carcinoma (ATC), malignant lymphoma (ML), or acute deterioration of Hashimoto's thyroiditis were initially suspected, and an emergent tracheostomy was required for progressive airway obstruction; a simultaneous biopsy from the thyroid tissue was performed. Histopathologically, the lesion consisted of sclerotic fibrosis and diffuse and dense infiltration by small lymphoid cells without atypia and plasma cells, many of which were IgG4-positive. Blood examination also revealed high serum IgG4 levels. Riedel's thyroiditis was suspected. However, despite medical treatments, a firm swelling of the thyroid still remained. In an in situ hybridization study, IgG4-negative plasma cells showed immunoglobulin light-chain restriction (kappa-monotype), and immunoglobulin heavy (IgH) chain gene monoclonal re-arrangement was detected by polymerase chain reaction. The lesion was finally diagnosed as MALT lymphoma. When IgG4-related disease is suspected, it is important to thoroughly exclude other possibilities. (C) 2013 Elsevier Ireland Ltd. All rights reserved.

    DOI: 10.1016/j.anl.2012.12.004

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  • Cutting needle biopsy combined with imrnunohistochemical study of myeloperoxidase for the diagnosis of histiocytic necrotizing lymphadenitis

    Hiroyuki Hanakawa, Yorihisa Orita, Yasuharu Sato, Mai Takeuchi, Kyotaro Ohno, Noriko Iwaki, Toshihiro Ito, Kazunori Nishizaki, Tadashi Yoshino

    ACTA OTO-LARYNGOLOGICA   133 ( 12 )   1328 - 1332   2013年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:INFORMA HEALTHCARE  

    Conclusion: Cutting needle biopsy (CNB) combined with immunohistochemical study of myeloperoxidase (MPO) is a useful minimally invasive diagnostic procedure for histiocytic necrotizing lymphadenitis (HNL). Objectives: HNL is mainly diagnosed by pathological findings of open surgical biopsy (OSB) specimens. Recently the appearance of anti-MPO positive histiocytes has been reported as a highly specific pathological diagnosis for HNL. Considering the cosmetic impact and burden on the patients, we performed CNB combined with immunohistochemical study of MPO for the diagnosis of HNL. Few studies have reported the utility of this method in the diagnosis of HNL. Methods: A retrospective study was conducted using clinical data from 20 HNL patients. Results: CNB was performed in 8 patients and OSB in 13 (OSB after CNB in 1). MPO-positive histiocytes were observed in all of the 20 cases. The accuracy of the diagnoses was finally confirmed by the clinical courses in all cases.

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  • Factors that make it difficult to diagnose cervical tuberculous lymphadenitis

    Tomoyasu Tachibana, Yorihisa Orita, Masayoshi Fujisawa, Michihiro Nakada, Yuya Ogawara, Yuko Matsuyama, Iku Abe, Yasuharu Sato, Koichi Uesaka, Kazunori Nishizaki

    JOURNAL OF INFECTION AND CHEMOTHERAPY   19 ( 6 )   1015 - 1020   2013年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPRINGER JAPAN KK  

    Cervical tuberculous lymphadenitis is mainly diagnosed by analyzing tissue samples obtained by fine-needle aspiration (FNA). However, some cases remain diagnostic challenges even after polymerase chain reaction analysis of FNA specimens. To delineate differences between cases that are relatively easy to diagnose and those for which diagnosis is difficult, 22 patients with cervical tuberculous lymphadenitis were studied retrospectively. FNA tissues were used to diagnose 14 cases (group A), whereas excisional biopsy was required for accurate diagnosis of 8 cases (group B). These two groups were compared with regard to results of blood examinations, ultrasound appearance, and various other procedures required to reach the final diagnosis. The results indicated that diagnosis of cervical tuberculous lymphadenitis was more difficult for patients with lower white blood cell counts, lower serum C-reactive protein levels, and absence of lymph node fusion or abscess formation on ultrasonography. The possibility of tuberculosis as a cause of cervical lymphadenopathy should always be considered, even when the presenting symptoms are not typical of this disease.

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  • Nestin is a wide-spectrum abluminal cell marker of salivary gland tumors

    Hiroyuki Yanai, Yasuharu Sato, Hitoshi Nagatsuka, Tadashi Yoshino

    PATHOLOGY INTERNATIONAL   63 ( 10 )   496 - 501   2013年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-BLACKWELL  

    Nestin is an intermediate filament that was first identified in neural progenitor cells. It is expressed in various cell types in the nervous system as well as in other systems. In the present study, we investigated nestin expression in non-neoplastic salivary gland tissue and in salivary gland tumors. In non-neoplastic salivary glands, nestin expression was observed in only a few abluminal cells. In contrast, diffuse nestin staining was observed in the abluminal cells of pleomorphic adenoma (11 of 11 cases), basal cell adenoma (7 of 7 cases), and epithelial-myoepithelial carcinoma (2 of 2 cases). The stromal cells in basal cell adenoma also expressed nestin. In adenoid cystic carcinoma (6 of 7 cases) and polymorphous low-grade adenocarcinoma (3 of 3 cases), nestin positive cells were observed focally. Nestin was not detected in Warthin tumor (6 cases), classical acinic cell carcinoma (2 cases), mucoepidermoid carcinoma (5 cases), or salivary duct carcinoma (4 cases). Because the nestin expression pattern in each histological salivary gland tumor type is unique, nestin could be a very useful abluminal cell marker for the diagnosis of salivary gland tumors.

    DOI: 10.1111/pin.12103

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  • B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and classical Hodgkin lymphoma without mediastinal disease: mimicking nodular sclerosis classical Hodgkin lymphoma

    Noriko Iwaki, Yasuharu Sato, Toshiro Kurokawa, Yoshinobu Maeda, Kyotaro Ohno, Mai Takeuchi, Katsuyoshi Takata, Yorihisa Orita, Shinji Nakao, Tadashi Yoshino

    MEDICAL MOLECULAR MORPHOLOGY   46 ( 3 )   172 - 176   2013年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPRINGER JAPAN KK  

    B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and classical Hodgkin lymphoma (BCLu-DLBCL/CHL), also known as gray-zone lymphoma, has overlapping clinical and biological characteristics of both diffuse large B-cell lymphoma and classical Hodgkin lymphoma (CHL). These lymphomas are typically associated with mediastinal disease, and extranodal involvement is rare. In the present report, we describe a case of a 78-year-old woman with BCLu-DLBCL/CHL found to have extranodal lesions and no evidence of mediastinal disease. Although biopsy specimens were histologically similar to nodular sclerosis CHL, the tumor cells were positive for CD30 and mature B-cell markers, such as CD20, CD79a, PAX5, BOB.1, and OCT-2, but negative for CD15. Furthermore, the patient had extranodal lesions and an increased level of soluble IL-2 receptor. These findings are unusual in CHL. Therefore, we diagnosed the patient with BCLu-DLBCL/CHL. She received adriamycin, bleomycin, vincristine, and dacarbazine therapy and exhibited partial response. Some cases without mediastinal disease, such as our case, have been reported; however, these cases are rare and further studies are required.

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  • Distinct morphologic, phenotypic, and clinical-course characteristics of indolent peripheral T-cell lymphoma

    Eiko Hayashi, Katsuyoshi Takata, Yasuharu Sato, Yukie Tashiro, Yoshiro Tachiyama, Seiko Sawada-Kitamura, Yasushi Hiramatsu, Shun Sugiguchi, Soichiro Nose, Mitsuyoshi Hirokawa, Midori Ando, Lamia Abd Mader, Yoshinobu Maeda, Mitsune Tanimoto, Tadashi Yoshino

    HUMAN PATHOLOGY   44 ( 9 )   1927 - 1936   2013年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:W B SAUNDERS CO-ELSEVIER INC  

    Peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) consists of a heterogeneous group of lymphomas. Patients. generally show an aggressive clinical course and very poor outcome. Although the 2008 World Health Organization classification of PTCL-NOS includes 3 variants, low-grade lymphoma is not Included. Of 277 PTCL-NOS cases recorded in our consultation files, we examined the clinicopathologic characteristics of 10 patients with T-cell lymphomas composed of small-sized cells with slight nuclear atypia. Eight patients showed extranodal involvement (5 patients, spleen; 3 patients, thyroid), and 5 patients were at clinical stage I or II. Histologically, all samples presented diffuse infiltrate of small lymphoid cells, with few mitotic figures. Immunohistologically, all samples were positive for CD3, and CD:20 Was detected in 5 samples. All samples showed a low Ki-67 labeling index (mean, 1.05%), and 7 samples were positive for central memory T-cell markers. Clonal T-cell receptor gamma chain and/or alpha-beta chain gene rearrangements were detected in all 10 patients. Five patients received chemotherapy, whereas for 3 patients, treatment consisted only of observation following surgical resection of the spleen or thyroid. Nine patients were alive at a median follow-up time of 19.5 months, whereas 1 patient died of an unrelated disease. The present study strongly indicates that T-cell lymphoma with small-sized lymphoma cells and a low Ki-67 labeling index is a distinct variant. Recognition of this novel lymphoma subtype, which should not be defined merely as PTCL-NOS, should be seriously considered. Crown Copyright (C) 2013 Published by Elsevier Inc. All rights reserved.

    DOI: 10.1016/j.humpath.2013.03.002

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  • Large Ulceration of the Oropharynx Induced by Methotrexate-Associated Lymphoproliferative Disorders

    Hiroyuki Hanakawa, Yorihisa Orita, Yasuharu Sato, Kinya Uno, Kazunori Nishizaki, Tadashi Yoshino

    ACTA MEDICA OKAYAMA   67 ( 4 )   265 - 269   2013年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:OKAYAMA UNIV MED SCHOOL  

    We present a case of a 67-year-old Japanese man with a serious oropharyngeal ulceration that at first seemed to be destructive malignant lymphoma or oropharyngeal carcinoma. We suspected methotrexate (MTX)-associated lymphoproliferative disorder (LPD) induced by MTX treatment for rheumatoid arthritis (RA). About 3 weeks after simple discontinuation of MTX, complete regression of the disease was observed, confirming our diagnosis.

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  • 十二指腸濾胞性リンパ腫はAIDの発現を欠くがBACH2の発現を有しmemory B細胞としての性質を有する

    高田 尚良, 佐藤 康晴, 中村 直哉, 徳中 摩美, 三木 由香里, 菊池 イアーラ幸江, 五十嵐 和彦, 伊藤 悦郎, 張替 秀雄, 加藤 省一, 林 詠子, 岡 剛史, 星井 嘉信, 田利 晶, 岡田 裕之, Mohamad Abd Alkader Lamia, 前田 嘉信, 谷本 光音, 木下 朝博, 吉野 正

    岡山医学会雑誌   125 ( 2 )   103 - 107   2013年8月

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    記述言語:日本語   出版者・発行元:岡山医学会  

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  • Duodenal follicular lymphoma lacks AID but expresses BACH2 and has memory B-cell characteristics (vol 26, pg 22, 2013)

    Katsuyoshi Takata, Yasuharu Sato, Naoya Nakamura, Mami Tokunaka, Yukari Miki, Yara Yukie Kikuti, Kazuhiko Igarashi, Etsuro Ito, Hideo Harigae, Seiichi Kato, Eiko Hayashi, Takashi Oka, Yoshinobu Hoshii, Akira Tari, Hiroyuki Okada, Lamia Abd Al-Kader, Yoshinobu Maeda, Mitsune Tanimoto, Tomohiro Kinoshita, Tadashi Yoshino

    MODERN PATHOLOGY   26 ( 8 )   1152 - 1152   2013年8月

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    記述言語:英語   出版者・発行元:NATURE PUBLISHING GROUP  

    DOI: 10.1038/modpathol.2013.118

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  • De novo CD5-positive diffuse large B-cell lymphomas show high specificity for cyclin D2 expression

    Takuro Igawa, Yasuharu Sato, Katsuyoshi Takata, Noriko Iwaki, Takehiro Tanaka, Naoko Asano, Yoshinobu Maeda, Yorihisa Orita, Naoya Nakamura, Shigeo Nakamura, Tadashi Yoshino

    DIAGNOSTIC PATHOLOGY   8 ( 1 )   81   2013年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:BIOMED CENTRAL LTD  

    D cyclins positively regulate the cell cycle and mediate the pathogenesis of some lymphomas. Cyclin D1 overexpression is the hallmark of mantle cell lymphoma, whereas cyclins D2 and D3 are reportedly not as specific to certain lymphomas as cyclin D1. In this study, cyclin D2 was found to be overexpressed in 98% of de novo CD5-positive diffuse large B-cell lymphomas (DLBCLs) (50/51) and in 28% of CD5-negative DLBCLs (14/51). A statistically significant difference was observed between these two groups (p&lt;0.0001). In contrast, no statistical difference was found in the cyclin D3 expression between CD5-positive (18/51) and CD5-negative (24/51) DLBCLs (p=0.23). Based on these findings, cyclin D2 is therefore considered to be closely associated with de novo CD5-positive DLBCLs. This insight may be useful for overcoming the inferior survival of this aggressive lymphoma. Virtual slides: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1382856320966453

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  • Clinicopathologic analysis of IgG4-related skin disease

    Yasuharu Sato, Mai Takeuchi, Katsuyoshi Takata, Kyotaro Ohno, Noriko Iwaki, Yorihisa Orita, Naoe Goto, Akira I. Hida, Toshiyuki Iwamoto, Naoko Asano, Toshihiro Ito, Hiroyuki Hanakawa, Hiroyuki Yanai, Tadashi Yoshino

    Modern Pathology   26 ( 4 )   523 - 532   2013年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    IgG4-related disease is a recently recognized systemic syndrome characterized by mass-forming lesions with lymphoplasmacytic infiltration, increase in the number of IgG4 + cells in affected tissues and elevation of serum IgG4 levels. In 2009, we were the first to report skin lesions in patients with IgG4-related disease, but no large case series has been reported and clinicopathological findings remain unclear. To clarify these features, we herein report 10 patients (9 men and 1 woman
    median age, 64 years
    age range, 46-81 years) with IgG4-related skin disease. All patients had erythematous and itchy plaques or subcutaneous nodules on the skin of the head and neck, particularly in the periauricular, cheek, and mandible regions, except for one patient, whose forearm and waist skin were affected. In addition, eight patients had extracutaneous lesions: these were found on the lymph nodes in six patients, the lacrimal glands in three patients, the parotid glands in three patients, and the kidney in one patient. Histologically examined extracutaneous lesions were consistent with IgG4-related disease
    five of six lymph node lesions showed progressively transformed germinal centers-type IgG4-related lymphadenopathy. Cases of IgG4-related skin disease were classified into two histological patterns: those exhibiting a nodular dermatitis pattern and those with a subcutaneous nodule pattern. The infiltrate was rich in plasma cells, small lymphocytes, and eosinophils
    the majority of the plasma cells were IgG4 +. The IgG4 + cell count was 49-396 per high-power field (mean±s.d., 172±129), with an IgG4 +/IgG + cell ratio ranging from 62 to 92%. Serum IgG4 levels were elevated in all examined patients. In conclusion, patients with IgG4-related skin disease had uniform clinicopathology. Lesions were frequently present on the skin of the periauricular, cheek, and mandible regions, and were frequently accompanied by IgG4-related lymphadenopathy. © 2013 USCAP, Inc. All rights reserved.

    DOI: 10.1038/modpathol.2012.196

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  • Clinicopathologic Analysis of Localized Nasal/Paranasal Diffuse Large B-Cell Lymphoma

    Hiroko Toda, Yasuharu Sato, Katsuyoshi Takata, Yorihisa Orita, Naoko Asano, Tadashi Yoshino

    PLoS ONE   8 ( 2 )   e57677   2013年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Diffuse large B-cell lymphoma (DLBCL) comprises 2 molecularly distinct subgroups of non-germinal center B-cell-like (non-GCB) and germinal center B-cell-like (GCB) DLBCLs, with the former showing relatively poor prognosis. In the present study, we analyzed the clinicopathological features of 39 patients with localized nasal/paranasal DLBCL. Immunohistochemistry-based subclassification revealed that 11 patients (28%) were of the GCB-type according to Hans' algorithm and 11 (28%) were of the GCB-type according to Choi's algorithm. According to both Hans' and Choi's algorithms, the non-GCB type was predominant. Nevertheless, prognosis was good. Overall survival did not differ significantly between the GCB and non-GCB subgroups (Hans' algorithm: p = 0.57, Choi's algorithm: p = 0.99). Furthermore, the prognosis of localized nasal/paranasal DLBCL was better than that of other localized extranodal DLBCLs. The prognosis of extranodal DLBCL is usually considered poorer than that of nodal DLBCL. However, in our study, no difference was noted between patients with localized nasal/paranasal DLBCL and patients with localized nodal DLBCL. In conclusion, although the non-GCB subtype is thought to show poor prognosis, in our study, the prognosis for localized nasal/paranasal DLBCL patients was good irrespective of subclassification. © 2013 Toda et al.

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  • Elevated serum interferon γ-induced protein 10 kDa is associated with TAFRO syndrome 査読

    Iwaki N, Gion Y, Kondo E, Kawano M, Masunari T, Moro H, Nikkuni K, Takai K, Hagihara M, Hashimoto Y, Yokota K, Okamoto M, Nakao S, Yoshino T, Sato Y

    Scientific Report   13 ( 7 )   42316 - 42323   2013年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

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  • Ectopic hamartomatous thymoma is distinct from lipomatous pleomorphic adenoma in lacking PLAG1 aberration

    Peir-In Liang, Chien-Feng Li, Yasuharu Sato, Victor Kwan Min Lee, Armita Bahrami, Shih-Sung Chuang

    Histopathology   62 ( 3 )   518 - 522   2013年2月

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  • Duodenal follicular lymphoma lacks AID but expresses BACH2 and has memory B-cell characteristics

    Katsuyoshi Takata, Yasuharu Sato, Naoya Nakamura, Mami Tokunaka, Yukari Miki, Yara Yukie Kikuti, Kazuhiko Igarashi, Etsuro Ito, Hideo Harigae, Seiichi Kato, Eiko Hayashi, Takashi Oka, Yoshinobu Hoshii, Akira Tari, Hiroyuki Okada, Abd Alkader Lamia Mohamad, Yoshinobu Maeda, Mitsune Tanimoto, Tomohiro Kinoshita, Tadashi Yoshino

    Modern Pathology   26 ( 1 )   22 - 31   2013年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    We have reported previously that duodenal follicular lymphoma (FL) is distinct from nodal FL and showed more resemblance to mucosa-associated lymphoid tissue lymphoma, and that FL frequently involved the duodenal second portion. In the present study, we examined duodenal FLs and gastric/colonic FLs to clarify the clinicopathological and immunological differences between the tumor types. We analyzed 8 samples of gastric FL, 17 of duodenal ones, and 5 of colonic/rectal ones, and characterized them by immunohistochemistry, immunogenotyping, and histology. Gastric and colonic FLs presented in submucosal to subserosal areas, whereas duodenal ones presented in the mucosal to submucosal layers. Immunohistochemical analysis revealed that duodenal FLs exhibited the following phenotypes: CD10 (+), B-cell lymphoma 2 (BCL-2) (+), BCL-6 (+), activation-induced cytidine deaminase (AID) (-), BACH2 (+), CD27 (+), MUM-1 (-), Blimp-1 (-), and loose CD21 network (duodenal pattern). Gastric/colonic FLs exhibited the following phenotypes: CD10 (+), BCL-2 (+), BCL-6 (+), AID (+), BACH2 (+), CD27 (-), MUM-1 (-), Blimp-1 (-), and a dense CD21 network (nodal pattern). Expression of AID and CD27 in lymphoma cells and the CD21 network pattern were considerably different between duodenal FLs and gastric/colonic ones. Moreover, in situ hybridization revealed that, in the duodenal FLs, BACH2 was expressed at the periphery of the tumor follicle and tumor villi. The number of immunoglobulin heavy-chain variable domains VH4 and VH5 were higher in duodenal follicular lymphomoas than in gastric FLs. The lymphoma cells of duodenal FLs are different from those of gastric/colonic FLs, and duodenal FL is distinct even within the gastrointestinal tract. Somatic hypermutation in immunoglobulin genes and CD27 expression are hallmarks of memory B cells. We suggest that duodenal FL cells are in the memory B-cell stage, and require BACH2 instead of AID for ongoing mutation. © 2013 USCAP, Inc.

    DOI: 10.1038/modpathol.2012.127

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  • Cervical lymph node extirpation for the diagnosis of malignant lymphoma

    Yorihisa Orita, Soichiro Nose, Yasuharu Sato, Kentaro Miki, Shuhei Domae, Misato Hirai, Yasuyuki Noyama, Kazuo Hamaya, Norio Kasai, Kazunori Nishizaki, Tadashi Yoshino

    SURGERY TODAY   43 ( 1 )   67 - 72   2013年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPRINGER  

    Lymph node enlargement in the neck is a common presentation of malignant lymphoma (ML) and requires tissue sampling for accurate diagnosis. Although delayed diagnosis may be critical for some patients, unnecessary biopsy should be avoided wherever possible. This study examined the process for determining the necessity to perform a biopsy and evaluated the value of an open biopsy as a diagnostic tool to enable definite subclassification of the disease.
    The subjects included 20 patients with suspected ML who underwent cervical lymph node extirpation at Okayama Saiseikai general hospital between 2007 and 2010. The decision to perform a biopsy was made based on the results of sonographic evaluation, fine needle aspiration cytology (FNAC), and serum levels of lactate dehydrase (LDH) and soluble interleukin-2 receptor (sIL-2r).
    The diagnosis was ML in 15 patients (75%), Castleman's disease in 1 (5%), and benign lymphadenopathy in 4 (20%).
    A lymph node biopsy remains the gold standard for the diagnostic evaluation of ML. Sonographic evaluation combined with serum levels of LDH and sIL-2r is useful in determining the need for biopsy. Many of the cases of ML where it was difficult to determine whether a biopsy should be performed were relatively low grade and critical conditions could be avoided by close observation of the patient.

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  • Usefulness of immunoglobulin light-chain restriction on immunocytochemical double staining for the cytological diagnosis of B cell non-Hodgkin’s lymphoma

    Shimoura Y, Sato Y, Takata K, Orita Y, Nakamura S, Mano S, Yoshino T

    Acta Cytologica   57 ( 1 )   84 - 90   2013年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1159/000342475

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  • Atypical hyaline vascular-type Castleman’s disease with thrombocytopenia, anasarca, fever, and systemic lymphadenopathy. 査読

    Iwaki N, Sato Y, Takata K, Kondo E, Ohno K, Takeuchi M, Orita Y, Nakao S, Yoshino T

    J Clin Exp Hematop   53 ( 1 )   87 - 93   2013年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.3960/jslrt.53.87

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  • Time-lag between symptom onset and laboratory findings in patients with subacute thyroiditis.

    Tachibana T, Orita Y, Ogawara Y, Matsuyama Y, Abe I, Nakada M, Sato Y, Nishizaki K

    Auris Nasus Larynx   54 ( 1 )   3 - 9   2013年

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  • A case of IgG4-related dacryoadenitis that regressed without systemic steroid administration.

    Ohshima K, Sato Y, Yoshino T

    Jornal of Clinical Experimental Hematopathology   53 ( 1 )   53 - 56   2013年

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    記述言語:英語   出版者・発行元:The Japanese Society for Lymphoreticular Tissue Research  

    There are no reports on the effect of anti-allergic agents against IgG4-related disease. We herein report a case of IgG4-related dacryoadenitis that is believed to have regressed due to the administration of anti-allergic agents. A 57-year-old woman consulted us because of bilateral temporal upper eyelid swelling and induration. She had also been suffering from allergic rhinitis and allergic conjunctivitis for 20 years. We performed an incisional biopsy of the lesion. With respect to the pathology, extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue type was strongly suspected. On obtaining consent from the patient, follow-up alone was to be continued without radiation therapy. In addition to the observation of lacrimal gland lesions, the administration of epinastine hydrochloride at a dosage of 20 mg/day and 0.01% betamethasone eye drops twice a day to both eyes was commenced in order to treat both allergic rhinitis and allergic conjunctivitis. The lacrimal gland lesion decreased in size over time, becoming predominantly normal 7 years after the commencement of agent administration. We therefore re-examined the blood and pathology specimens. As a result, the serum IgG4 level was found to have increased to 540 mg/dl, while IgG4/IgG was 36.2%. The pathological diagnosis was revised to IgG4-related dacryoadenitis. The hypotheses of spontaneous remission and/or the effect of epinastine hydrochloride administration can be proposed regarding the mechanism by which the lacrimal gland lesion decreased in size. [J Clin Exp Hematop 53(1): 53-56, 2013]

    DOI: 10.3960/jslrt.53.53

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  • A case of conjunctival follicular lymphoma mimicking mucosa-associated lymphoid tissue lymphoma.

    Lamia AA, Sato Y, Takata K, Ohshima K, Sogabe Y, Fujii K, Iwaki N, Yoshino T

    Jornal of Clinical Experimental Hematopathology   53 ( 1 )   49 - 52   2013年

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    記述言語:英語   出版者・発行元:The Japanese Society for Lymphoreticular Tissue Research  

    Ocular adnexal lymphoma may involve the eyelids, conjunctiva, orbital tissue, or lacrimal structures. The majority are non-Hodgkin's B-cell lymphomas of mucosa-associated lymphoid tissue (MALT) lymphoma type. Follicular lymphomas represent a small percentage of ocular adnexa lymphomas, particularly in Japan. We report a 68-year-old female patient who presented with a salmon pink patch-like lesion of the left conjunctiva, suspected of being (MALT) lymphoma. However, histologic and immunohistologic examinations were consistent with follicular lymphoma. This case demonstrates the importance of considering such rare lymphomas when making a diagnosis of ocular adnexal lymphoid neoplasms. [J Clin Exp Hematop 53(1): 49-52, 2013]

    DOI: 10.3960/jslrt.53.49

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  • A20 (TNFAIP3) deletion in Epstein-Barr virus-associated lymphoproliferative disorders/lymphomas. 国際誌

    Midori Ando, Yasuharu Sato, Katsuyoshi Takata, Junko Nomoto, Shigeo Nakamura, Koichi Ohshima, Tamotsu Takeuchi, Yorihisa Orita, Yukio Kobayashi, Tadashi Yoshino

    PloS one   8 ( 2 )   e56741   2013年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    A negative regulator of the nuclear factor (NF)-κB pathway, A20 (TNFAIP3), is inactivated in several types of lymphomas; particularly in diffuse large B-cell lymphoma (DLBCL), classical Hodgkin's lymphoma, and extranodal marginal zone lymphoma of the mucosa-associated lymphoid tissue. These findings suggest that the NF-κB activation is related to A20 inactivation. Recently, A20 inactivation has also been observed in Epstein-Barr virus (EBV)-related lymphomas; however, this occurrence has not been well investigated. Moreover, NF-κB is a key molecule in activated B-cell-like (ABC)-type DLBCL; EBV-associated DLBCL is of the ABC type. Therefore, we focused on A20 deletions in EBV-associated lymphoproliferative disorders/lymphomas. Using fluorescent in situ hybridization analysis, A20 deletions were identified in 4 of 13 samples from patients with pyothorax-associated lymphoma (PAL) (31%), 3 of 20 samples from nasal-type NK/T cell lymphomas (NKTLs) (15%), 1 of 8 samples of EBV-positive DLBCL of the elderly (DLBCL-e) (13%), but not in any of the 11 samples from individuals with methotrexate-related lymphoproliferative disorder (MTX-LPD) (0%). Among the samples with A20 deletions, EBV latent membrane protein 1 (LMP-1) expression was detected in all 4 of the PAL samples with A20 deletions and in the DLBCL-e sample with an A20 deletion, but not in any of the 3 NKTL samples. This finding indicated that A20 deletions were not directly related to the EBV latency pattern of lymphomas, although such deletions might be related to the diagnostic category. Immunohistologically, the A20 protein was absent in 2 (15%) of the 13 PAL samples, 1 (9%) of 11 MTX-LPD samples, and in none of the 20 NKTL (0%) or 8 DLBCL-e samples. In conclusion, A20 deletion and/or dysfunctional expression are frequently associated with PALs, and A20 abnormalities may be related to the pathogenesis of PAL.

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  • Clinicopathological characteristics of human epidermal growth factor receptor 2-positive Barrett’s adenocarcinoma.

    Tanaka T, Fujimura A, Ichimura K, Yanai H, Sato Y, Takata K, Okada H, Kawano S, Tanabe S, Yoshino T

    World Journal of Gastroenterology   18 ( 43 )   6263 - 6268   2012年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

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  • Recommendations for the nomenclature of IgG4-related disease and its individual organ system manifestations

    John H. Stone, Arezou Khosroshahi, Vikram Deshpande, John K. C. Chan, J. Godfrey Heathcote, Rob Aalberse, Atsushi Azumi, Donald B. Bloch, William R. Brugge, Mollie N. Carruthers, Wah Cheuk, Lynn Cornell, Carlos Fernandez-Del Castillo, Judith A. Ferry, David Forcione, Guenter Kloeppel, Daniel L. Hamilos, Terumi Kamisawa, Satomi Kasashima, Shigeyuki Kawa, Mitsuhiro Kawano, Yasufumi Masaki, Kenji Notohara, Kazuichi Okazaki, Ji Kon Ryu, Takako Saeki, Dushyant Sahani, Yasuharu Sato, Thomas Smyrk, James R. Stone, Masayuki Takahira, Hisanori Umehara, George Webster, Motohisa Yamamoto, Eunhee Yi, Tadashi Yoshino, Giuseppe Zamboni, Yoh Zen, Suresh Chari

    ARTHRITIS AND RHEUMATISM   64 ( 10 )   3061 - 3067   2012年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-BLACKWELL  

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  • Consensus statement on the pathology of IgG4-related disease. (共著)

    Modern Pathology   25 ( 9 )   1181 - 1192   2012年9月

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  • Pathological findings of infraorbital nerve enlargement in IgG4-related ophthalmic disease

    Yuka Sogabe, Katsuya Miyatani, Rieko Goto, Gengo Ishii, Koh-ichi Ohshima, Yasuharu Sato

    JAPANESE JOURNAL OF OPHTHALMOLOGY   56 ( 5 )   511 - 514   2012年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPRINGER JAPAN KK  

    We report a case of bilateral infraorbital nerve enlargement (IONE) associated with immunoglobulin (Ig)G4-related ophthalmic disease and describe the associated histopathologic findings.
    An otherwise healthy 59-year-old man presented with bilateral exophthalmos and right visual disturbance. Orbital magnetic resonance imaging showed bilateral IONE and a soft tissue mass in the right orbit. Excisional biopsy in the left infraorbital canal was performed. Histopathologic assessment revealed IgG4-related disease involving the epineurium of the infraorbital nerve. The patient received systemic steroid therapy, to which he responded well.
    IONE in IgG4-related ophthalmic disease is due to IgG4-related disease involving the epineurium.

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  • The usefulness of infraorbital nerve enlargement on MRI imaging in clinical diagnosis of IgG4-related orbital disease

    Koh-ichi Ohshima, Yuka Sogabe, Yasuharu Sato

    JAPANESE JOURNAL OF OPHTHALMOLOGY   56 ( 4 )   380 - 382   2012年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPRINGER TOKYO  

    To investigate the frequency of infraorbital nerve enlargement (IONE) in orbital lymphoproliferative disorders, and to show that IONE can contribute to the clinical diagnosis of IgG4-related orbital diseases (IgG4-ROD).
    71 cases in which orbital lymphoproliferative disorders were diagnosed at Okayama Medical Center and Mitoyo General Hospital from April, 2004 to March, 2011 were investigated. The male-to-female ratio was 39:32, and the age range 27-87 years old (average age 64.1 years). Whenever the coronal section of the infraorbital nerve was larger than that of the optic nerve on MRI, it was defined as IONE.
    The breakdown of the 71 cases was: 45 cases of non-Hodgkin lymphoma, 16 cases of IgG4-ROD, 5 cases of reactive lymphoid hyperplasia, and 5 cases of idiopathic orbital inflammation. Of these, a total of 9 cases had IONE. The incidence of IONE was compared between the IgG4-ROD patient group and the non-IgG4-ROD patient group and was significantly higher in the IgG4-ROD patient group (p &lt; 0.0001).
    If IONE is observed in a case of orbital lymphoproliferative disorders on MRI, then it is highly possible that such a case is IgG4-ROD.

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  • Association between IgG4-related disease and progressively transformed germinal centers of lymph nodes

    Yasuharu Sato, Dai Inoue, Naoko Asano, Katsuyoshi Takata, Hideki Asaoku, Yoshinobu Maeda, Toshiaki Morito, Hirokazu Okumura, Shin Ishizawa, Shoko Matsui, Takayoshi Miyazono, Tamotsu Takeuchi, Naoto Kuroda, Yorihisa Orita, Kiyoshi Takagawa, Masaru Kojima, Tadashi Yoshino

    MODERN PATHOLOGY   25 ( 7 )   956 - 967   2012年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:NATURE PUBLISHING GROUP  

    Progressively transformed germinal centers is a benign condition of unknown pathogenesis characterized by a distinctive variant form of reactive follicular hyperplasia in lymph nodes. We recently reported Ig G4-related disease in progressively transformed germinal centers. However, no large case series has been reported and clinicopathologic findings remain unclear. Here, we report 40 Japanese patients (28 men, 12 women; median age, 56 years) with progressively transformed germinal centers of the lymph nodes who fulfilled the histological diagnostic criteria for IgG4-related disease (IgG4(+) progressively transformed germinal centers), with asymptomatic localized lymphadenopathy involving the submandibular nodes in 24, submandibular and cervical nodes in 14, cervical nodes only in 1, and cervical and supraclavicular nodes in 1. In all, 16 (52%) of 31 examined patients had allergic disease. Histologically, the lymph nodes demonstrated uniform histological findings, namely marked follicular hyperplasia with progressively transformed germinal centers, and localization of the majority of IgG4(+) plasma cells in the germinal centers. Serum IgG4, serum IgE and peripheral blood eosinophils were elevated in 87%, 92% and 53% of examined patients, respectively. Eighteen patients subsequently developed extranodal lesions (including five who developed systemic disease), which on histological examination were consistent with IgG4-related disease. IgG4(+) progressively transformed germinal centers presents with uniform clinicopathological features of asymptomatic localized submandibular lymphadenopathy, which persists and/or relapses, and sometimes progresses to extranodal lesions or systemic disease. Nine patients were administered steroid therapy when the lesions progressed, to which all responded well. We suggest that IgG4+ progressively transformed germinal centers should be included in the IgG4-related disease spectrum. Modern Pathology (2012) 25, 956-967; doi:10.1038/modpathol.2012.54; published online 6 April 2012

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  • Minimally Invasive Procedure for Accurate Diagnosis of Mucosa-associated Lymphoid Tissue Lymphoma of the Head and Neck

    Yorihisa Orita, Yasuharu Sato, Eisei Kondo, Hisashi Ishihara, Haruka Hirai, Hiroyuki Hanakawa, Tomoo Onoda, Takuro Igawa, Ryusuke Saito, Kazunori Nishizaki, Tadashi Yoshino

    JAPANESE JOURNAL OF CLINICAL ONCOLOGY   42 ( 4 )   325 - 330   2012年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:OXFORD UNIV PRESS  

    Sonography-guided cutting needle biopsy for the diagnosis of malignant lymphoma has recently come into wide use. However, surgery is sometimes unavoidable for the diagnosis of malignant lymphoma, particularly for low-grade malignant lymphoma such as extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue, because cutting needle biopsy offers limited diagnostic accuracy for low-grade malignant lymphoma. Of course, unnecessary invasive procedures like open biopsy should be avoided wherever possible, given the cosmetic problems and burden on the patient. We tried to diagnose malignant lymphoma using the combination of cutting needle biopsy, flow cytometry and polymerase chain reaction to identify monoclonal rearrangement of immunoglobulin heavy chain genes. We have used this method in two cases in whom malignant lymphoma was suspected in the head and neck region, allowing diagnosis of mucosa-associated lymphoid tissue lymphoma in both cases. One case involved a 23-year-old woman with mucosa-associated lymphoid tissue lymphoma in the parotid glands, and the other involved a 77-year-old man with mucosa-associated lymphoid tissue lymphoma in the thyroid. The combination of cutting needle biopsy, flow cytometry and immunoglobulin heavy chain gene rearrangement testing might offer a useful alternative to open biopsy for the diagnosis of mucosa-associated lymphoid tissue lymphoma. We recommend this procedure, particularly for young women or patients with poor performance status in whom malignant lymphoma is suspected.

    DOI: 10.1093/jjco/hys011

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  • Cutaneous multicentric Castleman’s disease mimicking IgG4-related disease.

    Takeuchi M, Sato Y, Takata K, Kobayashi K, Iwaki N, Orita Y, Yoshino T

    Pathology Reserch and Practice   208 ( 12 )   746 - 749   2012年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1016/j.prp.2012.09.006

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  • Germinal center B-cell-like versus non-germinal center B-cell-like as important prognostic factor for localized nodal DLBCL.

    Habara T, Sato Y, Takata K, Iwaki N, Okumura H, Sonobe H, Tanaka T, Orita Y, Al-kader AL, Ennishi D, Asano N, Yoshino T

    Journal of Clinical and Experimental Hematopathology   52 ( 2 )   91 - 99   2012年

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    掲載種別:研究論文(学術雑誌)  

    DOI: 10.3960/jslrt.52.91

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  • Ocular adnexal IgG4-producing mucosa-associated lymphoid tissue lymphoma mimicking IgG4-related disease.

    Sato Y, Ohshima K, Takata K, Huang X, Cui W, Ohno K, Yoshino T

    Journal of Experimental Hematopathology   52 ( 1 )   51 - 55   2012年

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    記述言語:英語   出版者・発行元:The Japanese Society for Lymphoreticular Tissue Research  

    IgG4-related disease is a recently proposed clinical entity with several unique clinicopathological features. A chronic inflammatory state with marked fibrosis, which can often be mistaken for malignancy, especially by clinical imaging analyses, unifies these features. In the present report, we describe a case of IgG4-producing mucosa-associated lymphoid tissue lymphoma mimicking IgG4-related disease. The patient was a 55-year-old male who was being followed for right orbital tumor over 1.5 years. The lesion had recently increased in size, so a biopsy was performed. Histologically, the lesion was consistent with IgG4-related disease ; however, IgG4+ plasma cells showed immunoglobulin light-chain restriction and immunoglobulin heavy chain gene rearrangement was detected in the lesion. Therefore, the lesion was diagnosed as IgG4-producing mucosa-associated lymphoid tissue lymphoma. In conclusion, in histological diagnosis of IgG4-related disease, it is important to examine not only IgG4-immunostain but also immunoglobulin light-chain restriction. [J Clin Exp Hematopathol 52(1) : 51-55, 2012]

    DOI: 10.3960/jslrt.52.51

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  • Rheumatoid lymphadenopathy with abundant IgG4+ plasma cells: a case of mimicking IgG4-related disease.

    Asano N, Sato Y

    Journal of Experimental Hematopathology   52 ( 1 )   57 - 61   2012年

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    記述言語:英語   出版者・発行元:The Japanese Society for Lymphoreticular Tissue Research  

    Immunoglobulin (Ig) G4-related disease is a recently confirmed clinical entity with several unique clinicopathological features. Here we report a case of rheumatoid lymphadenopathy mimicking IgG4-related disease. The patient was a 63-year-old woman who had been treated for rheumatoid arthritis (RA) for six years. The patient noted cervical lymphadenopathy. Upon radiological examination, systemic lymphadenopathy was detected, and enlarged right brachial lymph node biopsy was performed. Histologically, the lymph node showed marked follicular hyperplasia and interfollicular plasmacytosis without eosinophil infiltration. Although the histological findings were compatible with rheumatoid lymphadenopathy, numerous plasma cells were IgG4+ (IgG4+/IgG+ plasma cell ratio > 50%). However, laboratory findings revealed elevation of C-reactive protein level, polyclonal hyper-γ-globulinemia, anemia, and hypoalbuminemia. These findings were compatible with hyper-interleukin (IL)-6 syndrome, namely, RA. It is known that hyper-IL-6 syndromes, such as multicentric Castleman's disease, RA, and other autoimmune diseases, fulfill the histological diagnostic criteria for IgG4-related disease. Therefore, hyper-IL-6 syndromes and IgG4-related disease cannot be differentially diagnosed by immunohistochemical staining alone. In conclusion, rheumatoid lymphadenopathy sometimes occurs with abundant IgG4+ plasma cells, which is required for the differential diagnosis of IgG4-related disease. [J Clin Exp Hematopathol 52(1) : 57-61, 2012]

    DOI: 10.3960/jslrt.52.57

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  • IgG4-related perineural disease

    Dai Inoue, Yoh Zen, Yasuharu Sato, Hitoshi Abo, Hiroshi Demachi, Akio Uchiyama, Toshifumi Gabata, Osamu Matsui

    International Journal of Rheumatology   2012   572539   2012年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Aims. To elucidate characteristics of IgG4-related disease involving the peripheral nervous system. Methods. Retrospective review of 106 patients with IgG4-related disease identified 21 peripheral nerve lesions in 7 patients. Clinicopathological and radiological features were examined. Results. Peripheral nerve lesions were commonly identified in orbital or paravertebral area, involving orbital (n=9), optic (n=4), spinal (n=7), and great auricular nerves (n=1). The predominant radiological feature was a distinct perineural soft tissue mass, ranging 8 to 30mm in diameter. Histologically, the epineurium was preferentially involved by massive lymphoplasmacytic infiltration rich in IgG4 plasma cells. All lesions were neurologically asymptomatic and steroid-responsive at the first presentation, but one recurrent lesion around the optic nerve caused failing vision. Conclusion. IgG4-related disease of the peripheral nervous system is characterized by orbital or paravertebral localization, perineural mass formation, and rare neurologic symptoms. The term IgG4-related perineural disease seems appropriate to describe this entity. © Copyright 2012 Dai Inoue et al.

    DOI: 10.1155/2012/401890

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  • IgG4-related lymphadenopathy 招待 査読

    Yasuharu Sato, Tadashi Yoshino

    International Journal of Rheumatology   2012   572539   2012年

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    記述言語:英語  

    Lymphadenopathy is frequently observed in patients with immunoglobulin G4-related disease (IgG4-RD) and sometimes appears as the first manifestation of the disease. The diagnosis of IgG4-related lymphadenopathy is complicated owing to a great histological diversity, with at least 5 histological subtypes. Indeed, lymph node biopsy may be performed under the suspicion that the lymphadenopathy is a malignant lymphoma or other lymphoproliferative disorder. The diagnosis of IgG4-RD is characterized by both elevated serum IgG4 (135mg/dL) and histopathological features, including a dense lymphoplasmacytic infiltrate rich in IgG4 + plasma cells (IgG4 +/IgG + plasma cell ratio 40%). However, patients with hyper-interleukin (IL-) 6 syndromes such as multicentric Castlemans disease, rheumatoid arthritis, and other immune-mediated conditions frequently show lymph node involvement and often fulfill the diagnostic criteria for IgG4-RD. Owing to these factors, IgG4-RD cannot be differentiated from hyper-IL-6 syndromes on the basis of histological findings alone. Laboratory analyses are crucial to differentiate between the 2 diseases. Hyper-IL-6 syndromes are characterized by elevated serum levels of IgG, IgA, IgM, and C-reactive protein (CRP)
    thrombocytosis
    anemia
    hypoalbuminemia
    hypocholesterolemia. In contrast, IgG4-RD does not share any of these characteristics. Therefore, the diagnosis of IgG4-RD requires not only pathological findings but also clinical and laboratory analyses. © 2012 Yasuharu Sato and Tadashi Yoshino.

    DOI: 10.1155/2012/572539

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  • Germinal center B-cell-like diffuse large B-cell lymphoma of the duodenum is associated with t(14;18) translocation

    Maiko Tamura, Katsuyoshi Takata, Yasuharu Sato, Naoya Nakamura, Yara Yukie Kikuti, Koichi Ichimura, Takehiro Tanaka, Akira Tari, Yoshinobu Maeda, Mitsune Tanimoto, Hiroyuki Okada, Tadashi Yoshino

    PATHOLOGY INTERNATIONAL   61 ( 12 )   742 - 748   2011年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-BLACKWELL  

    Diffuse large B-cell lymphoma (DLBCL) rarely involves the duodenum, and its clinicopathological characteristics have not been well elucidated. We performed clinicopathological examinations and identified 15 patients with duodenal DLBCL using 18 gastric or colonic DLBCL as a control. Eleven of the 15 patients (73%) were subclassified by immunohistochemical analysis according to the Choi algorithm as germinal center B-cell-like (GCB) type, whereas the 18 control gastric and colonic DLBCL were predominantly subclassified as activated B-cell-like (ABC) type. The classifications according to organ involvement were statistically significant (P= 0.011 and P= 0.035). Macroscopically, the GCB lesions were varied, while all ABC lesions were ulcerative. Fluorescence in situ hybridization analysis revealed a higher frequency of t(14;18) translocation in patients with duodenal DLBCL (3 of 13) as compared with non-duodenal gastrointestinal tract DLBCL (0 of 18), however, the difference was not significant (P = 0.064). Furthermore, the three patients with t(14;18) translocations were classified as GCB. In addition, overall survival of patients was statistically different between those with and without t(14;18) translocation (P= 0.040). In conclusion, duodenal DLBCL predominantly exhibits GCB-type tumors and the frequency of t(14;18) translocation appears to be higher in duodenal GCB-type DLBCL compared to non-duodenal tumors.

    DOI: 10.1111/j.1440-1827.2011.02748.x

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  • Nodal follicular lymphoma without complete follicular dendritic cell networks is related to localized clinical stage

    Wei Cui, Lisha Che, Yasuharu Sato, Xingang Huang, Katsuyoshi Takata, Yorihisa Orita, Naoe Goto, Yoshinobu Maeda, Mitsune Tanimoto, Tadashi Yoshino

    PATHOLOGY INTERNATIONAL   61 ( 12 )   737 - 741   2011年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-BLACKWELL  

    Follicular lymphoma is the most common low-grade lymphoma and it frequently presents with a systemic disease, often showing advanced clinical stage (III/IV). The lymphoma cells are usually growing associated with follicular dendritic cell (FDC) networks. Abnormal FDC networks have been reported in duodenal follicular lymphoma, in which cases exhibit lower clinical stages than the nodal cases. In the present study, we analyzed the FDC network distribution pattern of 242 nodal follicular lymphomas by immunohistochemistry. Out of the 242 cases, 27 cases (11%) demonstrated an atypical pattern of FDC networks, in which the CD21 staining totally or partially disappeared in the neoplastic follicles. Furthermore, we compared the clinical data of these 27 cases and 58 typical FDC network cases of follicular lymphoma. We found that in the typical cases, 52 out of 58 patients (90%) showed advanced clinical stage (III or IV), whereas 10 of 27 (37%) atypical FDC network cases showed localized clinical stage (I or II) (P &lt; 0.01). In conclusion, nodal follicular lymphoma with total loss or partially disrupted FDC networks therefore show a lower clinical stage.

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  • Cyclin D2 is overexpressed in proliferation centers of chronic lymphocytic leukemia/small lymphocytic lymphoma

    Takuro Igawa, Yasuharu Sato, Katsuyoshi Takata, Soichiro Fushimi, Maiko Tamura, Naoya Nakamura, Yoshinobu Maeda, Yorihisa Orita, Mitsune Tanimoto, Tadashi Yoshino

    CANCER SCIENCE   102 ( 11 )   2103 - 2107   2011年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-BLACKWELL  

    The D cyclins are important cell cycle regulatory proteins involved in the pathogenesis of some lymphomas. Cyclin D1 overexpression is a hallmark of mantle cell lymphoma, whereas cyclins D2 and D3 have not been shown to be closely associated with any particular subtype of lymphoma. In the present study, we found that cyclin D2 was specifically overexpressed in the proliferation centers (PC) of all cases of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) examined (19/19). To examine the molecular mechanisms underlying this overexpression, we immunohistochemically examined the expression of nuclear factor (NF)-kappa B, p15, p16, p18, and p27 in the PC of six patients. Five cases showed upregulation of NF-kappa B expression, which is known to directly induce cyclin D2 by binding to the promoter region of CCND2. All six PC examined demonstrated downregulation of p27 expression. In contrast, upregulation of p15 expression was detected in five of six PC examined. This discrepancy suggests that unknown cell cycle regulatory mechanisms involving NF-kappa B-related pathways are also involved, because NF-kappa B upregulates cyclin D2 not only directly, but also indirectly through c-Myc, which is believed to downregulate both p27 and p15. In conclusion, cyclin D2 is overexpressed in the PC of CLL/SLL and this overexpression is due, in part, to the upregulation of NF-kappa B-related pathways. (Cancer Sci 2011; 102: 2103-2107)

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  • Review of acquired cystic disease-associated renal cell carcinoma with focus on pathobiological aspects 査読

    Naoto Kuroda, Chisato Ohe, Shuji Mikami, Ondrej Hes, Michal Michal, Matteo Brunelli, Guido Martignoni, Yasuharu Sato, Tadashi Yoshino, Yoshiyuki Kakehi, Taro Shuin, Gang-Hong Lee

    HISTOLOGY AND HISTOPATHOLOGY   26 ( 9 )   1215 - 1218   2011年9月

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    記述言語:英語   出版者・発行元:F HERNANDEZ  

    Acquired cystic disease (ACD)-associated renal cell carcinoma (RCC) is a recently established entity. In this article, we introduce the general view of this new entity. Macroscopically, the disease exclusively occurs in ACD and may arise as a dominant mass or non-dominant masses. Histologically, the tumor is characterized by a microcystic pattern, neoplastic cells with an eosinophilic or oncocytic cytoplasm and frequent intratumoral oxalate crystal deposition. Prominent nucleoli of tumor cells are often observed. Immunohistochemically, neoplastic cells are generally positive for AMACR but negative for cytokeratin 7. Ultrastructurally, neoplastic cells contain abundant mitochondria in the cytoplasm. Genetically, the gain of chromosomes 3, 7, 17 and abnormality of the sex chromosome were frequently observed in several studies. In conclusion, ACD-associated RCC may be widely recognized as a distinct entity in the near future because this tumor is morphologically and genetically different from other renal tumor entities that have been previously established.

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  • Immunoglobulin G4-related lymphadenopathy with inflammatory pseudotumor-like features 査読

    Yasuharu Sato, Masaru Kojima, Katsuyoshi Takata, Xingang Huang, Eiko Hayashi, Akihiro Manabe, Yukari Miki, Tadashi Yoshino

    MEDICAL MOLECULAR MORPHOLOGY   44 ( 3 )   179 - 182   2011年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPRINGER TOKYO  

    Immunoglobulin (Ig) G4-related disease has been recently described. This disease affects various organs, including lymph nodes. We describe the case of a 52-year-old Japanese man with IgG4-related lymphadenopathy with inflammatory pseudotumor (IPT)-like features. Five years ago, the patient noticed a painless mass in the mandible but did not consult a doctor. Recently, he noted that the mass had increased in size and consulted an oral surgeon in the hospital. Excisional biopsy was performed for diagnosis. Histopathological examination revealed that most of the enlarged lymph node was occupied by the hyalinized tissue. A few residual lymphoid follicles with hyperplastic germinal centers and infiltration of plasma cells and eosinophils were observed. Most of the plasma cells expressed IgG4, and the ratio of IgG4-positive cells to IgG-positive cells was 57.1%. These findings were consistent with IgG4-related lymphadenopathy. In conclusion, pathologists should consider IgG4-related lymphadenopathy when diagnosing a lesion with IPT-like features.

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  • BCL2、C-MYC、BCL6転座を有するtriple-hit lymphomaの3例

    鈴木 優子, 増成 太郎, 二宮 貴一朗, 益田 加奈, 田村 朋季, 木村 耕介, 園部 宏, 佐藤 康晴, 吉野 正, 瀬崎 伸夫

    臨床血液   52 ( 9 )   1194 - 1194   2011年9月

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    記述言語:日本語   出版者・発行元:(一社)日本血液学会-東京事務局  

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  • Primary gastrointestinal follicular lymphoma involving the duodenal second portion is a distinct entity: A multicenter, retrospective analysis in Japan

    Katsuyoshi Takata, Hiroyuki Okada, Naoki Ohmiya, Shotaro Nakamura, Yasuhiko Kitadai, Akira Tari, Taiji Akamatsu, Hiroki Kawai, Shu Tanaka, Hiroshi Araki, Takashi Yoshida, Hirokazu Okumura, Hogara Nishisaki, Tamotsu Sagawa, Norihiko Watanabe, Nobuyoshi Arima, Noritaka Takatsu, Masanao Nakamura, Shunichi Yanai, Hiroyasu Kaya, Toshiaki Morito, Yasuharu Sato, Hisataka Moriwaki, Choitsu Sakamoto, Yasumasa Niwa, Hidemi Goto, Tsutomu Chiba, Takayuki Matsumoto, Daisuke Ennishi, Tomohiro Kinoshita, Tadashi Yoshino

    CANCER SCIENCE   102 ( 8 )   1532 - 1536   2011年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-BLACKWELL  

    We conducted a multicenter, retrospective study to determine the anatomical distribution and prognostic factors of gastrointestinal (GI) follicular lymphoma (FL). This study included 125 patients with stage I and II(1) GI-FL. Of the 125 patients, the small intestine was examined in 70 patients, with double-balloon endoscopy and/or capsule endoscopy. The most frequently involved GI-FL site was the duodenal second portion (DSP) (81%), followed by the jejunum (40%); 85% of patients with involvement of the DSP also had jejunal or ileal lesions. The absence of abdominal symptoms and macroscopic appearance of multiple nodules were significantly present in the DSP-positive group. During a median follow up of 40 months, six patients showed disease progression. Patients with involvement of the DSP had better progression-free survival (PFS) than those without such involvement (P = 0.001). A multivariate analysis revealed that male sex, the presence of abdominal symptoms, and negative involvement of the DSP were independently associated with poor PFS. In conclusion, most patients with GI-FL have duodenal lesions associated with multiple jejunal or ileal lesions. Gastrointestinal follicular lymphomas involving the DSP might be a distinct entity showing a favorable clinical course. (Cancer Sci 2011; 102: 1532-1536)

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  • [Frequent inactivation of A20 through gene mutation in B-cell lymphomas]. 査読

    Kato M, Sanada M, Kato I, Sato Y, Takita J, Takeuchi K, Niwa A, Chen Y, Nakazaki K, Nomoto J, Asakura Y, Akatsuka M, Hayashi Y, Mori H, Igarashi T, Kurokawa M, Chiba S, Mori S, Ishikawa Y, Okamoto K, Tobinai K, Nakagama H, Nakahata T, Yoshino T, Kobayashi Y, Ogawa S

    [Rinsho ketsueki] The Japanese journal of clinical hematology   52 ( 6 )   313 - 319   2011年6月

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    記述言語:日本語   出版者・発行元:「臨床血液」編集部  

    DOI: 10.11406/rinketsu.52.313

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  • Follicular variant of peripheral T-cell lymphoma mimicking follicular lymphoma: A case report with a review of the Literature

    Naoe Goto, Hisashi Tsurumi, Michio Sawada, Nobuhiro Kanemura, Takeshi Hara, Senji Kasahara, Yusuke Kito, Katsuyoshi Takada, Yasuharu Sato, Tadashi Yoshino, Hisataka Moriwaki, Tsuyoshi Takami

    PATHOLOGY INTERNATIONAL   61 ( 5 )   326 - 330   2011年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-BLACKWELL  

    Peripheral T-cell lymphoma (PTCL) with a follicular growth pattern is very rare. Herein, a case of follicular variant of PTCL in a 50-year-old man who complained of tonsillar and generalized lymph node swelling is reported. The resected tonsil revealed a vague nodular growth pattern of atypical cells, medium to large in size, with abundant pale cytoplasm. The lymphoma cells were CD3+ CD4+ CD5+ CD8- CD10+ CD56- CD57- BCL6+ PD-1+ CXCL13+ and were associated with a meshwork of CD21+ follicular dendritic cells. Molecular studies revealed clonal rearrangement of the T-cell receptor gamma chain gene but not of the immunoglobulin gene. Cytogenetic analysis disclosed a complex abnormality in 18 of 20 cells with the exclusion of t(5; 9). These findings suggest that the present case is a follicular variant of PTCL derived from follicular T-helper cells.

    DOI: 10.1111/j.1440-1827.2011.02656.x

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  • Downregulation of the B-cell receptor signaling component CD79b in plasma cell myeloma: A possible post transcriptional regulation.lymphomas.

    Huang X, Takata K, Sato Y, Tanaka T, Ichimura K, Tamura M, Oka T, Yoshino T

    Pathol Int   61 ( 3 )   122 - 129   2011年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1111/j.1440-1827.2010.02634.x

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  • Multicentric Castleman&apos;s disease with abundant IgG4-positive cells: a clinical and pathological analysis of six cases

    Yasuharu Sato, Masaru Kojima, Katsuyoshi Takata, Toshiaki Morito, Kohichi Mizobuchi, Takehiro Tanaka, Dai Inoue, Hideyuki Shiomi, Haruka Iwao, Tadashi Yoshino

    JOURNAL OF CLINICAL PATHOLOGY   63 ( 12 )   1084 - 1089   2010年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:B M J PUBLISHING GROUP  

    Background Differentiation between multicentric Castleman&apos;s disease and systemic immunoglobulin (Ig) G4-related lymphadenopathy is sometimes difficult. It has been suggested that measurement of the IgG4-/IgG-positive cell ratio is useful for the differential diagnosis of the two diseases. However, the authors present a detailed report of six patients with multicentric Castleman&apos;s disease with abundant IgG4-positive cells (IgG4-/IgG-positive cell ratio, &gt;40%).
    Results In the present series, the patients showed systemic lymphadenopathy, polyclonal hypergammaglobulinaemia and elevated serum interleukin-6 (IL-6) and C-reactive protein levels. Further, anaemia, hypoalbuminaemia, hypocholesterolaemia and thrombocytosis were observed. These findings were consistent with those of multicentric Castleman&apos;s disease. Although five patients showed elevated serum IgG4 levels, only two patients showed an increased serum IgG4/IgG ratio. However, the two patients showed highly elevated serum IgG4 levels, but the serum IgG4/IgG ratios were, although increased, not very high. Also, a patient with increased serum IgG4/IgG ratio showed a good response to antihuman IL-6 receptor monoclonal antibody (tocilizumab). Histologically, the germinal centres were mostly small and regressive, and frequently penetrated by hyalinised blood vessels, and there was no eosinophil infiltration. These findings were different from those of IgG4-related lymphadenopathy.
    Conclusions The authors conclude that multicentric Castleman&apos;s disease sometimes occurs with abundant IgG4-positive cells and elevated serum IgG4 levels. Therefore, the two diseases cannot be differentially diagnosed by immunohistochemical staining alone. Laboratory findings, especially IL-6 level, C-reactive protein level and platelet count, are important for the differential diagnosis of the two diseases.

    DOI: 10.1136/jcp.2010.082958

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  • Epstein-Barr virus-associated primary central nervous system lymphomas in immunocompetent elderly patients: analysis for latent membrane protein-1 oncogene deletion and EBNA-2 strain typing

    Yasuo Sugita, Mizuhiko Terasaki, Daisuke Niino, Koichi Ohshima, Arakawa Fumiko, Minoru Shigemori, Yasuharu Sato, Naoko Asano

    JOURNAL OF NEURO-ONCOLOGY   100 ( 2 )   271 - 279   2010年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPRINGER  

    Epstein-Barr virus (EBV) has been implicated in the pathogenesis of primary central nervous system lymphomas (PCNLs) in immunocompetent hosts. To investigate the role of EBV in the pathogenesis of PCNLs in immunocompetent hosts, this study assessed six PCNL cases (elderly male immunocompetent patients; age a parts per thousand yen60 years) histologically and immunohistochemically, and an EBV genetic study was performed. Histologically, all cases were diagnosed as diffuse large B-cell lymphoma with extensive necrosis. In all six cases, PCNL cells showed immunohistochemical positivity for latent membrane protein 1 (LMP-1) and Epstein-Barr nuclear 2 (EBNA2). Lymphoma cells also showed positive signals for EBV-encoded small RNAs (EBERs) on in-situ hybridization. EBV subtyping-PCR analysis demonstrated that one case was EBNA 2B type and the other five cases were EBNA 2A type, and two cases were EBV wild-type and four cases showed 30-bp LMP-1 deletion by PCR analysis. It is therefore possible that LMP gene deletion or EBNA-2 strain type are important in the tumorigenesis of EBV-positive PCNLs. In addition, EBV-positive PCNLs in immunocompetent hosts may be related to immunological deterioration derived from the aging process.

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  • A duodenal follicular lymphoma associated with the lesion mimicking MALT lymphoma in terminal ileum and Bauhin valve

    Akira Tari, Yasuharu Sato, Hideki Asaoku, Masaki Kunihiro, Akira Fukumoto, Shinji Tanaka, Megumu Fujihara, Tadashi Yoshino

    MEDICAL MOLECULAR MORPHOLOGY   43 ( 3 )   174 - 177   2010年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPRINGER TOKYO  

    This is a case report of a 66-year-old woman who consulted us with a 1-week history of postprandial epigastric discomfort and dyspepsia. Upper and lower gastrointestinal endoscopy and double-balloon enteroscopy revealed lesions in three parts: a swelling with a shallow depression in the ampulla of Vater, flat and rough nodules in the jejunum, and a mixture of lymphoid polyposis and rough surface of follicular lymphoma of the terminal ileum and Bauhin valve. The histological, immunophenotypic, and molecular findings of the duodenal lesion confirmed the diagnosis of follicular lymphoma. We initially diagnosed the ileal lesion as MALT lymphoma immunohistochemically. However, Southern blot hybridization analysis for immunoglobulin heavy chain gene rearrangement showed identical monoclonal bands in both the duodenal and ileal lesions. The molecular cytogenetic studies were also positive for the 14;18 translocation in both lesions. Therefore, the true diagnosis of this ileal lesion should be a follicular lymphoma with marginal zone differentiation. Primary follicular lymphomas of gastrointestinal tract were suggested to have intermediate features between nodal follicular lymphoma and MALT lymphoma. This case is an important clue to prove the similarity of follicular lymphoma of gastrointestinal tract to MALT lymphoma and will be crucial in considering the therapeutic strategy.

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  • IgG4-related disease: Historical overview and pathology of hematological disorders

    Yasuharu Sato, Kenji Notohara, Masaru Kojima, Katsuyoshi Takata, Yasufumi Masaki, Tadashi Yoshino

    PATHOLOGY INTERNATIONAL   60 ( 4 )   247 - 258   2010年4月

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    記述言語:英語   出版者・発行元:WILEY-BLACKWELL  

    IgG4-related diseases comprise a recently recognized systemic syndrome characterized by mass-forming lesions in mainly exocrine tissue that consist of lymphoplasmacytic infiltrates and sclerosis. There are numerous IgG4-positive plasma cells in the affected tissues, and the serum IgG4 level is increased in these patients. The present study describes the history, autoimmune pancreatitis (AIP), IgG4-related lymphadenopathy and lymphomagenesis based upon ocular adnexal IgG4-related disease. Lymphoplasmacytic sclerosing pancreatitis, a prototypal histological type of AIP, is now recognized as a systemic IgG4-related disease. Lymph node lesions can be subdivided into at least five histological subtypes, and systemic IgG4-related lymphadenopathy should be distinguished from multicentric Castleman's disease. Interleukin-6 and CRP levels are abnormally high in multicentric Castleman's disease, but are normal in the majority of systemic IgG4-related lymphadenopathy. Ocular adnexal IgG4-related disease frequently involves bilateral lacrimal glands swelling, and obliterative phlebitis is rare. Moreover, some malignant lymphomas, especially mucosa-associated lymphoid tissue lymphoma, arise from ocular adnexal IgG4-related disease. In addition, IgG4-producing lymphoma also exists.

    DOI: 10.1111/j.1440-1827.2010.02524.x

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  • Immunoglobulin G4 (IgG4)-positive or –negative ocular adnexal benign lymphoid lesions in relation to systemic involvement.

    Matsuo T, Ichimura K, Sato Y, Tanimoto Y, Kiura K, Kanazawa S, Okada T, Yoshino T

    Journal of Clinical and Experimental Hematopathology   50 ( 2 )   129 - 142   2010年

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    記述言語:英語   出版者・発行元:The Japanese Society for Lymphoreticular Tissue Research  

    The purpose of this study is to determine the relationship of ocular adnexal benign or reactive lymphoid hyperplasia, including orbital pseudotumor, with immunoglobulin G4 (IgG4)-related diseases. Medical charts of 9 consecutive patients with ocular adnexal benign lymphoid lesions, seen in the Department of Ophthalmology, Okayama University Hospital, were reviewed, and pathological sections were restained immunohistochemically for IgG4-, IgG-, and CD138-positive plasma cells. The diagnosis of IgG4-positive lesions was based on 10 or more IgG4-positive plasma cells in a high-power field and greater than 40% ratios of IgG4-positive plasma cells/CD138-positive plasma cells and IgG4-positive plasma cells/IgG-positive plasma cells. IgG4-positive lesions were determined as absent in 5 patients (4 with bilateral lacrimal/orbital lesions and one with a unilateral conjunctival lesion), none of whom showed systemic manifestations. In contrast, IgG4-positive lesions were present in 4 patients (3 with bilateral lacrimal/orbital lesions and one with a unilateral lacrimal/orbital lesion), who showed systemic manifestations : one with Hashimoto thyroiditis, one with IgG4-positive bilateral interstitial lung disease and hepatic inflammatory pseudotumor, one with bilateral interstitial lung disease, and one with systemic lymphadenopathy and antiphospholipid syndrome. In conclusion, IgG4-positive ocular adnexal benign lymphoid lesions might be used as a benchmark for the probable presence of other systemic lymphoid lesions.

    DOI: 10.3960/jslrt.50.129

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    その他リンク: http://search.jamas.or.jp/link/ui/2011254628

  • BAFF-R is expressed on B-cell lymphomas depending on their origin, and related to proliferation index of nodal diffuse large B-cell lymphomas.

    Takahata H, Ohara N, Ichimura K, Tanaka T, Sato Y, Morito T, Takata K, Kojima M, Kobata T, Yoshino T

    Journal of Clinical and Experimental Hematopathology   50 ( 2 )   121 - 127   2010年

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    記述言語:英語   出版者・発行元:The Japanese Society for Lymphoreticular Tissue Research  

    B-cell activating factor receptor (BAFF-R) is one of three known receptors for BAFF. BAFF-R is required for B-cell maturation and survival. We tried to determine the normal pattern of BAFF-R expression in non-neoplastic and neoplastic B- and T-cells. We used immunohistochemistry to evaluate the expression pattern of BAFF-R in non-neoplastic and neoplastic lymphoid tissues of routinely fixed paraffin-embedded samples, and examined the relationships among BAFF-R and expressions of CD10, bcl-6, MUM-1, and MIB-1. BAFF-R expression was detected on B-cells of the mantle zones, some cells within germinal centers, and scattered cells in the interfollicular areas of reactive lymph nodes. BAFF-R expression was only found in B-cell lymphoma (60/120, positive samples/examined samples), but not in T/NK cell lymphoma (0/10) or Hodgkin lymphoma (0/10). The proportions were as follows : follicular lymphoma (14/16), diffuse large B-cell lymphoma (DLBCL) (27/61), mantle cell lymphoma (4/4), and Burkitt lymphoma (0/4). According to Hans' criteria, DLBCLs were subclassified into germinal center B-cell-like (GCB) and non-germinal center B-cell-like (non-GCB) types. Interestingly, in nodal lymphomas, in the GCB subgroup (n=12), 9 of 12 (75%) were positive for BAFF-R, while 6 of 20 (30%) were positive in the non-GCB subgroup (n=20) (p < 0.05). In addition, expression of BAFF-R related to lower MIB-1 index was associated with GCB-type DLBCL. In conclusion, BAFF-R was only found in some B-cell lymphomas, which was closely associated with the expression pattern in normal counterparts, although BAFF-R expression on follicular lymphoma is different from that on germinal center cells, which is similar to bcl-2. BAFF-R was rather specifically related to low growth activity of GCB-type DLBCL of nodal origin.

    DOI: 10.3960/jslrt.50.121

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  • Chronic sclerosing pyelitis with an increased number of IgG4-positive plasma cells

    Naoto Kuroda, Shoichiro Nakamura, Katsushi Miyazaki, Kaori Inoue, Masahiko Ohara, Keiko Mizuno, Yasuharu Sato, Tadashi Yoshino

    MEDICAL MOLECULAR MORPHOLOGY   42 ( 4 )   236 - 238   2009年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPRINGER TOKYO  

    IgG4-related disease has been recently described. This disease occurs in various anatomic locations including pancreas, biliary tract, liver, retroperitoneum, kidney, breast, lung, thyroid gland, prostate, salivary gland, lacrimal gland, and lymph node. In this article, we report the first case of IgG4-related disease arising in the renal pelvis. A 49-year-old Japanese woman was found to show left hydronephrosis by a medical checkup. Histological examination of the renal pelvic tumor showed IgG4-related disease. Her postoperative serum IgG4 was elevated, and this was compatible with IgG4-related disease. Systemic examination showed swelling of major and minor salivary glands and the lacrimal glands, and biopsy of the minor salivary gland revealed the finding of IgG4-related disease. Finally, pathologists and clinicians should be aware of the possibility that the renal pelvis may be involved in IgG4-related systemic disease.

    DOI: 10.1007/s00795-008-0425-8

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  • Aberrations of Genes Regulating NF Kappa B Pathway in B-Cell Malignant Lymphoma 査読

    Kato Motohiro, Sanada Masashi, Kato Itaru, Sato Yasuharu, Takita Junko, Kawahata Ryoichiro, Takeuchi Kengo, Niwa Akira, Chen Yuyan, Nakazaki Kumi, Nomoto Junko, Asakura Yoshitaka, Akatsuka Yoshiki, Hayashi Yasuhide, Igarashi Takashi, Kurokawa Mineo, Chiba Shigeru, Mori Shigeo, Ishikawa Yuichi, Okamoto Koji, Tobinai Kensei, Nakagama Hitoshi, Nakahata Tatsutoshi, Yoshino Tadashi, Kobayashi Yukio, Ogawa Seishi

    BLOOD   114 ( 22 )   401 - 401   2009年11月

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    記述言語:英語  

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  • Frequent downregulation or loss of CD79a expression in plasma cell myelomas: potential clue for diagnosis. 国際誌

    Takehiro Tanaka, Kouichi Ichimura, Yasuharu Sato, Katsuyoshi Takata, Toshiaki Morito, Maiko Tamura, Eisaku Kondo, Nobuya Ohara, Hiroyuki Yanai, Masaharu Sakai, Satoru Takahashi, Tadashi Yoshino

    Pathology international   59 ( 11 )   804 - 8   2009年11月

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    記述言語:英語  

    Plasma cell myeloma is a frequent hematogeneous disorder that occurs mainly in older people. Not only bone marrow smears but also clots and/or biopsied specimens are often taken for confirmation of pathological diagnosis. Some specimens show sheet-like plasma cell proliferation associated with immunoglobulin monotype on immunohistology, which readily leads to diagnosis, but many samples do not clearly show light-chain restriction. The aim of the present study was therefore to examine CD79a expression because some samples had reduced expression or none at all. The immunoreactivity of CD79a was categorized into three groups: positive, weakly positive and negative, compared with scattering non-neoplastic plasma cells in the same specimen. Out of 100 specimens of plasma cell myeloma, 48% were positive for CD79a, 15% were weakly positive, and 37% were negative. In contrast, overexpression of cyclinD1 was detected in 26% of examined samples. CD79a-negative cases had a significantly lower percentage of positive staining for cyclinD1 than CD79a-positive or weakly positive cases. Clinicopathological data showed that CD79a-negative expression was associated with decreased platelet numbers in patients. The present study indicates that downregulation or loss of CD79a and/or overexpression of cyclin D1, observed in 59% of neoplastic plasma cell samples, could provide a strong diagnostic clue without regard to the results of immunoglobulin light-chain restriction.

    DOI: 10.1111/j.1440-1827.2009.02448.x

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  • Duodenal and nodal follicular lymphomas are distinct: the former lacks activation-induced cytidine deaminase and follicular dendritic cells despite ongoing somatic hypermutations. 国際誌

    Katsuyoshi Takata, Yasuharu Sato, Naoya Nakamura, Yara Yukie Kikuti, Koichi Ichimura, Takehiro Tanaka, Toshiaki Morito, Maiko Tamura, Takashi Oka, Eisaku Kondo, Hiroyuki Okada, Akira Tari, Tadashi Yoshino

    Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc   22 ( 7 )   940 - 9   2009年7月

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    記述言語:英語  

    Although most follicular lymphomas are believed to be of nodal origin, they sometimes originate from the duodenum. We have reported that the latter differ from nodal follicular lymphomas in having lower clinical stages and uniformly low histological grades, along with variable region of immunoglobulin heavy chain gene (VH) usage that is more similar to mucosa-associated lymphoid tissue (MALT) lymphomas. Little is known, however, about whether they possess other characteristics of nodal follicular lymphomas, particularly ongoing mutations with follicular dendritic cells. We examined 17 cases for which PCR identified the monoclonal bands of the immunoglobulin gene. The duodenal cases showed ongoing mutations, but they lacked activation-induced cytidine deaminase (AID) expression, a statistically significant difference from the nodal cases (P<0.001), and their follicular dendritic cell networks were disrupted. Moreover, not only were VH deviations observed but also they used very restricted VH genes. Although the mechanisms of ongoing mutation without AID and follicular dendritic cell were not clarified, restricted VH usage strongly suggested that antigen stimulation was involved, and that was similar to MALT lymphomas. In conclusion, duodenal follicular lymphomas were shown to be unique, in that they had ongoing hypermutations such as nodal cases, but the mechanisms involved in the hypermutation were quite different; furthermore, restricted VH usage suggested a strong similarity to the antigen-dependent origin of MALT lymphomas.

    DOI: 10.1038/modpathol.2009.51

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  • Serum soluble interleukin-2 receptor level and immunophenotype are prognostic factors for patients with diffuse large B-cell lymphoma

    Toshiaki Morito, Megumu Fujihara, Hideki Asaoku, Akira Tari, Yasuharu Sato, Kouichi Ichimura, Takehiro Tanaka, Katsuyoshi Takata, Maiko Tamura, Tadashi Yoshino

    CANCER SCIENCE   100 ( 7 )   1255 - 1260   2009年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-BLACKWELL PUBLISHING, INC  

    Diffuse large B-cell lymphoma is the most common form of non-Hodgkin lymphoma. Although many studies have attempted to identify prognostic factors, most have focused on conventionally treated patients. The influence of anti-CD20 antibody (rituximab) should be considered now. We evaluated the prognostic significance of serum soluble interleukin-2 receptor levels and germinal center B-cell-like or non-germinal center B-cell like subgroups in 80 patients with diffuse large B-cell lymphoma, who had been treated with rituximab. Serum soluble interleukin-2 receptor levels ranged from 322 to 39900 U/mL (median 1365 U/mL). Sixteen (20%) were germinal center B-cell-like subgroups, and the remainder (80%) non-germinal center B-cell-like. Survival analysis associated lower serum soluble interleukin-2 receptor level and germinal center B-cell-like phenotype with better overall survival (P = 0.015), whereas multivariate analysis, including International Prognostic Index factors, revealed that only higher performance status score and higher serum lactate dehydrogenase levels significantly affected survival. However, serum soluble interleukin-2 receptor levels were elevated in patients with higher International Prognostic Index scores as well as in the non-germinal center B-cell-like subgroup. Serum soluble interleukin-2 receptor levels, International Prognostic Index, and subphenotypes were strongly correlated with each other. Our study showed that soluble interleukin-2 receptor is quite useful and may serve as a substitute for the International Prognostic Index, especially for patients undergoing treatment. Moreover, the differentiation between the germinal center B-cell-like and non-germinal center B-cell-like phenotypes is also useful for predicting patients with diffuse large B-cell lymphoma, even among those treated with rituximab. (Cancer Sci 2009; 100: 1255-1260)

    DOI: 10.1111/j.1349-7006.2009.01167.x

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  • Frequent inactivation of A20 in B-cell lymphomas

    Motohiro Kato, Masashi Sanada, Itaru Kato, Yasuharu Sato, Junko Takita, Kengo Takeuchi, Akira Niwa, Yuyan Chen, Kumi Nakazaki, Junko Nomoto, Yoshitaka Asakura, Satsuki Muto, Azusa Tamura, Mitsuru Iio, Yoshiki Akatsuka, Yasuhide Hayashi, Hiraku Mori, Takashi Igarashi, Mineo Kurokawa, Shigeru Chiba, Shigeo Mori, Yuichi Ishikawa, Koji Okamoto, Kensei Tobinai, Hitoshi Nakagama, Tatsutoshi Nakahata, Tadashi Yoshino, Yukio Kobayashi, Seishi Ogawa

    NATURE   459 ( 7247 )   712 - U118   2009年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:NATURE PUBLISHING GROUP  

    A20 is a negative regulator of the NF-kappa B pathway and was initially identified as being rapidly induced after tumour-necrosis factor-alpha stimulation(1). It has a pivotal role in regulation of the immune response and prevents excessive activation of NF-kappa B in response to a variety of external stimuli(2-7); recent genetic studies have disclosed putative associations of polymorphic A20 (also called TNFAIP3) alleles with autoimmune disease risk(8,9). However, the involvement of A20 in the development of human cancers is unknown. Here we show, using a genome-wide analysis of genetic lesions in 238 B-cell lymphomas, that A20 is a common genetic target in B-lineage lymphomas. A20 is frequently inactivated by somatic mutations and/or deletions in mucosa-associated tissue lymphoma (18 out of 87; 21.8%) and Hodgkin's lymphoma of ;nodular sclerosis histology (5 out of 15; 33.3%), and, to a lesser extent, in other B-lineage lymphomas. When re-expressed in a lymphoma-derived cell line with no functional A20 alleles, wildtype A20, but not mutant A20, resulted in suppression of cell growth and induction of apoptosis, accompanied by down-regulation of NF-kappa B activation. The A20-deficient cells stably generated tumours in immunodeficient mice, whereas the tumorigenicity was effectively suppressed by re-expression of A20. In A20-deficient cells, suppression of both cell growth and NF-kappa B activity due to re-expression of A20 depended, at least partly, on cell-surface-receptor signalling, including the tumour-necrosis factor receptor. Considering the physiological function of A20 in the negative modulation of NF-kappa B activation induced by multiple upstream stimuli, our findings indicate that uncontrolled signalling of NF-kappa B caused by loss of A20 function is involved in the pathogenesis of subsets of B-lineage lymphomas.

    DOI: 10.1038/nature07969

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  • Systemic IgG4-related lymphadenopathy: a clinical and pathologic comparison to multicentric Castleman&apos;s disease

    Yasuharu Sato, Masaru Kojima, Katsuyoshi Takata, Toshiaki Morito, Hideki Asaoku, Tamotsu Takeuchi, Kohichi Mizobuchi, Megumu Fujihara, Kazuya Kuraoka, Tokiko Nakai, Kouichi Ichimura, Takehiro Tanaka, Maiko Tamura, Yuriko Nishikawa, Tadashi Yoshino

    MODERN PATHOLOGY   22 ( 4 )   589 - 599   2009年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:NATURE PUBLISHING GROUP  

    IgG4-related disease sometimes involves regional and/or systemic lymph nodes, and often clinically and/or histologically mimics multicentric Castleman&apos;s disease or malignant lymphoma. In this study, we examined clinical and pathologic findings of nine patients with systemic IgG4-related lymphadenopathy. None of these cases were associated with human herpes virus-8 or human immunodeficiency virus infection, and there was no T-cell receptor or immunoglobulin gene rearrangement. Histologically, systemic IgG4-related lymphadenopathy was classified into two types by the infiltration pattern of IgG4-positive cells: interfollicular plasmacytosis type and intra-germinal center plasmacytosis type. The interfollicular plasmacytosis type showed either Castleman&apos;s disease-like features or atypical lymphoplasmacytic and immunoblastic proliferation-like features. By contrast, the intra-germinal center plasmacytosis type showed marked follicular hyperplasia, and infiltration of IgG4-positive cells mainly into the germinal centers, and some cases exhibited features of progressively transformed germinal centers. Interestingly, eight of our nine (89%) cases showed eosinophil infiltration in the affected lymph nodes, and examined patients showed high elevation of serum IgE. Laboratory examinations revealed elevation of serum IgG4 and soluble interleukin-2 receptors. However, the levels of interleukin-6, C-reactive protein, and lactate dehydrogenase were within normal limits or only slightly elevated in almost all patients. One patient showed a high interleukin-6 level whereas C-reactive protein was within the normal limit. Autoantibodies were examined in five patients and detected in four. Compared with the previously reported cases of multicentric Castleman&apos;s disease, our patients with systemic IgG4-related lymphadenopathy were significantly older and had significantly lower C-reactive protein and interleukin-6 levels. In conclusion, in our systemic IgG4-related lymphadenopathy showed pathologic features only partially overlapping those of multicentric Castleman&apos;s disease, and serum data (especially C-reactive protein and interleukin-6) are useful for differentiating the two. Our findings of eosinophil infiltration in the affected tissue and elevation of serum IgE may suggest an allergic mechanism in the pathogenesis of systemic IgG4-related lymphadenopathy.

    DOI: 10.1038/modpathol.2009.17

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  • Patients with localized primary non-tonsillar oral diffuse large B-cell lymphoma exhibit favorable prognosis despite a non-germinal center B-cell-like phenotype

    Yasuharu Sato, Naoko Onishi, Toshiaki Morito, Katsuyoshi Takata, Kohichi Mizobuchi, Hitoshi Nagatsuka, Kouichi Ichimura, Takehiro Tanaka, Maiko Tamura, Tadashi Yoshino

    CANCER SCIENCE   100 ( 1 )   42 - 46   2009年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-BLACKWELL PUBLISHING, INC  

    Diffuse large B-cell lymphomas are detected frequently in the oral cavity. Although tonsillar lymphomas have been rather well characterized, lymphomas originating from non-tonsillar regions, such as the gingiva, palate, and tongue, have not been well studied. We examined the pathology of clinical samples obtained from 21 patients with localized primary non-tonsillar oral diffuse large B-cell lymphoma. Immunohistological examination of CD10, Bcl-6, and MUM1 determined that 17 of 21 (81%) samples exhibited non-germinal center B-cell type, an increased proportion of non-germinal center B-cell type compared with previous reports in samples of tonsillar origin (P &lt; 0.05). The four remaining samples exhibited germinal center B-cell type, although one sample expressed MUM1. Follow-up clinical survival data were obtained from the 17 patients over a range from 4 to 173 months (mean 52 months). All patients were treated with chemotherapies, irradiation, or surgical resection. Sixteen patients achieved complete remission and two patients relapsed, but no patient has died of disease. Extranodal diffuse large B-cell lymphomas of non-germinal center B-cell type are generally characterized by poor prognosis, regardless of localized disease. Interestingly, our results indicate that, unlike similar lymphomas of tonsillar origin, localized primary non-tonsillar oral diffuse large B-cell lymphomas exhibit favorable prognosis, suggesting that these lymphomas may be clinicopathologically distinct. (Cancer Sci 2009; 100: 42-46).

    DOI: 10.1111/j.1349-7006.2008.00995.x

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  • Genome-Wide Analysis of B Cell Non-Hodgkin's Lymphoma Disclosed Frequent Involvement of Genes in NFkB Pathway 査読

    Kato Motohiro, Nakazaki Kumi, Sato Yasuharu, Takeuchi Kengo, Sanada Masashi, Asakura Yoshitaka, Muto Satsuki, Chen Yuyan, Takita Junko, Hayashi Yasuhide, Igarashi Takashi, Watanabe Toshiki, Tobinai Kensei, Ishikawa Yuichi, Mori Shigeo, Kurokawa Mineo, Yoshino Tadashi, Kobayashi Yukio, Ogawa Seishi

    BLOOD   112 ( 11 )   300   2008年11月

  • IgG4-producing marginal zone B-cell lymphoma

    Yasuharu Sato, Katsuyoshi Takata, Kouichi Ichimura, Takehiro Tanaka, Toshiaki Morito, Maiko Tamura, Tadashi Yoshino

    INTERNATIONAL JOURNAL OF HEMATOLOGY   88 ( 4 )   428 - 433   2008年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPRINGER JAPAN KK  

    IgG4-related disease is a recently proposed clinical entity with several unique clinicopathological features. A chronic inflammatory state with marked fibrosis, which can often be mistaken for malignancy, especially by clinical imaging analyses, unifies these features. Little is known about lymphomagenesis in the context of IgG4-related disease, we recently first reported the ocular adnexal marginal zone B-cell lymphomas arising from IgG4-related disease. To the best of our knowledge, no existing study has ever established the neoplastic potential of IgG4-producing cells. In the present report, we describe the first IgG4-producing lymphoma. The patient was a 72-year-old male who was being followed for an asbestos-related pleural plaque. During follow-up, computed tomography revealed bilateral renal masses and multiple swollen retroperitoneal lymph nodes. A retroperitoneal lymph node biopsy was performed. Histologically, the interfollicular areas were expanded by medium to large plasmacytoid cells. These plasmacytoid cells showed nuclear pleomorphism and had prominent Russell bodies. Immunohistochemistry and double immunofluorescence staining of these cells revealed IgG4 positivity and monotypic lambda-light chain predominance. A portion of these cells were partially positive for CD20, negative for CD3, and somewhat faintly positive for CD138. In addition, serum IgG4 was elevated. Southern blot analysis of the lymph node specimen detected immunoglobulin heavy chain gene rearrangement. The present study indicates that, not only can malignant lymphomas occur in the setting of IgG4-related disease, but IgG4-producing cells can also be neoplastic.

    DOI: 10.1007/s12185-008-0170-8

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  • Ocular adnexal IgG4-related disease has uniform clinicopathology. 国際誌

    Yasuharu Sato, Koh-ichi Ohshima, Kouichi Ichimura, Masakazu Sato, Ichiro Yamadori, Takehiro Tanaka, Katsuyoshi Takata, Toshiaki Morito, Eisaku Kondo, Tadashi Yoshino

    Pathology international   58 ( 8 )   465 - 70   2008年8月

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    記述言語:英語  

    IgG4-related disease is a recently proposed clinical entity with several unique clinicopathological features. Ocular adnexal IgG4-related disease, however, has not well been clarified. The purpose of the present study was to examine 21 patients (10 men, 11 women; age range, 39-86 years) with ocular adnexal IgG4-related disease. In 17 out of 21 patients (81%), the lacrimal glands were involved and bilateral lacrimal gland swelling was frequently observed (n = 12; 70.6%). In contrast, the conjunctiva was not involved in any of the patient. Histology was uniform with marked lymphoplasmacytic infiltration admixed with dense fibrosis, similar to previous reports of IgG4-related disease. Immunostaining detected numerous aggregates of IgG4-positive plasma cells. Serum IgG4 was higher than normal in 10 of the 13 patients tested, although it was measured after treatment in almost all cases. Interestingly, immunoglobulin heavy chain gene rearrangement was detected in two of 17 patients (12%) examined. The present results show that ocular adnexal IgG4-related disease has uniform clinicopathology: that is, disease involving the bilateral lacrimal glands with lymphoid hyperplasia and fibrosis, but not the conjunctiva. And presence of immunoglobulin heavy chain gene rearrangement suggests the possibility of B-cell lymphoma arising in a background of IgG4-related chronic inflammation.

    DOI: 10.1111/j.1440-1827.2008.02257.x

    PubMed

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  • Duodenal follicular lymphomas share common characteristics with mucosa-associated lymphoid tissue lymphomas

    Y. Sato, K. Ichimura, T. Tanaka, K. Takata, T. Morito, H. Sato, Y. Sato, E. Kondo, H. Yanai, N. Ohara, T. Oka, T. Yoshino

    JOURNAL OF CLINICAL PATHOLOGY   61 ( 3 )   377 - 381   2008年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:B M J PUBLISHING GROUP  

    Background: Follicular lymphomas occasionally arise in the extra-nodal organs and are frequently found in the duodenum. They are often localised tumours with multiple polyps around the ampulla of Vater.
    Aims: To examine a IgH/bcl-2 hybrid gene and VH gene to investigate the nature of the lymphoma cells and how they differ from nodal follicular lymphomas and MALT lymphomas.
    Methods: Of 40 patients reported previously, 35 with duodenal follicular lymphoma were studied in detail with respect to clinicopathological characteristics.
    Results: 37/40 patients were in clinical stage I (n= 30) or stage II (n= 7). Clonal immunoglobulin gene rearrangement was detected in 53.3% of examined cases, and rearrangement of IgH/bcl-2 gene at the major break point was detected in 27% of cases. Three of 8 examined cases were VH4 (38%); 2 out of them were VH4-34. As VH4 deviation is one of the common characteristics of MALT lymphomas and 2/3 were identical, duodenal follicular lymphomas have a similar aetiology to MALT lymphomas. Clinical course was also similar to that of MALT lymphomas.
    Conclusions: Results suggest that duodenal follicular lymphomas have intermediate characteristics of MALT lymphomas and nodal follicular lymphomas.

    DOI: 10.1136/jcp.2007.049825

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  • HHV-8/KSHV-Negative and CD20-Positive Primary Effusion Lymphoma Successfully Treated by Pleural Drainage Followed by Chemotherapy Containing Rituximab

    Yasushi Terasaki, Hirokazu Okumura, Katsuhiko Saito, Yasuharu Sato, Tadashi Yoshino, Ryo Ichinohasama, Youichi Ishida

    INTERNAL MEDICINE   47 ( 24 )   2175 - 2178   2008年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:JAPAN SOC INTERNAL MEDICINE  

    The present patient was diagnosed as having human herpes virus-8 (HHV-8)/Kaposi sarcoma herpes virus (KSHV)-negative and CD20-positive primary effusion lymphoma (PEL) of the right-sided pleural effusion. After pleural drainage, malignant cells disappeared spontaneously in a small amount of the remaining pleural effusion without chemotherapy. The patient was treated with six cycles of chemotherapy consisting of rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone. He has been in complete remission for more than 22 months. It is suggested that effusion drainage followed by chemotherapy containing rituximab is a potential treatment strategy for patients with HHV-8/KSHV-negative and CD20-positive PEL.

    DOI: 10.2169/internalmedicine.47.1565

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  • ラット中脳動脈閉塞・再灌流モデルにおける抗 HMGB1 単クローン抗体の治療効果

    劉 克約, 森 秀治, 高橋 英夫, 友野 靖子, 和気 秀徳, 菅家 徹, 佐藤 康晴, 平賀 憲人, 足立 尚登, 吉野 正, 西堀 正洋

    岡山医学会雑誌   120 ( 3 )   271 - 277   2008年

  • Synchronous pulmonary MALT lymphoma and pulmonary adenocarcinoma after metachronous gastric MALT lymphoma and gastric adenocarcinoma.

    Ichihara E, Tabata M, Takigawa N, Sato Y, Kondo E, Aoe M, Kiura K, Tanimoto M

    J Thorac Oncol   3 ( 11 )   1362 - 1363   2008年

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  • Anti-high mobility group box1 monoclonal antibody ameliorates brain infarction induced by transient ischemia in rats

    Keyue Liu, Shuji Mori, Hideo Takahashi, Yasuko Tornono, Hidenori Wake, Toru Kanke, Yasuharu Sato, Norihito Hiraga, Naoto Adati, Tadashi Yoshino, Masahiro Nishibori

    JOURNAL OF PHARMACOLOGICAL SCIENCES   106   129P - 129P   2008年

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    記述言語:英語   出版者・発行元:JAPANESE PHARMACOLOGICAL SOC  

    Web of Science

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  • Anti-high mobility group box 1 monoclonal antibody ameliorates brain infarction induced by transient ischemia in rats

    Keyue Liu, Shuji Mori, Hideo K. Takahashi, Yasuko Tomono, Hidenori Wake, Toru Kanke, Yasuharu Sato, Norihito Hiraga, Naoto Adachi, Tadashi Yoshino, Masahiro Nishibori

    FASEB JOURNAL   21 ( 14 )   3904 - 3916   2007年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:FEDERATION AMER SOC EXP BIOL  

    The high mobility group box-1 (HMGB1), originally identified as an architectural nuclear protein, exhibits an inflammatory cytokine- like activity in the extracellular space. Here we show that treatment with neutralizing anti- HMGB1 monoclonal antibody ( mAb; 200 mu g, twice) remarkably ameliorated brain infarction induced by 2- h occlusion of the middle cerebral artery in rats, even when the mAb was administered after the start of reperfusion. Consistent with the 90% reduction in infarct size, the accompanying neurological deficits in locomotor function were significantly improved. Anti- HMGB1 mAb inhibited the increased permeability of the blood- brain barrier, the activation of microglia, the expression of TNF-alpha and iNOS, and suppressed the activity of MMP- 9, whereas it had little effect on blood flow. Intracerebroventricular injection of HMGB1 increased the severity of infarction. Immunohistochemical study revealed that HMGB1 immunoreactivity in the cell nuclei decreased or disappeared in the affected areas, suggesting the release of HMGB1 into the extracellular space. These results indicate that HMGB1 plays a critical role in the development of brain infarction through the amplification of plural inflammatory responses in the ischemic region and could be an outstandingly suitable target for the treatment. Intravenous injection of neutralizing anti- HMGB1 mAb provides a novel therapeutic strategy for ischemic stroke.

    DOI: 10.1096/fj.07-8770com

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書籍等出版物

  • 非腫瘍性疾患病理アトラス リンパ組織

    佐藤康晴, 竹内賢吾( 担当: 編集)

    文光堂  2023年4月  ( ISBN:9784830604911

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    総ページ数:viii, 292p   記述言語:日本語

    CiNii Books

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  • 【病理診断クイックリファレンス 2023】(第15章)リンパ節・脾臓 良性上皮封入像(卵管内膜症)

    西村 碧フィリーズ, 佐藤 康晴

    (株)文光堂  2023年4月 

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    記述言語:日本語

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  • 【病理診断クイックリファレンス 2023】(第15章)リンパ節・脾臓 Castleman病

    西村 碧フィリーズ, 佐藤 康晴

    (株)文光堂  2023年4月 

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    記述言語:日本語

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  • 病理学

    村雲, 芳樹, 佐藤, 康晴, 齊尾, 征直, 伊藤, 彰彦(病理学), 高橋, 博之(病理学), 伊藤, 智雄, 西村, 広健, 川井, 久美, 吉田, 眞理, 安倍, 雅人, 細, 正博, 渡邉, 純( 担当: 編集)

    医学書院  2022年10月  ( ISBN:9784260049863

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    総ページ数:xv, 309p   記述言語:日本語

    CiNii Books

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  • キャッスルマン病, TAFRO症候群

    吉崎, 和幸, 川上, 純( 範囲: 5. キャッスルマン病の病理)

    フジメディカル出版  2022年3月  ( ISBN:9784862702500

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    総ページ数:viii, c15, 251p   記述言語:日本語

    CiNii Books

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  • 細胞診鑑別アトラス

    金城, 満, 亀井, 敏昭, 樋口, 佳代子, 青笹, 克之( 担当: 共著 ,  範囲: 第Ⅱ編・第13章・造血器・リンパ組織)

    医歯薬出版  2021年6月  ( ISBN:9784263731994

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    総ページ数:xiii, 410p   記述言語:日本語

    CiNii Books

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  • 悪性リンパ腫治療マニュアル

    永井, 宏和, 山口, 素子, 丸山, 大, 飛内, 賢正, 木下, 朝博, 塚崎, 邦弘( 担当: 共著 ,  範囲: 免疫組織化学とフローサイトメトリー)

    南江堂  2020年11月  ( ISBN:9784524226450

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    総ページ数:x, 395p   記述言語:日本語

    CiNii Books

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  • 臨床医必読 最新IgG4関連疾患 改訂第2版

    佐藤康晴, 吉野 正( 担当: 共著 ,  範囲: リンパ節病変 p167-170)

    診断と治療社  2019年12月 

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  • WHO分類改訂第4版による白血病・リンパ系腫瘍の病態学(木崎昌弘,田丸淳一・編集)

    佐藤 康晴( 担当: 共著)

    中外医学社  2019年2月 

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  • リンパ腫セミナー 基本から学べるWHO分類改訂第4版(2017年)

    佐藤 康晴( 担当: 共著 ,  範囲: Ⅰ章 総論 セミナー6 リンパ節スタンプ標本の見方 p43-46)

    南江堂  2018年10月 

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  • リンパ腫アトラス第5版

    佐藤 康晴( 担当: 共著)

    文光堂  2018年10月 

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  • WHO血液腫瘍分類 ~WHO分類2017をうまく活用するために 改訂版

    佐藤 康晴( 担当: 共著 ,  範囲: 6. リンパ形質細胞性リンパ腫 p206-p208)

    医薬ジャーナル社  2018年10月 

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  • 血液細胞アトラス第6版(編集: 通山 薫,張替秀郎)

    佐藤康晴( 担当: 共著)

    文光堂  2018年2月 

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  • Castleman disease (Frits van Rhee, Nikhil C. Munshi, ed)

    Takuro Igawa, Yasuharu Sato( 担当: 共著)

    ELSEVIER  2018年 

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  • ~基礎から学ぶ~ 細胞診のすすめ方(第4版)

    佐藤康晴( 担当: 共著 ,  範囲: リンパ節および節外の細胞診 ~リンパ腫・非腫瘍性病変の細胞診~ P222-P242)

    近代出版  2018年 

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  • よく分かるIgG4関連疾患; 類縁疾患 Case 18 IgG4関連疾患との鑑別を要した涙腺MALTリンパ腫の1例

    佐藤康晴

    中外医学社  2017年 

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  • よく分かるIgG4関連疾患; 2. 類縁疾患 Case 17 IgG4高値を示した肺キャッスルマン病の1例

    佐藤康晴

    中外医学社  2017年 

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  • よく分かるIgG4関連疾患; 類縁疾患 Case 16 IgG4高値を示した形質細胞型キャッスルマン病の1例

    佐藤康晴

    中外医学社  2017年 

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  • よく分かるIgG4関連疾患; 1. IgG4関連疾患 Case 9 悪性リンパ腫との鑑別を要したIgG4関連リンパ節症の1例

    佐藤康晴

    中外医学社  2017年 

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  • 別冊BIO Clinica 慢性炎症と疾患「慢性炎症とがん」 / IgG4関連疾患とリンパ腫の発症

    北隆館  2016年 

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  • IgG4関連疾患 ~実践的臨床から病因へ~; リンパ節からみた鑑別診断(Castleman病を中心に)

    前田書店  2015年 

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  • IgG4関連疾患 実践的臨床から病因へ

    前田書店  2015年 

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  • IgG4関連疾患 ~実践的臨床から病因へ~; IgG4関連疾患とリンパ腫

    前田書店  2015年 

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  • 日本臨牀(増刊号) リンパ腫学~最新の研究動向~ / X 節外リンパ腫の臓器別特徴と治療 7. 甲状腺リンパ腫

    日本臨牀社  2015年 

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  • 日本臨牀(増刊号) リンパ腫学~最新の研究動向~ / XI 特論 3. IgG4関連疾患

    日本臨牀社  2015年 

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  • 臨床医必読 最新IgG4関連疾患 / リンパ節病変

    診断と治療社  2015年 

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  • 悪性リンパ腫治療マニュアル 改訂第4版 / 低悪性度リンパ腫・マントル細胞リンパ腫の病理診断のポイント

    南江堂  2015年 

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  • IgG4関連疾患 ~実践的臨床から病因へ~; IgG4関連疾患におけるマスト細胞の役割

    前田書店  2015年 

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  • リンパ腫アトラス 改訂・改題 第4版

    文光堂  2014年 

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  • レベルアップのためのリンパ腫セミナー

    南江堂  2014年 

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  • 細胞診断マニュアル ―細胞像の見方と診断へのアプローチ―

    篠原出版新社  2014年 

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  • IgG4-related disease

    Springer  2014年 

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  • IgG4関連腎臓病のすべて

    南江堂  2014年 

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  • IgG4-related disease

    Springer  2013年 

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  • 胸膜全書

    医薬ジャーナル社  2013年  ( ISBN:9784753226030

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  • IgG4関連疾患アトラス –IgG4研究会モノグラフ-

    前田書店  2012年 

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  • –基礎から学ぶ- 細胞診のすすめ方(第3版) (共著)

    近代出版  2012年 

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  • 自己評価型 病理学ノート(共著)

    西村書店  2011年 

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  • 整形外科専門医テキスト(共著)

    南江堂  2010年  ( ISBN:9784524242313

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  • 血液診療エキスパート 悪性リンパ腫(共著)

    中外医学社  2010年 

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  • 細胞診と病理診断(共著)

    医学書院  2010年 

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  • 病理と臨床 臨時増刊号 Vol.28 病理形態学キーワード(共著)

    文光堂  2010年 

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  • WHO血液腫瘍分類~WHO分類2008をうまく活用するために~(共著)

    医薬ジャーナル社  2010年 

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  • 悪性リンパ腫診療ハンドブック(共著)

    南江堂  2010年 

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  • ダイナミック病理学-365症例からのアプローチ-(共著)

    西村書店  2010年  ( ISBN:9784890134021

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  • 腫瘍鑑別アトラス 皮膚腫瘍Ⅱ メラノサイト系腫瘍とリンパ・組織球・造血系腫瘍(共著)

    文光堂  2010年  ( ISBN:9784830622298

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  • 悪性リンパ腫治療マニュアル(共著)

    南江堂  2009年 

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▼全件表示

MISC

  • 【キャッスルマン病・TAFRO症候群:病態・病理・診療の最新情報】特発性多中心性キャッスルマン病のリンパ節病理

    西村 碧フィリーズ, 錦織 亜沙美, 西村 義人, 佐藤 康晴

    炎症と免疫   31 ( 5 )   430 - 434   2023年8月

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    記述言語:日本語   出版者・発行元:(株)先端医学社  

    特発性多中心性キャッスルマン病(iMCD)は,TAFRO症候群を伴うTAFRO typeと,TAFRO症候群を伴わないもののうちポリクローナルな高γグロブリン血症に特徴づけられるIPL type,そしてそれら以外のNOS typeの3つの臨床病型に分類される.iMCDはリンパ節の組織像からも血管増生型と形質細胞型とに分類され,組織型は臨床病型とおおよそ相関し診断を補完する.また,TAFRO症候群はiMCD以外の病態でも呈しうることから,臨床と病理をあわせた充分な検討が必須である.本稿ではiMCDのリンパ節病理について解説するとともに,iMCDの基準を満たさないTAFRO症候群との鑑別点にも触れる.(著者抄録)

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  • IgG4関連疾患大全-自己免疫性膵炎とIgG4関連硬化性胆管炎を中心に-IV.その他のIgG4関連疾患の病態,診断と治療 IgG4関連リンパ節症 招待

    錦織亜沙美, 西村碧フィリーズ, 佐藤康晴

    胆と膵   43   2022年11月

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    担当区分:最終著者   記述言語:日本語  

    J-GLOBAL

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  • リンパ腫と関連疾患のトピックスII-T細胞リンパ腫とリンパ腫関連疾患-Idiopathic multicentric Castleman diseaseの分類と臨床病理学的特徴 招待

    錦織亜沙美, 西村碧フィリーズ, 佐藤康晴

    病理と臨床   40 ( 11 )   2022年11月

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    担当区分:最終著者  

    J-GLOBAL

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  • リンパ腫と関連疾患のトピックスII-T細胞リンパ腫とリンパ腫関連疾患-Castleman病の歴史的背景とunicentric Castleman disease 招待

    西村碧フィリーズ, 錦織亜沙美, 佐藤康晴

    病理と臨床   40 ( 11 )   2022年11月

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    担当区分:最終著者  

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  • ANL Secondary Publication 上顎洞癌に対する動注化学放射線治療の病理学的評価

    牧野 琢丸, 橘 智靖, 假谷 伸, 松井 裕輔, 松崎 秀信, 藤本 将平, 折田 頼尚, 藤井 邦明, 平木 隆夫, 佐藤 康晴, 金澤 右, 西崎 和則

    日本耳鼻咽喉科頭頸部外科学会会報   125 ( 5 )   913 - 915   2022年5月

  • 【知っておきたい病理の知識】頭頸部領域におけるリンパ腫およびリンパ増殖異常症 招待

    佐藤 康晴, 折田 頼尚

    耳鼻咽喉科   1 ( 5 )   641 - 644   2022年5月

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    担当区分:筆頭著者, 最終著者, 責任著者   記述言語:日本語   出版者・発行元:(有)科学評論社  

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  • 腫瘍とウイルスーヒトパピローマウイルス 招待

    折田頼尚, 佐藤康晴

    耳鼻咽喉科   1 ( 1 )   21 - 25   2022年1月

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    担当区分:最終著者   記述言語:日本語  

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  • 特発性多中心性キャッスルマン病とIPL 招待

    佐藤 康晴, 錦織 亜沙美, 西村 碧フィリーズ

    病理と臨床   39 ( 9 )   938 - 940   2021年9月

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    担当区分:筆頭著者, 責任著者   記述言語:日本語   出版者・発行元:(株)文光堂  

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  • IgG4関連疾患-診断と治療の最新動向 IgG4関連疾患の病態・病理 招待

    佐藤康晴

    カレントテラピー   38 ( 7 )   2020年

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    担当区分:筆頭著者, 最終著者, 責任著者  

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  • Castleman-Kojima diseaseとTAFRO症候群 招待

    佐藤康晴

    病理と臨床   37 ( 9 )   899 - 901   2019年9月

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    担当区分:筆頭著者, 責任著者   記述言語:日本語  

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  • その他の医原性免疫不全関連リンパ増殖性疾患 招待

    佐藤康晴, 祇園由佳, 西田圭一郎, 吉野 正

    病理と臨床   37 ( 4 )   360 - 363   2019年4月

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    担当区分:筆頭著者, 責任著者   記述言語:日本語  

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  • 頭頸部領域におけるリンパ腫とその鑑別アプローチ 招待

    折田頼尚, 佐藤康晴

    耳鼻咽喉科展望   62 ( 2 )   68 - 73   2019年4月

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    担当区分:最終著者  

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  • 濾胞性リンパ腫 招待

    吉野 正, 田端哲也, 佐藤康晴

    病理と臨床   37 ( 3 )   256 - 261   2019年3月

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    担当区分:最終著者   記述言語:日本語  

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  • IgG4関連眼疾患の病理 招待

    佐藤康晴, 大島浩一

    眼科   60 ( 5 )   449 - 458   2018年5月

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    担当区分:筆頭著者, 責任著者   記述言語:日本語  

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  • IgG4関連リンパ節症 招待

    佐藤康晴

    日本医師会雑誌   147 ( 2 )   285 - 287   2018年5月

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    担当区分:筆頭著者, 責任著者   記述言語:日本語  

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  • 頭頸部領域におけるリンパ腫および類縁疾患 招待

    佐藤康晴, 吉野 正

    病理と臨床   36 ( 4 )   353 - 357   2018年4月

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    担当区分:筆頭著者, 責任著者   記述言語:日本語  

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  • リンパ節の見方

    中村直哉, 佐藤康晴

    病理と臨床   35 ( 6 )   502 - 503   2017年

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    担当区分:最終著者  

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  • IgG4関連疾患における病理組織診断の重要性

    アレルギーの臨床   36 ( 13 )   36 - 40   2016年

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  • IgG4関連疾患とリンパ腫の発症

    竹内真衣, 佐藤康晴, 吉野 正

    別冊Bio Clinica 慢性炎症とがん   5   43 - 47   2016年

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  • 血清IL-8、IL-4、IL-1βは消化管低悪性度B細胞性リンパ腫患者において高値を示す

    高田 友子, 高田 尚良, 都地 友紘, 後藤 尚絵, 笠原 千嗣, 高橋 健, 田 利晶, 佐藤 康晴, 吉野 正

    日本リンパ網内系学会会誌   55   102 - 102   2015年6月

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    記述言語:日本語   出版者・発行元:(一社)日本リンパ網内系学会  

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  • 消化管低悪性度B細胞性リンパ腫患者では血清IL-8、IL-4、IL-1βは高値を示す

    高田 友子, 高田 尚良, 都地 友紘, 後藤 尚絵, 笠原 千嗣, 高橋 健, 田利 晶, 佐藤 康晴, 吉野 正

    日本病理学会会誌   104 ( 1 )   280 - 280   2015年3月

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    記述言語:日本語   出版者・発行元:(一社)日本病理学会  

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  • リンパ節におけるIgG4関連疾患(特集: 全身性疾患としてのIgG4関連疾患)

    Modern Physician   35 ( 11 )   1351 - 1353   2015年

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  • 血液病理学におけるIgG4関連疾患

    病理と臨床   2015年

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  • リンパ腫のWHO分類と病型頻度

    日本臨牀   2014年

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  • IgG4関連疾患の病理 -神経系を中心に-

    神経内科   2014年

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  • Epstein‐Barr virus関連リンパ腫/リンパ増殖性疾患におけるA20の不活性化

    安藤翠, 佐藤康晴, 高田尚良, 野本順子, 中村栄男, 大島孝一, 竹内保, 小林幸夫, 吉野正

    日本病理学会会誌   102 ( 1 )   481 - 481   2013年4月

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    記述言語:日本語   出版者・発行元:(一社)日本病理学会  

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  • MTX中止直後に一過性の白血球増多を認め、その後自然退縮したMTX-LPDの一例

    近藤 英生, 葛島 清隆, 市村 浩一, 前田 嘉信, 藤井 伸治, 松岡 賢市, 品川 克至, 長谷川 詠子, 黒井 大雅, 佐伯 恭昌, 浅野 豪, 高田 尚良, 佐藤 康晴, 吉野 正, 谷本 光音

    日本リンパ網内系学会会誌   53   133 - 133   2013年4月

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    記述言語:日本語   出版者・発行元:(一社)日本リンパ網内系学会  

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  • IgG4関連疾患の病理診断 : 鑑別診断を中心に (特集 IgG4関連疾患 : 21世紀に生まれた新たな疾患概念) -- (IgG4関連疾患の診断)

    佐藤 康晴, 吉野 正

    最新医学   67 ( 4 )   958 - 964   2012年4月

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    記述言語:日本語   出版者・発行元:最新医学社  

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    その他リンク: http://search.jamas.or.jp/link/ui/2012208402

  • IgG4-related lymphadenopathy.(共著)

    International Journal of Rheumatology   2012年

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  • IgG4関連疾患とは?(共著)

    Medical Technology   2012年

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  • IgG4関連疾患(共著)

    臨床病理   2012年

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  • IgG4関連疾患の病理.

    佐藤康晴, 吉野 正

    腎と透析   73 ( 5 )   639 - 643   2012年

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  • IgG4関連疾患の病理診断―識別診断を中心に―.

    佐藤康晴, 吉野 正

    最新医学   67 ( 4 )   7 - 21   2012年

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  • 慢性リンパ性白血病/小細胞性リンパ腫(CLL/SLL)とcyclin D2.

    佐藤康晴, 井川卓朗, 吉野 正

    血液内科   65 ( 1 )   27 - 32   2012年

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    記述言語:日本語   出版者・発行元:(有)科学評論社  

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  • PTGC型IgG4関連リンパ節症の臨床病理学的解析

    佐藤 康晴, 小島 勝, 高田 尚良, 井上 大, 吉野 正

    日本リンパ網内系学会会誌   51   90 - 90   2011年6月

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    記述言語:日本語   出版者・発行元:(一社)日本リンパ網内系学会  

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  • ステロイド治療に対し良好な反応性を示したIgG4関連多臓器リンパ増殖症候群(MOLPS)による前立腺炎の1例

    能勢 宏幸, 神原 太樹, 佐々木 克己, 上原 慎也, 渡辺 豊彦, 雑賀 隆史, 那須 保友, 公文 裕巳, 佐藤 康晴, 吉野 正, 松本 裕子, 村田 匡, 明比 直樹

    西日本泌尿器科   73 ( 4 )   201 - 201   2011年4月

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    記述言語:日本語   出版者・発行元:西日本泌尿器科学会  

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  • 唾液腺悪性リンパ腫の病理

    病理と臨床   2011年

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  • gG4関連疾患の病理診断-リンパ節病変を中心に(IgG4関連疾患-日本発あらたな疾患概念).

    佐藤康晴, 吉野 正

    医学のあゆみ   236 ( 3 )   214 - 218   2011年

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  • BCL2,C-MYC,BCL6転座を有するtriple-hit lymphomaの3例

    鈴木優子, 増成太郎, 二宮貴一朗, 益田加奈, 田村朋季, 木村耕介, 園部宏, 佐藤康晴, 吉野正, 瀬崎伸夫, 瀬崎伸夫

    臨床血液   52 ( 9 )   2011年

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  • IgG4関連疾患と悪性リンパ腫(共著)

    佐藤康晴, 小島 勝, 吉野 正

    病理と臨床   2010年

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  • IgG4関連疾患(共著)

    佐藤康晴, 吉野 正

    岡山医学会雑誌   2010年

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  • IgG4関連疾患の病理診断-リンパ節病変を中心に(共著)

    佐藤康晴, 吉野 正

    医学のあゆみ   2010年

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  • B細胞性悪性リンパ腫に対する網羅的ゲノム解析によるがん抑制遺伝子A20の同定(Genome-wide analysis identifies frequent inactivation of A20 in B-cell lymphomas)

    加藤 元博, 真田 昌, 加藤 格, 佐藤 康晴, 竹内 賢吾, 丹羽 明, 野本 順子, 中釜 斉, 石川 雄一, 中畑 龍俊, 吉野 正, 小林 幸夫, 小川 誠司

    日本癌学会総会記事   68回   82 - 82   2009年8月

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    記述言語:英語   出版者・発行元:日本癌学会  

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  • 悪性リンパ腫におけるNFκB経路制御遺伝子の変異解析(Mutation analysis of genes regulating NFkappaB pathway in malignant lymphoma)

    川幡 亮一郎, 加藤 元博, 真田 昌, 佐藤 康晴, 竹内 賢吾, 滝田 順子, 野本 順子, 朝倉 義崇, 渡邉 俊樹, 吉野 正, 小林 幸夫, 小川 誠司

    日本癌学会総会記事   68回   82 - 82   2009年8月

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    記述言語:英語   出版者・発行元:日本癌学会  

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  • IgG4関連硬化性疾患でのリンパ節病変(共著)

    小島 勝, 佐藤康晴, 大月寛郎, 小林 寛, 吉野 正, 中村栄男

    病理と臨床   2009年

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  • 消化管濾胞性リンパ腫.

    吉野 正, 佐藤康晴, 市村浩一, 田中健大, 高田尚良, 守都敏晃, 大西尚子, 田村麻衣子, 岡田裕之, 河原祥朗, 竹中龍太, 田利 晶

    胃と腸   43 ( 7 )   1039 - 1046   2008年

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  • 十二指腸原発濾胞性リンパ腫の臨床病理学的特徴.

    大西尚子, 佐藤康晴, 市村浩一, 高田尚良, 守都敏晃, 田村麻衣子, 吉野 正, 岡田裕之, 田利 晶

    血液・腫瘍科   56 ( 5 )   603 - 609   2008年

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    記述言語:日本語   出版者・発行元:科学評論社  

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  • 悪性リンパ腫における分子病理診断の役割.

    市村浩一, 佐藤康晴, 高田尚良, 守都敏晃, 吉野 正

    病理と臨床   26 ( 7 )   690 - 700   2008年

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  • 悪性リンパ腫の分類・予後.

    佐藤康晴, 吉野 正

    Medical Technology   35   751 - 754   2007年

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  • 除菌無効胃MALTリンパ腫の分子病理的特徴.

    守都敏晃, 佐藤康晴, 高田尚良, 田中健大, 市村浩一, 吉野 正

    胃と腸   42 ( 8 )   1191 - 1197   2007年

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  • リンパ腫とその発生母地となる病変.

    守都敏晃, 佐藤康晴, 田中健大, 市村浩一, 高田尚良, 大町尚子, 田村麻衣子, 吉野 正

    分子細胞治療   6 ( 6 )   22 - 28   2007年

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  • 腸管悪性リンパ腫の分子病理学的特徴.

    吉野 正, 市村浩一, 佐久川純枝, 佐藤由美子, 田中健大, 佐藤康晴

    胃と腸   41,3,295-303   2006年

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▼全件表示

講演・口頭発表等

  • リンパ腫及び類縁疾患のトピックス:研究から診断へ 多中心性Castleman病の分類と展望

    西村 碧フィリーズ, 錦織 亜沙美, 吉野 正, 佐藤 康晴

    日本病理学会会誌  2023年3月  (一社)日本病理学会

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    開催年月日: 2023年3月

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  • 遺伝子解析に有用な細胞固定液と保存方法の検討

    湯浅 凌雅, 木山 仁, 氏家 英貴, 前濱 かんな, 前川 倖希奈, 吉田 紗弥子, 錦織 亜沙美, 西村 碧フィリーズ, 佐藤 康晴

    日本病理学会会誌  2023年3月  (一社)日本病理学会

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    開催年月日: 2023年3月

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  • 特発性多中心性キャッスルマン病における増生血管の病理学的特徴

    錦織 亜沙美, 西村 碧フィリーズ, 佐藤 康晴

    日本病理学会会誌  2023年3月  (一社)日本病理学会

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    開催年月日: 2023年3月

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  • 特発性多中心性キャッスルマン病における臨床病理学的検討

    前濱 かんな, 錦織 亜沙美, 西村 碧フィリーズ, 佐藤 康晴

    日本病理学会会誌  2023年3月  (一社)日本病理学会

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    開催年月日: 2023年3月

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  • リンパ節の細胞診:各領域における最近の進歩 リンパ腫およびリンパ増殖性疾患への分子病理学的アプローチ

    錦織 亜沙美, 西村 碧フィリーズ, 前濱 かんな, 佐藤 康晴

    日本臨床細胞学会雑誌  2022年10月  (公社)日本臨床細胞学会

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    開催年月日: 2022年10月

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  • DLBCL日本人コホートにおけるCell-of-OriginとDouble hit-signatureの臨床学的意義:OHSG DLBCL 1K-project

    浦田 知宏, 遠西 大輔, 角南 一貴, 今井 利, 名和 由一郎, 平松 靖史, 山本 和彦, 藤井 総一郎, 吉田 功, 矢野 朋文, 佐藤 康晴, 吉野 正, 前田 嘉信

    日本リンパ網内系学会会誌  2022年6月  (一社)日本リンパ網内系学会

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    開催年月日: 2022年6月

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  • IL-6蛋白発現による特発性多中心性キャッスルマン病(iMCD)の分類

    錦織 亜沙美, 前川 倖希奈, 西村 碧フィリーズ, 佐藤 康晴

    日本リンパ網内系学会会誌  2022年6月  (一社)日本リンパ網内系学会

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    開催年月日: 2022年6月

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  • リンパ腫診断における細胞診の活用

    前濱 かんな, 錦織 亜沙美, 西村 碧フィリーズ, 佐藤 康晴

    日本リンパ網内系学会会誌  2022年6月  (一社)日本リンパ網内系学会

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    開催年月日: 2022年6月

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  • 硝子血管型単中心性キャッスルマン病38例の臨床病理学的特徴の解析

    西村 碧フィリーズ, 錦織 亜沙美, 佐藤 康晴

    日本リンパ網内系学会会誌  2022年6月  (一社)日本リンパ網内系学会

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    開催年月日: 2022年6月

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  • 過去の細胞診標本を用いたIgH遺伝子再構成の検出 26年前の標本は解析可能か

    前濱 かんな, 錦織 亜沙美, 木山 仁, 前川 倖希奈, 吉田 紗弥子, 吉野 正, 佐藤 康晴

    日本臨床細胞学会雑誌  2022年5月  (公社)日本臨床細胞学会

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    開催年月日: 2022年5月

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  • ANL Secondary Publication 上顎洞癌に対する動注化学放射線治療の病理学的評価

    牧野 琢丸, 橘 智靖, 假谷 伸, 松井 裕輔, 松崎 秀信, 藤本 将平, 折田 頼尚, 藤井 邦明, 平木 隆夫, 佐藤 康晴, 金澤 右, 西崎 和則

    日本耳鼻咽喉科頭頸部外科学会会報  2022年5月  (一社)日本耳鼻咽喉科頭頸部外科学会

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    吉田紗弥子, 江草侑厘安, 木山仁, 前川倖希奈, 錦織亜沙美, 藤田梓, 佐藤康晴

    第111回日本病理学会総会  2022年4月14日 

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    西村碧フィリーズ, 錦織亜沙美, 西村義人, 吉野正, 佐藤康晴

    第111回日本病理学会総会  2022年4月14日 

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    開催年月日: 2022年4月16日

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  • 形質細胞型特発性多中心性キャッスルマン病におけるIL-6免疫染色の検討

    前川倖希奈, 錦織亜沙美, 前濱かんな, 木山仁, 吉田紗弥子, 江草侑厘安, 藤田梓, 西村碧フィリーズ, 佐藤康晴

    第111回日本病理学会総会  2022年4月14日 

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    開催年月日: 2022年4月16日

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  • 遺伝子解析・細胞形態保持に有用な細胞固定液の検討

    木山仁, 藤田梓, 前川倖希奈, 吉田紗弥子, 錦織亜沙美, 江草侑厘安, 佐藤康晴

    第111回日本病理学会総会  2022年4月14日 

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    開催年月日: 2022年4月16日

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  • 抗PD-1 抗体薬(オプジーボ)治療後に2つの異なる皮膚CD8+T 細胞リンパ腫を発症した症例

    山下理子, 錦織亜沙美, 渡邉俊介, 佐藤康晴, 吉野正

    第111回日本病理学会総会 

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    開催年月日: 2022年4月14日 - 2022年4月16日

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  • メトトレキサートリンパ増殖性疾患におけるNOTCHシグナルの発現解析

    吉田 紗弥子, 江草 侑厘安, 木山 仁, 前川 倖希奈, 錦織 亜沙美, 藤田 梓, 佐藤 康晴

    日本病理学会会誌  2022年3月  (一社)日本病理学会

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    開催年月日: 2022年3月

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  • 遺伝子解析・細胞形態保持に有用な細胞固定液の検討

    木山 仁, 藤田 梓, 前川 倖希奈, 吉田 紗弥子, 錦織 亜沙美, 江草 侑厘安, 佐藤 康晴

    日本病理学会会誌  2022年3月  (一社)日本病理学会

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    開催年月日: 2022年3月

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  • 硝子血管型単中心性キャッスルマン病の臨床病理学的特徴 過去20年間の後方視的検討〜

    西村 碧フィリーズ, 錦織 亜沙美, 西村 義人, 吉野 正, 佐藤 康晴

    日本病理学会会誌  2022年3月  (一社)日本病理学会

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    開催年月日: 2022年3月

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  • 抗PD-1抗体薬(オプジーボ)治療後に2つの異なる皮膚CD8+T細胞リンパ腫を発症した症例

    山下 理子, 錦織 亜沙美, 渡邉 俊介, 佐藤 康晴, 吉野 正

    日本病理学会会誌  2022年3月  (一社)日本病理学会

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    開催年月日: 2022年3月

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  • 難病レジストリ研究の進捗状況 キャッスルマン病・TAFRO症候群のレジストリ研究

    川上 純, 古賀 智裕, 住吉 玲美, 清水 俊匡, 細萱 直希, 森本 心平, 正木 康史, 矢野 真吾, 清水 隆之, 吉崎 和幸, 水木 満佐央, 中村 直哉, 佐藤 康晴, 新納 宏昭

    日本リウマチ学会総会・学術集会プログラム・抄録集  2022年3月  (一社)日本リウマチ学会

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    開催年月日: 2022年3月

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  • 間質性肺疾患単独のIgG4関連疾患と鑑別を要した抗ARS抗体症候群の一例

    早稲田 優子, 木村 聡美, 園田 智明, 三ツ井 美穂, 門脇 麻衣子, 梅田 幸寛, 安斎 正樹, 江頭 玲子, 田畑 和宏, 佐藤 康晴, 石塚 全

    アレルギー  2022年2月  (一社)日本アレルギー学会

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  • Investigation of IgG4-positive cells in idiopathic multicentric Castleman disease and validation of the 2020 exclusion criteria for IgG4-related disease

    Asami Nishikori, Midori Filiz Nishimura, Yoshito Nishimura, Kenji Notohara, Akira Satou, Masafumi Moriyama, Seiji Nakamura, Yasuharu Sato

    The 4th international symposium on IgG4-related disease 

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    開催年月日: 2021年12月2日 - 2021年12月4日

    記述言語:英語   会議種別:口頭発表(一般)  

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  • Pulmonary manifestations of IgG4-related disease and plasma cell type idiopathic multicentric Castleman disease: A proposal for new differential diagnostic approach

    Midori Filiz Nishimura, Yoshito Nishimura, Asami Nishikori, Yasuharu Sato

    The 4th international symposium on IgG4-related disease 

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    開催年月日: 2021年12月2日 - 2021年12月4日

    記述言語:英語   会議種別:口頭発表(一般)  

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  • IgG4関連疾患およびリンパ腫との鑑別を要したALPIBPの一例

    西村 碧フィリーズ, 直井 友亮, 佐藤 康晴, 吉野 正

    日本病理学会会誌  2021年10月  (一社)日本病理学会

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    開催年月日: 2021年10月

    記述言語:日本語  

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  • リンパ節・リンパ腫の細胞診:その使命とゲノム医療への展望 リンパ腫細胞診におけるフローサイトメトリーの活用

    藤田 梓, 江草 侑厘安, 錦織 亜沙美, 祇園 由佳, 吉野 正, 佐藤 康晴

    日本臨床細胞学会雑誌  2021年10月  (公社)日本臨床細胞学会

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  • The clinical and pathologic findings of idiopathic multicentric Castleman disease.

    Yasuharu Sato

    The 1st International Symposium on Castleman disease 

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    開催年月日: 2021年8月13日 - 2021年10月31日

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  • 抗カルジオリピン抗体陽性であったTAFRO症状を呈するリンパ節病変の3症例

    錦織亜沙美, 西村碧フィリーズ, 西村義人, 祇園由佳, 佐藤康晴, 吉野正

    第61回日本リンパ網内系学会総会 

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    開催年月日: 2021年6月24日 - 2021年6月26日

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  • 形質細胞型特発性多中心性キャッスルマン病およびIgG4関連疾患における肺病変の臨床組織学的検討

    西村碧フィリーズ, 井川卓朗, 西村義人, 吉野 正, 佐藤康晴

    第61回日本リンパ網内系学会総会 

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  • 傍腫瘍性神経症候群の合併が疑われたホジキンリンパ腫の一例

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    第61回日本リンパ網内系学会総会 

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  • Deletion of Epstein-Barr virus related BART miRNA cluster in classic Hodgkin lymphoma

    川月章弘, 井川卓朗, 佐藤康晴, 吉野正

    第61回日本リンパ網内系学会総会 

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  • Follicular lymphomaの治療中にclassic Hodgkin lymphomaを新規に発症したMTX-LPDの1例

    上田 弥生, 朝倉 昇司, 矢野 朋文, 池田 知佳, 田中 健大, 佐藤 康晴, 吉野 正

    臨床血液  2021年6月  (一社)日本血液学会-東京事務局

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  • 形質細胞型特発性多中心性キャッスルマン病およびIgG4関連疾患における肺病変の臨床組織学的検討

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    日本リンパ網内系学会会誌  2021年5月  (一社)日本リンパ網内系学会

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  • 形質細胞増多を伴う炎症性疾患の多様性

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    日本臨床細胞学会雑誌  2021年5月  (公社)日本臨床細胞学会

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  • 傍腫瘍性神経症候群の合併が疑われたホジキンリンパ腫の一例

    綾田 善行, 井川 卓朗, 田端 哲也, 田中 健大, 佐藤 康晴, 吉野 正

    日本リンパ網内系学会会誌  2021年5月  (一社)日本リンパ網内系学会

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  • Deletion of Epstein-Barr virus related BART miRNA cluster in classic Hodgkin lymphoma(和訳中)

    川月 章弘, 井川 卓朗, 佐藤 康晴, 吉野 正

    日本リンパ網内系学会会誌  2021年5月  (一社)日本リンパ網内系学会

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    開催年月日: 2021年5月

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  • B細胞性リンパ腫の診断におけるIRTA-1免疫染色の有用性

    田端 哲也, 井川 卓朗, 田中 健大, 佐藤 康晴, 吉野 正

    日本リンパ網内系学会会誌  2021年5月  (一社)日本リンパ網内系学会

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  • IgG4関連唾液腺炎の病型を呈した医原性免疫不全関連リンパ増殖性疾患の1例

    守都 敏晃, 大原 信哉, 井川 卓朗, 佐藤 康晴, 吉野 正

    日本リンパ網内系学会会誌  2021年5月  (一社)日本リンパ網内系学会

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    開催年月日: 2021年5月

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  • IgG4関連疾患の診断基準を満たしたリウマチ結節の1例

    植田 向夏花, 錦織 亜沙美, 江草 侑厘安, 重西 邦浩, 大野 京太郎, 佐藤 康晴

    日本リンパ網内系学会会誌  2021年5月  (一社)日本リンパ網内系学会

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  • 抗カルジオリピン抗体陽性であったTAFRO症状を呈するリンパ節病変の3症例

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    日本リンパ網内系学会会誌  2021年5月  (一社)日本リンパ網内系学会

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    開催年月日: 2021年5月

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  • 関節リウマチ(RA)患者における制御性T細胞(Treg)の解析

    横山 あき, 内山 孝由, 祇園 由佳, 佐藤 康晴, 小山 芳伸, 青木 定夫

    日本リンパ網内系学会会誌  2021年5月  (一社)日本リンパ網内系学会

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    開催年月日: 2021年5月

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  • An autopsy case of Epstein-Barr virus-positive primary intestinal T/NK-cell lymphoma associated with iatrogenic immunodeficiency(和訳中)

    永喜多 敬奈, 井川 卓朗, 佐藤 康晴, 神農 陽子, 須藤 和樹, 高橋 達也, 吉野 正

    日本リンパ網内系学会会誌  2021年5月  (一社)日本リンパ網内系学会

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    開催年月日: 2021年5月

    記述言語:英語  

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  • これからのリンパ腫細胞診断に有用なツールは? リンパ腫細胞診における補助診断 遺伝子再構成とFCM

    江草 侑厘安, 藤田 梓, 祇園 由佳, 吉野 正, 佐藤 康晴

    日本臨床細胞学会雑誌  2021年5月  (公社)日本臨床細胞学会

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    開催年月日: 2021年5月

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  • サイトメガロウイルス胃炎を合併した移植後リンパ増殖異常症の1例

    福岡 威人, 岩本 結衣, 岩本 唯花, 吉野 正, 佐藤 康晴

    日本リンパ網内系学会会誌  2021年5月  (一社)日本リンパ網内系学会

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    開催年月日: 2021年5月

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  • リンパ節細胞診検体を用いた遺伝子解析のための固定液の検討

    藤田 梓, 木山 仁, 錦織 亜沙美, 江草 侑厘安, 祇園 由佳, 佐藤 康晴

    日本リンパ網内系学会会誌  2021年5月  (一社)日本リンパ網内系学会

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    開催年月日: 2021年5月

    記述言語:日本語  

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  • B細胞性リンパ腫におけるIRTA-1発現の検討

    田端哲也, 井川卓朗, 田中健大, 佐藤康晴, 吉野正

    第110回日本病理学会総会 

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    開催年月日: 2021年4月22日 - 2021年4月25日

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  • リンパ腫細胞診における補助診断~遺伝子再構成とFCM~

    江草侑厘安, 藤田梓, 祇園由佳, 吉野正, 佐藤康晴

    日本臨床細胞学会雑誌(Web)  2021年 

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    開催年月日: 2021年

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  • 自然消退を来したplasmablastic lymphomaの二例

    小野早和子, 佐藤康晴, 井川卓朗, 池田知佳, 柳井広之, 長塚仁, 吉野正, 吉野正

    日本口腔腫瘍学会総会・学術大会プログラム・抄録集  2021年 

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    開催年月日: 2021年

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  • CD5陽性びまん性大細胞型B細胞性リンパ腫とdouble-expressor lymphomaの臨床病理学的検討

    田端哲也, 佐藤康晴, 吉野正

    第79回日本癌学会学術総会 

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    開催年月日: 2020年10月1日 - 2020年10月3日

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  • メトトレキサート関連リンパ増殖性疾患Classical Hodgkin Lymphoma-typeの臨床病理学的解析

    祇園由佳, 吉野正, 佐藤康晴

    第60回日本リンパ網内系学会総会 

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    開催年月日: 2020年8月20日 - 2020年8月21日

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  • Clinicopathological analysis of lung lesions in plasma cell type idiopathic multicentric Castleman disease and IgG4-related disease

    第109回日本病理学会総会 

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    開催年月日: 2020年7月1日 - 2020年7月31日

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  • 涙腺腫脹でIgG4関連疾患と診断された6例の血清IgG4値による長期経過観察

    松尾俊彦, 松尾俊彦, 田中健大, 佐藤康晴, 片岡仁美, 片岡仁美, 宇賀麻由, 遠西大輔, 矢野朋文

    日本リンパ網内系学会会誌  2020年 

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    開催年月日: 2020年

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  • 形質細胞増多を伴うリンパ節炎症性疾患の細胞学的鑑別

    錦織亜沙美, 祇園由佳, 吉野正, 佐藤康晴

    日本臨床細胞学会雑誌(Web)  2020年 

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    開催年月日: 2020年

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  • B細胞性免疫不全関連リンパ増殖性疾患の病態と病理

    池田知佳, 祇園由佳, 祇園由佳, 吉野正, 佐藤康晴, 佐藤康晴

    日本リンパ網内系学会会誌  2020年 

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    開催年月日: 2020年

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  • メトトレキサート関連リンパ増殖性疾患Classical Hodgkin lymphoma-typeの臨床病理学的解析

    祇園由佳, 吉野正, 佐藤康晴

    日本リンパ網内系学会会誌  2020年 

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    開催年月日: 2020年

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  • 原発性マクログロブリン血症から形質転換したGerminal Center B-cellタイプのびまん性大細胞型B細胞リンパ腫の症例

    小林宏紀, 淺田騰, 遠西大輔, 阿部将也, 池田知佳, 坂本美彩, 江草侑厘安, 廻勇輔, 西森久和, 藤井伸治, 松岡賢市, 佐藤康晴, 吉野正, 前田嘉信

    日本リンパ網内系学会会誌  2020年 

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    開催年月日: 2020年

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  • 末梢性T細胞リンパ腫におけるLEF1発現の解析

    坂本美彩, 祇園由佳, 吉野正, 佐藤康晴, 佐藤康晴

    日本病理学会会誌  2020年 

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    開催年月日: 2020年

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  • 耳下腺分泌癌の1例

    江草侑厘安, 重西邦浩, 竹内賢吾, 佐藤康晴

    日本病理学会会誌  2020年 

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    開催年月日: 2020年

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  • 自然消退を来したplasmablastic lymphomaの二例

    池田知佳, 井川卓朗, 吉野正, 佐藤康晴

    日本病理学会会誌  2020年 

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    開催年月日: 2020年

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  • 婦人科LBC検体を用いたPCR法によるHPV検出~ハイブリッドキャプチャー法との比較~

    錦織亜沙美, 藤田梓, 祇園由佳, 佐藤康晴

    日本病理学会会誌  2020年 

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    開催年月日: 2020年

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  • CHL-type MTX-LPDにおけるPD-L1発現および臨床病理学的解析

    祇園由佳, 土井美里, 吉野正, 佐藤康晴

    日本病理学会会誌  2020年 

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    開催年月日: 2020年

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  • 形質細胞型キャッスルマン病とIgG4関連疾患の肺病変の鑑別におけるIL-6免疫染色の有用性

    西村碧フィリーズ, 井川卓朗, 吉野正, 佐藤康晴, 佐藤康晴

    日本病理学会会誌  2020年 

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    開催年月日: 2020年

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  • リンパ節細胞診検体を用いた遺伝子診断の応用-固定液の検討-

    藤田梓, 錦織亜沙美, 江草侑厘安, 祇園由佳, 佐藤康晴

    日本病理学会会誌  2020年 

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    開催年月日: 2020年

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  • 特徴的な組織像を呈したPeripheral T-cell lymphoma with T-cell follicular helper phenotype の一例

    西村 碧フィリーズ, 井川卓朗, 田端哲也, 田中健大, 佐藤康晴, 吉野 正

    第59回日本リンパ網内系学会総会 

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    開催年月日: 2019年6月27日 - 2019年6月29日

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  • 梅毒性リンパ節の組織学的検討

    宮宗愛理, 祇園由佳, 吉野 正, 佐藤康晴

    第108回日本病理学会総会 

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    開催年月日: 2019年5月9日 - 2019年5月11日

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  • EBV-positive mucocutaneous ulcerの遺伝子再構成の検索

    池田知佳, 祇園由佳, 吉野 正, 佐藤康晴

    第108回日本病理学会総会 

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    開催年月日: 2019年5月9日 - 2019年5月11日

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  • Cyclophosphamide(CY)が奏効した難治性TAFRO症候群の一例

    浦田 知宏, 遠西 大輔, 水原 健太郎, 阿部 将也, 住居 優一, 藤原 悠紀, 佐伯 恭昌, 廻 勇輔, 淺田 騰, 西森 久和, 藤井 伸治, 藤井 敬子, 佐藤 康晴, 松岡 賢市, 吉野 正, 前田 嘉信

    日本リンパ網内系学会会誌  2019年5月  (一社)日本リンパ網内系学会

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    開催年月日: 2019年5月

    記述言語:日本語  

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  • IgG4関連疾患との鑑別に苦慮したhyper-IL-6 syndrome

    寺尾 俊紀, 山本 和彦, 池内 一廣, 若林 宏, 井川 卓朗, 井上 大, 小田 和歌子, 大山 矩史, 鴨井 千尋, 住居 優一, 白石 雄太郎, 山本 宜和, 新谷 大悟, 塩手 康弘, 佐藤 康晴, 吉野 正, 今城 健二

    臨床血液  2019年5月  (一社)日本血液学会-東京事務局

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    開催年月日: 2019年5月

    記述言語:日本語  

    発熱、頸部リンパ節腫脹で受診した69歳男性。IgG、IgG4は著明に上昇し、CTで全身リンパ節腫脹、両側涙腺顎下腺腫大、膵体尾部腫大を認め、MRIで膵のソーセージ様腫大を呈し、IgG4関連疾患(IgG4-RD)の臨床所見に合致していた。リンパ節生検では、IgG4/IgG陽性細胞比は40%を超えていたが、拡張した濾胞間領域にIL-6陽性形質細胞の浸潤を認め、組織学的にidiopathic multicentric Castleman disease(iMCD)を含むhyper-IL-6 syndromeの像であった。初期治療であるPSLの内服にて症状は軽快し、低用量で長期寛解を維持している。IgG4-RDとiMCDを含むhyper-IL-6 syndromeとの鑑別が困難であった例を経験し、その骨髄所見も含め、文献的考察を加え報告する。(著者抄録)

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  • Hepatic Campylobacter jejuni infection present in three idiopathic multicentric Castleman disease patients with TAFRO syndrome

    井川卓朗, 影山千紘, 横田憲治, 吉野正, 佐藤康晴

    第58回日本リンパ網内系学会総会 

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    開催年月日: 2018年6月28日 - 2018年6月30日

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  • 小児に発症したprimary cutaneous CD4+ small/medium T-cell lymphoproliferative disorder の一例

    西田賢司, 佐藤康晴, 藤木俊寛, 前田進太郎, 田端哲也, 井川卓朗, 田中健大, 吉野正

    第58回日本リンパ網内系学会総会 

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    開催年月日: 2018年6月28日 - 2018年6月30日

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  • MALTリンパ腫と骨髄腫の鑑別が問題となった一例

    小野早和子、佐藤康晴、西森久和、吉野正

    第107回日本病理学会総会  2018年6月21日 

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    開催年月日: 2018年6月21日 - 2018年6月23日

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  • AZA加療中の潰瘍性大腸炎患者に発症したEBV-associated B-cell lymphoproliferative disordersの一例

    表梨華, 田中健大, 井川卓朗, 佐藤康晴, 吉野正

    第107回日本病理学会総会 

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    開催年月日: 2018年6月21日 - 2018年6月23日

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  • 好酸球性副鼻腔炎におけるIgG4陽性細胞の発現とその臨床的意義

    大浦季恵、土井美里、岡野光博、吉野正、佐藤康晴

    第107回日本病理学会総会 

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    開催年月日: 2018年6月21日 - 2018年6月23日

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  • 好酸球性副鼻腔炎におけるマスト細胞の解析とその臨床的意義

    土井美里, 大浦季恵, 岡野光博, 吉野正, 佐藤康晴

    第107回日本病理学会総会 

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    開催年月日: 2018年6月21日 - 2018年6月23日

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  • Plasma-Cell Type Castleman Disease におけるIL-6発現の検討

    杉 貴臣, 川本雅也, 井川卓朗, 佐藤康晴, 吉野正

    第107回日本病理学会総会 

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    開催年月日: 2018年6月21日 - 2018年6月23日

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  • 涙腺腫脹をきたし多数のIgG4陽性細胞浸潤を伴ったRosai-Dorfman diseaseの一例

    田端哲也, 佐藤康晴, 永喜多敬奈, 神農陽子, 吉野正

    第107回日本病理学会総会 

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    開催年月日: 2018年6月21日 - 2018年6月23日

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  • 濾胞性T細胞性リンパ腫の一例

    池田知佳, 佐藤康晴, 小田和歌子, 吉野正

    第107回日本病理学会総会 

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    開催年月日: 2018年6月21日 - 2018年6月23日

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  • MYD88変異解析が診断に有用であった非IgM型リンパ形質細胞性リンパ腫の一例

    山口 公大, 金田 裕人, 柴田 悠平, 後藤 尚絵, 笠原 千嗣, 田端 哲也, 佐藤 康晴, 吉野 正, 高橋 健

    日本リンパ網内系学会会誌  2018年5月  (一社)日本リンパ網内系学会

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    開催年月日: 2018年5月

    記述言語:日本語  

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  • MALTリンパ腫と骨髄腫の鑑別が問題となった一例

    小野 早和子, 佐藤 康晴, 西森 久和, 吉野 正

    日本リンパ網内系学会会誌  2018年5月  (一社)日本リンパ網内系学会

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    開催年月日: 2018年5月

    記述言語:日本語  

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  • MALTリンパ腫と骨髄腫の鑑別が問題となった一例

    小野 早和子, 佐藤 康晴, 西森 久和, 吉野 正

    日本病理学会会誌  2018年4月  (一社)日本病理学会

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    開催年月日: 2018年4月

    記述言語:日本語  

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  • 小児に発症したprimary cutaneous CD4+ small/medium T-cell lymphoproliferative disorderの一例

    西田賢司, 佐藤康晴, 佐藤康晴, 藤木俊寛, 前田進太郎, 田端哲也, 井川卓朗, 田中健大, 吉野正

    日本リンパ網内系学会会誌  2018年 

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    開催年月日: 2018年

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  • A novel treatment for brain infarction targeting alarmin/HMGB1

    Masahiro Nishibori, Kayue Liu, Shuji Mori, Hideo Takahashi, Yasuko Tomono, Hideriori Wake, Toru Kanke, Yasuharu Sato, Norihito Hiraga, Naoto Adachi, Tadashi Yoshino

    NEUROSCIENCE RESEARCH  2008年  ELSEVIER IRELAND LTD

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    開催年月日: 2008年

    記述言語:英語  

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  • IMMUNOHISTOCHEMICAL ANALYSES OF PTPN6 (SHP1) ON LANGERHANS CELL HISTIOCYTOSIS

    Ichiro Murakami, Takashi Oka, Hiaki Sato, Yuta Kitamura, Toshiaki Morito, Katsuyoshi Takata, Yoko Shinno, Masayuki Takano, Kana Washio, Xingang Huang, Maiko Tamura, Naoko Ohnishi, Koichi Ichimura, Yasuharu Sato, Hiroyuki Yanai, Nobuya Ohara, Eisaku Kondo, Kiyoshi Takahashi, Takehiro Tanaka, Jean Gogusev, Francis Jaubert, Akira Morimoto, Shinsaku Imashuku, Tadaatsu Akagi, Tadashi Yoshino

    Proceedings of XXIV Annual Meeting of the Histiocyte Society  2008年 

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    開催年月日: 2008年

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  • キャッスルマン病の病理とTAFRO症候群の多様性 招待

    佐藤 康晴

    第36回 奈良悪性リンパ腫談話会  2022年1月29日 

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    記述言語:日本語  

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  • 特発性多中心性キャッスルマン病、TAFRO症候群の病理とその多様性 招待

    佐藤 康晴

    第35回 悪性リンパ腫臨床・病理セミナー  2022年1月19日 

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    記述言語:日本語  

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  • リンパ節細胞診におけるフローサイトメトリーの活用 招待

    藤田 梓, 江草 侑厘安, 錦織 亜沙美, 祇園由佳, 吉野 正, 佐藤康晴

    第60回日本臨床細胞学会秋期大会  2021年11月21日 

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    会議種別:シンポジウム・ワークショップ パネル(指名)  

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  • 特発性多中心性キャッスルマン病を知る 招待

    錦織亜沙美, 前川倖希奈, 前濱かんな, 祇園由佳, 吉野 正, 佐藤康晴

    第60回日本臨床細胞学会秋期大会  2021年11月20日 

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    会議種別:シンポジウム・ワークショップ パネル(指名)  

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  • リウマチ膠原病関連疾患の病理とその多様性 招待

    佐藤康晴

    第27回TAKI研究会  2021年11月16日 

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  • IgG4関連疾患およびリンパ腫との鑑別を要したALPIBP の一例

    西村 碧フィリーズ, 直井 友亮, 佐藤 康晴, 吉野 正

    第67回日本病理学会秋期特別総会  2021年11月4日 

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  • Hemosiderin Deposition in Lymph Nodes of Patients with Plasma Cell Type Castleman Disease

    Yanyan Han, Takuro Igawa, Yasuharu Sato, Tadashi Yoshino

    第67回日本病理学会秋期特別総会  2021年11月4日 

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  • 涙腺および唾液腺領域におけるIgG4関連疾患の病理学的鑑別

    佐藤康晴

    第29回日本シェーグレン症候群学会学術集会【シンポジウム4】  2021年9月25日 

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  • 特発性多中心性キャッスルマン病の病理学的アプローチ ~TAFRO症状を伴う病態も含めて~

    佐藤康晴

    Castleman病および類縁疾患を考える会  2021年1月22日 

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  • リンパ腫病理の基礎と臨床データの活用

    佐藤康晴

    第82回日本血液学会学術集会 コーポレートセミナー  2020年10月12日 

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  • 臨床検査を活用したリンパ腫の診断

    佐藤康晴

    日本医療検査科学会第52回大会 ランチョンセミナー  2020年9月25日 

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  • これだけは押さえておきたい! リンパ腫の基礎知識

    佐藤康晴

    第20回静岡血液フォーラム  2020年2月2日 

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  • リンパ腫の診断 ~技師が知っておきたいポイント~

    佐藤康晴

    第78回細胞検査士教育セミナー  2019年9月8日 

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  • キャッスルマン病の病理学的回顧

    佐藤康晴

    第4回埼玉リンパ腫研究会  2019年8月3日 

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  • キャッスルマン病の臨床および病理学的再考

    佐藤康晴

    第19回茨城リンパ腫セミナー  2019年6月7日 

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  • キャッスルマン病の臨床・病理学的再考

    佐藤康晴

    第104回神奈川リンパ腫病理研究会  2019年4月20日 

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  • キャッスルマン病に埋もれていた疾患たち ~IgG4関連疾患とTAFRO症候群~

    佐藤康晴

    第27回近畿小児リウマチ・膠原病研究会(PADK)  2019年4月6日 

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  • リンパ腫の診断とWHO分類 ~検査技師が知っておきたい診断のポイント~

    佐藤康晴

    大阪府臨床検査技師会 病理特別講習会  2019年1月18日 

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  • キャッスルマン病の臨床および病理学的再考

    佐藤康晴

    奈良県立医科大学免疫学講座セミナー  2018年11月1日 

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  • 関節リウマチ患者におけるリンパ増殖性疾患

    佐藤康晴

    第115回梶ヶ谷腎・膠原病研究会  2018年8月23日 

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  • リンパ腫分類WHO2017 ~これからの診断に求められるもの~

    佐藤康晴

    第3回FISH検査技術標準化研究会  2018年8月19日 

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  • リンパ腫 up to date ~検査技師が知っておきたいkey point~

    佐藤康晴

    第67回日本医学検査学会【教育講演Ⅸ】  2018年5月13日 

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  • キャッスルマン病に埋もれていた新規疾患単位 ~IgG4関連疾患とTAFRO症候群~

    佐藤康晴

    第29回膠原病臨床病理研究会  2018年2月9日 

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  • キャッスルマン病に埋もれていた新規疾患単位~IgG4関連疾患とTAFRO症候群~

    佐藤康晴

    第48回神戸免疫・膠原病懇話会  2018年1月27日 

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  • リンパ腫分類WHO2016 ~検査技師が知っておきたい改訂のポイント~

    佐藤康晴

    広島県臨床検査技師会 血液病理合同研修会  2017年10月21日 

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  • 関節リウマチ患者におけるリンパ増殖性疾患~病理医の視点で解剖する~

    佐藤康晴

    第94回関節疾患フォーラム  2017年9月5日 

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  • 病理医からみたMTX関連リンパ増殖性疾患

    佐藤康晴

    第104回膠原病研究会  2017年6月6日 

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  • 病理医からみたMTX関連リンパ増殖性疾患

    佐藤康晴

    第21回リウマチフォーラム  2017年1月29日 

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  • IgG4関連疾患におけるAIDの発現解析

    第106回日本病理学会総会  2017年 

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  • 自然消退したperipheral T-cell lymphoma with EBV infection, IVL-like featureの一例

    第106回日本病理学会総会  2017年 

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  • 免疫染色によるIgAの発現検索はIgG4関連疾患と形質細胞型キャッスルマン病の鑑別を可能にする

    第106回日本病理学会総会  2017年 

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  • IgG4関連唾液腺炎の上皮におけるランゲルハンス細胞様樹状細胞を介した抗原提示の可能性

    第106回日本病理学会総会  2017年 

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  • IgA immunostaining differentiates IgG4-related disease from plasma cell-type Castleman disease

    第57回日本リンパ網内系学会総会  2017年 

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  • 自然消退したIVL-like, EBV-associated T-cell lymphoproliferative disorderの一例

    第57回日本リンパ網内系学会総会  2017年 

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  • 精巣に発生したplasmablastic lymphomaの一例

    第57回日本リンパ網内系学会総会  2017年 

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  • IgG4関連疾患におけるランゲルハンス細胞様樹状細胞による抗原提示の可能性

    第57回日本リンパ網内系学会総会  2017年 

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  • IgG4関連リンパ節症;細胞診の可能性と限界を見極める

    第58回日本臨床細胞学学会総会  2017年 

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  • A case of diffuse large B-cell lymphoma occupying right atrium and inferior vena cava.

    第106回日本病理学会総会  2017年 

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  • 頭頸部扁平上皮乳頭腫におけるHPV感染について

    第106回日本病理学会総会  2017年 

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  • 胃腺癌にマントル細胞リンパ腫が混在した一例

    第106回日本病理学会総会  2017年 

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  • 十二指腸濾胞性リンパ腫の無治療経過観察中にびまん性大細胞型B細胞性リンパ腫への形質転換が疑われた1例

    第106回日本病理学会総会  2017年 

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  • 病理からみたMTX関連リンパ増殖性疾患

    CIMZIA Forum 2016 in OKAYAMA  2016年12月1日 

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  • いったい何者!? MTX関連リンパ増殖性疾患

    佐藤康晴

    第26回日本リウマチ学会近畿支部学術集会【特別講演2】  2016年9月3日 

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  • 病理医からみたMTX関連リンパ増殖性疾患

    佐藤康晴

    第11回京都リウマチネットワークフォーラム懇話会  2016年8月27日 

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  • これだけは押さえておきたい! リンパ腫の基礎知識

    佐藤康晴

    愛知県臨床検査技師会 血液検査研究班講演会“病理からみたリンパ腫”  2016年7月16日 

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  • いったい何者!? MTX関連リンパ増殖性疾患

    佐藤康晴

    第12回東備リウマチ研究会  2016年7月9日 

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  • IgG4-related lymphadenopathy and Castleman disease

    Yasuharu Sato

    ISEHARA LYMPHOMA SUPERIOR LECTURE  2016年5月31日 

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    記述言語:英語  

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  • IgG4関連リンパ腫節症におけるマスト細胞のIgE発現とその意義

    第105回日本病理学会総会  2016年 

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  • メソトレキサート関連リンパ増殖性疾患の臨床病理学的解析

    第105回日本病理学会総会  2016年 

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  • Catsleman’s diseaseに類似した組織像を呈するMantle cell lymphoma の2症例

    第105回日本病理学会総会  2016年 

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  • Follicular lymphoma in situ で経過観察中にHodgkin lymphoma とのcomposite lymphoma を発症した一例

    第105回日本病理学会総会  2016年 

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  • 中枢神経原発extranodal NK/T-cell lymphoma, nasal typeの一例

    第105回日本病理学会総会  2016年 

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  • 胃MALTリンパ腫から発生した、形質細胞への分化を示すびまん性大細胞型B細胞性リンパ腫の一例

    第105回日本病理学会総会  2016年 

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  • MTX関連リンパ増殖性疾患とは?

    金沢リウマチ膠原病治療懇話会  2016年 

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  • 胃MALTリンパ腫から発生した、形質細胞への分化を示すびまん性大細胞型B細胞性リンパ腫の一例

    第56回日本リンパ網内系学会総会  2016年 

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  • メソトレキサート関連リンパ増殖性疾患の臨床病理学的解析

    第56回日本リンパ網内系学会総会  2016年 

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  • 喉頭乳頭腫におけるヒト乳頭腫ウィルス感染との関連について

    第105回日本病理学会総会  2016年 

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  • Verrucous carcinoma とHPV感染の関連性について

    第105回日本病理学会総会  2016年 

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  • IgG4-producing lymphoma arising in a patient with IgG4-related disease

    第105回日本病理学会総会  2016年 

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  • Hodgkinリンパ腫と病理学的鑑別が必要な症例

    第4回リンパ腫スキルアップセミナー  2015年 

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  • IgG4関連疾患の病態形成における樹状細胞による抗原提示の関与

    第104回日本病理学会総会  2015年 

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  • BACH2はEBV陽性びまん性大細胞型B細胞リンパ腫において高率に発現低下を示しNFκB pathway活性化に関与する

    第104回日本病理学会総会  2015年 

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  • 消化管低悪性度B細胞性リンパ腫患者では血清IL-8,IL-4,IL-1βは高値を示す

    第104回日本病理学会総会  2015年 

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  • IgG4関連疾患の病態形成における樹状細胞の関与

    第55回日本リンパ網内系学会総会  2015年 

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  • 壊死性リンパ節炎におけるCD30の発現と分子病理学的意義

    第55回日本リンパ網内系学会総会  2015年 

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  • 未治療で自然消褪をきたした右上顎歯肉plasmablastic lymphomaの一例

    第55回日本リンパ網内系学会総会  2015年 

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  • 消化管DLBCLにおけるMYD88L265P変異の解析

    第55回日本リンパ網内系学会総会  2015年 

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  • 消化管原発濾胞性リンパ腫におけるCD10 発現低下とその意義

    第55回日本リンパ網内系学会総会  2015年 

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  • 肝細胞癌および肺扁平上皮癌に血管内大細胞型B細胞リンパ腫を合併した1剖検例

    第55回日本リンパ網内系学会総会  2015年 

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  • BACH2はEBV陽性びまん性大細胞型B細胞リンパ腫において高率に発現低下を示しNFB pathway活性化に関与する

    第55回日本リンパ網内系学会総会  2015年 

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  • リンパ腫増殖性疾患における良・悪性の病理学的鑑別

    第55回日本リンパ網内系学会総会  2015年 

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  • 葉酸レセプターαは膵癌において高率に発現し予後不良な経過を示す

    第104回日本病理学会総会  2015年 

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  • 真菌塞栓による消化管壊死を来たした成人T細胞性白血病リンパ腫の一剖検例

    第104回日本病理学会総会  2015年 

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  • IgG4関連疾患 A to Z

    第4回自己免疫疾患研究会  2015年 

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  • リンパ腫診療のスキルアップ ~病理医からのメッセージ~

    第77回日本血液学会学術集会 Meet the Expert 4  2015年 

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  • IgG4-related disease ~approach to the pathogenesis and risk of malignancy~

    京都大学院医学研究科大学院教育コース「病理形態学・病態医学」  2015年 

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  • 胃MALTリンパ腫におけるc-METの発現

    第104回日本病理学会総会  2015年 

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  • IgG4関連疾患の病理

    第104回日本病理学会総会  2015年 

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  • リンパ節におけるIgG4関連疾患

    第104回日本病理学会総会  2015年 

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  • De novo CD5-positive diffuse large B-cell lymphomas show high specificity for cyclin D2

    第104回日本病理学会総会  2015年 

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  • 壊死性リンパ節炎におけるCD30の発現と分子病理学的意義

    第104回日本病理学会総会  2015年 

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  • 消化管原発濾胞性リンパ腫におけるCD10発現低下とその意義

    第104回日本病理学会総会  2015年 

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  • IgG4関連疾患と鑑別が困難だった上眼瞼腫瘤の1例

    第104回日本病理学会総会  2015年 

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  • 多数のlgG4陽性細胞を伴ったびまん性大細胞型B細胞リンパ腫の1例

    第104回日本病理学会総会  2015年 

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  • 消化管DLBCLにおけるMYD88L265P変異の解析

    第104回日本病理学会総会  2015年 

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  • 低悪性度B細胞リンパ腫におけるLEF1発現

    坂本美彩, 祇園由佳, 玉田祐里, 吉野 正, 佐藤康晴

    第108回日本病理学会総会 

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産業財産権

  • 細胞固定液及びその製造方法

    佐藤 康晴, 佐藤 あやの, 祇園 由佳, 藤田 梓

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    出願人:国立大学法人 岡山大学

    出願番号:特願2020-180224  出願日:2020年10月28日

    公開番号:特開2022-071327  公開日:2022年5月16日

    J-GLOBAL

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受賞

  • Top Cited Article 2021-2022 (Pathology International)

    2023年3月  

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  • Top Downloaded Article (Pathology International)

    2023年3月  

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  • The Best Doctors in Japan 2022-2023

    2022年7月  

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  • Top Cited Article 2020-2021 (Pathology International)

    2022年4月  

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  • 平成23年度日本病理学会学術奨励賞

    2012年4月  

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  • 公益財団法人岡山医学振興会研究助成

    2010年7月  

     詳細を見る

  • 国際病理アカデミー日本支部2009年病理診断学術奨励賞

    2009年11月  

     詳細を見る

  • 平成20年度日本リンパ網内系学会学術奨励賞

    2009年7月  

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共同研究・競争的資金等の研究

  • 疾患特異的環境下における自己抗体産生B 細胞とその抗原の同定

    研究課題/領域番号:23K18362  2023年06月 - 2026年03月

    日本学術振興会  科学研究費助成事業  挑戦的研究(萌芽)

    金子 直樹, 金子 一成, 川野 真太郎, 佐藤 康晴, 林 慶和

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    配分額:6500000円 ( 直接経費:5000000円 、 間接経費:1500000円 )

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  • HHV8陰性・形質細胞型キャッスルマン病における新規バイオマーカーの探索

    研究課題/領域番号:20K07407  2020年04月 - 2023年03月

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    佐藤 康晴

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    配分額:4290000円 ( 直接経費:3300000円 、 間接経費:990000円 )

    キャッスルマン病は、1954年、マサチューセッツ総合病院の病理医であるDr. Benjamin Castlemanが、縦隔に限局した巨大腫瘤の1例を報告したことに始まる。これがキャッスルマン病の原型であり、現在は硝子血管型(hyaline-vascular type, HV type)と呼ばれている。1970年にFlendrigがキャッスルマン病の新たな亜型として形質細胞型(plasma cell type, PC type)の存在を報告した。これらはいずれも限局性病変であり、unicentric Castleman disease(UCD)とよばれている。1983年にFrizzeraらが、病理学的にPC type UCDに類似していながら、多発病変を形成し、臨床的にも発熱、盗汗、体重減少などの強い全身症状を伴った15例を報告し、multicentric Castleman disease(MCD)と呼ばれるようになった。後にMCDはKSHV/HHV8関連MCDとKSHV/HHV8に関連しないidiopathic multicentric Castleman disease(iMCD)に大別されるようになった。しかしながら、iMCDは未だ病態形成メカニズムが不明であり、病理学的にiMCDと診断された症例であっても治療反応性や臨床経過が異なっており、非常にヘテロな疾患単位となっている。我々は、このiMCDの明確な診断基準となり得るバイオマーカーを見出すべくRNA-seqによる解析を行った。その結果、iMCDは遺伝子発現パターンにより2群に分類されることが明らかとなった。また、IL-6免疫染色において、蛋白発現群と非発現群の2群に大別され、IL-6阻害剤の治療反応性が異なることも明らかとなった。

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  • CD30阻害療法による実験的関節炎モデルマウスの関節破壊抑制効果の検討

    研究課題/領域番号:20K09433  2020年04月 - 2023年03月

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    西田 圭一郎, 佐藤 康晴

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    配分額:4290000円 ( 直接経費:3300000円 、 間接経費:990000円 )

    TNFαレセプターファミリーのうちの一つであるCD30は、Hodgkinリンパ腫等に高率に発現し治療ターゲットとして臨床利用されている表面抗原である。関節リウマチ(RA)患者の血清および関節液中で、CD30から切断された外部ドメインである可溶性CD30が有意に上昇していることが報告されている。しかし、これまで滑膜組織でのCD30の発現とその発現刺激、病的意義については十分研究されていない。本研究ではCD30がRAの新規治療標的になり得るか検討を行った。
    変形性関節症(OA)患者およびRA患者の手術時に採取した滑膜組織に対し免疫染色にてCD30の発現を検討し、OA患者滑膜に対しRA患者滑膜で、CD30の高発現を認めた。蛍光二重免疫染色で検討すると滑膜組織でCD30は形質細胞、B細胞、滑膜線維芽細胞での発現を認めた。in vivoではRAモデルであるコラーゲン抗体誘導関節炎をマウスに惹起し、ブレンツキシマブ・ベトチン(BV)の投与を行い関節炎に対する治療効果を関節腫脹臨床スコア、体重、血清中のSAA, IL-6, TNFαに加え両足部組織標本に対して各種染色方法で評価した。高濃度投与群では関節腫脹に基づく臨床スコアが有意に低下し、血清中のSAAも低値であり炎症が抑制されていることを示していた。病理組織検査では滑膜増生や骨軟骨破壊が高濃度投与群で抑制されていた。
    本研究の結果は、RAの滑膜組織では活発な炎症が惹起されている状態で、形質細胞や滑膜線維芽細胞にCD30が発現しており、BV投与によりCD30発現細胞にアポトーシスが誘導され、滑膜増殖による関節破壊を抑制する可能性があることを示唆している。

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  • 舌癌発生過程におけるTreg排除療法の研究

    研究課題/領域番号:20K09695  2020年04月 - 2023年03月

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    折田 頼尚, 佐藤 康晴

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    配分額:4160000円 ( 直接経費:3200000円 、 間接経費:960000円 )

    近年多くの癌種において制御性T細胞regulatory T cell (Treg)の浸潤が予後不良因子として報告されています。我々は舌癌モデルマウスにて癌の発生・進行と Tregの浸潤の関係を観察し、前癌病変~初期癌にTreg、IL-10等が増加し、癌進行とともにそれらは減少することをつきとめました[Miki K, Orita Y, et al. Cancer Immunol Immunother 65: 1401-10, 2016]。そして、次のステップとして、ジフテリアトキシン誘導性にTregを体内から排除することが可能な DEREG(Depletion of regulatory T cell)マウス(Foxp3陽性制御性T細胞特異的ジフテリアトキシンレセプタートランスジェニックマウス)に同様の手法で舌癌 を発症させ、種々のタイミングでTregを排除しその効果を観察したところ、ジフテリアトキシンでTregを排除しないDEREGマウスでは野生型と同様に発癌が観察 されますが、前癌病変から扁平上皮癌に進行する時期にTregを排除すると舌癌が発症しないことを発見しました。癌が発症してしまってからTregを排除しても個 体差はあるもののやはり舌癌の進行が抑えられることもわかりました。しかしDEREGマウスの繁殖力が弱く、統計解析できるまでNを増やしての検討がまだできておらず、至適Treg排除時期まではまだ突きとめられていません。更にジフテリアトキシンによるTreg排除の効果が実際どのくらいTregを排除できるのか、ジフテ リアトキシン投与後何日までその効果は続くのかなど、未解決な点が多く残っています。
    現在は、マウス繁殖の専門施設に依頼しDEREGマウスを十分繁殖させている段階です。

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  • 舌癌に対する制御性T細胞除去療法の研究

    研究課題/領域番号:17K11385  2017年04月 - 2021年03月

    日本学術振興会  科学研究費助成事業 基盤研究(C)  基盤研究(C)

    折田 頼尚, 三木 健太郎, 佐藤 康晴

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    配分額:4420000円 ( 直接経費:3400000円 、 間接経費:1020000円 )

    近年多くの癌種において制御性T細胞regulatory T cell (Treg)の浸潤が予後不良因子として報告されています。Tregは胸腺・抗原に暴露した末梢で産生されeffector T cellの抗腫瘍作用を抑制します。我々は4NQOを用いた舌癌モデルマウスにて癌の発生・進行とTregの浸潤の関係を観察し、前癌病変~初期癌にTreg、IL-10等が増加し、癌進行とともにそれらは減少することをつきとめました[Miki K, Orita Y, et al. Cancer Immunol Immunother 65: 1401-10, 2016]。つまり、Tregは主として舌癌発生初期段階で癌発生・進行の役割を果たすのではないかと思われ、治療としてTregを抑制するならば癌発生初期が最も有効であると予想しました。今回、次のステップとして、ジフテリアトキシン誘導性にTregを体内から排除することが可能なDEREG(Depletion of regulatory T cell)マウス(Foxp3陽性制御性T細胞特異的ジフテリアトキシンレセプタートランスジェニックマウス)に同様の手法で舌癌を発症させ、種々のタイミングでTregを排除し、どの段階でTregを排除するのが最も有効であるのかを観察しました。まず、ジフテリアトキシンでTregを排除しないDEREGマウスでは野生型と同様に発癌が観察されますが、ちょうど前癌病変から扁平上皮癌に進行する時期にTregを排除すると舌癌は発症せず、マウスの毛並みも良く元気であることを発見しました。その他の舌癌が発症しある程度進行してしまってからTregを排除しても個体差はあるもののやはり舌癌の進行が抑えられることもわかりました。ただ、DEREGマウスは繁殖力に難があり、当初予定していた個体数が確保できず統計処理には至っていません。

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  • 日米共同研究によるIgG4関連疾患の国際的疾患概念の構築と新規診断法への展開

    研究課題/領域番号:17H04671  2017年04月 - 2020年03月

    日本学術振興会  科学研究費助成事業 基盤研究(B)  基盤研究(B)

    森山 雅文, 佐藤 康晴, 中村 誠司

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    配分額:15990000円 ( 直接経費:12300000円 、 間接経費:3690000円 )

    平成30年度の研究は、日米のIgG4関連疾患(IgG4-RD)の免疫学的差異について、以下の研究を行った。
    1)IgG4-RD 患者の唾液腺における免疫細胞(ヘルパーT(Th) 細胞やマクロファージ)の検索
    当科および米国のRagon研究所で収集した IgG4-RD 患者の唾液腺を用いて、自然免疫の中心的役割を担うマクロファージとCD4 陽性細胞(Th 細胞)の発現と局在について検討を行った。その結果、日米ともにIgG4-RD 患者の唾液腺では、シェーグレン症候群(SS)や慢性唾液腺炎(CS)患者に比べて、マクロファージでは M2 マクロファージ(CD163 陽性細胞)が優位に浸潤していた。さらに、DNAマクロアレイおよびバリデーションにて発現上昇を認める自然免疫関連分子を検索したところ、TLR7が候補分子として抽出された。唾液腺病変におけるTLR7の発現細胞を二重蛍光染色法にて確認すると、IgG4-RD患者のみM2マクロファージとほぼ発現が一致していた。
    また、多重蛍光染色より免疫細胞の構成比を測定する最新の技術であるTissueFAXSTMで解析した結果、Th 細胞では濾胞性T細胞(CD4+IL-4+BATF+CXCR5+細胞)およびCD陽性細胞傷害性T細胞(CD4+GZMA+TGF-β+細胞)が優位に浸潤しており、特異的な免疫細胞の浸潤パターンがIgG4-RD の唾液腺に認められた。日米間での明らかな免疫学的な差異は認めなかったが、これらの濾胞性T細胞とCD陽性細胞傷害性T細胞は、患者の血清IgG4値と正の相関を示し。IgG4-RDの病態形成に深く関与していることが示唆された。

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  • IgG4関連疾患における発がん関連蛋白の探索

    研究課題/領域番号:16K08666  2016年04月 - 2019年03月

    日本学術振興会  科学研究費助成事業 基盤研究(C)  基盤研究(C)

    佐藤 康晴

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    配分額:4940000円 ( 直接経費:3800000円 、 間接経費:1140000円 )

    IgG4関連疾患 (IgG4-RD)では、健常人と比べ発がんリスクが約3.5倍高いことが報告されており、我々も眼窩領域のIgG4-RDを背景にMALTリンパ腫が発症する可能性について報告してきた。そこでAIDによる発がんの可能性を疑い研究を開始した。その結果、IgG4-RD群では大将軍に比して有意にAIDが高発現していることが明らかとなった。さらにAIDが胚中心外にも過剰発現していることも明らかにした。以上より、IgG4-RDの発がんにAIDが強く関係している可能性が示唆された。

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  • IgG4関連疾患の病態形成メカニズムの解明

    研究課題/領域番号:24591447  2012年04月 - 2015年03月

    日本学術振興会  科学研究費助成事業 基盤研究(C)  基盤研究(C)

    佐藤 康晴

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    配分額:5070000円 ( 直接経費:3900000円 、 間接経費:1170000円 )

    IgG4関連疾患においては、Th2およびTregサイトカインが病態形成に重要とされており、それらサイトカインはT細胞によって産生されていると考えられていた。しかしながらT細胞による産生とするにはunusalな点が多々あったことから、サイトカイン産生細胞を同定すべく本研究助成において研究を開始した。唾液腺領域のIgG4関連疾患、唾石および正常顎下腺を対象として、各種サイトカインのmRNAの定量および免疫染色によるサイトカイン産生細胞の解析を行った。その結果、IgG4関連疾患において各種サイトカインmRNAおよび陽性細胞が有意に増加していた。またこれらはマスト細胞であることを明らかにした。

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  • 加齢性EBV陽性びまん性大細胞型B細胞リンパ腫のNFkBに着目した分子病態の解明

    研究課題/領域番号:24590411  2012年04月 - 2014年03月

    日本学術振興会  科学研究費助成事業 基盤研究(C)  基盤研究(C)

    浅野 直子, 佐藤 康晴

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    配分額:5330000円 ( 直接経費:4100000円 、 間接経費:1230000円 )

    加齢性EBV陽性びまん性大細胞型B細胞リンパ腫は、免疫機能不全や先行リンパ腫のない中高齢の患者に発生するEBV陽性B細胞腫瘍であり、WHO分類(2008)において、EBV-positive DLBCL of the elderlyとして分類されている。EBV+DLBCL of the elderlyは、しばしば節外臓器に病変を認め、壊死、反応性要素に富む病理像を示し、臨床的にはEBV陰性DLBCLに比べ予後不良を示す。病理形態学的にバリエーションを認め、形態学的細分類として、Large lymphoma cell typeおよびpolymorphous subtypeが従来から提唱されていた。この度、それに加え腫瘍細胞が形質芽細胞様の形態を有したPlasmablastic lymphoma in the eldely (PBL-e)を提唱した。このPBL-eは、皮膚・粘膜に病変の主座を認め、また形態学的にはPlasmablastic lymphomaに類似する。この疾患に関しては、Histopathology誌(2012 Dec;61(6):1183-97)に掲載した。A20およびLMP1の発現を検討した結果、PBL-eでは他のsubtypeよりLMP1-/ A20-を多く認めた。しかしこれらの症例において組織標本からのFISHを施行したところ、A20欠失所見の増加は認められていない。 今後多数例での検討が必要であると考える。またEBV-positive DLBCL of the elderlyで皮膚浸潤を認める症例、皮膚限局症例の蓄積および解析から、節外病変(特に皮膚)におけるEBV+DLBCL of the elderlyの新たな側面が明らかになりつつある。皮膚症例に関する報告は現在投稿中である。

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